FDA approves new liquid bowel-cleansing prep for colonoscopy August 8, 2006
FDA approves new hyaluronic acid dermal fillers from Allergan August 2, 2006
AstraZeneca wins approval in US for new asthma drug July 25, 2006
Contraceptive implant approved by US FDA July 19, 2006
New biologic treatment for wet age-related macular degeneration ok’d in US July 10, 2006
FDA approves new treatment for rare type of leukemia June 30, 2006
New vaccine approved to prevent cervical cancer, genital warts, and other HPV-caused diseases June 9, 2006
Oral drug approved in US for treatment of rosacea May 31, 2006
FDA approves new vaccine for the prevention of shingles May 30, 2006
Transdermal patient-activated analgesic system wins approval in US May 24, 2006
Cannabinoid Cesamet now approved to treat nausea and vomiting in the US May 16, 2006
Extended-release minocycline approved to treat acne vulgaris May 9, 2006
First treatment of Pompe disease approved in US May 1, 2006
FDA approves monthly injection for treatment of alcohol dependence April 17, 2006
FDA approves Berlex's oral contraceptive pill with drospirenone March 20, 2006
FDA ok's first transdermal patch to treat major depressive disorder March 1, 2006
Merck's rotavirus gastroenteritis vaccine approved by FDA February 6, 2006
FDA approves new chronic angina treatment January 31, 2006
US approves new treatment for stomach and kidney cancers January 27, 2006
New postsurgical adhesion reduction solution approved in US August 2, 2006
First treatment for Hunter syndrome approved in US July 25, 2006
Ovation launches second-line treatment for patent ductus arteriosus July 24, 2006
Drugmakers collaborate on first once-daily, 3-drug treatment of HIV-1, FDA gives the nod July 7, 2006
Endo Pharmaceuticals to begin marketing local dermal analgesic patch July 7, 2006
FDA approves new HIV treatment for patients who do not respond to existing drugs June 27, 2006
Sandoz granted approval for recombinant human growth hormone June 1, 2006
Seasonique approved for extended-cycle oral contraception May 30, 2006
New treatment for Parkinson's disease approved by US FDA May 18, 2006
Smoking cessation drug approved by the FDA May 12, 2006
FDA ok’s new drug to treat myelodysplastic syndromes May 3, 2006
Biovail wins approval of once-daily extended-release painkiller April 19, 2006
Transdermal patch approved to treat ADHD, FDA announces April 10, 2006
New bowel-cleansing preparation for colonoscopy approved in US March 20, 2006
Injection approved to prevent serious infections in primary immune deficiency diseases March 7, 2006
New treatment for fungal infection approved in US February 22, 2006
New treatment for chronic idiopathic constipation wins US approval February 1, 2006
Inhaled recombinant human insulin approved by FDA January 30, 2006
August 8, 2006
ST. LOUIS (MD Consult) - Salix Pharmaceuticals, Ltd, announced on August 2, 2006, that the US Food and Drug Administration has granted marketing approval for prescription MoviPrep (polyethylene glycol [PEG] 3350, sodium sulfate, sodium chloride, potassium chloride, sodium ascorbate, and ascorbic acid for oral solution). The agent is indicated for bowel cleansing before colonoscopy in adults aged 18 years or older.
"MoviPrep is unique among the available purgatives in that it is the only liquid PEG bowel cleansing agent that incorporates ascorbic acid in its formulation, which contributes to MoviPrep’s efficacy and taste,"stated Bill Forbes, PharmD, Vice President, Research and Development, and Chief Development Officer at Salix. "The addition of ascorbic acid provides a novel osmotic cleansing action that enables 2-liter MoviPrep to provide the level of bowel cleansing previously only associated with 4-liter bowel cleansing agents. MoviPrep’s approval reflects data from patients that were allowed to eat a regular breakfast, a light lunch, and a snack the day of administering the purgative... MoviPrep, unlike the current market-leading bowel prep, is the only 2-liter purgative that eliminates the concomitant need for the laxative bisacodyl."
The majority of colonoscopies performed in the United States are indicated for colorectal cancer screening, and more than 10 million uses of bowel cleansing agents were prescribed during 2005. Colonoscopy is very effective in the early detection of colorectal cancer, and about 90% of colorectal cancers and deaths are preventable if detected early. The American Cancer Society estimates that more than 30,000 lives could be saved annually by widespread screening. However, fewer than half of adults aged 50 years and older in the United States reportedly undergo recommended colorectal cancer screening. Results of a study conducted by the Mayo Clinic demonstrated that patient unwillingness to take a bowel preparation is the single largest barrier to colorectal cancer screening.
MoviPrep should be used with caution in patients using concomitant medications that increase the risk of electrolyte abnormalities (eg, diuretics or angiotensin-converting enzyme inhibitors) or in patients with known or suspected hyponatremia. Caution should also be exercised in prescribing MoviPrep to patients with severe ulcerative colitis, ileus, gastrointestinal obstruction or perforation, gastric retention, toxic colitis, or toxic megacolon. In clinical trials, abdominal distension, anal discomfort, thirst, nausea, and abdominal pain were the most common adverse reactions to MoviPrep administration. Vomiting occurred less frequently.
Salix Pharmaceuticals, Ltd, is headquartered in Raleigh, NC. The company expects to launch MoviPrep during the fourth quarter of 2006. For full prescribing information on Salix products, visit salix.com.
August 2, 2006
ST. LOUIS (MD Consult) - Innovata PLC and Baxter Healthcare Corporation announced on August 1, 2006, that the US Food and Drug Administration has approved Adept Adhesion Reduction Solution (4% icodextrin solution) for use in gynecologic laparoscopic procedures in the United States. Because the product is a liquid, it can be delivered directly and rapidly to the site through a laparoscopic port during surgery.
Adept is indicated for use intraperitoneally as an adjunct to good surgical technique for the reduction of postsurgical adhesions in patients undergoing gynecologic laparoscopic adhesiolysis. Adhesions are abnormal attachments between tissues or organs. Gynecologic adhesions can cause pain, secondary infertility, or other complications in women.
Adept has been studied in 3 randomized, controlled US clinical trials involving a total of 548 patients undergoing gynecologic laparoscopic surgery with a follow-up laparoscopic procedure after the initial procedure. In the pivotal study, for the patients in the Adept group, 45.4% were defined as a "clinical success" compared with 35.6% in the control group. Clinical success was identified as a decrease in the number of adhesions between the baseline and second laparoscopies. Patients in the Adept group had significantly fewer sites with adhesions at follow-up compared with initial adhesiolysis laparoscopy (P = .016).
Adept contains icodextrin derived from cornstarch and is contraindicated in patients with known or suspected allergy to icodextrin and similar polymers. The product is contraindicated in laparotomy, in cases involving bowel resection or repair or appendectomy, and in surgical cases involving frank abdominopelvic infection. Rare reports of sterile peritonitis have been made after the use of icodextrin. Leakage of Adept from port sites may lead to wound-healing complications; meticulous fascial closure is advised. In addition, rare reports of hypersensitivity reactions, pulmonary edema, pulmonary effusion, and arrhythmia have been received. In such cases, the risk/benefit profile should be assessed before use of Adept is initiated.
For more information on Adept, visit innovataplc.com.
August 2, 2006
ST. LOUIS (MD Consult) - Allergan, Inc, announced on June 5, 2006, that the US Food and Drug Administration (FDA) has approved the Juvéderm dermal filler gel products, a collection of hyaluronic acid dermal fillers indicated to correct facial wrinkles and folds. Desired results occur with a single treatment in the majority of patients, and results are sustained for 6 months or longer.
Juvéderm adds volume to facial wrinkles, such as nasolabial folds. It is natural, biodegradable, and currently the only approved hyaluronic acid dermal filler that has demonstrated its safety and effectiveness in patients of all skin types and colors. Hyaluronic acid dermal fillers represent the fastest growing noninvasive aesthetic procedure in the United States. Occurring naturally in the body, hyaluronic acid is a natural complex sugar found in all living organisms and creates volume and elasticity in the skin.
The Juvéderm dermal filler products offer the highest concentration of cross-linked hyaluronic acid available in a dermal filler, which results in a long duration of effect. The smooth consistency of the Juvéderm formula also may help to minimize the discomfort that can sometimes occur during the injection procedure.
The FDA approved 3 formulations for Juvéderm dermal filler: Juvéderm 24HV, intended for contouring and volumizing of facial wrinkles and folds; Juvéderm 30HV dermal filler, for volumizing and correction of deeper folds and wrinkles; and Juvéderm 30, for subtle correction of facial wrinkles and folds.
The approval was made on the basis of data from a double-blind, randomized, controlled clinical trial. A total of 439 subjects were followed up for 6 months after injection with 1 of 3 Juvéderm formulations (ie, Juvéderm 24HV, Juvéderm 30HV, Juvéderm 30) in 1 nasolabial fold and Zyplast bovine-based collagen in the other. Juvéderm was found to provide a more persistent wrinkle correction than Zyplast over the 6-month course of the study, with up to 90% of subjects maintaining at least a 1-grade improvement in nasolabial fold correction with Juvéderm compared with 36% to 45% with Zyplast.
At the conclusion of the study, up to 88% of subjects expressed a preference for Juvéderm, whereas only 5% to 12% expressed a preference for Zyplast. In addition, among patients from non-white ethnic groups (all Fitzpatrick skin types), Juvéderm was found to be safe and effective and demonstrated no increased risk of hyperpigmentation or hypertrophic scarring.
In clinical studies, adverse events were usually mild to moderate in nature, did not require intervention, and lasted 7 days or less. The most common adverse effects included temporary injection site reactions including redness, pain/tenderness, firmness, swelling, lumps and bumps, and bruising. Juvéderm should only be administered by a trained and qualified health care provider.
Allergan expects to make its Juvéderm products available later in 2006. For updates on product availability, in addition to further product and prescribing information, visit the JuvedermComingSoon.com.
July 25, 2006
ST. LOUIS (MD Consult) - The US Food and Drug Administration (FDA) announced on July 24, 2006, its approval of Elaprase (idursulfase), the first product for the treatment of Hunter syndrome (ie, mucopolysaccharidosis II), a rare inherited disease that can lead to premature death. Elaprase is a new molecular entity, containing an active ingredient never before marketed in the United States.
Hunter syndrome, which usually becomes apparent in children at 1 to 3 years of age, is a disease in which the person’s body is defective in producing iduronate-2-sulfatase. This chemical is needed to adequately breakdown complex sugars produced in the body. Symptoms include growth delay, joint stiffness, and coarsening of facial features. In severe cases, patients experience respiratory and cardiac problems, enlargement of the liver and spleen, neurologic deficits, and death.
Elaprase was approved after a randomized, double-blind, placebo-controlled study of 96 patients with Hunter syndrome showed that the treated participants had an improved capacity to walk. At the end of the 53-week trial, patients who received Elaprase infusions experienced an average 38-yard greater increase in the distance walked in 6 minutes compared with the patients receiving placebo.
Hypersensitivity reactions to Elaprase, which were considered life threatening, were the most serious adverse events reported during the trial. They included respiratory distress, drop in blood pressure, and seizure. Other frequent but less serious adverse events included fever, headache, and joint pain.
Because of the potential for severe hypersensitivity reactions, appropriate medical support should be readily available when Elaprase is administered. Patients and their physicians are encouraged to participate in a voluntary Hunter Outcome Survey, which has been established to monitor and evaluate the safety and effects of long-term treatment with Elaprase.
Manufactured by Shire Human Genetic Therapies, Inc, in Cambridge, Mass, Elaprase has been designated an orphan product by the FDA. This status indicates a product developed to treat conditions that affect fewer than 200,000 persons in the United States, and it grants a 7-year period of exclusive marketing to the first sponsor to obtain marketing approval. Hunter syndrome is diagnosed in approximately 1 of 65,000 to 132,000 births.
More information about Elaprase, contact the manufacturer at 1-800-536-7878 or visit shire.com.
July 25, 2006
ST. LOUIS (MD Consult) - Pharmaceutical company AstraZeneca announced on July 22, 2006, that the US Food and Drug Administration (FDA) has approved Symbicort (budesonide/formoterol) for the maintenance treatment of asthma in patients aged 12 years and older. Symbicort is a twice-daily asthma therapy combining budesonide, an inhaled corticosteroid, and formoterol, a rapid and long-acting beta2-agonist into 1 inhaler. Symbicort will be available in a pressurized metered-dose inhaler in 2 dose strengths: 80/4.5 and 160/4.5 mcg of budesonide and formoterol, respectively.
Twenty-seven phase I, II, and III trials were conducted to assess the efficacy and safety of Symbicort in a metered-dose inhaler. The approved indication was granted because of data from 2 pivotal double-blind, placebo-controlled, 12-week trials involving 1,076 patients in the United States, aged 12 years and older. These studies showed that both dosage strengths of Symbicort produced a greater improvement in lung function compared with the same doses of budesonide or formoterol (administered alone) or placebo. In addition, these studies demonstrated a more rapid improvement in lung function compared with budesonide and placebo. Significant improvement in lung function occurred within 15 minutes of beginning treatment with Symbicort. The combined medication is not indicated for the relief of acute bronchospasm.
The combination therapy of long-acting inhaled beta-agonists and inhaled corticosteroids for long-term control and prevention of symptoms in moderate and severe persistent asthma is recommended by the National Asthma Education and Prevention Program of The National Institutes of Health.
Asthma is a reversible obstructive lung disease caused by increased reaction of the airways to various stimuli. It is a serious chronic medical condition and can be life threatening if not properly managed. In 2002, the Centers for Disease Control and Prevention estimated that nearly 20 million Americans had asthma, and nearly 12 million of these had an attack or episode during the previous year. Despite the availability of many treatments in the United States to treat adults with asthma, the disease is still poorly controlled. Studies have shown that patients experience emergency department visits, hospitalizations, or attacks at a steady rate. Additionally, asthma patients who have experienced an asthma attack are twice as likely to experience additional exacerbations as other patients.
AstraZeneca plans to launch Symbicort in the United States in mid 2007. For more information, including the approved Symbicort product label, visit astrazeneca.com.
July 24, 2006
ST. LOUIS (MD Consult) - On July 20, 2006, Ovation Pharmaceuticals announced its launch of NeoProfen (ibuprofen lysine) Injection (10 mg/mL), a new pharmaceutical product indicated as a second-line treatment to close a clinically patent ductus arteriosus (PDA) in premature infants weighing between 500 and 1,500 g who are no more than 32 weeks’ gestational age. It is indicated for use when usual medical management (eg, fluid restriction and respiratory support) is ineffective.
The ductus arteriosus is part of the fetal pathway that helps to distribute oxygen from the mother to the baby’s organs in utero. A PDA allows blood flow to avoid the lungs, which are not needed before birth because the baby receives its oxygen from the mother across the placenta; PDA is present in all babies before birth. When the baby is born, the lungs expand, blood vessels relax to accept more flow, and the ductus arteriosus usually closes on its own within the first hours or days of life.
Premature infants, particularly neonates of very low birthweight, are more likely to have problems related to PDA. If the ductus arteriosus is large, does not close shortly after birth, and becomes symptomatic, the infant has a higher likelihood of pulmonary morbidity, necrotizing enterocolitis, and the need for surgery. According to the March of Dimes, 2% of all live births in the United States in 2003 were infants who had completed fewer than 32 weeks of gestation and were at risk of PDA-related problems. Approximately 30,000 infants are treated pharmacologically each year for PDA.
NeoProfen was approved by the US Food and Drug Administration (FDA) on April 13, 2006. The approval made on the basis of a priority review of data from a double-blind, placebo-controlled, multicenter clinical study in 136 premature infants (mean birth age, 1.5 days; mean gestational age, 26 weeks; mean weight, 798 g). Results showed that, compared with placebo, treatment with ibuprofen lysine significantly decreased the need for rescue therapy with indomethacin, open-label ibuprofen, or surgery (25% vs 48%; P = .003).
Among infants requiring rescue within the first 14 days of receiving ibuprofen lysine or placebo, no statistically significant difference was observed between the 2 groups with respect to mean age at start of first rescue treatment (8.7 vs 6.9 days). These findings were supported by data from 2 studies that revealed a benefit for ibuprofen lysine over placebo in preventing the need for rescue therapy, whether given prophylactically (n = 433; weight range, 400-2,165 g) or as treatment (n = 210; weight range, 400-2,370 g).
NeoProfen Injection has been shown to prolong bleeding time, to decrease urinary output, and to cause renal insufficiency. There are no long-term evaluations of ibuprofen's effects on neurodevelopmental outcome, growth, and disease processes associated with prematurity. The most frequent adverse effects associated with NeoProfen in the primary clinical trial supporting FDA approval include sepsis, anemia, total bleeding, and intraventricular hemorrhage.
Ibuprofen lysine injection is available in single-use vials containing 2 mL of 10-mg/mL sterile solution. It is administered intravenously as a 3-dose regimen consisting of an initial 10-mg/kg dose followed by doses of 5 mg/kg at 24 and 48 hours. All doses should be based on birthweight and diluted to an appropriate volume with dextrose or saline.
Because the formulation contains no preservatives, it should be administered within 30 minutes of preparation, and any solution remaining after the first withdrawal from the vial must be discarded.
The drug should be infused continuously for a period of 15 minutes via the intravenous port that is nearest the insertion site; careful administration is advised to avoid extravasation. The FDA notes that ibuprofen lysine may not be administered in the same intravenous line with total parenteral nutrition; total parenteral nutrition should be interrupted for a 15-minute period before and after ibuprofen lysine is given.
If anuria or marked oliguria (urinary output, < 0.6 mL/kg/h) is evident at the 24- and 48-hour scheduled times, no additional doses should be administered until laboratory studies indicate that renal function has normalized.
A second course of ibuprofen lysine therapy, alternative pharmacologic therapy, or surgery may be indicated to treat PDA that fails to close or that reopens during continued medical management.
For more information, including full prescribing information, visit ovationpharma.com/prod_hos_neopro.htm.
July 19, 2006
ST. LOUIS (MD Consult) - On July 18, 2006, biopharmaceutical company Organon announced that the US Food and Drug Administration has approved Implanon (etonogestrel, 68 mg) for contraception in women. The single-rod, subdermal implantable product is effective for up to 3 years. The average hormone release rate is 40 mcg/d.
Made of a soft medical polymer, Implanon is inserted just under the skin of a woman’s upper inner arm by a health care professional during an outpatient procedure, after which it is generally not visible. The product continuously releases a low, steady dose of progestogen (etonogestrel) for a period of 3 years. Removal can occur at anytime at the request of the user, after which the woman’s fertility rapidly returns to preexisting fertility, commensurate with age. Implanon must be removed at the end of the third year and may be replaced by a new Implanon rod at the time of removal if continued contraceptive protection is desired.
In clinical trials involving more than 2,300 women, the implant took an average of 1.1 minutes to be inserted and 2.6 minutes to be removed. If implanted according to instructions, Implanon was shown to be a reliable contraceptive method; in the trials, no pregnancies occurred during use over approximately 73,000 monthly cycles. The high reliability is also supported by data obtained after the launch of Implanon in 1998. This efficacy is achieved by ovulation inhibition and the fact that, in contrast to some other contraceptive methods, user compliance is not an issue because the Implanon user cannot forget to take the product. However, it is important for women to know that no form of contraception is 100% effective.
Like other progestogen-only contraceptives, the use of Implanon is associated with irregular menstrual bleeding and sometimes absence of bleeding. The product may be less effective in in women who are overweight or who are chronically taking medications that induce liver enzymes.
Implanon does not contain estrogen, making it suitable for women who do not tolerate or are contraindicated to take estrogens. Implanon is contraindicated in women with the following conditions:
Organon USA will be conducting a national clinical training program to train health care providers on the insertion and removal procedures associated with Implanon. Only health care professionals trained through the company-sponsored programs will be able to prescribe the medication for their patients. The clinical training program is scheduled to begin later in 2006.
For full prescribing information and other details on this contraceptive, visit implanon-usa.com.
July 13, 2006
ST. LOUIS (MD Consult) - On July 12, 2006, the US Food and Drug Administration (FDA) announced its approval of Atripla tablets, a fixed-dose combination of 3 widely used antiretroviral drugs, in a single tablet to be taken once a day. Atripla can be taken alone or in combination with other antiretroviral products for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults.
Atripla, the first single-pill, once-a-day product approved to treat HIV/acquired immunodeficiency syndrome (AIDS), combines the active ingredients of Sustiva (efavirenz), Emtriva (emtricitabine), and Viread (tenofovir disoproxil fumarate). Bristol-Myers Squibb and Gilead Sciences have formed a joint venture to commercialize Atripla in the United States. In certain territories, Merck holds the rights to efavirenz. Now, all 3 companies will work together to deliver the product to patients and physicians. Atripla will be available for use in the United States as a new product approved under a new drug application.
Atripla was approved in less than 3 months under the FDA's fast-track program. The manufacturer plans to make the drug available for purchase in the United States within 96 hours of this approval.
"The approval of Atripla simplifies the treatment regimen for HIV-1–infected adults, and will potentially improve the ability of patients to adhere to treatment resulting in long-term effective control of HIV-1," said Dr Andrew C. von Eschenbach, Acting Commissioner of Food and Drugs at the FDA. "This offers a particularly important advantage for patients in many countries that are most affected by the AIDS epidemic and will also have a major impact in the US. Atripla illustrates the outstanding achievements that are attainable when several pharmaceutical companies cooperate with our agency toward a common public health goal."
The FDA approved Sustiva in 1998, Viread in 2001, and Emtriva in 2003. The safety and effectiveness of the combination of these 3 drugs were shown in a 48-week clinical study with 244 adults infected with HIV-1 who received the drugs contained in Atripla. In this trial, 80% of the participants achieved a marked reduction of HIV and a substantial increase in the number of healthy CD4 cells.
The labeling of Atripla includes a boxed warning that the drug’s use can cause lactic acidosis. In patients with chronic hepatitis B infection, the discontinuation of the treatment with Atripla (which is not approved for this use) can result in severe flare-ups of hepatitis B infection. Other potential serious adverse events reported for the use of Atripla’s ingredients include serious liver toxicity, renal impairment, and severe depression. The most common adverse events experienced by participants in the combination trial included headache, dizziness, abdominal pain, nausea, vomiting, and rash.
According to the FDA, more than 1 million persons currently live with HIV and AIDS in the United States, and 40,000 new cases are reported each year. Twenty-eight FDA-approved products in the United States are used in the treatment of HIV infection. Within the last 2 years, the FDA has approved more than 20 treatments to be used as part of the President’s Emergency Plan for AIDS Relief, a $15 billion initiative first announced by President Bush in his 2003 State of the Union Address, which was undertaken to fight the international HIV/AIDS pandemic.
For more information on Atripla, including full prescribing information, a question-and-answer sheet, and an FDA fact sheet, visit fda.gov/cder/drug/infopage/atripla/default.htm.
July 10, 2006
ST. LOUIS (MD Consult) - On June 30, 2006, the US Food and Drug Administration (FDA) approved Lucentis (ranibizumab injection) for the treatment of neovascular (ie, wet) age-related macular degeneration (AMD). Lucentis is the first treatment that, when dosed monthly, can maintain the vision of more than 90% of patients with this type of AMD. Lucentis is a new molecular entity, meaning it contains an active substance that has never before been approved for marketing in any form in the United States.
"This approval is of great importance for the 155,000 Americans who are diagnosed each year with AMD, a common cause of severe and irreversible vision loss in older adults," said Dr Andrew von Eschenbach, Acting Commissioner of Food and Drugs. "At a time when our elderly population is rapidly increasing, this product preserves quality of life for those affected by this disease, helping them to regain the ability to participate in everyday activities such as reading and driving."
AMD, a retinal disease causing severe and irreversible vision loss, is a major cause of blindness in persons older than 55 years. Untreated, the majority of eyes affected with neovascular AMD may become functionally impaired. Neovascular AMD, which accounts for 10% of all AMD, is responsible for 80% of the associated vision loss.
The vision loss in neovascular AMD is caused by the growth of abnormal leaky blood vessels that eventually damage the area of the eye responsible for central vision. Lucentis is designed to block new blood vessel growth and leakiness, which ultimately lead to disease progression and such vision loss.
Lucentis, a biologic product, is administered by injection into the eye. It was shown to be safe and clinically effective in 3 multicenter, randomized studies of patients representative of the population usually affected with AMD. In clinical trials, nearly 95% of the participants who received a monthly injection maintained their vision at 12 months compared with approximately 60% of patients who received the control treatment.
Approximately one third of patients in these trials had improved vision at 12 months. In a single study carried out for 24 months, these findings have been maintained with continued monthly dosing. The most commonly reported adverse events included conjunctival hemorrhage, eye pain, floaters, increased eye pressure, and inflammation of the eye. Serious adverse events were rare and often related to the injection procedure, including endophthalmitis, intraocular inflammation, retinal detachment, retinal tear, increased eye pressure, and traumatic cataract.
Lucentis is manufactured by Genentech, Inc, in South San Francisco, California. For more details, including full prescribing information, visit lucentis.com.
July 7, 2006
ST. LOUIS (MD Consult) - On June 19, 2006, Endo Pharmaceuticals Inc announced the commercial availability of Synera (lidocaine 70 mg and tetracaine 70 mg), a topical anesthetic patch approved by the US Food and Drug Administration on June 23, 2005. Synera is the first self-contained topical patch for prevention of pain associated with superficial venous access and superficial dermatologic procedures in patients aged 3 years and older.
According to published data, children under the age of 15 are hospitalized for an estimated 11.5 million days annually. Hospitalized children are routinely subjected to multiple superficial venous access procedures such as intravenous infusions and blood draws. In a joint statement issued in 2001, the American Academy of Pediatrics and the American Pain Society acknowledged that a substantial number of children are undertreated for their pain, and they underscored the responsibility of physicians to "ensure humane and competent treatment of pain and suffering."
The Synera patch is indicated for local dermal analgesia and consists of a thin, uniform, local anesthetic formulation with an integrated, oxygen-activated heating component that is intended to enhance the delivery of the local anesthetic. An Endo spokesperson described Synera as having a "two-step, peel-and-stick application, with a familiar, Band-Aid–like appearance." The recommended application time for the patch is 20 to 30 minutes.
Synera is indicated for use on intact skin to provide local dermal analgesia for superficial venous access and superficial dermatologic procedures such as excision, electrodessication, and shave biopsy of skin lesions. Synera is contraindicated in patients with a known history of sensitivity to lidocaine, tetracaine, local anesthetics of the amide or ester type, hypersensitivity to paraaminobenzoic acid, or sensitivity to any other component of the product. Synera should not be used for a longer duration than recommended.
The simultaneous or sequential application of multiple Synera patches is not recommended. Contact with the eyes should be avoided. During or immediately after treatment with this patch, the skin at the site of treatment may develop erythema, blanching, edema, or abnormal sensation. In clinical studies, the most common local reactions were erythema (71%), blanching (12%), and edema (12%). These reactions were generally mild, resolving spontaneously after treatment.
For full prescribing information, visit synera.com.
Effective immediately, Endo will begin marketing the Synera patch in the institutional setting. To read more about the manufacturer, visit endo.com.
June 30, 2006
ST. LOUIS (MD Consult) - On June 29, 2006, the US Food and Drug Administration (FDA) granted accelerated approval for Sprycel (dasatinib), a new oral treatment for patients with chronic myeloid leukemia (CML), a rare cancer characterized by the uncontrolled growth of white blood cells. In addition, the FDA granted regular approval to Sprycel for use in the treatment of adults who have Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph + ALL), a more serious form of leukemia. Both approvals are for patients who have experienced resistance or intolerance to prior therapy.
Sprycel is intended for patients with CML who are no longer responding to, or who can no longer tolerate, therapy with Gleevec (imatinib), a drug approved in 2001 for this life-threatening disease. This new treatment option works by reducing the activity of one or more proteins responsible for the uncontrolled growth of the leukemia cells. Treatment with Sprycel has been shown to reduce, and in some cases eliminate, detectable leukemia cells in the blood and bone marrow of patients with CML. As provided for under FDA accelerated approval regulations, studies are underway to demonstrate that these improved white blood cell counts also result in clinical benefit such as improved survival or improvement in leukemia-related symptoms.
"Sprycel offers an important alternative for patients with Ph + ALL whose disease has not responded to or has stopped responding to other therapies," said Dr Steven Galson, director of FDA's Center for Drug Evaluation and Research. "Although the long-term benefits of Sprycel in CML are not yet known, early studies have suggested that Sprycel may offer a significant improvement for many patients whose disease is resistant to other therapies; however, further data from ongoing studies are needed to evaluate whether Sprycel provides an actual clinical benefit in CML."
Sprycel is considered an orphan drug for each of these indications. Under the Orphan Drug program, sponsors of medications intended for fewer than 200,000 patients in the United States can receive 7-year marketing exclusivity, tax credit for the product-associated clinical research, research design assistance by the FDA, and grants of up to $200,000 per year.
The approval of Sprycel is based on evidence from 4 single-arm studies of more than 400 patients who were no longer responsive to or tolerant of treatment with Gleevec. The efficacy of Sprycel was determined by response rate, defined as the percentage of patients in whom treatment resulted in the elimination of detectable leukemia cells or a significant reduction in the number of leukemia cells.
Responses were measured primarily in the bone marrow for patients with the earliest stage of disease and in the blood for patients with later-stage disease. For patients with the earliest stage of CML (chronic phase), treatment with Sprycel resulted in response in 45% of patients. Response rates for patients with advanced phases of CML and for Ph + ALL ranged from 31% to 59%. Most patients who had a response to Sprycel still had a response 6 months after they began taking Sprycel.
Adverse effects reported in these trials included fluid retention, bleeding, diarrhea, skin rash, infections, headache, fatigue, and nausea. Sprycel also frequently caused anemia, neutropenia, and thrombocytopenia. Sprycel is manufactured by Bristol-Myers Squibb Company, Princeton, NJ.
According to Bristol-Myers Squibb, Sprycel is not recommended for use in pregnant women, nor those contemplating pregnancy, because the drug may cause fetal harm. They recommend that sexually active men and women taking Sprycel use adequate contraception. In addition, women who are taking Sprycel should avoid breastfeeding.
For full prescribing information, visit the Bristol-Myers Squibb Web site.
June 27, 2006
ST. LOUIS (MD Consult) - On June 23, 2006, the US Food and Drug Administration (FDA) approved Prezista (darunavir), a new drug for adults whose infection with the human immunodeficiency virus (HIV) has not responded to treatment with other antiretroviral drugs. Prezista, a new HIV protease inhibitor, is approved for coadministration with low-dose ritonavir and other active anti-HIV agents. Ritonavir, a protease inhibitor approved in 1996, slows the breakdown of Prezista in the body, thereby increasing the concentration of Prezista in a patient’s system.
The accelerated approval was based on evidence from 2 randomized, controlled studies comparing the safety and effectiveness of a Prezista–ritonavir combination with other ritonavir–boosted protease inhibitor combinations. Patients in both arms of the trials also used other anti-HIV agents (nucleoside reverse transcriptase inhibitors) with or without enfuvirtide, a fusion inhibitor that interferes with the entry of the virus into cells.
In these studies, patients taking a Prezista–ritonavir combination experienced higher rates of reduction of their HIV viral load compared with patients on other ritonavir–boosted protease inhibitor combinations. Seventy percent of treatment-experienced patients achieved a virologic response with Prezista–ritonavir in combination compared with 21% of patients in the control group at week 24.
The most common adverse effects reported by patients taking the Prezista–ritonavir regimen included diarrhea, nausea, and headache. About 7% of patients receiving this combination therapy experienced skin rashes ranging from mild to serious.
The risks and benefits of Prezista have not been established for adults who have not been previously treated for HIV, nor for children.
As a condition of the accelerated approval, the manufacturer is required to conduct postmarketing trials to verify and describe the clinical benefits of Prezista. Other postmarketing studies that the manufacturer has committed to conduct include studies in pediatric populations, studies to better define certain drug–drug interactions, and studies to evaluate the drug in patients with varying degrees of liver impairment to identify appropriate dosing for this patient population.
Patients are advised to take Prezista and ritonavir with food and to not use the combination therapy together with St. John’s wort or various other drugs, including certain anticonvulsants, antihistamines, sedatives, and a few of the protease inhibitors.
Prezista is manufactured for Tibotec, Inc, a division of Ortho Biotech Products, LP, Raritan, NJ, by JOLL, Gurabo, Puerto Rico.
June 9, 2006
ST. LOUIS (MD Consult) - The US Food and Drug Administration (FDA) announced on June 8, 2006, the approval of Gardasil (quadrivalent human papillomavirus [HPV] recombinant vaccine), the first vaccine developed to prevent cervical cancer, precancerous genital lesions, and genital warts caused by HPV types 6, 11, 16, and 18. The vaccine is approved for use in females aged 9 to 26 years. Gardasil was evaluated and approved in 6 months under FDA’s priority review process, which is engaged for products with potential to provide significant health benefits.
HPV is the most common sexually transmitted infection in the United States. The Centers for Disease Control and Prevention estimates that about 6.2 million Americans become infected with genital HPV each year and that more than half of all sexually active men and women become infected at some time in their lives. On average, there are 9,710 new cases of cervical cancer and 3,700 deaths attributed to it in the United States each year, according to the FDA. Worldwide, cervical cancer is the second most common cancer in women and is estimated to cause over 470,000 new cases and 233,000 deaths each year.
For most women, the body's own defense system will clear the virus and infected women do not develop related health problems. However, some HPV types can cause abnormal cells to develop on the lining of the cervix that years later can turn into cancer. Other HPV types can cause genital warts. The new vaccine is effective against HPV types 16 and 18, which cause approximately 70% of cervical cancers, and against HPV types 6 and 11, which cause approximately 90% of genital warts.
Gardasil is a recombinant vaccine that is given as 3 injections over a 6-month period. Immunization with Gardasil is expected to prevent most cases of cervical cancer caused by HPV types included in the vaccine. However, females are not protected if they have been infected with that HPV type(s) before vaccination, indicating the importance of immunization before potential exposure to the virus. Also, Gardasil does not protect against less common HPV types not included in the vaccine, thus routine and regular Papanicolaou screening remain critically important to detect precancerous changes in the cervix to allow treatment before cervical cancer develops.
Four studies—1 in the United States and 3 multinational—were conducted in 21,000 women between the ages of 16 and 26. Participants were given either the vaccine or placebo. The results showed that in women who had not already been infected, Gardasil was nearly 100% effective in preventing precancerous cervical lesions, precancerous vaginal and vulvar lesions, and genital warts caused by infection with the HPV types against which the vaccine is directed. Although the study period was not long enough for cervical cancer to develop, the prevention of these cervical precancerous lesions is believed highly likely to result in the prevention of those cancers.
Two studies were also performed to measure the immune response to the vaccine among girls aged 9 to 15 years. Their immune response was as good as that found in 16- to 26-year-olds, indicating that the vaccine should have similar effectiveness when used in the 9- to 15-year age group.
The safety of the vaccine was evaluated in approximately 11,000 persons. Most adverse experiences in study participants who received Gardasil included mild or moderate local reactions, such as pain or tenderness at the site of injection.
The manufacturer, Merck & Co, Inc, has agreed to conduct several studies after licensure, including additional studies to further evaluate general safety and long-term effectiveness. The manufacturer will also monitor the pregnancy outcomes of women who receive Gardasil while unknowingly pregnant. Also, Merck has an ongoing study to evaluate the safety and effectiveness of Gardasil in males.
For more information on the Gardasil approval, visit fda.gov/cber/products/hpvmer060806.htm. Full prescribing information is available on the Merck Web site.
To learn more about HPV, read the FDA's Office of Women's Health’s fact sheet at fda.gov/womens/getthefacts/hpv.html.
June 1, 2006
ST. LOUIS (MD Consult) - On May 30, 2006, the US Food and Drug Administration (FDA) approved Sandoz, Inc's Omnitrope (somatropin [rDNA origin]) for long-term treatment of pediatric patients who have growth failure caused by an inadequate secretion of endogenous growth hormone, and for long-term replacement therapy in adults with growth hormone deficiency (GHD) of either childhood or adult onset.
Omnitrope is a recombinant human growth hormone product that has been categorized by the FDA as a follow-on protein product. This term generally refers to protein and peptide products that are intended to be sufficiently similar to a product already approved or licensed to permit the applicant to rely for approval on certain existing scientific knowledge about the safety and effectiveness of the approved protein product.
In vitro, preclinical, and clinical tests have demonstrated that somatropins are therapeutically equivalent to human growth hormone of pituitary origin and achieve similar pharmacokinetic profiles in normal adults. In pediatric patients who have GHD, treatment with somatropin stimulates linear growth and normalizes concentrations of insulin-like growth factor I (IGF-I). In adults with GHD, treatment with somatropin results in reduced fat mass, increased lean body mass, metabolic alterations that include beneficial changes in lipid metabolism, and normalization of IGF-I concentrations.
Omnitrope should not be used when there is any evidence of neoplastic activity. Intracranial lesions must be inactive and antitumor therapy complete before therapy begins. Treatment with Omnitrope should be discontinued if there is evidence of tumor growth.
Growth hormone should not be used for growth promotion in pediatric patients with fused epiphyses, nor should it be used to treat patients with acute critical illness attributable to complications after open heart or abdominal surgery, patients who have sustained multiple accidental traumas, nor patients having acute respiratory failure. Two placebo-controlled trials in non–growth hormone deficient adult patients with these conditions revealed a significant increase in mortality among somatropin-treated patients compared with those receiving placebo.
Therapy with growth hormone is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment.
For more information, including full text of the Omnitrope drug label and details about the process of securing FDA approval of a follow-on product, visit fda.gov/cder/drug/infopage/somatropin/default.htm.
May 31, 2006
ST. LOUIS (MD Consult) - CollaGenex Pharmaceuticals, Inc, announced on May 30, 2006, that the US Food and Drug Administration (FDA) has approved Oracea (doxycycline) for the treatment of papules and pustules of rosacea in adult patients. Oracea is the first FDA-approved, orally administered, systemically delivered drug to treat rosacea.
Rosacea primarily affects the face and is characterized by the appearance of papules and pustules, erythema, and telangiectasia. If allowed to progress to a moderate to severe condition, rosacea can cause itching, pain, and thickening of the skin. Approximately 14 million adults in the United States have this dermatologic condition.
Oracea is a 40-mg capsule formulation dosed once a day that contains a combination of immediate and delayed-release beads. The FDA granted its approval primarily on the basis of the safety and efficacy results of 2 phase III, double-blind, placebo-controlled clinical trials. These studies enrolled a total of 537 patients in 28 centers across the United States. In the 2 studies, patients receiving Oracea experienced a 61% and 46% mean reduction in inflammatory lesions compared with 29% and 20% mean reduction, respectively, in patients receiving placebo. The differences were clinically and statistically highly significant (P < 0.001 in each study). Adverse effects of the drug were similar to those experienced with placebo.
CollaGenex plans to make Oracea available beginning in July 2006. For additional information, visit collagenex.com.
May 30, 2006
ST. LOUIS (MD Consult) - Barr Pharmaceuticals, Inc, announced on May 25, 2006, that the US Food and Drug Administration (FDA) has approved Duramed Pharmaceuticals, Inc’s new drug application for Seasonique (levonorgestrel/ethinyl estradiol tablets 0.15 mg/0.03 mg and ethinyl estradiol tablets 0.01 mg) extended-cycle oral contraceptive for the prevention of pregnancy.
Under the Seasonique extended-cycle regimen, women take active tablets of 0.15 mg of levonorgestrel/0.03 mg of ethinyl estradiol for 84 consecutive days, followed by 7 days of 0.01 mg of ethinyl estradiol. The regimen is designed to reduce the number of withdrawal bleeding periods from monthly to 4 per year. The clinical data supporting the Seasonique application resulted from 1 large pivotal randomized, open-label, multicenter trial and 1 supportive randomized, open-label, multicenter trial, both of which ended in April 2004. The trials involved approximately 2,500 female patients between the ages of 18 and 40 years at 43 sites in the United States. Patients were enrolled in the pivotal trial for the duration of 12 months (four 91-day cycles).
It is estimated that more than 16 million women currently take oral contraceptives in the United States. Serious as well as minor adverse effects have been reported with the use of hormonal contraceptives, including blood clots, stroke, and heart attack. Cigarette smoking increases the risk of serious cardiovascular adverse effects, especially in women older than 35 years. Oral contraceptives do not protect against infection with the human immunodeficiency virus nor other sexually transmitted diseases.
Seasonique will be available by prescription to women in July 2006. For more information, including full prescribing information, visit seasonique.com.
May 24, 2006
ST. LOUIS (MD Consult) - Alza Corporation announced on May 23, 2006, that the US Food and Drug Administration has approved Ionsys (fentanyl iontophoretic transdermal system), the first needle-free, patient-activated analgesic system. The new medication is indicated for the short-term management of acute postoperative pain in adults requiring opioid analgesia during hospitalization.
Ionsys uses iontophoresis, a process in which a low-intensity electric field (generally imperceptible to the patient) is used to rapidly transport fentanyl across the skin and into the circulatory system of the body. The Ionsys system securely adheres to the upper outer arm or chest. When pain medication is needed, the patient double-clicks the dosing button, which delivers a pre-programmed, 40-mcg dose of fentanyl through the skin. Each dose is delivered over a 10-minute period. More than one Ionsys system should not be applied to a patient at the same time.
Fentanyl is a potent opioid agonist and a schedule II controlled substance with high potential for abuse similar to that of hydromorphone, methadone, morphine, and oxycodone. Fentanyl can be abused in a manner similar to other opioid agonists, legal or illicit. Health care professionals who are concerned about an increased risk of misuse, abuse, or diversion should consider this risk when prescribing or dispensing Ionsys. After the maximum dosage administration, a significant amount of fentanyl remains in the device. Ionsys should be prescribed only by persons knowledgeable in the administration of potent opioids and in the management of patients receiving potent opioids for treatment of pain. Patients treated with Ionsys should be under the supervision of medical personnel with expertise in the detection and management of hypoventilation, including airway management and the use of opioid antagonists.
Patients should be titrated to an acceptable level of analgesia before initiating treatment with Ionsys. Ionsys should be applied to intact, nonirritated, nonirradiated skin on the chest or upper outer arm. Patients must have access to supplemental analgesia.
Ionsys is not intended for home use and should only be used for the treatment of hospitalized patients. Treatment with this medication should be discontinued before patients are discharged from the hospital, and before discharge, medical personnel must remove the Ionsys system and dispose of it properly.
The use of fentanyl may result in potentially life-threatening respiratory depression and death. To avoid potential overdosing, only the patient should activate Ionsys dosing. Inappropriate use of Ionsys leading to ingestion or contact with mucous membranes or unintended exposure to the fentanyl hydrogel could lead to the absorption of a potentially fatal dose of fentanyl. Therefore, the hydrogels should not come into contact with the fingers or mouth.
If the fentanyl hydrogel becomes separated from the Ionsys system, contact can be harmful to humans and animals. If this happens during system removal, gloves or tweezers should be used to remove the hydrogel from the skin and properly dispose of the material in accordance with state and federal regulations for controlled substances. The skin area that had been in contact with the hydrogel should be thoroughly flushed with water. Soap, alcohol, or other solvents should not be used to remove the hydrogel because they may enhance the drug's ability to penetrate the skin. In the event that the Ionsys system falls off, the entire Ionsys system (ie, with hydrogel) should be collected and properly disposed of.
Because serum fentanyl concentrations decline gradually after system removal, patients who have experienced serious adverse events, including overdose, will require continued monitoring after the removal of Ionsys.
Ionsys is not recommended for patients under the age of 18 years and should always be kept out of reach of children. In addition, the medication is contraindicated in patients with known hypersensitivity to fentanyl, cetylpyridinium chloride (eg, Cepacol), or any components of the Ionsys system.
Three placebo-controlled trials and 4 active comparator trials versus intravenous patient-controlled analgesia morphine were used to investigate 2,114 patients treated with Ionsys (40-mcg dose). Regardless of relationship to study medication, the most common adverse events (>10%) were nausea, vomiting, application site reaction-erythema, fever, and headache.
To obtain a copy of the full prescribing information for Ionsys, contact the Ortho-McNeil Janssen Customer Communications Center at 1-800-526-7736.
May 30, 2006
ST. LOUIS (MD Consult) - On May 26, 2006, Merck & Co, Inc, announced that the US Food and Drug Administration (FDA) has approved the new vaccine Zostavax (zoster vaccine live) for the prevention of herpes zoster in persons 60 years of age and older.
Herpes zoster, also known as shingles, is a frequently painful disease marked by a blistering rash. Caused by the reactivation of the virus that causes chickenpox, shingles can lead to severe complications including postherpetic neuralgia, which can last for months or even years.
Zostavax, the first drug approved for the prevention of shingles, is not a treatment for shingles or postherpetic neuralgia. Zostavax is given as a single dose by injection. As with any vaccine, vaccination with Zostavax may not result in protection of all vaccine recipients.
Anyone who has been infected with chickenpox (ie, more than 90% of adults in the United States) is at risk for developing shingles. The incidence and severity of shingles, as well as the frequency and severity of its complications, increase with age. Approximately 40% to 50% of the estimated 1 million cases of shingles that occur in the United States each year occur in persons age 60 and older. Shingles can occur without warning at any time.
Shingles usually starts as an unusual or painful sensation on 1 side of the body or face, followed by a blistering rash. Pain from shingles can be mild to severe and may occur just before the development of the rash, during the eruption of the rash, and as long-term nerve pain. Postherpetic neuralgia has been described as tender, burning, throbbing, stabbing, shooting or sharp pain. Other complications, such as scarring, allodynia, pneumonia, visual impairment, and hearing loss also can occur as the result of shingles. Treating shingles and postherpetic neuralgia can be difficult, often requiring a multifaceted approach.
Zostavax is contraindicated in persons with a history of anaphylactic/anaphylactoid reaction to gelatin, neomycin, or any other component of the vaccine; persons with a history of primary or acquired immunodeficiency states including leukemia, lymphomas of any type, or other malignant neoplasms affecting the bone marrow or lymphatic system; persons with acquired immunodeficiency syndrome or other clinical manifestations of infection with human immunodeficiency viruses; and persons with active untreated tuberculosis. Zostavax is also contraindicated in persons receiving immunosuppressive therapy, including high-dose corticosteroids, and in women who are or may be pregnant.
Vaccination with a live, attenuated vaccine, such as Zostavax, may result in a more extensive vaccine-associated rash or disseminated disease in immunosuppressed persons. Safety and efficacy of Zostavax have not been evaluated in persons receiving immunosuppressive therapy, nor in persons receiving daily topical or inhaled corticosteroids or low-dose oral corticosteroids. The use of Zostavax in persons with a previous history of shingles has not been studied.
The approval of Zostavax is was made on the basis of studies of more than 40,000 persons, more than 21,000 of whom received active vaccine. The efficacy and safety of a single dose of Zostavax was evaluated in the largest of these studies, the landmark Shingles Prevention Study (SPS), which involved 38,546 men and women aged 60 years and older who had no previous history of shingles. In this randomized, double-blind, placebo-controlled study, participants were randomly assigned to groups given either Zostavax (n = 19,270) or placebo (n = 19,276) and were followed up for the development of shingles for a median duration of 3.1 years. All subjects with clinically diagnosed shingles were offered antiviral treatment, as well as standard-of-care treatment for pain, as necessary.
Zostavax significantly (P < .001) reduced the risk of developing shingles compared with placebo by 51% in the SPS. Specifically, 315 cases of shingles occurred (5.4 cases per 1,000 person-years) among persons taking Zostavax versus 642 cases (11.1 cases per 1,000 person-years) among those taking placebo. The efficacy of Zostavax for the prevention of shingles was highest for those 60 to 69 years of age and declined with increasing age.
Overall, the benefit of Zostavax in the prevention of postherpetic neuralgia from shingles can be primarily attributed to the vaccine's effect on the prevention of shingles. Vaccination with Zostavax reduced the incidence of long-term nerve pain from shingles in persons 70 years of age and older who were vaccinated with Zostavax but went on to develop shingles. After completion of the SPS, a separate analysis was conducted to evaluate the reduction in postherpetic neuralgia in the group of persons who had been vaccinated with Zostavax but who had developed shingles. In the analysis, Zostavax reduced the overall incidence of postherpetic neuralgia by a statistically significant 39% compared with the placebo group. A statistically significant reduction in postherpetic neuralgia was seen in persons aged 70 to 79 years (55%) and a nonstatistically significant reduction in postherpetic neuralgia was seen in those aged 60 to 69 years (5%) and 80 and older (26%) in the analysis.
In the Adverse Event Monitoring Study (AEMS), which included a subgroup of persons from the SPS, vaccine-related injection site and systemic adverse events seen in the first 42 days after vaccination in 1% or more of the persons who received Zostavax (n = 3,345) included headache (1.4%) and the following injection-site reactions: erythema (33.7%), pain/tenderness (33.4%), swelling (24.9%), hematoma (1.4%), pruritus (6.6%), and warmth (1.5%). Most of these adverse experiences were reported as mild in intensity.
In the overall study population in the SPS, serious adverse experiences occurred at a similar rate (1.4%) in subjects vaccinated with Zostavax or placebo. In the AEMS, the rate of serious adverse events was increased in the group who received Zostavax (1.9%) compared with the placebo group (1.3%) in the first 42 days after vaccination. Investigator-determined, vaccine-related serious adverse experiences were reported for 2 subjects vaccinated with Zostavax (ie, asthma exacerbation and polymyalgia rheumatica) and 3 subjects who received placebo (ie, Goodpasture's syndrome, anaphylactic reaction, and polymyalgia rheumatica).
In the entire SPS study population, the rates of overall cardiovascular events (0.4%) including coronary artery disease–related conditions (0.2%) were similar in subjects vaccinated with Zostavax or placebo. In the AEMS of the SPS, in the first 42 days after vaccination, the rate of overall cardiovascular events was higher after Zostavax was taken (0.6%) than after placebo (0.4%), including the rate of coronary artery disease–related conditions (Zostavax, 0.3%; placebo, 0.2%).
Patients should be informed of the theoretical risk of transmitting the vaccine virus to close contacts (including household contacts) who may be pregnant and have not had chickenpox nor been vaccinated against chickenpox, or contacts who have problems with their immune system. The risk of transmitting the attenuated vaccine virus to a susceptible person should be weighed against the risk of developing natural shingles that could be transmitted to a susceptible person.
The duration of protection after vaccination with Zostavax is unknown. In the SPS, protection with Zostavax was demonstrated through 4 years of follow-up. The need for revaccination has not been defined. Zostavax is not a substitute for Varivax (varicella virus vaccine live), and Zostavax should not be used in children.
Concurrent administration of Zostavax and antiviral medications known to be effective against the varicella zoster virus has not been evaluated. Concurrent administration of Zostavax and other vaccines has also not been evaluated.
For more information on Zostavax, including full prescribing information, visit zostavax.com.
May 18, 2006
ST. LOUIS (MD Consult) - On May 17, 2006, the US Food and Drug Administration (FDA) approved Azilect (rasagiline), a new molecular entity, for the treatment of Parkinson’s disease. The drug is a monoamine oxidase type B inhibitor that blocks the breakdown of dopamine, a chemical that sends information to the parts of the brain that control movement and coordination.
Parkinson’s disease is a chronic, progressive neurodegenerative condition caused by the destruction of the brain cells that produce dopamine. As the level of this chemical declines, messages from the brain telling the body how and when to move are delivered more slowly, leaving a person incapable of initiating and controlling movements in a normal way. More than 50,000 Americans are diagnosed with Parkinson's disease annually, according to the FDA’s Center for Drug Evaluation and Research.
Azilect, manufactured by Teva Pharmaceutical Industries in Tel Aviv, Israel, is approved for use as an initial single drug therapy in early stages of Parkinson’s disease and as an addition to levodopa in more advanced cases. Levodopa is a standard treatment for Parkinson’s disease. The safety and effectiveness of Azilect was demonstrated in three 18- to 26-week controlled clinical trials.
One of the studies compared the effects of Azilect with the effects of placebo in 404 patients with early Parkinson’s disease. Compared with patients taking placebo, the condition of patients taking Azilect showed significantly less worsening on a rating scale that measures the ability to perform mental and motor tasks as well as daily living activities.
The other 2 studies compared the effects of Azilect with placebo when taken together with levodopa by more than 1,100 patients with more advanced Parkinson’s disease. In these studies, patients using Azilect together with levodopa had significantly less time per day with relatively poor function and mobility compared with patients taking levodopa and placebo.
Azilect may be associated with hypertensive crisis if patients also ingest amines contained in many cough/cold medications or consume tyramine-rich foods (eg, cheese), beverages (eg, red wine), or dietary supplements. Therefore, patients will need to avoid these sources of amines and tyramine when taking Azilect. As with most other medications taken to treat Parkinson’s disease, Azilect has the potential to cause dyskinesias, hallucinations, and lowered blood pressure. These adverse effects are described in the product labeling.
During development, melanoma was diagnosed in a small number of patients treated with Azilect. Although the FDA has concluded that the available data do not establish that Azilect is associated with an increased risk for melanoma, it appears that compared with the general population, patients with Parkinson’s disease have an increased risk for this form of skin cancer. To address the question of whether Azilect itself increases such risk, the drug’s manufacturer will perform a phase 4 (postmarket) study. The product labeling will recommend that patients undergo periodic dermatologic examinations.
For more information, visit azilect.com.
May 16, 2006
ST. LOUIS (MD Consult) - Valeant Pharmaceuticals International announced on May 16, 2006, that the US Food and Drug Administration has granted marketing approval for Cesamet (CII) (nabilone) oral capsules. Cesamet is used to treat nausea and vomiting associated with cancer chemotherapy in patients whose conditions have not responded adequately to conventional antiemetic treatments.
Cesamet is a synthetic cannabinoid that is thought to act as an omnineuromodulator that interacts with the cannabinoid receptor CB1, which is present throughout the nervous system. This receptor is involved in regulating nausea and vomiting. Because of this omnineuromodulation, the mechanism of action for Cesamet is significantly different from conventional antiemetics. Cesamet has a long duration of action that allows for less frequent dosing, typically twice daily.
The American Cancer Society estimates that there will be nearly 1.4 million new cases of cancer in 2006. Approximately 70% to 80% of all patients receiving chemotherapy experience chemotherapy-induced nausea and vomiting. Although the use of antiemetic agents decreases the incidence and severity of chemotherapy-induced nausea and vomiting, symptoms continue to occur in 40% to 60% of patients.
Cesamet was evaluated for its effectiveness and safety in the treatment of nausea and vomiting induced by cancer chemotherapy in patients receiving a wide variety of chemotherapy regimens, including low-dose cisplatin (20 mg/m2) in both placebo-controlled and active controlled (prochlorperazine) trials. Efficacy and safety results were derived from 11 well-controlled antiemetic, double-blind, crossover studies with optional continuation into Cesamet open-label therapy. Either prochlorperazine or placebo was used as the comparator. The prochlorperazine-controlled studies consisted of 2 flexible-dose crossover studies (n = 143 patients, of which 112 were evaluable for efficacy) and 3 fixed-dose crossover studies (n = 126 patients, of which 73 patients were evaluable for efficacy). The placebo-controlled studies were 6 fixed-dose crossover studies (n = 199 patients, of which 129 were evaluable for efficacy). The crossover studies comprised 2 cycles of cancer treatment: Cesamet in one cycle and control drug in the other. The order of cycles for each patient was randomized. The most frequent dose regimen of nabilone was 2 mg twice-a-day, except in the 2 flexible-dose studies, where Cesamet daily doses of over 4 mg were frequent. Efficacy was evaluated by comparing the number of vomiting incidents and the severity of nausea.
All statistical comparisons significantly favored nabilone, with the exception of 1 prochlorperazine-controlled flexible-dose study. However, even in this study, nabilone had a lower overall average frequency of vomiting episodes and a lower average severity of nausea score than prochlorperazine.
Cesamet, a synthetic cannabinoid similar to the active ingredient found in naturally occurring Cannabis sativa L (marijuana; delta-9-THC), is contraindicated in any patient who has a history of hypersensitivity to any cannabinoid. Patients receiving treatment with Cesamet should be specifically warned not to drive, operate machinery, or engage in any hazardous activity while taking Cesamet.
During controlled clinical trials of Cesamet, virtually all patients experienced at least 1 adverse reaction. The most commonly encountered events were drowsiness, vertigo, dry mouth, euphoria, ataxia, headache, and concentration difficulties. Cesamet should not be taken with alcohol, sedatives, hypnotics, or other psychoactive substances because these substances can potentiate the central nervous system effects of nabilone. Because Cesamet can elevate supine and standing heart rates and can cause postural hypotension, it should be used with caution in elderly persons and in patients with hypertension or heart disease. Cesamet should also be used with caution in patients with current or previous psychiatric disorders (including manic depressive illness, depression, and schizophrenia) because the symptoms of these disease states may be revealed by the use of cannabinoids. Caution must be used when administering Cesamet in combination with any central nervous system depressant.
Cesamet should be used with caution in patients with a history of substance abuse, including alcohol abuse or dependence and marijuana use, because Cesamet is similar to the active ingredient found in naturally occurring marijuana. Cesamet should be used with caution in pregnant patients, nursing mothers, or pediatric patients because it has not been studied in these patient populations.
Valeant currently sells Cesamet in Canada. The company anticipates launch of Cesamet in the several weeks following approval.
For more information, contact Valeant Pharmaceuticals International at 1-877-361-2719 or visit valeant.com.
May 12, 2006
ST. LOUIS (MD Consult) - On May 11, 2006, the US Food and Drug Administration (FDA) approved Chantix (varenicline tartrate) tablets to help cigarette smokers stop smoking. The active ingredient is a new molecular entity that received a priority FDA review because of its significant potential benefit to public health.
Chantix, which is manufactured and distributed by Pfizer, Inc, acts at sites in the brain affected by nicotine and may help those who wish to give up smoking in 2 ways: by providing some nicotine effects to ease the withdrawal symptoms, and by blocking the effects of nicotine from cigarettes if persons taking the medication resume smoking.
"Tobacco use, particularly cigarette smoking, is the single most preventable cause of death in the United States and is responsible for a growing list of cancers as well as chronic diseases including those of the lung and heart," said Scott Gottlieb, MD, Deputy Commissioner for Medical and Scientific Affairs at the FDA. According to the Centers for Disease Control and Prevention, an estimated 44.5 million adults in the United States smoke cigarettes, and more than 8.6 million of them have at least 1 serious illness caused by smoking.
The effectiveness of Chantix in smoking cessation was demonstrated in 6 clinical trials, which included a total of 3,659 chronic cigarette smokers who were treated with varenicline. Five of the 6 studies were randomized, controlled clinical trials in which Chantix was shown to be superior to placebo in helping people quit smoking. These smokers had previously averaged 21 cigarettes a day for approximately 25 years. In 2 of the 5 placebo-controlled studies, Chantix-treated patients were also more successful in giving up smoking than patients treated with Zyban (bupropion).
The approved course of Chantix treatment is 12 weeks. Patients who successfully quit smoking during Chantix treatment may continue with an additional 12 weeks of Chantix treatment to further increase the likelihood of long-term smoking cessation.
In clinical trials, the most common adverse effects of Chantix were nausea, headache, vomiting, flatulence, insomnia, abnormal dreams, and dysgeusia.
For more information on Chantix, including full prescribing information, visit chantix.com.
May 9, 2006
ST. LOUIS (MD Consult) - Medicis announced on May 8, 2006, that the US Food and Drug Administration (FDA) has approved its new drug application for Solodyn (minocycline hydrocholride) extended-release tablets. Solodyn is the only oral minocycline approved for once-daily dosage in the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients aged 12 years and older.
Solodyn is lipid soluble, and its mode of action occurs in the skin and sebum. Solodyn is not bioequivalent to any other minocycline products and is in no way interchangeable with other forms of minocycline.
On the basis of extensive multiyear clinical trials conducted by Medicis in which over 1,000 patients participated, the recommended dosage for Solodyn is 1 mg/kg daily. In Medicis-sponsored studies, higher doses of minocycline were tested against Solodyn, and these did not show additional therapeutic benefits in the treatment of inflammatory lesions of acne. These higher doses, consistent with traditional minocycline use, may actually be associated with more acute vestibular adverse effects, the company stated.
In 2005, patients with acne collectively paid more than 7.5 million visits to physicians. More than 5 million prescriptions were written by dermatologists for minocycline, doxycycline, and/or tetracycline. Less than 20% of the 5 million prescriptions were written for branded products.
Solodyn, manufactured by AAIPharma Inc in Wilmington, NC, is available by prescription in extended-release tablet dosages of 45, 90, and 135 mg.
The most commonly reported adverse effects associated with the use of Solodyn were headache, fatigue, dizziness, and pruritus. Central nervous system adverse effects, including light-headedness, dizziness, and vertigo, have been reported with minocycline therapy but were not significant in Solodyn clinical investigations. In rare cases, photosensitivity has been reported. This medication should not be used during pregnancy nor by persons of either sex who are attempting to conceive a child. Concurrent use of tetracyclines with oral contraceptives may render oral contraceptives less effective. Solodyn is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines. Safety beyond 12 weeks of use has not been established.
Full prescribing information for Solodyn can be obtained on the Medicis Web site at medicis.com/products/pi/pi_solodyn.pdf. For more information about Solodyn, visit solodyn.com.
May 3, 2006
ST. LOUIS (MD Consult) - On May 3, 2006, the US Food and Drug Administration (FDA) approved Dacogen (decitabine) injection for the treatment of myelodysplastic syndromes (MDS). Dacogen is a new molecular entity that received orphan drug status. Orphan products are developed to treat rare diseases or conditions that affect fewer than 200,000 people in the United States. The Orphan Drug Act provides a 7-year period of exclusive marketing to the first sponsor that obtains marketing approval for a designated orphan drug.
Patients with MDS have bone marrow that does not produce enough mature blood cells. This causes a lack of healthy blood cells that can function properly in the body. Dacogen is thought to work by promoting normal development of blood cells. Different types of MDS exist, resulting in different manifestations of the disease. For example, some patients with MDS require chronic blood transfusions.
MDS can occur after treatment with drugs or radiation therapy for other diseases, or it can develop without any known cause. Some forms of MDS can progress to acute myeloid leukemia.
An estimated 7,000 to 12,000 new cases of MDS are diagnosed yearly in the United States. Although MDS occurs in all age groups, the highest prevalence is in persons older than 60 years of age. Typical symptoms include weakness, fatigue, infections, easy bruising, bleeding, and fever.
The safety and effectiveness of Dacogen were demonstrated in a randomized, controlled trial in which patients received either Dacogen or the standard therapy and in 2 non-randomized studies in which all of the patients received Dacogen. The new drug was evaluated in a total of 268 patients. About 22% of patients in the 3 trials had complete or partial responses to Dacogen. Responses consisted of complete or partial normalization of blood counts and fewer immature cells in the bone marrow. In those who responded, the need for transfusions was eliminated during the period of response.
The most common adverse effects reported in clinical trials included neutropenia, thrombocytopenia, anemia, fatigue, fever, nausea, cough, bleeding in the skin, constipation, diarrhea, and hyperglycemia.
Dacogen is manufactured by Pharmachemie B.V. of Haarlem, The Netherlands, for MGI Pharma, Inc, of Bloomington, Minn. For full prescribing information, visit mgipharma.com.
May 1, 2006
ST. LOUIS (MD Consult) - On April 28, 2006, the US Food and Drug Administration (FDA) approved a biologics license application for Myozyme (alglucosidase alfa, rhGAA), the first treatment for patients with Pompe disease, a rare but severely debilitating disease. Pompe disease, which affects 1 in 40,000 to 300,000 persons, drastically reduces muscle and respiratory function.
Myozyme had been granted FDA orphan drug designation and was approved under a priority review. Orphan products are developed to treat rare diseases or conditions that affect fewer than 200,000 people in the United States. The Orphan Drug Act provides a 7-year period of exclusive marketing to the first sponsor who obtains marketing approval for a designated orphan drug.
Pompe disease is an inherited disease caused by the deficiency or lack of the enzyme acid alpha-glucosidase, which is essential for normal muscle development and function. The disease, which usually results in death from respiratory failure, is rapidly fatal in newborn babies.
The FDA approved Myozyme for administration by intravenous infusion of solution into a vein. The safety and efficacy of Myozyme were assessed in 2 separate clinical trials in 39 infantile-onset patients with Pompe disease ranging in age from 1 month to 3.5 years at the time of the first infusion.
Patient survival without needing invasive ventilatory support was substantially greater in the Myozyme-treated infants than would be expected given the known high mortality of untreated patients of similar age and disease severity. The drug's safety and effectiveness in other forms of Pompe disease have not been adequately studied.
The most serious adverse reactions reported with Myozyme, which is manufactured by Genzyme Corp in Cambridge, Mass, were heart and lung failure and allergic shock. Most common reactions included pneumonia, respiratory failure and distress, infections, and fever. A boxed warning is included in the Myozyme label to warn about the possibility of life-threatening allergic reactions.
Genzyme Corp has created a Web site with information on Pompe disease; for an overview of the disease and more information for patients and health care professionals, visit pompe.com.
For more details on Myozyme, including full prescribing information, visit myozyme.com.
April 19, 2006
ST. LOUIS (MD Consult) - On February 21, 2006, Ortho-McNeil, Inc, and Biovail Corporation announced that once-daily Ultram ER (tramadol hydrochloride) tablets are now available by prescription in the United States. Ultram ER is the first extended-release tramadol product approved in the United States for relief of moderate to moderately severe chronic pain in adults who require uninterrupted treatment of their pain for an extended period of time. The drug is available in once-daily dosage strengths of 100, 200, and 300 mg.
The US Food and Drug Administration approved Ultram ER in September 2005 based on clinical and safety data obtained from 4 well-controlled clinical trials. More than 3,000 patients have been treated with Ultram ER in clinical trials.
Tramadol is a nonscheduled, centrally acting, synthetic opioid analgesic that has been used in the treatment of moderate to moderately severe pain since its introduction in the United States in 1995. Ultram ER provides appropriate patients effective pain control over a 24-hour period. In contrast, patients may need to take immediate-release tramadol tablets every 4 to 6 hours for pain relief.
Ultram ER is contraindicated in any situation in which opioids are contraindicated, including in those patients with a history of anaphylactoid reactions to opioids.
Seizures have been reported in patients receiving tramadol. The risk of seizure is increased with doses of tramadol above the recommended range and in patients taking certain medications such as tricyclic antidepressants, selective serotonin reuptake inhibitors, or opioids. The administration of tramadol may enhance the seizure risk in patients taking monoamine oxidase inhibitors, neuroleptics, or other drugs that reduce the seizure threshold, or in patients with epilepsy, a history of seizures, or a recognized risk for seizure (eg, head trauma, metabolic disorders, alcohol and drug withdrawal, central nervous system infections).
Tramadol, like other opioids used in analgesia, can be abused. Ultram ER should not be used in patients who are suicidal or prone to addiction, nor should it be taken with alcohol-containing beverages. Ultram ER tablets are intended for oral use only and should be swallowed whole. The tablets should not be chewed, crushed, or split. The drug should not be administered at a dose exceeding 300 mg/d.
In clinical trials, the most frequently reported adverse effects associated with Ultram ER were dizziness, nausea, constipation, somnolence, and flushing.
"Chronic pain affects a large segment of the US population, with an estimated 45% of all Americans seeking care for persistent pain at least once during their lifetime," said Dr Warren A. Katz, Clinical Professor of Medicine, University of Pennsylvania School of Medicine, Director of the Osteoporosis Center and Rheumatology at the Rothman Institute. According to Biovail, approximately one third of all Americans have some element of chronic pain. Up to 700 million workdays are lost in the United States each year as a result of pain-related disabilities. Moreover, chronic pain has a significant economic impact, with estimated direct and indirect costs in the United States exceeding $100 billion annually.
For more information about Ultram ER, including full US prescribing information, visit ultram-er.com/prescribing_info.html.
April 17, 2006
ST. LOUIS (MD Consult) - Alkermes, Inc, and Cephalon, Inc, announced on April 13, 2006, that the US Food and Drug Administration (FDA) has approved Vivitrol (naltrexone for extended-release injectable suspension) for the treatment of alcohol dependence. Vivitrol, the first once-monthly injectable medication for alcohol dependence, is indicated for patients who are able to abstain from drinking in an outpatient setting and are not actively drinking at the initiation of treatment. Vivitrol is non-addictive and non-aversive. It is administered by a health care provider and should be used in combination with psychosocial support such as counseling or group therapy.
Vivitrol works by binding to opioid receptors in the brain. Although the mechanism responsible for the reduction in alcohol consumption observed with Vivitrol treatment is not entirely understood, preclinical data suggest that occupation of the opioid receptors results in the blockade of the neurotransmitters in the brain that are believed to be involved with alcohol dependence. This blockade may result in the reduction in alcohol consumption observed in patients treated with Vivitrol.
The efficacy of Vivitrol was studied in a 6-month, phase III, double-blind, placebo-controlled, randomized clinical trial of patients with alcohol dependence. The primary end point of the study was the reduction in the event rate of heavy drinking days, and heavy drinking was defined as 5 or more drinks per day for men and 4 or more drinks per day for women. In the overall study population, patients treated with 380 mg of Vivitrol and psychosocial support demonstrated a greater reduction in days of heavy drinking than those treated with only psychosocial support and placebo injection over the 6-month treatment period. Over the same 6-month period, in a subset of patients who abstained from drinking in the week before receiving their first dose of medication, those treated with 380 mg of Vivitrol were more likely to maintain complete abstinence and showed a greater reduction in drinking days, as well as a greater reduction in heavy drinking days, compared with the placebo-treated group.
In clinical trials, Vivitrol was generally well tolerated, and the majority of adverse events were mild to moderate in intensity. The most common adverse events associated with Vivitrol clinical trials were nausea, vomiting, headache, dizziness, fatigue, and injection site reactions.
Naltrexone has the capacity to cause hepatocellular injury when given in excessive doses. The drug is contraindicated in patients with acute hepatitis or liver failure, and its use in patients with active liver disease must be carefully considered in light of its hepatotoxic effects. The margin of separation between the apparently safe dose of naltrexone and the dose causing hepatic injury appears to be only fivefold or less. Vivitrol does not appear to be a hepatotoxin at the recommended doses. Patients should be warned of the risk of hepatic injury and advised to seek medical attention and discontinue use of the drug if they experience symptoms of acute hepatitis.
Vivitrol is contraindicated in patients receiving opioid analgesics, those with current physiologic dependence on opioids, those experiencing acute opioid withdrawal, and those with previously exhibited hypersensitivity to naltrexone, polylactide-co-glycolide, or any other components of the diluent.
Vivitrol is a potent opioid antagonist. Patients must be opioid free for a minimum of 7 to 10 days before beginning treatment with this medication. Any attempt to overcome the opioid blockade produced by Vivitrol using exogenous opioids may result in fatal overdose. In patients with a previous history of opioid abuse, administration of exogenous opioids may result in potentially life-threatening opioid intoxication. When reversal of Vivitrol blockade is required for pain management, patients should be monitored in a setting equipped and staffed for cardiopulmonary resuscitation.
Should a patient receiving Vivitrol experience progressive dyspnea and hypoxemia, the diagnosis of eosinophilic pneumonia should be considered. Patients should be advised to seek medical attention for injection site reactions such as pain, tenderness, induration, or pruritus that do not improve within 1 month after the injection. Patients with alcohol dependece, including those taking Vivitrol, should be monitored for the development of depression or suicidal thinking.
Alcohol dependence is a serious and chronic disease that affects multiple regions of the brain, providing rationale for the use of medication with psychosocial support as part of an integrated treatment plan. Of the more than 18 million Americans who abuse or are dependent on alcohol, approximately 2.2 million seek treatment for their alcohol problems. More than 75% of these patients relapse back to drinking within the first year of beginning treatment using currently available treatment approaches.
Underlying neurologic and genetic factors are involved in alcohol dependence. According to the National Institute on Alcohol Abuse and Alcoholism, the 4 symptoms most commonly associated with alcohol dependence are cravings, loss of control over drinking, withdrawal symptoms (including sweating, nausea, shakiness, and anxiety), and an increased tolerance for alcohol. Psychosocial support, such as counseling, is the traditional approach for treating alcohol dependence; however, experts in the field increasingly recommend and support a treatment approach that includes a combination of medication and psychosocial support.
Cephalon and Alkermes expect Vivitrol to be available to physicians and patients in the United States by the end of June 2006. The drug will be available as a single-dose 380-mg intramuscular injection. For full prescribing information and other details on Vivitrol, visit vivitrol.com or call 1-800-896-5855.
April 10, 2006
ST. LOUIS (MD Consult) - On April 6, 2006, the US Food and Drug Administration approved Daytrana (methylphenidate transdermal system), the first transdermal patch indicated for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children aged 6 to 12 years. Daytrana, a once-daily treatment, will be available in 10-, 15-, 20-, and 30-mg dosage strengths.
Data from phase II and phase III clinical trials demonstrated statistically significant improvements in the primary and secondary end points analyzed for children (aged 6-12 years) treated with Daytrana compared with children treated with placebo. In both studies, Daytrana was generally well tolerated during both the dose optimization and double-blind phases. Adverse events typically were mild to moderate, resolved with continued therapy, and were consistent with known effects of methylphenidate. Common adverse events seen in clinical trials included decreased appetite, insomnia, nausea, vomiting, weight loss, tic, and affect lability.
ADHD is a condition that affects approximately 3% to 7% of school-aged children. The 3 main symptoms of ADHD are inattention, hyperactivity, and impulsivity. Children with ADHD may have difficulty in school, troubled relationships with family and peers, and low self-esteem.
Daytrana should be applied each morning to the alternating hip and should be worn for 9 hours. Parents and caregivers will be provided a chart to track the application and removal of the patch.
The prescriber may change the amount of time the patch is worn to help manage how long the medication works each day and some of the adverse effects that may be caused by methylphenidate. If the patch is worn for longer than the recommended 9 hours, methylphenidate-induced effects such as insomnia may occur with greater frequency in some children. Other possible adverse effects include blurred vision, mild skin irritation or allergic skin rash, and slower weight gain and height growth. Stimulant products generally should not be used in children with known structural cardiac abnormalities because of a concern that stimulants may further increase the risk of sudden death above the risk that is already present with such abnormalities.
Daytrana should not be used if a child:
Daytrana, manufactured for Shire US Inc by Noven Pharmaceuticals Inc, has been shown to be safe and effective in 2 placebo-controlled studies in children 6 to 12 years of age with ADHD. Daytrana is indicated as part of a total treatment program for ADHD that may include other measures such as psychological, education, and social factors.
For more information, including full prescribing information, visit daytrana.com.
March 20, 2006
ST. LOUIS (MD Consult) - On March 17, 2006, Berlex, Inc, announced that the US Food and Drug Administration has approved Yaz (3 mg drospirenone/20 mcg ethinyl estradiol), a new monophasic oral contraceptive and the first pill to combine 20 mcg of ethinyl estradiol with the innovative progestin drospirenone. The 24-day, active-hormone pill regimen results in less hormonal fluctuation than traditional oral contraceptives that provide 21 days of active pills. Yaz will be available by prescription in the United States in April 2006.
Yaz contains the progestin drospirenone, a spironolactone analog with antimineralocorticoid properties. The 24-day active-hormone pill regimen of Yaz combined with the 30-hour half-life of drospirenone results in less hormonal fluctuation between cycles compared with traditional oral contraceptives with 21 days of active pills and 7 days of placebo. Preclinical studies indicate that drospirenone also provides an antiandrogenic effect.
Oral contraceptives have evolved dramatically since their introduction in the 1960s. The traditional dosing regimen, which includes 21 days of active pills and 7 days of placebo, was an attempt to simulate the natural menstrual cycle. A longer (7-day) placebo interval was used at the time to help counteract higher-estrogen-dose oral contraceptives and to enable monthly withdrawal bleeding. Today's birth control pills now appreciably lower estrogen doses, thus allowing for shorter pill-free intervals. In addition to lower estrogen doses, a variety of progestins have been introduced, and the regimens have been altered to provide women with dosing schedules that may better fit their needs.
A large clinical trial involving 1,027 women, who completed 11,480 treatment cycles, established the safety of Yaz and demonstrated 99% contraceptive efficacy. The clinical trial also found that Yaz provides women with predictable monthly periods, with breakthrough bleeding rates comparable to other low-dose oral contraceptives. Only 0.7% (7 of 1,027) of women participating in the clinical trial discontinued Yaz because of irregular bleeding.
Yaz was well tolerated by the majority of women in the clinical trial. The most common adverse effects were similar to those experienced with other oral contraceptives and included upper respiratory infection, headache, breast pain, vaginal moniliasis, leukorrhea, diarrhea, and nausea.
Yaz contains 3 mg of the progestin drospirenone that has antimineralocorticoid activity, including the potential for hyperkalemia in high-risk patients, comparable to a 25-mg dose of spironolactone. Yaz should not be used in patients with conditions that predispose to hyperkalemia (ie, renal insufficiency, hepatic dysfunction, or adrenal insufficiency). Women receiving daily, long-term treatment for chronic conditions or diseases with medications that may increase serum potassium concentrations should have their serum potassium levels checked during the first treatment cycle. Medications that can increase serum potassium concentrations include angiotensin-enzyme inhibitors, angiotensin-II receptor antagonists, potassium-sparing diuretics, potassium supplementation medications, aldosterone antagonists, and nonsteroidal anti-inflammatory drugs.
Oral contraceptives do not protect against HIV infection and other sexually transmitted diseases. The use of oral contraceptives is associated with increased risks of several serious adverse effects. Cigarette smoking increases the risk of serious cardiovascular side effects; women who take oral contraceptives are strongly advised not to smoke.
More information about Yaz is available online at yaz.com and by contacting Berlex, Inc, a US affiliate of German pharmaceutical company Schering AG.
March 20, 2006
ST. LOUIS (MD Consult) - Salix Pharmaceuticals, Ltd, announced on March 17, 2006, that the US Food and Drug Administration has granted marketing approval for prescription OsmoPrep Tablets (sodium phosphate monobasic monohydrate, USP, and sodium phosphate dibasic anhydrous, USP). OsmoPrep Tablets are indicated for cleansing of the colon as a preparation for colonoscopy in adults aged 18 years or older.
The majority of colonoscopies performed in the United States are indicated for colorectal cancer screening, and more than 10 million uses of bowel-cleansing agents were prescribed during 2005. Today, less than half of adults age 50 and older in the United States undergo recommended colorectal cancer screening. Colonoscopy is very effective in the early detection of colorectal cancer, and about 90% of colorectal cancers and deaths are preventable if detected early. The American Cancer Society estimates that more than 30,000 lives could be saved annually as a result of widespread screening. Results of a study conducted by the Mayo Clinic demonstrated that patient unwillingness to take a bowel preparation is the single largest barrier to colorectal cancer screening.
Douglas Rex, MD, Professor of Medicine, Indianapolis University School of Medicine and Director of Endoscopy, Indiana University Hospital, stated, "OsmoPrep provides excellent colon cleansing in a highly tolerable tablet formulation making colonoscopies simple for both the physician and the patient. It represents a new choice for patients unable to tolerate high volume liquid preparations."
Considerable caution should be advised before OsmoPrep Tablets are used in patients with severe renal insufficiency, congestive heart failure, ascites, unstable angina, gastric retention, ileus, acute obstruction or pseudo-obstruction of the bowel, severe chronic constipation, bowel perforation, acute colitis, toxic megacolon, gastric bypass or stapling surgery, or hypomotility syndrome. The drug should be used with caution in patients with impaired renal function, a history of acute phosphate nephropathy, or known or suspected electrolyte disturbances (such as dehydration), as well as in persons taking drugs that affect electrolyte levels. Patients with electrolyte abnormalities such as hypernatremia, hyperphosphatemia, hypokalemia, or hypocalcemia should have their electrolyte levels corrected before treatment with OsmoPrep Tablets.
OsmoPrep is patent protected until 2013, and additional patent protection is being sought through 2024. For more information on the drug and its manufacturer, visit salix.com.
March 7, 2006
ST. LOUIS (MD Consult) - On January 9, 2006, the US Food and Drug Administration announced the approval of the first immune globulin product for subcutaneous injection to prevent serious infections in patients with primary immune deficiency diseases (PIDDs). Vivaglobin, manufactured by ZLB Behring GmbH of Marburg, Germany, from human plasma collected at US-licensed plasma centers, provides new delivery options for patients with PIDD. It is administered subcutaneously on a weekly basis using an infusion pump, which means patients can self-administer the product at home. Some patients develop problems that make chronic intravenous administration of needed medicines difficult, and Vivaglobin may be helpful in providing them with an alternative route.
PIDDs are inherited disorders that affect an estimated 50,000 people in the United States. These patients require regular treatment with immune globulin to fight off or prevent potentially serious or life-threatening infections. Other immune globulin products are administered either intravenously or intramuscularly.
In clinical studies, Vivaglobin was well tolerated. The most common adverse effect is mild or moderate injection site reaction such as swelling, redness, and itching. The contraindications for Vivaglobin are similar to other immune globulin products.
As for all immune globulin preparations, plasma used for Vivaglobin is tested and found to be nonreactive for human immunodeficiency virus and hepatitis viruses before its use, and the manufacturing process includes steps that further reduce the risk of transmission of viruses.
For more information, visit the vivaglobin.com.
March 1, 2006
ST. LOUIS (MD Consult) - On February 28, 2006, Bristol-Myers Squibb Company and Somerset Pharmaceuticals, Inc, announced that the US Food and Drug Administration (FDA) has approved Emsam (selegiline transdermal system), the first transdermal patch for the treatment of major depressive disorder (MDD) in adults. Emsam, which is manufactured by Mylan Technologies, Inc, for Somerset, is a monoamine oxidase inhibitor (MAOI) that has been shown to relieve depressive symptoms in patients with MDD.
Although their mechanisms of action are not fully understood, MAOIs, including Emsam, are presumed to work through potentiation of monoamine neurotransmitter activity in the brain by inhibiting the MAO enzyme. In an in vivo animal model, Emsam exhibited antidepressant properties only at doses that inhibited both MAO-A and MAO-B in the brain. In the brain, MAO-A and MAO-B play important roles in the breakdown of neurotransmitter amines such as norepinephrine, dopamine, and serotonin.
Oral MAOI antidepressants pass through the digestive tract, thus inhibiting intestinal MAO-A, which is needed to break down tyramine, a substance found in certain foods and beverages such as aged cheese and draught beer. If a large amount of tyramine is absorbed systemically, it can lead to a sudden and large increase in blood pressure called a hypertensive crisis, which is potentially life-threatening and requires immediate medical treatment. Although most foods contain negligible amounts or no tyramine, a few food products may contain amounts large enough to represent a potential risk for patients with significant inhibition of intestinal MAO-A resulting from administration of MAO inhibitors. As a result, patients taking oral MAOIs for MDD are required to avoid foods high in tyramine.
Through transdermal delivery, Emsam is directly and continuously absorbed into the bloodstream over a 24-hour period. As a result, initial exposure of the drug to the digestive tract is minimized. As indicated in animal studies, the Emsam 6 mg/24 h patch allows for levels of medicine to inhibit MAO in the brain thought to be necessary for antidepressant effect while sufficiently preserving MAO-A in the digestive tract to break down tyramine. The known data for Emsam 6 mg/24 h support the recommendation that tyramine dietary modifications are not needed. However, to reduce the risk of hypertensive crisis, dietary modifications are required for patients using the Emsam 9 mg/24 h patch and the 12 mg/24 h patch.
The efficacy of Emsam in relieving depressive symptoms was established in 2 double-blind, placebo-controlled studies of 6-week (N = 176) and 8-week (N = 265) durations that included adult outpatients aged 18 to 70 years with single and recurrent episodes of MDD. The antidepressant action of Emsam in hospitalized depressed patients has not been studied.
The 6-week trial showed that a 6 mg/24 h dose of Emsam was significantly more effective than placebo in improving depressive symptoms as determined using the 17-item Hamilton Depression Rating Scale (HAM-D).
In the 8-week dose titration trial, patients with MDD who received Emsam or placebo at a starting dose of 6 mg/24 h, with possible increases to 9 mg/24 h or 12 mg/24 h made because of clinical response, showed significant improvement compared with placebo on the primary outcome measure, the 28-item HAM-D total score.
The benefit of maintaining patients with MDD on therapy with Emsam after achieving a responder status for an average of 25 days was demonstrated in a controlled clinical trial. Three hundred twenty-two patients with MDD who had responded to Emsam 6 mg/24 h during an initial 10-week open-label treatment phase were randomly assigned either to continue taking Emsam 6 mg/24 h (n = 159) or to take a placebo (n = 163) under double-blind conditions for observation of relapse. Approximately 52% of the Emsam-treated patients and about 52% of the placebo-treated patients had discontinued treatment by week 12 of the double-blind phase. Patients continually receiving Emsam experienced a significantly longer time to relapse.
In clinical trials with Emsam, application site reaction was the most commonly reported adverse event (Emsam, 24%; placebo, 12%). Most were mild to moderate in severity, with only 2% resulting in discontinuation. Overall, the rate of discontinuation because of adverse events was low (Emsam, 7.1%; placebo, 3.6%). Additionally, patients taking Emsam reported sexual dysfunction at a rate similar to that of those taking placebo and experienced minimal weight change (mean weight change from baseline: Emsam, –1.2 lb; placebo, +0.3 lb).
The recommended starting and target dose of Emsam is one 6 mg/24 h patch administered once daily without tyramine dietary modifications; 9 mg/24 h and 12 mg/24 h once-daily doses (one patch per day) will also be available. The trials were not designed to assess whether higher doses are more effective than the starting and target dose of 6 mg/24 h. To reduce the risk of hypertensive crisis, patients must avoid consuming foods and beverages high in tyramine while using Emsam 9 mg/24 h or 12 mg/24 h and for 2 weeks after discontinuation of Emsam at these doses or reducing the dose to Emsam 6 mg/24 h. Patients should be instructed to inform all of their health care professionals that they are using Emsam, and not to stop or change treatment with Emsam without consulting a health care professional.
Bristol-Myers Squibb has issued following cautions regarding the use of Emsam in specific patient cohorts and in conjunction with some medications:
Treatment-emergent adverse events in short-term clinical trials that occurred at a ≥2% incidence with Emsam and for which the incidence was greater than placebo include application site reaction (Emsam 24% vs placebo 12%), headache (18% vs 17%), insomnia (12% vs 7%), diarrhea (9% vs 7%), dry mouth (8% vs 6%), dyspepsia (4% vs 3%), rash (4% vs 2%), pharyngitis (3% vs 2%), and sinusitis (3% vs 1%).
According to the Diagnostic and Statistical Manual of Mental Disorders, 4th ed, diagnosis, major depressive disorder is characterized by 1 or more major depressive episodes (ie, at least 2 weeks of depressed mood or loss of interest accompanied by at least 4 additional symptoms of depression) and impairs social and occupational or other important areas of functioning. Major depression affects approximately 14 million American adults in a given year and is the most common mental health disorder after anxiety. It is a leading cause of disability and disease burden worldwide.
The illness is 1.5 to 3 times more common among persons with a family history of MDD than among the general population, and studies indicate that depressive episodes occur twice as frequently in women as in men.
Today, many patients with MDD do not achieve adequate symptom relief. If depression is not treated successfully, the chances that it will become recurrent increase. More than 80% of patients who have 1 episode of MDD will have at least 1 subsequent episode.
Full prescribing information for Emsam, including Boxed Warning information, can be found on the Bristol-Myers Squibb Web site.
February 22, 2006
ST. LOUIS (MD Consult) - On February 21, 2006, the US Food and Drug Administration (FDA) announced it has approved Eraxis (anidulafungin) to treat certain infections caused by Candida species, a yeast-like fungus that can cause serious infections in hospitalized patients and patients with compromised immune systems.
"This product offers a new alternative therapy for several types of infections associated with Candida," said Dr Steven Galson, director of the FDA's Center for Drug Evaluation and Research. "It is a helpful addition to the available antifungal medications that can be used in the treatment of these potentially serious fungal conditions."
A new molecular entity that has never been marketed in the United States, Eraxis is an antifungal drug that is administered intravenously. It is used to treat esophageal candidiasis, candidemia, and other forms of Candida infection, including abdominal abscesses and peritonitis. The safety and efficacy of Eraxis was evaluated in clinical studies, and the drug was shown to be safe and effective in the treatment of all of these types of infection.
Eraxis was generally well tolerated in clinical studies. The most commonly reported adverse events were headache, mild diarrhea, and mild elevations in laboratory measurements of liver enzymes. Some patients experienced infusion-related reactions, most of which were mild. In a few patients with significant underlying medical conditions who were taking multiple concomitant medications, there were reports of serious hepatic abnormalities.
For more information, visit www.pfizer.com.
February 6, 2006
ST. LOUIS (MD Consult) - On February 3, 2006, the US Food and Drug Administration (FDA) announced the approval of the live, oral vaccine RotaTeq for use in preventing rotavirus gastroenteritis in infants. It is the only vaccine approved in the United States that can help protect against rotavirus, a viral infection that can cause diarrhea, vomiting, fever, and dehydration.
"This vaccine gives health care providers an important new tool that can effectively prevent an illness that affects almost all children within the first few years of life," said Jesse L. Goodman, MD, MPH, director of the FDA’s Center for Biologics Evaluation and Research.
Infection with rotavirus is a leading cause of severe diarrhea in infants and young children in the United States and worldwide. The Centers for Disease Control and Prevention (CDC) has estimated that rotavirus infection results in approximately 55,000 annual hospitalizations of infants and young children in the United States; death from rotavirus is rare in this country. However, in developing countries, rotavirus gastroenteritis has been estimated to cause up to several hundred thousand deaths annually in infants and young children.
The safety of RotaTeq was evaluated in randomized placebo-controlled studies involving approximately 72,000 healthy infants in the United States and other countries. The vaccine was also tested for efficacy in almost 7,000 of these infants who were from the United States and Finland. In these studies, RotaTeq prevented 74% of all rotavirus gastroenteritis cases and 98% of the severe cases. In addition, the new vaccine prevented approximately 96% of hospitalizations caused by rotavirus gastroenteritis.
In 1998, the FDA approved a different live vaccine against rotavirus that was later withdrawn from the market because of its association with an increased risk of intussusception, a rare, life-threatening type of blockage or twisting of the intestine. Intussusception occurs spontaneously in approximately 1 in 2,000 healthy young infants and children per year, but the condition occurred at an increased rate during the first 2 weeks after vaccination with the previous rotavirus vaccine.
The risk of intussusception for RotaTeq was evaluated in a large-scale trial of over 70,000 children, of whom half received vaccine and the remaining half received placebo. In this study, RotaTeq was not associated with an increased risk of intussusception when compared with placebo. In addition, RotaTeq was not associated with an increased risk of other serious adverse events when compared with placebo.
"Although this large study did not show an increased risk of intussusception associated with RotaTeq, given the experience with the previous vaccine, safety of this vaccine will be closely monitored in additional studies conducted after licensure," said Dr Goodman. The manufacturer has committed to conducting a postlicensure study of approximately 44,000 children. The CDC will also conduct a large study designed to rapidly detect any association of intussusception with RotaTeq through its Vaccine Safety Datalink Program, which evaluates vaccine safety in approximately 80,000 US infants every year. In addition, for the first 3 years of licensure, the manufacturer will report cases of intussusception and all serious and unexpected adverse events to the FDA within 15 days of receiving them, and all other adverse effects will be communicated on a monthly basis.
RotaTeq is a liquid vaccine that is given by mouth in 3 doses to infants between the ages of 6 and 32 weeks. The following were reported more often in infants who received RotaTeq compared with infants who received placebo: diarrhea (24.1% in vaccine recipients vs 21.3% in those receiving placebo), vomiting (15.2% vs 13.6%), ear infection (14.5% vs 13.0%), runny nose and sore throat (6.9% vs 5.8%), and wheezing and coughing (1.1% vs 0.7%).
Additional information regarding the approval of RotaTeq is available from the FDA at fda.gov/cber/products/rotamer020306.htm, and full prescribing information is available from the FDA or from Merck at merck.com/product/usa/pi_circulars/r/rotateq/rotateq_pi.pdf.
February 1, 2006
ST. LOUIS (MD Consult) - On January 31, 2006, the US Food and Drug Administration (FDA) approved Amitiza (lubiprostone), the first drug of its chemical type, for the treatment of chronic constipation in the adult population when there is no known cause for the condition. The product will be available as capsules for use by adults to treat idiopathic constipation.
Chronic idiopathic constipation is generally defined as infrequent and difficult passage of stool and is one of the most common disorders experienced by Americans. This condition affects women more often than men and patients older than 65 years more frequently than younger persons. Symptoms of chronic idiopathic constipation are abdominal pain and discomfort, bloating, straining, and hard stools.
Amitiza works by increasing the intestinal fluid secretion, which helps ease the passage of stool and helps alleviate symptoms associated with chronic idiopathic constipation. The FDA based its decision to approve Amitiza on the results from 2 clinical trials conducted in patients with, on average, fewer than 3 spontaneous bowel movements per week with symptoms of constipation for at least 6 months before entry into the studies. The studies demonstrated that subjects treated with Amitiza had a higher frequency of bowel movements in the first week than subjects receiving placebo. In both studies, results similar to those in week 1 were also observed in weeks 2, 3, and 4 of therapy. In addition, 3 long-term studies showed that Amitiza decreased constipation severity, abdominal bloating, and discomfort over 6 to 12 months of use.
The most common adverse events reported in the trials included headache, nausea, diarrhea, abdominal pain, and distension. Whether these events are related to the drug is not known at present, said the FDA.
Amitiza should be taken twice a day with food. Physicians and patients should periodically assess the need for continued treatment.
Amitiza is marketed by Sucampo Pharmaceuticals, Inc, Bethesda, Md, and by Takeda Pharmaceuticals America, Lincolnshire, Ill. For complete prescribing information, visit amitiza.com.
January 31, 2006
ST. LOUIS (MD Consult) - On January 31, 2006, the US Food and Drug Administration (FDA) announced the approval of Ranexa (ranolazine), a new drug for the treatment of chronic angina. A new molecular entity, Ranexa is the first drug approved to treat chronic angina in more than 10 years.
Although several pharmacologic activities of ranolazine have been described, the precise way the drug works is not fully understood. Because Ranexa affects electrical conduction in the heart (prolonging the QT interval), it should only be used by patients whose conditions have not responded to other antianginal drugs (eg, long-acting nitrates, calcium channel blockers, and beta blockers).
Chronic angina is characterized by episodes of chest pain, pressure, or discomfort that occur during exercise because the heart muscle is not getting enough oxygen. The most common cause of angina is coronary heart disease, in which the coronary arteries that supply the heart with oxygen-rich blood become blocked with plaque deposits. According to the American Heart Association, approximately 6.8 million Americans are diagnosed with angina every year. Although many of these patients respond to other treatments, including surgery and other approved drugs, some remain with angina despite receiving these treatments. Acute attacks of angina are treated with nitroglycerin placed under the tongue, whereas treatments for chronic angina are given to increase the amount of exercise a person can do before angina occurs. This is usually tested by showing that persons with angina can exercise longer on a treadmill or bicycle when they take the drug.
Ranexa was studied in patients with chronic angina who still had symptoms despite being treated with other antianginal drugs. Two clinical trials, Efficacy of Ranolazine in Chronic Angina (ERICA) and Combination Assessment of Ranolazine In Stable Angina (CARISA) were conducted. In ERICA, 565 patients who were experiencing about 4.5 angina attacks per week while taking a full dose of a calcium channel blocker were randomly assigned to receive Ranexa or placebo for 6 weeks. Patients receiving Ranexa had a reduction in angina attacks of about 1 attack per week, compared with those in the placebo group.
In CARISA, 823 patients receiving either a calcium channel blocker or beta blocker (ie, atenolol) were randomly assigned to receive Ranexa or placebo, and follow-up was undertaken for 12 weeks using a formal exercise treadmill test. Patients in the Ranexa group had a mean exercise improvement similar to that seen with other antianginal therapies.
In both studies, Ranexa appeared to be less effective in women than in men.
In clinical studies, common adverse effects included dizziness, headache, constipation, and nausea.
Ranexa is manufactured by CV Therapeutics, Inc. in Palo Alto, Calif. Full prescribing information is available at cvt.com.
January 30, 2006
ST. LOUIS (MD Consult) - A new, potential alternative has been approved in the United States for persons who take insulin injections, announced the US Food and Drug Administration (FDA) on January 27, 2006. The first ever inhaled insulin, Exubera, is an inhaled powder form of recombinant human insulin. Approved for use in adult patients with type 1 and type 2 diabetes, Exubera is the first new insulin delivery option introduced since the discovery of insulin in the 1920s.
"Until today, patients with diabetes who need insulin to manage their disease had only one way to treat their condition," said Dr Steven Galson, Director, Center for Drug Evaluation and Research, FDA. "It is our hope that the availability of inhaled insulin will offer patients more options to better control their blood sugars."
Diabetes is a disease that affects the amount of insulin and sugar in the body. Exubera is a human form of insulin and, as such, lowers blood sugar concentrations by allowing the blood sugar to be taken up by cells as a source of fuel. Exubera is a powdered form of insulin that is able to be inhaled into the lungs through the patient's mouth using a specially designed inhaler.
There are 2 major types of diabetes. Persons with type 1 diabetes produce virtually no insulin. In type 2, the most common form of the disease, the body does not produce enough insulin nor does it effectively use insulin. If persons with diabetes do not properly control their blood sugar levels, serious complications including heart disease, kidney failure, blindness, and nerve damage may develop. According to the FDA, more than 5 million Americans take insulin injections to manage their diabetes.
The safety and efficacy of Exubera have been studied in approximately 2,500 adult patients with type 1 and type 2 diabetes. In clinical studies, Exubera reached peak insulin concentration more quickly than injected regular insulin. Peak insulin levels were achieved at 49 minutes (range, 30-90 minutes) with Exubera inhaled insulin compared with 105 minutes (range, 60-240 minutes) with regular insulin. In type 1 diabetes, inhaled insulin may be added to longer-acting insulins as a replacement for short-acting insulin taken with meals. In type 2 diabetes, inhaled insulin may be used alone, in combination with oral (non-insulin) pills that control blood sugar, or with longer-acting insulins.
Exubera prescriptions will be accompanied by a medication guide containing FDA-approved information written especially for patients. Pharmacists are required to distribute medication guides with products the FDA has determined to be important to health and in cases in which patient adherence to the directions for use is crucial to the product's effectiveness. Patients are advised to read the entire medication guide and talk to their health care providers if they have further questions.
As with any insulin product, low blood sugar levels are an adverse effect of Exubera, and patients should carefully monitor their blood sugar levels regularly. Other adverse effects associated with Exubera therapy seen in clinical trials included cough, shortness of breath, sore throat, and dry mouth.
Exubera is not to be used by patients who smoke or who recently quit smoking (within the last 6 months). The drug is not recommended in patients with asthma, bronchitis, or emphysema. Baseline tests for lung function are recommended after the first 6 months of treatment and every year thereafter, even if there are no pulmonary symptoms.
Although Exubera has been extensively studied for safety, the sponsor has committed itself to performing long-term studies to confirm the continued safety of Exubera after it is marketed and to examine more thoroughly the efficacy and safety of Exubera in patients with underlying lung disease.
Exubera is manufactured by Pfizer Inc of New York. For more information, call 1-800-EXUBERA (1-800-398-2372).
January 27, 2006
ST. LOUIS (MD Consult) - The US Food and Drug Administration (FDA) on January 26, 2006, announced its approval of Sutent (sunitinib), a new targeted anti-cancer treatment for patients with gastrointestinal stromal tumors (GISTs), a rare stomach cancer, and advanced kidney cancer. This action marks the first time the agency has approved a new oncology product for 2 indications simultaneously.
Sutent, which received a priority review and was approved in less than 6 months, is a tyrosine kinase inhibitor working through multiple targets to deprive the tumor cells of the blood and nutrients needed to grow.
"Today's approval is a major step forward in making breakthrough treatments available for patients with rare and difficult to treat forms of cancer," said Steven Galson, MD, Director of the FDA's Center for Drug Evaluation and Research. "New targeted therapies such as Sutent are helping [the] FDA expand options for patients for whom there are limited alternatives."
According to the American Cancer Society, about 32,000 new cases of advanced kidney cancer and 5,000 cases of GIST are diagnosed each year.
Sutent was approved for the treatment of patients with GIST whose disease has progressed or who are unable to tolerate treatment with Gleevec (imatinib mesylate), the current treatment for GIST. While studying the treatment in patients, researchers conducted an early (interim) analysis of data that showed Sutent delayed the time it takes for tumors or new lesions to grow in patients with this rare type of stomach cancer. Specifically, the median time-to-tumor progression for patients treated with Sutent was 27 weeks compared with 6 weeks for patients who were not treated.
The FDA also granted accelerated approval for Sutent in the treatment of patients with advanced renal cell carcinoma. In contrast to the approval for GIST, which was based on the drug's ability to delay the growth of the tumors, this approval was based on Sutent's ability to reduce the size of the tumors in patients. An overall response rate ranging from 26% to 37% was found in patients with metastatic kidney cancer whose tumors had progressed after cytokine-based therapy.
"Today's approval of this drug for these indications provides compelling evidence that the use of alternative data end points allows us to see the benefits of novel therapies earlier in patients," said Richard Pazdur, MD, Director of the FDA's Office of Oncology Drug Products.
In the GIST clinical trial, significant clinical benefit was determined through an early interim analysis of data, thereby allowing researchers to convert all patients in the trial to treatment. For the renal cell carcinoma indication, the FDA used its accelerated approval process, a regulatory mechanism that expedites drug approvals for serious and life-threatening diseases.
The FDA worked with the product's sponsor to offer an expanded access program before approval was granted, making the product available to patients not enrolled in a clinical trial. Currently, more than 1,700 patients are being treated with Sutent through the expanded access program.
"Expanded access programs have proven to be an effective way to get treatment to patients who need it most, especially in cancer," said Ellen Stovall, President of the National Coalition of Cancer Survivorship. "There needs to be a greater awareness among patients and doctors about both the option to participate in clinical research as well as in these expanded access programs in order to make promising new therapies available to as many patients as possible."
The most commonly reported Sutent-related adverse effects included diarrhea, skin discoloration, mouth irritation, weakness, and altered taste. Patients treated with Sutent also experienced fatigue, high blood pressure, bleeding, swelling, and taste disturbance. Hypothyroidism was also observed.
For more details, including full prescribing information, visit sutent.com.
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