Lilly announces FDA approval of first medication for bipolar depression December 30, 2003
FDA approves Restylane for facial wrinkles December 15, 2003
FDA approves Serono's Zorbtive for use in patients with SBS December 3, 2003
FDA approves new drug to treat erectile dysfunction November 21, 2003
Psoriasis indication approved for Raptiva October 29, 2003
Memantine approved in U.S. for Alzheimer's disease OCtober 20, 2003
FDA approves drug for cancer-related hypercalcemia September 19, 2003
Extended oral contraceptive formulation approved by FDA September 9, 2003
Serono wins full FDA approval of Serostim for AIDS wasting September 2, 2003
FDA approves new drug for treatment of erectile dysfunction in men August 20, 2003
FDA approves recombinant factor VIII hemophilia therapy July 29, 2003
FDA approves Lilly's Zyprexa with other drugs for treating manic episodes July 16, 2003
Glaxo, Corixa receive FDA approval for lymphoma drug Bexxar July 1, 2003
FluMist influenza vaccine receives FDA approval June 18, 2003
Alfuzosin approved by the FDA for treating benign prostatic hyperplasia June 16, 2003
Benicar HCT approved by FDA for second-line treatment of hypertension June 10, 2003
FDA approves Amphastar's Duocaine for ophthalmologic anesthetic May 28, 2003
AstraZeneca's Iressa approved for non-small cell lung cancer May 6, 2003
Twice-daily Viracept is approved by the FDA May 2, 2003
FDA approves Genzyme's Fabrazyme for Fabry disease April 25, 2003
FDA approves South Korean company's new pneumonia drug April 8, 2003
FDA approves Merck's nausea antiemetic March 27, 2003
FDA approves HIV fusion inhibitor Fuzeon March 14, 2003
Overactive bladder skin patch approved by FDA February 28, 2003
Avonex for early MS treatment receives FDA approval February 10, 2003
Alpha receives FDA approval for A1P1 augmentation therapy January 10, 2003
Mylan announces FDA approval for Ertaczo cream December 18, 2003
Risperdal gains U.S. approval for treatment of bipolar disorder December 8, 2003
FDA approves new drug for advanced prostate cancer November 26, 2003
FDA Approves Ovcon 35 as the First Chewable Oral Contraceptive Tablet for Women November 17, 2003
U.S. clears GlaxoSmithKline, Vertex AIDS drug October 22, 2003
Topical estrogen wins FDA approval October 14, 2003
Cubicin the first in new class of antibiotics September 16, 2003
U.S. approves Glaxo once-daily antidepressant, Wellbutrin XL September 2, 2003
Bayer wins FDA approval for new once-daily Cipro August 29, 2003
FDA approves MGI Pharma, Helsinn anti-nausea drug July 28, 2003
U.S. FDA approves Enbrel for ankylosing spondylitis July 28, 2003
FDA approves Gilead's HIV reverse transcriptase inhibitor Emtriva July 3, 2003
FDA grants approval to Bristol-Myers to co-package statin with aspirin June 26, 2003
FDA approves Stalevo for treating Parkinson's disease June 16, 2003
Prempro approved by FDA for treating menopause symptoms and osteoporosis June 10, 2003
Bausch & Lomb receives FDA approval for contested generic glaucoma drug May 30, 2003
FDA approves Pfizer's Adriamycin in combination with cyclophosphamide May 12, 2003
FDA grants supplementary approvals for Flonase, Lantus May 5, 2003
FDA approves Aldurazyme for treating rare genetic mucopolysaccharidosis, MPS-I May 1, 2003
Bristol-Myers earns FDA approval for higher dose Glucophage April 15, 2003
J&J given FDA approval for orally disintegrating Risperdal tablets April 4, 2003
FDA approves estrogen-eluting vaginal ring March 24, 2003
Avelox for penicillin-resistant S. pneumoniae approved by FDA March 4, 2003
Atrix receives FDA approval for four-month Eligard product February 19, 2003
FDA approves low-dose Flexeril February 5, 2003
FDA approves Abbott's Humira arthritis drug January 3, 2003
December 30, 2003
ST. LOUIS (MD Consult) - On December 29, 2003, Eli Lilly and Company announced that the U.S. Food and Drug Administration (FDA) has approved Symbyax (olanzapine and fluoxetine HCl) for the treatment of depressive episodes associated with bipolar disorder. Symbyax—a combination of olanzapine, the active ingredient in Zyprexa, and fluoxetine, the active ingredient in Prozac—is the first FDA-approved medication for bipolar depression, a notoriously difficult-to-treat condition that afflicts millions of Americans.
According to a study published in the November 2003 issue of Archives of General Psychiatry, Symbyax helped to treat the symptoms of bipolar depression more effectively and at a significantly faster rate than placebo. In the pooled 8-week studies, patients in the Symbyax group experienced significantly greater improvement in depressive symptoms at weeks 1, 3, 4, 6, and 8, compared with patients taking placebo. Symptom improvement was sustained throughout the entire 8 weeks of the study. In addition, Symbyax patients had no statistically greater risk of treatment-emergent mania than did patients taking placebo.
The most common adverse events reported in patients taking Symbyax in clinical trials was drowsiness. Other common events noticed in clinical trials were weakness, swelling, tremor, weight gain, increased appetite, sore throat, and difficulty concentrating.
Hyperglycemia—in some cases associated with ketoacidosis, coma, or death—has been reported in patients treated with atypical antipsychotic drugs, including olanzapine, and concomitant olanzapine and fluoxetine. Assessment of the relation between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population.
Available data are insufficient to provide reliable estimates of differences in hyperglycemia-related adverse-event risk among the marketed atypical antipsychotic drugs. All patients taking atypical antipsychotic drugs should be monitored for symptoms of hyperglycemia. Persons with diabetes who are started on atypical antipsychotic drugs should be monitored regularly for worsening of glucose control; those with risk factors for diabetes should undergo baseline and periodic fasting blood-glucose testing. Patients who develop symptoms of hyperglycemia during treatment should undergo fasting blood-glucose testing.
Although Symbyax is not approved for elderly patients with dementia, it is important to note the label for Symbyax includes a warning for patients in this population. The warning states that strokes or transient ischemic attacks, including fatalities, were reported in elderly patients with dementia-related psychosis who participated in clinical trials for olanzapine, an active ingredient in Symbyax. Symbyax has not been studied in elderly patients with dementia, nor does the company expect Symbyax to be used to treat these patients.
Symbyax may induce orthostatic hypotension associated with dizziness, speeding or slowing of heart rate, and in some patients, fainting, especially during initial therapy.
Symbyax prescribing should be consistent with the need to minimize the risk of neuroleptic malignant syndrome, tardive dyskinesia, and orthostatic hypotension.
Symbyax should not be administered until at least 2 weeks have passed since discontinuing a monoamine oxidase (MAO) inhibitor, and an MAO inhibitor is contraindicated for at least 5 weeks after discontinuation of treatment with Symbyax. Thioridazine should not be administered with Symbyax or within a minimum of 5 weeks after discontinuing Symbyax. Symbyax should be discontinued immediately if rash or other possibly allergic phenomena appear for which an alternative explanation cannot be identified.
Because of the cyclical nature of bipolar disorder, patients should be monitored for signs of mania and hypomania during treatment with Symbyax.
Patients should inform their physicians whether they are taking Zyprexa, Prozac, Sarafem, or fluoxetine.
Full prescribing information is accessible at www.symbyax.com.
Symbyax will be available in pharmacies by mid-January 2004.
December 18, 2003
ST. LOUIS (MD Consult) - On December 11, 2003, Mylan Laboratories Inc. announced that the U.S. Food and Drug Administration has approved Ertaczo (sertaconazole nitrate) cream, 2%. Sertaconazole is an imidazole derivative antifungal indicated for the topical treatment of interdigital tinea pedis in immunocompetent patients 12 years of age and older.
The product will be marketed by OrthoNeutrogena.
December 15, 2003
ST. LOUIS (MD Consult) - On December 12, 2003, the U.S. Food and Drug Administration (FDA) approved an injectable gel to treat facial wrinkles.
Studies conducted by the manufacturer showed that the device, Restylane, is safe and effective for filling moderate to severe wrinkles around the nose and mouth. Most patients needed one injection to get optimal correction; about one third of patients needed more than one injection to get a satisfactory result. The effect lasted about 6 months. Restylane is made with hyaluronic acid.
Two other injectable products are also approved by the FDA for treating wrinkles. Collagen injections are approved for correcting soft tissue deficiencies such as wrinkles and acne scars, and botulinum toxin is approved for treating frown lines between the eyebrows. Other treatments for wrinkles include topical creams, chemical peels, and laser and electro-surgical resurfacing.
The FDA's approval was based on a review of the clinical studies conducted by the manufacturer and on the recommendation of the General and Plastic Surgery Devices Panel of the FDA's Medical Devices Advisory Committee.
In the pivotal study, conducted at 6 medical centers in the United States, 138 patients with naso-labial folds were injected with Restylane on one side of the face and Zyplast, a bovine collagen product, on the other side of the face. Most of the patients were caucasian women who did not smoke and had minimal previous sun exposure.
The results showed that, 6 months after treatment, the effects of Restylane and Zyplast as wrinkle fillers were comparable.
As reported by patients within 14 days following the first treatment, the Restylane-treated side had a lower incidence of severe redness (5.1% vs 5.8%) and an increased incidence of severe bruising (3.6% vs 0.7%), severe swelling (3.6% vs 1.4%), severe pain (3.6% vs 1.4%), and severe tenderness (2.9% vs 1.4%) compared with the Zyplast-treated side. These incidents were lower with follow-up injections for both products.
There was limited data in the study on the safety of Restylane in non-caucasians. The firm, Q-Med AB of Sweden, has agreed to conduct a post-approval study in people of color to determine the product's safety for this population. The firm will also provide training to physicians on the correct use of the device.
December 8, 2003
ST. LOUIS (MD Consult) - On December 5, 2003, the U.S. Food and Drug Administration (FDA) approved Risperdal (risperidone) for short-term treatment of acute manic or mixed episodes associated with bipolar I disorder, also known as bipolar mania. The approval included Risperdal alone or in combination with lithium or valproate. In research studies, patients with bipolar mania who took Risperdal showed significant improvement in manic symptoms compared with placebo.
According to Johnson & Johnson, Risperdal's manufacturer, bipolar disorder affects more than 2 million people in the United States. The disease is characterized by dramatic mood swings, alternating between the highs of mania and the lows of depression. In mixed episodes, people with bipolar disorder experience symptoms of both mania and depression. Mania, a state of excessive excitement and hyperactivity, can lead to delusional thinking and dangerous risk-taking behavior. Nearly 40% of people with untreated bipolar illness abuse alcohol or drugs. Job loss, divorce, and even suicide are not uncommon consequences of the illness.
"Bipolar mania is a serious, life-long illness with many hazardous consequences. We are desperately in need of new treatment options," said Robert Hirschfeld, M.D., chair of the department of psychiatry at the University of Texas Medical Branch in Galveston, Texas. "Because Risperdal is effective and generally well tolerated, it offers an attractive choice for patients and physicians."
The effectiveness of Risperdal in treating acute manic or mixed episodes of bipolar disorder was established in 3 studies—2 that analyzed the medication as monotherapy and 1 in which Risperdal was used in combination with lithium or valproate. In all studies, patients who received Risperdal, given in doses of 1 to 6 mg/d, experienced significantly greater symptom improvements than those in the control groups.
In all studies, efficacy was measured using the Young Mania Rating Scale (YMRS), which clinicians use to assess the degree of a patient's manic symptoms (such as irritability, disruptive/aggressive behavior, elevated mood, increased activity, language/thought disorder, and other measures) from zero (no manic features) to 60 (maximum score). The primary outcome in these studies was change from baseline in the YMRS total score. Clinical response was also defined as a 50% or greater reduction in the total YMRS score from baseline to end point.
In one 3-week, placebo-controlled study of 246 adult patients diagnosed with bipolar I disorder who were in an acute manic episode, with or without psychotic symptoms, Risperdal was superior to placebo in reducing the YMRS total score. Participants taking Risperdal, on average, experienced an 11-point reduction on the YMRS compared with a 5-point reduction among patients in the placebo group. Forty-three percent of the patients treated with Risperdal versus 24% of the patients given placebo had at least a 50% reduction in total manic symptom scores.
The second, similarly designed, monotherapy trial studied 286 bipolar I patients with manic or mixed episodes. Again, Risperdal monotherapy was superior to placebo. On average, Risperdal patients had a total reduction of 22.7 points on the YMRS, versus a 10.5-point reduction among the placebo patients. At end point, 73% of patients receiving Risperdal compared with 36% of patients given placebo achieved clinical response.
The combination therapy study was a 3-week, placebo-controlled trial involving 148 adults diagnosed with bipolar I disorder experiencing a manic or mixed episode, with or without psychotic features, and with or without rapid cycling between moods. At the conclusion of the study, participants taking Risperdal had experienced, on average, a 14.3 total YMRS point reduction versus an 8.2-point reduction among patients taking placebo. Fifty-seven percent of patients treated with Risperdal versus 38% of patients who received placebo had at least a 50% improvement in manic symptoms.
In these studies, all doses of Risperdal were generally well tolerated, with the percentage of patients who discontinued the study due to adverse effects comparable to the dropout rate among those who received placebo. In one of the monotherapy studies, 3.9% of patients experienced a 7% or greater increase in body weight. In the other monotherapy trial, 2.8% of patients had a weight increase of 7% or greater. In the combination therapy study, 10.5% of patients had a weight increase of 7% or greater.
The most common adverse effects experienced in the Risperdal monotherapy studies included extrapyramidal symptoms (reversible movement disorders or muscle disturbances such as restlessness, tremors, and muscle stiffness), sleepiness, dyspepsia, nausea, abnormal vision, and increased saliva. In the combination therapy study, the most common adverse effects included sleepiness, dizziness, Parkinsonism, increased saliva, akathisia (restlessness), abdominal pain, and urinary incontinence.
Drug interactions with some anticonvulsants and Risperdal have been noted. Coadministration of carbamazepine and Risperdal led to a 50% reduction in plasma concentrations of Risperdal. Risperdal had no effect on the average plasma concentration of valproate; however, a 20% increase in peak plasma concentrations was seen. In addition, Risperdal had no affect on the plasma concentrations of lithium.
When in a manic state, a person's behavior becomes unpredictable, and his or her judgment is impaired. People often make reckless decisions during periods of mania, and they become oblivious to the negative consequences of their extreme actions. Spending sprees, alcohol and drug abuse, and hypersexuality are common. In patients with mixed mania, both symptoms of mania and depression occur within the same episode. For example, a person experiencing a mixed episode may have a very sad, hopeless mood while at the same time feel extremely energized.
Nearly 80% of those suffering from bipolar disorder are either misdiagnosed or undiagnosed altogether. One reason for misdiagnosis is that the symptoms of the disease are common to other conditions, such as depression and substance abuse. In some cases, patients don't seek treatment because the feelings associated with acute mania can be exhilarating. Often, they deny that they have any sort of problem or illness. Once patients are diagnosed, there are a variety of treatments available that can help manage the symptoms of bipolar disorder.
Risperdal was discovered and developed at the Janssen Research Foundation, now part of Johnson & Johnson Pharmaceutical Research & Development. Risperdal has been marketed in tablet form in the United States by Janssen Pharmaceutica Products since 1994, and is also available in oral solution and quick-dissolving tablet forms.
For more information on Risperdal, including full prescribing information, visit risperdal.com or janssen.com.
November 26, 2003
ST. LOUIS (MD Consult) - On December 2, 2003, Serono, Inc., announced that the U.S Food and Drug Administration (FDA) had approved Zorbtive (somatropin [rDNA origin] for injection), a recombinant human growth hormone, for use in the treatment of patients with short bowel syndrome (SBS).
Short bowel syndrome is a rare, serious, and potentially life-threatening condition that follows extensive surgical removal of portions of the small intestine as a treatment for acute or chronic disorders of the intestine. Removal of a large portion of the bowel results in impaired absorption of nutrients. Currently, the standard treatment for SBS involves careful management of dietary intake and hydration or, where appropriate, parenteral nutrition. On rare occasions, surgical transplant of the intestine may also be performed for this condition. There are an estimated 10,000 to 20,000 patients in the United States who are receiving intravenous parenteral nutrition for SBS.
In a randomized, double-blind, controlled, parallel-group Phase III clinical study, Zorbtive administered with specialized nutritional support was shown to significantly reduce patient dependence on total parenteral nutrition as measured by total volume, total calories, and frequency of infusion. Zorbtive was granted an orphan drug designation for use in the treatment of patients with SBS by the FDA Office of Orphan Products Development.
The most common adverse events associated with growth hormone therapy are mild to moderate muscle and joint pain and swelling/edema, which occur in a dose-related manner and often subside with continued treatment or dose reduction. Cases of new-onset impaired glucose intolerance, new-onset type 2 diabetes mellitus, and exacerbation of preexisting diabetes mellitus have been reported. Some patients develop diabetic ketoacidosis and diabetic coma. In some patients, therapy with growth hormone necessitates initiation or adjustment of anti-diabetic treatment. Patients with a history of hyperglycemia or other risk factors for glucose intolerance should be monitored closely. Transient increases in glucose levels occur early in treatment and should be monitored.
Use of growth hormone is contraindicated in treatment of patients in intensive care units due to complications following open-heart surgery or abdominal surgery, multiple accidental trauma, or acute respiratory failure; patients with active neoplasia; and patients with known hypersensitivity to growth hormone.
November 26, 2003
ST. LOUIS (MD Consult) - On November 25, 2003, the U.S. Food and Drug Administration (FDA) approved the New Drug Application that permits marketing of Plenaxis (abarelix), a drug indicated for the treatment of symptoms of advanced prostate cancer in men who cannot take other hormone therapies and who have refused surgical castration.
The drug will be marketed under a voluntary risk management program (RMP) agreed to and administered by the sponsor that will restrict the use of Plenaxis to patients with advanced prostate cancer, who have no alternative therapy, because of an increased risk of serious and potentially life-threatening allergic reactions associated with its use.
About 5% to 10% of men with prostate cancer have the type of advanced, symptomatic disease that would make them candidates for Plenaxis.
Plenaxis is a gonadotropin-releasing hormone (GnRH) antagonist that lowers the male hormone testosterone, which is a key factor involved in most prostate cancer growth. The effectiveness of Plenaxis in lowering testosterone production in men with advanced, symptomatic prostate cancer was demonstrated in a study of 81 men. The study showed that such patients could avoid surgical castration by undergoing at least 12 weeks of treatment. Some of the men also experienced other benefits from the use of this product, including decreased pain and relief from urinary problems. However, 3 of the 81 patients in the clinical trial experienced serious allergic reactions, one of which included loss of consciousness.
The FDA and the manufacturer have agreed that marketing of Plenaxis should be restricted to those patients with advanced, symptomatic prostate cancer who do not have other treatment options because of this increased risk of serious, potentially life-threatening allergic reactions. Because of the risk of low blood pressure and fainting as part of the allergic reaction to Plenaxis, patients who receive the drug are to be monitored for at least 30 minutes after receiving a dose of the drug in their health care provider's office setting. Moreover, the manufacturer will not be distributing the drug through retail pharmacies; rather, the drug will be distributed directly to physicians and hospital pharmacies enrolled in the Plenaxis RMP.
Plenaxis is administered as an injection into the muscles of the buttocks every 2 weeks for the first month of therapy, followed by once every 4 weeks thereafter. Because the drug may stop working in certain patients, doctors should perform blood tests every 2 months to make sure Plenaxis is working by keeping the level of testosterone low.
The most common adverse effects seen in the clinical trial were constipation, hot flashes, sleep disturbances, breast enlargement, and pain (including back and breast pain).
The Plenaxis RMP that the drug's manufacturer will be implementing is designed to help ensure that patients and physicians are fully informed of the risks and benefits of Plenaxis before using it. The RMP emphasizes the need for doctors, patients, and hospital pharmacists to work together to maximize the benefit of Plenaxis and minimize the risk.
As part of the program, the sponsor will only be distributing Plenaxis to physicians who attest to certain qualifications and are enrolled in Praecis' Plenaxis PLUS (Plenaxis User Safety) Program. In addition, the company is establishing educational programs for physicians, patients, and hospital pharmacists about the risks and benefits of Plenaxis. Patients will be asked to read and sign a patient information leaflet before receiving the drug. The company will also establish a system that collects and reports adverse events to the FDA. Enrolled physicians should also report serious adverse events to Praecis at 1-866-753-6294 or to FDA's MedWatch Program at 1-800-FDA-1088.
Finally, the company will also be conducting studies and assessments of the risk management program, including an assessment of the prescribing and actual use of Plenaxis.
Plenaxis is marketed by Praecis Pharmaceuticals Inc., Waltham, Mass.
November 21, 2003
ST. LOUIS (MD Consult) - On November 21, 2003, the U.S. Food and Drug Administration (FDA) approved Cialis (tadalafil), an oral medication to treat erectile dysfunction (ED) in men. This is the third oral product approved for this condition. This drug is different than currently approved products for ED in that it stays in the body longer.
ED affects millions of men in the United States. Cialis acts by relaxing muscles in the penis and blood vessels, allowing increased blood flow into the penis, which produces an erection.
Cialis was evaluated in randomized, placebo-controlled trials involving more than 4,000 men with ED. In two of these trials, men had ED associated with diabetes mellitus or following radical prostatectomy for prostate cancer.
The drug's effectiveness was assessed using a sexual function questionnaire. In addition, patients were asked to report whether they were able to achieve an erection adequate for intercourse and whether that erection was maintained to allow completion of intercourse. In all of these trials, Cialis improved patients' ability to achieve and maintain a penile erection. In other studies, sexual activity was improved in some patients at 30 minutes after taking a dose; additional studies demonstrated improvements for up to 36 hours after taking Cialis when compared with placebo.
The recommended starting dose for most patients is 10 mg taken before anticipated sexual activity. A higher dose of 20 mg is available for patients whose response to the 10-mg dose is not adequate. A lower dose (5 mg) is also available and may be necessary for patients taking other medicines or having medical conditions that may decrease the body's ability to metabolize tadalafil. Cialis should not be used more than once per day.
Cialis should not be used with nitrates (such as nitroglycerin tablets or patches) or with an alpha blocker other than Flomax 0.4 mg daily (alpha blockers are medicines used to treat benign prostatic hyperplasia and high blood pressure) because the combination can significantly lower blood pressure and lead to fainting, or even death, in some men.
Because some drugs affect the metabolism of Cialis, patients should inform their doctors that they are taking Cialis. For example, patients taking ketoconazole or ritonoavir should not take more than a 10-mg dose of Cialis once every 72 hours.
Also, in patients with moderately or severely decreased kidney function, the starting dose is 5 mg taken once daily. In this group, the dose may be increased to 10 mg taken once every 48 hours. In patients with mild or moderate liver impairment, the maximum dose of Cialis is 10 mg.
In most patients, after taking a single dose of Cialis, some of the drug will remain in the body for more than 2 days. In those with decreased kidney function, impairment of the liver, or those taking certain medications (eg, ketoconazole or ritonavir) tadalafil can remain in the body longer.
Cialis should not be taken by men in whom sexual activity is inadvisable because of their underlying cardiovascular status. Patients should inform their doctor about any heart problems they have experienced before taking Cialis.
Cialis is not recommended for patients who have suffered a heart attack or stroke within the last 6 months, or patients who have significantly low blood pressure, uncontrolled high blood pressure, unstable angina, severe liver impairment, or retinitis pigmentosa.
The most common side effects reported in clinical trials included headache, indigestion, back pain, muscle aches, flushing, and stuffy or runny nose. Patients who get back pain and muscle aches usually get it 12 to 24 hours after taking Cialis, and these usually go away by themselves within 48 hours. A small number of patients taking Cialis also reported abnormal vision.
Before taking Cialis, patients are advised to undergo a thorough medical history and physical examination to attempt to diagnose the underlying cause of the erectile dysfunction and to identify appropriate treatment.
Cialis confers no resistance to AIDS or other sexually transmitted diseases.
Cialis is manufactured for Lilly ICOS LLC by Eli Lilly and Company.
November 17, 2003
ST. LOUIS (MD Consult) - On November 14, 2003, the U.S. Food and Drug Administration (FDA) approved Ovcon 35, an oral, spearmint-flavored contraceptive tablet that can be chewed and swallowed. This new version of Ovcon 35, indicated for the prevention of pregnancy, provides one more alternative to the many types of oral contraceptives currently on the market. Ovcon 35 contains a progestin (norethindrone) and an estrogen (ethinyl estradiol) found in products that are already marketed.
The directions for use tell women that the pill may be swallowed whole or chewed and swallowed. If the pill is chewed and then swallowed, the woman should drink a full glass (8 oz) of liquid immediately afterwards so that the full dose of medication reaches the stomach and no residue is left in the mouth.
Ovcon 35 is available only in a 28-day regimen. Each package contains 21 round, white tablets, with norethindrone and ethinyl estradiol followed by seven reminder green (inactive) tablets to complete a 4-week cycle.
Like other birth control pills, Ovcon 35 is effective for prevention of pregnancy when used as directed. The risks of using this product are similar to those of all birth control pills and include an increased risk of blood clots, heart attack, and stroke. The labeling also carries the warning that cigarette smoking by women, especially those over age 35 years, increases the risk of serious cardiovascular side effects from use of combination hormonal contraceptives.
The product is manufactured by Bristol Myers Squibb Company of Princeton, NJ, and will be marketed by Warner Chilcott, Inc., Rockaway, NJ.
October 29, 2003
ST. LOUIS (MD Consult) - On October 27, 2003, San Francisco-based Genentech Inc. announced the U.S. Food and Drug Administration (FDA) had approved its medication Raptiva (efalizumab) as a treatment for moderate to severe chronic plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.
Raptiva is the first biologic therapy that is designed to provide continuous control of chronic moderate to severe plaque psoriasis and can be self-administered by patients as a single, once-weekly, subcutaneous injection.
"I've been treating psoriasis for over 15 years and have always been frustrated by the limited options available to treat patients with this chronic disease. Safety limitations of traditional therapies have made it difficult to offer patients continuous relief," said Craig Leonardi, MD, clinical associate professor of dermatology of Saint Louis University, St. Louis, Mo, and a Raptiva clinical investigator. "Raptiva has the potential to break the cycle of intermittent therapy by offering patients and their doctors a convenient treatment regimen that can be used continuously."
Raptiva is a humanized therapeutic antibody designed to selectively and reversibly block the activation, reactivation, and trafficking of T cells that lead to the development of psoriasis symptoms. In clinical studies, Raptiva demonstrated a rapid onset of action in the reduction of symptoms associated with psoriasis, in some patients within 4 weeks of initiating treatment. Raptiva is administered once weekly via subcutaneous injection and can be self-administered by patients at home.
"Since there is no cure for psoriasis, people have to manage their disease over their lifetime. It is a major challenge to find a treatment that works, has a favorable track record for safety, and can be easily integrated into a patient's life," said Gail M. Zimmerman, president and chief executive officer of the National Psoriasis Foundation. "Raptiva offers a new treatment option for psoriasis that, because of its convenience and ease of administration, may provide patients with a sense of control over their disease."
Genentech and Xoma Ltd of Berkeley, Calif, are collaborating on the development of Raptiva in the United States. Serono SA, Genentech's marketing partner outside the United States and Japan, announced earlier in the year that it had submitted a Marketing Authorization Application (MAA) to the European Agency for the Evaluation of Medicinal Products (EMEA) for European Union Approval of Raptiva in psoriasis. Serono has also submitted Raptiva data for marketing approval in Canada, Switzerland, Australia, and New Zealand and is filing in additional countries.
The companies submitted this latest application to the FDA in December 2002. They first sought approval in April 2002, but the agency asked for confirmation that Genentech facilities could duplicate earlier batches of the drug without changing its chemical composition.
The FDA's approval decision was based on data from four randomized, placebo-controlled phase III studies. The phase III trials were designed to evaluate the safety and efficacy of Raptiva in treating chronic moderate to severe plaque psoriasis. The studies had a primary efficacy end point of 75% improvement in the Psoriasis Area and Severity Index (PASI). The PASI is a composite score that takes into consideration both the fraction of body surface area affected and the nature and severity of the psoriatic changes within the affected regions (erythema, infiltration/plaque thickness, and desquamation). Secondary end points for the phase III studies included physician assessment and patient-reported outcomes.
Raptiva demonstrated efficacy and maintained response in most patients after 12 weeks of treatment. Sustained responses to Raptiva have also been observed in uncontrolled open-label extension treatment trials in which patients received Raptiva without interruption for 24 weeks.
Common adverse events that occurred at least 2% more frequently in Raptiva patients than in placebo included acne, chills, pain, fever, nausea, headache, back pain, flu syndrome, myalgia (muscle pain), and infection (mostly upper respiratory infections). Five of these events (chills, fever, nausea, headache, and myalgia) were predominantly acute adverse events and were principally seen following the first 2 injections of Raptiva. For the third and subsequent doses, the incidence of acute adverse events was similar between the Raptiva and placebo groups. Less than 1% of patients were discontinued from treatment due to acute adverse events.
Raptiva is an immunosuppressive agent and has the potential to increase the risk of infection and reactivate latent, chronic infections. Many immunosuppressive agents have the potential to increase the risk of malignancy. The role of Raptiva in the development of malignancies is not known. Serious adverse events occurring in clinical studies with Raptiva were serious infections (0.4% in Raptiva vs 0.1% in placebo), malignancy (the overall incidence of malignancies of any kind was 1.8 per 100 patient-years for Raptiva-treated patients compared with 1.6 per 100 patient-years for placebo-treated patients), thrombocytopenia (0.3% Raptiva vs 0.0% placebo), and worsening of psoriasis, typically upon discontinuation (0.7% in Raptiva vs. 0.0% in placebo).
Psoriasis occurs when new skin cell growth rapidly accelerates, resulting in thick, red, scaly, inflamed patches on the skin surface. According to Genentech, psoriasis affects approximately 4.5 million persons in the United States. Plaque psoriasis, the most common form of the disease, is characterized by inflamed patches of skin ("lesions") topped with silvery white scales. Psoriasis can be limited to a few spots or can involve extensive areas of the body, appearing most commonly on the scalp, knees, elbows, and trunk. Although it is highly visible, psoriasis is not a contagious disease. Although there are a number of medications that can help control the symptoms of psoriasis, there is currently no cure.
Spokespersons at Genentech have said they expect to start shipping Raptiva in mid-November 2003.
For more information on psoriasis, log on to allaboutpsoriasis.com or visit the National Psoriasis Foundation's Web site at psoriasis.org.
For full prescribing information, visit gene.com or call 1-877-RAPTIVA. For more information on Raptiva, including information on comprehensive support services, visit raptiva.com or call 1-877-RAPTIVA.
October 22, 2003
ST. LOUIS (MD Consult) - On October 22, 2003, London-based GlaxoSmithKline announced that the U.S. Food and Drug Administration granted marketing clearance for Lexiva (fosamprenavir calcium), a new protease inhibitor (PI) for the treatment of HIV infection in adults in combination with other antiretroviral medications. Lexiva was co-discovered by GlaxoSmithKline and Vertex Pharmaceuticals.
The following points should be considered when initiating therapy with Lexiva/ritonavir (Lexiva/r) in PI-experienced patients: the PI-experienced patient study was not large enough to reach a definitive conclusion that Lexiva/r and lopinavir/ritonavir are clinically equivalent. Once-daily administration of Lexiva plus ritonavir is not recommended for PI-experienced patients.
Lexiva, a PI that can be taken once or twice daily without food or water restrictions, has been evaluated in clinical trials with both PI-experienced and antiretroviral therapy (ART)-naive HIV patients.
Lexiva may be dosed three different ways: (1) two 700-mg tablets twice daily (BID); (2) two 700-mg tablets once daily (QD) in combination with two 100-mg capsules of ritonavir QD (Lexiva/r QD); or (3) one 700-mg tablet BID in combination with one 100-mg capsule of ritonavir BID (Lexiva/r BID). For PI-experienced patients, the recommended dose is one 700-mg tablet BID in combination with one 100-mg capsule of ritonavir BID.
More than 1,200 people—both ART-naive and PI-experienced patients—participated in three phase III trials to test the safety and efficacy of Lexiva with and without ritonavir. In all three trials, study drugs were taken as part of combination therapy that included two nucleoside reverse transcriptase inhibitors. In these clinical trials, Lexiva demonstrated the following:
"It's important for patients to comply with therapy because current treatment is lifelong," said Jeffrey P. Nadler, MD, Professor of Medicine and Director of Clinical Research in Infectious Diseases, University of South Florida College of Medicine, Tampa. "Patients need something they can tolerate, so that they are able to take the medicines as prescribed. Lexiva fits that picture."
Lexiva is contraindicated in patients with previously demonstrated clinically significant hypersensitivity to any of the components of this product or to amprenavir. New onset or exacerbations of diabetes mellitus and hyperglycemia, as well as spontaneous bleeding in hemophiliacs have been reported with protease inhibitors. Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy. The causal relationship, mechanism, and long-term consequences of these events are currently unknown. Lexiva is contraindicated with ergot derivatives, cisapride, pimozide, midazolam, and triazolam. If Lexiva is coadministered with ritonavir, flecainide and propafenone are also contraindicated.
For full prescribing information, call GlaxoSmithKline at 919-483-2839.
October 20, 2003
ST. LOUIS (MD Consult) - On October 17, 2003, the U.S. Food and Drug Administration (FDA) approved memantine (Namenda) for treatment of moderate to severe Alzheimer's disease. This is the first drug approved for the treatment of patients with this severity of disease. Previous treatments for Alzheimer's disease have been studied in less severely affected (mild to moderate) patients. Memantine's mechanism of action is different from that of the drugs currently available for treating this disease.
Alzheimer's disease, which affects about 4.5 million Americans, is a degenerative condition affecting memory, judgment, and the ability to reason. The new drug, an N-methyl-D-asparate (NMDA) antagonist, is thought to work by blocking the action of the chemical glutamate.
Although memantine helps treat the symptoms of Alzheimer's disease in some patients, there is no evidence that it modifies the underlying pathology of the disease.
FDA Commissioner Mark McClellan, MD, PhD, said, "The approval of memantine is good news for Alzheimer's disease patients. This is the first drug shown to have an effect on the symptoms of moderate to severe Alzheimer's disease, and shows a low incidence of minor side effects."
The first two double-blind studies, each of about 6 months' duration, were conducted in the United States and involved about 250 and about 400 patients, respectively. The larger study was carried out in patients already taking donepezil, a drug already approved for the treatment of Alzheimer's disease. Both studies showed that patients taking memantine experienced less advancement of their symptoms compared with patients treated with placebo during the study. The third study, conducted in nursing homes in Latvia, was a 12-week double-blind study in 166 patients with severe Alzheimer's disease and also showed a statistically significant advantage of memantine over placebo.
The studies used a variety of measures to evaluate the effectiveness of memantine. For the two studies conducted in the United States, the measures included the Severe Impairment Battery (SIB) to assess attention, orientation, language, memory, and social interactions, and the modified Alzheimer's disease Cooperative Study–Activities of Daily Living (ADCS-ADL) scale, which assessed the ability of patients to eat, dress, bathe, travel, shop, and perform household chores.
The third study used the Behavioral Rating Scale for Geriatric patients (BGP), which assessed day-to-day functioning, and the Clinical Global Impression of Change (CGI-C), which assessed the overall condition of the patients.
The most frequently reported adverse events were dizziness (7%), headache (6%), and constipation (6%).
In September 2003, the FDA's Peripheral and Central Nervous System Drugs Advisory Committee unanimously agreed that memantine is effective and safe for the treatment of moderate to severe Alzheimer's disease. Memantine will be marketed under the trade name Namenda by Forest Labs of Jersey City, NJ.
October 14, 2003
ST. LOUIS (MD Consult) - On October 10, 2003, the U.S. Food and Drug Administration (FDA) approved Estrasorb (estradiol topical emulsion), an estrogen therapy product in a topical form. Current estrogen products available for treatment include oral pills, transdermal patches, and a vaginal ring. Estrasorb has been proved effective for the treatment of severe hot flashes and night sweats associated with menopause.
Estrasorb is a white lotion-like emulsion that women apply only to their legs, thighs, or calves on a daily basis. The product is absorbed through the skin into the bloodstream to achieve its effect. As a precaution, women are advised not to apply sunscreen and Estrasorb at the same time because this may affect the amount of estradiol absorbed.
In January 2003, the FDA advised women and their doctors that menopausal hormone therapy—estrogen and estrogen with progestins—may be associated with an increased risk of heart disease, heart attacks, strokes, and breast cancer. This was based on the findings of the Women's Health Initiative (WHI) conducted by the National Institutes of Health (NIH). Label warnings and cautions for Estrasorb are similar to those for other menopausal hormonal therapy products.
To help women make decisions about whether to take hormone therapy, the FDA and the NIH initiated a nationwide information campaign to raise awareness about the recent WHI findings. The FDA, the NIH, and a variety of organizations developed a menopause and hormone-therapy fact sheet, as well as a purse guide that women can use to discuss their options with a health professional. These materials are available in both English and Spanish from the National Women's Health Information Center (NWHIC) at 4woman.gov.
Based on the latest evidence, the FDA believes that estrogens and estrogen with progestin products, such as this new product, provide valuable therapy for many postmenopausal women, particularly those experiencing "hot flashes." The FDA reminds women that these treatments also have important risks and should be used in the lowest dose and for the least duration required to provide relief.
This new approval gives postmenopausal women a new option for getting the benefits of estrogen.
Postmenopausal women who use or are considering the use of these treatments should discuss with their physicians whether the benefits outweigh the risks for them individually. The FDA also reminds women that estrogens and estrogen with progestin products should not be used to prevent heart disease, heart attacks, or strokes.
Estrasorb is manufactured and distributed by Novavax, Columbia, Md. The drug is expected to be available in early 2004.
September 19, 2003
ST. LOUIS (MD Consult) - On September 18, 2003, Genta Inc. announced that the U.S. Food and Drug Administration (FDA) had approved its drug Ganite (gallium nitrate injection) for the treatment of cancer-related hypercalcemia that is resistant to hydration. Ganite is the first drug from New Jersey-based Genta to receive marketing approval.
Cancer-related hypercalcemia is a life-threatening elevation of blood calcium that can occur in up to 50% of patients with advanced cancer, according to Genta. The disorder is usually caused by the release of factors from tumor cells, which markedly accelerate the loss of calcium from bone. Hypercalcemia is particularly common in patients with cancers of the lung, breast, head and neck, and kidney, as well as those with multiple myeloma.
Ganite was originally developed by the National Cancer Institute as a cancer chemotherapy drug. A separate series of studies showed that the drug markedly reduced the loss of calcium from bone, suggesting the drug may be useful in hypercalcemia and other conditions associated with loss of bone mass.
Ganite is contraindicated in patients with severe renal impairment (serum creatinine > 2.5 mg/dL). Although Ganite was generally well tolerated by patients who received the drug in clinical trials, concurrent use of Ganite with other potentially nephrotoxic drugs such as aminoglycosides and amphotericin B may increase the risk for developing severe renal insufficiency in patients with cancer-relapsed hypercalcemia. If use of a potentially nephrotoxic drug is indicated during Ganite therapy, Ganite should be discontinued and hydration is recommended for several days. Full prescribing information is available at ganite.com.
September 16, 2003
ST. LOUIS (MD Consult) - On September 12, 2003, the U.S. Food and Drug Administration (FDA) announced the approval of Cubicin (daptomycin for injection) for the treatment of complicated skin and skin structure infections. These serious infections, usually occurring in hospitalized patients, include major abscesses, postsurgical skin wound infections, and infected ulcers.
Cubicin is the first approved product in a new class of antibiotics called cyclic lipopeptide antibacterial agents. Cubicin treats infections in a way that is distinct from any other antibiotic.
The approval of Cubicin is part of the FDA's ongoing efforts to help bring new types of antibiotics to patients to make sure there are treatment options available for serious infections. In 2002, doctors prescribed an estimated 7 million courses of IV antibiotics for patients with complicated skin and skin structure infections in U.S. hospitals.
Cubicin is specifically indicated for the treatment of complicated skin and skin structure infections caused by susceptible strains of the following gram-positive microorganisms: Staphylococcus aureus (including methicillin-resistant strains), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae subspecies equisimilis, and Enterococcus faecalis (vancomycin-susceptible strains only). Cubicin is not indicated for the treatment of pneumonia.
The FDA based its decision to approve Cubicin on a review of clinical studies involving over 1,400 adults that demonstrated the drug's safety and efficacy. The clinical studies demonstrated Cubicin was equivalent to standard treatments (i.e., vancomycin or a semi-synthetic penicillin such as oxacillin or nafcillin) in the treatment of complicated skin and skin structure infections.
Most adverse events reported in the clinical studies of Cubicin were mild to moderate in intensity. The most common adverse events included gastrointestinal disorders, injection site reactions, fever, headache, insomnia, dizziness, and rash.
Blood tests showing muscle injury were found rarely in patients in clinical trials. Most of these patients had no symptoms, and the blood tests returned to normal after therapy. Patients receiving Cubicin should be monitored for muscle pain or weakness. Blood tests measuring creatine phosphokinase (CPK) levels should be monitored weekly in patients who receive Cubicin. Those who experience unexplained elevations in CPK while on Cubicin should be monitored more frequently.
Cubist Pharmaceutical Inc., of Lexington Mass., is the sponsor of the approved New Drug Application (NDA) for Cubicin.
September 9, 2003
ST. LOUIS (MD Consult) - On September 5, 2003, the U.S. Food and Drug Administration (FDA) approved Seasonale, a new oral contraceptive for women for the prevention of pregnancy. Seasonale is a 91-day oral contraceptive regimen. Tablets containing the active hormones are taken for 12 weeks (84 days), followed by 1 week (7 days) of placebo tablets. Conventional oral contraceptive use is based on a 28-day regimen (21 days of active tablets followed by 7 days of placebo tablets). Seasonale contains a progestin (levonorgestrel, 0.15 mg) and an estrogen (ethinyl estradiol, 0.03 mg), which are active ingredients in already approved oral contraceptives.
Under Seasonale's dosing regimen, the number of expected menstrual periods that a woman usually experiences is reduced from about once a month to about once every 3 months. As with the conventional 28-day regimen, women will have their period while taking the placebo tablets.
Although Seasonale users have fewer scheduled menstrual cycles, the data from clinical trials show that many women, especially in the first few cycles of use, had more unplanned bleeding and spotting between the expected menstrual periods than women taking a conventional 28-day cycle oral contraceptive.
Like other available oral contraceptives, Seasonale is effective for the prevention of pregnancy when used as directed. Clinical trials of Seasonale found that it prevented pregnancy and was as safe as traditional birth control pills. The risks of using Seasonale are similar to the risks of other conventional oral contraceptives, including an increased risk of blood clots, heart attack, and stroke. The labeling also carries the warning that cigarette smoking increases the risk of serious cardiovascular side effects from use of combination estrogen and progestin containing contraceptives. Birth control pills do not protect against HIV infection or other sexually transmitted diseases.
Since Seasonale users can expect to have fewer periods, the label also advises women to consider the possibility that they may be pregnant if they miss any scheduled periods. Women should discuss contraceptive use and the precautions and warnings for use of the drug with their doctors.
Seasonale is manufactured by Barr Laboratories of Pomona, New York. The company said the extended-cycle pill would be available by prescription at the end of October 2003. A Barr spokesperson said Seasonale will be available for about $1 a pill, which is comparable to other branded oral contraceptives.
September 2, 2003
ST. LOUIS (MD Consult) - On August 28, 2003, the U.S. Food and Drug Administration (FDA) approved Wellbutrin XL (bupropion hydrochloride extended-release tablets) for the treatment of major depressive disorder in patients 18 years and older. According to the drug's manufacturer, GlaxoSmithKline, this once-daily antidepressant carries a low risk of sexual side effects and weight gain.
"Depressive illness affects approximately 14 million adults or 6.6% of the U.S. population in a given year," GlaxoSmithKline representatives stated in an August 28 press release. "Nearly two thirds of people fail to get help for their depression, yet treatment can alleviate symptoms in more than 80% of cases."
This FDA approval comes just months before generic versions of Wellbutrin SR, GlaxoSmithKline's twice-daily formulation of bupropion, and Paxil CR, the company's top-selling antidepressant, become available. Wellbutrin XL is expected to be on pharmacy shelves in mid-September.
"[W]e know that for many doctors twice-daily dosing is a major prescribing barrier," said Chris Viehbacher, President of US Pharmaceuticals at GlaxoSmithKline. "We are confident that the convenient once-daily dosing of Wellbutrin XL will be a welcome improvement for patients coping with depressive illness and for the physicians who are treating them."
Wellbutrin XL tablets have a two-layered coating designed to release the drug slowly in the body. GlaxoSmithKline licensed the once-daily formulation of bupropion hydrochloride from Biovail Corporation in October 2001.
Placebo-controlled trials of Wellbutrin SR show it to be generally well tolerated. Adverse events in at least 10% of patients treated with Wellbutrin SR 300 or 400 mg/d included dry mouth, nausea, insomnia, dizziness, weight loss, and pharyngitis. Similar side effects would be expected with the use of Wellbutrin XL, although clinical trials have not been undertaken to formally evaluate the drug.
Wellbutrin XL is contraindicated in patients who have or have had a seizure disorder, patients who have or have had bulimia or anorexia nervosa, patients undergoing abrupt discontinuation of alcohol or sedatives (including benzodiazepines), patients taking monoamine oxidase (MAO) inhibitors, and patients taking Zyban (bupropion hydrochloride) Sustained-Release Tablets, Wellbutrin SR, or any other medications that contain bupropion.
In treating depression, physicians should be aware that Wellbutrin XL is associated with a dose-related risk of seizures. Although clinical trials to evaluate Wellbutrin XL specifically have not been performed, the drug's incidence of seizure may be similar to that of the immediate-release and the sustained-release formulations of bupropion because it has demonstrated bioequivalence to both. At doses of up to 300 mg/d of Wellbutrin SR, the incidence of seizure is approximately 0.1%. At doses of 300 to 450 mg/d of the immediate-release formulation (Wellbutrin), the incidence of seizure is approximately 0.4%. To reduce the risk of seizures, refer to the Warnings section of the Prescribing Information for patient selection considerations, including concomitant medications and dosing recommendations.
Wellbutrin XL will be available in two strengths, 150 mg and 300 mg, to allow for dosing flexibility. The usual target dose is 300 mg given once daily-initiated at 150 mg/d and then increased to 300 mg/d as early as day 4, if adequately tolerated. The maximum total daily dose of Wellbutrin XL is 450 mg.
The weight loss potential of Wellbutrin XL should be considered if weight loss is a major presenting sign of the depressive illness. When treating patients with severe hepatic cirrhosis, extreme caution should be exercised and a reduced dosage and/or frequency is required to avoid accumulation.
For more information on this new medication, contact GlaxoSmithKline at 919-483-2839.
September 2, 2003
ST. LOUIS (MD Consult) - On August 29, 2003, Switzerland-based Serono announced that the U.S. Food and Drug Administration (FDA) had approved the drug Serostim (somatotropin) for treatment of muscle wasting in HIV-positive patients.
The drug can now be used to increase lean body mass and body weight and improve physical endurance in patients fighting wasting, also known as cachexia.
In 1996, Serostim received accelerated approval, a special regulatory status granted by the FDA for approval of a drug that is used to treat patients with serious or life-threatening illnesses. Under the terms of the accelerated approval, the drug's manufacturer conducted a multi-center, confirmatory placebo-controlled study with Serostim. Data from this trial were used to substantiate previous study findings of increased lean body mass and improvement in physical endurance occurring with use of Serostim. In addition, patients in this study perceived an improvement in their wasting symptoms with Serostim treatment.
"Wasting continues to be a major concern in the management of HIV and AIDS treatment, even with the benefits of highly active antiretroviral therapy," said James Sapirstein, Executive Vice President, Metabolic Endocrinology, Serono, Inc., in a press release. It is hoped that Serostim will make a "positive difference in the physical endurance of people experiencing HIV wasting."
HIV-associated wasting is a chronically debilitating and potentially life-threatening condition. It is a metabolic disorder that causes the body to use vital muscle and organ tissue, which are critical for survival, for energy instead of primarily using the body's stored fat. Loss of lean body mass, which consists of muscle tissue, important body organ tissue, and blood cells, can lead to increased risk of opportunistic infections, illness, and extreme fatigue and can profoundly diminish a patient's quality of life.
Serostim was granted orphan drug designation by the FDA in 1991 for treatment of HIV-associated wasting.
According to Serono, the recommended dose of Serostim is 0.1 mg/kg daily (6 mg/d for patients > 55 kg). Serostim 0.1 mg/kg every other day should be considered as a starting dose in patients thought to be at risk for certain adverse effects (i.e., glucose intolerance).
The most common adverse events associated with Serostim therapy are mild to moderate muscle and joint pain and swelling/edema, which occur in a dose-related manner and often subside with continued treatment or dose reduction. Cases of new-onset impaired glucose intolerance, new-onset type 2 diabetes mellitus, and exacerbation of preexisting diabetes mellitus have been reported in patients receiving Serostim. Some patients develop diabetic ketoacidosis and diabetic coma. In some patients, therapy with Serostim necessitated initiation or adjustment of anti-diabetic treatment. Patients with a history of hyperglycemia or other risk factors for glucose intolerance should be monitored closely during treatment with Serostim. Transient increases in glucose levels occur early in treatment and should be monitored.
Use of growth hormone is contraindicated in treatment of patients with active neoplasia, patients with known hypersensitivity to growth hormone, and patients in intensive care units due to complications after open-heart surgery or abdominal surgery, multiple accidental trauma, or acute respiratory failure. Serostim must be used in conjunction with antiretroviral therapy.
Full prescribing information for Serostim, including important safety information, is available at serostim.com.
August 29, 2003
ST. LOUIS (MD Consult) - On August 28, 2003, the U.S. Food and Drug Administration (FDA) approved higher-dose extended-release tablets of Cipro XR (ciprofloxacin).
Cipro's manufacturer, Bayer AG, announced that the FDA had approved a 1,000-milligram form of Cipro XR, to be taken once a day for 7 to 14 days. In 2002, a 500-mg version of the drug was approved; this dose was to be taken once daily for 3 days.
This dosage was approved for the treatment of complicated urinary tract infections (cUTIs) and acute uncomplicated pyelonephritis (AUP).
Cipro XR is specifically formulated to be taken just once daily to kill certain bacteria causing UTIs. The new formulation was developed using a bilayer matrix of the active ingredient ciprofloxacin, which enables two different release mechanisms. The first is a rapid release of ciprofloxacin, which quickly distributes to the serum and tissues. This is followed by a second extended release of the active ingredient to achieve high concentrations of ciprofloxacin in the urine for the full 24-hour dosing interval.
"The once-a-day convenience of Cipro XR may contribute to compliance among patients, thereby helping to reduce the risk of UTI relapse and subsequent resistant infection," said Dr. David Talan, Professor of Medicine, David Geffen School of Medicine at UCLA. "By combining once-a-day dosing with excellent antimicrobial activity, Cipro XR may be recommended as a convenient option for the appropriate and targeted treatment of complicated UTIs."
Results of a prospective, randomized, double-blind, multicenter trial were included in the New Drug Application (NDA) submitted to the FDA in October 2002. The study enrolled 1,042 patients and compared 1,000-mg once-daily Cipro XR to a twice-daily 500-mg dose of conventional Cipro (ciprofloxacin HCl). Adult male and female patients were evaluated based on the presence of cUTI and AUP. Evaluation was based on bacteriologic and clinical outcomes.
Bacteriologic eradication (evaluated 5-11 days post-therapy) was achieved in 89% of patients with cUTI treated with once-daily Cipro XR and 81% of patients treated with conventional twice-daily Cipro. For patients with AUP, bacteriologic eradication of Escherichia coli was achieved in 97% treated with once-daily Cipro XR and 100% of patients treated with conventional twice-daily Cipro.
Clinical cure (evaluated 5-11 days post-therapy) was observed in 96% of cUTI patients treated once a day with Cipro XR 1,000 mg, compared with 91% of patients receiving the traditional Cipro 500 mg twice daily. For patients with AUP, clinical cure was observed in 98% of patients percent treated with once-daily Cipro XR and 96% of patients treated with conventional twice-daily Cipro.
Rates of drug-related adverse events were similar in both groups. Adverse reactions determined to be at least possibly drug-related occurring in at least 1% of patients were nausea (3%), diarrhea (2%), headache (1%), dyspepsia (1%), dizziness (1%), and vaginal moniliasis (1%). Vomiting (1%) occurred in the 1,000-mg group.
Serious and fatal reactions have been reported in patients receiving concurrent administration of ciprofloxacin and theophylline. Monitor theophylline levels if concurrent administration cannot be avoided. The safety and effectiveness of Cipro XR in children, adolescents younger than 18 years, pregnant women, and lactating women have not been established. Cipro XR is contraindicated in persons with a history of hypersensitivity to ciprofloxacin or any quinolone and should be discontinued at the first sign of an allergic reaction.
Cipro XR should be administered at least 2 hours before or 6 hours after antacids containing magnesium, aluminium, calcium, or other products containing metal cations. A 2-hour window between substantial calcium intake (>800 mg) and dosing with Cipro XR is recommended.
Full prescribing information for CIPRO XR can be viewed at ciproxr.com.
August 20, 2003
ST. LOUIS (MD Consult) - On August 19, 2003, the US Food and Drug Administration approved Levitra (vardenafil), an oral medication to treat erectile dysfunction in men. This is the second oral product approved for the treatment of erectile dysfunction.
Erectile dysfunction affects millions of men in the United States. Levitra acts by relaxing muscles in the penis and blood vessels, allowing increased blood flow into the penis, which produces an erection.
Levitra was evaluated in randomized, placebo-controlled trials involving more than 2,000 men with erectile dysfunction. In two of the trials, men had erectile dysfunction associated with diabetes mellitus or following radical prostatectomy for prostate cancer.
The drug's effectiveness was assessed using a sexual function questionnaire. In addition, patients were asked to report whether they were able to achieve an erection adequate for intercourse and whether the erection was maintained to allow completion of intercourse. In all of the trials, Levitra improved patients' ability to achieve and maintain a penile erection.
The recommended dose is 10 mg taken 1 hour before sexual activity. A higher dose of 20 mg is available for patients whose response to the 10-mg dose is not adequate. Two lower doses (2.5 and 5.0 mg) are also available and may be necessary for patients taking other medicines or those who have medical conditions that may decrease the body's ability to metabolize vardenafil. Levitra should not be used more than once a day.
Levitra should not be used with nitrates or with alpha-blockers (medicines used to treat benign prostatic hyperplasia and/or high blood pressure such as tamsulosin, terazosin, doxazosin, and alfuzosin) because the combination may significantly lower blood pressure and lead to fainting in some men. Currently there is no information available to support the safety of even the lower doses of vardenafil taken together with alpha-blockers. In addition, Levitra should not be used in patients who have a rare heart condition known as "prolongation of the QT interval" because of the possibility of producing abnormal heart rhythm. This issue was discussed at a Cardio-Renal Advisory Committee Meeting on May 29, 2003, and the committee recommended drug approval.
Because some drugs may affect the metabolism of Levitra, patients should inform their doctors that they are taking Levitra and they should not begin taking new medicines without informing their doctors. For example, patients taking erythromycin should not take more than a 5-mg dose of Levitra, and a maximum dose of 2.5 mg Levitra once every 72 hours is the maximum recommended dose for patients who are taking ritonavir.
Levitra should not be taken by men in whom sexual activity is inadvisable because of their underlying cardiovascular status. Patients should inform their doctors about any heart problems they have experienced before taking Levitra.
Levitra is not recommended in patients who have suffered a heart attack or stroke within the last 6 months, or patients who have significantly low blood pressure, uncontrolled high blood pressure, unstable angina, severe liver impairment, end-stage renal disease requiring dialysis, or retinitis pigmentosa.
The most common side effects reported in clinical trials included headache, flushing, rhinitis, and indigestion. Dizziness was reported in about 2% of patients. A small number of patients taking Levitra also reported abnormal vision.
Before taking Levitra, patients are advised to undergo a thorough medical history and physical examination to diagnose the underlying cause of the erectile dysfunction and to identify appropriate treatment.
Levitra confers no resistance to AIDS or other sexually transmitted diseases.
Levitra is manufactured by Bayer Corporation in Germany and will be distributed by GlaxoSmithKline. The drug is currently available in Europe.
July 29, 2003
ST. LOUIS (MD Consult) - On July 25, 3003, the U.S. Food and Drug Administration (FDA) licensed a new recombinant DNA-derived clotting factor to treat people with hemophilia A. This new antihemophilic human factor VIII product from Baxter Healthcare Corporation, Deerfield, Illinois, is the first such product made without additives derived from human or animal blood.
This advancement provides added reassurance against any theoretical infectious risks that may arise from the use of blood-derived additives in the manufacturing of factor VIII.
The new product, called Advate Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method (rAHF-PFM), is approved to prevent and control bleeding episodes or to prepare persons with hemophilia for surgery. It is produced by genetically engineered Chinese hamster ovary cells that have been altered to produce factor VIII.
A number of human factor VIII products have been approved to treat hemophilia A, an inherited disorder in which the blood-clotting protein factor VIII is deficient or abnormal. According to the World Health Organization, more than 400,000 people worldwide may have hemophilia A, including 15 to 20 out of every 100,000 males. Replacement therapy with any of the factor VIII products, which requires intravenous administration, corrects the defect only temporarily. For this reason, factor VIII products frequently must be given several times a week or more to prevent or treat bleeding episodes.
Current factor VIII products (both plasma-derived and recombinant) are considered safe as a result of many technological advances in the last two decades. These include viral inactivation and removal steps in manufacturing that are believed to effectively prevent transmission of hepatitis B, hepatitis C, or HIV from plasma-derived products. These same procedures are considered effective to minimize any infectious risks from products made by DNA technology, which uses living cells. None of these products has transmitted HIV, hepatitis B, or hepatitis C since 1987.
The first recombinant antihemophilic factor was approved in 1992. However, up until now, all recombinant factor VIII products were still made with the use of blood-derived additives of human or animal origin, such as albumin. These additives were needed to keep the cells viable so they could make the factor VIII protein. In this new product, non-human and non-animal materials replaced these additives.
July 28, 2003
ST. LOUIS (MD Consult) - On July 25, 2003, the U.S. Food and Drug Administration approved a new drug, Aloxi (palonosetron hydrochloride), for the prevention of nausea and vomiting associated with chemotherapy. The medication is manufactured and marketed by MGI Pharma Inc, a Minneapolis-based pharmaceutical company, and Helsinn Healthcare SA, a private Swiss drug maker.
The companies said the drug was approved to treat acute nausea and vomiting and to prevent delayed nausea and vomiting associated with the most types of chemotherapy. The recommended injection dose is 0.25 mg.
In a July 25 press release, Edward B. Rubenstein, MD, Chief of the Section of Medical Supportive Care at M.D. Anderson Cancer Center, stated: "Despite standard treatment with currently available medications, our research shows that thirty percent of patients are not well controlled during the acute CINV [chemotherapy-induced nausea and vomiting] phase and one half of all chemotherapy patients still experience delayed nausea and vomiting."
Results from three Phase 3 clinical trials conducted by Helsinn demonstrate that Aloxi is effective in preventing both acute and delayed CINV in patients receiving moderately emetogenic chemotherapy, the most common chemotherapy regimen currently used. If not prevented, CINV is estimated to afflict the majority of cancer patients undergoing chemotherapy and can result in a delay or even discontinuation of chemotherapy treatment.
Adverse reactions were similar in frequency and severity with Aloxi and the comparator agents. The most common adverse reactions related to the study drug at a dose of 0.25 mg were headache (9%) and constipation (5%). The effect of Aloxi on ECG parameters was comparable to ondansetron and dolasetron in clinical trials; it should be administered with caution in patients who have or may develop prolongation of cardiac conduction intervals.
For more information, contact David Melin, MGI Pharma, at 952-346-4749 or Rachid BenHamza, Helsinn Healthcare, at (+41) 91-9852121.
July 28, 2003
ST. LOUIS (MD Consult) - On July 24, 2003, the U.S. Food and Drug Administration (FDA) approved an application for etanercept (trade name Enbrel), a genetically engineered protein, for a new indication for treatment of patients with active ankylosing spondylitis (AS), a chronic inflammatory disease affecting primarily the lower back and joints. The product is manufactured by Immunex Corporation (Thousand Oaks, California) and marketed by Amgen and Wyeth Pharmaceuticals. Etanercept is also licensed for treatment of patients with rheumatoid arthritis, juvenile rheumatoid arthritis, and psoriatic arthritis.
Approximately 350,000 patients in the United States have AS. The disease affects men more often than women. Symptoms of the disease may start in adolescence and are usually present by age 30. Patients often have lower back pain and stiffness, chest pain, joint pain and swelling, and tenderness due to the inflammation. In some patients, the disease can cause significant pain and disability for many years.
Currently approved drugs for AS include some nonsteroidal anti-inflammatory drugs (NSAIDs) that are approved to treat the symptoms of AS. Disease-modifying anti-rheumatic drugs (DMARDs) that are approved for use in other inflammatory joint diseases are sometimes used when NSAIDs are ineffective, but none are FDA approved for use in the treatment of AS.
Etanercept binds to tumor necrosis factor (TNF), a naturally occurring protein in the body, and inhibits its action. TNF, which promotes inflammation in the body, is found at elevated levels in the blood and certain tissues of patients with AS. It is believed that interference with TNF plays a role in the beneficial effects of etanercept in the treatment of this disease.
The major efficacy trial of etanercept for AS was a randomized, double-blind, placebo-controlled study of 277 patients. The study excluded patients with the most severe forms of AS. After 6 months of twice-weekly treatments, 58% of patients who received etanercept showed significant improvement on a scale that measured pain, function, and inflammation compared with 23% who received a placebo.
The main side effects of etanercept in the study were similar to those previously seen for this drug for other indications, including injection site reactions and upper respiratory infections. The approved labeling warns physicians about post-marketing reports of serious infections. The labeling says that Enbrel should not be given to patients with any active infection, including chronic or localized infections. It also recommends that patients who develop a new infection while being treated with Enbrel should be monitored closely.
Amgen will continue to monitor patients in the trial to evaluate the long-term safety of etanercept in patients with AS. The FDA has received a request from Amgen to approve the marketing of Enbrel as a treatment for moderate-to-severe forms of psoriasis.
July 16, 2003
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration (FDA) has approved Eli Lilly and Company's Zyprexa (olanzapine) for use combined with lithium or valproate (Depakote, Abbott) for treating acute manic episodes associated with bipolar disorder.
Zyprexa is the first agent to be approved for use in combination with other mood stabilizers to treat acute bipolar mania. Zyprexa was approved by the FDA in 2000 as a monotherapy for the short-term treatment of acute manic episodes associated with bipolar disorder and is the only atypical antipsychotic approved by the FDA to treat this patient population.
The FDA approval is based on data from two double-blind, randomized, placebo-controlled trials which showed that bipolar patients in manic or mixed episodes, treated with Zyprexa in combination therapy, demonstrated improved manic and depressive symptoms when compared to patients treated only with lithium or valproate alone.
In addition to its approval more than three years ago for short-term treatment of acute bipolar mania, Zyprexa is currently under FDA review for long-term maintenance of response in the treatment of bipolar disorder.
Zyprexa is also indicated in the U.S. for treating schizophrenia, the short-term treatment of acute manic episodes associated with bipolar disorder and for the long-term therapy and maintenance of treatment response of schizophrenia.
The most common treatment-emergent adverse event associated with Zyprexa in placebo-controlled, short-term schizophrenia and bipolar mania trials was somnolence. Other common events were dizziness, weight gain, personality disorder (COSTART term for non-aggressive objectionable behavior), constipation, akathisia, postural hypotension, dry mouth, asthenia, dyspepsia, increased appetite and tremor. A small number of patients experienced asymptomatic elevations of hepatic transaminase; none of these patients experienced jaundice.
In short-term (six-week) acute bipolar mania trials in combination with lithium or valproate, the most common treatment emergent adverse event associated with Zyprexa and lithium or valproate was dry mouth. Other common events were weight gain, increased appetite, dizziness, back pain, constipation, speech disorder, increased salivation, amnesia and paresthesia.
July 3, 2003
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration has given approval to Gilead Sciences Inc. to market a second HIV drug that can be taken once daily rather than several times daily.
The drug, Emtriva (emtricitabine), is a nucleoside reverse transcriptase inhibitor, or NRTI, Gilead said. Emtriva, formerly known as Coviracil, was acquired by Gilead with its January 2003 purchase of Triangle Pharmaceuticals.
Emtriva will be available and shipped to wholesalers in mid-July. The U.S. wholesaler acquisition cost for Emtriva is $252.83 for 30 capsules, or one month of therapy, Gilead said.
Emtriva is Gilead Sciences' second once-daily antiretroviral for treating HIV. The company's first anti-HIV medication, Viread (tenofovir disoproxil fumarate), a one-tablet, once-daily acyclic nucleotide analog, was cleared for marketing by the FDA in October 2001.
Gilead is developing a fixed-dose co-formulation of Emtriva and Viread, which it said could be available by early 2005.
July 1, 2003
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration has given approval to drugmakers GlaxoSmithKline Plc and Corixa Corp. to market Bexxar (tositumomab) for non-Hodgkin's lymphoma.
Last December, an FDA panel backed Bexxar, a monoclonal antibody linked to radioactive iodine 131, but didn't vote on approval. The companies and the FDA have been negotiating since then.
The treatment, intended for patients with severe lymphoma who have failed other therapies such as Rituximab, involves four components. It is administered in two steps over 7 to 14 days.
Corixa and GlaxoSmithKline, a British company, will co-market Bexxar in the United States.
Bexxar was approved for patients whose disease is resistant to other treatments and has relapsed following chemotherapy.
The most common adverse reactions occurring in clinical trials of Bexxar included neutropenia, thrombocytopenia and anemia. The incidence of these problems could be both prolonged and severe in some patients, the companies said. But standard chemotherapy also frequently causes these problems.
June 26, 2003
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration (FDA) has approved Pravigard PAC (co-packaged pravastatin sodium and buffered aspirin tablets) for use when treatment with both Pravachol (pravastatin) and buffered aspirin is appropriate.
This co-packaged product may be more convenient for some patients.
Pravachol and buffered aspirin are both indicated to reduce the occurrence of cardiovascular events, including death, myocardial infarction or stroke, in patients who have clinical evidence of cardiovascular and/or cerebrovascular disease. Patients treated with Pravigard should also be placed on a standard cholesterol-lowering diet.
Pravachol is a prescription medication that both lowers the amount of "bad" (or LDL) cholesterol and raises the amount of "good" (or HDL) cholesterol. High cholesterol levels can lead to plugs or clots in blood vessels.
Buffered aspirin stops the normal blood clotting process and keeps clots from forming in blood vessels that can lead to myocardial infarctions or strokes. Buffered aspirin has aspirin in it plus other ingredients that may lower patients' chances of getting an upset stomach.
Pravigard PAC shouldn't be taken by patients with certain liver or kidney problems, women who are pregnant or planning to become pregnant, people younger than 18 or those allergic to non-steroidal anti-inflammatory medicines or any of the ingredients in Pravigard PAC.
Possible serious side effects associated with using Pravigard PAC include muscle damage, liver damage, bleeding and stomach problems. It is therefore important for patients taking Pravigard PAC to tell their doctors if they experience any of the following: unexplained muscle pain or weakness, unusual bleeding, heartburn, nausea or vomiting, stomach pain or bowel movements or stools that look like black tar. Liver function tests may be performed prior to the initiation of Pravigard PAC.
The usual dose of Pravigard PAC is 1 aspirin tablet with 1 Pravachol tablet once a day. Pravigard PAC is available in cartons containing either 30 buffered aspirin 81mg or 325mg tablets packed with either 30 Pravachol 20mg, 40mg or 80mg tablets.
The Bristol-Myers Squibb Company of Princeton, N.J., is the sponsor of the approved New Drug Application (NDA) for Pravigard PAC.
June 18, 2003
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration (FDA) has approved FluMist, an influenza vaccine that is the first nasally administered vaccine to be marketed in the United States. It is also the first live virus influenza vaccine approved in the U.S.
FluMist (Influenza Virus Vaccine Live, Intranasal) is approved to prevent influenza illness due to influenza A and B viruses in healthy children and adolescents, ages 5-17 years, and healthy adults, ages 18-49. Children 5-8 years old need two doses at least 6 weeks apart in their first year of influenza vaccination with FluMist, and people 9-49 years old need one dose.
According to the Centers for Disease Control and Prevention (CDC), influenza, or "flu," is responsible for an average of approximately 36,000 deaths per year in the United States. Rates of infection are highest among children ages 5-14 years. However, the most severe illnesses and deaths occur among people with underlying medical conditions, children younger than 2 and those over age 65.
"This new vaccine provides another option for protection against influenza and will potentially increase the availability of the injected killed virus vaccine for those people at highest risk," said FDA Commissioner Mark B. McClellan, M.D., Ph.D. "Having enough supplies of flu vaccine available has sometimes been a challenge because there are few manufacturers, the vaccine needs to be changed every year, and certain strains of the virus grow slowly during the vaccine development process."
In addition, for those people who are eligible for the new vaccine and are reluctant to get a shot, such as healthy children over the age of 5, the availability of FluMist will be especially welcome."
Each dose of FluMist contains each of the three influenza virus strains recommended by the U.S. Public Health Service for the 2003-2004 influenza season: two strains of influenza A, which causes the most severe and widespread outbreaks, and one strain of B which usually causes a milder illness. However, unlike these circulating virus strains, the strains of live virus in the vaccine are modified so they don't grow well at body temperature but replicate enough to induce protective immunity.
In clinical trials, FluMist was evaluated in 20,228 people, including approximately 10,000 healthy children 5-17 years old. The efficacy of the vaccine in preventing influenza was approximately 87 percent among children included in the trial.
In healthy adults ages 18-49 years, FluMist was effective in reducing severe illnesses with fever, and upper respiratory problems which may be caused by influenza infection.
As with other live virus vaccines, FluMist should not be given for any reason to people with immune suppression, including those with immune deficiency diseases, such as AIDS or cancer, and people being treated with drugs that cause immunosuppression.
The safety of FluMist in people with asthma or other reactive airway diseases has not been established. FluMist should not be given to people with a history of these problems. In a large safety study, children under age five had an increased rate of asthma and wheezing within 42 days of vaccination compared to placebo recipients, so FluMist isn't recommended for young children. For people age 50 and over, the safe and effective use of FluMist hasn't been established.
FluMist should also not be given to people with chronic underlying medical conditions that may predispose them to severe flu infections. For these people, the injected vaccine is indicated.
People should not receive FluMist, or any other flu vaccine, if they have had an allergic reaction to eggs or to a previous dose of the vaccine. The most common adverse events associated with the vaccine were nasal congestion, runny nose, sore throat, and cough.
FluMist is manufactured by MedImmune Vaccines Inc., Gaithersburg, Md. It will be marketed by MedImmune and Wyeth, Philadelphia, Pa.
June 16, 2003
ST. LOUIS (MD Consult) - Sanofi-Synthélabo said the U.S. Food and Drug Administration (FDA) has approved its alfuzosin HCl extended-release tablets for treating the signs and symptoms of benign prostatic hyperplasia.
Alfuzosin, a compound from Sanofi-Synthélabo Research, is an alpha1-blocker in a 10 mg once-daily extended-release formulation.
Alfuzosin exhibits selectivity for alpha1-adrenergic receptors in the lower urinary tract. Blocking these adrenoreceptors can cause smooth muscle in the bladder neck and prostate to relax, improving urine flow and reducing symptoms of benign prostatic hyperplasia (BPH).
BPH is a very common disorder, leading to urinary symptoms of varying severity. The resulting symptoms affect 22% of men aged 50-59 years, but up to 45% of men aged 70-80 years. These symptoms may have an impact on men's day-to-day activities and may lead to serious complications such as acute urinary retention. Clinical efficacy data for alfuzosin from placebo-controlled trials have demonstrated efficacy compared to placebo in urinary flow improvement and improving urinary symptoms without the need for dose titration.
In the clinical trials, the most common side effects occurring more frequently than placebo were dizziness, upper respiratory tract infection, headache and fatigue.
Alfuzosin shouldn't be used in patients with moderate to severe hepatic insufficiency and shouldn't be co-administered with potent inhibitors of the cytochrome P3A4. As with other alpha-blockers, some patients may experience postural hypotension or syncope. Alfuzosin shouldn't be used with other alpha-blockers. If symptoms of angina pectoris appear or worsen, the use of alfuzosin should be discontinued.
Caution should be used when giving alfuzosin to patients with severe renal insufficiency. Consideration should be given in deciding to prescribe alfuzosin for patients with a known QT prolongation or who are taking medications known to prolong QT, although there has been no signal of Torsades de Pointes in extensive postmarketing experience with alfuzosin outside the United States. There are no known PK/PD studies of the effects of other alpha-blockers on cardiac repolarization.
Alfuzosin is marketed in approximately 80 countries throughout Europe, Latin America, Africa and Asia. Outside of the U.S., the once-daily formulation (Xatral® OD) is registered in 70 countries worldwide. It is currently marketed in 14 countries in Europe and in more than 35 other countries.
The U.S. launch of alfuzosin HCl extended-release tablets is scheduled to occur in the second half of 2003.
June 16, 2003
ST. LOUIS (MD Consult) - Novartis Pharmaceuticals Corporation said the U.S. Food and Drug Administration (FDA) has approved Stalevo (carbidopa, levodopa and entacapone) tablets for patients with idiopathic Parkinson's disease (PD) who have signs and symptoms of end-of-dose "wearing-off."
Stalevo, the first new drug for Parkinson's disease in over three years, contains levodopa, the most widely used agent for Parkinson's disease, plus carbidopa and entacapone. While carbidopa reduces the side effects of levodopa, entacapone extends its benefits, permitting Parkinson's disease patients to have an improved ability to perform everyday tasks and a reduction in symptoms associated with the disease.
Within one to two years, almost 50 percent of PD patients receiving levodopa therapy begin to notice their levodopa lasts for shorter periods of time, known as "wearing off." In about 15 to 20 percent of patients, "wearing off" becomes extreme and disabling. Eventually, the effect of a levodopa dose may decrease from eight hours when patients begin levodopa therapy to only one to two hours.
"Levodopa is recognized as the cornerstone of Parkinson's disease therapy, but its long-term use is limited by its reduced ability to fully control Parkinson's disease symptoms," said Warren Olanow, MD, professor and chairman, Department of Neurology, Mount Sinai School of Medicine in New York City. "By blocking the enzymatic breakdown of levodopa, Stalevo provides more levodopa to the brain for a longer period of time. Potential patient benefits include more "on" time during which Parkinson's symptoms are well-controlled and daily activities are improved, and simpler, more convenient dosing."
The effectiveness of levodopa administered with carbidopa and entacapone in the treatment of Parkinson's disease was established in three 24-week multicenter, randomized, double blind placebo-controlled trials in patients with Parkinson's disease experiencing "wearing off." In these trials, this combination increased "on" time, reduced "off" time and improved motor function and daily activities such as patients' ability to walk and dress.
The most common side effects of Stalevo therapy are dopaminergic in nature (e.g. dyskinesia, nausea). These side effects may be manageable with alteration in the drug dosing schedule. Other common side effects include diarrhea, hyperkinesias, urine discoloration, hypokinesia, abdominal pain, dizziness, constipation, fatigue, pain and hallucinations. For full prescribing information, visit stalevo.com.
Entacapone alone is sold in the United States as Comtan and like Stalevo is marketed by Novartis Pharmaceuticals Corporation and manufactured by Orion Pharma.
June 10, 2003
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration (FDA) has given approval to Sankyo Pharma Inc. for Benicar HCT, a product combining its Benicar (olmesartan medoxomil) angiotensin II receptor blocker with hydrochlorothiazide.
The approval covers the combination therapy for second-line treatment of hypertension. Sankyo, the U.S. subsidiary of Japan's Sankyo Co. Ltd., said the combination product helps reduce systolic and diastolic blood pressure.
In a trial presented at the American Society of Hypertension meeting in May, Benicar HCT was more effective than either Benicar or hydrochlorothiazide alone, Sankyo said.
Distribution of Benicar HCT is scheduled to begin in the second half of 2003, the company said.
Benicar HCT will be offered in three fixed-dose combinations.
June 10, 2003
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration (FDA) has granted approval to Wyeth Pharmaceuticals to market a lower-dose version of its menopause therapy Prempro (0.3 mg of conjugated estrogen and 1.5 mg of medroxyprogesterone acetate).
The drug is indicated for treating moderate to severe symptoms associated with menopause, such as hot flashes, night sweats and vaginal dryness, and for preventing postmenopausal osteoporosis.
The FDA also approved Prempro 0.45 mg conjugated estrogen /1.5 mg medroxyprogesterone acetate for preventing postmenopausal osteoporosis. That dosage was previously approved in the U.S. for various menopausal symptoms.
The Women's Health Initiative study was halted in 2002, three years earlier than expected, when Prempro use at higher doses was associated with an increased risk of heart attacks, strokes, breast cancer and blood clots.
Shortly after the study was stopped, Wyeth made some labeling changes. The FDA has since required manufacturers of estrogen-containing products used for menopausal symptoms to make label changes addressing safety concerns. The new labeling requirements affect Wyeth's other estrogen-containing products -- Premphase and Premarin.
The lower-dose versions of the Wyeth drugs are intended to address calls from the National Institutes of Health and the FDA for women to switch to low-dose therapy or consider abandoning treatment.
Postmenopausal estrogen/hormone therapy is the only FDA-approved treatment indicated for relieving menopausal symptoms and preventing postmenopausal osteoporosis, Wyeth said in a statement.
Distribution of Prempro 0.45 mg/1.5 mg is scheduled to start in early summer and Prempro 0.3 mg/1.5 mg should be available by late 2003, Wyeth said.
Data supporting the efficacy and tolerability of both approvals was based on the Women's Health, Osteoporosis, Progestin, and Estrogen (HOPE) Study, a prospective, randomized, double-blind, placebo-controlled trial involving 2,673 healthy postmenopausal women, the company said.
May 30, 2003
ST. LOUIS (MD Consult) - Bausch & Lomb has received U.S. Food and Drug Administration approval of its brimonidine tartrate ophthalmic solution, 0.2 percent, indicated for use in lowering intraocular pressure in people with open-angle glaucoma or ocular hypertension.
In addition to the approval, Bausch & Lomb received FDA marketing exclusivity for this generic medication until September 20, 2003.
Brimonidine tartrate ophthalmic solution, 0.2 percent, was sold under the brand name Alphagan by Allergan, Inc., which unsuccessfully tried to block Bausch & Lomb's efforts to bring to market a generic version of the medicine by filing two patent infringement lawsuits, both of which Bausch & Lomb won.
Bausch & Lomb's generic version of the prescription eye drop is available immediately.
Bausch & Lomb manufactures this and other proprietary and generic prescription medicines at its U.S. pharmaceuticals facility in Tampa, Fla.
May 30, 2003
ST. LOUIS (MD Consult) - Bausch & Lomb has received U.S. Food and Drug Administration approval of its brimonidine tartrate ophthalmic solution, 0.2 percent, indicated for use in lowering intraocular pressure in people with open-angle glaucoma or ocular hypertension.
In addition to the approval, Bausch & Lomb received FDA marketing exclusivity for this generic medication until September 20, 2003.
Brimonidine tartrate ophthalmic solution, 0.2 percent, was sold under the brand name Alphagan by Allergan, Inc., which unsuccessfully tried to block Bausch & Lomb's efforts to bring to market a generic version of the medicine by filing two patent infringement lawsuits, both of which Bausch & Lomb won.
Bausch & Lomb's generic version of the prescription eye drop is available immediately.
Bausch & Lomb manufactures this and other proprietary and generic prescription medicines at its U.S. pharmaceuticals facility in Tampa, Fla.
May 28, 2003
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration (FDA) has given approval to Amphastar Pharmaceuticals Inc. to market its anesthetic Duocaine for ophthalmologic surgeries.
The indication covers the production of local or regional anesthesia for ophthalmologic surgery by peripheral nerve block techniques such as parabulbar, retrobulbar and facial nerve blocks, the FDA said in a notice.
Duocaine is a combination of lidocaine and bupivacaine, both of which have been off patent for several years.
Amphastar is a generic and specialty drugmaker concentrating on parenteral products.
May 12, 2003
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration (FDA) has given Pfizer Inc. a supplemental approval to market Adriamycin (doxorubicin hydrochloride) combined with cyclophosphamide as a component of adjuvant therapy following resection of primary breast cancer that has spread to the axillary lymph nodes.
Both anticancer drugs already had separate indications for adjuvant chemotherapies.
Cyclophosphamide is sold under several brand names, including Neosar by Pharmacia, and in generic form.
May 6, 2003
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration has approved AstraZeneca Plc's drug Iressa for treating advanced cases of non-small cell lung cancer, the most common form of lung cancer.
Iressa, the first of a new class of anti-cancer drugs -- epidermal growth factor receptor inhibitors -- won majority backing from an FDA expert panel in September, 2002. Final approval had been delayed while regulators examined additional clinical data.
"With the approval of Iressa, thousands of patients with lung cancer will now have access to an additional treatment after others haven't worked to stop the progression of their disease," FDA Commissioner Mark McClellan said in a statement.
The FDA said it approved Iressa for patients with non-small cell lung cancer whose cancer has progressed despite treatment with platinum-based and docetaxel chemotherapy, two drugs considered the standard of care for this form of lung cancer.
Iressa was well-received among oncologists when it was first discovered. But Iressa had a setback last year when it failed to work in combination therapy trials. In addition, safety concerns have been raised following 246 deaths from interstitial lung disease among people taking Iressa in Japan.
May 5, 2003
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration (FDA) has given supplemental approval to GlaxoSmithKline to include new pediatric data on the label of its allergy therapy Flonase (fluticasone propionate) and to Aventis for a more flexible dosing regimen with its long-acting insulin Lantus (insulin glargine [rDNA origin]).
The Lantus approval clears a change in dosing from once daily at bedtime to flexible daily dosing.
Aventis earned a similar approval in the European Union in December, 2002. At the time, Aventis said the flexible dosing would allow earlier administration of Lantus.
Lantus was made available in the U.S. in May 2001 and in Britain in May 2002. In the U.S., the drug is indicated for treating adult and pediatric patients with either type I or type 2 diabetes requiring basal insulin.
The Flonase approval provides for including data from a long-term study intended to gather additional pediatric safety data.
According to the new Flonase label, results of the year-long, placebo-controlled trial showed there was no statistical difference in the growth rate of pediatric patients. The label previously said the long-term effects on growth velocity were unknown.
A total of 150 pediatric patients ages 3 to 9 participated in the study.
May 2, 2003
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration (FDA) has given Pfizer Inc. subsidiary Agouron Pharmaceuticals Inc. a supplementary approval to market a 625-mg tablet of its HIV protease inhibitor Viracept (nelfinavir mesylate) intended to reduce the dosing burden from five tablets to two tablets twice daily.
The San Diego-based company said the new 625-mg formulation would be available in the early third quarter through retail and mail-order pharmacies, and through institutional suppliers.
Viracept was approved by the FDA in 1997 for use with other drugs to treat HIV infection. The recommended dosage is 1250 mg twice daily. Under the current regimen, patients generally take either five 250 mg tablets twice daily or three 250 mg tablets three times a day.
The supplementary approval was based on a study of healthy volunteers, demonstrating that the 625 mg tablet had greater bioavailability than the 250 mg five-tablet regimen under fasted or fed conditions, the company said. Studies are also ongoing to evaluate the efficacy and safety of the 625-mg tablet, Agouron Pharmaceuticals said.
May 1, 2003
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration has approved Genzyme General Corp. and BioMarin Pharmaceutical Inc.'s drug Aldurazyme for treating the rare genetic mucopolysaccharidosis, MPS-I.
Aldurazyme will receive seven years of market exclusivity as an orphan drug for a rare disease, the companies said. Aldurazyme is the first drug specifically approved for MPS-I, the companies said.
MPS-I can damage the heart and lungs, stiffen joints and stunt growth, and often kills people in childhood or early adulthood. The disease affects 3,000 to 4,000 people worldwide, including about 1,000 in the United States, the companies said.
The illness is caused by an enzyme deficiency. Aldurazyme is a weekly intravenous infusion of a genetically engineered form of the missing enzyme.
The companies said they have agreed with the FDA to conduct additonal study on Aldurazyme after it is released to the market.
Genzyme, based in Cambridge, Massachusetts, also recently earned approval for another enzyme-replacement therapy, Fabrazyme, to treat Fabry disease.
April 25, 2003
ST. LOUIS (MD Consult) - Genzyme Corp.'s enzyme replacement therapy Fabrazyme for treating the rare genetic condition Fabry disease has been approved by the U.S. Food and Drug Administration (FDA).
To gain a recommendation for approval from the advisory panel, Genzyme agreed to conduct a post-approval clinical trial intended to prove Fabrazyme (agalsidase beta) improves kidney function. That trial is scheduled for completion by early 2004.
With the approval, Genzyme has seven years of market exclusivity under the FDA's orphan drug program, which offers drugmakers incentives to develop treatments for rare conditions.
April 15, 2003