Akorn's Injectable Droperidol Gets FDA Black Box Warning on Label
Safety Concerns Cause Germany's Merck to Pull Two Kava Drugs
Recently Approved Colorectal Cancer Treatment Increases Early Death Risk
Early Deaths with Chemotherapy Regimen for Colorectal Cancer
FDA Health Advisory Cites Risks Associated with Antifungal Drugs
Dexamethasone Impairs Cerebral Cortical Gray Matter Growth in Premature Infants
Moderate-dose Dexamethasone Linked to Complications in Preterm Infants
Varicella, MMR Vaccines Should be Given at Least 30 Days Apart, CDC Says
TIA Followed by Stroke Associated with Erectile Dysfunction Drug
Topamax Use Linked to Myopia, Glaucoma; Ortho-McNeil Adds Warning to Label
Celgene's Thalomid (thalidomide) Label to Warn of Seizure Risk
Estrogen Therapy Affects Thyrotropin Level and Thyroxine Requirement in Hypothyroid Women
Interferon Linked to Asymptomatic Ocular Complications in Cancer Patients
ACE Inhibitors Don't Lower Restenosis Risk after Coronary Stenting
CDC Warns of Severe Hepatitis Resulting from Combination Therapy for TB
Distributor Recalls Anso Comfort Capsules for Containing Librium
Iron Ion Preparations Decrease Absorption of Mycophenolate Mofetil in Transplant Patients
Osteonecrosis: a New Complication of Highly Active Antiretroviral Therapy
FDA/Bristol Myers Squibb Issues Warning About use of Zerit and Videx During Pregnancy
Infliximab Linked to Tuberculosis Infection Levacethylmethadol Linked to Ventricular Arrhythmias
December 10, 2001
ST. LOUIS (MD Consult) - Drugmaker Bristol-Myers Squibb Co. has been told by the US Food and Drug Administration (FDA) to add a black-box warning on its label for the antidepressant Serzone (nefazodone) informing patients that rare but possibly life-threatening liver damage can result from using the drug.
The FDA will soon require New York-based Bristol-Myers to warn doctors that a small number of patients could suffer from liver failure, leading to death or the need for a liver transplant, according to an online Wall Street Journal article.
The FDA estimated the reported rate of liver failure in this country is about one case for every 250,000 to 300,000 patients using the drug for one year, the newspaper said.
The language the FDA will require on Serzone package labels will include warnings that cases of life-threatening hepatic failure have been reported in patients treated with Serzone.
A number of US psychiatrists became concerned about the Serzone liver-failure problem after Canadian government authorities issued a warning during the summer of 2001, the newspaper said.
December 10, 2001
ST. LOUIS (MD Consult) - Aventis Pasteur MSD recalled all of its VAQTA hepatitis A vaccine this week because of fears it might not be potent enough to protect people against the travel disease.
The firm, the European vaccines joint venture set up by Merck and Aventis, said the withdrawal involves pre-filled syringes of VAQTA vaccine for adults and VAQTA K for children. The vaccine is made by Merck and loaded into syringes in the UK by Evans Vaccines, part of PowderJect.
The problem is an apparent reduction in the potency of the vaccine, but only a fraction of the syringes are affected, a spokesman for the companies said. Due to the difficulty of identifying which syringes were affected, all batches were recalled.
A spokesman for PowderJect said the precise nature of the problem was unclear.
December 7, 2001
NEW YORK (MD Consult) - The US Food and Drug Administration has strengthened the warnings and precautions for Akorn Pharmaceutical's injectable droperidol, which is associated with fatal cardiac arrhythmias.
Droperidol solution, sold by Akorn under the name Inapsine, is indicated as a sedative and anti-nausea agent in surgical patients. Akorn has sent a "Dear Doctor" letter to US healthcare professionals explaining the label change.
The FDA has changed Akorn's droperidol label to include a "black box" warning, the most serious warning assigned to drugs approved for sale in the US, the agency said. The FDA said it wants to increase doctor awareness about the potential for cardiac arrhythmias in patients using the drug.
The label has included a warning that high doses of droperidol (over 25 mg) have resulted in cases of sudden patient death. But recent research has shown that dosages at the upper end of the labeled range can cause QT prolongation minutes after injection, the FDA said.
In the last year there have been reports of torsades de pointes within or below the currently labeled dose range for droperidol, plus reports of sudden death, the FDA said.
In January, Johnson & Johnson unit Janssen-Cilag enacted a global withdrawal of its oral tricyclic antidepressant Droleptan (droperidol) due to reports it might increase the chance of cardiac arrhythmia.
November 30, 2001
ST. LOUIS (MD Consult) - The US Centers for Disease Control and Prevention (CDC) repeated its recommendation that physicians should either administer varicella vaccine simultaneously with the measles-mumps-rubella (MMR) vaccine or wait at least 30 days if the vaccines are given separately.
Because both are live vaccines, antibody titers do not get as high as needed for immunity if one vaccine is followed by the other within 30 days, the CDC said. The 30-day period is needed for the body to respond well to the second vaccine.
CDC researchers investigated the interaction with varicella vaccine because of previously reported interactions between the MMR vaccine and the smallpox (variola) vaccine. They suspected a similar reaction might occur because both the varicella vaccine and the smallpox vaccine contain live pox viruses.
The CDC analyzed data taken from the Vaccine Safety Datalink project, which included over 100,000 children between the ages of 12 and 71 months. The researchers also checked the occurrence of breakthrough disease after administration of other types of vaccines including the diphtheria, tetanus, and pertussis vaccine; Haemophilus influenzae type B vaccine; oral poliovirus vaccine; inactivated poliovirus vaccine; and hepatitis B vaccine.
Whether given simultaneously or within 30 days of varicella vaccine, MMR appeared to be the only one of the vaccines to increase breakthrough disease.
Less than 1% of children receiving varicella vaccine received another vaccine in less than 30 days, according to the CDC.
Clinicians should be aware of this recommendation for administering MMR and varicella vaccines. There is no increased risk for problems administering the vaccines simultaneously, and it reduces the number of visits to the clinic.
MMWR 2001;50:1038-1041.
November 29, 2001
ST. LOUIS (MD Consult) - Two drugs based on the organic product Kava have been withdrawn by German drugs group Merck KGaA due to concerns about possible damaging side effects to the liver.
The two nonprescription treatments, kavadura 120 mg and Kytta-Kava, used to relax people suffering from physical or nervous exhaustion, were only sold in Germany, Merck said.
German government tests had shown 24 suspected cases of side effects on the liver, Merck said. A connection with the kava-based products couldn't be ruled out, although there was no indication of liver problems resulting from its treatments.
November 28, 2001
ST. LOUIS (MD Consult) - The use of sildenafil (Viagra; Pfizer US Pharmaceutical Group, New York) appears to be the cause of a case of transient ischemic attack (TIA) followed by a stroke 6 days later, physicians report.
Dr. Karen C. Johnston, of the University of Virginia in Charlottesville, and colleagues, described the case of a 50-year-old man who complained of a funny feeling after using sildenafil in doses of 50 to 100 mg three times previously. After taking sildenafil a fourth time, he developed TIA symptoms within 2 hours which resolved after 4 hours.
He used sildenafil again 6 days later,and similar TIA symptoms developed but did not stop. The patient went to the hospital with weakness, partial paralysis, and other symptoms indicative of stroke. The results of an MRI performed the next day were consistent with cerebral infarction.
During hospitalization he was hypertensive, but his cardiovascular examination was otherwise ordinary.
Six months later, the patient had residual mild right hemiparesis and right arm spasticity.
Dr. Johnston and her associates concluded that the patient's TIA and subsequent could have resulted from a slight lowering of blood pressure across a diseased artery -- caused by effects on cerebral arterial vasculature, venodilatory effects, or brief arrhythmia.
Increased sympathetic activity could also be responsible, the clinicians said. They suggest sildenafil be prescribed with caution in patients with a history of stroke.
Neurology 2001;57:1730-1731.
November 21, 2001
ST. LOUIS (MD Consult) - Consumers and healthcare professionals have been warned by the US Food and Drug Administration (FDA) to immediately stop using a weight-loss aid sold as Lipokinetix by Cape Girardeau, Missouri-based Syntrax Innovations Inc.
The FDA said it has received at least six reports of acute liver failure associated with the dietary supplement, involving individuals ranging between 20 and 32 years of age. In each case, there was no other identifiable cause of the liver injury, the FDA said.
Lipokinetix contains phenylpropanolamine (PPA), as well as caffeine, yohimbine, diiodothyronine and sodium usniate, the FDA said.
PPA, which the FDA has been moving to ban, is a compound once commonly used in dietary aids and cold medications. The FDA declared this intention after two studies and a committee of expert advisors to the agency said the ingredient might cause strokes in young, healthy people, especially when combined with stimulants such as caffeine.
In issuing the Lipokinetix warning, the FDA encouraged consumers to see a physician if they have experienced nausea, weakness, fatigue, fever, abdominal pain or any change in skin color.
The FDA also encouraged consumers and physicians to report any additional cases of liver injury or other side effects that might be related to the dietary supplement. Reports can be made by telephone at 1-800-332-1088 or on the Internet at www.fda.gov/medwatch, the FDA said.
Syntrax officials said the product has been off the market for over a year.
November 2, 2001
ST. LOUIS (MD Consult) - Hoffman-La Roche's cancer treatment Xeloda (capecitabine) has added a black box label warning to strengthen a concern about a possible interaction with Dupont Pharmaceuticals' anticoagulant Coumadin (warfarin), the US Food and Drug Administration (FDA) said.
Post-marketing studies indicate patients receiving concomitant capecitabine and oral coumarin-derivative anticoagulant therapy should have their anticoagulant response (INR or prothrombin time) monitored frequently in order to adjust the anticoagulant dose accordingly, the FDA said.
Xeloda's package insert has also been updated with the agency's concerns.
The FDA initially approved Xeloda in May 2001 for the treatment of colorectal cancer. In September 2001, it was approved for treatment of breast cancer in combination with Aventis Pharmaceuticals' Taxotere (docetaxel).
October 29, 2001
ST. LOUIS (MD Consult) - The US Food and Drug Administration (FDA) announced in late September 2001 that Pharmacia Corp. initiated a voluntary recall of three lots of its oral diabetes drug Micronase (glyburide) due to the presence in some lots of fungal organisms resulting from contaminated raw material used in the formulation.
The medical literature shows that, in rare cases, the fungi/mold detected, such as Paecilomyces, Aspergillus and Penicillium, can cause infections if they are inhaled or enter the body through damaged skin. The problem can be especially severe for immuno-compromised individuals, including diabetics and HIV and renal transplant patients who have diabetes.
Because the FDA is not aware of any cases of infection associated with swallowing the fungus, the agency said patients should continue to take their medication until a replacement is obtained.
The recalled lot numbers are 84DWB (1.25 mg tablets), 91DYR (2.5 mg tablets) and 67FPP (5 mg tablets).
October 26, 2001
ST. LOUIS (MD Consult) - In late September 2001, Johnson & Johnson's Ortho-McNeil Pharmaceuticals issued a "Dear Doctor" letter to healthcare professionals warning that its epilepsy drug Topamax (topiramate) has been linked to cases of severe myopia and secondary angle-closure glaucoma.
The letter, distributed to almost half a million physicians, said that as of August 17 there were 23 reported cases involving 22 adults and one child. Since the US Food and Drug Administration (FDA) approved Topamax in 1996, the drug has been used in more than 825,000 patients, Ortho-McNeil noted.
Patients who develop the eye condition should discontinue use of the drug "as rapidly as possible" after consulting with a physician, the company advised. The condition generally appears to be self-resolving, the firm said.
Symptoms usually begin within a month of starting Topamax therapy. Ortho-McNeil said it will add a warning and recommendations regarding the potential adverse event to the drug's label. The company encouraged Topamax patients who experience blurred vision or eye pain to seek immediate medical attention. It also asked doctors to report any adverse events they observe.
In premarketing clinical trials of more than 2,000 epilepsy patients, the most common side effects of Topamax were difficulty concentrating, drowsiness, dizziness and coordination problems. Most were mild to moderate and disappeared over the course of treatment.
October 15, 2001
ST. LOUIS (MD Consult) - Treating advanced colorectal cancer patients with irinotecan plus bolus fluorouracil/leucovorin (IFL) could triple the rate of treatment-associated death compared to patients receiving other treatments, according to a report in the September 15th Journal of Clinical Oncology.
Two recent studies discussed an unusual number of early deaths among patients receiving the treatment, the authors said. Dr. Mace L. Rothenberg from Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, and colleagues served on an independent panel formed to characterize the early deaths in these studies.
The early deaths resulted from a cluster of toxicities that could be categorized as either a gastrointestinal syndrome or a vascular syndrome, the report said. The gastrointestinal and vascular syndromes were seen in three patients who died early, and only two deaths were due to neither syndrome.
Their report indicates that the gastrointestinal syndrome, seen in 16 of 21 early deaths, included nausea,anorexia, diarrhea, vomiting and abdominal cramping, often in association with severe dehydration, neutropenia, fever, and electrolyte abnormalities.
The vascular syndrome, seen in six of the early deaths, involved pulmonary embolus, acute, fatal myocardial infarction or cerebrovascular accident during or shortly following receipt of chemotherapy.
In both studies, the median time of death was 12 to 18 days earlier in IFL-treated patients than in patients receiving another treatment, the authors found, but few baseline differences could be identified between patients who died and those who survived.
During at least the first cycle of treatment, IFL patients should undergo weekly assessment by a clinician experienced in using this regimen and in the treatment of gastrointestinal cancer, the authors said. This is particularly important before the third and fourth weeks of treatment, when most of the severe treatment-related toxicities that led to early death occurred.
The researchers propose other safety recommendations, including clinical trials.
J Clin Oncol 2001;19:3801-3807.
September 12, 2001
ST. LOUIS (MD Consult) - Ongoing evaluation of Celgene Corporation's Thalomid (thalidomide) by the U.S. Food and Drug Administration's (FDA) System for Thalidomide Education and Prescribing Safety (STEPS) program has led to changes in the drug's label; the label now advises that Thalomid use may induce seizures.
The labeling change was implemented when seizures, including grand mal seizures, were reported in patients taking Thalomid. The text of the label advises physicians to closely monitor any patient taking Thalomid who has a history of seizures or who may be at risk for developing them. The label does not advise physicians to not prescribe the drug to such patients.
The STEPS program was specifically designed so that thalidomide may be safely and effectively prescribed and used. The program hopes to prevent the birth defects that were caused when thalidomide was used for the treatment of morning sickness. STEPS was formed in 1998 when thalidomide was approved as a leprosy treatment; in addition to the FDA, drug companies, advocacy groups, and government agencies are involved in the STEPS program.
August 17, 2001
ST. LOUIS (MD Consult) - On August 15, American Home Products announced that it was recalling two lots of Premarin, its hormone replacement therapy. The company withdrew the lots voluntarily upon finding out that they did not meet government quality standards.
American Home Products states that the safety and efficacy of the product that is being recalled are not in question. According to a spokesperson from the company, changes in government standards that occurred in 1998 are what caused the discrepancies in quality.
This recall has raised some concern that there may be shortages of one or more dosage levels of the drug; 896 bottles of one lot and 1174 bottles of another are affected by these recalls, and each bottle contains 5000 pills. Five lots of Premarin were also recalled in December 2000.
August 17, 2001
ST. LOUIS (MD Consult) - Perrigo Company, a leading manufacturer of store-brand pharmaceuticals, has recalled nearly 8000 bottles of its pediatric liquid pain reliever because they may have as much as 29 percent more acetaminophen than their labels state.
The number of the recalled lot is 1AD0228. The lot contains 7788 bottles; of these approximately 6500 have been purchased, and the rest have been removed from store shelves.
The medicine in question is cherry-flavored and is used to treat headache and fever. It was nationally distributed with the Good Sense label, and in some states it also carried the Hy-Vee and Kroger store brand labels.
This recall came shortly after the company had been warned by the U.S. Food and Drug Administration (FDA) that its quality-control standards did not appear to sufficiently protect against accidents; the warning was issued when the company had to recall 500-mg acetaminophen caplets that had been labeled as 200-mg ibuprofen caplets. Perrigo has worked with the FDA in the months since that recall to improve its standards, and recent reviews by the FDA have shown their changes to be satisfactory.
It was found that this latest problem was machinery-related, and the company has already taken corrective action. Perrigo is encouraging consumers to stop using the recalled product and to return it to where it was purchased for a refund. Currently the company has not received any reports of problems associated with the use of the recalled product.
Contact Perrigo at 1-800-321-0105 or the FDA's MedWatch Program at 1-800-FDA-1088 with any questions or concerns about this product.
August 09, 2001
ST. LOUIS (MD Consult) - Germany's Bayer AG has withdrawn Baycol (cerivastatin), its lipid-lowering medication, from all distribution. This move is a result of reports of sometimes fatal rhabdomyolysis in patients taking the drug; 31 deaths have been reported to the U.S. Food and Drug Administration (FDA).
Baycol was originally approved in 1997. It is a statin, which is a class of drugs that lowers cholesterol levels by blocking an enzyme that is necessary for cholesterol synthesis. According to the FDA, all statins have the potential to cause rhabdomyolysis, but the fatal form of the condition has occurred with a much higher frequency in patients taking Baycol. The condition was particularly prevalent in older patients who were taking high doses of the drug, and 12 of the patients who died were taking Baycol with gemfibrozil. Bayer AG had already recommended in its prescribing information for Baycol that the two drugs not be given together, but apparently that warning was not always heeded.
According to a “Dear Healthcare Professional” letter issued by Bayer AG on August 8, “Since the co-prescription of Baycol and gemfibrozil has continued despite communications by Bayer against this practice, the company has decided to take the following voluntary action to prevent further cases of rhabdomyolysis: Effective immediately, Bayer has discontinued the marketing and distribution of all dosage strengths of Baycol.”
Bayer AG had recently planned to change the label to reiterate Baycol's association with rhabdomyolysis and to reinforce their recommendation that patients receive no more than 0.4 mg to start with, regardless of their history with other lipid medications.
The company is recalling the drug from all distributors as a patient safety measure; participating pharmacies will be refunded.
The FDA recommends that patients who have been taking Baycol should talk with their physicians about alternative treatments. There are currently five other statins that may be considered: lovastatin, pravastatin, simvastatin, fluvastatin, and atorvastatin. Anyone taking Baycol who is having muscle pain or who has also been taking gemfibrozil should discontinue their Baycol treatment immediately.
For more information about the Baycol withdrawal, contact Bayer Customer Service at 1-800-758-9794, or call the U.S. Food and Drug Administration's Drug Information Office at 1-888-INFO-FDA.
July 26, 2001
ST. LOUIS (MD Consult) - As of July 25, changes were made to the prescribing information of Purdue Pharma's OxyContin (oxycodone hydrochloride) in an effort to reduce abuse, diversion, and the writing of inappropriate prescriptions.
OxyContin is a prescription pain medication that was often being crushed and snorted or dissolved and injected by those who were abusing it; through these methods, the controlled-release mechanism of delivery of the drug was rendered ineffective. According to a report released by the Justice Department earlier this year, at least 37 deaths have occurred as a result of OxyContin abuse.
OxyContin is an opioid agonist, and, according to the U.S. Food and Drug Administration (FDA), it is nearly as addictive as morphine, to which it is chemically related. The drug is currently approved for patients with moderate to severe pain that is expected to last for an extended period of time.
A “black box warning” was added voluntarily by Purdue Pharma; the company worked closely with the FDA to develop it. This is the strongest warning that is carried by a prescription drug. A “Dear Healthcare Professional” letter was sent to prescribers of this drug on July 18. Following is the “black box warning,” which was included in the letter:
WARNING:This information is also reiterated in the “Warnings” and “Indications and Usage” sections of the physician prescribing information.
According to the FDA Talk Paper for this drug, “Although abuse, misuse, and diversion are potential problems for all opioids, including OxyContin®, opioids are a very important part of the medical armamentarium for the management of pain when used appropriately under the careful supervision of a physician.” Purdue Pharma is the first pharmaceutical manufacturing company to address these issues in its prescribing information; the FDA is encouraging other companies to follow suit.
June 21, 2001
ST. LOUIS (MD Consult) - Investigators conducting trials of combination chemotherapy with irinotecan, fluorouracil, and leucovorin for metastatic colon cancer have found an excess of early mortality among patients receiving this regimen, reported in a letter to the New England Journal of Medicine.
The letter from researchers involved in two National Cancer Institute-sponsored trials of chemotherapy for advanced colorectal cancer will be published in the June 21 issue of the Journal. However, because of its important clinical implications, the Journal's editors have placed the letter online as "Early Release Correspondence."
In the letter, Daniel J. Sargent, Ph.D., and colleagues report "an imbalance" in deaths within 60 days after the start of treatment with irinotecan, fluorouracil, and leucovorin. Fourteen deaths occurred in a trial of patients with metastatic colon cancer, 12 of them resulting from dehydration, neutropenia, and sepsis. Thirteen of the deaths occurred during or immediately after the first cycle of chemotherapy.
Another 14 deaths occurred among patients after surgery for stage III colon cancer. In this group, causes of death included pulmonary embolism, sepsis, and aspiration.
Enrollment in both trials has been suspended by their safety and monitoring boards. Dose modifications have been made in an attempt to reduce the toxicity of the regimen.
The regimen of irinotecan, fluorouracil, and leucovorin has been approved by the FDA for initial treatment of metastatic colorectal cancer and is emerging as the new standard of care for patients with advanced colorectal cancer. Dr. Sargent and colleagues write that, "irinotecan, fluorouracil, and leucovorin should continue to be an option in this treatment setting, but in our experience has been associated with an excessive rate of early deaths." They recommend caution in its use
June 7, 2001
ST. LOUIS (MD Consult) - Hypothyroid women receiving estrogen therapy may require a higher dose of thyroxine for treatment of their hypothyroidism, reports a study in the June 7 New England Journal of Medicine.
Dr. Baha M. Arafah of Case Western Reserve University, Cleveland, analyzed thyroid function before and during estrogen therapy in two groups of postmenopausal women: 25 women with hypothyroidism and 11 controls with normal thyroid function. Of the hypothyroid women, 18 were taking thyroxine-replacement therapy while 7 were taking thyrotropin-suppressing doses of thyroxine. Thyroid function measures were repeated every 6 weeks during 48 weeks of estrogen therapy.
In the controls with normal thyroid function, serum thyroxine increased from 8.0 to 10.4 µ/dL by 12 weeks, while serum thyroxine-binding globulin increased from 20.3 to 31.3 mg/L. The women with hypothyroidism showed similar changes in serum thyroxine and thyroxine-binding globulin. The hypothyroid women also had a significant decrease in serum free thyroxine concentration (from 1.7 to 1.4 ng/dL) and a significant increase in serum thyrotropin (from 0.9 to 3.2 µU/mL). These measures were unchanged in euthyroid controls. Serum thyrotropin increased higher than 7 µU/mL in 39% of women taking thyroxine-replacement therapy and higher than 1 µU/m in 43% of women on thyrotropin-suppression therapy.
Pregnant women with hypothyroidism commonly require an increased dose of thyroxine. However, it has been unclear whether this is the result of increased serum thyroxine-binding globulin caused by estrogen, or whether other factors play a role. The new findings suggest that women with normal thyroid function adapt to estrogen-induced increases in serum thyroxine-binding globulin. However, in hypothyroid women, estrogen causes a decrease in in serum free thyroxine, thus increasing serum thyrotropin and leading to an increased need for thyroxine. Dr. Arafah recommends monitoring serum thyrotropin during estrogen therapy in women with hypothyroidism, particularly those receiving thyrotropin-suppressive therapy for thyroid cancer.
June 4, 2001
ST. LOUIS (MD Consult) - New findings from the Avon Longitudinal Study of Parents and Children (ALSPAC) provide intriguing clues into the possible relationship between eczema and peanut allergy, and suggest that maternal testosterone levels during pregnancy may be related to masculine behavior in girls.
The findings were presented at a June 4 meeting at the Royal Society in London, marking the tenth anniversary of the ALSPAC study, also known as the "Children of the 90s" study.
A research team led by Dr. Gideon Lack of St. Mary's Hospital, London, found that eczema occurs before peanut allergy in about 90% of children. The findings raise the possibility that the topical medications used to treat eczema in children may actually be a contributing cause of peanut allergy. In addition, the researchers found evidence of peanut allergy in up to 1 in 100 children, a higher proportion that previously thought.
At the same meeting, Drs. Melissa Hines and Susan Golombok of City University, London, reported a "clear relationship" between high maternal testosterone levels during pregnancy and subsequent masculine sex-typed behaviors in girls, such as engaging in rough or active play. Boys' behavior was unaffected by maternal testosterone levels. Even for girls, however, the behavior of older siblings and parents had a greater effect on behavior than testosterone levels did.
The ALSPAC study was initiated in 1991, when 14,000 pregnant women were enrolled to study the genetic and environmental causes of common diseases. More valuable results can be expected for the future, as the Wellcome Trust announced a grant to continue the ALSPAC project over the next 5 years.
May 2001
ST. LOUIS (MD Consult) - Cancer patients receiving interferon must be monitored for signs of retinal toxicity, which may be asymptomatic, according to a report in the May issue of Ophthalmology.
Dr. Bita Esmaeli and colleagues of M.D. Anderson Cancer Center, Houston, describe three patients in whom retinopathy developed during interferon therapy for various forms of cancer. The patients had funduscopic findings such as cotton-wool spots and intraretinal hemorrhages.
In one of the three cases, the retinopathy was asymptomatic--the patient was referred only after routine optometric examination.
In all three cases, the ocular findings resolved after interferon was stopped. Some patients resumed interferon treatment at a reduced dose, without recurrent symptoms.
Interferon has known ocular complications--including retinal
ischemia and ischemic optic neuropathy--that lead to visual loss.
Interferon-induced retinal toxicity can be completely asymptomatic, the new
findings suggest, indicating the need for close follow-up of cancer patients
receiving interferon. Dr. Esmaeli and colleagues recommend a dilated
funduscopic evaluation at the start of treatment and every 3 months thereafter.
They also call for further studies to define the scope of the problem of
interferon retinopathy in cancer patients.
Ophthalmology 108:858-860,
2001.
May 9, 2001
ST. LOUIS (MD Consult) - The FDA has issued a Public Health Advisory concerning serious health risks associated with two drugs used to treat onychomycosis and other fungal infections.
The Health Advisory cites a "small but real risk" of congestive heart failure (CHF) in patients taking itraconazole, as well as a risk of liver problems in patients taking either itraconazole or terbinafine hydrochloride.
Recent studies have found that itraconazole can have a "negative inotropic effect." Postmarketing data show 94 cases of CHF in patients taking itraconazole. In 58 of these cases, itraconazole is thought to have caused or contributed to the development of CHF.
The product labeling for itraconazole--marketed by Janssen Pharmaceutica Products as Sporanox--will be changed to include a "black box" warning that the drug should not be used in patients with CHF or other forms of cardiac dysfunction.
The warning also includes information on drug interactions with the potential to cause heart-related adverse events, and the need to discontinue itraconazole if signs of CHF develop during treatment.
The Safety Advisory also warns of several cases of liver failure in patients taking itraconazole or oral terbinafine hydrochloride, marketed by Novartis Pharmaceuticals as Lamisil. Both products will carry a recommendation that nail specimens be obtained to confirm the diagnosis of fungal infection before starting treatment.
The FDA encourages prescribers to report adverse events associated with either of these antifungal medications to its Medwatch program by telephone at 1-800-FDA-1088 or online at http://www.fda.gov/medwatch.
April 28, 2001
ST. LOUIS (MD Consult) - High-dose angiotensin-converting enzyme (ACE) inhibitor therapy does not lower the rate of restenosis after coronary stenting in a group of patients at high genetic risk, according to a French study in the April 28 issue of The Lancet.
Dr. Thibaud Meurice of Universitaire de Lille assessed the genotype of the ACE I deletion allele (ACE I/D) polymorphism in 345 consecutive patients undergoing coronary stent placement. Of these, 115 had the DD genotype, which has been linked to a high risk of restenosis after stenting. These patients were randomized to ACE inhibitor therapy (quinapril 40 mg/d) or placebo, beginning 48 hours after stent placement and continuing for 6 months. Follow-up angiograms were evaluated in 79 patients to assess the effect of treatment on restenosis.
Surprisingly, the mean late loss in minimum lumen diameter was significantly higher in the quinapril group than in the placebo group. Mean values were 1.11 vs 0.76 mm, respectively. Other angiographic parameters also pointed to an increased restenosis rate in patients receiving ACE inhibitor therapy.
For patients with the DD genotype, ACE inhibitor therapy does not decrease the risk of restenosis after coronary stenting. The researchers conclude that, for patients in this high-risk group, quinapril therapy may lead to an exaggerated restenotic response.
Lancet 357:1321-1324, 2001.
April 20, 2001
ST. LOUIS (MD Consult) - The FDA has announced new and stronger safety warnings to be added to the product labeling for levomethadyl acetate HCl, a drug for treatment of opiate addiction, according to an April 20 "Talk Paper." The product is marketed by Roxane Laboratories, Inc., as Orlaam.
Prompted by reports of serious cardiac adverse events, the new warnings include a change in indication: levomethadyl is no longer to be used as initial therapy for opiate addiction. It may still be used for patients who do not respond adequately to other treatments, however. The new warnings are to be highlighted in a "black box," the Talk Paper says.
According to postmarketing surveillance data, at least 10 cases of serious arrhythmias in patients receiving levomethadyl have been reported to the FDA. Other cases have been reported in Europe.
The original labeling for levomethadyl, approved in 1993, included precautions about cardiac events, based on observations of prolonged cardiac conduction. The drug should not be used in patients with known or suspected cardiac arrhythmias, nor in combination with any drug with the potential to cause heart rhythm abnormalities. Patients who experience symptoms while taking the drug--including palpitations, dizziness, light-headedness, or seizures--should be advised to seek medical attention.
For more information on the labeling changes, contact Roxane Laboratories at (800) 962-8364.
April 19, 2001
ST. LOUIS (MD Consult) - Combined treatment with rifampin and pyrazinamide for latent tuberculosis has been linked to two cases of severe hepatitis--one of them fatal--according to a report in the April 20 Morbidity and Mortality Weekly Report.
The report summarizes two patients who developed hepatitis while receiving rifampin-pyrazinamide therapy for latent tuberculosis. The first patient was a 53-year-old prisoner who started treatment after screening revealed a positive tuberculin skin test, though no evidence of active tuberculosis. Five weeks later, he died of liver necrosis and failure resulting from hepatitis.
The second patient, a 59-year-old woman, developed severe hepatitis requiring hospital admission 7 weeks after starting treatment with rifampin and pyrazinamide. She gradually responded to treatment with prednisone, and was discharged after a 25-day hospital stay.
For patients with latent tuberculosis, the combination of rifampin and pyrazinamide is sometimes used as an alternative to isoniazid. In the fatal case, the combination was standard treatment at the jail where the patient was incarcerated. In the other, suspected exposure to drug-resistant tuberculosis was a factor in the treatment decision.
The report emphasizes the need for close monitoring of patients being treated for latent tuberculosis infection. They should be reminded repeatedly to stop treatment if they develop symptoms of hepatitis--in the reported cases, both patients continued treatment despite symptoms. The CDC Division of Tuberculosis Elimination encourages physicians to be on the lookout for further cases of severe hepatitis in patients being treated for latent tuberculosis. Suspected cases may be reported by telephone at (404) 639-8125.
MMWR 50:289-291, 2001.
March 21, 2001
ST. LOUIS (MD Consult) - An article published recently in Blood (Unnikrishnan, et al, 1 March 2001;97:1514-1516) describes prolonged QT interval and torsade de pointes in 3 patients being treated with arsenic trioxide for acute myeloid leukemia (AML). In one patient, the torsade resolved upon correction of serum potassium to 3.1 mEq/L and magnesium to 1.7 mg/dL. The other two patients died from cardiac arrhythmia. All 3 patients had been intubated due to respiratory distress. The arsenic trioxide used in the reported study was not Cell Therapeutics' Trisenox (arsenic trioxide) injection.
QT prolongation is a well described toxic effect of arsenic trioxide. Of 40 patients evaluated in the trial that was the basis of approval of Trisenox, 16 patients (40%) had at least one ECG tracing with a QTc interval greater than 500 msec. One case of torsade de pointes had occurred in these 40 patients. Prolongation of the QTc was observed between 1 and 5 weeks of daily Trisenox infusion, and then returned to baseline by the end of 8 weeks after Trisenox infusion. These observations led to the boxed warning in the Trisenox label regarding the importance of ECG and electrolyte monitoring in patients given arsenic trioxide.
No cardiac deaths have been reported in post-marketing surveillance to date. Based on available data on >360 patients treated in clinical investigations, the safety of administration of Trisenox can be optimized with appropriate monitoring and management of ECG abnormalities as described in the label.
WARNING
ECG Abnormalities:
Arsenic trioxide can cause QT interval prolongation and complete atrioventricular block. QT prolongation can lead to a torsade de pointes-type ventricular arrhythmia, which can be fatal. The risk of torsade de pointes is related to the extent of QT prolongation, concomitant administration of QT prolonging drugs, a history of torsade de pointes, preexisting QT interval prolongation, congestive heart failure, administration of potassium-wasting diuretics, or other conditions that result in hypokalemia or hypomagnesemia.
One patient (also receiving amphotericin B) had torsade de pointes during induction therapy for relapsed APL with arsenic trioxide.
ECG and Electrolyte Monitoring Recommendations:
Prior to initiating therapy with Trisenox, a 12-lead ECG should be performed and serum electrolytes (potassium, calcium, and magnesium) and creatinine should be assessed; preexisting electrolyte abnormalities should be corrected and, if possible, drugs that are known to prolong the QT interval should be discontinued. For QTc greater than 500 msec, corrective measures should be completed and the QTc reassessed with serial ECGs prior to considering using Trisenox.
During therapy with Trisenox, potassium concentrations should be kept above 4 mEq/L and magnesium concentrations should be kept above 1.8 mg/dL. Patients who reach an absolute QT interval value > 500 msec should be reassessed and immediate action should be taken to correct concomitant risk factors, if any, while the risk/benefit of continuing versus suspending Trisonex therapy should be considered. If syncope, rapid or irregular heartbeat develops, the patient should be hospitalized for monitoring, serum electrolytes should be assessed, Trisenox therapy should be temporarily discontinued until the QTc interval regresses to below 460 msec, electrolyte abnormalities are corrected, and the syncope and irregular heartbeat cease. There are no data on the effect of Trisonex on the QTc interval during the infusion.
February 16, 2001
ST. LOUIS (MD Consult) - Anso Comfort Capsules, a product distributed by NuMeridian, are part of a voluntary national recall following an investigation by the California Department of Health Services. The investigation revealed that the capsules contained chlordiazepoxide (Librium).
Librium, a controlled substance, is used for anxiety and as a sedative. It may intensify the effects of alcohol and other central nervous system depressants and may be habit forming. Librium can be extremely dangerous if taken without a physician's supervision.
Anso Comfort Capsules were manufactured in California and contained ingredients that were imported from China.
According to a press release posted by the U.S. Food and Drug Administration (FDA), "Advertising for the product claims the capsules are useful for the treatment of a wide variety of illnesses, including high blood pressure and high cholesterol, as well as being a natural herbal diet supplement. The advertising also claims that the product only contains Chinese herbal ingredients and that consumers may reduce or stop their need for prescribed medicines. No clear medical evidence supports any of these claims."
Diana Bonta R.N., Dr. P.H., the California State Health Director, urges consumers to stop taking Anso Comfort Capsules and to see a doctor, especially if other prescription medications are being taken.
Anso Capsules were sold through the distributor by mail or telephone order. The capsules are available in 60-capsule bottles and are clear with a dark green powder inside. The label on the bottle is yellow with green printing and includes a picture of a plant. The UPC number is 7-63148-58798-6.
The FDA will be involved in the follow-up investigation and the recall throughout the United States.
February 9, 2001
ST. LOUIS (MD Consult) - Results from a study appearing in the February issue of Pediatrics suggests that treatment with postnatal systemic dexamethasone does impair brain growth and development in premature infants with neonatal chronic lung disease. According to researchers, this brain growth impairment primarily affects cerebral cortical gray matter.
Dr. Brendan P. Murphy and colleagues studied eighteen premature infants (born at 23 to 31 weeks). Of these, seven had been treated with dexamethasone and eleven had not. The infants were studied at term (38 to 41 weeks postconception). Fourteen healthy infants were also studied for comparison.
According to the article, the researchers used "an advanced quantitative volumetric 3-dimensional magnetic resonance imaging (MRI) technique to quantify cerebral tissue volumes." Results of the study demonstrated that cerebral cortical gray matter was decreased by 35% in the dexamethasone-treated group when compared with the gray matter volume of infants who did not receive the drug (130.3 vs. 200.6, respectively).
The study showed that subcortical gray matter volume and myelinated/unmyelinated white matter volume did not differ among the two groups of infants. The researchers note however, "Premature infants treated with dexamethasone exhibited a reduction in total cerebral tissue volume (30%) compared with total cerebral tissue volume in both the premature infants not treated with dexamethasone and the control term infants (312.7 vs. 448.2 vs. 471.6, respectively). They report that this decrease in total cerebral tissue volume relates primarily to the decrease in cerebral cortical gray matter volume.
In conclusion, Dr. Murphy and colleagues report that, "Although the premature infants who received dexamethasone were smaller, with more severe respiratory disease, these findings are consistent with growing evidence of a potential deleterious effect of dexamethasone on neonatal brain and subsequent neurodevelopmental outcome and...should be taken into consideration by clinicians when weighing the potential risks and benefits of this therapy for low birth weight infants with neonatal chronic lung disease".
Pediatrics 2001;107:217-221
February 2, 2001
ST. LOUIS (MD Consult) - Japanese researchers have reported that concomitant dosing of mycophenolate mofetil and iron ion preparations given to transplant recipients should be avoided. According to the researchers, this dosing results in a significant decrease in mycophenolate mofetil absorption.
Dr. Kazuyuki Ueno and his colleagues from the National Cardiovascular Center in Osaka, Japan completed the trial leading to this finding. The trial involved administration of 1.0 g of mycophenolate mofetil to each of seven volunteers. After a 7-day washout period, the volunteers were given 1.0 g of mycophenolate mofetil and two tablets of iron ion preparation each. Reverse-phase HPLC was used to measure the serum concentrations of mycophenolic acid in each phase of the study.
The December 2000 issue of Clinical Pharmacology & Therapeutics stated that the area under the plasma concentration-time curve from 0 to 12 hours for mycophenolic acid was significantly decreased during the second phase of the trial. The first phase showed the mean area under the curve to be 32.9 mcg/mL per hour, while the mean area under the curve was 2.92 mcg/mL per hour during the second phase.
Maximum concentrations of mycophenolic acid were significantly lower during the second phase. Mean maximum mycophenolic acid concentrations per hour in the first phase were 20.1 mcg/mL; concentrations in the second phase were 1.30 mcg/mL. According to Dr. Ueno, "The mechanism of interaction between mycophenolate mofetil and iron ion preparations may be the formation of chelation complex; this complex probably restricts gastrointestinal absorption."
January 24, 2001
ST. LOUIS (MD Consult) - Serono, Inc., in conjunction with the U.S. Food and Drug Administration (FDA), released a statement on January 22nd to inform physicians, patients and distributing pharmacies about a counterfeit version of Serostim 6mg [somatropin (rDNA origin) for injection], an approved medication for the treatment of AIDS wasting.
According to Serono's statement, the counterfeit product is definitely not Serostim and was neither manufactured nor distributed by the company. The safety and efficacy of the counterfeit product is unknown and may pose a serious health risk to patients.
The company recently became aware of the counterfeit drug. In an effort to prevent any patient currently undergoing therapy with Serostim from receiving this product, Serono has issued a "Notification of Potential Counterfeit Product" to alert wholesalers, physicians, pharmacists, and AIDS service organizations.
The counterfeit product is packaged to appear as lot number MNK612A. There are many indicators distinguishing it from the true Serostim, such as differences in the packaging. The carton of the authentic product has the lot number and expiration date appearing on a dark blue box that is printed directly on the packaging, while the counterfeit product has a separate dark blue label affixed to one end of the carton. The counterfeit drug bears an expiration date of 08/02, while the genuine Serostim is dated 08/01.
In addition, the true drug product itself is distinguishable from the counterfeit. Specifically, Serono describes its product as a "white lyophilized cake, thick at the bottom of the vial" and the counterfeit drug is a "white, powdery snow-like substance" that has a tendency to stick to the vial's stopper.
Finally, the lot number on the diluent vial that is packaged with the counterfeit drug appears as 99h124 and is dated 08/02. The real product's lot number reads 99H124 and has an expiration date of 06/02.
The Office of Criminal Investigations for the FDA is investigating this matter.
January 23, 2001
ST. LOUIS (MD Consult) - An herbal medicine marketed for the treatment of allergies is being recalled after tests showed trace amounts of aristocholic acid, a carcinogen and nephrotoxin.
The voluntary recall of "Neo Concept Aller Relief" was announced by the manufacturer, BMK International. The product is distributed to health care practitioners as well as retail outlets in the United States. Lot numbers affected are #003480 and #0006480.
Tests conducted by the FDA determined that Aller Relief contained trace amounts of aristocholic acid, which has previously been linked to cases of kidney failure and kidney cancer. No such events have been reported among users of Aller Relief.
The manufacturer is reformulating Aller Relief to eliminate contamination with aristocholic acid. Meanwhile, patients should be advised not to take the product.
January 12, 2001
ST. LOUIS (MD Consult) - On January 12, 2001, Houston pharmaceutical manufacturer, Great Southern Laboratories, announced a voluntary recall of Cydec drops Lot #02950. Cydec drops are a prescription pediatric cold medicine manufactured by Cypress Pharmaceuticals. The drops are contained in a one-ounce bottle with a calibrated dropper and are packaged in a carton, each bearing the Cypress Pharmaceutical label.
According to an U.S. Food and Drug Administration (FDA) press release, Great Southern began the recall upon learning that the outer carton of Lot #02950 in which the medicine bottle is packaged had an incorrect dosage correlation chart printed on it. The chart incorrectly equates a dropperful to a teaspoonful and a partial dropperful to a partial teaspoon full. If a consumer used the incorrect chart and measured the medication to be given using a teaspoon instead of using the packaged dropper, an overdose could occur. The press release states that an overdose of Cydec can cause "serious illness or death, depending on...the health of the patient and the extent of the overdose."
Great Southern Laboratories have not yet received any reports of illness or death in connection with the labeling error. Any patients in possession of Cydec Drops, lot #02950, should be asked to discontinue use of this product and return it to their pharmacist.
Only Cydec Drops from Lot #02950 are involved in the recall. The product label bears NDC #60258-439-30 and has an expiration date of 12/2005. Each one-ounce bottle contains 2 mg of the antihistamine carbinoxamine maleate and 25 mg of the decongestant pseudoephedrine hydrochloride in each 1 ml of product.
Great Southern Laboratories is conducting the recall with the full knowledge of the FDA. Cypress Pharmaceuticals had distributed 6,135 bottles of the antihistamine/decongestant prescription drug product to wholesalers for distribution to pharmacies beginning nationally on December 19, 2000. The company is contacting all pharmacies that received any shipments of Cydec Drops after December 19, 2000. The pharmacies are being asked to contact their customers to ensure that Cydec Drops from Lot #02950 are not used and are returned to the pharmacy.
January 12, 2001
ST. LOUIS (MD Consult) - Patients receiving highly active antiretroviral therapy (HAART) for HIV infection appear to be at risk of osteonecrosis, according to a recent study in Clinical Infectious Diseases.
Dr. Paul Monier and colleagues of University of Tennessee, Nashville, encountered 5 patients who developed osteonecrosis while receiving HAART. In their report, they combine these 5 cases with 28 cases of HIV-related osteonecrosis previously reported in the literature.
The patients' mean age was 35 years. In 33% of patients, the only risk factor for osteonecrosis was HIV infection. Fifty-five percent were receiving antiretroviral therapy at the time osteonecrosis was diagnosis. Data on CD4 lymphocyte count were available in 16 patients, whose mean CD4 count was 350 cells/mL. Symptom onset or exacerbation was linked to successful antiretroviral therapy in 10 of these patients.
Although the precise mechanisms are unclear, these cases suggest that osteonecrosis is an "emerging manifestation" of HIV infection and/or HAART. It is unknown whether this complication arises from the immunologic and virologic effects of therapy, or as a complication of the drugs themselves. However, the authors believe that osteonecrosis may be more common among HIV-infected patients than currently recognized.
Clin Infect Dis 31:1488-1492, 2001
January 11, 2001
ST. LOUIS (MD Consult) - Early treatment with moderate-dose dexamethasone in preterm infants may cause serious complications and does not reduce the risk of chronic lung disease, according to a study published in The New England Journal of Medicine earlier this month.
Researchers for the National Institute of Child Health and Human Development Neonatal Research Network randomized 200 mechanically ventilated, extremely low-birth-weight infants--501 to 1,000 g--to receive dexamethasone or placebo. The infants were also randomized to receive routine ventilatory support or permissive hypercapnia. Dexamethasone treatment started within 24 hours after birth at a dose of 0.15 mg/kg for 3 days, tapering over the subsequent 7 days.
At follow-up through 36 weeks' postmenstrual age, there was no difference in the rates of mortality and chronic lung disease between the dexamethasone and placebo groups. On pooling of the two different ventilation groups, those receiving dexamethasone were less likely to receive supplemental oxygen but more likely to have hypertension and hyperglycemia requiring insulin therapy. Thirteen percent of infants in the dexamethasone group developed spontaneous GI perforation during the initial 2 weeks of life. There was also evidence of adverse growth effects in the dexamethasone group, ie, lower body weight and smaller head circumference.
Previous studies had found that early treatment with high-dose dexamethasone can reduce the risk of chronic lung disease but carries a risk of complications. The new findings suggest that moderate-dose dexamethasone is also associated with a high rate of serious complications--especially GI perforation--with no benefits in terms of preventing chronic lung disease or death.
N Engl J Med 344:95-101, 2001
January 8, 2001
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration (FDA) and Bristol Myers Squibb have issued a warning to health care professionals regarding the use of the HIV drugs stavudine (Zerit) and didanosine (Videx or Videx EC) in combination with other antiretroviral agents during pregnancy because of an increased risk of fatal lactic acidosis and liver damage.
According to an FDA Talk Paper released on the fifth of January 2001, the warning was issued following the report of fatal lactic acidosis, with or without pancreatitis (a known complication of Videx and Zerit) that occurred in three pregnant women taking the medications along with other HIV drugs. One of the reports was identified through post-marketing surveillance and the other cases were reported from clinical trials of a new HIV drug.
In addition, the Talk Paper states that the FDA has received several reports of nonfatal of lactic acidosis, with or without pancreatitis, that occurred in pregnant women taking only Videx and Zerit and goes on to say that "Although data has suggested that women may be at an increased risk for the development of lactic acidosis and liver toxicity, it is unclear whether pregnancy potentiates these known side effects."
Also on January 5th, Bristol Myers Squibb issued a "Dear Healthcare Provider" letter to inform healthcare professionals of the risks identified with the use of these medications. The company recommends that "the combination of stavudine and didanosine should be used with caution during pregnancy...and only if the potential benefits clearly outweigh the potential risks." Additionally, the warning letter states that "Decisions regarding antiretroviral therapy for pregnant women...should be made by healthcare providers experienced in the treatment of HIV infection."
Although the Videx, Videx EC and Zerit labels have always warned of the risk of lactic acidosis, the company is strengthening the "black box" warning to include this new information. The FDA Talk Paper recommends that all women who receive this combination HIV drug therapy should be monitored closely for any signs of lactic acidosis or liver damage.
January 5, 2001
ST. LOUIS (MD Consult) - The Centers for Disease Control and Prevention have reported a number of cases of severe hepatotoxicity and other adverse effects in health care workers receiving the antiretroviral drug nevirapine after occupational HIV exposure.
Appearing earlier this month in Morbidity and Mortality Weekly Report, the article details two cases of life-threatening hepatotoxicity in health care workers receiving nevirapine as part of a postexposure prophylaxis regimen. Both patients developed fulminant hepatitis, which in one case progressed to end-stage liver failure requiring transplantation.
Subsequent review identified 20 additional serious adverse events related to the use of nevirapine for postexposure prophylaxis, including 12 cases of hepatotoxicity. Other adverse events included skin reactions in 14 patients and rhabdomyolysis in one.
An editorial note in MMWR points out the nevirapine is not recommended for use in postexposure prophylaxis regimens. Nevertheless, many clinicians prescribe nevirapine for HIV-exposed health care workers, apparently because of its efficacy in preventing perinatal HIV transmission.
The report recommends following recommended guidelines and dosing instructions for postexposure prophylaxis. The editors note, "[i]n many circumstances, the risks associated with nevirapine as part of a postexposure prophylaxis regimen outweigh the anticipated benefits"--especially since most occupational HIV exposures do not result in HIV transmission.
January 03, 2001
ST. LOUIS (MD Consult) - Several patients have developed life-threatening ventricular rhythm disturbances while taking levacethylmethadol (Orlaam) for the treatment of opiate addiction, according to a public statement by the European Agency for the Evaluation of Medicinal Products (EMEA).
Pending completion of a full comparative risk/benefit assessment, the EMEA recommends that physicians not start any new patients on levacethylmethadol.
The report describes 10 patients who have developed life-threatening cardiac rhythm disorders while taking levacethylmethadol. Five patients had cardiac arrest associated with ventricular arrhythmias, three had cardiac arrhythmias, and two had syncopal episodes. Other findings included QT-interval prolongation in seven patients and torsade des pointes in four. Three patients required pacemaker insertion.
The cases are especially worrisome given the young age of the patients involved: 23 to 57 years, with a mean of 39 years. There is also the possibility that other patients cardiac complications may have gone unrecognized or unreported.
Levacethylmethadol is indicated as substitution maintenance therapy for opiate addiction in patients previously treated with methadone. It is marketed as Orlaam by Boehringer Ingelheim and its subsidiaries.
In addition to stopping treatment of new patients, the EMEA recommends that patients currently taking levacethylmethadol contact their physicians. The statement includes a warning to patients that they should not suddenly stop taking the medication without medical advice.
January 3, 2001
ST. LOUIS (MD Consult) - Postmarketing data indicate a possible risk of tuberculosis infection among patients taking the tumor necrosis factor (TNF)-inhibitor infliximab (Remicade).
Last month, the European Agency for the Evaluation of Medicinal Products (EMEA) released a public statement citing 28 cases of tuberculosis developing among patients who recently started infliximab treatment. The report included one patient who died of disseminated tuberculosis.
Of the 28 cases, 19 occurred in Europe and 9 in the United States. Some cases were miliary tuberculosis, while others were in atypical, extrapulmonary locations. Most of the affected patients had previously received immunosuppressant and corticosteroid therapy. In many patients, tuberculosis developed within the first three infusions of infliximab, supporting the putative link.
In the United States and Europe, infliximab has been approved for the treatment of Crohn's disease and methotrexate-resistant rheumatoid arthritis. Earlier this month, the FDA announced its approval of infliximab, given in combination with methotrexate, to reduce progressive joint destruction in rheumatoid arthritis. Infliximab is marketed as Remicade by Centocor, Inc., a subsidiary of Johnson & Johnson.
Infliximab is contraindicated for use in patients with chronic infections or a history of recurrent infections. Based on the newly reported cases, the EMEA recommends stopping infliximab treatment in patients with suspected active tuberculosis. In addition, all patients should be thoroughly evaluated for active and latent tuberculosis before starting infliximab.
Patients taking infliximab should be instructed to contact their physician if they develop any signs or symptoms of tuberculosis, such as persistent cough, weight loss, or low-grade fever.
January 3, 2001
ST. LOUIS (MD Consult) - Asthma patients receiving the leukotriene receptor antagonist zafirlukast may be at risk of severe hepatitis, according to a recent report in the Annals of Internal Medicine.
Dr. John F. Reinus of Montefiore Medical Center, New York, and colleagues report on three patients who developed severe liver damage while taking zafirlukast for the treatment of asthma. All patients were middle-aged women taking a zafirlukast dosage of 20 mg twice daily.
One patient was asymptomatic, but stopped taking zafirlukast after 9 months when her liver function studies became abnormal. A few months later, when she was inadvertently rechallenged with zafirlukast, she developed jaundice and other symptoms. The symptoms and liver function abnormalities resolved when zafirlukast was stopped.
The other two patients experienced more serious consequences. One developed subfulminant liver failure requiring hepatic transplantation. The other developed severe hepatitis, which responded to corticosteroid therapy. In both cases, liver biopsy findings were consistent with a drug-induced reaction.
Although clinical trials found a 5% rate of abnormal liver function studies in patients taking zafirlukast, there have been no previous reports of severe hepatitis caused by this medication. The frequency of such hepatotoxic effects remains unclear. The authors recommend that patients receiving zafirlukast be followed up closely for clinical evidence of hepatitis.
Ann Intern Med 133:964-968, 2000
News Updates are brought to you by
An Imprint of .
To order a Mosby's Drug Consult product or to check on your order, please call Elsevier Science Customer Service Department at 800-545-2522 or Order Online