Topamax associated with hyperchloremic, non-anion gap metabolic acidosis
Hepatic injury warrants new prescribing information for Arava
FDA reports adverse incidents associated with sirolimus-coated Cypher stent
Roche warns of increased mortality with use of prophylaxis medication
U.S. warns against using short-course rifampin-pyrazinamide for latent TB
Major adverse reactions to TB drug pyrazinamide greater than other first-line agents
Aventis urges caution with Ketek in myasthenia gravis patients
Drugmakers concerned about Serzone, Seroquel dispensing errors
Listeria monocytogenes infection possible with use of anti-TNF-alpha agents
Ectopic pregnancy risk possible with progestogen-only emergency contraceptive
Dixon's OTC acetaminophen tablets recalled due to wrong dosage
UCB Pharma warns against prescribing errors for Keppra vs Kaletra
U.S. FDA cautions against coadministration of Reyataz and Viread
European agency advises against tenofovir-lamivudine-abacavir combination
Barr announces voluntary recall of 3 lots of Nortrel 7/7/7 - 28 Day
FDA issues alert concerning additional counterfeit lots of Lipitor
Antipsychotic drug Risperidone may increase stroke risk in elderly
FDA strengthens warnings about lindane treatments for lice, scabies
December 30, 2003
ST. LOUIS (MD Consult) - In a letter addressed to health care professionals dated December 18, 2003, Ortho-McNeil Pharmaceuticals Inc. warned health care professionals that Topamax (topiramate) tablets/sprinkle capsules can cause hyperchloremic, non-anion gap metabolic acidosis (decreased serum bicarbonate). Measurement of baseline and periodic serum bicarbonate during topiramate treatment is recommended. The Warnings and Precautions sections of the prescribing information for Topamax have been revised to reflect this.
Topamax is approved and marketed for the adjunctive treatment of partial-onset seizures, generalized tonic-clonic seizures, and seizures associated with the Lennox-Gastaut syndrome in adults and children 2 years of age and older.
Data on hyperchloremic, non-anion gap metabolic acidosis are derived from placebo-controlled trials and post-marketing experience in over 2.5 million patients. In clinical trials, the rate of occurrence of a persistently decreased serum bicarbonate ranged from 23% to 67% for patients treated with topiramate and 1% to 10% for placebo. The incidence of markedly low serum bicarbonate in clinical trials ranged from 3% to 11% for topiramate and 0% to <1% for placebo.
Generally, decreases in serum bicarbonate occur soon after initiation of topiramate, though they can occur at any time during treatment. Bicarbonate decrements are usually mild to moderate, with an average decrease of 4 mEq/L at daily doses of 400 mg in adults and approximately 6 mg/kg/d in pediatric patients. Rarely, patients can experience decrements to values below 10 mEq/L.
Conditions or therapies that predispose to acidosis (such as renal disease, severe respiratory disorders, status epilepticus, diarrhea, surgery, ketogenic diet, or drugs) may be additive to the bicarbonate-lowering effects of topiramate.
Some manifestations of acute or chronic metabolic acidosis may include hyperventilation, nonspecific symptoms such as fatigue and anorexia, or more severe sequelae including cardiac arrhythmias or stupor. Chronic, untreated metabolic acidosis may increase the risk for nephrolithiasis or nephrocalcinosis and may also result in osteomalacia and/or osteoporosis with an increased risk for fractures. Chronic metabolic acidosis in pediatric patients may also reduce growth rates. A reduction in growth rate may eventually decrease the maximal height achieved. The effect of topiramate on growth and bone-related sequelae has not been systematically investigated.
Measurement of baseline and periodic serum bicarbonate during topiramate treatment is recommended. If metabolic acidosis develops and persists, consideration should be given to reducing the dose or discontinuing topiramate (using dose tapering). If the decision is made to continue patients on topiramate in the face of persistent acidosis, alkali treatment should be considered.
Any questions regarding Topamax tablets and Topamax Sprinkle Capsules can be directed to Ortho-McNeil Medical Affairs Division at 1-800-682-6532.
December 22, 2003
ST. LOUIS (MD Consult) - In a letter addressed to health care professionals and dated December 15, 2003, Eli Lilly and Company advised that its dopamine agonist Permax (pergolide mesylate) may be associated with patients falling asleep without warning.
The U.S. Food and Drug Administration (FDA) and Lilly modified the Warnings and Precautions sections of the Permax label to inform health care professionals of the possibility of patients falling asleep while performing daily activities, including operation of motor vehicles, while receiving treatment with Permax. Permax is indicated as adjunctive treatment to levodopa/carbidopa in the management of the signs and symptoms of Parkinson's disease.
Many patients who have fallen asleep have perceived no warning of somnolence, and many believed they were alert immediately before the event. Some of these events were reported as late as 1 year after the initiation of treatment with Permax.
Health care professionals should be alerted to the potentially serious risks associated with these events and should carefully evaluate their patients for the presence of somnolence.
Somnolence is a common occurrence in patients receiving Permax. Many clinical experts believe that falling asleep while engaged in activities of daily living always occurs in a setting of preexisting somnolence, although patients may not give such a history. For this reason, prescribers should continually reassess patients for drowsiness or sleepiness, especially because some of the events occur well after the start of treatment. Prescribers should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities.
Before initiating treatment with Permax, patients should be advised of the potential to develop drowsiness and should be specifically asked about factors that may increase the risk with Permax, such as concomitant sedating medications or the presence of sleep disorders. If a patient develops significant daytime sleepiness or episodes of falling asleep during activities that require participation (eg, conversations, eating), administration of Permax should ordinarily be discontinued. If a decision is made to continue Permax, patients should be advised to not drive and to avoid other potentially dangerous activities.
Although dose reduction may reduce the degree of somnolence, there is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living.
December 9, 2003
ST. LOUIS (MD Consult) - According to an announcement made by the U.S. Food and Drug Administration (FDA) on December 4, 2003, Magno-Humphries, Inc., voluntarily recalled one lot (504 bottles) of Dixon's, APAP Acetaminophen 325-mg analgesic tablets, an over-the-counter product sold in 100-tablet bottles with lot number 319687, expiration date 03/05.
The recall is effective immediately and is being undertaken because this lot contains an excess of the labeled amount of acetaminophen. The tablets contained in the mislabeled bottles are 500 mg acetaminophen, instead of 325 mg acetaminophen. The acetaminophen is being recalled because overdoses of this medication can lead to severe health problems including liver toxicity and liver failure. The acetaminophen was sold under the Dixon's label at retail stores and pharmacies nationwide beginning in August 2003.
Consumers who purchased bottles with lot number 319687 are urged to discontinue use of the product immediately and return it to the place of purchase for a full refund. Consumers with questions can contact Magno-Humphries, Inc., at 1-800-935-6737.
This recall is being made in cooperation with the FDA. To date, no consumer complaints have been reported.
Any adverse reactions experienced with the use of this product should also be reported to the FDA's MedWatch Program by phone at 1-800-FDA-1088; by fax at 1-800-FDA-0178; by mail at MedWatch, HF-410, FDA, 5600 Fishers Lane, Rockville, MD 20852-9787; or on the MedWatch website at fda.gov/medwatch.
November 24, 2003
ST. LOUIS (MD Consult) - In October 2003, Aventis Pharmaceuticals and the U.S. Food and Drug Administration (FDA) updated the prescribing information for Arava (leflunomide), indicated for the treatment of active rheumatoid arthritis. In postmarketing experience worldwide, rare, serious hepatic injury, including cases with fatal outcome, have been reported during treatment with Arava. This information was delivered in a letter addressed to health care professionals, which can be found on the FDA's Web site.
Most cases occurred within 6 months of therapy and in a setting of multiple risk factors for hepatotoxicity. Multiple confounding factors were present in most of the cases, such as preexisting hepatic disease, comorbid illness predisposing to hepatic complications, and concomitant potentially hepatotoxic medications.
Rare postmarketing reports of severe infections, including sepsis, which may be fatal, were also received. Most of the reports were confounded by concomitant immunosuppressant therapy or comorbid illness, which, in addition to rheumatoid disease, may predispose patients to infection.
The new prescribing information includes a warning of these rare but serious adverse events.
Specifically, the hepatotoxicity section of the prescribing information provides further guidance regarding duration of the initial monthly liver enzyme monitoring, intervals for monitoring in the maintenance of treatment, and dose discontinuation for confirmed alanine aminotransferase (ALT) elevations more than three times the upper limit of normal.
The "Immunosuppression Potential/Bone Marrow Suppression" section of the warnings label has been edited to emphasize that interruption of therapy with Arava may be necessary if a serious infection occurs while a patient is taking the medication. This script has been added to the previous warning that Arava is not recommended for patients with severe immunodeficiency, bone marrow dysplasia, or severe, uncontrolled infections.
For more information about the revised prescribing information, contact Aventis Pharmaceuticals Medical Information Services at 800-633-1610.
The FDA requests that any adverse events be reported to the FDA MedWatch program by phone at 800-FDA-1088, by fax at 800-FDA-0178, via the MedWatch Web site, or by U.S. Mail at MedWatch, HF-2 5600 Fishers Lane, Rockville, MD 20857-9787.
November 19, 2003
ST. LOUIS (MD Consult) - On November 14, 2003, the U.S. Food and Drug Administration (FDA) issued a Talk Paper alerting U.S. residents to the recent recall of certain GlaxoSmithKline "Diskus" medicines sold in Canada to treat asthma and chronic obstructive pulmonary disease (COPD). The three asthma products—Ventolin Diskus, Flovent Diskus, and Serevent Diskus—were recalled in Canada on November 12, 2003, because the products' drug delivery system may not function properly and may deliver too little of the drug, or none at all. Canadian patients are being advised to return the affected product to the pharmacy or physician's office where it was obtained so that they can get a replacement.
The FDA emphasizes that FDA-approved Diskus products (Advair and Serevent) sold in the United States through legally sanctioned marketing channels are not subject to this recall. The agency warns that consumers buying medications outside the United States may have received potentially substandard and ineffective products.
The specific affected lots of the products recalled in Canada, and additional information from the product manufacturer, are available on the Canadian website of GlaxoSmithKline at gsk.ca/en/media_room/news/public_advisory_en.pdf.
This alert was issued as a precaution because of the recent trend of U.S. residents obtaining precription drugs from Canada and elsewhere through online or storefront operations. Proponents of these purchases cite rising prescription drug costs in the United States. Some consumers have turned to sources outside the United States in an attempt to secure their medications at lower cost. However, this practice is discouraged by the FDA, which argues that the safety of non–FDA-approved medications cannot be guaranteed.
The FDA reminds patients that asthma, COPD, and related diseases can be serious and life-threatening. No one taking medications for these conditions should stop taking them abruptly without first talking with a physician. The FDA also emphasizes that all asthma drugs should be given as part of a comprehensive treatment plan that takes into account the patient's disease severity and fully educates the patient about the disease and its proper treatment.
U.S. patients who may have obtained these affected medications from Canada who have questions or concerns about these products should discuss them with their physicians, pharmacists, or health care providers. Consumers and health care professionals have been asked to report any suspected adverse events associated with the use of these products directly to GlaxoSmithKline, at 800-387-7374, or Health Canada, at 1-866-678-6789.
October 30, 2003
ST. LOUIS (MD Consult) - On October 29, 2003, the U.S. Food and Drug Administration (FDA) informed physicians about adverse events associated with Cordis Corporation's Cypher Coronary Stent. The FDA posted the information on its Web site as a public health notification to physicians. This was the second such warning sent to physicians since the April 2003 launch of the sirolimus-coated Cypher stent.
The FDA has received more than 290 reports of thrombosis (clotting) occurring 1 to 30 days after the procedure to implant the device. In more than 60 of these reports, use of the device was associated with the death of the patient; in the remainder, the device was associated with injury requiring medical or surgical intervention.
The FDA has also received more than 50 reports, including some deaths, that Cordis considers to be possible hypersensitivity reactions. The symptoms include pain, rash, hives, itching, fever, respiratory alterations, and blood pressure changes.
Hundreds of thousands of patients have been successfully treated with the Cypher stent. The FDA does not have enough information to determine whether the incidents of thrombosis and hypersensitivity reaction with the Cypher stent differs from those experienced with bare metal stents.
The FDA approved the Cypher stent in April 2003 for patients undergoing angioplasty procedures to open clogged coronary arteries. The stent, a cylindrical metal mesh, is designed to keep the arteries from re-clogging after the procedure. It is coated with a thin polymer containing the drug sirolimus that is slowly released into the patient and is intended to reduce the rate of re-blockage that occurs with other stents.
The cause of these adverse events has not yet been determined. The FDA and Cordis are working quickly to gather as much information as possible about the circumstances surrounding these events. The FDA is also working with the regulatory bodies of other countries to get more information about foreign experience with the Cypher stent.
Until the FDA gets to the root of the problems, the agency is encouraging doctors to follow the instructions for use of the stent and urging them to be vigilant for any patient symptom that may be attributed to hypersensitivity.
Patients who have received this stent should continue to follow their regularly scheduled plan for follow-up appointments with their doctors.
As a condition of approval, the FDA is requiring Cordis to conduct a 2,000-patient postapproval study and to continue evaluating patients from ongoing clinical trials to assess the long-term safety and effectiveness of the stent and to look for rare adverse events that may result from use of the product.
Doctors and patients who have experienced an adverse event related to the stent are encouraged to report the incident to the FDA. Reports may be made one of four ways: online at accessdata.fda.gov/scripts/medwatch/; by telephone at 1-800-FDA-1088; by fax at 1-800-FDA-0178; or by mail to MedWatch, FDA, HF-2, 5600 Fishers Lane, Rockville, MD 20857.
The notification to physicians is available at fda.gov/cdrh/safety/cypher.html.
October 15, 2003
ST. LOUIS (MD Consult) - On October 27, 2003, the U.S. Food and Drug Administration (FDA) issued a public health advisory to alert physicians to reports of suicidal thinking (and suicide attempts) in clinical studies of various antidepressant drugs in pediatric patients with major depressive disorder (MDD).
Experts say an estimated 750,000 adolescents in the United States have depression, and 500,000 attempt suicide every year. About 1,700 succeed.
In a statement, the FDA recognized that pediatric MDD is a serious condition for which there are few established treatment options. The agency acknowledged that, in addition to use of nonmedication approaches to treatment, clinicians must often make choices among drug treatments available for adult MDD. Currently, Prozac (fluoxetine) is the only drug labeled for use in pediatric MDD, and was approved recently under the Pediatric Exclusivity provision.
The FDA recently completed a preliminary review of reports for 8 antidepressant drugs—citalopram, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, sertraline, and venlafaxine—all studied under the pediatric exclusivity provision of the FDA Modernization Act (1997). (Although fluvoxamine data were reviewed along with the other antidepressant drugs, it should be noted that it is not approved by the FDA as an antidepressant in the United States.)
To date, noted the FDA, the data do not clearly establish an association between the use of these drugs and increased suicidal thoughts or actions by pediatric patients. Nevertheless, it is not possible at this point for the agency to rule out an increased risk of these adverse events for any of these drugs, including Paxil (paroxetine). In June 2003, the FDA announced it is reviewing the safety concerns related to off-label use of Paxil in children based on recent trials of that drug.
The FDA emphasized that, for the 7 drugs evaluated for use in the treatment of pediatric MDD, data the agency reviewed were adequate to establish effectiveness in MDD only for Prozac. Failure to show effectiveness in any particular study in pediatric MDD, however, is not definitive evidence that the drug is not effective because trials may fail for many reasons.
The FDA acknowledged press and medical journal reports of suicide attempts and completed suicides in pediatric patients receiving antidepressants, and many such reports have also been submitted to the FDA as spontaneous reports. Such reports are very difficult to interpret, however, in the absence of a control group, because these events also occur in untreated patients with depression. The agency emphasized the need for additional data, analyses, and a public discussion of the available data. The FDA recognizes that this is a serious illness and that a better understanding of how to use the products is needed.
To promote a public discussion of data and pertinent regulatory actions, the FDA has scheduled a meeting on February 2, 2004, before the Psychopharmacologic Drugs Advisory committee and the Pediatric Subcommittee of the Anti-Infective Drugs Advisory Committee.
The agency also reminds physicians and patients that these drugs must be used with caution, both in adults and children. The labeling of antidepressant drugs already carries precautionary language that the possibility of a suicide attempt is inherent in MDD and may persist until significant remission occurs. Close supervision of high-risk patients should accompany initial drug therapy.
In its Public Health Advisory, the FDA recommends that caretakers of pediatric patients receiving treatments with any of these antidepressants talk to their doctors before discontinuing the use of these drugs. Patients should not stop taking any of these drugs without first consulting with their physicians, and for some of these drugs it is important that they not be abruptly discontinued.
The FDA sent the advisory through its Medwatch partners, which includes doctors and organizations. The agency provides more information on the clinical study data in its Public Health Advisory, which is available on the FDA Web site at fda.gov/cder/drug/advisory/mdd.htm.
October 15, 2003
ST. LOUIS (MD Consult) - On October 6, 2003, Elan Pharmaceuticals reissued a letter (originally released June 13, 2003) addressed to health care professionals reporting serious adverse events and deaths resulting from accidental overdose of high-concentration morphine sulfate oral solutions. In most of these cases, morphine oral solutions ordered in milligrams (mg) were mistakenly interchanged for milliliters (mL) of the product, resulting in 20-fold overdoses.
Elan Biopharmaceuticals currently distributes three concentrated morphine sulfate oral solutions:
Prescribers and dispensers should be aware that these and other concentrations of morphine sulfate are available from various manufacturers with the concentration expressed in mg/tablespoon (5 mL).
Elan urged health care professionals to ensure that patients receive the proper dose of morphine sulfate oral solution by writing prescriptions for morphine sulfate oral solution clearly, making sure to include: (1) the concentration of morphine sulfate oral solution to be dispensed and (2) the intended dose of morphine in milligrams (mg) with the corresponding volume in milliliters (mL or cc) written out in the directions.
It is important that the prescription is filled with the proper concentration of morphine sulfate oral solution to prevent potential medication errors.
For additional information, please contact the Elan Pharmaceuticals Medical Information Services Department at 1-888-638-7605.
October 15, 2003
ST. LOUIS (MD Consult) - On October 9, 2003, the U.S. Food and Drug Administration (FDA) made public an open letter from UCB Pharma advising health care professionals of the risk of dispensing errors between Keppra (levetiracetam), an antiepileptic drug, and Kaletra (lopinavir/ritonavir), an antiretroviral medication.
Patients erroneously receiving either medication would be unnecessarily subjected to the risk of adverse effects. Patients with epilepsy who do not receive their antiepileptic drug due to a dispensing error would be inadequately treated and could experience serious consequences, including status epilepticus.
Keppra (manufactured by UCB Pharma) is available in tablet form and as an oral solution. Keppra tablets 250 mg are blue, 500 mg are yellow, and 750 mg are orange, oblong-shaped, scored, film-coated tablets with "ucb" and "strength" on one side. They are supplied in containers of 120 tablets. Keppra oral solution is a clear, colorless, grape-flavored liquid that comes in 16–fl oz white HDPE bottles containing 500 mg levetiracetam per 5 mL.
Kaletra (an Abbott Laboratories medication), on the other hand, is available in capsule form or as an oral solution. Capsules containing 133.3 mg lopinavir and 33.3 mg ritonavir are orange soft gelatin capsules imprinted with the Abbott corporate logo and "PK." Kaletra is available in bottles of 180 capsules. Kaletra oral solution is light yellow– to orange-colored liquid supplied in amber-colored 160-mL glass bottles containing 400 mg lopinavir and 100 mg ritonavir per 5 mL.
Clearly communicating both written and verbal prescriptions is a vital step in the prevention of future dispensing errors. When appropriate, consider including the intended use on prescriptions for these products. Patients should also be informed that they should carefully check all medications they receive, and immediately bring any problems, questions, or concerns to a pharmacist's attention.
Anyone aware of a prescription dispensing error involving either Keppra or Kaletra should contact the USP Medication Errors Reporting Program at 800-233-7767 or the FDA MEDWATCH program at 800-FDA-1088 or fda.gov/medwatch.
September 18, 2003
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration (FDA) has advised that 6 of the most widely used antipsychotic medications carry a warning that the drugs can increase the risk of elevated blood sugar and diabetes, according to a September 17, 2003, press release from Eli Lilly and Company.
Indianapolis-based Lilly, which manufactures the top-selling schizophrenia treatment Zyprexa, said the FDA is also seeking the warning on the product labeling for Risperdal (risperidone; Johnson & Johnson), Clozaril (clozapine; Novartis Pharmaceuticals), Abilify (aripiprazole; Bristol-Myers Squibb Co.), Seroquel (quetiapine fumarate; AstraZeneca Plc), and Geodon (ziprasidone; Pfizer Inc.).
All six of the drugs are called "atypical antipsychotics," a newer generation of medications that do not cause some of the troublesome side effects, such as tremors, seen among patients taking older treatments for psychotic disorders.
"Increased attention to the signs and symptoms of diabetes mellitus may lead to earlier detection and appropriate treatment, and thus may reduce the risk for the most serious outcomes," the FDA stated in its letter to Lilly received September 15, 2003.
The requested labeling states, "Assessment of the relationship 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."
The labeling further states that patients with diabetes who begin taking atypical antipsychotic drugs should be monitored for a worsening of glucose control, and those with risk factors for diabetes (e.g., obesity, family history of diabetes) should undergo fasting glucose testing at baseline and periodically throughout treatment. Any patient developing suggestive symptoms during treatment with an atypical antipsychotic medication should be tested for diabetes.
It has been suggested that the FDA might require the diabetes warning for some or all of the atypical drugs, based on August 2003 results of a long-awaited study that linked 3 of the medicines to a higher incidence of the disease.
The study, which involved almost 20,000 patients with schizophrenia treated at veterans hospitals and clinics across the United States, showed a 3.34-fold increase in diabetes among patients taking Seroquel compared with those taking older drugs.
With Risperdal, the rate was 1.49 times (49%) greater than that of the older drugs. The incidence of diabetes was 27% higher for Zyprexa.
Zyprexa is indicated in the United States for the short- and long-term treatment of schizophrenia and for acute bipolar mania. The most common adverse event associated with Zyprexa in placebo-controlled, short-term schizophrenia and bipolar mania trials was somnolence. Other common events were tremor, dizziness, constipation, akathisia, asthenia, dyspepsia, dry mouth, weight gain, personality disorder, postural hypotension, and increased appetite.
A small number of patients in premarketing trials experienced asymptomatic elevations of hepatic transaminase; none of these patients developed jaundice. Periodic assessment of transaminases is recommended in patients with significant hepatic disease.
Prescribing should be consistent with the need to minimize the risk of neuroleptic malignant syndrome, tardive dyskinesia, seizures, and orthostatic hypotension. Full prescribing information is available at zyprexa.com.
August 26, 2003
ST. LOUIS (MD Consult) - On August 21, 2003, the U.S. Food and Drug Administration (FDA) and Roche Pharmaceuticals revised the prescribing information for Roche's drug Zenapax (daclizumab). Zenapax is indicated for the prophylaxis of acute organ rejection in patients receiving renal transplants.
The changes included the addition of two new warning statements, along with revisions to the precautions, adverse reactions, and clinical studies sections of the prescribing information. Important new safety information describing the increased mortality seen in a cardiac transplant study and other updated information regarding hypersensitivity reactions was announced. Other sections of the Zenapax labeling affected by the addition of the information from the cardiac transplant study have also been revised.
The new warning label reads as follows:
| WARNING: Only physicians experienced in immunosuppresive therapy and management of organ transplant patients should prescribe Zenapax (daclizumab). The physician responsible for Zenapax administration should have complete information requisite for the follow-up of the patient. Zenapax should only be administered by health care personnel trained in the administration of the drug who have available adequate laboratory and supportive medical resources. |
In a randomized, placebo-controlled trial of Zenapax for the prevention of allograft rejection in 434 cardiac transplant recipients receiving concomitant cyclosporine, mycophenate mofetil, and corticosteroids, mortality at 6 and 12 months was increased in those patients receiving Zenapax compared with those receiving placebo. Some but not all of the increase in mortality appeared related to a higher incidence of severe infections. Concomitant use of anti-lymphocyte antibody therapy may also be a factor in some of the fatal infections.
Additionally, the following adverse reactions occurred more frequently in pediatric transplant patients than adult transplant patients: diarrhea, fever, pruritus, vomiting, aggravated hypertension, postoperative pain, and infections of the upper respiratory and urinary tracts.
Health care professionals are encouraged to report any serious adverse events that occur with Zenapax to the Roche Pharmaceuticals Service Center at 1-800-526-6367 or to the FDA's MedWatch program by phone 1-800-FDA-1088.
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August 26, 2003
ST. LOUIS (MD Consult) - On August 8, 2003, Bristol-Myers Squibb Company (BMS) and the U.S. Food and Drug Administration (FDA) notified clinicians caring for HIV-infected patients of important new safety data concerning the coadministration of Reyataz (atazanavir sulfate) and Viread (tenofovir disoproxil fumarate.)
Clinicians should use caution when administering unboosted Reyataz with Viread. Unboosted Reyataz may be less effective due to decreased atazanavir concentrations in patients taking Reyataz and Viread. As a result, the coadministration of unboosted Reyataz with Viread may lead to loss or lack of virologic response and possible resistance to Reyataz.
In a letter addressed to health care professionals, BMS cited studies conducted by the company to evaluate interactions between the two drugs as well as the safety profile of the combination. As a result of these studies, it was determined that caution was warranted when unboosted Reyataz is used in combination with tenofovir.
Reyataz, manufactured by Princeton, NJ-based BMS, was approved by the FDA in June 2003 for use as a protease inhibitor. Both it and Gilead Sciences' Viread, first approved in October 2001, are indicated in combination with other antiretroviral agents for treatment of HIV-1 infection.
Health care professionals are encouraged to report adverse reactions to BMS at 1-800-426-7644 (select option 2) or to the FDA's MedWatch program by telephone at 1-800-332-1088.
August 15, 2003
ST. LOUIS (MD Consult) - On August 14, 2003, the US Food and Drug Administration (FDA) announced the addition of new safety information and warnings to the labeling for drug products that contain salmeterol, a long-acting bronchodilator used to treat asthma and chronic obstructive pulmonary disease (COPD). The products affected by these changes are Serevent Inhalation Aerosol, Serevent Diskus, and Advair Diskus. The new labeling for these products will contain a boxed warning about a small, but significant, increased risk of life-threatening asthma episodes or asthma-related deaths observed in patients taking salmeterol in a large, recently completed US safety study.
On January 23, 2003, the FDA released a talk paper announcing the preliminary results of an interim analysis of the Salmeterol Multi-center Asthma Research Trial (SMART), which compared the effects of salmeterol (Serevent Inhalation Aerosol, 42 mcg twice daily) to placebo in patients with asthma for a period of 28 weeks. Since that time, the FDA has worked closely with GlaxoSmithKline, the sponsor of the study and the manufacturer of Serevent and Advair, to carefully review the study results and to develop appropriate labeling to reflect the new information provided by this study.
The primary end point for the SMART study was the occurrence of either respiratory-related death or a respiratory-related life-threatening experience (eg, requirement for mechanical ventilation). Secondary end points included all-cause death, asthma-related death, and asthma-related death or life-threatening experience.
Although the study was intended to enroll 60,000 patients, it was stopped by the sponsor after review of the results of a planned interim analysis, which was performed after approximately half of the intended number of patients was enrolled. The analysis includes 13,174 patients treated with Serevent and 13,179 patients treated with placebo. No significant differences were shown between treatment groups for the primary end point; however, a higher number of asthma-related deaths (13 vs 4) and a higher number of asthma-related deaths or life-threatening experiences (36 vs 23) were observed in the Serevent group compared with placebo.
The SMART study was not prospectively designed to analyze differences in outcome based on demographic characteristics, although post-hoc subgroup analyses based on race and ethnicity were conducted. These analyses showed no increase in respiratory- or asthma-related events among white patients; however, among African American patients there was a statistically significant increase in primary events (respiratory-related death of life-threatening experience) in the Serevent group (20 vs 7). In addition, the occurrence of asthma-related death (8 vs 1) and asthma-related death or life-threatening experience (19 vs 4) was statistically significantly greater in African American patients treated with Serevent compared with placebo.
The FDA emphasizes that based on available data, the benefits of treatment with salmeterol in patients with asthma and COPD continue to outweigh the potential risks when used according to the instructions contained in the product labeling. The FDA strongly advises patients that they should NOT stop taking products that contain salmeterol or any other medication for asthma or COPD without first talking to their physicians. Abruptly stopping drugs for the treatment of asthma and COPD can result in serious worsenings of these diseases that could be life-threatening. The FDA further emphasizes that all asthma drugs, including salmeterol, should be prescribed as part of a comprehensive plan that takes into account the patient's asthma severity and fully educates the patient in the disease and its proper treatment.
Serevent Inhalation Aerosol, Serevent Diskus, and Advair Diskus, which all contain salmeterol as an active ingredient, are manufactured by GlaxoSmithKline of Research Triangle Park, North Carolina, USA. For more information, contact GlaxoSmithKline at 1-888-825-5249.
August 11, 2003
ST. LOUIS (MD Consult) - On August 7, 2003, the Centers for Disease Control and Prevention (CDC) issued an updated advisory warning against the combination of rifampin and pyrazinamide in the treatment of latent tuberculosis (TB) infection.
The announcement came after the completion of a study conducted by the CDC in which high rates of hospitalization and death from liver injury were associated with the use of rifampin in conjunction with pyrazinamide. Together with the American Thoracic Society, the CDC now recommends that this treatment not be given to patients with latent TB.
If the potential benefits significantly outweigh the demonstrated risk of severe liver injury and death associated with this regimen, and the patient has no contraindications, a TB expert should be consulted before the use of this regimen is introduced.
The CDC study involved data collected between October 2002 and June 2003. Of the patients, who received treatment with rifampin and pyrazinamide between January 2000 and June 2002, 11 died due to complications of severe liver injury.
On the basis of the investigation of potential cofactors in the 48 patients in the study with serious liver injury, this combination should never be offered to patients who are concurrently taking other medications associated with liver injury; those who drink excessive amounts of alcohol, even if alcohol use is discontinued during treatment; those who have underlying liver disease; or those who have a history of isoniazid-associated liver injury.
Clinicians are advised to use the recommended alternative regimens for the treatment of latent TB. According to the CDC, rifampin and pyrazinamide should continue to be administered in multidrug regimens for the treatment of persons with active TB disease.
The CDC continues to collect reports of severe liver injury leading to hospital admission or death in persons receiving any treatment for latent TB infection. Health care providers are encouraged to report such events to CDC's Division of Tuberculosis Elimination at 404-639-8442.
August 1, 2003
ST. LOUIS (MD Consult) - On July 30, 2003, the European Medicines Evaluation Agency (EMEA) announced a high rate of early virologic non-response observed in a GlaxoSmithKline (GSK)-sponsored clinical study of therapy-naive adults with HIV infection receiving a once-daily combination therapy with lamivudine (Epivir, GSK), abacavir (Ziagen, GSK) and tenofovir (Viread, TDF, Gilead Sciences).
Based on these results, abacavir and lamivudine in combination with tenofovir should not be used as a triple antiretroviral therapy when considering a new treatment regimen for therapy-naive or pretreated patients.
The EMEA recommended that patients currently receiving or about to receive this combination of medications alert their physicians immediately. Modification of therapy should be considered. In addition, any usage of this triple combination with other antiretroviral drugs should be closely monitored for signs of treatment failure.
For more information, contact Noel Wathion, Head of Unit of Evaluation of Medicines for Human Use, at 44-20-7418-8592.
Adverse reactions should be reported to GSK's Product Surveillance Department at 1-888-825-5249 or to the U.S. Food and drug Administration's MedWatch program at 1-800-332-1088.
July 28, 2003
ST. LOUIS (MD Consult) - In a letter dated May 30, 2003, Pharamacia & Upjohn company, a subsidiary of Pfizer Inc, notified health care professionals that its Genotropin growth hormone has been linked to seven deaths around the world. On July 25, the letter was posted on the Web site of the U.S. Food and Drug Administration (FDA).
As a result, the FDA revised the CONTRAINDICATIONS and WARNINGS sections of the prescribing information for Genotropin, indicated for the long-term treatment of pediatric patients who have growth failure due to Prader-Willis syndrome (PWS).
CONTRAINDICATIONS: Growth hormone is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment.
WARNINGS: There have been reports of fatalities with the use of growth hormone in pediatric patients with Prader-Willi syndrome who had one or more of the following risk factors: severe obesity, history of respiratory impairment or sleep apnea, or unidentified respiratory infection. Male patients with one or more of these risk factors may be at increased risk. Patients with Prader-Willi syndrome should be evaluated for upper airway obstruction before initiation of treatment with growth hormone. If during treatment with growth hormone, patients show signs of upper airway obstruction (including onset of or increased snoring), treatment should be interrupted. All patients with Prader-Willi syndrome should be evaluated for sleep apnea and monitored if sleep apnea is suspected. All patients with Prader-Willi syndrome should have effective weight control and be monitored for signs of respiratory infections, which should be diagnosed as early as possible and treated aggressively.
The fatalities were reported with the use of growth hormone in pediatric patients with PWS with one or more of the following risk factors: severe obesity, history of respiratory impairment or sleep apnea, or unidentified respiratory infection. Male patients with these factors may be at increased risk.
Pfizer recommended that patients with PWS be evaluated, especially for sleep apnea. Persons with questions should contact Pfizer Medical Information at 800-323-4204.
July 15, 2003
ST. LOUIS (MD Consult) - Barr Laboratories, Inc. has initiated a voluntary recall of 3 lots of its Nortrel 7/7/7 - 28 day (norethindrone and ethinyl estradiol tablets, USP) oral contraceptive product to the pharmacy level.
Barr encourages women taking the product to examine their blister cards to confirm that the color-coded tablets are packaged in the proper color sequence. The first three rows (labeled "Start," "Week 2" and "Week 3") of a properly packaged product contain colored tablets. The last row (labeled "Week 4") of a properly packaged product contains white tablets.
The recall is being implemented because two people have told Barr the color-coded tablets in their blister cards of the product were in an improper sequence, which may increase the risk for pregnancy.
The recall is effective immediately and involves Lot Numbers 290122001, 290122002 and 290122003. The Lot Numbers should appear in a window labeled "LOT" on the upper right-hand corner of the back side of the package. Any Nortrel 7/7/7 - 28 day product that doesn't bear a Lot Number in that location is also subject to the recall. No other lots of Nortrel or other Barr oral contraceptive products are affected by this recall.
Doctors, pharmacists or women seeking additional information on this recall are encouraged to call Barr Laboratories, Inc.'s Drug Information at 1-800-222-0190 extension 33302.
Nortrel 7/7/7 - 28 day is packaged in a blister card containing four horizontal rows of seven tablets each, with each row representing one week of tablets. The first (i.e. top) row should contain yellow tablets. The second row should contain blue tablets. The third row should contain peach tablets. The fourth (i.e. bottom) row should contain white tablets. The colored tablets contain the active hormonal ingredients. The white tablets are placebos that contain no active ingredient.
Any woman who has received a Nortrel 7/7/7 - 28 day blister card with tablets in the wrong sequence could be at increased risk of pregnancy. In addition, changes to the menstrual cycle, including delayed bleeding, irregular bleeding or spotting, may occur. Barr recommends that women taking Nortrel 7/7/7 - 28 day check their blister cards and take the following steps:
Out of approximately 470,000 packages of marketed Nortrel 7/7/7 - 28 day that are subject to the recall, Barr has received two reports in which the tablets in the blister are reversed, causing the white placebo row to be in the first row labeled "start" (i.e., week one) rather than in the last row labeled "Week 4." Additionally, the lot number and expiration date were not visible on the back of these two cards.
The U.S. Food and Drug Administration (FDA) has been notified of the recall. All manufacturing and packaging processes related to the product have been reviewed, and Barr said it believes the mispackaging was an isolated incident limited to the lots in question. Corrective actions have been taken.
Nortrel 7/7/7 - 28 day is a generic version of Ortho-McNeil Pharmaceutical's Ortho-Novum 7/7/7 oral contraceptive and is indicated for the prevention of pregnancy in women who elect to use this product as a method of contraception. It is supplied in a 28-day regimen.
July 11, 2003
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration announced that Topamax, the antiepileptic drug made by Johnson & Johnson's Ortho-McNeil unit, will now include warnings about the risks of hyperthermia and oligohidrosis.
Ortho-McNeil sent a letter to the FDA warning patients using Topamax (topiramate/topiramate capsules) to watch for symptoms of oligohidrosis and hyperthermia. The "Dear Healthcare Professional" letter was published on the FDA's Web site.
Topamax's previous label mentioned decreased sweating as a potential side effect without calling it oligohidrosis. The previous warning didn't mention hyperthermia.
Reports of these side effects have generally involved children. Most cases have occurred during hot weather or while participating in vigorous activity, the letter said.
As of February 2002, the rate for reports of all potential cases of oligohidrosis is approximately 35 per one million patients treated and 1.6 per one million patients treated for serious or medically significant oligohidrosis or its sequelae, the letter said. Topamax has been on the U.S. market since 1996.
Patients should properly hydrate before and during exercise and exposure to warm temperatures, the letter said.
The letter also said caution should be exercised when Topamax is prescribed with other drugs that predispose patients to heat-related disorders. These drugs include, but are not limited to, other carbonic anhydrase inhibitors and drugs with anticholinergic activity.
Patients, especially pediatric patients, treated with Topamax should be monitored closely for evidence of decreased sweating and increased body temperature, especially in hot weather.
Adverse events can be reported to Ortho-McNeil at the contact numbers listed below or to the FDA MedWatch Program by phone (1-800-FDA-1088), by fax (1-800-FDA-0178), by mail (using postage-paid form to MedWatch, FDA, 5600 Fishers Lane, Rockville, MD 20852-9787) or via accessdata.fda.gov/scripts/medwatch/. For questions about Topamax, call Ortho-McNeil Medical Affairs Division at 1-800-682-6532.
July 9, 2003
ST. LOUIS (MD Consult) - Cordis Corporation (Cordis) has issued a letter to health care professionals to inform them of the rare but potential risk of thrombosis associated with the use of its product, the CYPHER Sirolimus-Eluting Coronary Stent (CYPHER stent).
This letter also provides clarification on the safe use of the product in accordance with the scientific evidence that led to product approval.
The CYPHER stent was approved in April 2003 for patients undergoing angioplasty procedures to open clogged coronary arteries. Since the product's introduction, it is estimated that approximately 50,000 patients have received a CYPHER stent. To date, The Food and Drug Administration (FDA) has received 47 Medical Device Reports (MDRs) of stent thrombosis occurring at the time of implantation or within a few days of implantation.
The FDA is reviewing the reports of adverse events and working closely with the company to determine the exact causes and reduce the incidence of thrombosis, according to the FDA web site. From the reports received so far, it is unclear what effect the CYPHER stent has on thrombosis risk and what factors may contribute to the risk.
As part of the approval for this product, the FDA required Cordis to undertake post-approval studies which will help the FDA track adverse events more accurately and help determine whether the thrombosis rate in current clinical experience differs from the rate seen in pre-approval studies.
Until more is known about the situation, the FDA fully supports Cordis' recommendations to health care professionals which may help reduce the incidence of adverse events. These include:
All health care professionals are reminded and encouraged to report their experiences to FDA's Medical Device Reporting (MDR) System through MedWatch (telephone 1-800-FDA-1088 or fda.gov/MedWatch).
Cordis, in cooperation with FDA, will continue to monitor the issue.
June 10, 2003
ST. LOUIS (MD Consult) - The incidence of major adverse reactions to the antituberculosis drug pyrazinamide (PZA) is greater than other first-line agents, according to study results from the Montreal Chest Institute in Quebec.
Authoritative treatment guidelines indicate that adding PZA to isoniazid and rifampin isn't associated with significant increase in hepatotoxicity, according to Dr. Dick Menzies and associates. Serious adverse reactions are associated with prolonged therapy, higher risk of hospitalization and increased treatment costs, so they examined the medical records of 430 patients treated between 1990 and 1999.
Forty-six adverse events resulted in treatment modification or hospitalization. Twenty-one patients developed rash and/or drug fever, while 12 patients developed drug-induced hepatitis. There were also 11 instances of severe GI upset, and 1 each of visual toxicity and arthralgia.
The incidence of major adverse effects was 1.48 per 100 person-months of exposure to PZA, higher than that observed in randomized trials, the Canadian investigators said. Corresponding rates were 0.49 for isoniazid, 0.43 for rifampin, and 0.07 for ethambutol.
Average therapy duration was 380 days for patients with serious adverse reactions compared with 228 days for the other subjects. Patients with serious adverse reactions also made more visits to healthcare professionals.
Female gender, HIV infection, older age and birth in Asia were associated with greater risk.
Am J Respir Crit Care Med 2003;167:1461-1462,1472-1477.
June 4, 2003
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration (FDA) announced that its continuing investigation of counterfeit Lipitor has turned up additional counterfeit quantities of the cholesterol-lowering pharmaceutical product.
Two additional lots of 10 mg tablets in 90-tablet bottles, coded 20842V and 16092V, and one lot of 20 mg tablets in 90-tablet bottles, coded D270481, are involved. The labeling on each of these bottles states, "Repackaged by: MED-PRO, INC., Lexington, NE 68850."
The FDA initially alerted consumers and healthcare professionals to watch for counterfeit Lipitor last month. That warning involved lots of 90-tablet bottles coded 20722V, 04132V and 16942V.
The FDA said it has since pursued various supply and distribution leads, but the investigation is ongoing.
April 16, 2003
ST. LOUIS (MD Consult) - Patients with myasthenia gravis should use extreme caution with the antibiotic Ketek (telithromycin), the manufacturer warned.
The warning, from Aventis Pharma Deutschland, a subsidiary of drugs group Aventis, said several patients who had used Ketek for respiratory infections experienced exacerbation in already diagnosed myasthenia gravis. One patient died, according to the warning, released by the Drug Commission of the German Medical Association.
In the reported cases, the warning said, myasthenia gravis patients experienced an intensification of muscle weakness, dyspnea or heavy acute breathing insufficiency within hours of taking Ketek.
Ketek, the first in a new class of antibiotic, has been sold since 2001 in some European and Latin American countries, but hasn't been approved in the U.S.
The FDA had been expected to approve Ketek in January 2003 after agency advisers backed the drug to treat certain respiratory infections resistant to penicillin or macrolide antibiotics. But the U.S. launch of Ketek was delayed following receipt of a second "approvable letter" from the FDA requesting extra analysis of data.
Aventis doesn't recommend Ketek for patients with myasthenia gravis, but if no alternative is available, patients should be closely monitored, the company said. At the first sign of exacerbation of myasthenia gravis, Ketek usage should be stopped.
April 14, 2003
ST. LOUIS (MD Consult) - Johnson & Johnson is sending letters to thousands of U.S. doctors concerning possible increased risk of stroke among elderly patients taking its antipsychotic drug risperidone (Risperdal).
The company also plans to change the package insert label of the pill to note the possible stroke risk.
Johnson & Johnson sent a similar warning letter to Canadian doctors and pharmacists last October, citing 37 reports of stroke or stroke-like events, including 16 deaths, among patients who have taken Risperdal.
The company also mentioned two clinical trials of elderly dementia patients in which a higher proportion of patients taking Risperdal experienced strokes or related events than those receiving placebo. However, J&J said in the Canadian warning letter that the elderly typically have increased risk of stroke.
Although Risperdal is only approved for schizophrenia, it is commonly used to control behavioral disorders, such as delusions, aggressive and anxiety, in elderly patients with dementia and Alzheimer's disease.
Risperdal and other schizophrenia drugs already include label information about strokes in patients taking these drugs in either clinical trials or after the drugs reach the market. The Risperdal label will be changed to include more specific information about strokes among the elderly.
March 12, 2003
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration (FDA) has found three contaminated, counterfeit lots of Procrit (epoetin alfa), marketed in the U.S. by Johnson & Johnson for the treatment of anemia.
The counterfeit drugs are contaminated with bacteria, and some don't have any active ingredient, according to the FDA.
The FDA said Johnson & Johnson is sending out "Dear Doctor" letters to warn healthcare professionals about the problem. The suspect lots are numbered P007645, P004677 and P004839, the agency said.
Anyone finding the counterfeit product should contact the FDA's Center for Biologics Evaluation and Research at 1-800-835-4709, the agency said.
Additional details about counterfeit Procrit and how to distinguish the packaging are available on Ortho's Web site at procrit.com.
In June 2002, Ortho issued two "Dear Doctor" letters warning about other counterfeit Procrit lots distributed in the U.S. In that case, the counterfeiters apparently purchased 2,000 U/mL vials of Procrit and relabeled them as 40,000 U/mL.
J&J licenses Procrit in the US from Amgen Inc. Counterfeit vials of Epogen, an epoetin alpha drug sold in the US by Amgen, were discovered last spring.
March 31, 2003
ST. LOUIS (MD Consult) - The U.S. Food and Drug Administration (FDA) has added new warnings to the labels of lindane-containing lotions and shampoos marketed for treating scabies and lice.
The boxed warnings repeat that, because of the neurotoxicity potential, the products are approved only as second-line therapy in patients who haven't responded to or can't tolerate other treatments.
In addition, the warnings say the products should be used with caution in patients weighing less than 110 pounds. The FDA said about half the reported adverse events associated with the products are in children.
Because lindane is absorbed through the skin and children have more skin surface area relative to body weight, pediatric patients may end up with higher blood levels of the drug, the FDA said.
The new labeling also stresses that reapplication of lindane is inappropriate, even if itching continues after the first application. To help prevent overuse, lindane-containing shampoos and lotions will be sold only in one- and two-ounce packages, the FDA said.
Along with the label changes, a medication guide for patients will educate them about the safety concerns.
Lindane, or gamma benzene hexachloride, is a pesticide. It has been banned in some countries because of fear it may be carcinogenic.
The consumer advocacy group Public Citizen said the FDA should have removed the drug from the market.
Public Citizen, which has twice petitioned the FDA to pull lindane from the market, believes the lice treatment permethrin is a safer alternative. Permethrin is the active ingredient in the over-the-counter product Nix.
March 17, 2003
ST. LOUIS (MD Consult) - SuperGen Inc, in a press release, exaggerated the benefits of its cancer drug Mitozytrex (mitomycin) and failed to mention serious risks associated with the drug, according to the U.S. Food and Drug Administration (FDA).
The FDA said the company's Nov. 15, 2002, press release announcing approval for Mitozytrex did not mention the drug is linked with serious side effects such as suppressing bone marrow activity, which can contribute to infections. The press release also failed to mention possible acute reactions such as fever, nausea and vomiting, the FDA said.
The FDA said the company made unsupported claims that Mitozytrex was "supergeneric."
In another unsupported statement, SuperGen said its technology was designed to "shield" the drug from the injection site, thus protecting against tissue ulceration, the FDA said.
The agency said it rejected the name "MitoExtra" for the drug because it suggested unsubstantiated clinical benefits. Despite the FDA's objection, SuperGen used the name in the press release, the agency said.
March 13, 2003
ST. LOUIS (MD Consult) - Bristol-Myers Squibb Co. and AstraZeneca have issued an alert concerning mix-ups between Bristol-Myers' depression drug Serzone (nefazodone HCL) and AstraZeneca's schizophrenia medication Seroquel (quetiapine fumarate), according to the US Food and Drug Administration (FDA).
In a notice on the FDA Web site, the agency's MedWatch division said the two drugmakers have issued another "dear doctor" letter to warn that verbal and written prescriptions for two similarly named drugs are being incorrectly filled.
The companies blamed the dispensing errors on overlapping strengths, dosing intervals and the two products being stocked close together in pharmacies. But in the latest letter to healthcare providers, the companies said the two pills aren't at all similar. Serzone tablets are hexagonal and imprinted with "BMS" while Seroquel is a round, coated tablet imprinted with its own brand name.
Bristol-Myers said it has revised the Serzone logo and would issue a new patient-information leaflet to help make sure patients are receiving the correct medication. The company further encouraged doctors to ensure correct matches by providing patients with a picture card enclosed in the letter.
The company said, along with AstraZeneca, it will make certain packaging changes, such as highlighting the end of the product names.
The first alert about the potential confusion was first noted in an alert issued in 2001 by the Institute for Safe Medication Practices. This latest notice follows a similar "dear doctor" letter issued by AstraZeneca to healthcare providers in May, outlining seven case reports that resulted in either hospitalization or an emergency room visit.
March 12, 2003
ST. LOUIS (MD Consult) - Wyeth has repeated to US physicians the warning about off-label use of its immunosuppressive therapy Rapamune (sirolimus) to prevent organ rejections in lung transplant recipients, according to a "dear doctor" letter posted on the US Food and Drug Administration (FDA) Web site.
In the letter, the US drugmaker said it has received several reports of bronchial anastomotic dehiscence, including four deaths, when the drug was used off-label to treat lung transplant recipients. The drug is approved for use with cyclosporin to prevent renal graft rejection.
The reports were received from two transplant centers where patients were treated with Rapamune in combination with tacrolimus and corticosteroids, Wyeth said.
Further information regarding these events will be published in the journal Transplantation sometime in 2003, Wyeth said.
Wyeth said it will update the warning section on the label to recommend against the use of Rapamune in lung transplant recipients, for which the safety and efficacy of the drug has never been established.
The company issued a similar "dear doctor" letter to physicians in the Netherlands in early February, 2003.
In Europe, Rapamune is approved for kidney transplant patients, and as a coating for a Johnson & Johnson stent designed to prevent formation of new blockages. A similar US approval is anticipated in the second quarter of 2003.
March 5, 2003
ST. LOUIS (MD Consult) - A growing concern exists about Listeria monocytogenes infection as a serious complication of treatment with tumor necrosis factor alpha (TNF-alpha) antagonists, particularly infliximab (Remicade) and possibly etanercept (Enbrel).
Through December 2001, 15 cases of L. monocytogenes infection associated with these two agents were reported to the US Food and Drug Administration's Adverse Event Reporting System. Fourteen of the cases involved infliximab. There were 6 deaths, 5 in infliximab-treated subjects. All 15 patients were receiving concurrent immunosuppressant medication.
In analyses limited to infliximab-treated patients, listeriosis developed in almost twice as many subjects with rheumatoid arthritis as in those with Crohn's disease, 9 patients vs 5 patients, respectively, Dr. M. Miles Braun and colleagues from the FDA report in the February issue of Arthritis and Rheumatism.
The possibility for this complication was recognized at the time of FDA approval and noted in product labeling.
The FDA encourages physicians to report all cases of L. monocytogenes infection to state or local health departments and "clinically important" adverse events to the FDA MedWatch program 800-332-1088 or fda.gov/medwatch.
January 31, 2003
ST. LOUIS (MD Consult) - Emergency contraception using Levonelle, a progestogen preparation, carries the risk of ectopic pregnancy, according to Britain's Chief Medical Officer.
In a letter to all doctors, Sir Liam Donaldson said 12 cases of ectopic pregnancy out of 201 unintended pregnancies had been reported to the Committee on Safety of Medicines following use of Schering's Levonelle (levonorgestrel 0.75mg).
Known as the "morning-after" pill, Levonelle is licensed for use up to 72 hours after unprotected sex. However, the letter says, the longer women delay taking it, the less effective it is.
The pills prevented 95 percent of pregnancies when taken in the first 24 hours, 85 percent on the second day and 58 percent on the third day.
The letter said pregnancies occuring in women taking progestogen-only pills are more likely to be ectopic.
The Committee on Safety of Medicines said women should seek treatment as early as possible after unprotected sex, and be told the treatment can fail.
The letter says women who don't have a normal period after using Levonelle should be contacted so pregnancy can be excluded. Ectopic pregnancy is possible, particularly in women with a previous ectopic pregnancy, fallopian tube surgery or pelvic inflammatory disease.
Patient information leaflets already referred to the small risk of ectopic pregnancy, Schering's UK division said. The company is discussing changes with the Medicines Control Agency to make this clearer.
January 9, 2003
ST. LOUIS (MD Consult) - The US Food and Drug Administration said makers of estrogen-containing products used for menopause symptoms will be required to make label changes reflecting new safety concerns.
In addition, women who take the drugs are being advised to take the lowest dose for the shortest possible time.
The announcement comes six months after a US government-sponsored study, the Women's Health Initiative (WHI), was terminated three years earlier than planned. The study found that women taking a hormone replacement product had a slightly higher risk of heart disease, breast cancer, stroke and blood clots compared to women not taking the hormones.
In that study, women took the drug Prempro, a combination of estrogen and progestin. Another arm of the WHI, in which women are taking an estrogen-only product called Premarin, continues. Women who have a uterus typically take estrogen combined with progestin, while those who have had a hysterectomy just take estrogen.
Shortly after the WHI was halted, Wyeth Pharmaceuticals made some labeling changes which will affect the company's estrogen-containing products -- Prempro, Premphase and Premarin. The FDA is asking all other manufacturers of estrogen or estrogen/progestin products to make similar changes.
Although the FDA never approved estrogen-containing products for heart disease prevention, many doctors prescribed them off label because there was preliminary evidence the drugs might help.
Patient information accompanying the products will be revised to reflect the new changes.
A labeling policy will be published soon for the makers of these drugs, according to the FDA.
Currently there are three FDA-approved indications for the use of Prempro, Premarin and Premphase. One is the treatment of hot flashes and night sweats, two common symptoms of menopause. This indication and the FDA labeling hasn't changed, the FDA said.
The two other indications have been revised. While the drugs are still recommended for moderate to severe vulvar and vaginal atrophy symptoms, labeling now says when prescribing solely for treating symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered, the FDA said.
Although HRT drugs can still be prescribed to prevent osteoporosis, the label will say they should only be considered for women at significant risk for osteoporosis and non-estrogen treatments should be carefully considered.
There are now several different drugs on the market for patients at risk for osteoporosis, including a class of drugs called bisphosphonates.
The FDA will continue to study whether low doses of the estrogen/progestin products are safer than higher doses and compare the safety of different products containing the hormones.
Anyone using or considering using estrogen-containing products should consult a doctor about the individual risks and benefits of the hormones.
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