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ELDEPRYL (selegiline HCl) - The product labeling for Eldepryl has been modified to note that, although rare, a few reports of hypertensive reactions associated with the ingestion of tyramine-containing foods have occurred in patients receiving Eldepryl at the recommended dose (5 mg, b.i.d.) To date, two reports have been received. An additional case of a hypertensive reaction in a patient on the recommended dose of selegiline taking several concomitant drugs is described in the article "Pseudo-pheochromocytoma After Multiple Drug Interactions Involving the Selective Monoamine Oxidase Inhibitor Selegiline" [Clin Endocrinol (Oxf) 1995;42(1):95 - 99]. The risks of the hypertensive events increase significantly when patients are exposed to doses higher than the labeled dose regimen. Careful monitoring is required for patients who are prescribed Eldepryl in doses exceeding 10 mg per day and for those who are switched from one selegiline preparation to another. [December 23, 1996 (letter) - Somerset Pharmaceuticals, Inc.]
CYLERT (pemoline) - The product labeling for Cylert has been modified to include a boxed warning describing liver failure and to indicate that Cylert should not ordinarily be considered as first-line drug therapy for attention deficit hyperactivity disorder (ADHD). Since Cylert went onto the market in 1975, 13 cases of acute hepatic failure have been reported to FDA. While the absolute number of reported cases is not large, the rate of reporting ranges from 4 to 17 times the rate expected in the general population. This estimate may be conservative because of underreporting and because long latency may make it difficult to recognize the association between Cylert and hepatic failure. Thus the risk could be substantially higher. Of the 13 reported cases, 11 resulted in death or liver transplantation, usually within 4 weeks of the onset of signs and symptoms of liver failure. The earliest onset of hepatic abnormalities occurred 6 months after initiation of Cylert. Although some reports described dark urine and nonspecific prodromal symptoms (e.g., anorexia, malaise, and gastrointestinal symptoms), in other reports it was not clear whether any prodromal symptoms preceded the onset of jaundice. It is also not clear whether the recommended baseline and periodic liver function testing are predictive of these instances of acute liver failure. Cylert should be discontinued if clinically significant hepatic dysfunction is observed during its use. [December 1996 (letter) - Abbott Laboratories]
REDUX (dexfenfluramine HCl) - The product labeling for Redux has been modified to reflect the information communicated to health care professionals in the August 1996 letter from Wyeth-Ayerst Laboratories. "Important Patient Information" sheets are available from the company (1-800-934-5556) to aid in counseling patients about the risks and benefits of Redux therapy. Health care professionals are reminded that Redux is an appetite suppressant and that appetite suppressants increase the risk of developing primary pulmonary hypertension (PPH), an often-fatal disorder. Use of appetite suppressants for longer than 3 months is associated with a 23-fold increase in the risk of developing PPH. Based on a 2-year case-control study, the risk associated with the long-term use of appetite uppressants is estimated to be about 23 to 46 cases per 1 million persons per year. Redux should not be used in patients with hypersensitivity to dexfenfluramine or related compounds or in patients with diagnosed pulmonary hypertension. Redux should not be used concomitantly with a monoamine oxidase inhibitor or within 14 days of discontinuation. Redux should not be taken in combination with other selective serotonin reuptake inhibitors. Redux is not recommended for pregnant or nursing women or people under 18 years of age. [December 1996 (letter) - Wyeth-Ayerst Laboratories]
CELLULOSE ACETATE DIALYZERS - CDC and FDA are investigating a recent occurrence involving serious patient injury following hemodialysis treatment. Within 24 hours of treatment, seven patients who received inpatient dialysis using cellulose acetate dialyzers developed one or more of the following symptoms: conjunctivitis, visual loss, and hearing loss. The investigation should be completed within the next several months. In the meantime, due to potential adverse effects of storing cellulose acetate dialyzers at warm temperatures or over long periods of time, it is recommended that the dialysis stock be rotated using first-in, first-out practices. [December 16,1996 (letter)-CDC/FDA]
NORVIR (ritonavir) - Based on postmarketing experience, the Norvir product information has been updated to reflect new information about drug interactions. Ergot alkaloid preparations and pimozide have been added as contraindications. Cardiac and neurologic events have been reported with coadministration of disopyramide, mexiletine, nefazodone, or fluoxetine. Plasma concentrations of saquinavir increased more than 20-fold when it was coadministered with ritonavir 400 mg or 600 mg b.i.d. However, the appropriate doses for this combination, with respect to activity and safety, have not been established.
Additionally, the "WARNING" and "ADVERSE REACTION" sections have been revised to include information regarding allergic reactions; hepatic transaminase elevations; and postmarketing reports of hepatic dysfunction, seizure, hyperglycemia, syncope, orthostatic hypotension, and renal insufficiency.
The "PRECAUTIONS" and "OVERDOSAGE" sections have been updated. Also included is a review of the importance of dose titration upon initiation of Norvir therapy to help reduce treatment-emergent adverse events while maintaining appropriate plasma levels. [November 1996 (letter) - Abbott Laboratories]
TRANCOPAL (chlormezanone) - Sanofi Winthrop is discontinuing Trancopal worldwide. A recent retrospective European inquiry confirmed that a low incidence of serious cutaneous reactions (toxic epidermal necrolysis) was associated with the use of chlormezanone. [November 7, 1996 (letter) - Sanofi Winthrop]
VISTIDE (cidofovir) - There have been several reports of severe renal impairment associated with the use of Vistide. Guidelines are provided that reinforce the importance of appropriate patient selection, treatment administration, and monitoring to ensure that Vistide is used safely and to alert prescribers about two new contraindications (preexisting renal disease and concomitant administration with agents having nephrotoxic potential). [September 1996 (letter) - Gilead Sciences, Inc.]
ALBUMINAR (human albumin) and PLASMA-PLEX (plasma protein fraction) Recall - Centeon announced a voluntary recall of all in-date lots of Albuminar and Plasma-Plex that expire prior to September 30, 1999. Centeon has received several reports of septicemia that may be associated with these products. No other Centeon products are affected by this voluntary action. Centeon is taking this action as a precaution because of manufacturing concerns related to these two products. [October 9, 1996 (announcement) - Centeon]
GLUCOPHAGE (metformin HCl) - The manufacturer reinforced the importance of appropriate patient selection in order to minimize the risk of lactic acidosis and highlighted key considerations in selecting patients for Glucophage therapy. The risk of lactic acidosis with Glucophage therapy can be minimized by avoiding its use in patients at risk for significant drug accumulation (e.g., those with renal impairment) or in patients at an increased risk for developing lactic acidosis independent of therapy because of impaired ability to clear lactate (e.g., those with conditions associated with tissue hypoperfusion or hypoxic states and those with substantial liver impairment). There are also clinical circumstances under which Glucophage therapy should be withheld or discontinued: patients with evidence of renal disease or dysfunction, patients about to undergo procedures using intravenous iodinated contrast media, acutely ill or hemodynamically unstable patients, and patients with impaired hepatic function or excessive alcohol intake. [September 11, 1996 (letter) - Bristol-Myers Squibb]
HALCION (triazolam) and XANAX (alprazolam) - Prescribing information has been changed to indicate that triazolam and alprazolam are metabolized via the cytochrome P450 3A (CYP 3A) pathway and may interact with other drugs and foods that use this pathway. Halcion is contraindicated with ketoconazole, itraconazole, and nefazodone -medications that significantly inhibit oxidative metabolism mediated by CYP 3A. Xanax is contraindicated with ketoconazole and itraconazole. [August 23, 1996 (letter) - Pharmacia and Upjohn]
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