FDA Safety Changes: Axert, Tarka, Macrobid, Macrodantin

Yael Waknine

May 06, 2009

This activity is part of an ongoing CME/CE initiative to provide information on labeling changes reported by the FDA. Activities of this nature will be posted on Medscape on a weekly basis.

May 6, 2009 — The US Food and Drug Administration (FDA) has approved safety labeling revisions to warn clinicians of the risk for serotonin syndrome in patients receiving combination therapy with almotriptan malate, drug interactions with verapamil HCl/trandolapril fixed-dose combination therapy, and to advise against reinitiating therapy in patients who have experienced hepatotoxic reactions to nitrofurantoin monohydrate.

Almotriptan Malate (Axert) Linked to Risk for Serotonin Syndrome

On March 27, the FDA approved class labeling changes for almotriptan malate (Axert tablets; Ortho-McNeil Pharmaceutical, Inc) to provide updated information regarding the risk for potentially life-threatening serotonin syndrome in patients receiving treatment with 5-hydroxytryptamine receptor agonists (triptans).

Although this reaction has occurred in patients receiving triptans alone, the risk for its occurrence is significantly increased by concomitant use of selective serotonin reuptake inhibitors (SSRIs: eg, fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, and escitalopram) or serotonin-norepinephrine reuptake inhibitors (SNRIs: eg, venlafaxine and duloxetine).

Symptoms of serotonin syndrome may include mental status changes (eg, agitation, hallucinations, and coma), autonomic instability (eg, tachycardia, labile blood pressure, and hyperthermia), neuromuscular aberrations (eg, hyperreflexia and incoordination), and/or gastrointestinal symptoms (eg, nausea, vomiting, and diarrhea).

Patients who are treated with SSRIs or SNRIs and receiving triptans should be observed closely, particularly during initiation of therapy and dose increases.

Almotriptan is indicated for the acute treatment of migraine with or without aura in adults.

Verapamil/Trandolapril (Tarka) Linked to Drug Interactions With Certain Macrolides and Injectable Gold

On March 5, the FDA approved safety labeling revisions for a calcium channel blocker (verapamil HCl) and angiotensin-converting enzyme (trandolapril) combination tablet (Tarka; Abbott) to include warnings regarding 2 drug interactions.

Coadministration of certain macrolide antibiotics (clarithromycin and erythromycin ethylsuccinate) may decrease hepatic first-pass and metabolic clearance of verapamil, thereby increasing plasma concentrations and pharmacologic effects.

Hypotension, bradyarrhythmias, and lactic acidosis have been reported in patients receiving concomitant treatment with verapamil/trandolapril and erythromycin or clarithromycin, the FDA noted.

The agency also warned of rare nitritoid reactions reported in patients receiving concomitant treatment with injectable gold (sodium aurothiomalate) and angiotensin-converting enzyme inhibitors such as trandolapril. Symptoms may include facial flushing, nausea, vomiting, and hypotension.

Verapamil plus trandolapril is indicated for the treatment of hypertension.

Clarithromycin and erythromycin are macrolide antimicrobials indicated for the treatment of infections caused by susceptible strains of designated microorganisms.

Intramuscular gold therapy is used to treat rheumatic diseases such as rheumatoid and psoriatic arthritis and is generally reserved for patients who show evidence of continued or additional disease activity despite conservative drug therapy with salicylates or other anti-inflammatory agents.

Nitrofurantoin (Macrobid and Macrodantin) Contraindicated in Patients With Previous Hepatotoxicity

On March 5, the FDA approved safety labeling revisions for nitrofurantoin monohydrate/macrocrystals capsules (Macrobid and Macrodantin; Proctor and Gamble Pharmaceuticals, Inc) to advise of a new contraindication.

Nitrofurantoin is contraindicated in patients with a history of cholestatic jaundice/hepatic dysfunction associated with treatment, the FDA warned.

The agency has received rare and sometimes fatal reports of hepatic reactions to nitrofurantoin, including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis. Because the onset of chronic active hepatitis may be insidious, patients should be monitored periodically for changes in biochemical tests that would indicate liver injury. If hepatitis occurs, the drug should be withdrawn immediately and appropriate measures taken.

Nitrofurantoin (Macrobid) is available in 100-mg capsules and is indicated only for the treatment of acute uncomplicated urinary tract infections (acute cystitis) caused by susceptible strains of Escherichia coli or Staphylococcus saprophyticus.

Nitrofurantoin (Macrodantin) is available in 25-, 50-, and 100-mg capsules for the specific treatment of urinary tract infections when due to susceptible strains of E coli, enterococci, S aureus, and certain susceptible strains of Klebsiella and Enterobacter species.

Axert Prescribing Information

Macrobid Prescribing Information

Macrodantin Prescribing Information


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