FDA Safety Changes: Luvox/Luvox CR, Altace, Capozide, Monopril/Monopril HCT, Furadantin

Yael Waknine

April 08, 2009

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April 8, 2009 — The US Food and Drug Administration (FDA) has approved safety labeling revisions to provide updated information regarding drug interactions that raise the risk for serotonin syndrome in patients receiving treatment with fluvoxamine maleate, drug interactions between angiotensin-converting enzyme inhibitors and injectable gold therapy, and the risk for hepatotoxicity in patients receiving nitrofurantoin therapy.

Additional Agents Implicated in SSRI-Related Risk for Serotonin Syndrome

On February 24, the FDA approved class labeling changes for fluvoxamine maleate tablets and extended-release capsules (Luvox and Luvox CR, Jazz Pharmaceuticals) to provide updated information regarding drug interactions that increase the risk for serotonin-related adverse events in patients receiving treatment with selective serotonin reuptake inhibitors (SSRIs) such as fluvoxamine. This information also applies to selective serotonin-norepinephrine reuptake inhibitors.

The agency previously warned of the risk for potentially life-threatening serotonin syndrome in patients receiving 5-hydroxytryptamine receptor agonists (triptans) in conjunction with SSRIs.

An expanded section of the monograph now warns that serotonin syndrome or neuroleptic malignant syndrome (NMS)-like reactions can occur with use of SSRIs alone but are more likely with concomitant use of serotonergic drugs (including triptans), agents that impair serotonin metabolism (including monoamine oxidase inhibitors [MAOIs]), or antipsychotics and other dopamine antagonists.

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). Severe cases can resemble NMS, which includes hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes. Patients should be monitored for the emergence of serotonin syndrome or NMS-like signs and symptoms.

Clinicians are reminded that concomitant treatment of depression with MAOIs and SSRIs is contraindicated. SSRI-treated patients receiving triptans should be followed up closely, particularly during initiation of therapy, dose increases, or the addition of another serotonergic drug.

Concomitant use of SSRIs with serotonin precursors (eg, tryptophan) is not recommended. Treatment with SSRIs and any concomitant serotonergic or antidopaminergic agents, including antipsychotics, should be discontinued immediately in patients who develop symptoms of serotonin syndrome.

Fluvoxamine tablets and controlled-release capsules are indicated for the treatment of obsessive-compulsive disorder; the capsules can also be used to treat social anxiety disorder.

ACE Inhibitor Drug Interaction With Injectable Gold Linked to Nitritoid Reactions

The FDA approved safety labeling revisions in February for angiotensin-converting enzyme (ACE) inhibitors to warn of drug interactions with gold.

Updated monographs include those for ramipril tablets and capsules (Altace, King Pharmaceuticals, Inc), captopril plus hydrochlorothiazide tablets (Capozide, Bristol-Myers Squibb), fosinopril sodium tablets (Monopril, Bristol-Myers Squibb), and fosinopril plus hydrochlorothiazide tablets (Monopril HCT, Bristol-Myers Squibb).

According to the FDA, nitritoid reactions have been reported rarely in patients receiving concomitant treatment with injectable gold (sodium aurothiomalate) and ACE inhibitors. Symptoms may include facial flushing, nausea, vomiting, and hypotension.

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.

Ramipril is indicated to reduce the risk for myocardial infarction, stroke, and death from cardiovascular causes in high-risk patients aged 55 years or older. It is also indicated for use alone or in combination with thiazide diuretics in the treatment of hypertension and to reduce the risk for adverse cardiovascular events and death in stable patients with clinical signs of congestive heart failure after acute myocardial infarction.

Captopril plus hydrochlorothiazide tablets are indicated for the treatment of hypertension.

Fosinopril and fosinopril plus hydrochlorothiazide are indicated for the treatment of hypertension and as adjunctive therapy for the management of heart failure.

Nitrofurantoin (Furadantin) Linked to Rare Cases of Hepatotoxicity

On February 6, the FDA approved safety labeling revisions for nitrofurantoin oral suspension (Furadantin, Sciele Pharma, Inc) to more adequately characterize and communicate the risk for hepatotoxicity.

Rare and sometimes fatal hepatic reactions to nitrofurantoin, including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis, have been reported. The onset of chronic active hepatitis may be insidious, the FDA warns, noting that patients should be monitored periodically for changes in liver function. The development of hepatitis warrants permanent discontinuation of nitrofurantoin and the initiation of appropriate treatment.

Nitrofurantoin is specifically indicated for the treatment of urinary tract infections when they are the result of susceptible strains of Escherichia coli, enterococci, Staphylococcus aureus, and certain susceptible strains of Klebsiella and Enterobacter species.


Luvox Prescribing Information

Altace Prescribing Information

FDA Safety Changes


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