News
FDA Safety Changes: Pexeva, Vfend, Suprane
The US Food and Drug Administration (FDA) has approved safety labeling revisions to advise of the risk for serotonin syndrome in patients receiving concomitant treatment with paroxetine mesylate and triptans, drug interactions between voriconazole and efavirenz requiring dose adjustments for both drugs when used concomitantly, and the risk for respiratory adverse events associated with use of desflurane in certain pediatric settings.
Concomitant Use of Paroxetine Mesylate (Pexeva) and Triptans Linked to Risk for Serotonin Syndrome On December 9, 2006, the FDA approved safety labeling revisions for paroxetine mesylate (Pexeva tablets, made by Synthon Pharmaceuticals, Ltd) to advise of the potential increased risk for serotonin syndrome in patients receiving concomitant treatment with other serotonergic drugs (including 5-hydroxytryptamine-receptor agonists [triptans]) or drugs that impair serotonin metabolism (including monoamine oxidase inhibitors [MAOIs]).
Concurrent treatment with paroxetine and MAOIs is therefore contraindicated. Concomitant use of other selective serotonin reuptake inhibitors (SSRIs), serotonin/norepinephrine reuptake inhibitors (SNRIs), or the serotonin precursor tryptophan is not recommended. Caution is advised when using paroxetine in combination with other drugs or agents that can affect serotonergic neurotransmitter systems, such as the antibiotic linezolid (a reversible nonselective MAOI), lithium, tramadol, St. John's Wort, and triptans.
According to the FDA, rare postmarketing cases of serotonin syndrome have been reported with use of SSRIs and triptans. Associated symptoms may include changes in mental status (eg, agitation, hallucinations, and coma), autonomic instability (eg, tachycardia, labile blood pressure, and hyperthermia), neuromuscular aberrations (eg, hyperreflexia and incoordination), and/or gastrointestinal tract symptoms, such as nausea, vomiting, and diarrhea.
Paroxetine-treated patients in whom concomitant triptan therapy is clinically warranted should be carefully monitored, particularly during initiation of therapy, dose increases, or the addition of another serotonergic drug.
Triptans are used to treat migraines. The drug class includes naratriptan HCl (Amerge, made by GlaxoSmithKline), almotriptan malate (Axert, made by Ortho-McNeil Pharmaceutical, Inc), frovatriptan succinate (Frova, made by Endo Pharmaceuticals), sumatriptan/sumatriptan succinate (Imitrex, made by GlaxoSmithKline), rizatriptan benzoate (Maxalt and Maxalt-MLT, made by Merck and Co, Inc), eletriptan HBr (Relpax, made by Pfizer, Inc), and zolmitriptan (Zomig and Zomig ZMT, made by AstraZeneca Pharmaceuticals LP).
Paroxetine mesylate is indicated for the treatment of major depressive, obsessive-compulsive, panic, and generalized anxiety disorders. Although the risk for suicidal behavior/thoughts (suicidality) warrants monitoring of all patients regardless of the condition being treated, it is of particular importance in patients with a history of suicidality, those exhibiting a significant degree of suicidal ideation prior to treatment, and young adults.
FDA Warns of 2-Way Drug Interaction Between Voriconazole (Vfend) and Efavirenz
On December 1, 2006, the FDA approved safety labeling revisions for voriconazole (Vfend injection, tablets, and oral suspension, made by Pfizer, Inc) to advise of a 2-way drug interaction with coadministered efavirenz (Sustiva tablets and capsules, made by Bristol-Myers Squibb).
Standard doses of voriconazole are contraindicated with efavirenz because efavirenz significantly decreases voriconazole plasma concentrations while voriconazole significantly increases efavirenz plasma concentrations.
The warning was based on data from a pharmacokinetic study of healthy subjects, showing that systemic exposure of voriconazole (400 mg given orally every 12 hours for 1 day followed by 200 mg every 12 hours for 8 days) was significantly decreased (mean area under the curve [AUC], 61%; Cmax, 77%) when given concurrently with efavirenz (400 mg every 12 hours for 9 days). The AUC and Cmax for efavirenz increased by an average of 38% and 44%, respectively.
Concomitant therapy therefore requires dosage adjustments for both agents. Voriconazole maintenance dosing should be increased from 200 to 400 mg and given every 12 hours. The once-daily dose of efavirenz should be decreased from 600 to 300 mg using the capsule formulation.