Medication Adverse Effect Alert

October 25, 2006

MEDICATION: venlafaxine hydrochloride, -XR

Description:	Approved for use major depressive disorder, generalized anxiety disorder (extended release formulation), and social anxiety disorder. Off-labeled uses include premenstrual dysphoric disorder and post traumatic distress disorder.
Dosage:	Available tablets and extended-release capsules
Manufacturer:	Wyeth-Ayerst (Effexor, -XR), Teva (generic tablets)
Strength:	Tablets 25mg, 37.5mg, 50mg, 75mg, 100mg, extended-release capsules 37.5mg, 75mg, and 150mg

Event Description: Postmarketing surveillance of venlafaxine has revealed reports of overdosage resulting in an increased risk of fatal outcome compared to SSRI antidepressant agents, but the risk was lower than that for tricyclic antidepressants. The FDA has required Wyeth to amend the OVERDOSAGE/Human Experience section of the Prescribing Information to reflect these findings. Wyeth's newly revised section states that the overdoses commonly occur in combination with alcohol and/or other drugs and symptoms may include, change in level of consciousness, mydriasis, seizures, vomiting, ventricular tachycardia, ECG changes, hypotension, bradycardia, rhabdomyolysis, vertigo, liver necrosis, serotonin syndrome and death.

Clinical Considerations and Recommendations: The FDA MedWatch and Wyeth's most recent "Dear Health Care Provider" letters both reiterated that prescriptions for venlafaxine "should be written for the smallest quantity of drug consistent with good patient management" and to prevent risk of overdose. Wyeth also has available unit-of-use packages of venlafaxine with smaller quantities for use in dispensing to minimize overdosage.