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CYP2C19: Venlafaxine did not inhibit the metabolism of diazepam, which is partially metabolized by CYP2C19 (see Diazepam above).
Monoamine Oxidase Inhibitors See CONTRAINDICATIONS and WARNINGS. CNS-Active Drugs The risk of using venlafaxine in combination with other CNS-active drugs has not been systematically evaluated (except in the case of those CNS-active drugs noted above). Consequently, caution is advised if the concomitant administration of venlafaxine and such drugs is required. Based on the mechanism of action of venlafaxine and the potential for serotonin syndrome, caution is advised when venlafaxine is co-administered with other drugs that may affect the serotonergic neurotransmitter systems, such as triptans, serotonin reuptake inhibitors (SRIs), or lithium. Text Continues Below
Electroconvulsive Therapy There are no clinical data establishing the benefit of electroconvulsive therapy combined with Effexor XR (venlafaxine hydrochloride) extended-release capsules treatment. Postmarketing Spontaneous Drug Interaction Reports See ADVERSE REACTIONS, Postmarketing Reports. Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Venlafaxine was given by oral gavage to mice for 18 months at doses up to 120 mg/ kg per day, which was 1.7 times the maximum recommended human dose on a mg/ m 2 basis. Venlafaxine was also given to rats by oral gavage for 24 months at doses up to 120 mg/ kg per day. In rats receiving the 120 mg/ kg dose, plasma concentrations of venlafaxine at necropsy were 1 times (male rats) and 6 times (female rats) the plasma concentrations of patients receiving the maximum recommended human dose. Plasma levels of the O-desmethyl metabolite were lower in rats than in patients receiving the maximum recommended dose. Tumors were not increased by venlafaxine treatment in mice or rats. Mutagenesis Venlafaxine and the major human metabolite, O-desmethylvenlafaxine (ODV), were not mutagenic in the Ames reverse mutation assay in Salmonella bacteria or the Chinese hamster ovary/ HGPRT mammalian cell forward gene mutation assay. Venlafaxine was also not mutagenic or clastogenic in the in vitro BALB/ c-3T3 mouse cell transformation assay, the sister chromatid exchange assay in cultured Chinese hamster ovary cells, or in the in vivo chromosomal aberration assay in rat bone marrow. ODV was not clastogenic in the in vitro Chinese hamster ovary cell chromosomal aberration assay, but elicited a clastogenic response in the in vivo chromosomal aberration assay in rat bone marrow. Impairment of Fertility Reproduction and fertility studies in rats showed no effects on male or female fertility at oral doses of up to 2 times the maximum recommended human dose on a mg/ m 2 basis. Pregnancy Teratogenic Effects -Pregnancy Category C Venlafaxine did not cause malformations in offspring of rats or rabbits given doses up to 2.5 times (rat) or 4 times (rabbit) the maximum recommended human daily dose on a mg/ m 2 basis. However, in rats, there was a decrease in pup weight, an increase in stillborn pups, and an increase in pup deaths during the first 5 days of lactation, when dosing began during pregnancy and continued until weaning. The cause of these deaths is not known. These effects occurred at 2.5 times (mg/ m 2 ) the maximum human daily dose. The no effect dose for rat pup mortality was 0.25 times the human dose on a mg/ m 2 basis. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Non-teratogenic Effects If venlafaxine is used until or shortly before birth, discontinuation effects in the newborn should be considered. Labor and Delivery The effect of venlafaxine on labor and delivery in humans is unknown. Nursing Mothers Venlafaxine and ODV have been reported to be excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from Effexor XR, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use Safety and effectiveness in pediatric patients have not been established.
In pediatric clinical trials, there were increased reports of hostility and, especially in Major Depressive Disorder, suicide-related adverse events such as suicidal ideation and self-harm. Geriatric Use Approximately 4 (14/ 357), 6 (77/ 1381), and 2% (6/ 277) of Effexor XR-treated patients in placebo-controlled premarketing major depressive disorder, GAD, and Social Anxiety Disorder trials, respectively, were 65 years of age or over. Of 2,897 Effexor-treated patients in premarketing phase major depressive disorder studies, 12 (357) were 65 years of age or over. No overall differences in effectiveness or safety were observed between geriatric patients and younger patients, and other reported clinical experience generally has not identified differences in response between the elderly and younger patients. However, greater sensitivity of some older individuals cannot be ruled out. As with other antidepressants, several cases of hyponatremia and syndrome of inappropriate antidiuretic hormone secretion (SIADH) have been reported, usually in the elderly.
The pharmacokinetics of venlafaxine and ODV are not substantially altered in the elderly (see CLINICAL PHARMACOLOGY). No dose adjustment is recommended for the elderly on the basis of age alone, although other clinical circumstances, some of which may be more common in the elderly, such as renal or hepatic impairment, may warrant a dose reduction (see DOSAGE AND ADMINISTRATION). Page: << Prev | 1 | 2 | 3 | 4 | 5
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