Company:

Wyeth

Antidepressant (SNRI)

Desvenlafaxine (as succinate) 50mg, 100mg; ext-rel tabs.

Major depressive disorder (MDD).

Desvenlafaxine, the major active metabolite of venlafaxine (Effexor XR, also from Wyeth), is a potent and selective serotonin and norepinephrine reuptake inhibitor (SNRI). The increase in the effects of these neurotransmitters in the CNS may be responsible for its clinical efficacy.

Desvenlafaxine is primarily metabolized by conjugation (mediated by UGT isoforms) and, to a minor extent, through oxidative metabolism mediated by the CYP3A4 enzyme; the CYP2D6 metabolic pathway is not involved. It is eliminated primarily by the kidneys.

Four 8-week, double-blind, placebo-controlled fixed-dose studies were conducted to assess the efficacy and safety of desvenlafaxine in treating major depressive disorder. The first study compared desvenlafaxine 100mg, 200mg, and 400mg once daily to placebo. In a second study, patients received desvenlafaxine 200mg or 400mg once daily or placebo, and in two other studies, patients were given desvenlafaxine 50mg or 100mg once daily or placebo. Desvenlafaxine was shown to be better than placebo, as measured by improvement using the 17-item Hamilton Rating Scale for Depression score in four studies, and it was better than placebo in overall improvement (measured by the Clinical Global Impressions Scale-Improvement) in three of the four studies. Doses above 50mg/day were not shown to be more effective, but adverse reactions and discontinuations were more frequent at the higher dose.

Swallow whole. 50mg once daily. Severe renal impairment (CrCl <30mL/min), ESRD: 50mg every other day. Do not give supplemental dose after dialysis. Moderate renal impairment: max 50mg/day. Hepatic impairment: max 100mg/day. Withdraw gradually.

Not recommended.

MAOIs: see Interactions.

Monitor BP; reduce dose or discontinue if elevated BP persists. Cardio- or cerebrovascular disease. Hypercholesterolemia. Increased intraocular pressure. Mania/hypomania. Severe renal dysfunction. Seizure disorder. Reevaluate periodically. Suicidal ideation. Write prescription for smallest practical amount. Elderly. Labor & delivery. Pregnancy (Cat.C; avoid in 3rd trimester; taper). Nursing mothers: not recommended.

Allow ≥14 days after MAOI discontinuance before starting desvenlafaxine; allow ≥7 days after desvenlafaxine discontinuance before starting an MAOI. Avoid alcohol, concomitant venlafaxine, other forms of desvenlafaxine. Concomitant serotonin precursors (eg, tryptophan): not recommended. May potentiate anticoagulants. Monitor for serotonin syndrome with SSRIs, SNRIs, triptans. May be potentiated by potent CYP3A4 inhibitors. May antagonize CYP3A4 substrates. Caution with serotonergics, other CNS-active drugs.

GI upset, dizziness, insomnia, hyperhidrosis, constipation, somnolence, decreased appetite, anxiety, sexual dysfunction; rare: hyponatremia/SIADH (esp in elderly), interstitial lung disease, eosinophilic pneumonia, serotonin syndrome, mydriasis.

Tabs—14, 30, 90

5/2/08