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PRODUCT: Pristiq

COMPANY: Wyeth

PHARMACOLOGIC CLASS: Antidepressant (SNRI)

ACTIVE INGREDIENTS: Desvenlafaxine (as succinate) 50mg, 100mg; ext-rel tabs

INDICATION: Major depressive disorder (MDD)

PHARMACOLOGY: 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.

CLINICAL TRIALS: 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.

ADULTS: 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.

CHILDREN: Not recommended.

CONTRAINDICATIONS: MAOIs: see Interactions.

PRECAUTIONS: 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 for smallest practical amount. Elderly. Labor & delivery. Pregnancy (Cat.C; avoid in 3rd trimester; taper). Nursing mothers: not recommended.

INTERACTIONS: 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.

ADVERSE REACTIONS: 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.

HOW SUPPLIED: Tabs—14, 30, 90

Facts about major depressive disorder

Major depressive disorder (MDD) affects 15 million adults (5% to 8% of the adult population in this country) each year. It’s not clear why, but twice as many women are affected by depression as are men.
More than 50% of people who have an episode of MDD will have subsequent episodes that occur as frequently as once or twice a year.
If depression is left untreated, the frequency of the episodes and the severity of the symptoms increase over time. Depression that is not adequately treated can lead to suicide.
Symptoms of depression include persistently sad or irritable mood; pronounced changes in sleep, appetite, and energy; difficulty thinking, concentrating, and remembering; physical slowing or agitation; lack of interest in or pleasure from activities that were once enjoyed; feelings of guilt, worthlessness, hopelessness, and emptiness; recurrent thoughts of death or suicide; and persistent physical symptoms that do not respond to treatment, such as chronic headaches, digestive disorders, and chronic pain.
When a person has several of these symptoms at the same time, they persist longer than 2 weeks, and they interfere with the ability to function, the depression should be treated.

Data from the National Alliance on Mental Illness. www.nami.org. Accessed May 2, 2008.