Mood disorders:
Indications for: PRISTIQ
Major depressive disorder.
Clinical Trials:
Studies 1–4
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Efficacy of Pristiq (50–400 mg per day) was evaluated in four 8-week, randomized, double-blind, placebo-controlled, fixed-dose studies in adult outpatients who met the DSM-IV criteria for major depressive disorder.
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Study 1 – Patients received Pristiq 100 mg, 200 mg, or 400mg once daily or placebo.
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Study 2 – Patients received either Pristiq 200 mg or 400 mg once daily or placebo.
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Studies 3 and 4 – Patients received Pristiq 50 mg or 100 mg once daily or placebo.
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Pristiq achieved superiority over placebo as measured by improvement in the 17-item Hamilton Rating Scale for Depression (HAM-D17) total score in four studies and overall improvement, as measured by the Clinical Global Impressions Scale - Improvement (CGI-I), in three of the 4 studies.
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For studies comparing Pristiq 50 mg/day to 100 mg/day, there was no evidence that the higher dose had greater effect. There were more frequent adverse reactions and discontinuations at higher doses.
Study 5
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Study 5 was a longer-term trial which included adult outpatients who met the DSM-IV criteria for MDD, who responded to 8 weeks of open-label acute treatment with desvenlafaxine 50 mg per day and remained stable for 12 weeks. Patients were randomly assigned to remain on Pristiq or switch to placebo for up to 26 weeks of observation for relapse.
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Relapse during the double-blind phase was defined as follows: (1) a HAM-D17 total score of at least 16 at any office visit, (2) discontinuation for unsatisfactory efficacy response, (3) hospitalized for depression, (4) suicide attempt, or (5) suicide.
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Patients who received Pristiq achieved statistically significantly longer time to relapse compared with placebo. At 26 weeks, 14% of patients in the desvenlafaxine arm had relapsed compared with 30% of patients in the placebo arm.
Study 6
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Study 6 was a longer-term trial which included adult outpatients who met the DSM-IV criteria for MDD, who responded to 12 weeks of acute treatment with desvenlafaxine. Patients were randomly assigned to remain on Pristiq (200 or 400 mg/day) or switch to placebo for up to 26 weeks of observation for relapse.
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Relapse during the double-blind phase was defined as follows: (1) a HAM-D17 total score of at least 16 at any office visit, (2) a CGI-I score of ≥ 6 (versus day 84) at any office visit, or (3) discontinuation from the trial due to unsatisfactory response.
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Patients who received Pristiq achieved statistically significantly longer time to relapse compared with placebo. At 26 weeks, 29% of patients in the desvenlafaxine arm had relapsed compared with 49% of patients in the placebo arm.
Postmarketing Study
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Efficacy of Pristiq at a lower dose than 50 mg per day was evaluated in an 8-week, multicenter, randomized, double-blind, placebo-controlled, fixed-dose study in adult outpatients with MDD. Patients were randomly assigned to receive Pristiq 25 mg, 50 mg, or placebo.
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Pristiq 50 mg achieved superiority to placebo, as measured by HAMD-17. The 25 mg dose was not superior to placebo.
Adult Dosage:
Swallow whole. 50mg once daily. Moderate renal impairment (CrCl 30–50mL/min): max 50mg/day. Severe renal impairment (CrCl <30mL/min), ESRD: max 25mg daily or 50mg every other day. Do not give supplemental dose after dialysis. Moderate to severe hepatic impairment: max 100mg/day. Withdraw gradually.
Children Dosage:
Not established.
PRISTIQ Contraindications:
During or within 14 days of MAOIs; do not start an MAOI during or within 7 days of desvenlafaxine. Concomitant linezolid or IV methylene blue.
Boxed Warning:
Suicidal thoughts and behaviors.
PRISTIQ Warnings/Precautions:
Increased risk of suicidal thinking or behavior; monitor for clinical worsening or unusual changes. Screen for bipolar disorder. Monitor for serotonin syndrome; discontinue immediately if occurs. Monitor BP; reduce dose or discontinue if elevated BP persists. Cardio- or cerebrovascular disease. Angle closure glaucoma. Avoid in untreated anatomically narrow angles. History of mania/hypomania. Seizure disorder. Volume depleted. Hyponatremia (esp. in elderly). Sexual dysfunction. Renal or hepatic impairment. Avoid abrupt cessation; monitor. Reevaluate periodically. Write ℞ for smallest practical amount. Elderly. Labor & delivery. Pregnancy (avoid in 3rd trimester); see full labeling for effects on neonate. Nursing mothers.
PRISTIQ Classification:
SNRI.
PRISTIQ Interactions:
See Contraindications. Avoid alcohol, concomitant venlafaxine, other forms of desvenlafaxine. Increased risk of serotonin syndrome with other serotonergic drugs (eg, other SNRIs, SSRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, St. John's Wort) or with drugs that impair serotonin metabolism (eg, MAOIs such as linezolid, IV methylene blue). Increased risk of bleeding with concomitant aspirin, NSAIDs, warfarin, or other drugs that affect coagulation; monitor closely. May affect CYP2D6 substrates (eg, desipramine, atomoxetine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine); reduce dose by up to ½ if concomitant with desvenlafaxine 400mg dose. May cause false (+) urine immunoassay screening tests for PCP and amphetamine.
Adverse Reactions:
Nausea, dizziness, insomnia, hyperhidrosis, constipation, somnolence, decreased appetite, anxiety, specific male sexual dysfunction; rare: interstitial lung disease or eosinophilic pneumonia (consider discontinuing if occurs).
Drug Elimination:
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Approximately 45% of desvenlafaxine is excreted unchanged in urine at 72 hours after oral administration.
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Approximately 19% of the administered dose is excreted as the glucuronide metabolite and <5% as the oxidative metabolite (N,O-didesmethylvenlafaxine) in urine.
Generic Drug Availability:
YES
How Supplied:
Tabs 25mg—30; 50mg, 100mg—14, 30, 90
