desvenlafaxine

ROUTE	ONSET	PEAK	DURATION
PO	unknown	7.5 hr	24 hr

Contraindicated in:

Hypersensitivity to venlafaxine or desvenlafaxine;
Concurrent use of MAO inhibitors or MAO-like drugs (linezolid or methylene blue);
Should not be used concurrently with venlafaxine.

Use Cautiously in:

Untreated cerebrovascular or cardiovascular disease, including untreated hypertension (control BP before initiating therapy);
Bipolar disorder (may activate mania/hypomania);
Moderate or severe renal impairment;
History of seizures or neurologic impairment;
Moderate or severe hepatic impairment;
Angle-closure glaucoma;
OB: Safety not established in pregnancy;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: risk of suicidal thinking and behavior (suicidality) in children and adolescents with major depressive disorder and other psychiatric disorders;
Geri: Appears on Beers list. May worsen or cause syndrome of inappropriate antidiuretic hormone (SIADH) secretion and/or hyponatremia in older adults. Use with caution in older adults and closely monitor sodium concentrations when starting therapy or dose .

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension

Derm: sweating, ERYTHEMA MULTIFORME, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS

EENT: ↑intraocular pressure, mydriasis

Endo: SIADH

F and E: hyponatremia

GI: ↓appetite, constipation, nausea, PANCREATITIS

GU: ↓libido, delayed/absent orgasm, ejaculatory delay/failure, erectile dysfunction

Hemat: BLEEDING

Metab: hyperlipidemia

Neuro: anxiety, dizziness, drowsiness, insomnia, headache, NEUROLEPTIC MALIGNANT SYNDROME, SEIZURES, SUICIDAL THOUGHTS, teeth grinding, vertigo

Resp: eosinophilic pneumonia, interstitial lung disease

Misc: discontinuation syndrome, SEROTONIN SYNDROME

Interactions ⬆ ⬇

Drug-drug:

Concurrent use with MAO inhibitors may result in serious, potentially fatal reactions (wait at least 2 wk after stopping MAO inhibitor before initiating desvenlafaxine; wait at least 1 wk after stopping desvenlafaxine before starting an MAO inhibitor).
Concurrent use with MAO-inhibitor like drugs, such as linezolid or methylene blue may ↑ risk of serotonin syndrome; concurrent use contraindicated; do not start therapy in patients receiving linezolid or methylene blue; if linezolid or methylene blue need to be started in a patient receiving desvenlafaxine, immediately discontinue desvenlafaxine and monitor for signs/symptoms of serotonin syndrome for 2 wk or until 24 hr after last dose of linezolid or methylene blue, whichever comes first (may resume desvenlafaxine therapy 24 hr after last dose of linezolid or methylene blue).
↑risk of bleeding with NSAIDs, aspirin, clopidogrel, prasugrel, ticagrelor, dabigatran, apixaban, edoxaban, rivaroxaban, or warfarin.
Use cautiously with other CNS-active drugs, including alcohol or sedative/hypnotics; effects of combination are unknown.
Drugs that affect serotonergic neurotransmitter systems, including tricyclic antidepressants, SNRIs, fentanyl, lithium, buspirone, tramadol, meperidine, methadone, amphetamines, and triptans↑ risk of serotonin syndrome
Ketoconazole may ↑ the effects of desvenlafaxine.
May ↑ levels of CYP2D6 substrates, including desipramine, atomoxetine, dextromethorphan, metoprolol, nebivolol, perphenazine, and tolterodine; if using desvenlafaxine at dose of 400 mg/day, ↓ dose of CYP2D6 substrate by 50%.

Route/Dosage ⬆ ⬇

PO (Adults ): 50 mg once daily (range = 50–400 mg/day).

Hepatic Impairment

PO (Adults ): Moderate-to-severe hepatic impairment: 50 mg once daily (not to exceed 100 mg/day).

Renal Impairment

PO (Adults ): CCr 30–50 mL/min: 50 mg once daily; CCr <30 mL/min: 50 mg every other day or 25 mg once daily.

Availability ⬆ ⬇

(Generic available)

Extended-release tablets: 25 mg; 50 mg; 100 mg

Assessment ⬆ ⬇

Assess mental status and mood changes, especially during initial few mo of therapy and during dose changes. Inform health care professional if patient demonstrates significant increase in signs of depression (depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, suicide attempt or suicidal ideation).
Assess suicidal tendencies, especially in early therapy. Restrict amount of drug available to patient. Risk may be increased in children, adolescents, and adults ≤24 yr.
Monitor BP before and periodically during therapy. Sustained hypertension may be dose related; decrease dose or discontinue therapy if this occurs.
Monitor appetite and nutritional intake; weigh weekly. Report continued weight loss. Adjust diet as tolerated to support nutritional status.
Assess for serotonin syndrome (mental changes [agitation, hallucinations, coma], autonomic instability [tachycardia, labile BP, hyperthermia], neuromuscular aberrations [hyperreflexia, incoordination], and/or GI symptoms [nausea, vomiting, diarrhea]), especially in patients taking other serotonergic drugs (SSRIs, SNRIs, triptans).
Assess patient for skin rash frequently during therapy. Discontinue at first sign of rash; may be life-threatening. SJS may develop. Treat symptomatically; may recur once treatment is stopped.
Assess sexual function before starting desvenlafaxine. Assess for changes in sexual function during treatment, including timing of onset; patient may not report.

Lab Test Considerations:

May cause ↑ fasting serum total cholesterol, LDL cholesterol, and triglycerides.
- May cause transient proteinuria, not usually associated with ↑ BUN or serum creatinine.
- May cause hyponatremia.
- May cause false-positive immunoassay screening tests for phencyclidine and amphetamine.

Implementation ⬆ ⬇

PO: Administer at the same time each day, with or without food. DNC: Swallow tablets whole; do not crush, break, chew, or dissolve.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication exactly as directed at the same time each day. Take missed doses as soon as possible unless almost time for next dose. Do not double doses or discontinue abruptly; gradually decrease before discontinuation to prevent dizziness, nausea, headache, irritability, insomnia, diarrhea, anxiety, fatigue, abnormal dreams, and hyperhidrosis; discontinuation may take several mo.
Advise patient, family, and caregivers to look for suicidality, especially during early therapy or dose changes. Notify health care professional immediately if thoughts about suicide or dying, attempts to commit suicide, new or worse depression or anxiety, agitation or restlessness, panic attacks, insomnia, new or worse irritability, aggressiveness, acting on dangerous impulses, mania, or other changes in mood or behavior or if symptoms of serotonin syndrome occur.
May cause drowsiness or dizziness. Caution patient to avoid driving or other activities requiring alertness until response to the drug is known.
Caution patient to avoid taking alcohol or other CNS-depressant drugs, including opioids during therapy and of increased risk of bleeding with concomitant use of NSAIDs, aspirin, or other drugs that affect coagulation. Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken, especially St. John's wort, and to consult health care professional before taking other Rx, OTC, or herbal products.
Instruct patient to notify health care professional if signs of allergy (rash, hives, swelling, difficulty breathing) occur.
Inform patient that desvenlafaxine may cause symptoms of sexual dysfunction. In males, ejaculatory delay or failure, decreased libido, and erectile dysfunction may occur. In female patients, may result in decreased libido and delayed or absent orgasm. Advise patient to notify health care professional if symptoms occur.
Inform patient that remains of tablet may pass into stool, but medication has already been absorbed.
Rep: May cause fetal harm. Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Exposure to desvenlafaxine in mid- to late pregnancy may increase risk for preeclampsia and exposure near delivery may increase risk of postpartum hemorrhage. Fetal exposure late in pregnancy may lead to increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding. Monitor neonates exposed to desvenlafaxine in the third trimester for drug discontinuation syndrome. Inform patient of pregnancy exposure registry to monitor pregnancy outcomes in women exposed to antidepressants during pregnancy. Register patients by calling the National Pregnancy Registry for Antidepressants at 1-866-961-2388.
Emphasize the importance of follow-up exams to monitor progress.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇