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);
May ↑ risk of suicide attempt/ideation, especially during early treatment or dose adjustment; this risk appears to be greater in adolescents or children
;
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: Safety and effectiveness not established in children;
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: constipation, nausea, PANCREATITIS

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

Hemat: BLEEDING

Metab: ↓appetite, hyperlipidemia

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

Resp: eosinophilic pneumonia, interstitial lung disease

Misc: discontinuation syndrome, SEROTONIN SYNDROME

Interactions ⬆ ⬇

Drug-drug:

MAO inhibitors may result in serious, potentially fatal reactions; wait ≥2 wk after stopping MAO inhibitor before initiating desvenlafaxine; wait ≥1 wk after stopping desvenlafaxine before starting an MAO inhibitor.
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, may ↑ risk of serotonin syndrome.
Ketoconazole may ↑ levels and risk of toxicity.
May ↑ levels and risk of toxicity 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 provider if patient demonstrates significant ↑ 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, ↑ fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, suicide attempt or suicidal ideation).
Assess for suicidal tendencies, especially during early therapy and dose changes. Restrict amount of drug available to patient. Risk may be ↑ in children, adolescents, and adults ≤24 yr. After starting therapy, young adults should be seen by health care provider at least weekly for 4 wk, every 3 wk for the next 4 wk, and on advice of health care provider thereafter.
Monitor BP before and periodically during therapy. Sustained hypertension may be dose related; ↓ 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 signs and symptoms of serotonin syndrome (confusion, delirium, agitation, coma, dilated pupils, tachycardia, hyperthermia, shivering, hyperreflexia, muscle rigidity, hypertension, vomiting, diarrhea, seizures). ↑ risk of serotonin syndrome with concurrent use of other serotonergic drugs (SSRIs, SNRIs, triptans); monitoring recommended; discontinuation may be required.
Assess patient for skin rash frequently during therapy. Discontinue at first sign of rash; may be life-threatening. Erythema multiforme, SJS, or TEN may develop. Treat symptomatically; may recur once treatment is stopped.
Assess sexual function before starting therapy. Assess for changes in sexual function during treatment, including timing of onset; patient may not report.

Lab Test Considerations:

May ↑ fasting serum total cholesterol, LDL-C, and triglycerides.
- May cause transient proteinuria, not usually associated with ↑ BUN or serum creatinine.
- May cause hyponatremia. Monitor sodium levels at baseline and after 3–4 wk in high-risk patients (>65 yr, previous history of antidepressant-induced hyponatremia, ↓ body weight, concurrent use of thiazides or other hyponatremia-inducing agents).
- 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 ⬆ ⬇

Explain the purpose and side effects of desvenlafaxine. Instruct 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 ↓ dose before discontinuation to prevent dizziness, nausea, headache, irritability, insomnia, diarrhea, anxiety, fatigue, abnormal dreams, and hyperhidrosis; discontinuation may take several mo. Advise patient to read Patient Information before starting and with each Rx refill in case of changes.
Emphasize the importance of follow-up exams to monitor progress.
Advise patient, family, and caregivers to look for suicidality, especially during early therapy or dose changes. Notify health care provider 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 occur.
May cause drowsiness or dizziness. Caution patient to avoid driving or other activities requiring alertness until response to the drug is known.
Counsel patient to report symptoms of serotonin syndrome (agitation, confusion, diaphoresis, hallucinations, hyper-reflexia).
Caution patient to avoid taking alcohol or other CNS-depressant drugs, including opioids, during therapy and of ↑ risk of bleeding with concurrent use of NSAIDs, aspirin, or other drugs that affect coagulation. Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken, especially St. John's wort, and to consult health care provider before taking other Rx, OTC, or herbal products.
Instruct patient to notify health care provider if signs of allergy (rash, hives, swelling, difficulty breathing) occur.
Inform patient that desvenlafaxine may cause symptoms of sexual dysfunction. In men, ejaculatory delay or failure, ↓ libido, and erectile dysfunction may occur. In women, may result in ↓ libido and delayed or absent orgasm. Advise patient to notify health care provider if symptoms occur.
Inform patient that remains of tablet may pass into stool, but medication has already been absorbed.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding. Exposure to desvenlafaxine in mid- to late pregnancy may ↑ risk for pre-eclampsia and exposure near delivery and may ↑ risk of postpartum hemorrhage. Fetal exposure late in pregnancy may lead to ↑ risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding. Monitor neonates exposed to desvenlafaxine in the 3rd 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.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇