desvenlafaxine (des-ven-la-fax-een) Khedezla, Pristiq

 Indications

Major depressive disorder.

Action

Inhibits serotonin and norepinephrine reuptake in the

CNS. Therapeutic Effects: Decrease in depressive

symptomatology, with fewer relapses/recurrences.

Pharmacokinetics

Absorption: 80% absorbed following oral administration.

Distribution: Enters breast milk.

Metabolism and Excretion: 55% metabolized by

the liver, 45% excreted unchanged in urine.

Half-life: 10 hr.

TIME/ACTION PROFILE (blood levels)

ROUTE ONSET PEAK DURATION

PO unknown 7.5 hr 24 hr

Contraindications/Precautions

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); Renal impairment

(consider modifications, dose should not exceed

50 mg/day, especially in moderate to severe renal impairment);

History of seizures or neurologic impairment;

Hepatic impairment (dose should not exceed

100 mg/day); Angle-closure glaucoma; Geri: Consider

age-relatedpin renal function,pbody mass, concurrent

disease states, and medications; OB, Lactation: Use

only if maternal benefit outweighs fetal/infant risk; Pedi:

qrisk of suicidal thinking and behavior (suicidality) in

children and adolescents with major depressive disorder

and other psychiatric disorders. Observe closely for

suicidality and behavior changes.

Adverse Reactions/Side Effects

CNS: NEUROLEPTIC MALIGNANT SYNDROME, SEIZURES, SUICIDAL

THOUGHTS, anxiety, dizziness, drowsiness, insomnia,

headache, teeth grinding, vertigo. EENT:qintraocular

pressure, mydriasis. Resp: eosinophilic

pneumonia, interstitial lung disease. CV: hypertension.

GI: PANCREATITIS,pappetite, constipation, nausea.

GU: male sexual dysfunction. Derm: ERYTHEMA MULTIFORME,

STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL

NECROLYSIS, sweating. F and E: hyponatremia. Hemat:

qrisk of bleeding. Metab: hypercholesterolema,

hyperlipidemia. Misc: 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 mayqrisk 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).q

risk of bleeding with other drugs thatqbleeding

risk including anticoagulants, antithrombotics,

platelet aggregation inhibitors, and NSAIDs. 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, buspirone, tramadol, amphetamines,

and triptansqrisk of serotonin

syndrome. Ketoconazole mayqthe effects of desvenlafaxine.

Mayqlevels of CYP2D6 substrates, including

desipramine, atomoxetine, dextromethorphan,

metoprolol, nebivolol, perphenazine, and tolterodine;

if using desvenlafaxine at dose of 400 mg/day,

pdose of CYP2D6 substrate by 50%.

Route/Dosage

PO (Adults): 50 mg once daily (range50–400 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.

Hepatic Impairment

PO (Adults): Moderate-to-severe hepatic impairment—

50 mg once daily (not to exceed 100 mg/day).

Availability (generic available)

Extended-release tablets: 25 mg, 50 mg, 100 mg.

Cost: Generic—All strengths $174.14/30.