Dosing and uses of Pristiq, Khedezla (desvenlafaxine)
Adult dosage forms and strengths
tablet, extended release
- 25mg
- 50mg
- 100mg
Major Depressive Disorder
50 mg PO once daily
Higher dosages, up to 400 mg/day, have been used but have not been proved more efficacious; increased side effects have been reported
Assess periodically to determine need for continued treatment
Dosing Modifications
Renal impairment
- CrCl ≥50 mL/min: Dosage adjustment not necessary
- CrCl 30-50 mL/min: Not to exceed 50 mg once daily
- CrCl <30 mL/min: 25 mg once daily or 50 mg every other day
- Moderate-to-severe renal impairment: Do not increase dosing interval
- End stage renal disease, requiring hemodialysis: 25 mg PO once daily
- Do not administer supplemental dose after hemodialysis
Hepatic impairment
- Recommended dosage: 50 mg PO once daily; dosages >100 mg/day not recommended
Dosing Considerations
When discontinuing, reduce dosage gradually, because abrupt discontinuance may result in adverse effects; if intolerable effects still occur, resume therapy at previously prescribed dosage and then decrease even more gradually
To minimize discontinuance symptoms, taper initial antidepressant before switching to desvenlafaxine
Wait at least 14 days between discontinuance of monoamine oxidase inhibitor (MAOI) and initiation of desvenlafaxine; wait at least 7 days between discontinuance of desvenlafaxine and initiation of MAOI
Administration
Take whole with fluid; do not divide, crush, chew, or dissolve
Take at approximately the same time every day
Pediatric dosage forms and strengths
Safety and efficacy not established
Pristiq, Khedezla (desvenlafaxine) adverse (side) effects
Adverse drug reactions (ADRs) shown occur with 50 mg/day dosage at rate higher than seen with placebo
>10%
Nausea (22-41%)
Headache (20-29%)
Dry mouth (11-25%)
Hyperhidrosis (10-21%)
Dizziness (13-16%)
Insomnia (9-15%)
Constipation (9-14%)
Fatigue (7-11%)
Diarrhea (5-11%)
1-10%
Decreased appetite (5-10%)
Anxiety (0-10%)
Elevated cholesterol and triglycerides (0-10%)
Insomnia (0-10%)
Tremor (2-9%)
Proteinuria (5-8%)
Mydriasis (2-6%)
Male sexual dysfunction (0-6%)
Anxiety (3-5%)
Vertigo (1-5%)
Blurred vision (3-4%)
Abnormal dreams (2-4%)
Urinary hesitation (2-4%)
Yawning (1-4%)
Feeling jittery (1-3%)
Female sexual dysfunction (0-3%)
Irritability (2%)
Other (eg, abnormal liver function tests, increased blood prolactin, convulsion, syncope, extrapyramidal disorders, musculoskeletal stiffness, depersonalization, hypomania, bruxism, epistaxis, orthostatic hypotension) (<2%)
Asthenia (1-2%)
Nervousness (1-2%)
Hot flush (1-2%)
Rash (1-2%)
Frequency not defined
Ischemic cardiac events in patients with multiple underlying cardiac risk factors
Gastrointestinal (GI) bleeding, hallucinations, photosensitivity reactions and severe cutaneous reactions (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) have occurred with other serotonin-norepinephrine reuptake inhibitors (SNRIs) or selective serotonin reuptake inhibitors (SSRIs)
Suicidal thoughts and behaviors in adolescents and young adults
Hyponatremia
Interstitial lung disease and eosinophilic pneumonia
Serotonin syndrome
Elevated blood pressure
Abnormal bleeding
Narrow-angle glaucoma
Activation of mania or hypomania
Discontinuance syndrome
Seizure
Postmarketing Reports
Angioedema
Pancreatitis acute
Warnings
Black box warnings
Antidepressants increase risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years) in short-term studies
Increased risk not observed in patients >24 years; slight decrease observed in patients >65 years
In children and young adults, initiate only if benefits greatly outweigh risks
Monitor closely for changes in behavior, clinical worsening, and suicidal tendencies during initial 1-2 months of therapy and dosage adjustments
Patient’s family should communicate any abrupt behavioral changes to healthcare provider
Worsening behavior and suicidal tendencies that are not part of presenting symptoms may necessitate discontinuance of therapy
Not approved for use in pediatric patients
Contraindications
Hypersensitivity
Coadministration with serotonergic drugs
- Coadministration with MAOIs increases risk of serotonin syndrome
- Use of MAOIs concomitantly within 14 days before initiating desvenlafaxine or within 7 days after discontinuing desvenlafaxine
- Symptoms include tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, hyperthermia with features resembling neuroleptic malignant syndrome (NMS), seizures, rigidity, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma
- Starting desvenlafaxine in patient being treated with linezolid or IV methylene blue is contraindicated because of increased risk of serotonin syndrome
- If linezolid or IV methylene blue must be administered, discontinue desvenlafaxine immediately and monitor for central nervous system (CNS) toxicity; therapy may be resumed 24 hours after last linezolid or methylene blue dose or after 2 weeks of monitoring, whichever comes first
Cautions
Suicidality; monitor for clinical worsening and suicide risk (especially in children, adolescents, and young adults aged 18-24 years), during early phases of treatment and alterations in dosages
Serotonin syndrome or NMS-like reactions may occur; discontinue and initiate supportive therapy; closely monitor patients concomitantly receiving triptans, antipsychotics, or serotonin precursors
Neonates exposed to SNRIs or SSRIs late in 3rd trimester of pregnancy have developed complications necessitating prolonged hospitalization, respiratory support, and tube feeding
Control hypertension before initiating treatment; monitor blood pressure regularly during treatment; if sustained hypertension is observed, consider dosage reduction or discontinuance
SSRIs and SNRIs may impair platelet aggregation and increase the risk of bleeding events, ranging from ecchymoses, hematomas, epistaxis, petechiae, and GI hemorrhage to life-threatening hemorrhage; concomitant use of aspirin, NSAIDs, warfarin, other anticoagulants, or other drugs known to affect platelet function may add to this risk
Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy
Seizure disorder
Screen patients for bipolar disorder; risk of mixed or manic episodes is increased in patients treated with antidepressants
Activation of mania or hypomania
Cardiovascular, cerebrovascular or lipid metabolism disorders; monitor patients who have history of or are at risk for these disorders
Monitor serum lipids periodically; risk of elevations in fasting serum total cholesterol, low-density lipoprotein (LDL) and triglycerides is increased
Hyponatremia due to syndrome of inappropriate antidiuretic hormone (SIADH); cases of serum sodium ≤110 mmol/L have been reported; monitor patients who are taking diuretics or at risk for volume depletion
Rare reports of interstitial lung disease and eosinophilic pneumonia; monitor patients for progressive dyspnea, cough, or chest discomfort
Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy
Dosages >50 mg/day offer no additional benefit but have worse adverse effects
Prescriptioin should be written for smallest quantity consistent with good patient care
May cause anxiety, nervousness, and insomnia
May impair congnitive abilities; use caution operating heavy machinery
Bone fractures reported with antidepressant treatment; consider possibility of fracture if antidepressant-treated patient presents with unexplained bone pain
May cause or exacerbate sexual dysfunction
Taper dose when possible and monitor for discontinuation symptoms
Pregnancy and lactation
Pregnancy category: C
Lactation: Drug is excreted in breast milk; discontinue drug, or do not nurse; use only if benefits greatly outweigh risks
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Pristiq, Khedezla (desvenlafaxine)
Mechanism of action
Potent SNRI; major active metabolite of venlafaxine
Absorption
Bioavailability: 80%
Peak plasma time: 7.5 hr
Distribution
Protein bound: 30%
Vd: 3.4 L/kg
Metabolism
Primary: Conjugation (UDP-glucuronosyltransferase isoform mediated)
Minor: CYP3A4 oxidative metabolism (N-demethylation)
Enzymes inhibited: CYP2D6 (minimally)
Elimination
Half-life: 11 hr (prolonged in renal or hepatic dysfunction)
Dialyzable: No
Excretion: Urine (69%)
