Desvenlafaxine Succinate
Pronunciation: (des-VEN-la-FAX-een SUX-i-nate)Class: Serotonin and norepinephrine reuptake inhibitor
Trade Names:
Pristiq
- Tablets, extended-release 50 mg
- Tablets, extended-release 100 mg
Pharmacology
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 User Reviews & Ratings
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Potentiates serotonin and norepinephrine in the CNS.
Pharmacokinetics
Absorption
Absolute bioavailability after oral administration is about 80%. T max is about 7.5 h.
Distribution
Plasma protein binding is about 30%. Vd at steady state following IV administration is 3.4 L/kg, indicating distribution into nonvascular compartment.
Metabolism
Primarily by conjugation (UGT isoforms) and to a lesser extent through oxidative metabolism (CYP3A4).
Elimination
After oral administration, about 45% is excreted unchanged in the urine within 72 h, approximately 19% excreted as the glucuronide and less than 5% as the oxidative metabolites. Mean t ½ is 11 h.
Special Populations
Renal Function ImpairmentElimination is correlated with CrCl. The AUC increases about 42% in mild renal function impairment, about 56% in moderate renal function impairment, about 108% in severe renal function impairment, and about 116% in end-stage renal disease (ESRD), compared with healthy subjects. The mean terminal t ½ is prolonged from 11.1 h in control subjects to about 13.5, 15.5, 17.6, and 22.8 h in mild, moderate, severe, and ESRD, respectively. Less than 5% of the drug is cleared during standard 4-h hemodialysis.
Hepatic Function ImpairmentAverage AUC is increased by about 31% and 35% in patients with moderate and severe hepatic function impairment, respectively, compared with healthy subjects. Average AUC is similar in subjects with mild hepatic function impairment compared with healthy subjects. Cl is decreased about 20% and 36% in patients with moderate and severe hepatic function impairment compared with healthy subjects. Cl is comparable in mild hepatic function impairment and healthy subjects. The mean t ½ increased from 10 h in healthy subjects to 13 and 14 h in patients with moderate and severe hepatic function impairment, respectively. No dosage adjustment is needed in the starting dose for patients with hepatic function impairment.
ElderlyThere is an increase in the AUC and C max of about 55% and 32%, respectively, in patients older than 75 yr of age, compared with subjects 18 to 45 yr of age. Patients 65 to 75 yr of age had a 32% increase in AUC but no change in C max , compared with patients 18 to 45 yr of age.
GenderThere is an increase in the AUC and C max of about 10% and 25%, respectively, in women compared with men; however, no dosage adjustment is needed.
RaceRace has no apparent effect on pharmacokinetics.
Indications and Usage
Treatment of major depressive disorder (MDD)
Contraindications
Concomitant use with MAOIs; hypersensitivity to any component of the product.
Dosage and Administration
AdultsPO 50 mg once daily. No benefit has been demonstrated at doses greater than 50 mg/day.
Renal function impairmentAdults
PO
Mild renal function impairment (CrCl = 50 to 80 mL/min)No dosage adjustment is needed.
Moderate renal function impairment (CrCl = 30 to 50 mL/min)50 mg/day.
Severe renal function impairment (CrCl less than 30 mL/min) or ESRD50 mg every other day.
DialysisDo not give supplemental doses.
General Advice
- Can be taken without regard to meals.
- When discontinuing therapy, gradually reduce the dose.
- Tablets should be swallowed whole with fluid and not divided, crushed, chewed, or dissolved.
Storage/Stability
Store at 59° to 86°F.
Drug Interactions
Aspirin, NSAIDs, warfarinRisk of bleeding may be increased.
CNS-active agents, serotonergic drugs (eg, fluoxetine)Coadminister with caution. Risk of life-threatening serotonin syndrome may be increased.
CYP3A4 inhibitors (eg, ketoconazole)Desvenlafaxine plasma concentrations may be elevated.
Drugs metabolized by CYP2D6 (eg, desipramine)Plasma concentrations may be elevated by desvenlafaxine.
Drugs metabolized by CYP3A4 (eg, midazolam)Plasma concentrations may be decreased by desvenlafaxine.
MAOIsSerious, even fatal reactions may occur. Do not use desvenlafaxine with MAOIs or within 14 days of MAOI use. Allow at least 7 days after stopping desvenlafaxine before starting MAOIs.
Laboratory Test Interactions
None well documented.
Adverse Reactions
Cardiovascular
Palpitations (3%); hot flush, increased BP, tachycardia (2%); orthostatic hypotension, syncope (less than 2%).
CNS
Headache (29%); dizziness (16%); insomnia (15%); somnolence (12%); fatigue (11%); tremor (9%); decreased libido in men (6%); anxiety (5%); abnormal dreams (4%); paresthesia (3%); asthenia, disturbance in attention, irritability, nervousness (2%); convulsion, depersonalization, extrapyramidal disorder, hypomania (less than 2%).
Dermatologic
Hyperhidrosis (21%); rash (2%).
EENT
Mydriasis (6%); blurred vision (4%); dysgeusia, tinnitus (2%); epistaxis (less than 2%).
GI
Nausea (41%); dry mouth (25%); constipation (14%); diarrhea (11%); vomiting (9%).
Genitourinary
Erectile dysfunction (11%); anorgasmia (men, 8%; women, 3%); proteinuria (8%); delayed ejaculation (7%); ejaculation disorder (5%); abnormal orgasm in men (3%); ejaculation failure, sexual dysfunction, urinary hesitation (2%).
Hypersensitivity
Hypersensitivity (less than 2%).
Lab Tests
Increased total cholesterol (10%); increased fasting triglycerides (6%); increased LDL (2%); abnormal liver function, increased blood prolactin (less than 2%).
Metabolic-Nutritional
Decreased appetite (10%); decreased weight (2%).
Respiratory
Yawning (4%).
Miscellaneous
Chills (4%); feeling jittery (3%).
Precautions
WarningsIncreased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants for MDD and other psychiatric disorders. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. |
MonitorClosely observe patient for clinical worsening, suicidality, or unusual changes in behavior during initial few months of therapy or when increasing or decreasing the dose. Monitor patients with elevated intraocular pressure or acute narrow-angle glaucoma. Consider monitoring serum lipids. Monitor blood pressure regularly. |
Pregnancy
Category C.
Lactation
Excreted in breast milk.
Children
Safety and efficacy not established.
Renal Function
Dosage adjustment is recommended in patients with impaired renal function.
Hepatic Function
No dosage adjustment in starting dosage is needed in patients with hepatic function impairment.
Abnormal bleeding
Risk of bleeding events, ranging from ecchymosis to life-threatening hemorrhages, may be increased.
Discontinuation of treatment
When discontinuing treatment, a gradual reduction in dose rather than abruptly stopping therapy is recommended.
Hypertension
Sustained increases in BP may occur. Preexisting hypertension should be controlled before starting treatment. Use with caution in patients with CV disease, or cerebrovascular or preexisting hypertension.
Hyponatremia
Hyponatremia as a result of SIADH may occur. Elderly patients and patients taking diuretics or who are otherwise volume depleted may be at increased risk.
Interstitial lung disease and eosinophilic pneumonia
Because these conditions have been associated with venlafaxine, the parent drug of desvenlafaxine, consider the possibility that these adverse reactions may occur.
Mania/Hypomania
Activation of mania/hypomania has been reported. Use with caution in patients with a history of mania or hypomania.
Narrow-angle glaucoma
Mydriasis may occur.
Seizure
Use with caution in patients with a history of seizure disorder.
Serotonin syndrome
Potentially life-threatening serotonin syndrome, including mental status changes, may occur.
Serum cholesterol and triglyceride elevations
Dose-related elevations in fasting serum total cholesterol, LDL cholesterol, and triglycerides may occur. Use with caution in patients with lipid metabolism disorders.
Venlafaxine-containing drugs
Desvenlafaxine is the active metabolite of venlafaxine. Do not coadminister drugs containing venlafaxine.
Overdosage
Symptoms
Agitation, constipation, diarrhea, dizziness, dry mouth, headache, nausea, paresthesia, tachycardia, vomiting.
Patient Information
- Advise patients to look for emergence of suicidality, especially early during treatment and when the dose is increased or decreased.
- Advise patients to observe for signs of activation of mania/hypermania.
- Advise patients not to stop taking desvenlafaxine without talking to their health care provider.
- Caution patients about driving or operating hazardous machinery until they are certain that their ability to engage in such activities is not impaired.
- Advise patients to notify health care provider if they develop allergic reactions, such as rash, hives, swelling, or difficulty breathing.
- Advise patients that if they miss a dose to take it as soon as they remember. If it is almost time for the next dose, skip the missed dose. Do not take 2 doses at the same time to make up for the missed dose.
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