Brand name
- Pr GD-Venlafaxine XR®
Drug Class
- Anti-Depressant
- Anxiolytic
Preparations
- Extended Release Capsules 37.5 Mg, 75 Mg and 150 Mg
Indications
- Depression
- Generalized Anxiety Disorder (GAD)
- Social Anxiety Disorder (Social Phobia)
- Panic Disorder
Pharmacology
- Inhibition of neuronal serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake
- Anticholinergic, sedative, and cardiovascular effects.
Metabolism
Absorption:
- Peak plasma concentrations: 6.0 ±1.5 hours
- Elimination half-life = absorption half-life: 15 ±6 hours
- No effect of food on the absorption
Distribution:
- Distributes beyond the total body water.
- Plasma Proteins Bindings: Venlafaxine (27%)
Metabolism:
- Extensive pre-systemic metabolism in the liver
- Absolute bioavailability: 45%
- Primary metabolite of venlafaxine: ODV(active metabolite)
Excretion:
- 87% in urine within 48 hours
- Primary route of excretion: kidney
Dosing
ADULT
1. Major Depressive Disorder (MDD)
- Recommended dose:
- 75 mg/day, once daily
- Initial dose:
- Start at 37.5 mg/day for 4-7 days >>> increase to 75 mg/day (Either morning or in the evening).
- Max dose:
- 225 mg/day, once daily
- Dosage increase: Intervals of 2 weeks or more, but not less than 4 days >>> Depends on tolerability and the need for further clinical effect.
- Maintenance Treatment:
- Dosage should be maintained at the lowest effective dose >>> periodically reassess the patient.
2. Generalized Anxiety Disorder (GAD)
- Recommended dose:
- 75 mg/day, once daily
- Initial dose:
- 37.5 mg/day, once daily for 4-7 days.
- Max dose:
- 225 mg/day, once daily
- Dosage increase: Intervals of not less than 4 days >>> Depends on tolerability and the need for further clinical effect.
- Maintenance Treatment:
- Dosage should be maintained at the lowest effective dose >>> periodically reassess the patient.
3. Social Anxiety Disorder (Social Phobia)
- Recommended dosage:
- 75 mg/day, once daily
- Initial dose:
- 75 mg/day, once daily
- For better adjustment: start at 37.5 mg/day for 4-7 days before increasing to 75 mg/day.
- Max dose:
- 225 mg/day, once daily
- Dosage increase:
- Intervals of not less than 4 days.
- Depends on tolerability and the need for further clinical effect.
- Maintenance Treatment:
- Dosage should be maintained at the lowest effective dose >>> periodically reassess the patient.
4. Panic Disorder:
- Recommended dosage:
- 75 mg/day, once daily
- Initial dose:
- 37.5 mg/day for 7 days before increasing to 75 mg/day
- Max dose:
- 225 mg/day, once daily
- Dosage increase: Intervals of at least 7 days.
- Maintenance Treatment:
- Dosage should be maintained at the lowest effective dose >>> periodically reassess the patient.
SPECIAL POPULATIONS
- Patients with Hepatic Impairment:
- Desirable start dosage: 37.5 mg/day
- Total daily dose must be reduced by more than 50%
- Patients with Renal Impairment: In patients undergoing hemodialysis:
- Total daily dose must be reduced by 50%
- Dose must be withheld until the dialysis treatment is completed (4 hrs).
- Desirable start dose: 37.5 mg/day.
Drug Interactions
- Monoamine Oxidase Inhibitors
- CNS-Active Drugs
- Serotonergic Drugs:
- Triptans (Almotriptan, Sumatriptan, Rizatriptan, Naratriptan, Zolmitriptan)
- Selective Serotonin reuptake inhibitor (SSRIs)
- Serotonin Norepinephrine reuptake inhibitor (SNRIs)
- Tricyclic Anti-Depressant (TCAs)
- Linezolid
- Lithium
- Sibutramine
- Fentanyl (and its analogues, dextromethorphan, tramadol, tapentadol, meperidine, methadone and pentazocine)
- Tryptophan supplements
- Drugs with serotonergic activity such as fenfluramine tryptophan and silbutramine
- Methylene blue
- St. John’s Wort
- Drugs that Prolong the QT Interval:
- Class IA anti-arrhythmics (e.g., quinidine, procainamide, disopyramide)
- Class III anti-arrhythmics (e.g., amiodarone, sotalol, ibutilide, dronedarone)
- Class 1C anti-arrhythmics (e.g., flecainide, propafenone)
- Antipsychotics (e.g., chlorpromazine, pimozide, haloperidol, droperidol, ziprasidone)
- Antidepressants (e.g., citalopram, fluoxetine, sertraline, tricyclic/tetracyclic antidepressants e.g., amitriptyline, imipramine, maprotiline)
- Opioids (e.g., methadone)
- Macrolide Antibiotics and Analogues (e.g., erythromycin, clarithromycin, telithromycin, tacrolimus)
- Quinolone Antibiotics (e.g., moxifloxacin, levofloxacin, ciprofloxacin)
- Anti-malarials (e.g., quinine, chloroquine)
- Azole Antifungals (e.g., ketoconazole, fluconazole, voriconazole)
- Domperidone
- 5-HT3 Receptor Antagonists (e.g., dolasetron, ondansetron)
- Tyrosine Kinase Inhibitors (e.g., vandetanib, sunitinib, nilotinib, lapatinib)
- Histone Deacetylase Inhibitors (e.g., vorinostat)
- Beta-2 Adrenoceptor Agonists (e.g., salmeterol, formoterol)
- Drugs that Affect Electrolytes:
- Loop diuretic (thiazide) & related diuretics
- laxatives and enemas
- amphotericin B
- high dose corticosteroids
- Alcohol
- Cimetidine
- Haloperidol
- Metoprolol
- Risperidone
- Ketoconazole
- Drugs Affecting Platelet Function (e.g. NSAIDS, ASA and other anticoagulants)
- Drugs Metabolized by Cytochrome P450 Isoenzymes
- Drugs that Inhibit Cytochrome P450 Isoenzymes
- Drug-Herb Interactions:
- St. John’s Wort
- Drug-Laboratory Test Interactions:
- phencyclidine (PCP) & amphetamine
Adverse Effects
FREQUENT:
- Palpitations, Chest pain
- Increased appetite
- Edema, serum cholesterol increase
- Hyperesthesia
- Pruritus
- Erectile dysfunction
- Headache
- Nausea
INFREQUENT:
- Lose weight
- Hypertension
- Impotence
- Paresthesia
- Tremor
- Vomiting
- Dry mouth
- Mydriasis
- Dyspepsia
- Abnormal vision
- Angioedema,
- Agranulocytosis
- Suicidal ideation
- Syncope
- Myasthenia
Contraindications
- Hypersensitivity
- Monoamine Oxidase Inhibitors (MAOIs)
Pregnancy and Breastfeeding
- Pregnancy: category C
- Lactation: not recommended for nursing mothers
Precautions
- Geriatrics (> 65 years of age):
- Caution in treating the elderly is advise
- Pediatrics (< 18 years of age):
- Not indicated for treating children under 18 years of age >>> Associated with Behavioral and Emotional Changes, Including Self-Harm (suicidality)
- Hepatic Impairment:
- Dosage adjustment is necessary.
- Renal Impairment:
- Dosage adjustment is necessary.
- Genetic Polymorphism:
- Plasma concentrations of venlafaxine is higher in poor metabolizers than extensive metabolizers >>> but no need for different dosing regimens.
- Discontinuing Venlafaxine
- Taper gradually to minimize the risk of discontinuation symptoms >>> No abrupt discontinuation:
- abrupt discontinuation symptoms: aggression, agitation, anorexia, anxiety, asthenia, confusion, convulsions, impaired coordination and balance, diarrhea, dizziness, dry mouth, dysphoric mood, fasciculation, fatigue, flu-like symptoms, headache, hypomania, insomnia, nausea, nightmares, nervousness, paresthesia, electric shock sensations, sensory disturbances (including shock like electrical sensations), sleep disturbances, somnolence, sweating, tinnitus, vertigo, and vomiting.
- Caution in switching Patients to or from a Monoamine Oxidase Inhibitor:
- At least 14 days should elapse between discontinuation or initiation
- Caution in switching Patients from Immediate Release Tablets:
- They can switch to GD-venlafaxine XR at the nearest equivalent dose
- Individual dosage adjustments may be necessary.
- Each capsule should be swallowed whole with water and food.
- Should not be divided, crushed, and chewed.
- Missed Dose:
- Should not be made up for it by doubling up on the dose next time >>> Next dose should be taken as scheduled.
- Overdose:
- Symptoms: paresthesia, sleepiness, dizziness, nausea, hot-cold spells.
- Overdose Management:
- General measures: Provide adequate airway, oxygenation, and ventilation, monitor cardiac rhythm and vital signs
- Gastric lavage:
- Indicated soon after ingestion,
- Symptomatic patients.
- Activated charcoal
- Antidote: No specific antidotes
- CNS-Active Drugs:
- caution is advised.
- Serotonergic Drugs:
- caution is advised for serotonin syndrome, in co-administering with other drugs
- Drugs that Prolong the QT Interval:
- caution in concomitant use
- Drugs that Affect Electrolytes:
- Concomitant use is discouraged
- Alcohol:
- Psychomotor impairment in combination use >>> avoid alcohol while taking venlafaxine.
- Cimetidine:
- Caution is advised in:
- pre-existing hypertension,
- elderly,
- hepatic or renal dysfunction.
- Caution is advised in:
- Haloperidol, Metoprolol, Risperidone, Ketoconazole:
- caution in concomitant use >>> Dosage adjustment is needed.
- Drugs Affecting Platelet Function (NSAIDS, ASA and other anticoagulants):
- caution in concomitant use >>> Dosage adjustment is needed.
- Warfarin:
- should be carefully monitored when GD-venlafaxine XR is initiated/ discontinued >>> Caution in concomitant use >>> Dosage adjustment is needed.
- Drugs Metabolized by Cytochrome P450 Isoenzymes(dextromethorphan):
- Caution in concurrent usage
- Drugs that Inhibit Cytochrome P450 Isoenzymes (enzyme inhibitor effects):
- Caution in concurrent usage
- Drug-Herb Interactions:
- St. John’s Wort >>> caution for serotonin syndrome
- Drug-Laboratory Test Interactions:
- False-positive urine tests for phencyclidine (PCP) and amphetamine:
- Expected for several days following discontinuation of venlafaxine therapy.
- Confirmatory tests for distinguishing is required.
- Interference with Cognitive and Motor Performance:
- Patients should be cautioned about operating hazardous machinery, avoid driving
- Drug Abuse:
- Caution of usage in patients with history of drug abuse
Section
This document is prepared by the “Mental Health for All” team. This document is provided for information purposes only and does not necessarily represent endorsement by or an official position of the Essentials of Medicine. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient’s medical history.