Venlaxine®37.5: Each scored tablet contains Venlafaxine (as HCl),37.5 mg.
Venlaxine®75: Each scored tablet contains Venlafaxine (as HCl),75 mg.
Actions and Pharmacokinetic:
Venlafaxine is a structurally novel antidepressant which is chemically unrelated to tricyclic, tetracyclic, or other available antidepressant agents. It is a racemate with two active enantiomers.
The mechanism of Venlafaxine's antidepressant action in humans is believed to be associated with its potentiation of neurotransmitter activity in the central nervous system. Preclinical studies have shown that venlafaxine and its major metabolite, Odesmethylvenlafaxine, are potent neuronal serotonin and noradrenaline re-uptake inhibitors (SNRI) and weak inhibitors of dopamine reuptake. In addition, venlafaxine and O-desmethylvenlafaxine reduce β-adrenergic responsiveness in animals after both acute (single dose) and chronic administration. Venlafaxine and its major metabolite appear to be equipotent with respect to their overall action on neurotransmitter reuptake.
Venlafaxine is well absorbed and undergoes extensive first-pass metabolism. Mean peak plasma concentrations of venlafaxine range from approximately 33 to 172ng/ml after 25 to 150mg single doses, and are reached in approximately 2.4 hours. Venlafaxine is extensively metabolised in the liver. O-desmethylvenlafaxine is the major active metabolite of venlafaxine. The mean disposition half-life of venlafaxine and O-desmethylvenlafaxine is approximately 5 and 11 hours, respectively. Mean peak O-desmethylvenlafaxine plasma concentrations range from approximately 61 to 325ng/ml and are reached in approximately 4.3 hours. Plasma concentrations of venlafaxine and O-desmethylvenlafaxine generally correlated well with dose levels.
Venlafaxine and O-desmethylvenlafaxine are 27% and 30% bound to plasma proteins respectively. O-desmethylvenlafaxine, other minor venlafaxine metabolites, and nonmetabolised venlafaxine are excreted primarily through the kidneys. 2
Venlafaxine is indicated for the treatment of depressive illness including depression accompanied by anxiety.
Following an initial response Venlafaxine is indicated for the prevention of relapses of the initial episode of depression or for the prevention of the recurrence of new episodes. 2
Hypersensitivity to venlafaxine hydrochloride or to any excipients in the formulation.
Concomitant use of monoamine oxidase inhibitors. 1
Venlafaxine should not be used in children and adolescents under the age of 18 years with Major Depressive Disorder.2
MAOI's: concomitant use contraindicated. Avoid MAOI's 14 days before starting venlafaxine and 7 days after stopping venlafaxine.
Cimetidine: Caution in patients with pre-existing hypertension, in elderly patients and patients with hepatic dysfunction.
Haloperidol: Increase in Haloperidol AUC and Cmax.
Ketoconazole: Increase in venlafaxine and O-desmethylvenlafaxine AUC and Cmax. Caution when using venlafaxine with substances that inhibit both CYP2D6 and CYP3A4.
Metoprolol: Possibly reduced blood-pressure lowering effect despite increased metoprolol plasma levels. Caution should be exercised with co-administration of venlafaxine and metoprolol.
CNS-active drugs: Caution when using venlafaxine with such drugs.
Serotonergic drugs (e.g., triptans, SSRIs, other SNRIs, linezolid, lithium, tramadol, or St. John's Wort): Potential for serotonin syndrome. Careful patient observation advised.
Tryptophan supplements: Concomitant use not recommended. 1
Warnings & Precautions:
Increased risk of suicidal thinking and behavior in children, adolescents and young adults taking antidepressants for major depressive disorder (MDD) and other psychiatric disorders.
Venlafaxine Tablets are not approved for use in pediatric patients.
Suicidality: Monitor for clinical worsening and suicide risk.
Monoamine Oxidase Inhibitors (MAOIs): Serious interactions possible. Concomitant use contraindicated. Avoidance of MAOIs recommended for at least 14 days before starting venlafaxine. A MAOI should not be started within 7 days after stopping venlafaxine.
Serotonin Syndrome, or Neuroleptic Malignant Syndrome (NMS)-like reactions: Serotonin syndrome or NMS-like reactions have been reported with SSRIs and SNRIs. Discontinue Venlafaxine extended-release tablets and initiate supportive treatment.
Sustained hypertension may occur. Blood pressure monitoring recommended.
Mydriasis may occur. Patients with raised intraocular pressure or those at risk of acute narrow-angle glaucoma should be monitored.
Abrupt discontinuation or dose reduction: Discontinuation symptoms may occur (generally self-limiting; serious symptoms possible). Dose reduction recommended to be gradual.
Activation of Mania/Hypomania has occurred.
Symptomatic hyponatremia may occur.
Seizures have been reported. Use with caution in patients with seizure history.
Abnormal bleeding (most commonly ecchymosis) has been reported.
Serum cholesterol: Clinically relevant cholesterol increases may occur. Cholesterol measurements should be considered during long-term therapy.
Interstitial lung disease and eosinophilic pneumonia have been reported. 1
Although venlafaxine has been shown not to affect psychomotor, cognitive, or complex behavior performance in healthy volunteers, any psychoactive drug may impair judgement, thinking or motor skills. Therefore patients should be cautioned about their ability to drive or operate hazardous machinery.2
Pregnancy Category C.2,3 Use during pregnancy only if clearly needed. Neonates exposed to venlafaxine in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Benefits and risk of venlafaxine use in the third trimester should be carefully considered.1
Potential for serious adverse reactions in the infant. Discontinue nursing or drug, considering the importance of the drug to the mother . 1
greater sensitivity of some older individuals cannot be ruled out. SSRIs and SNRIs, including Venlafaxine, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event. The pharmacokinetics of venlafaxine and ODV are not substantially altered in the elderly. No dose adjustment is recommended for the elderly on the basis of age alone, although other clinical circumstances, some of which may be more common in the elderly, such as renal or hepatic impairment, may warrant a dose reduction. 1
Safety and effectiveness in the pediatric population have not been established. 1
Major Depressive Disorder - Adverse events in short-term studies that occurred in at least 5% of the patients receiving venlafaxine and at a rate at least twice that of the placebo group were abnormal ejaculation, gastrointestinal complaints (nausea, dry mouth, and anorexia), CNS complaints (dizziness, somnolence, and abnormal dreams), and sweating.
Social Anxiety Disorder - Adverse events in short-term studies that occurred in at least 5% of the patients receiving venlafaxine at a rate at least twice that of the placebo group were asthenia, gastrointestinal complaints (anorexia, dry mouth, nausea), CNS complaints (anxiety, insomnia, libido decreased, nervousness, somnolence, dizziness), abnormalities of sexual function (abnormal ejaculation, orgasmic dysfunction, impotence), yawn, sweating, and abnormal vision. 1
Administration and Dosage:
Treatment with Venlafaxine should not be started until 14 days after discontinuing a monoamine oxidase inhibitor (MAOI).
The recommended dose is 75mg per day given in two divided doses (37.5mg twice daily). Most patients respond to this dose. It is recommended that venlafaxine tablets are taken with food. If, after an adequate trial and evaluation, further clinical improvement is required, the dose may be increased to 150mg per day given in two divided doses (75mg twice daily). There may be an increased risk of side effects at higher doses and dose increments should be made only after a clinical evaluation and after at least 3-4 weeks of therapy. The lowest effective dose should be maintained.
In more severely depressed or hospitalized patients, and under close supervision of a physician, the daily dose may then be increased by up to 75mg every two or three days until the desired response is achieved. In those more severely depressed and hospitalized patients who require daily doses of 300 mg or more, treatment should be initiated under specialist supervision including shared care arrangements. The maximum recommended dose is 375 mg per day. The dose should then be gradually reduced to the minimal effective dose, consistent with patient response and tolerance.
A limited amount of venlafaxine should be provided to reduce the risk from overdose.
Usually, the dosage for prevention of relapse or for prevention of recurrence of a new episode is similar to that used during the index episode. Patients should be re-assessed regularly in order to evaluate the benefit of long-term therapy. 2
Store at controlled room temperature under 30°C in a dry place. Keep out of sight and reach of children.1