Venlafaxine Hydrochloride
The exact mechanism of action of venlafaxine is unknown, but appears to be associated with the its potentiation of neurotransmitter activity in the CNS. Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), inhibit the reuptake of both serotonin and norepinephrine with a potency greater for the 5-HT than for the NE reuptake process. Both venlafaxine and the ODV metabolite have weak inhibitory effects on the reuptake of dopamine but, unlike the tricyclics and similar to SSRIs, they are not active at histaminergic, muscarinic, or alpha(1)-adrenergic receptors.
Initial Treatment: The recommended starting dose for venlafaxine tablets is 75 mg/day, administered in two or three divided doses, taken with food. Depending on tolerability and the need for further clinical effect, the dose may be increased to 150 mg/day. If needed, the dose should be further increased up to 225 mg/day. When increasing the dose, increments of up to 75 mg/day should be made at intervals of no less than 4 days. In outpatient settings there was no evidence of usefulness of doses greater than 225 mg/day for moderately depressed patients, but more severely depressed inpatients responded to a mean dose of 350 mg/day. Certain patients, including more severely depressed patients, may therefore respond more to higher doses, up to a maximum of 375 mg/day, generally in three divided dosesDosage For Elderly Patients: No dose adjustment is recommended for elderly patients on the basis of age. As with any antidepressant, however, caution should be exercised in treating the elderly. When individualizing the dosage, extra care should be taken when increasing the dose.Maintenance Treatment: It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacological therapy beyond response to the acute episode. In one study, in which patients responding during 8 weeks of acute treatment with venlafaxine hydrochloride extendedrelease capsules were assigned randomly to placebo or to the same dose of venlafaxine hydrochloride extended-release capsules (75, 150, or 225 mg/day, qAM) during 26 weeks of maintenance treatment as they had received during the acute stabilization phase, longer-term efficacy was demonstrated. A second longer-term study has demonstrated the efficacy of venlafaxine tablets in maintaining an antidepressant response in patients with recurrent depression who had responded and continued to be improved during an initial 26 weeks of treatment and were then randomly assigned to placebo or venlafaxine tablets for periods of up to 52 weeks on the same dose (100 to 200 mg/day, on a b.i.d. schedule) (see Clinical Trials). Based on these limited data, it is not known whether or not the dose of venlafaxine tablets / extended-release capsules needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment.Discontinuing Venlafaxine Tablet: Symptoms associated with discontinuation of venlafaxine tablets, other SNRIs, and SSRIs, have been reported. Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate.
Increased risk of serotonin syndrome with TCA, SSRI, SNRI, lithium, sibutramine, tramadol. May increase serum levels with CYP3A4 inhibitors (e.g. ketoconazole, atazanavir, clarithromycin). May increase serum levels of haloperidol. May decrease serum levels of indinavir. May increase bleeding risk with aspirin, NSAIDs, warfarin and other anticoagulants.
Concomitant use with MAOIs or within 14 days of discontinuing the MAOI. Use with linezolid or IV methylene blue.
Changes in behaviour, suicidal ideation, agitation, tremor, nervousness, anxiety, insomnia, confusions, abnormal dreams, HTN, nausea, headache, asthenia, somnolence, dizziness, dry mouth, vomiting, constipation, diarrhoea, dyspepsia, abdominal pain, anorexia, sexual dysfunction, urinary frequency, visual disturbances, mydriasis, vasodilatation, paraesthesia, hypertonia, chills or fever, palpitations, wt gain or loss, arthralgia, myalgia, tinnitus, pruritus, dyspnoea, yawning, rashes, sweating, increased serum cholesterol, may impair platelet aggregation.
Treatment Of Pregnant Women During The Third TrimesterNeonates exposed to venlafaxine tablets, USP, other SNRIs, or SSRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. When treating pregnant women with venlafaxine tablets during the third trimester, the physician should carefully consider the potential risks and benefits of treatment.
History of MI or unstable cardiac disease, seizure; hypomania or mania, increased intraocular pressure or at risk of acute narrow-angle galaucoma, at risk of bleeding. Renal and hepatic impairment. Gradual dose reduction is recommended rather than abrupt withdrawal. Pregnancy and lactation. Patient Counselling May impair ability to drive or operate machinery.
Symptoms: Sweating, dizziness, somnolence, mydriasis, convulsions, vomiting, ECG changes, cardiac arrhythmias and seizures.Management: Symptomatic and supportive treatment. Ensure adequate airway, oxygenation and ventilation. Initiate gastric lavage immediately after ingestion. Admin activated charcoal to reduce absorption. Monitor cardiac rhythm and vital signs.
Serotonin-norepinephrine reuptake inhibitor (SNRI)
Store between 20-25° C.
Dosage For Patients With Hepatic Impairment: Given the decrease in clearance and increase in elimination half-life for both venlafaxine and ODV that is observed in patients with hepatic cirrhosis and mild and moderate hepatic impairment compared to normal subjects, it is recommended that the total daily dose be reduced by 50% in patients with mild to moderate hepatic impairment. Since there was much individual variability in clearance between subjects with cirrhosis, it may be necessary to reduce the dose even more than 50%, and individualization of dosing may be desirable in some patients.Dosage For Patients With Renal Impairment: Given the decrease in clearance for venlafaxine and the increase in elimination half-life for both venlafaxine and ODV that is observed in patients with renal impairment (GFR = 10 to 70 mL/min) compared to normals, it is recommended that the total daily dose be reduced by 25% in patients with mild to moderate renal impairment. It is recommended that the total daily dose be reduced by 50% in patients undergoing hemodialysis. Since there was much individual variability in clearance between patients with renal impairment, individualization of dosing may be desirable in some patients.
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