Venlafaxine

Brand Names: Effexor, Effexor XR

Description

Venlafaxine is an antidepressant used to treat depression.

The mechanism of the antidepressant action of venlafaxine in humans is believed to be associated with its potentiation of neurotransmitter activity in the CNS. Preclinical studies have shown that venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), are potent inhibitors of neuronal serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake.

Steady-state concentrations of both venlafaxine and ODV in plasma were attained within 3 days of multiple-dose therapy.

You may have to take venlafaxine for 4 weeks or longer before you begin to feel better. Also, you will probably need to keep taking this medicine for at least 6 months, even if you feel better, to help prevent your depression from returning. Your doctor should check your progress at regular visits during this time.

Indications and Usage

Venlafaxine is indicated for the treatment of depression.

Contraindications

Venlafaxine HCl is contraindicated in patients known to be hypersensitive to it.

Concomitant use in patients taking monoamine oxidase inhibitors (MAOIs) is contraindicated

Warnings

POTENTIAL FOR INTERACTION WITH MONOAMINE OXIDASE INHIBITORS

Adverse reactions, some of which were serious, have been reported in patients who have recently been discontinued from a monoamine oxidase inhibitor (MAOI) and stated on venlafaxine HCl, or who have recently had venlafaxine HCl therapy discontinued prior to initiation of an MAOI. These reactions have included tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, hyperthermia with features resembling neuroleptic malignant syndrome, seizures, and death. In patients receiving antidepressants with pharmacological properties similar to venlafaxine in combination with a monoamine oxidase inhibitor, there have also been reports of serious, sometimes fatal, reactions. For a selective serotonin reuptake inhibitor, these reactions have included hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma. Some cases presented with featured resembling neuroleptic malignant syndrome. Severe hyperthermia and seizures, sometimes fatal, have been reported in association with the combined use of tricyclic antidepressants and MAOIs. These reactions have also been reported in patients who have recently discontinued these drugs and have been started on an MAOI. Therefore, it is recommended that venlafaxine HCl not be used in combination with an MAOI, or within at least 14 days of discontinuing treatment with an MAOI. Based on the half-life of venlafaxine HCl, at least 7 days should be allowed after stopping venlafaxine HCl before starting an MAOI.

Sustained Hypertension: Venlafaxine treatment is associated with sustained increases in blood pressure. Therefore, it is recommended that patients receiving venlafaxine have regular monitoring of blood pressure. For patients who experience a sustained increase in blood pressure while receiving venlafaxine, either dose reduction or discontinuation should be considered.

Precautions

Suicide: The possibility of a suicide attempt in seriously depressed patients is inherent to the illness and may persist until significant remission occurs. Close supervision of high-risk patients should accompany initial drug therapy, and consideration should be given to the need for hospitalization. In order to reduce the risk of overdose, prescriptions for venlafaxine should be written for the smallest quantity of tablets consistent with good patient management.

Anxiety and Insomnia: Treatment-emergent anxiety, nervousness, and insomnia were more commonly reported for venlafaxine-treated patients.

Changes in Appetite and Weight: Treatment-emergent anorexia was more commonly reported for venlafaxine-treated (11%) than placebo-treated patients (2%) in the pool of short-term, double-blind, placebo-controlled depression studies. A dose-dependent weight loss was often noted in patients treated with venlafaxine for several weeks. Significant weight loss, especially in underweight depressed patients, may be an undesirable result of venlafaxine treatment. A loss of 5% or more of body weight occurred in 6% of patients treated with venlafaxine compared with 1% of patients treated with placebo and 3% of patients treated with another antidepressant.

Activation of Mania/Hypomania: During phase 2-3 trials, hypomania or mania occurred in 0.5% of patients treated with venlafaxine. Activation of mania/hypomania has also been reported in a small proportion of patients with major affective disorder who were treated with other marketed antidepressants. As with all antidepressants, venlafaxine should be used cautiously in patients with a history of mania.

Seizures: During premarketing testing, seizures were reported in 0.26% (8/3082) of venlafaxine-treated patients. Most seizures (5 of 8) occurred in patients receiving doses of 150 mg/day or less. Venlafaxine HCl should be used cautiously in patients with a history of seizures. It should be discontinued in any patient who develops seizures.

Use in Patients With Concomitant Illness: Clinical experience with venlafaxine in patients with concomitant systemic illness is limited. Caution is advised in administering venlafaxine to patients with diseases or conditions that could affect hemodynamic responses or metabolism. Venlafaxine has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease.

Pregnancy & Nursing: There are no adequate and well controlled studies with venlafaxine in pregnant women. Therefore, venlafaxine should only be used during pregnancy if clearly needed and women should not nurse their child.

Usage in Children: Safety and efficacy in children below the age of 18 have not been established.

Interference with Cognitive or Motor Performance: Any psychoactive drug may impair judgment, thinking, or motor skills. Patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that venlafaxine therapy does not adversely affect their ability to engage in such activities.

Drug Interactions

As with all drugs, the potential for interaction by a variety of mechanisms is a possibility.

BEFORE USING THIS MEDICINE: INFORM YOUR DOCTOR OR PHARMACIST of all prescription and over-the-counter medicine that you are taking. This includes monoamine oxidase inhibitors (MAOIs), cyproheptadine, selegiline, lithium, fenfluramine, dexfenfluramine, and tramadol. Inform your doctor of any other medical conditions, allergies, pregnancy, or breast-feeding.

CNS-Active Drugs: The risk of using venlafaxine in combination with other CNS-active drugs has not been systematically evaluated. Consequently, caution is advised if the concomitant administration of venlafaxine and such drugs is required.

Adverse Reactions

Side effects, that may go away during treatment, include drowsiness, dizziness, weakness, nausea, decreased appetite, dry mouth, constipation, change in sexual function, increased sweating, nervousness, or tremor. If they continue or are bothersome, check with your doctor.

CHECK WITH YOUR DOCTOR AS SOON AS POSSIBLE if you experience continuing headache, blurred vision, or continued weight loss. If you notice any unusual effects, contact your doctor, nurse, or pharmacist.

Other side effects include: Chest pain; feeling of fast or irregular heartbeat; mood or mental changes; ringing or buzzing in ears

Rare: Convulsions (seizures); lightheadedness or fainting; lockjaw; menstrual changes; swelling of feet or lower legs; talking, feeling, and acting with excitement and activity you cannot control; trouble in breathing

Physical/Psychological Dependence:
Venlafaxine is not a controlled substance.

There was no indication of addiction behavior in the clinical trials. However, it is not possible to predict on the basis of pre-marketing experience the extent to which a CNS active drug will be misused, diverted, and/or abused once marketed. Consequently, physicians should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of venlafaxine (e.g., development of tolerance, incrimination of dose, drug-seeking behavior).

Overdose

Signs and Symptoms

There were 14 reports of acute overdose with venlafaxine HCl, either alone or in combination with other drugs and/or alcohol, among the patients included in the pre-marketing evaluation.

Most patients reported no symptoms. Among the remaining patients, somnolence was the most commonly reported symptom.

Symptoms of overdose may include sleepiness, irregular heartbeat, and seizures.

Treatment

If you or someone you know may have used more than the recommended dose of this medicine, contact your local poison control center or emergency room immediately.

Treatment should consist of those general measures employed in the management of overdosage with any antidepressant. Ensure an adequate airway, oxygenation, and ventilation. Monitoring of cardiac rhythm and vital signs is recommended. General supportive and symptomatic measures are also recommended. Use of activated charcoal, induction of emesis, or gastric lavage should be considered. No specific antidotes for venlafaxine are known.

Dosage

Do not exceed the recommended dosage or take this medicine for longer than prescribed. Do not stop taking this medicine without first checking with your doctor. Continue to take this medicine even if you feel better. Do not miss any doses.

Follow the directions for using this medicine provided by your doctor.
Take this medicine with food.
Store this medicine at room temperature, away from heat and light.
If you miss a dose of this medicine, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Additional Information: Do not share this medicine with others for whom it was not prescribed. Do not use this medicine for other health conditions. Keep this medicine out of the reach of children.

IF YOU WILL BE USING THIS MEDICINE FOR AN EXTENDED PERIOD OF TIME, be sure to obtain the necessary refills before your supply runs out.

Children: This medication is not recommended for children up to 18 years of age.

For oral extended-release capsule dosage form:

Adults: At first, 75 milligrams (mg) a day, taken in one dose in the morning or evening. Your doctor may increase your dose if needed. However, the dose is usually not more than 225 mg a day.

For oral tablet dosage form:

Adults: At first, a total of 75 mg a day, taken in smaller doses two or three times during the day. Your doctor may increase your dose if needed. However, the dose is usually not more than 375 mg a day.

Patients With Hepatic Impairment: In patients with hepatic cirrhosis, it is recommended that the total daily dose be reduced by about 50% in patients with moderate hepatic impairment. It may be necessary to reduce the dose even more than 50%, and individualization of dosing may be desirable in some patients.

Patients with Renal Impairment: It is recommended that the total daily dose be decreased by 25% in patients with mild to moderate renal impairment. It is recommended that the total daily dose be reduced by 50% and the dose be withheld until the dialysis treatment is completed (4 hrs) in patients undergoing hemodialysis. Since there was so much individual variability in clearance between patients with renal impairment, individualization of dosing may be desirable in some patients.

Discontinuing Venlafaxine: When venlafaxine therapy that has been administered for more than 1 week is stopped, it is generally recommended that the dose be tapered gradually to minimize the risk of discontinuation symptoms. Patients who have received venlafaxine for 6 weeks or more should have their dose tapered gradually over a 2-week period.

How Supplied

Effexor (venlafaxine HCl tablets) is available in bottles of 100 tablets and in Redipak cartons of 100 tablets (10 blister strips of 10) in the following dosage strengths (expressed in equivalent amounts of venlafaxine):

venlafaxine hydrochloride equivalent to 25 mg, 37.5 mg, 50 mg, 75 mg, or 100 mg venlafaxine.

The information in this monograph is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects. This information is generalized and is not intended as specific medical advice. If you have questions about the medicines you are taking or would like more information, check with your doctor, pharmacist, or nurse.