Effexor

Effexor Information

Other Common Names: Efexor

Effexor XR is a prescription medication used to treat depression, generalized anxiety disorder, and social anxiety disorder, allowing you to get back to your life again. Effexor XR is an extended-release capsule for oral administration that contains venlafaxine hydrochloride, a structurally novel antidepressant.

Effexor XR is known as an Norepinephrine Reuptake Inhibitor">SNRI (serotonin and norepinephrine reuptake inhibitor) and is believed to help treat depression and the associated symptoms of anxiety by affecting the level of two chemicals in the brain-serotonin and norepinephrine. These two chemicals are thought to play a key role in depression and the associated symptoms of anxiety. Correcting the imbalance of these two chemicals may help relieve depression symptoms and the associated symptoms of anxiety-which can be a positive step toward getting your life back.

Venlafaxine hydrochloride is chemically unrelated to tricyclic, tetracyclic, and other available antidepressants and to other agents used to treat Generalized Anxiety Disorder.

Effexor XR is formulated as an extended-release capsule for once-a-day oral administration.

Drug release is controlled by diffusion through the coating membrane on the spheroids and is not pH dependent. Effexor capsules contain venlafaxine hydrochloride equivalent to 37.5 mg, 75 mg, or 150 mg venlafaxine. Inactive ingredients consist of cellulose, ethylcellulose, gelatin, hydroxypropyl methylcellulose, iron oxide, and titanium dioxide. The 37.5 mg capsule also contains D&C Red #28, D&C Yellow #10, and FD&C Blue #1.

Effexor Structural Formula and Composition

Contraindications to Effexor

Hypersensitivity to venlafaxine hydrochloride or to any excipients in the formulation.

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

Effexor Precautions and Contraindications

Before starting Effexor XR (venlafaxine HCl) Capsules, tell your doctor about any medicines you're taking, including over-the-counter drugs and herbal supplements. People taking MAO inhibitors should not take Effexor XR. Pregnant or nursing women shouldn't take any antidepressant without consulting their doctor. Side effects with Effexor XR may include anorexia, constipation, dizziness, dry mouth, ejaculation problems, impotence, insomnia, nausea, nervousness, sleepiness, sweating, and weakness. Effexor XR may raise blood pressure in some patients, so blood pressure should be monitored regularly. Effexor XR may impair judgment, thinking, or motor skills; patients should exercise caution until they have adapted to therapy. When people suddenly stop using or quickly lower their daily dose of Effexor XR, discontinuation symptoms may occur. Talk to your doctor before discontinuing or reducing your dose of Effexor XR. Ask your doctor if Effexor XR is right for you. Ask your doctor for additional information about Effexor XR.

Effexor Side Effects

Effexor Drug Interactions

Alcohol

Although venlafaxine has not been shown to increase the impairment of mental and motor skills caused by alcohol, patients should be advised to avoid alcohol while taking venlafaxine.

A single dose of ethanol (0.5 g/kg) had no effect on the pharmacokinetics of venlafaxine or O-desmethylvenlafaxine (ODV) when venlafaxine was administered at 150 mg/day in 15 healthy male subjects. Additionally, administration of venlafaxine in a stable regimen did not exaggerate the psychomotor and psychometric effects induced by ethanol in these same subjects when they were not receiving venlafaxine.

Allergic Reactions

Patients should be advised to notify their physician if they develop a rash, hives, or a related allergic phenomenon.

Pregnancy

Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy.

Cimetidine

Concomitant administration of cimetidine and venlafaxine in a steady-state study for both drugs resulted in inhibition of first-pass metabolism of venlafaxine in 18 healthy subjects. The oral clearance of venlafaxine was reduced by about 43%, and the exposure (AUC) and maximum concentration (Cmax) of the drug were increased by about 60%. However, co-administration of cimetidine had no apparent effect on the pharmacokinetics of ODV, which is present in much greater quantity in the circulation than venlafaxine. The overall pharmacological activity of venlafaxine plus ODV is expected to increase only slightly, and no dosage adjustment should be necessary for most normal adults. However, for patients with pre-existing hypertension, and for elderly patients or patients with hepatic dysfunction, the interaction associated with the concomitant use of venlafaxine and cimetidine is not known and potentially could be more pronounced. Therefore, caution is advised with such patients.

Diazepam

Under steady-state conditions for venlafaxine administered at 150 mg/day, a single 10 mg dose of diazepam did not appear to affect the pharmacokinetics of either venlafaxine or ODV in 18 healthy male subjects. Venlafaxine also did not have any effect on the pharmacokinetics of diazepam or its active metabolite, desmethyldiazepam, or affect the psychomotor and psychometric effects induced by diazepam.

Haloperidol

Venlafaxine administered under steady-state conditions at 150 mg/day in 24 healthy subjects decreased total oral-dose clearance (Cl/F) of a single 2 mg dose of haloperidol by 42%, which resulted in a 70% increase in haloperidol AUC. In addition, the haloperidol C_max increased 88% when coadministered with venlafaxine, but the haloperidol elimination half-life (t1/2) was unchanged. The mechanism explaining this finding is unknown.

Lithium

The steady-state pharmacokinetics of venlafaxine administered at 150 mg/day were not affected when a single 600 mg oral dose of lithium was administered to 12 healthy male subjects. ODV also was unaffected. Venlafaxine had no effect on the pharmacokinetics of lithium.

Drugs Highly Bound to Plasma Proteins

Venlafaxine is not highly bound to plasma proteins; therefore, administration of Effexor XR to a patient taking another drug that is highly protein bound should not cause increased free concentrations of the other drug.

Drugs that Inhibit Cytochrome P450 Isoenzymes

CYP2D6 Inhibitors: In vitro and in vivo studies indicate that venlafaxine is metabolized to its active metabolite, ODV, by CYP2D6, the isoenzyme that is responsible for the genetic polymorphism seen in the metabolism of many antidepressants. Therefore, the potential exists for a drug interaction between drugs that inhibit CYP2D6-mediated metabolism of venlafaxine, reducing the metabolism of venlafaxine to ODV, resulting in increased plasma concentrations of venlafaxine and decreased concentrations of the active metabolite. CYP2D6 inhibitors such as quinidine would be expected to do this, but the effect would be similar to what is seen in patients who are genetically CYP2D6 poor metabolizers. Therefore, no dosage adjustment is required when venlafaxine is coadministered with a CYP2D6 inhibitor.

The concomitant use of venlafaxine with drug treatment(s) that potentially inhibits both CYP2D6 and CYP3A4, the primary metabolizing enzymes for venlafaxine, has not been studied. Therefore, caution is advised should a patient's therapy include venlafaxine and any agent(s) that produce simultaneous inhibition of these two enzymes systems.

Drugs Metabolized by Cytochrome P450 Isoenzymes

CYP2D6: In vitro studies indicate that venlafaxine is a relatively weak inhibitor of CYP2D6. These findings have been confirmed in a clinical drug interaction study comparing the effect of venlafaxine with that of fluoxetine on the CYP2D6-mediated metabolism of dextromethorphan to dextrorphan.

Imipramine - Venlafaxine did not affect the pharmacokinetics of imipramine and 2-OH-imipramine. However, desipramine AUC,

C_max, and C_min increased by about 35% in the presence of venlafaxine. The 2-OH-desipramine AUC's increased by at least 2.5 fold (with venlafaxine 37.5 mg q12h) and by 4.5 fold (with venlafaxine 75 mg q12h). Imipramine did not affect the pharmacokinetics of venlafaxine and ODV. The clinical significance of elevated 2-OH-desipramine levels is unknown.

Risperidone

Venlafaxine administered under steady-state conditions at 150 mg/day slightly inhibited the CYP2D6-mediated metabolism of risperidone (administered as a single 1 mg oral dose) to its active metabolite, 9-hydroxyrisperidone, resulting in an approximate 32% increase in risperidone AUC. However, venlafaxine coadministration did not significantly alter the pharmacokinetic profile of the total active moiety (risperidone plus 9-hydroxyrisperidone.)

CYP3A4: Venlafaxine did not inhibit CYP3A4 in vitro. This finding was confirmed in vivo by clinical drug interaction studies in which venlafaxine did not inhibit the metabolism of several CYP3A4 substrates, including alprazolam, diazepam, and terfenadine.

Indinavir

In a study of 9 healthy volunteers, venlafaxine administered under steady-state conditions at 150 mg/day resulted in a 28% decrease in the AUC of a single 800 mg oral dose of indinavir and a 36% decrease in indinavir Cmax. Indinavir did not affect the pharmacokinetics of venlafaxine and ODV. The clinical significance of this finding is unknown.

CYP1A2: Venlafaxine did not inhibit CYP1A2 in vitro. This finding was confirmed in vivo by a clinical drug interaction study in which venlafaxine did not inhibit the metabolism of caffeine, a CYP1A2 substrate.

CYP2C9: Venlafaxine did not inhibit CYP2C9 in vitro. The clinical significance of this finding is unknown.

CYP2C19: Venlafaxine did not inhibit the metabolism of diazepam, which is partially metabolized by CYP2C19 (see Diazepam above.)

Taking Effexor during Pregnancy or Breast-feeding

Patients should be advised to notify their physician if they are breast-feeding an infant.

Teratogenic Effects - Pregnancy Category C

Venlafaxine did not cause malformations in offspring of rats or rabbits given doses up to 2.5 times (rat) or 4 times (rabbit) the maximum recommended human daily dose on a mg/m2 basis. However, in rats, there was a decrease in pup weight, an increase in stillborn pups, and an increase in pup deaths during the first 5 days of lactation, when dosing began during pregnancy and continued until weaning. The cause of these deaths is not known. These effects occurred at 2.5 times (mg/m2) the maximum human daily dose. The no effect dose for rat pup mortality was 0.25 times the human dose on a mg/m2 basis. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Non-teratogenic Effects

If venlafaxine is used until or shortly before birth, discontinuation effects in the newborn should be considered.

Labor and Delivery

The effect of venlafaxine on labor and delivery in humans is unknown.

Nursing Mothers

Venlafaxine and ODV have been reported to be excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from Effexor XR, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

How To Take Effexor and Effexor Dosage and Administration

Venlafaxine should be taken with food at doses specifically directed by a physician. Individual doses vary greatly among individuals. The anti-depressant effects are not maximal for 1-2 weeks. If discontinued, the dose of venlafaxine should gradually be reduced under the direction of a physician. For patients with difficulty swallowing tablets or capsules, capsules of Effexor XR can be opened and the contents sprinkled on a spoonful of applesauce.

Storing Effexor

Store in a dry place at 20-25°C (68-77°F).