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Venlafaxine Hydrochloride

FDA Drug Information • Also known as: Effexor Xr, Venlafaxine, Venlafaxine Hydrochloride, Venlafaxine Hydrochloride Er

Brand Names
Effexor Xr, Venlafaxine, Venlafaxine Hydrochloride, Venlafaxine Hydrochloride Er
Route
ORAL
Dosage Form
CAPSULE, EXTENDED RELEASE
Product Type
HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increased the risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and emergence of suicidal thoughts and behaviors [see Warnings and Precautions (5.1) ] . Venlafaxine hydrochloride extended-release capsules are not approved for use in pediatric patient s [see Use in Specific Populations (8.4) ] . WARNING: SUICIDAL THOUGHTS AND BEHAVIORS See full prescribing information for complete boxed warning. Increased risk of suicidal thoughts and behavior in pediatric patients and young adults taking antidepressants. Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors ( 5.1 ). Venlafaxine hydrochloride extended-release capsules are not approved for use in pediatric patients ( 8.4 ).

Description

11 DESCRIPTION Venlafaxine Hydrochloride Extended-Release Capsules, USP are an extended-release capsule for once-a-day oral administration that contains venlafaxine hydrochloride, a serotonin and norepinephrine reuptake inhibitor (SNRI). Venlafaxine is designated (R/S)-1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl] cyclohexanol hydrochloride or (±)-1-[α-[(dimethylamino)methyl]-p-methoxybenzyl] cyclohexanol hydrochloride and has the empirical formula of C 17 H 27 NO 2 HCl. Its molecular weight is 313.86. The structural formula is shown as follows: Venlafaxine hydrochloride is a white to off-white crystalline solid, with a solubility of 572 mg/mL in water (adjusted to ionic strength of 0.2 M with sodium chloride). Its octanol: water (0.2 M sodium chloride) partition coefficient is 0.43. Drug release is controlled by diffusion through the coating membrane on the spheroids and is not pH-dependent. Capsules contain venlafaxine hydrochloride equivalent to 37.5 mg, 75 mg, or 150 mg venlafaxine. Inactive ingredients consist of empty hard gelatin capsules, ethylcellulose, hypromellose, povidone, sugar spheres (composed of corn starch and sucrose) and talc. The 37.5 mg capsule shell contains red iron oxide, gelatin, and titanium dioxide. The 75 mg capsule shell contains black iron oxide, red iron oxide, gelatin, and titanium dioxide. The 150 mg capsule shell contains FD&C blue 1, FD&C red 3, FD&C yellow 6, gelatin, and titanium dioxide. The imprinting ink contains black iron oxide, potassium hydroxide and shellac. FDA approved dissolution test specifications differ from USP.

What Is Venlafaxine Hydrochloride Used For?

1 INDICATIONS AND USAGE Venlafaxine Hydrochloride Extended-Release Capsules, USP are indicated in adults for the treatment of: Major Depressive Disorder (MDD) [see Clinical Studies (14.1) ] Generalized Anxiety Disorder (GAD) [see Clinical Studies (14.2) ] Social Anxiety Disorder (SAD) [see Clinical Studies (14.3) ] Panic Disorder (PD) [see Clinical Studies (14.4) ] Venlafaxine hydrochloride extended-release capsules are a serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for the treatment of adults with: Major Depressive Disorder (MDD) ( 1 ) Generalized Anxiety Disorder (GAD) ( 1 ) Social Anxiety Disorder (SAD) ( 1 ) Panic Disorder (PD) ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Indication Starting Dose Target Dose Maximum Dose MDD ( 2.2 ) 37.5 to 75 mg/day 75 mg/day 225 mg/day GAD ( 2.3 ) 37.5 to75 mg/day 75 mg/day 225 mg/day SAD ( 2.4 ) 75 mg/day 75 mg/day 75 mg/day PD ( 2.5 ) 37.5 mg/day 75 mg/day 225 mg/day Take once daily with food. Capsules should be taken whole; do not divide, crush, chew, or dissolve ( 2.1 ). When discontinuing treatment, reduce the dose gradually ( 2.10 , 5.7 ). Renal impairment: reduce the total daily dose by 25% to 50% in patients with renal impairment. Reduce the total daily dose by 50% or more in patients undergoing dialysis or with severe renal impairment ( 2.9 ). Hepatic impairment: reduce the daily dose by 50% in patients with mild to moderate hepatic impairment. In patients with severe hepatic impairment or hepatic cirrhosis, it may be necessary to reduce the dose by more than 50% ( 2.8 ). 2.1 General Administration Information Administer venlafaxine hydrochloride extended-release capsules as a single dose with food, either in the morning or in the evening at approximately the same time each day [see Clinical Pharmacology (12.3) ] . Swallow capsules whole with fluid. Do not divide, crush, chew, or place in water. The capsule may also be administered by carefully opening the capsule and sprinkling the entire contents on a spoonful of applesauce. This drug/food mixture should be swallowed immediately without chewing and followed with a glass of water to ensure complete swallowing of the pellets (spheroids). 2.2 Major Depressive Disorder For most patients, the recommended starting dose for venlafaxine hydrochloride extended-release capsules is 75 mg per day, administered in a single dose. For some patients, it may be desirable to start at 37.5 mg per day for 4 to 7 days to allow new patients to adjust to the medication before increasing to 75 mg per day. Patients not responding to the initial 75 mg per day dose may benefit from dose increases to a maximum of 225 mg per day. Dose increases should be in increments of up to 75 mg per day, as needed, and should be made at intervals of not less than 4 days. In the clinical studies establishing efficacy, upward titration was permitted at intervals of 2 weeks or more. 2.3 Generalized Anxiety Disorder For most patients, the recommended starting dose for venlafaxine hydrochloride extended-release capsules is 75 mg per day, administered in a single dose. For some patients, it may be desirable to start at 37.5 mg per day for 4 to 7 days to allow new patients to adjust to the medication before increasing to 75 mg per day. Patients not responding to the initial 75 mg per day dose may benefit from dose increases to a maximum of 225 mg per day. Dose increases should be in increments of up to 75 mg per day, as needed, and should be made at intervals of not less than 4 days. 2.4 Social Anxiety Disorder (Social Phobia) The recommended dose is 75 mg per day, administered in a single dose. There was no evidence that higher doses...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling: Hypersensitivity [see Contraindications (4) ] Suicidal Thoughts and Behaviors in Adolescents and Young Adults [see Warnings and Precautions (5.1) ] Serotonin Syndrome [see Warnings and Precautions (5.2) ] Elevated Blood Pressure [see Warnings and Precautions (5.3) ] Increased Risk of Bleeding [see Warnings and Precautions (5.4) ] Angle-Closure Glaucoma [see Warnings and Precautions (5.5) ] Activation of Mania/Hypomania [see Warnings and Precautions (5.6) ] Discontinuation Syndrome [see Warnings and Precautions (5.7) ] Seizure [see Warnings and Precautions (5.8) ] Hyponatremia [see Warnings and Precautions (5.9) ] Weight and Height Changes in Pediatric Patients [see Warnings and Precautions (5.10) ] Appetite Changes in Pediatric Patients [see Warnings and Precautions (5.11) ] Interstitial Lung Disease and Eosinophilic Pneumonia [see Warnings and Precautions (5.12) ] Sexual Dysfunction [see Warnings and Precautions (5.13) ] Most common adverse reactions (incidence ≥5% and at least twice the rate of placebo): nausea, somnolence, dry mouth, sweating, abnormal ejaculation, anorexia, constipation, impotence (men), and libido decreased ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Epic Pharma, LLC at 1-888-374-2791 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice. Most Common Adverse Reactions The most commonly observed adverse reactions in the clinical study database in venlafaxine hydrochloride extended-release capsules treated patients in MDD, GAD, SAD, and PD (incidence ≥5% and at least twice the rate of placebo) were: nausea (30.0%), somnolence (15.3%), dry mouth (14.8%), sweating (11.4%), abnormal ejaculation (9.9%), anorexia (9.8%), constipation (9.3%), impotence (5.3%), and decreased libido (5.1%). Adverse Reactions Reported as Reasons for Discontinuation of Treatment Combined across short-term, placebo-controlled premarketing studies for all indications, 12% of the 3,558 patients who received venlafaxine hydrochloride extended-release capsules (37.5 to 225 mg) discontinued treatment due to an adverse experience, compared with 4% of the 2,197 placebo-treated patients in those studies. The most common adverse reactions leading to discontinuation in ≥1% of the venlafaxine hydrochloride extended-release capsules treated patients in the short-term studies (up to 12 weeks) across indications are shown in Table 7. Table 7: Incidence (%) of Patients Reporting Adverse Reactions Leading to Discontinuation in Placebo-controlled Clinical Studies (up to 12 Weeks Duration) Body System Adverse Reaction Venlafaxine Hydrochloride Extended-Release Capsules n = 3,558 Placebo n = 2,197 Body as a whole Asthenia 1.7 0.5 Headache 1.5 0.8 Digestive system Nausea 4.3 0.4 Nervous system Dizziness 2.2 0.8 Insomnia 2.1 0.6 Somnolence 1.7 0.3 Skin and appendages 1.5 0.6 Sweating 1.0 0.2 Common Adverse Reactions in Placebo-controlled Studies The number of patients receiving multiple doses of venlafaxine hydrochloride extended-release capsules during the premarketing assessment for each approved indication is shown in Table 8. The conditions and duration of exposure to venlafaxine in all development programs varied greatly, and included (in overlapping categories) open and double-blind studies, uncontrolled and controlled studies, inpatient (venlafaxine hydrochloride tablets only) and outpatient studies, fixed-dose, and titration studies. Table 8: Patients Receiving Venlafaxine Hydrochloride Extended-Release Capsules in Premarketing Clinical Studies Indication Venlafaxine Hydrochloride Extended-Release Capsules MDD 705 a GAD 1,381...

Drug Interactions

7 DRUG INTERACTIONS 7.1 Drugs Having Clinically Important Interactions with Venlafaxine Hydrochloride Extended-Release Capsules Table 15: Clinically Important Drug Interactions with Venlafaxine Hydrochloride Extended-Release Capsules Monoamine Oxidase Inhibitors (MAOI) Clinical Impact The concomitant use of SNRIs, including venlafaxine hydrochloride extended-release capsules, with MAOIs increases the risk of serotonin syndrome. Intervention Concomitant use of venlafaxine hydrochloride extended-release capsules is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [see Dosage and Administration (2.11) , Contraindications (4) and Warnings and Precautions (5.2) ]. Other Serotonergic Drugs Clinical Impact Concomitant use of venlafaxine hydrochloride extended-release capsules with other serotonergic drugs (including other SNRIs, SSRIs, triptans, tricyclic antidepressants, opioids, lithium, buspirone, amphetamines, tryptophan, and St. John's Wort) increases the risk of serotonin syndrome. Intervention Monitor for symptoms of serotonin syndrome when venlafaxine hydrochloride extended-release capsules is used concomitantly with other drugs that may affect the serotonergic neurotransmitter systems. If serotonin syndrome occurs, consider discontinuation of venlafaxine hydrochloride extended-release capsules and/or concomitant serotonergic drugs [see Dosage and Administration (2.11) and Warnings and Precautions (5.2) ]. Drugs that Interfere with Hemostasis Clinical Impact Concomitant use of venlafaxine hydrochloride extended-release capsules with an antiplatelet or anticoagulant drug may potentiate the risk of bleeding. This may be due to the effect of venlafaxine hydrochloride extended-release capsules on the release of serotonin by platelets. Intervention Closely monitor for bleeding for patients receiving an antiplatelet or anticoagulant drug when venlafaxine hydrochloride extended-release capsules are initiated or discontinued [see Warnings and Precautions (5.4) ] . Effect of CYP3A Inhibitors Clinical Impact Concomitant use of a CYP3A inhibitor increases the C max and AUC of venlafaxine and O-desmethylvenlafaxine (ODV) [see Clinical Pharmacology (12.3) ] , which may increase the risk of toxicity of venlafaxine hydrochloride extended-release capsules. Intervention Consider reducing the dose of venlafaxine hydrochloride extended-release capsules. CYP2D6 Substrates Clinical Impact Concomitant use of venlafaxine hydrochloride extended-release capsules increases C max and AUC of a CYP2D6 substrate, which may increase the risk of toxicity of the CYP2D6 substrate [see Clinical Pharmacology (12.3) ] . Intervention Consider reduction in dose of concomitant CYP2D6 substrates. 7.2 Other Drug Interactions with Venlafaxine Hydrochloride Extended-Release Capsules Central Nervous System (CNS)-Active Drugs The risk of using venlafaxine concomitantly with other CNS-active drugs (including alcohol) has not been...

Contraindications

4 CONTRAINDICATIONS Venlafaxine Hydrochloride Extended-Release Capsules are contraindicated in patients: with known hypersensitivity to venlafaxine hydrochloride, desvenlafaxine succinate or to any excipients in the formulation [see Adverse Reactions (6.2) ] . taking, or within 14 days of stopping, MAOIs (including the MAOIs linezolid and intravenous methylene blue) because of the risk of serotonin syndrome [see Dosage and Administration (2.11) , Warnings and Precautions (5.2) , and Drug Interactions (7.1) ] . Hypersensitivity to venlafaxine hydrochloride, desvenlafaxine succinate, or any excipients in the venlafaxine hydrochloride extended-release capsules formulation ( 4 ). Concomitant use of monoaminoxidase inhibitors (MAOIs) or within 14 days of discontinuing an MAOI ( 4 , 5.2 , 7.1 ).

Pregnancy and Breastfeeding

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants, including venlafaxine hydrochloride extended-release capsules, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/ . Risk Summary Based on data from published observational studies, exposure to SNRIs, particularly in the month before delivery, has been associated with a less than 2-fold increase in the risk of postpartum hemorrhage [see Warnings and Precautions (5.4) and Clinical Considerations ] . Available data from published epidemiologic studies on venlafaxine use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or adverse fetal outcomes (see Data ) . Available data from observational studies with venlafaxine have identified a potential increased risk for preeclampsia when used during mid to late pregnancy; exposure to SNRIs near delivery may increase the risk for postpartum hemorrhage (see Clinical Considerations ) . There are risks associated with untreated depression in pregnancy and poor neonatal adaptation in newborns with exposure to SNRIs, including venlafaxine hydrochloride extended-release capsules, during pregnancy (see Clinical Considerations ) . In animal studies, there was no evidence of malformations or fetotoxicity following administration of venlafaxine during organogenesis at doses up to 2.5 times (rat) or 4 times (rabbit) the maximum recommended human daily dose on a mg/m 2 basis. Postnatal mortality and decreased pup weights were observed following venlafaxine administration to pregnant rats during gestation and lactation at 2.5 times (mg/m 2 ) the maximum human daily dose. The estimated background risk of major birth defects...

Overdosage

10 OVERDOSAGE Human Experience During the premarketing evaluations of venlafaxine hydrochloride extended-release capsules (for MDD, GAD, SAD, and PD) and venlafaxine hydrochloride tablets (for MDD), there were twenty reports of acute overdosage with venlafaxine hydrochloride tablets (6 and 14 reports in venlafaxine hydrochloride extended-release capsules and venlafaxine hydrochloride tablets patients, respectively), either alone or in combination with other drugs and/or alcohol. Somnolence was the most commonly reported symptom. Among the other reported symptoms were paresthesia of all four limbs, moderate dizziness, nausea, numb hands and feet, and hot-cold spells 5 days after the overdose. In most cases, no signs or symptoms were associated with overdose. The majority of the reports involved ingestion in which the total dose of venlafaxine taken was estimated to be no more than several-fold higher than the usual therapeutic dose. One patient who ingested 2.75 g of venlafaxine was observed to have two generalized convulsions and a prolongation of QTc to 500 msec, compared with 405 msec at baseline. Mild sinus tachycardia was reported in two of the other patients. Actions taken to treat the overdose included no treatment, hospitalization and symptomatic treatment, and hospitalization plus treatment with activated charcoal. All patients recovered. In postmarketing experience, overdose with venlafaxine has occurred predominantly in combination with alcohol and/or other drugs. The most commonly reported events in overdosage include tachycardia, changes in level of consciousness (ranging from somnolence to coma), mydriasis, seizures, and vomiting. Electrocardiogram changes (e.g., prolongation of QT interval, bundle branch block, QRS prolongation), ventricular tachycardia, bradycardia, hypotension, rhabdomyolysis, vertigo, liver necrosis, serotonin syndrome, and death have been reported. Published retrospective studies report that venlafaxine overdosage may be...

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Venlafaxine Hydrochloride Extended-Release Capsules, USP are available as follows: 75 mg capsules, opaque light grey cap and opaque flesh body, imprinted with "YH" on cap and "129" on body in black ink. NDC: 71335-2421-1: 90 Capsules in a BOTTLE NDC: 71335-2421-2: 60 Capsules in a BOTTLE NDC: 71335-2421-3: 30 Capsules in a BOTTLE NDC: 71335-2421-4: 100 Capsules in a BOTTLE NDC: 71335-2421-5: 7 Capsules in a BOTTLE Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Keep out of the reach of children. Repackaged/Relabeled by: Bryant Ranch Prepack Burbank, CA 91504

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.