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Venlafaxine Hydrochloride is a brand name for Venlafaxine. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 1 INDICATIONS AND USAGE Venlafaxine extended-release tablets are a selective serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for: Major Depressive Disorder (MDD) ( 1.1 ) Social Anxiety Disorder (SAD) ( 1.2 ) 1.1 Major Depressive Disorder Venlafaxine extended-release tablets are indicated for the…
Verbatim from this product's FDA label. Tap a section to expand.
2 DOSAGE AND ADMINISTRATION Venlafaxine extended-release tablets should be administered in a single dose with food either in the morning or in the evening at approximately the same time each day. Each tablet should be swallowed whole with fluid and not divided, crushed, chewed, or placed in water.
5 mg/day for 4-7 days) 75 mg/day increments at intervals of 4 days or longer 225 mg/day Social Anxiety Disorder 75 mg/day No benefit at higher doses 75 mg/day Venlafaxine extended-release tablets should be taken as a single daily dose with food in either the morning or evening at the same time each day.
( 2 ) Discontinuation: Gradual; individualized as necessary. 1 Initial Treatment Major Depressive Disorder For most patients, the recommended starting dose for venlafaxine extended-release tablets is 75 mg/day, administered in a single dose.
In the clinical trials establishing the efficacy of venlafaxine hydrochloride extended-release capsules in moderately depressed outpatients, the initial dose of venlafaxine was 75 mg/day. 5 mg/day for 4 to 7 days to allow new patients to adjust to the medication before increasing to 75 mg/day.
While the relationship between dose and antidepressant response for venlafaxine hydrochloride extended-release capsules has not been adequately explored, patients not responding to the initial 75 mg/day dose may benefit from dose increases to a maximum of approximately 225 mg/day.
Dose increases should be in increments of up to 75 mg/day, as needed, and should be made at intervals of not less than 4 days, since steady state plasma levels of venlafaxine and its major metabolites are achieved in most patients by day 4.
In the clinical trials establishing efficacy, upward titration was permitted at intervals of 2 weeks or more; the average doses were about 140 to 180 mg/day [ see Clinical Studies ( 14 ) ]. It should be noted that, while the maximum recommended dose for moderately depressed outpatients is also 225 mg/day for venlafaxine hydrochloride immediate-release tablets, more severely depressed inpatients in one study of the development program for that product responded to a mean dose of 350 mg/day (range of 150 to 375 mg/day).
Whether or not higher doses of venlafaxine extended-release tablets are needed for more severely depressed patients is unknown; however, the experience with venlafaxine hydrochloride extended-release capsule doses higher than 225 mg/day is very limited .
6 ADVERSE REACTIONS Major Depressive Disorder - Adverse events in short-term studies that occurred in at least 5% of the patients receiving venlafaxine extended-release capsules 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 extended-release capsules and 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.
TO REPORT SUSPECTED ADVERSE REACTIONS, CONTACT RISING PHARMA HOLDINGS, INC. GOV/MEDWATCH . S. trials and one European trial), and on data up to 12 weeks from a pool of two controlled clinical trials in Social Anxiety Disorder. Information on additional adverse reactions associated with venlafaxine hydrochloride extended-release capsules in the entire development program for the formulation and with venlafaxine hydrochloride immediate-release tablets is included in the subsection "Other Adverse Reactions Observed During the Premarketing Evaluation of Venlafaxine Hydrochloride Immediate-Release Tablets and Venlafaxine Hydrochloride Extended-Release Capsules" [ see also Warnings and Precautions ( 5 ) ].
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 trials of another drug and may not reflect the rates observed in practice.
Adverse Findings Observed in Short-Term, Placebo-Controlled Studies with Venlafaxine Hydrochloride Extended-Release Capsules Adverse Reactions Associated with Discontinuation of Treatment Major Depressive Disorder : Approximately 11% of the 357 patients who received venlafaxine hydrochloride extended-release capsules in placebo-controlled clinical trials for major depressive disorder discontinued treatment due to an adverse reaction, compared with 6% of the 285 placebo-treated patients in those studies.
5 WARNINGS AND PRECAUTIONS Serotonin Syndrome : Serotonin syndrome has been reported with SSRIs and SNRIs, including venlafaxine extended-release tablets, both when taken alone, but especially when co-administered with other serotonergic agents.
If such symptoms occur, discontinue venlafaxine extended-release tablets and serotonergic agents and initiate supportive treatment. If concomitant use of venlafaxine extended-release tablets and serotonergic agents with other serotonergic drugs is clinically warranted, patients should be made aware of a potential increased risk for serotonin syndrome, particularly during treatment initiation and dose increases.
2 ) Suicidality: Monitor for clinical worsening and suicide risk. 1 ) Sustained hypertension may occur. Blood pressure monitoring recommended. 3 ) Angle Closure Glaucoma: Angle closure glaucoma has occurred in patients with untreated anatomically narrow angles treated with antidepressants.
4 ) Abrupt discontinuation or dose reduction: Discontinuation symptoms may occur (generally self-limiting; serious symptoms possible). Dose reduction recommended to be gradual. 5 ) Activation of Mania/Hypomania has occurred. 10 ) Symptomatic hyponatremia may occur.
11 ) Seizures have been reported. Use with caution in patients with seizure history. 12 ) Abnormal bleeding (most commonly ecchymosis) has been reported. 13 ) Serum cholesterol: Clinically relevant cholesterol increases may occur. Cholesterol measurements should be considered during long-term therapy.
14 ) Interstitial lung disease and eosinophilic pneumonia have been reported. 15 ) Sexual Dysfunction: Venlafaxine extended-release tablets may cause symptoms of sexual dysfunction. 1 Clinical Worsening and Suicide Risk Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs.
4 CONTRAINDICATIONS Serotonin Syndrome and MAOIs: Do not use MAOI’s intended to treat psychiatric disorders with venlafaxine extended-release tablets or within 7 days of stopping treatment with venlafaxine extended-release tablets.
Do not use venlafaxine extended-release tablets within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start venlafaxine extended-release tablets in a patient who is being treated with linezolid or intravenous methylene blue.
1 Monoamine Oxidase Inhibitors (MAOIs) The use of MAOI’s intended to treat psychiatric disorders with venlafaxine extended-release tablets or within 7 days of stopping treatment with venlafaxine extended-release tablets is contraindicated because of an increased risk of serotonin syndrome.
2 ) ]. 2 ) ].
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Social Anxiety Disorder (Social Phobia) The recommended dose is 75 mg/day, administered in a single dose. There was no evidence that higher doses confer any additional benefit . 2 Maintenance Treatment There is no body of evidence available from controlled trials to indicate how long patients with major depressive disorder should be treated with venlafaxine extended-release tablets.
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 extended-release capsules were assigned randomly to placebo or to the same dose of venlafaxine hydrochloride extended-release capsules (75, 150, or 225 mg per day, qAM) during 26 weeks of maintenance treatment as they had received during the acute stabilization phase, longer-term efficacy was demonstrated.
d. schedule)[ see Clinical Studies ( 14 ) ]. Based on these limited data, it is not known whether or not the dose of venlafaxine extended-release tablets 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. 1 ) ]. When treating pregnant women with venlafaxine extended-release tablets during the third trimester, the physician should carefully consider the potential risks and benefits of treatment.
3 ) ], 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 patients with cirrhosis, it may be necessary to reduce the dose even more than 50%, and individualization of dosing may be desirable in some patients.
3 ) ], it is recommended that the total daily dose be reduced by 25% to 50%. In patients undergoing hemodialysis, it is recommended that the total daily dose be reduced by 50%. Because there was much individual variability in clearance between patients with renal impairment, individualization of dosage may be desirable in some patients.
Elderly Patients No dose adjustment is recommended for elderly patients solely on the basis of age. As with any drug for the treatment of major depressive disorder or Social Anxiety Disorder, however, caution should be exercised in treating the elderly.
When individualizing the dosage, extra care should be taken when increasing the dose. 5 ) ]. 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.
In clinical trials with venlafaxine hydrochloride extended-release capsules, tapering was achieved by reducing the daily dose by 75 mg at 1 week intervals. Individualization of tapering may be necessary. 5 mg venlafaxine two-times-a-day to 75 mg venlafaxine extended-release tablets once daily.
However, individual dosage adjustments may be necessary. 6 Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with venlafaxine extended-release tablets.
1 ) ]. 7 Use of Venlafaxine Extended-Release Tablets with Other MAOIs, Such as Linezolid or Methylene Blue Do not start venlafaxine extended-release tablets in a patient who is being treated with linezolid or intravenous methylene blue because there is increased risk of serotonin syndrome.
1 ) ]. In some cases, a patient already receiving venlafaxine extended-release tablets therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, venlafaxine extended-release tablets should be stopped promptly, and linezolid or intravenous methylene blue can be administered.
The patient should be monitored for symptoms of serotonin syndrome for 7 days or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. 2 ) ]. The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with venlafaxine extended-release tablets is unclear.
2 ) ].
Adverse reactions that led to treatment discontinuation in a least 2% of drug-treated patients were nausea, dizziness, and somnolence.
Social Anxiety Disorder :
Approximately 17% of the 277 patients who received venlafaxine hydrochloride extended-release capsules in placebo-controlled clinical trials for Social Anxiety Disorder discontinued treatment due to an adverse reaction, compared with 5% of the 274 placebo-treated patients in those studies.
Adverse reactions that led to treatment discontinuation in a least 2% of drug-treated patients were nausea, insomnia, impotence, headache, dizziness, and somnolence. Adverse Reactions Occurring at an Incidence of 5% or More Major Depressive Disorder : Note in particular the following adverse reactions that occurred in at least 5% of the patients receiving venlafaxine hydrochloride extended-release capsules and at a rate at least twice that of the placebo group for all placebo-controlled trials for the major depressive disorder indication (see Table 6): Abnormal ejaculation, gastrointestinal complaints (nausea, dry mouth, and anorexia), CNS complaints (dizziness, somnolence, and abnormal dreams), and sweating.
S. placebo-controlled trials, the following additional reactions occurred in at least 5% of patients treated with venlafaxine hydrochloride extended-release capsules (n=192) and at a rate at least twice that of the placebo group: Abnormalities of sexual function (impotence in men, anorgasmia in women, and libido decreased), gastrointestinal complaints (constipation and flatulence), CNS complaints (insomnia, nervousness, and tremor), problems of special senses (abnormal vision), cardiovascular effects (hypertension and vasodilatation), and yawning.
Social Anxiety Disorder :
Note in particular the following adverse reactions that occurred in at least 5% of the patients receiving venlafaxine hydrochloride extended-release capsules and at a rate at least twice that of the placebo group for the 2 placebo-controlled trials for the Social Anxiety Disorder indication (see Table 7): Asthenia, gastrointestinal complaints (anorexia, constipation, dry mouth, nausea), CNS complaints (dizziness, insomnia, libido decreased, nervousness, somnolence), abnormalities of sexual function (abnormal ejaculation, impotence, libido decreased, orgasmic dysfunction), yawn, sweating, and abnormal vision.
Adverse Reactions Occurring at an Incidence of 2% or More Among Patients Treated with Venlafaxine Hydrochloride Extended-Release Capsules Tables 6 and 7 enumerate the incidence, rounded to the nearest percent, of adverse reactions that occurred during acute therapy of major depressive disorder (up to 12 weeks; dose range of 75 to 225 mg/day) and of Social Anxiety Disorder (up to 12 weeks; dose range of 75 to 225 mg/day), respectively, in 2% or more of patients treated with venlafaxine hydrochloride extended-release capsules where the incidence in patients treated with venlafaxine hydrochloride extended-release capsules was greater than the incidence for the respective placebo-treated patients.
The table shows the percentage of patients in each group who had at least one episode of a reaction at some time during their treatment. Reported adverse reactions were classified using a standard COSTART-based Dictionary terminology.
The prescriber should be aware that these figures cannot be used to predict the incidence of adverse reactions in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials.
Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the adverse reaction incidence rate in the population studied.
Table 6 Treatment-Emergent Adverse Reaction Incidence in Short-Term Placebo-Controlled Clinical Trials with Venlafaxine Hydrochloride Extended-Release Capsules in Patients with Major Depressive Disorder 1,2 % Reporting Reaction Body System Preferred Term Venlafaxine Hydrochloride Extended-Release Capsules Placebo (n = 357) (n = 285) Body as a Whole Asthenia 8% 7% Cardiovascular System Vasodilatation 3 4% 2% Hypertension 4% 1% Digestive System Nausea 31% 12% Constipation 8% 5% Anorexia 8% 4% Vomiting 4% 2% Flatulence 4% 3% Metabolic/Nutritional Weight Loss 3% 0% Nervous System Dizziness 20% 9% Somnolence 17% 8% Insomnia 17% 11% Dry Mouth 12% 6% Nervousness 10% 5% Abnormal Dreams 4 7% 2% Tremor 5% 2% Depression 3% <1% Paresthesia 3% 1% Libido Decreased 3% <1% Agitation 3% 1% Respiratory System Pharyngitis 7% 6% Yawn 3% 0% Skin Sweating 14% 3% Special Senses Abnormal Vision 5 4% <1% Urogenital System Abnormal Ejaculation (male) 6,7 16% <1% Impotence 7 4% <1% Anorgasmia (female) 8,9 3% <1% 1 Incidence, rounded to the nearest %, for reactions reported by at least 2% of patients treated with venlafaxine hydrochloride extended-release capsules, except for reactions which had an incidence equal to or less than placebo.
2 <1% indicates an incidence greater than zero but less than 1%. ” 7 Incidence is based on the number of male patients. ” 9 Incidence is based on the number of female patients. Table 7 Treatment-Emergent Adverse Reaction Incidence in Short-Term Placebo-Controlled Clinical Trials with Venlafaxine Hydrochloride Extended-Release Capsules in Social Anxiety Disorder Patients 1,2 % Reporting Reaction Body System Preferred Term Venlafaxine Hydrochloride Extended-Release Capsules (n = 277) Placebo (n = 274) Body as a Whole Headache 34% 33% Asthenia 17% 8% Flu Syndrome 6% 5% Accidental Injury 5% 3% Abdominal Pain 4% 3% Cardiovascular System Hypertension 5% 4% Vasodilatation 3 3% 1% Palpitation 3% 1% Digestive System Nausea 29% 9% Anorexia 4 20% 1% Constipation 8% 4% Diarrhea 6% 5% Vomiting 3% 2% Eructation 2% 0% Metabolic/Nutritional Weight Loss 4% 0% Nervous System Insomnia 23% 7% Dry Mouth 17% 4% Dizziness 16% 8% Somnolence 16% 8% Nervousness 11% 3% Libido Decreased 9% <1% Anxiety 5% 3% Agitation 4% 1% Tremor 4% <1% Abnormal Dreams 5 4% <1% Paraesthesia 3% <1% Twitching 2% 0% Respiratory System Yawn 5% <1% Sinusitis 2% 1% Skin Sweating 13% 2% Special Senses Abnormal Vision 6 6% 3% Urogenital System Abnormal Ejaculation 7,8 16% 1% Impotence 8 10% 1% Orgasmic Dysfunction 9,10 8% 0% 1 Adverse reactions for which the venlafaxine hydrochloride extended-release capsules reporting rate was less than or equal to the placebo rate are not included.
2 <1% means greater than zero but less than 1%. ” 8 Percentage based on the number of males (venlafaxine hydrochloride extended-release capsules = 158, placebo = 153). ” 10 Percentage based on the number of females (venlafaxine hydrochloride extended-release capsules = 119, placebo = 121).
Vital Sign Changes Treatment with venlafaxine hydrochloride extended-release capsules treatment for up to 12 weeks in premarketing placebo-controlled major depressive disorder trials was associated with a mean final on-therapy increase in pulse rate of approximately 2 beats per minute, compared with 1 beat per minute for placebo.
Treatment with venlafaxine hydrochloride extended-release capsules for up to 12 weeks in premarketing placebo-controlled Social Anxiety Disorder trials was associated with a mean final on-therapy increase in pulse rate of approximately 4 beats per minute, compared with an increase of 1 beat per minute for placebo.
3 ) for effects on blood pressure. ] In a flexible-dose study in MDD, with doses of venlafaxine hydrochloride immediate-release tablets in the range of 200 to 375 mg/day and mean dose greater than 300 mg/day, the mean pulse was increased by about 2 beats per minute compared with a decrease of about 1 beat per minute for placebo.
4 mg/dL for placebo. 9 mg/dL for placebo. 1 mg/dL among placebo-treated patients. This increase was duration dependent over the study period and tended to be greater with higher doses. 14 ) ]. 4 mg/dl for placebo. 16 ) ]. Other Adverse Reactions Observed During the Premarketing Evaluation of Venlafaxine Hydrochloride Immediate-Release Tablets and Venlafaxine Hydrochloride Extended-Release Capsules During its premarketing assessment, multiple doses of venlafaxine hydrochloride extended-release capsules were administered to 705 patients in Phase 3 major depressive disorder studies and venlafaxine hydrochloride immediate-release tablets was administered to 96 patients.
During its premarketing assessment, multiple doses of venlafaxine hydrochloride extended-release capsules were also administered to 3514 patients in other Phase 3 studies. In addition, in premarketing assessment of venlafaxine hydrochloride immediate-release tablets, multiple doses were administered to 2897 patients in Phase 2 to Phase 3 studies for major depressive disorder.
The conditions and duration of exposure to venlafaxine in both development programs varied greatly, and included (in overlapping categories) open and double-blind studies, uncontrolled and controlled studies, inpatient (venlafaxine hydrochloride immediate-release tablets only) and outpatient studies, fixed-dose, and titration studies.
Adverse reactions associated with this exposure were recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse reactions without first grouping similar types of untoward events into a smaller number of standardized reaction categories.
In the tabulations that follow, reported adverse reactions were classified using a standard COSTART-based Dictionary terminology. The frequencies presented, therefore, represent the proportion of the 7212 patients exposed to multiple doses of either formulation of venlafaxine who experienced a reaction of the type cited on at least one occasion while receiving venlafaxine.
All reported reactions are included except those already listed in Tables 6 and 7 and those reactions for which a drug cause was remote. If the COSTART term for a reaction was so general as to be uninformative, it was replaced with a more informative term.
It is important to emphasize that, although the reactions reported occurred during treatment with venlafaxine, they were not necessarily caused by it. Reactions are further categorized by body system and listed in order of decreasing frequency using the following definitions: frequent adverse reactions are defined as those occurring on one or more occasions in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1000 patients; rare reactions are those occurring in fewer than 1/1000 patients.
Body as a whole - Frequent : chest pain substernal, chills, fever, neck pain; Infrequent : face edema, intentional injury, malaise, moniliasis, neck rigidity, pelvic pain, photosensitivity reaction, suicide attempt, withdrawal syndrome; Rare : appendicitis, bacteremia, cellulitis, granuloma.
Cardiovascular system - Frequent : migraine, tachycardia; Infrequent : angina pectoris, bradycardia, extrasystoles, hypotension, peripheral vascular disorder (mainly cold feet and/or cold hands), postural hypotension, syncope; Rare : aortic aneurysm, arteritis, first-degree atrioventricular block, bigeminy, bundle branch block, capillary fragility, cerebral ischemia, coronary artery disease, congestive heart failure, heart arrest, hematoma, cardiovascular disorder (mitral valve and circulatory disturbance), mucocutaneous hemorrhage, myocardial infarct, pallor, sinus arrhythmia, thrombophlebitis.
Digestive system - Frequent : increased appetite; Infrequent : bruxism, colitis, dysphagia, tongue edema, eructation, esophagitis, gastritis, gastroenteritis, gastrointestinal ulcer, gingivitis, glossitis, rectal hemorrhage, hemorrhoids, melena, oral moniliasis, stomatitis, mouth ulceration; Rare : abdominal distension, biliary pain, cheilitis, cholecystitis, cholelithiasis, esophageal spasms, duodenitis, hematemesis, gastroesophageal reflux disease, gastrointestinal hemorrhage, gum hemorrhage, hepatitis, ileitis, jaundice, intestinal obstruction, liver tenderness, parotitis, periodontitis, proctitis, salivary gland enlargement, increased salivation, soft stools, tongue discoloration.
Endocrine system - Rare : galactorrhoea, goiter, hyperthyroidism, hypothyroidism, thyroid nodule, thyroiditis. Hemic and lymphatic system - Frequent : ecchymosis; Infrequent : anemia, leukocytosis, leukopenia, lymphadenopathy, thrombocythemia; Rare : basophilia, bleeding time increased, cyanosis, eosinophilia, lymphocytosis, multiple myeloma, purpura, thrombocytopenia.
Metabolic and nutritional - Frequent : edema, weight gain; Infrequent : alkaline phosphatase increased, dehydration, hypercholesteremia, hyperglycemia, hyperlipidemia, hypokalemia, SGOT (AST) increased, SGPT (ALT) increased, thirst; Rare : alcohol intolerance, bilirubinemia, BUN increased, creatinine increased, diabetes mellitus, glycosuria, gout, healing abnormal, hemochromatosis, hypercalcinuria, hyperkalemia, hyperphosphatemia, hyperuricemia, hypocholesteremia, hypoglycemia, hyponatremia, hypophosphatemia, hypoproteinemia, uremia.
Musculoskeletal system - Infrequent : arthritis, arthrosis, bone spurs, bursitis, leg cramps, myasthenia, tenosynovitis; Rare : pathological fracture, muscle cramp, muscle spasms, musculoskeletal stiffness, myopathy, osteoporosis, osteosclerosis, plantar fasciitis, rheumatoid arthritis, tendon rupture.
Nervous system - Frequent : amnesia, confusion, depersonalization, hypesthesia, trismus, vertigo; Infrequent : akathisia, apathy, ataxia, circumoral paresthesia, CNS stimulation, emotional lability, euphoria, hallucinations, hostility, hyperesthesia, hyperkinesia, hypotonia, incoordination, libido increased, manic reaction, myoclonus, neuralgia, neuropathy, psychosis, seizure, stupor, suicidal ideation; Rare : akinesia, alcohol abuse, aphasia, bradykinesia, buccoglossal syndrome, cerebrovascular accident, feeling drunk, loss of consciousness, delusions, dementia, dystonia, energy increased, facial paralysis, abnormal gait, Guillain-Barre Syndrome, homicidal ideation, hyperchlorhydria, hypokinesia, hysteria, impulse control difficulties, motion sickness, neuritis, nystagmus, paranoid reaction, paresis, psychotic depression, reflexes decreased, reflexes increased, torticollis.
Respiratory system - Frequent : cough increased, dyspnea; Infrequent : asthma, chest congestion, epistaxis, hyperventilation, laryngismus, laryngitis, pneumonia; Rare : atelectasis, hemoptysis, hypoventilation, hypoxia, larynx edema, pleurisy, pulmonary embolus, sleep apnea.
Skin and appendages - Frequent : pruritus; Infrequent : acne, alopecia, contact dermatitis, dry skin, eczema, maculopapular rash, psoriasis, urticaria; Rare : brittle nails, erythema nodosum, exfoliative dermatitis, lichenoid dermatitis, furunculosis, hirsutism, leukoderma, miliaria, petechial rash, pruritic rash, pustular rash, vesiculobullous rash, seborrhea, skin atrophy, skin hypertrophy, skin striae, sweating decreased.
Special senses - Frequent : abnormality of accommodation, mydriasis, taste perversion; Infrequent : conjunctivitis, diplopia, dry eyes, otitis media, parosmia, photophobia, taste loss; Rare : blepharitis, cataract, chromatopsia, conjunctival edema, corneal lesion, deafness, exophthalmos, eye hemorrhage, angle-closure glaucoma, retinal hemorrhage, subconjunctival hemorrhage, hyperacusis, keratitis, labyrinthitis, miosis, papilledema, decreased pupillary reflex, otitis externa, scleritis, uveitis, visual field defect.
Urogenital system - Frequent : albuminuria, urination impaired; Infrequent : amenorrhea, * cystitis, dysuria, hematuria, kidney calculus, kidney pain, leukorrhea, * menorrhagia, * metrorrhagia, * nocturia, breast pain, polyuria, pyuria, prostatic disorder (prostatitis, enlarged prostate, and prostate irritability), * urinary incontinence, urinary retention, urinary urgency, vaginal hemorrhage, * vaginitis * ; Rare : abortion, * anuria, breast discharge, breast engorgement, balanitis, * breast enlargement, endometriosis, * female lactation, * fibrocystic breast, calcium crystalluria, cervicitis, * orchitis, * ovarian cyst, * bladder pain, prolonged erection, * gynecomastia (male), * hypomenorrhea, * mastitis, menopause, * pyelonephritis, oliguria, salpingitis, * urolithiasis, uterine hemorrhage, * uterine spasm, * vaginal dryness.
* * Based on the number of men and women as appropriate. 2 Post-Marketing Experience Voluntary reports of other adverse reactions temporally associated with the use of venlafaxine have been received since market introduction. Because these reactions are reported from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
These reports include the following reactions: agranulocytosis, anaphylaxis, anosmia, aplastic anemia, catatonia, congenital anomalies, impaired coordination and balance, CPK increased, deep vein thrombophlebitis, delirium, Takotsubo cardiomyopathy, EKG abnormalities such as QT prolongation; cardiac arrhythmias including atrial fibrillation, supraventricular tachycardia, ventricular extrasystoles, and rare reports of ventricular fibrillation and ventricular tachycardia, including torsade de pointes; toxic epidermal necrolysis/Stevens-Johnson Syndrome, erythema multiforme, extrapyramidal symptoms (including dyskinesia and tardive dyskinesia), angle-closure glaucoma, hemorrhage (including eye and gastrointestinal bleeding), hyposmia, hepatic reactions (including GGT elevation; abnormalities of unspecified liver function tests; liver damage, necrosis, or failure; and fatty liver), interstitial lung disease, involuntary movements, LDH increased, neuroleptic malignant syndrome-like reactions (including a case of a 10-year-old who may have been taking methylphenidate, was treated and recovered), neutropenia, night sweats, pancreatitis, pancytopenia, panic, prolactin increased, renal failure, rhabdomyolysis, serotonin syndrome, shock-like electrical sensations or tinnitus (in some cases, subsequent to the discontinuation of venlafaxine or tapering of dose), and syndrome of inappropriate antidiuretic hormone secretion (usually in the elderly).
Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment.
Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18-24) with major depressive disorder (MDD) and other psychiatric disorders.
Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older. The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients.
The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied.
There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs placebo), however, were relatively stable within age strata and across indications.
These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 1 Table 1 Age Range Drug-Placebo Difference in Number of Cases of Suicidality per 1000 Patients Treated Increases Compared to Placebo <18 14 additional cases 18-24 5 additional cases Decreases Compared to Placebo 25-64 1 fewer case ≥65 6 fewer cases No suicides occurred in any of the pediatric trials.
There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide. , beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression.
All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.
The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric.
Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.
Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.
5 ) ]. Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers.
Such monitoring should include daily observation by families and caregivers. Prescriptions for venlafaxine extended-release tablets should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.
A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder.
Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression.
It should be noted that venlafaxine extended-release tablets are not approved for use in treating bipolar depression. 2 Serotonin Syndrome Serotonin-norepinephrine reuptake inhibitors (SNRIs), including venlafaxine extended-release tablets, can precipitate serotonin syndrome, a potentially life-threatening condition.
The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, meperidine, methadone, busipirone, amphetamines, and St. 1 )]. Serotonin syndrome can also occur when these drugs are used alone.
, nausea, vomiting, diarrhea). The concomitant use of venlafaxine extended-release tablets with MAOIs is contraindicated. In addition, do not initiate venlafaxine extended-release tablets in a patient being treated with MAOIs such as linezolid or intravenous methylene blue.
No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection). 9 ) ]. Monitor all patients taking venlafaxine extended-release tablets for the emergence of serotonin syndrome.
Discontinue treatment with venlafaxine extended-release tablets and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of venlafaxine extended-release tablets with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.
3 Sustained Hypertension Venlafaxine hydrochloride extended-release capsule treatment is associated with sustained hypertension (defined as treatment-emergent supine diastolic blood pressure (SDBP) ≥90 mm Hg and ≥10 mm Hg above baseline for 3 consecutive on-therapy visits) (see Table 2).
An analysis for patients in venlafaxine hydrochloride immediate-release tablet studies meeting criteria for sustained hypertension revealed a dose-dependent increase in the incidence of sustained hypertension for immediate-release venlafaxine hydrochloride (see Table 3).
An insufficient number of patients received mean doses of venlafaxine hydrochloride extended-release capsules over 300 mg/day to fully evaluate the incidence of sustained increases in blood pressure at these higher doses. 7% (5/705) of the venlafaxine hydrochloride extended-release capsule-treated patients discontinued treatment because of elevated blood pressure.
Among these patients, most of the blood pressure increases were in a modest range (12 to 16 mm Hg, SDBP). 6% (5/771) of the venlafaxine hydrochloride extended-release capsule-treated patients discontinued treatment because of elevated blood pressure.
In these patients, the blood pressure increases were modest (1 to 24 mm Hg, SDBP). Sustained increases of SDBP could have adverse consequences. Cases of elevated blood pressure requiring immediate treatment have been reported in post marketing experience.
Pre-existing hypertension should be controlled before treatment with venlafaxine. It is recommended that patients receiving venlafaxine hydrochloride extended-release tablets 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.
Elevations in Systolic and Diastolic Blood Pressure In placebo-controlled premarketing studies, there were changes in mean blood pressure (see Table 4 for mean change in supine systolic and supine diastolic blood pressure). Across most indications, a dose-related increase in supine systolic and diastolic blood pressure was evident in venlafaxine hydrochloride extended-release capsule-treated patients.
9% of patients in the placebo groups. 3% of patients in the placebo groups. 4 Angle Closure Glaucoma Angle-Closure Glaucoma: The pupillary dilation that occurs following use of many antidepressant drugs including venlafaxine may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.
5 Discontinuation of Treatment with Venlafaxine Extended-Release Tablets Discontinuation symptoms have been systematically evaluated in patients taking venlafaxine, to include prospective analyses of clinical trials and retrospective surveys of trials in major depressive disorder and social anxiety disorder.
Abrupt discontinuation or dose reduction of venlafaxine at various doses has been found to be associated with the appearance of new symptoms, the frequency of which increased with increased dose level and with longer duration of treatment.
Reported symptoms include agitation, anorexia, anxiety, confusion, impaired coordination and balance, diarrhea, dizziness, dry mouth, dysphoric mood, fasciculation, fatigue, headaches, hypomania, insomnia, nausea, nervousness, nightmares, sensory disturbances (including shock-like electrical sensations), somnolence, sweating, tremor, vertigo, and vomiting.
g. paresthesias such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. While these reactions are generally self-limiting, there have been reports of serious discontinuation symptoms.
Patients should be monitored for these symptoms when discontinuing treatment with venlafaxine extended-release tablets. 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.
4 ) ]. 6 Insomnia and Nervousness Treatment-emergent insomnia and nervousness were more commonly reported for patients treated with venlafaxine hydrochloride extended-release capsules than with placebo in pooled analyses of short-term major depressive disorder and other clinical studies, as shown in Table 5.
9% of the patients treated with venlafaxine hydrochloride extended-release capsules in major depressive disorder studies. In other clinical trials, insomnia and nervousness led to drug discontinuation in 2% and 1%, respectively, of the patients treated with venlafaxine hydrochloride extended-release capsules up to 12 weeks.
7 Changes in Weight Adult Patients: A loss of 5% or more of body weight occurred in 7% of patients treated with venlafaxine hydrochloride extended-release capsules and 2% of placebo-treated patients in the short-term placebo-controlled major depressive disorder trials.
1% in major depressive disorder studies. In other placebo-controlled trials, 4% of the patients treated with venlafaxine hydrochloride extended-release capsules and 1% of the placebo-treated patients sustained a loss of 7% or more of body weight during up to 6 months of treatment.
None of the patients receiving venlafaxine hydrochloride extended-release capsules in other studies discontinued for weight loss. The safety and efficacy of venlafaxine therapy in combination with weight loss agents, including phentermine, have not been established.
Co-administration of venlafaxine extended-release tablets and weight loss agents is not recommended. Venlafaxine extended-release tablets are not indicated for weight loss alone or in combination with other products.
Pediatric Patients:
Weight loss has been observed in pediatric patients (ages 6 -17) receiving venlafaxine hydrochloride extended-release capsules. 77 kg (n=333). 5% in the studies (18% of patients treated with venlafaxine hydrochloride extended-release capsules vs.
001). 76 kg (n=148). 5% in the study (47% of patients treated with venlafaxine hydrochloride extended-release capsules vs. 001). 9 )] . The risks associated with longer-term use of venlafaxine hydrochloride extended-release capsules were assessed in an open-label MDD study of children and adolescents who received venlafaxine hydrochloride extended-release capsules for up to six months.
The children and adolescents in the study had increases in weight that were less than expected based on data from age-and sex-matched peers. The difference between observed weight gain and expected weight gain was larger for children (<12 years old) than for adolescents (≥12 years old).
041. This difference in height increase was most notable in patients younger than twelve. 7 cm (n=147). 0 cm. In the six-month, open-label MDD study, children and adolescents had height increases that were less than expected based on data from age-and sex-matched peers.
The difference between observed growth rates and expected growth rates was larger for children (<12 years old) than for adolescents (≥12 years old). 9 Changes in Appetite Adult Patients: Treatment-emergent anorexia was more commonly reported for patients treated with venlafaxine hydrochloride extended-release capsules (8%) than for placebo-treated patients (4%) in the pool of short-term, double-blind, placebo-controlled major depressive disorder studies.
0% in major depressive disorder studies. Treatment-emergent anorexia was more commonly reported for patients treated with venlafaxine hydrochloride extended-release capsules (20%) than for placebo-treated patients (2%) in the pool of short-term, double-blind, placebo-controlled Social Anxiety Disorder studies.
4% for patients receiving venlafaxine hydrochloride extended-release capsules for up to 12 weeks in Social Anxiety Disorder studies.
Pediatric Patients:
Decreased appetite has been observed in pediatric patients receiving venlafaxine hydrochloride extended-release capsules. In placebo-controlled trials in MDD and another disorder, 10% of patients aged 6-17 treated with venlafaxine hydrochloride extended-release capsules for up to eight weeks and 3% of patients treated with placebo reported treatment-emergent anorexia (decreased appetite).
None of the patients receiving venlafaxine hydrochloride extended-release capsules discontinued for anorexia or weight loss. In a placebo-controlled non-MDD trial, 22% and 3% of patients aged 8-17 treated for up to 16 weeks with venlafaxine hydrochloride extended-release capsules and placebo, respectively, reported treatment-emergent anorexia (decreased appetite).
7% for patients receiving either venlafaxine hydrochloride extended-release capsules or placebo. 0% placebo patients. In premarketing Social Anxiety Disorder studies, no patients treated with venlafaxine hydrochloride extended-release capsules and no placebo-treated patients experienced mania or hypomania.
5% of venlafaxine-treated patients compared with 0% of placebo patients. Mania/hypomania has also been reported in a small proportion of patients with mood disorders who were treated with other marketed drugs to treat major depressive disorder.
As with all drugs effective in the treatment of major depressive disorder, venlafaxine extended-release tablets should be used cautiously in patients with a history of mania. 11 Hyponatremia Hyponatremia may occur as a result of treatment with SSRI's and SNRI's, including venlafaxine extended-release tablets.
In many cases, this hyponatremia appears to be the result of the Syndrome of Inappropriate antidiuretic hormone secretion (SIADH). Cases with serum sodium lower than 110 mmol/L have been reported. Elderly patients may be at greater risk of developing hyponatremia with SSRIs and SNRIs.
5 ) ]. Discontinuation of venlafaxine extended-release tablets should be considered in patients with symptomatic hyponatremia and appropriate medical intervention should be instituted. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls.
Signs and symptoms associated with more severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death. 12 Seizures During premarketing experience, no seizures occurred among 705 patients treated with venlafaxine hydrochloride extended-release capsules in the major depressive disorder studies or among 277 patients treated with venlafaxine hydrochloride extended-release capsules in Social Anxiety Disorder studies.
3% (8/3082) of venlafaxine-treated patients. Venlafaxine extended-release tablets, like many antidepressants, should be used cautiously in patients with a history of seizures and should be discontinued in any patient who develops seizures.
13 Increased Risk of Bleeding SSRIs and SNRIs, including venlafaxine extended-release tablets, may increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin, and other anticoagulants may add to this risk.
Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. 1 ) ]. Bleeding events related to SSRIs and SNRIs use have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages.
Patients should be cautioned about the increased risk of bleeding associated with the concomitant use of venlafaxine extended-release tablets and NSAIDs, aspirin, or other drugs that affect coagulation. 1 ) ]. Measurement of serum cholesterol levels should be considered during long-term treatment.
15 Interstitial Lung Disease and Eosinophilic Pneumonia Interstitial lung disease and eosinophilic pneumonia associated with venlafaxine therapy have been rarely reported. The possibility of these adverse reactions should be considered in venlafaxine-treated patients who present with progressive dyspnea, cough or chest discomfort.
Such patients should undergo a prompt medical evaluation, and discontinuation of venlafaxine therapy should be considered. 16 Use in Patients With Heart Disease Premarketing experience with venlafaxine in patients with concomitant systemic illness is limited.
Caution is advised in administering venlafaxine extended-release tablets to patients with diseases or conditions that could affect hemodynamic responses. Venlafaxine has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease.
Patients with these diagnoses were systematically excluded from many clinical studies during venlafaxine's premarketing testing. The electrocardiograms were analyzed for 275 patients who received venlafaxine hydrochloride extended-release capsules and 220 patients who received placebo in 8-to 12-week double-blind, placebo-controlled trials in major depressive disorder as well as for 195 patients who received venlafaxine hydrochloride extended-release capsules and 228 patients who received placebo in 12-week double-blind, placebo-controlled trials in Social Anxiety Disorder.
9 msec for placebo). 0 msec for placebo). In these same trials, the mean change from baseline in heart rate for patients treated with venlafaxine hydrochloride extended-release capsules in the major depressive disorder studies was significantly higher than that for placebo (a mean increase of 4 beats per minute for venlafaxine hydrochloride extended-release capsules and 1 beat per minute for placebo).
The mean change from baseline in heart rate for patients treated with venlafaxine hydrochloride extended-release capsules in the Social Anxiety Disorder studies was significantly higher than that for placebo (a mean increase of 5 beats per minute for venlafaxine hydrochloride extended-release capsules and no change for placebo).
7 beats per minute in the placebo group. , patients with hyperthyroidism, heart failure, or recent myocardial infarction). Evaluation of the electrocardiograms for 769 patients who received venlafaxine hydrochloride immediate-release tablets in 4- to 6-week double-blind, placebo-controlled trials showed that the incidence of trial-emergent conduction abnormalities did not differ from that with placebo.
17 Laboratory Tests There are no specific laboratory tests recommended. 1 )] . In male patients, SNRI use may result in ejaculatory delay or failure, decreased libido, and erectile dysfunction. In female patients, SNRI use may result in decreased libido and delayed or absent orgasm.
It is important for prescribers to inquire about sexual function prior to initiation of venlafaxine extended-release tablets and to inquire specifically about changes in sexual function during treatment, because sexual function may not be spontaneously reported.
When evaluating changes in sexual function, obtaining a detailed history (including timing of symptom onset) is important because sexual symptoms may have other causes, including the underlying psychiatric disorder. Discuss potential management strategies to support patients in making informed decisions about treatment.