Venlafaxine (Effexor) is a selective serotonin and norepinephrine reuptake inhibitor with little effect on dopamine receptors.

It is indicated for the treatment of the following conditions:

• Generalized anxiety disorder (extended-release capsules only)

• Unipolar Major depressive disorder

• Panic disorder with or without agoraphobia (extended-release capsules only)

• Use in Social anxiety disorder or social phobia (extended-release capsules and tablets only)

• Off Label Usage of Venlafaxine in Adults include:

  • Prevention of Episodic migraine

  • Narcolepsy along with cataplexy

  • Obsessive-compulsive disorder

  • Posttraumatic stress disorder

  • Premenstrual dysphoric disorder

  • Vasomotor symptoms with menopause

  • Neuropathic pain associated with diabetes mellitus

Venlafaxine (Effexor) dose in Adults

Episodic migraine prevention as off-label use: 

• Extended-release:
  • It is first administered 37.5 mg orally once daily for three days. Based on response and tolerability, the dose is then increased by 75 mg increments until it reaches the target dose of 75 to 150 mg once day.

Generalized anxiety disorder: 

• Extended-release:
  • It is first administered 37.5 to 75 mg orally once daily to patients. After 4 to 7 days, increase the dosage to 75 mg once daily.
  • Thereafter, the dosage can be increased by 75 mg/day increments every 4 days if the patient tolerates it. The typical dosage is 75
  • to 225 mg once daily, and the maximum dose is 225 mg/day.

Major Unipolar depressive disorder: 

• Extended-release:
  • At first, 37.5 to 75 mg are used once daily orally.
  • In patients who initially receive 37.5 mg once day, the dosage can be increased to 75 mg once daily after 4 to 7 days. Based on response and tolerability, the dosage may thereafter be increased in increments of 75 mg/day at intervals of 4 days (slower increase every 2 to 4 weeks are appropriate in less clinically urgent situations)
  • The usual dosage is 75 to 225 mg once daily, although for patients with psychotic characteristics, some doctors may use more rapid titrations (every 48 to 72 hours) in conjunction with an antipsychotic (such as quetiapine).
• Immediate-release:
  • At first, 37.5 to 75 mg per day are used orally.
  • If a patient responds well and it is tolerated, the dosage may be increased in increments of up to 75 mg per day every four days.
  • Daily doses more than 37.5 mg are delivered in two or three divided doses.
  • The typical dosage ranges from 75 to 375 mg per day; the daily maximum is 375 mg.

Dose in the treatment of Narcolepsy with cataplexy (off-label): 

• Immediate release and extended-release:
  • Some medical professionals advise dosages of 37.5 to 150 mg once daily or 37.5 to 75 mg twice daily (immediate-release) (extended release).
  • A low starting dose should be used, and the dosage should be gradually increased based on response and tolerability.

Off label dosage in the treatment of Neuropathic pain associated with diabetes mellitus :

• Extended-release:
  • Originally, 37.5 mg or 75 mg are administered orally once daily.
  • Then, up the dosage by 75 mg per week to a maximum of 225 mg once a day.

Off label dosage as an alternative agent in the treatment of Obsessive-compulsive disorder :

It is used as a substitute for patients whose responses to SSRI therapy are insufficient or nonexistent.

• Immediate release and extended-release:
  • For extended-release, 75 mg are initially administered orally once per day.
  • 75 mg/day in three evenly spaced dosages is another option for quick release.
  • The dosage is raised from 75 mg every two weeks to 225 mg each day.
  • Based on response and tolerance, an additional increase is possible up to 350 mg per day.

Dosage in the treatment of Panic disorder:

• Extended-release:
  • The usual dosage is 75 to 225 mg once daily; the maximum dose is 225 mg/day. Initially, 37.5 mg orally once daily for 7 days is given; after 7 days, it may be increased to 75 mg once daily; after that, it may be increased by 75 mg/day increments at intervals of 7 days.

Off label Dosage in the treatment of Posttraumatic stress disorder: 

• Extended-release:
  • At first, 37.5 mg are used once daily orally.
  • The dosage is then increased based on response and tolerance in increments of 75 mg/day every 4 days, up to 300 mg once every 24 hours.

Off label Dosage as an alternative agent in the treatment of Premenstrual dysphoric disorder :

Continuous daily dosing regimen: Oral:

• Extended-release:
  • First, 37.5 mg are administered orally once daily.
  • Increase the dosage throughout the first month to the typical effective dose of 75 mg once daily.
  • For certain patients, further dose increases up to 150 mg/day (e.g., in 37.5 mg increments per menstrual cycle) may be required in consecutive cycles to achieve the best result.

Off label Dosage in the treatment of Vasomotor symptoms associated with menopause (alternative agent):

For people unable or unwilling to take oestrogen, an alternative.

• Immediate release and extended-release:
  • At first, 37.5 mg are used once daily orally.
  • Then, it could be raised to 75 mg once daily for extended-release after about a week depending on response and tolerability.
  • For quick release, it can be be raised to 75 mg/day in two to three divided doses.

• Dosing conversion:
  • Patients can move from venlafaxine immediate-release to venlafaxine extended-release at the closest equivalent dose (mg/day).
  • There may be a need for individual dosage modifications after the formulation change.
• Discontinuation of therapy:
  • In order to decrease withdrawal symptoms and identify any new symptoms, treatment should be carefully weaned off over a period of 2 to 4 weeks.
  • Individuals on long-acting antidepressants, especially those on large doses, and those with a history of withdrawal symptoms may be encouraged to take off medication more gradually.
  • If the patient’s symptoms reappear, restart the previous dose on which the patient was stable and then start tapering more slowly.

• Switching antidepressants:

 There are 2 strategies :

• Cross-titration (gradually stopping the 1st antidepressant while at the same time gradually increasing the new antidepressant) (gradually discontinuing the 1st antidepressant while at the same time gradually increasing the new antidepressant)
• Straight switch (abruptly discontinuing the 1st antidepressant and then starting the new antidepressant at an equivalent dose or lower dose and increasing it slowly).
  • Cross-titration:
    • This method is usually followed especially when venlafaxine or the other antidepressant has been used for more than 2 – 4 weeks.
    • One drug is gradually tapered while the dose of the other drug is increased gradually at the same time.
  • Direct switch:
    • The direct switch is the abrupt discontinuation of one drug and initiating the other drug at an equivalent dose.
    • This method may be appropriate in cases where the drug has been used for less than 1 – 2 weeks or when the drug is discontinued because of the adverse effects.

• Switching to or from an MAOI:

  At least a 14 days drug-free interval should be allowed when switching from an MAOI to venlafaxine and vice versa.
• Cross titration is contraindicated when switching from an MAOI to an SSRI and vice versa.

Venlafaxine (Effexor) Dose in Children

Attention-deficit hyperactivity disorder (ADHD): 

• Children and Adolescents 8 to <17 years:
  • Immediate release:
    • With the intention of titrating, 12.5 mg is administered orally at first.
    • It should be increased by 12.5 mg/week in children under 40 kg, up to a maximum daily dose of 50 mg/day in two divided doses.

Dosage in the treatment of Autism spectrum disorders:

• Children ≥ 3 years and Adolescents:
•  Oral:
  • Immediate release:
  • Breakfast is the time for administering the initial dose of 12.5, which is then gradually increased based on clinical response and adverse effects.
  • 6.25 to 50 mg per day is the dose range.

Dose in the treatment of Depression:

• Children ≥7 years and Adolescents ≤17 years:
• Venlafaxine should be administered to paediatric major depressive patients who do not improve on fluoxetine or sertraline due to heightened concerns of suicide.
  • Immediate release:
    • Starting with 12.5 mg once day for 3 days, the dosage is then increased to 12.5 mg twice daily for 3 days.
    • After that, take 12.5 mg three times day.
  • For adolescents 13 to 17 years
    • Initial dosage is 25 mg once daily for three days.
    • Then, it is raised to 25 mg twice daily for three days.
    • 25 mg are taken three times day after it.

• Discontinuation of therapy:

  • Reduce the dosage gradually after ending antidepressant treatment to reduce the likelihood of withdrawal symptoms and make it possible to identify any symptoms that recur.
  • According to APA and NICE recommendations, tapering therapy over at least a few weeks is advised, taking the antidepressant's half-life into account.
  • The tapering of antidepressants with a shorter half-life may require a more cautious approach.
  • Moreover, WFSBP guidelines advise tapering over 4 to 6 months for individuals who have been receiving long-term treatment.
  • Consider repeating the initial dose or lowering the dose at a more slow rate if intolerable withdrawal symptoms appear after a dose reduction.

• MAO inhibitor recommendations:

  • Changing from or to an MAO inhibitor needed to treat mental disorders: Give venlafaxine two weeks to take effect after stopping an
  • MAO inhibitor used to treat psychiatric disorders.
  • Venlafaxine should be stopped 1 week before beginning an MAO inhibitor used to treat psychiatric problems.

• Use with other MAO inhibitors (linezolid or IV methylene blue):

  • In patients on linezolid or IV methylene blue, do not start venlafaxine.
  • If a patient who is already taking venlafaxine requires immediate therapy with linezolid or IV methylene blue and the potential advantages outweigh the potential dangers, cease taking venlafaxine right away and administer linezolid or IV methylene blue.
  • For one week or until 24 hours after the final dosage of linezolid or IV methylene blue, whichever comes first, keep an eye out for serotonin syndrome.
  • After 24 hours, venlafaxine can be resumed.

Pregnancy Risk Factor C

• Some animal reproduction studies have shown adverse events.
• ODV, the active metabolite of venlafaxine, can pass the placenta.
• Based on the available data, there has been no evidence of an increase in teratogenic effects following venlafaxine administration during pregnancy.
• There is a greater chance of spontaneous abortion.
• Neonatal seizures and symptoms of abstinence from maternal venlafaxine use during pregnancy have been documented in case reports.
• Late in the third trimester, SSRI/SNRI may have non-teratogenic effects on the infant. They include breathing difficulties, cyanosis, seizures, unstable temperature, vomiting, and hypoglycemia. tremor, hypertonia, hyperreflexia, jitteriness, and irritability.
• SNRI toxicity or a discontinuation syndrome may be to blame for symptoms. They may also be a part of the serotonin syndrome, a condition that is treated.
• Due to physiological changes brought on by pregnancy, some pharmacokinetic parameters may need to be altered.
• Monitoring of decreased efficacy in women is necessary.
• Individualized SSRI and SNRI treatment during pregnancy is advised by ACOG.
• The clinical skill of the primary care physician, obstetrician, and mental healthcare provider
• The American Psychiatric Association states that medication treatment can have side effects and should be considered in conjunction with other treatments.
• Women who have stopped antidepressant medication during pregnancy or who are at high risk of postpartum depression can resume their medications after delivery.

Use of venlafaxine while breastfeeding

• Breast milk contains venlafaxine as well as the active metabolite ODV.
• The RID should be less than 10%. In general, breastfeeding can be accepted. Some sources mention that breastfeeding should not be considered if psychotropic agents have a RID of less than 5%.
• Infant serum also contained ODV and Venlafaxine.
• Mothers who have been prescribed psychotropic medication should monitor their infants daily for any changes in sleep, feeding, behavior, or infant growth.
• When deciding whether to stop or continue breastfeeding during therapy, it is important to consider the risks to infants, the benefits to the infant and the benefits to the mother.
• Agents other than venlafaxine should be used when a woman is breastfeeding and the antidepressant is being started for the first time.
• If there are no contraindications, women who have been successfully treated with venlafaxine in pregnancy can continue to use it while breastfeeding.

Venlafaxine (Effexor) dose in Kidney Disease:

• Extended-release
  • CrCl 30 - 89 mL/minute
    • You can reduce your daily dose by 25% to half.
  • CrCl 30mL/minute
    • You can reduce your daily total dose by at least 50%
  • Hemodialysis
    • You can reduce your daily total dose by at least 50%
  • Instant-release
    • GFR 10 to 70% mL/minute
      • You can reduce your daily total dose by 25%
    • GFR 10mL/minute
      • The manufacturer's labeling does not contain any dosage adjustments (hasn't been studied); please use caution.
    • Hemodialysis
      • Reducing daily intake by 50%

Venlafaxine (Effexor) Dose in Liver Disease:

• Mild to moderate liver impairment (Child Puugh class A or B)
  • Reduce daily total dose by 50%
• Severe hepatic impairment (Child Puugh class C).
  • Patients with cirrhosis should reduce their daily total dose by at least 50%

Common Side Effects of Venlafaxine (Effexor) Include:

• Central Nervous System:
  • Insomnia
  • Dizziness
  • Drowsiness
• Dermatologic:
  • Diaphoresis
• Gastrointestinal:
  • Nausea
  • Xerostomia
• Neuromuscular & Skeletal:
  • Weakness

Less Common Side Effects of Venlafaxine Include:

• Cardiovascular:
  • Vasodilation
  • Hypotension
  • Orthostatic Hypotension
  • Syncope
  • Tachycardia
  • Increased Blood Pressure
• Central Nervous System:
  • Nervousness
  • Yawning
  • Anorgasmia
  • Abnormal Dreams
  • Paresthesia
  • Agitation
  • Akathisia
  • Apathy
  • Chills
  • Confusion
  • Depersonalization
  • Hallucination
  • Hypertonia
  • Manic Reaction
  • Myoclonus
  • Seizure
• Dermatologic:
  • Alopecia
  • Ecchymoses
  • Pruritus
  • Skin Photosensitivity
  • Skin Rash
  • Urticaria
• Endocrine & Metabolic:
  • Orgasm Abnormal
  • Decreased Libido
  • Hypercholesterolemia
  • Hypermenorrhea
  • Weight Gain
  • Weight Loss
• Gastrointestinal:
  • Anorexia
  • Constipation
  • Diarrhea
  • Vomiting
  • Bruxism
  • Dysgeusia
  • Gastrointestinal Hemorrhage
• Genitourinary:
  • Ejaculatory Disorder
  • Impotence
  • Abnormal Uterine Bleeding
  • Urinary Frequency
  • Urinary Incontinence
  • Urinary Retention
  • Urination Disorder
• Neuromuscular & Skeletal:
  • Tremor
• Ophthalmic:
  • Visual Disturbance
  • Accommodation Disturbance
  • Mydriasis
• Otic:
  • Tinnitus

Frequency Not Defined:

• Cardiovascular:
  • Hypertension
  • Increased Pulse
• Central Nervous System:
  • Suicidal Ideation
• Endocrine & Metabolic:
  • Increased Serum Triglycerides
• Hematologic & Oncologic:
  • Hematoma
  • Petechia
• Respiratory:
  • Epistaxis

Contraindication to Venlafaxine Include:

• Venlafaxine with any other component of this formulation allergy responses
• treatment of psychiatric diseases while taking MAOIs or within 14 days of quitting them;
• Within 7 days of stopping venlafaxine, initiate MAOI to treat mental disorders
• Patients receiving IV methyleneblue or linezolid should be started.

Warnings and precautions

• Anxiety and insomnia
  • An increase in anxiety, nervousness and insomnia can be a result.
• Bleeding Risk:
  • Use of anticoagulants such as warfarin, aspirin, NSAIDs, or other anticoagulants can cause platelet aggregation to be impaired, which can increase the risk of bleeding events.
  • Bleeding caused by SSRI/SNRI use can range from minor bruising and epistaxis up to life-threatening hemorhage.
• Depression in the CNS:
  • It is unlikely to cause impairments in motor or cognitive performance.
  • It is important to exercise caution when operating dangerous machinery or driving.
• Dyslipidemia
  • Triglycerides or serum total cholesterol levels may significantly rise as a result.
  • Long-term monitoring is necessary
• Fractures
  • Antidepressant treatment has been shown to reduce bone fractures.
  • Fragility fractures are possible in patients with undiagnosed bone pains, point tenderness or bruising.
• Hypertension
  • There have been reports of dose-related spikes in diastolic and systolic blood pressure.
  • Keep your blood pressure under control. If you notice persistent increases, reduce or stop taking the medication.
• Ocular effects
  • It may mildly dilate the pupils, which in some situations can result in narrow-angle glaucoma.
  • To lower the risk of narrow-angle glaucoma, you can think about checking patients who have not undergone an iridectomy.
• Events in the pulmonary system:
  • Eosinophilic pneumonia and interstitial lung disease are extremely uncommon.
  • Chest pain, increasing dyspnea, or coughing could be the symptoms of this.
  • It may be necessary to have a prompt evaluation and possibly stop the therapy.
• Serotonin syndrome
  • Serotonin syndrome, a potentially fatal condition, is associated with the use and abuse of serotonin.SSRIs. Patients who have the following symptoms should be suspect:
  • Mental status changes (hallucinations and agitations, delirium and coma).
  • autonomic instability: sweating, resting bradycardia/ tachycardia and changes in blood pressure
  • Neurological features (rigidity and tremor, seizures and myoclonus).
  • Gastrointestinal symptoms such as nausea, diarrhea, and vomiting can include:
• Sexual dysfunction
  • It can cause or exacerbate sexual dysfunction.
• SIADH and Hyponatremia
  • It could lead to reversible SIADH caused by hyponatremia.
  • Seizures may result from sodium levels below 120 mEq/l
  • The elderly and diuretics-addicted patients are at greatest risk for hyponatremia.
• Anorectic effects and weight loss
  • Both pediatric and adult patients have experienced dose-dependent weight loss.
• Cardiovascular disease
  • It can cause an increase in blood pressure and tachycardia.
  • It is important to control hypertension before venlafaxine can be started.
  • Patients with a history of myocardial injury, CVD, unstable or hyperthyroidism should be cautious.
  •  
• Hepatic impairment
  • Be careful
  • Plasma concentrations are higher and clearance is lower.
  • It is advised to reduce dosage.
• Hypomania and mania:
  • This could lead to hypomania or mania in bipolar disorder patients. Patients with bipolar disorder shouldn't be treated in monotherapy.
  • Increases are typically small and proportionate to the dose of hypertensive effects (12-15 mm Hg diastolic).
  • It has not been approved by the FDA for treatment of bipolar disorder.
• Renal impairment
  • Be careful
  • Plasma concentrations are higher and renal clearance is lower.
  • It is advised to reduce dosage.
• Seizure disorders
  • Individuals who have had seizure disorders in the past need to exercise caution.
  • Seizure sufferers should be treated immediately.

Venlafaxine: Drug Interaction

Monitor:

• Patients with high blood pressure, particularly those with high baselines, should have their blood pressure regularly checked.
• This may result in a 4-9 beats per minute increase in your heart rate
• Cholesterol
• Monitoring mental health for signs of depression, suicide ideation, anxiety, social functioning and mania (especially when therapy is just beginning or when the doses are being increased or decreased), and panic attacks and other symptoms.
• Be aware of signs and symptoms such as hyponatremia and serotonin syndrome.
• Children should be monitored for height and weight
• Keep an eye on your eye pressure (for patients at high risk for acute narrow-angle or raised ocular pressure)

How to administer Venlafaxine (Effexor)?

• Oral: Take with food.

Extended-release formulations:

• You can give either the morning or evening at the same time every day.
• An entire capsule or tablet should be swallowed.
• Never chop, crush, or submerge in water.
• You can also sprinkle the capsule's contents onto a spoonful of applesauce and consume it right away without chewing.
• To ensure that the pellets are fully swallowed, you can add a glass water to your bowl.

Mechanism of action of Venlafaxine:

• O-desmethylvenlafaxine, its active metabolite, and Venlafaxine are potent inhibitors neuronal norepinephrine/serotonin reuptake as well as weak inhibitors for dopamine reuptake.
• O-desmethylvenlafaxine, Venlafaxine, and Venlafaxine do not have significant activity in muscarinic Cholinergic, H-histaminergic, and alpha-adrenergic.

Absorption: Oral: >=92% The extended-release formulation absorbs slower than the immediate-release formulation.

Protein bindingVenlafaxine 27% + 2%, ODV 30 + 12%

It is metabolized by the liverCYP2D6 to O-desmethylvenlafaxine, the active metabolite (ODV), and other less active metabolites N,O,didesmethylvenlafaxine.

BioavailabilityAbout 45% of oral drug users are women.

Eliminating half-life:

• 5+- 2 hours (immediate release)
• 10.7 +-3.2 hours (extended release)
• ODV: 11 +- 2 Hours (immediate release).
• Extended-release: 12.5 hours +- 3 hours
• Extended with cirrhosis (venlafaxine - 30%; ODV - 60%)
• Renal impairment (venlafaxine: 50%; ODV:: 40%)
• During dialysis (venlafaxine, 180%; ODV:

Time required to reach peak serum concentration:

• Instant release formulation: 2 hours; ODV: 3-4 hours
• Extended-release formulation of Venlafaxine: 6.3 + 2.3 hours ODV: 11.6 + 2.9 hours

Most excretion occurs viaUrine (87%)

• 5% of the total dosage as an unchanged drug
• 29% of the total ODV is unconjugated
• Conjugated ODV accounts for 26% of total dose
• 27% of the total dosage is excreted in minor inactive metabolites

Clearance:

Individuals with cirrhosis have a nearly 50% reduction in clearance. ODV Clearance dropped by over 30%. Individuals with severe cirrhosis have a higher chance of receiving a diagnosis. Clearance of venlafaxine has decreased by over 90%. adults with impaired kidney function (GFR: 10 to 70 mL/min). ODV Clearance is the same as that of healthy subjects, however Venlafaxine Clearance is decreased by over 24%. Adult hemodialysis Almost 57% less was spent on clearance. ODV: Sales of clearance items fell by nearly 56%.

International Brands of Venlafaxine:

• Altven
• Alventa
• Ansifix SR
• Avenfax XR
• Blossom
• Calmdown
• Cofexor XL ER
• Delvena
• Deprevix
• Dobupal
• Easyfor SR
• Efectin
• Efectin EP
• Efectin ER
• Efexiva
• Efexor
• Efexor Depot
• Efexor ER
• Efexor XL
• Efexor XR
• Efexor-Exel
• Effexor
• Effexor SR
• Effexor XR
• Elafax
• Elafax XR
• Enlafax-XR
• Evaxiner
• Evaxiner XR
• Faxine
• Faxnerva
• Idixor
• Ireven
• Lafax
• Lanvexin
• Levensa SR
• Maxine
• Neurofax SR
• Nevola
• Rafax XR
• Rudomel XL
• Sesaren XR
• Trevilor
• Trewilor
• Valosine
• Valosine SR
• Vandral Retard
• Vaxor
• Vedixal
• Velapax
• Velaxin
• Venax
• Venex
• Venexor
• Venexor XR
• Venexor XR SR
• Veniz XR
• Veniz-XR
• Venla
• VenlaBlue XL
• Venlafact SR
• Venlalic XL
• Venlasand
• Venlax
• Venlax Retard
• Venlax XR
• Venlaxer
• Venlaxor
• Venlift OD 75
• Venlify OD
• Venlor XR
• Venorion
• Vensir
• Vensir XL
• Ventaxin OR
• Venxor
• Viepax
• Viepax XR
• ACT Venlafaxine XR
• APO-Venlafaxine XR
• Auro-Venlafaxine XR
• DOM-Venlafaxine XR
• Effexor XR
• GD-Venlafaxine XR
• M-Venlafaxine XR
• MYLAN-Venlafaxine XR
• PMS-Venlafaxine XR
• RAN-Venlafaxine XR
• RIVA-Venlafaxine XR
• SANDOZ Venlafaxine XR
• TEVA-Venlafaxine XR
• Venlafaxine XR

Venlafaxine brands in Pakistan: