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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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• 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.

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• 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.

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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.

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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.

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• 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%

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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

Risk Factor C (Monitor therapy)
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.)	Other agents with antiplatelet properties may have an enhanced antiplatelet impact.
Ajmaline	May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).
Alpha2-Agonists	The antihypertensive action of Alpha2-Agonists may be diminished by Serotonin/Norepinephrine Reuptake Inhibitors. Apraclonidine is an exception.
Anticoagulants	The anticoagulant impact of anticoagulants may be strengthened by agents with antiplatelet properties. Bemiparin, Enoxaparin, and Heparin are exceptions.
Antiemetics (5HT3 Antagonists)	Could make serotonin modulators' serotonergic effects stronger. Serotonin syndrome might occur from this.
Antipsychotic Agents	Serotonin modulators might make antipsychotic drugs more harmful or toxic. Serotonin modulators, in particular, may enhance dopamine blockade, potentially raising the risk for neuroleptic malignant syndrome. Serotonin modulators' serotonergic effects may be strengthened by antipsychotic drugs. Serotonin syndrome might occur from this.
Apixaban	Antiplatelet agents may intensify the toxic/unfavorable effects of apixaban. In particular, there may be an elevated risk of bleeding.
Aprepitant	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors)
ARIPiprazole	ARIPiprazole's serum levels may rise in response to CYP2D6 Inhibitors (Weak). Management: Keep an eye out for enhanced pharmacologic effects of aripiprazole. Depending on the concurrent therapy and/or the indication, aripiprazole dosage modifications may or may not be necessary. For detailed advice, refer to the complete interaction monograph.
Aspirin	Serotonin/Norepinephrine Reuptake Inhibitors may improve aspirin's ability to reduce blood clots.
Bosentan	May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Brexanolone	Serotonin/Norepinephrine Reuptake Inhibitors may increase Brexanolone's ability to depress the central nervous system.
Cephalothin	Substances having antiplatelet properties may intensify cephalothin's harmful or hazardous effects. In particular, there may be an elevated risk of bleeding.
CloBAZam	May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).
Clofazimine	May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).
Collagenase (Systemic)	Collagenase's harmful or toxic effects may be enhanced by substances with antiplatelet properties (Systemic). In particular, there may be an increased risk of bruising and/or bleeding at the injection site.
CYP2D6 Inhibitors (Moderate)	May lower the level of CYP3A4 substrates in the serum (High risk with Inducers).
CYP3A4 Inducers (Moderate)	May lower the level of CYP3A4 substrates in the serum (High risk with Inducers).
CYP3A4 Inhibitors (Moderate)	May lower the level of CYP3A4 substrates in the serum (High risk with Inducers).
Dabigatran Etexilate	Dabigatran Etexilate's anticoagulant activity may be strengthened by substances with antiplatelet properties. Dabigatran Etexilate's serum levels may rise in response to substances with antiplatelet properties. The drug clopidogrel is especially covered by this mechanism. Management: Thoroughly weigh the advantages and disadvantages of this combination, and keep a tight eye on things; Canadian labelling advises against using prasugrel or ticagrelor.
Dasatinib	Agents having antiplatelet properties may strengthen their anticoagulant effects. Management: Separate drug interaction monographs go into further detail about the medications indicated as exceptions to this book.
Deferasirox	May lower the level of CYP3A4 substrates in the serum (High risk with Inducers).
Deoxycholic Acid	Deoxycholic Acid's harmful or toxic effects may be increased by substances with antiplatelet properties. In particular, there may be a chance of bleeding or bruising in the treatment region.
Duvelisib	May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).
Edoxaban	Antiplatelet agents may intensify the toxic/unfavorable effects of edoxaban. In particular, there may be an elevated risk of bleeding.
Erdafitinib	May lower the level of CYP3A4 substrates in the serum (High risk with Inducers).
Erdafitinib	May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).
Fat Emulsion (Fish Oil Based)	May enhance the adverse/toxic effect of Agents with Antiplatelet Properties.
Fosaprepitant	May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).
Fosnetupitant	May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).
Glucosamine	Agents with antiplatelet properties may have an enhanced antiplatelet impact.
Ibritumomab Tiuxetan	Antiplatelet agents may intensify the toxic/unfavorable effects of ibritumomab tiuxetan. Both substances may raise the risk of bleeding and compromise platelet function.
Ibrutinib	Agents with poisonous or harmful effects may intensify their negative or hazardous effects.
Imatinib	May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).
Indinavir	Indinavir's serum concentration may drop if you take venlafaxine.
Inotersen	Agents with antiplatelet properties may have an enhanced antiplatelet impact.
Ioflupane I 123	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Ivosidenib	May lower the level of CYP3A4 substrates in the serum (High risk with Inducers).
Larotrectinib	Ioflupane I 123's ability to serve as a diagnostic tool may be diminished by serotonin/norepinephrine reuptake inhibitors.
Limaprost	Agents with antiplatelet properties may have an enhanced antiplatelet impact.
Lumefantrine	May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).
Metaxalone	Could make serotonin modulators' serotonergic effects stronger. Serotonin syndrome might occur from this.
Methylphenidate	Serotonin modulators' harmful or toxic effects could be exacerbated. In particular, there may be an increased risk of serotonin syndrome or serotonin poisoning.
Multivitamins/Fluoride (with ADE)	Agents with antiplatelet properties may have an enhanced antiplatelet impact.
Multivitamins/Minerals (with ADEK, Folate, Iron)	Agents with antiplatelet properties may have an enhanced antiplatelet impact.
Multivitamins/Minerals (with AE, No Iron)	Agents with antiplatelet properties may have an enhanced antiplatelet impact.
Netupitant	May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).
Nonsteroidal Anti-Inflammatory Agents (Nonselective)	Nonsteroidal Anti-Inflammatory Drugs may have a stronger antiplatelet impact when used with Serotonin/Norepinephrine Reuptake Inhibitors (Nonselective).
Obinutuzumab	Agents with antiplatelet properties may intensify Obinutuzumab's toxic/unfavorable effects. In particular, there may be an increased risk of life-threatening bleeding-related incidents.
Omega-3 Fatty Acids	Agents with antiplatelet properties may have an enhanced antiplatelet impact.
Opioid Agonists	Could make serotonin modulators' serotonergic effects stronger. Serotonin syndrome might occur from this.
Palbociclib	May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).
Panobinostat	May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).
Peginterferon Alfa-2b	May lower the serum level of CYP2D6 substrates (High risk with Inhibitors).
Pentosan Polysulfate Sodium	The concentration of CYP2D6 Substrates in the serum may rise when using Peginterferon Alfa-2b (High risk with Inhibitors).
Pentoxifylline	Agents with poisonous or harmful effects may intensify their negative or hazardous effects. In particular, the concurrent use of several drugs may raise the risk of bleeding.
Perhexiline	Agents with antiplatelet properties may have an enhanced antiplatelet impact. The quantity of perhexiline in the serum may rise in response to CYP2D6 Inhibitors (Weak).
Perhexiline	The serum levels of perhexiline may increase when exposed to CYP2D6 Substrates (High Risk with Inhibitors). The serum concentration of CYP2D6 Substrates may rise in response to perhexiline (High risk with Inhibitors).
Propafenone	Venlafaxine serum levels can rise. When starting or increasing propafenone, keep an eye out for any changes in venlafaxine levels or side effects (such as agitation, disorientation, or hallucinations). Conversely, while discontinuing or reducing the dosage of profapenone, keep an eye out for dropped venlafaxine levels.
Prostacyclin Analogues	Agents with antiplatelet properties may have an enhanced antiplatelet impact.
QuiNINE	May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).
Rivaroxaban	Rivaroxaban's anticoagulant impact may be increased by substances with antiplatelet properties. Management: Thoroughly weigh the advantages and disadvantages of this combination, and keep a tight eye on things; Canadian labelling advises against using prasugrel or ticagrelor.
Salicylates	The harmful or toxic effect of salicylates may be increased by substances with antiplatelet properties. Bleeding risk could rise as a result.
Sarilumab	May lower the level of CYP3A4 substrates in the serum (High risk with Inducers).
Serotonin Modulators	The negative or hazardous effects of other serotonin modulators might be increased. Serotonin syndrome may start to develop. Nicergoline and Tedizolid are exceptions.
Siltuximab	May lower the level of CYP3A4 substrates in the serum (High risk with Inducers).
Simeprevir	May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).
Solriamfetol	The antihypertensive effects of venlafaxine may be enhanced.
Tedizolid	Could make serotonin modulators' serotonergic effects stronger. Serotonin syndrome might occur from this.
Thrombolytic Agents	The anticoagulant impact of thrombolytic agents may be strengthened by agents with antiplatelet properties.
Tocilizumab	May lower the level of CYP3A4 substrates in the serum (High risk with Inducers).
TraMADol	Serotonin modulators may intensify TraMADol's harmful or hazardous effects. Seizures may become more likely. The serotonergic impact of serotonin modulators may be enhanced by TraMADol. Serotonin syndrome might occur from this.
Vitamin E (Systemic)	Agents with antiplatelet properties may have an enhanced antiplatelet impact.
Vitamin K Antagonists (eg, warfarin)	Venlafaxine may make Vitamin K Antagonists more harmful or hazardous. In particular, there may be an elevated risk of bleeding.
Voriconazole	Could make Venlafaxine's harmful or hazardous effects worse. Venlafaxine's serum levels may rise in response to voriconazole.
Risk Factor D (Consider therapy modification)
Abiraterone Acetate	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity.
Alcohol (Ethyl)	The negative or hazardous effects of serotonin/norepinephrine reuptake inhibitors may be increased. Particularly, there may be increased chances of psychomotor impairment. Serotonin/Norepinephrine Reuptake Inhibitors may have a stronger hepatotoxic impact when used with alcohol (Ethyl). especially milnacipran and duloxetine. Treatment: It is important to warn patients on serotonin/norepinephrine reuptake inhibitors (SNRIs) to stay away from alcohol. Observe patients who drink while taking SNRIs for increased hepatotoxicity and psychomotor impairment.
Alpha-/Beta-Agonists	The tachycardic action of beta- and alpha-agonists may be enhanced by serotonin/norepinephrine reuptake inhibitors. The vasopressor impact of alpha/beta agonists may be enhanced by serotonin/norepinephrine reuptake inhibitors.
Asunaprevir	May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).
Bemiparin	Bemiparin's anticoagulant impact may be strengthened by substances with antiplatelet properties. Management: Avoid taking bemiparin at the same time as antiplatelet medications. If concurrent use is unavoidable, keep a cautious eye out for bleeding signs and symptoms.
CYP2D6 Inhibitors (Strong)	CYP2D6 substrate metabolism may be decreased (High risk with Inhibitors).
CYP3A4 Inducers (Strong)	May speed up CYP3A4 substrate metabolism (High risk with Inducers). Management: Take into account a substitute for one of the interfering medications. Certain contraindications may apply to some combinations. the relevant manufacturer's label.
CYP3A4 Inhibitors (Strong)	May slow down CYP3A4 substrate metabolism (High risk with Inhibitors).
Dabrafenib	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Where possible, look for substitutes for the CYP3A4 substrate. If concurrent therapy cannot be avoided, pay special attention to the substrate's clinical consequences (particularly therapeutic effects).
Dacomitinib	May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors). Management: Steer clear of using dacomitinib at the same time as CYP2D6 subtrates with a limited therapeutic index.
Enoxaparin	Enoxaparin's anticoagulant impact may be strengthened by substances with antiplatelet properties. When feasible, stop using antiplatelet medications before starting enoxaparin. If simultaneous administration must occur, keep a cautious eye out for any bleeding signs and symptoms.
Enzalutamide	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Treatment: Enzalutamide should not be used concurrently with CYP3A4 substrates that have a limited therapeutic index. Enzalutamide use, like with the use of any other CYP3A4 substrate, should be done cautiously and under close observation.
Heparin	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required.
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry)	May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Management: Avoid combination when possible. If used, monitor more closely for evidence of bleeding. Discontinue herbal products with anticoagulant or antiplatelet actions 2 weeks prior to surgical, dental, or invasive procedures.
Linezolid	May enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. Management: Consider alternatives to this combination whenever possible, and discontinue serotonin/norepinephrine reuptake inhibitors (SNRIs) prior to administration of linezolid.
Linezolid	May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Management: Due to a risk of serotonin syndrome/serotonin toxicity, discontinue serotonin modulators 2 weeks prior to the administration of linezolid. If urgent initiation of linezolid is needed, discontinue serotonin modulators immediately and monitor closely.
Lorlatinib	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Avoid taking lorlatinib at the same time as any CYP3A4 substrates for which even a small drop in serum levels of the substrate could result in therapeutic failure and negative clinical outcomes.
Metoclopramide	The negative or hazardous effects of serotonin/norepinephrine reuptake inhibitors may be increased. Management: When possible, look for substitutions for this combination. Serotonin syndrome, neuroleptic malignant syndrome, and extrapyramidal symptoms should be kept an eye out for in individuals using metoclopramide along with serotonin/norepinephrine reuptake inhibitors.
MiFEPRIStone	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). Management: During and two weeks after mifepristone treatment, reduce doses of CYP3A4 substrates and keep an eye out for elevated amounts or toxicity. Fentanyl, pimozide, quinidine, sirolimus, and tacrolimus should all be avoided. Cyclosporine should also be avoided.
Mitotane	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Treatment: When administered in individuals receiving mitotane, doses of CYP3A4 substrates may need to be significantly modified.
Pitolisant	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Pitolisant should not be used in conjunction with a CYP3A4 substrate that has a limited therapeutic index. When administered with pitolisant, other CYP3A4 substrates need to be checked more carefully.
St John's Wort	May lower the serum level of CYP3A4 substrates (High risk with Inducers). Management: Take into account a substitute for one of the interfering medications. Certain contraindications may apply to some combinations. the relevant manufacturer's label.
Stiripentol	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). Management: Due to the increased potential for side effects and toxicity, stiripentol should not be used with CYP3A4 substrates that are thought to have a narrow therapeutic index. Use of stiripentol with any CYP3A4 substrate necessitates closer observation.
TraZODone	The serotonergic action of TraZODone may be enhanced by venlafaxine. Serotonin syndrome might occur from this.
Risk Factor X (Avoid combination)
Bromopride	The negative or hazardous effects of serotonin/norepinephrine reuptake inhibitors may be increased.
Conivaptan	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Dapoxetine	Serotonin modulators' harmful or toxic effects could be exacerbated.
Fusidic Acid (Systemic	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Idelalisib	May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Iobenguane Radiopharmaceutical Products	Iobenguane radiopharmaceutical products may have less of a therapeutic impact when taken with serotonin/norepinephrine reuptake inhibitors. Treatment: Before administering iobenguane, stop taking any medications that could impede or interfere with catecholamine transport or uptake for at least five biological half-lives. After each dose of iobenguane, wait at least 7 days before administering these medications.
Methylene Blue	Serotonin/Norepinephrine Reuptake Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome.
Methylene Blue	May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome.
Monoamine Oxidase Inhibitors	May enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This may cause serotonin syndrome. While methylene blue and linezolid are expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Exceptions: Linezolid; Methylene Blue; Tedizolid.
Urokinase	Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase.

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:

Venlafaxine (Hcl) [Tabs 50 Mg]
Amfax	Amson Vaccines & Pharma (Pvt) Ltd.
Efexiv	Panacea Pharmaceuticals
Efexor	Pfizer Laboratories Ltd.
Faxidep	Saydon Pharmaceutical Industries (Pvt) Ltd.
Faxine	Amarant Pharmaceuticals (Pvt)
Faxine	Semos Pharmaceuticals (Pvt) Ltd.
Nalfax	Dyson Research Laboratories
Peofax	Helix Pharma (Private) Limited
Pracit	Glitz Pharma
Snri	Semos Pharmaceuticals (Pvt) Ltd.
U-Safex	Usawa Pharmaceuticals
Usafex	Usawa Pharmaceuticals
Velax	The Schazoo Laboratories Ltd.
Venexine	Tagma Pharma (Pvt) Ltd.
Venxor F	Ferroza International Pharmaceuticals (Pvt) Ltd.
Vexine	Fassgen Pharmaceuticals
Vexor	Global Pharmaceuticals

Venlafaxine (Hcl) [Tabs 75 Mg]
Amfax Xr	Amson Vaccines & Pharma (Pvt) Ltd.
Efexiv	Panacea Pharmaceuticals
Efexor	Pfizer Laboratories Ltd.
Peofax	Helix Pharma (Private) Limited
Pracit	Glitz Pharma
Relaxine	Candid Pharmaceuticals
U-Safex	Usawa Pharmaceuticals
Usafex	Usawa Pharmaceuticals
Velax	The Schazoo Laboratories Ltd.
Velax Xr	The Schazoo Laboratories Ltd.
Venxor F	Ferroza International Pharmaceuticals (Pvt) Ltd.
Vexor	Global Pharmaceuticals
Vexor-Xr	Vision Pharmacueticals
Vinoxa	Wilshire Laboratories (Pvt) Ltd.

Venlafaxine (Hcl) [Tabs 75 Mg]
Amfax Xr	Amson Vaccines & Pharma (Pvt) Ltd.
Efexiv	Panacea Pharmaceuticals
Efexor	Pfizer Laboratories Ltd.
Peofax	Helix Pharma (Private) Limited
Pracit	Glitz Pharma
Relaxine	Candid Pharmaceuticals
U-Safex	Usawa Pharmaceuticals
Usafex	Usawa Pharmaceuticals
Velax	The Schazoo Laboratories Ltd.
Velax Xr	The Schazoo Laboratories Ltd.
Venxor F	Ferroza International Pharmaceuticals (Pvt) Ltd.
Vexor	Global Pharmaceuticals
Vexor-Xr	Vision Pharmacueticals
Vinoxa	Wilshire Laboratories (Pvt) Ltd.

Venlafaxine (Hcl) [Tabs 37.5 Mg]
Amfax	Amson Vaccines & Pharma (Pvt) Ltd.
Efexiv	Panacea Pharmaceuticals
Efexor	Pfizer Laboratories Ltd.
Enpress	Bryon Pharmaceuticals (Pvt) Ltd.
Faxidep	Saydon Pharmaceutical Industries (Pvt) Ltd.
Intefred	Friends Pharma (Pvt) Ltd
Nalfax	Dyson Research Laboratories
Peofax	Helix Pharma (Private) Limited
Pracit	Glitz Pharma
U-Safex	Usawa Pharmaceuticals
Usafex	Usawa Pharmaceuticals
Vanaxin	Hansel Pharmacueutical Pvt (Ltd)
Vela	Kurative Pak (Pvt) Ltd
Velax	The Schazoo Laboratories Ltd.
Venalax	Standpharm Pakistan (Pvt) Ltd.
Vendep	Danas Pharmaceuticals (Pvt) Ltd
Venice	Medisure Laboratories Pakistan (Pvt.) Ltd.
Vexine	Fassgen Pharmaceuticals
Vexor	Global Pharmaceuticals

Venlafaxine (Hcl) [Tabs Sr 75 Mg]
Xexor	Mass Pharma (Private) Limited
Zaxine	Mass Pharma (Private) Limited

Venlafaxine (Hcl) [Tabs Sr 37.5 Mg]
Faxine	Semos Pharmaceuticals (Pvt) Ltd.

Venlafaxine (Hcl) [Caps 75 Mg]
Efexor Xr	Pfizer Laboratories Ltd.
Efexze Xr	Z-Jans Pharmaceutical (Pvt) Ltd.
Faxine	Amarant Pharmaceuticals (Pvt)
Snri	Semos Pharmaceuticals (Pvt) Ltd.
Tifin Xr	Aptcure Private Limited
Veflex	Neutro Pharma (Pvt) Ltd.
Vela Xr	Kurative Pak (Pvt) Ltd
Venice Xr	Medisure Laboratories Pakistan (Pvt.) Ltd.
Venlaxine Sr	Medera Pharmaceuticals (Pvt) Ltd.
Vinoxa Xr	Wilshire Laboratories (Pvt) Ltd.
Xifexin Xr	Noa Hemis Pharmaceuticals

Venlafaxine (Hcl) [Caps 150 Mg]
Efexor Xr	Pfizer Laboratories Ltd.

Venlafaxine (Hcl) [Caps Sr 75 Mg]
Enpress	Bryon Pharmaceuticals (Pvt) Ltd.
Faxine	Semos Pharmaceuticals (Pvt) Ltd.
Venalax	Standpharm Pakistan (Pvt) Ltd.