Venlafaxine oral modified release
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Modified release oral formulations of venlafaxine.
Drugs List
Therapeutic Indications
Uses
Panic disorders with or without agoraphobia
Prevention of relapse or recurrence of depressive illness
Social anxiety disorder
Treatment of depressive illness
Treatment of generalised anxiety disorder (GAD)
Unlicensed Uses
Menopausal symptoms in women with breast cancer
Dosage
Patients should be treated for a sufficient period of time, usually several months or longer.
Treatment should be reassessed regularly on a case-by-case basis, taking into consideration the risk of relapse or recurrence of symptoms.
Dose increases should be made at 2 week intervals. In severe cases, doses may be increased more frequently but not less than every 4 days.
Adults
Depression
75mg once daily.
If initial response is poor, consider increasing the dose as needed to a maximum of 375mg daily.
Treatment should continue for 6 months following remission. This duration may be increased in patients at a higher risk of relapse or recurrence.
Generalised Anxiety Disorder
75mg once daily.
If initial response is poor, consider increasing the dose as needed to a maximum of 225mg daily.
Social Anxiety Disorder
75mg once daily.
If initial response is poor, consider increasing the dose as needed to a maximum of 225mg daily. There is no evidence there is any additional benefit of higher doses.
Panic disorders
37.5mg once daily for 7 days, increasing to 75mg once daily,
If initial response is poor, consider increasing the dose as needed to a maximum of 225mg daily.
Menopausal symptoms, particularly hot flushes, in women with breast cancer (unlicensed)
37.5mg once daily for 7 days,
If required, increase to 75mg once daily.
Patients with Renal Impairment
Severe renal impairment (GFR less than 30 ml/minute) and patients requiring haemodialysis: reduce dose by 50%.
Patients with Hepatic Impairment
In hepatic cirrhosis and mild to moderate hepatic impairment a dose reduction of 50% should be considered.
Caution in severe hepatic impairment, a dose reduction of greater than 50% should be considered.
Additional Dosage Information
Switching from immediate release preparations
Patients treated with venlafaxine immediate release preparations may be switched to venlafaxine modified release preparations at the nearest equivalent daily dosage. Individual dosage adjustments may be necessary.
Contraindications
Children under 18 years
Within 2 weeks of discontinuing MAOIs
Breastfeeding
Long QT syndrome
Serious cardiac arrhythmias
Torsade de pointes
Uncontrolled epileptic disorder
Uncontrolled hypertension
Precautions and Warnings
Elderly
Family history of bipolar disorder
Family history of long QT syndrome
Patients under 25 years
Predisposition to haemorrhage
Predisposition to narrow angle glaucoma
Recent anticoagulant therapy
Suicidal ideation
Aggression
Cardiac arrhythmias
Coagulopathy
Diabetes mellitus
Dysphagia
Electrolyte imbalance
Epileptic disorder
Galactosaemia
Gastrointestinal stenosis
Glaucoma
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hereditary fructose intolerance
History of bipolar disorder
History of seizures
History of torsade de pointes
Hypercholesterolaemia
Hypertension
Lactose intolerance
Pregnancy
Recent myocardial infarction
Renal impairment
Unstable cardiac disorder
Adjustment of hypoglycaemic therapy may be necessary in diabetes mellitus
Correct electrolyte disorders before treatment
Reduce dose in patients with hepatic impairment
Reduce dose in patients with severe renal impairment
Advise patient ability to drive or operate machinery may be impaired
Ensure hypertension is controlled prior to treatment
Not all available brands are licensed for all indications
Not all available strengths are licensed for all indications
Some brands contain Carmoisine (E122) - can trigger allergic reactions
Some brands contain Quinoline Yellow (E104) : May cause allergic reactions
Some brands contain Sunset Yellow (E110) - can trigger allergic reactions
Some formulations contain lactose
Some formulations contain sucrose
Screen patient for hypertension and control as appropriate
Consider monitoring ECG in patients at risk of QT prolongation
Discontinue treatment if patient develops seizures
Monitor cholesterol and triglyceride levels
Monitor for signs of suicide ideation or behaviour
Monitor heart rate and blood pressure regularly
Monitor patient closely during titration of dose
Monitor patients at risk of glaucoma for increases in intraocular pressure
Monitor patients for adverse reactions including restlessness & agitation
Monitor patients for signs and symptoms of Neuroleptic Malignant Syndrome
Monitor patients for signs and symptoms of Serotonin Syndrome
Monitor serum electrolytes
Advise patient to report any new or worsening depression/suicidal ideation
Aggressive behaviour may occur
Consider discontinuation if patient develops psychomotor restlessness
Consider hyponatraemia in all patients with drowsiness/confusion/seizures
Decreased salivary secretions may lead to dental caries
Do not increase dosage in patients who develop akathisia
Potential for increased risk of bleeding
Potential for withdrawal symptoms
May affect results of some laboratory tests
Avoid abrupt withdrawal
Avoid MAOIs for 7 days after discontinuing this drug
To discontinue, reduce dose gradually
Discontinue if patient enters a manic phase
Discontinue if serotonin syndrome develops
Maintain treatment at the lowest effective dose
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise patient of need for high oral hygiene standards
Advise patient/carers to report signs of suicide ideation or behaviour
Advise patients that empty tablet/capsule may be observed in stools
Some prolonged-release tablet formulations are nondeformable and do not appreciably change in shape in the gastrointestinal (GI) tract, therefore they should not be administered to patients with pre-existing severe GI narrowing (pathologic or latrogenic) or in patients with dysphagia or significant difficulty in swallowing tablets.
Close supervision is advised in all patients in particular those at high risk, during early treatment and following dose changes. Suicide, suicidal thoughts and aggression have been observed in patients during changes in venlafaxine dosing regime, including discontinuation. Therefore, patients should be closely monitored when the dose is reduced or during discontinuation.
Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of self harm is highest shortly after presentation and the risk of suicide may increase again in the early stages of recovery. Furthermore, there is evidence that in children, adolescents and adult under 25 years, antidepressants may increase the risk of suicidal thoughts and self harm.
Other psychiatric conditions for which venlafaxine is prescribed can also be associated with an increased risk of suicide related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.
Patients with a history of suicide related events, those exhibiting a significant degree of suicidal ideation prior to commencement of treatment, and young adults, are at a greater risk of suicidal thought or suicide attempt, and should receive careful monitoring during treatment.
If serotonin syndrome is suspected, a dose reduction or discontinuation of treatment should be considered depending on the severity of the symptoms.
Increases in heart rate can occur, particularly at high doses. Caution should be exercised in patients whose underlying conditions might be compromised by increased heart rate.
Pregnancy and Lactation
Pregnancy
Use venlafaxine with caution during pregnancy.
At the time of writing there is limited data regarding the use of venlafaxine in pregnancy. Manufacturers advise that venlafaxine must only be administered to pregnant women if the expected benefits outweigh any possible risk.
Animal studies have demonstrated reproductive toxicity, however effects have only been observed at supra-therapeutic doses. Whilst the limited human data has shown no evidence of structural anomalies, developmental toxicity including spontaneous abortions, low birth weight, premature birth, neonatal serotonin syndrome, neonatal behavioural syndrome (withdrawal including seizures) and respiratory distress have been reported.
Use of venlafaxine up until or shortly before birth can cause withdrawal effects or adaptation problems in the neonate. In the majority of cases, symptoms arise within 24 hours of delivery and include irritability, tremor, hypotonia, persistent crying, and difficulty in sucking or in sleeping. Complications requiring tube-feeding, respiratory support or prolonged hospitalisation have also been reported.
Persistent pulmonary hypertension in the newborn (PPHN) is also a potential risk. Whilst a link to venlafaxine has not been investigated, epidemiological data suggests an increased risk of PPHN following use of selective serotonin reuptake inhibitors, particularly during late pregnancy. Due to their similar mechanism of action, a risk with venlafaxine cannot be ruled out. SNRIs may also increase the risk of postpartum haemorrhage within the month prior to birth.
In patients established on venlafaxine prior to becoming pregnant, abrupt discontinuation should be avoided as this carries a higher risk of relapse. Ongoing management should balance potential risk to the foetus with potential risk to maternal health if treatment is discontinued/changed. Venlafaxine may be continued with caution in those at a significant risk of relapse. When managing new episodes of depression or anxiety during pregnancy, consider the use of psychological therapy where possible. Whilst no antidepressant is considered safe during pregnancy, alternative options with greater experience may be preferable.
Lactation
Venlafaxine is contraindicated in breastfeeding.
The manufacturers do not recommend concomitant venlafaxine and breastfeeding.
Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), transfer into breast milk. The effect on the nursing infant is unknown. LactMed states that ODV has been found in the plasma of most breastfed infants, with no proven drug-related side effects reported. Breastfed infants, especially newborn or preterm infants, should be monitored for excessive sedation and adequate weight gain if this drug is used during lactation. There have been reports crying, irritability, and abnormal sleep patterns. Discontinuation symptoms have been reported after stopping breastfeeding.
Briggs (2015) notes that venlafaxine provides a relatively high infant dose compared to other antidepressants and that long-term effects on neurobehaviour and cognitive development have not been adequately studied. If used, the infant should be monitored for short-term adverse effects. Schaefer (2015) concludes that venlafaxine is tolerable if compellingly indicated, but that whenever possible, drugs of choice among the tricyclic antidepressants or selective serotonin reuptake inhibitors should be used in preference.
Side Effects
Abdominal pain
Abnormal ejaculation
Aggression
Agitation
Akathisia
Alopecia
Anaphylaxis
Angioedema
Anorexia
Anxiety
Arrhythmias
Arthralgia
Asthenia
Blood dyscrasias
Blood pressure changes
Bruxism
Chest pain
Chills
Confusion
Constipation
Delirium
Diarrhoea
Disturbances in accommodation
Dizziness
Dream abnormalities
Drowsiness
Dry mouth
Dysarthria
Dyspepsia
Dyspnoea
Ecchymosis
Emotional lability
Epistaxis
Erythema multiforme
Extrapyramidal effects
Gastrointestinal bleeding
Haemorrhage
Hallucinations
Headache
Hepatitis
Hostility
Hypomania
Hyponatraemia
Impaired co-ordination
Impotence
Inappropriate secretion of antidiuretic hormone
Increase in plasma cholesterol
Increased prolactin
Increases in hepatic enzymes (reversible)
Insomnia
Loss of balance
Mania
Menstrual disturbances
Micturition disorders
Mucous membrane bleeding
Muscle spasm
Myalgia
Mydriasis
Nausea
Nervousness
Neuroleptic malignant syndrome-like effect
Orgasmic dysfunction
Palpitations
Pancreatitis
Paraesthesia
Photosensitivity
Postural hypotension
Prolongation of QT interval
Prolonged bleeding
Pruritus
Psychiatric disorders
Psychomotor restlessness
Pulmonary eosinophilia
Pyrexia
Rash
Reduced libido
Rhabdomyolysis
Seizures
Serotonin syndrome
Sexual dysfunction
Somnolence
Speech disturbances
Stevens-Johnson syndrome
Suicidal tendencies
Sweating
Syncope
Tachycardia
Tardive dyskinesia
Taste disturbances
Tinnitus
Torsades de pointes
Toxic epidermal necrolysis
Urticaria
Vasodilatation
Ventricular fibrillation
Vertigo
Visual disturbances
Vomiting
Weight changes
Withdrawal symptoms
Effects on Laboratory Tests
False-positive urine immunoassay screening tests for phencyclidine (PCP) and amphetamine have been reported in patients taking venlafaxine. This is due to lack of specificity of the screening tests. False positive test results may be expected for several days following discontinuation of venlafaxine therapy. Confirmatory tests, such as gas chromatography or mass spectrometry, will distinguish venlafaxine from PCP and amphetamine.
Withdrawal Symptoms and Signs
Dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor, headache, visual impairment and hypertension are the most commonly reported reactions.
Gradually reduce the dose over at least one to two weeks and monitor to minimise the risk of withdrawal reactions. The period required for discontinuation may depend on the dose, duration of therapy and the individual patient. It is recommended that high doses used for more than 6 weeks are tapered over a longer period.
If intolerable symptoms occur resume previous prescribed dose. Subsequently, continue decreasing the dose at a more gradual rate.
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: February 2018
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3nd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
Summary of Product Characteristics: Alventa XL 75 mg and 150mg. Consilient Health Ltd. Revised May 2015.
Summary of Product Characteristics: Apclaven XL 37.5mg prolonged release capsules. Torrent Pharma (UK) Ltd. Revised October 2018.
Summary of Product Characteristics: Apclaven XL 75mg prolonged release capsules. Torrent Pharma (UK) Ltd. Revised October 2018.
Summary of Product Characteristics: Apclaven XL 150mg prolonged release capsules. Torrent Pharma (UK) Ltd. Revised October 2018.
Summary of Product Characteristics: Depefex XL. Chiesi Limited. Revised January 2021.
Summary of Product Characteristics: Efexor XL 75mg hard prolonged release capsules. Upjohn UK Ltd. Revised September 2020.
Summary of Product Characteristics: Efexor XL 150mg hard prolonged release capsules. Upjohn UK Ltd. Revised September 2020.
Summary of Product Characteristics: Efexor XL 225mg capsules. Upjohn UK Ltd. Revised September 2020.
Summary of Product Characteristics: Majoven XL 37.5mg prolonged release tablets. Bristol Laboratories Ltd Pharma. Revised August 2017.
Summary of Product Characteristics: Majoven XL 75mg prolonged release tablets. Bristol Laboratories Ltd Pharma. Revised August 2017.
Summary of Product Characteristics: Majoven XL 150mg prolonged release tablets. Bristol Laboratories Ltd Pharma. Revised August 2017.
Summary of Product Characteristics: Politid XL. Actavis Pharmaceuticals. Revised November 2015.
Summary of Product Characteristics: Rodomel XL. Teva UK Ltd. Revised November 2011.
Summary of Product Characteristics: Tonpular XL. Wockhardt UK Ltd. Revised November 2018.
Summary of Product Characteristics: Vencarm XL 37.5mg prolonged release capsules. Aspire Pharma Ltd. Revised March 2018.
Summary of Product Characteristics: Vencarm XL 75mg prolonged release capsules. Aspire Pharma Ltd. Revised March 2018.
Summary of Product Characteristics: Vencarm XL 150mg prolonged release capsules. Aspire Pharma Ltd. Revised March 2018.
Summary of Product Characteristics: Vencarm XL 225mg prolonged release capsules. Aspire Pharma Ltd. Revised March 2018.
Summary of Product Characteristics: Venlalic XL. Ethypharm UK Ltd. Revised December 2012.
Summary of Product Characteristics: Venlablue XL 37.5mg. Bluefish Pharmaceuticals AG. Revised September 2010.
Summary of Product Characteristics: Venlablue XL 75mg. Bluefish Pharmaceuticals AG. Revised September 2010.
Summary of Product Characteristics: Venlablue XL 150mg. Bluefish Pharmaceuticals AG. Revised September 2010.
Summary of Product Characteristics: Venladex XL 225mg prolonged release tablets. Dexcel Pharma Ltd. Revised December 2018.
Summary of Product Characteristics: Venlafaxine XL 225mg prolonged release capsules. Teva. Revised March 2021.
Summary of Product Characteristics: Venlafaxine XL 225mg prolonged release capsules. Teva. Revised March 2021.
Summary of Product Characteristics: Venlalic (venlafaxine) XL 300mg prolonged-release tablet. Martindale Pharma. Revised November 2021.
Summary of Product Characteristics: Venlasov XL 150mg Capsules. Sovereign medical Ltd. Revised November 2016.
Summary of Product Characteristics: Vensir XL 75mg, 120mg, 225mg Capsules. Morningside Healthcare Ltd. Revised March 2018.
Summary of Product Characteristics: Venzip XL 75mg prolonged release capsules. Aurobindo Pharma - Milpharma Ltd. Revised April 2018.
Summary of Product Characteristics: Venzip XL 150mg prolonged release capsules. Aurobindo Pharma - Milpharm Ltd. Revised April 2018.
Summary of Product Characteristics: ViePax XL 75mg prolonged release tablets. Dexcel Pharma. Revised December 2018.
Summary of Product Characteristics: ViePax XL 150mg prolonged release tablets. Dexcel Pharma. Revised December 2018.
Summary of Product Characteristics: ViePax XL 225mg prolonged release tablets. Dexcel Pharma. Revised December 2018.
MHRA Drug Safety Update January 2021 Available at: https://www.mhra.gov.uk Last accessed: 11 February 2021
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 20 February 2018
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Venlafaxine Last revised: 10 March 2015.
Last accessed: 20 February 2018
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
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