Venlafaxine

Registered South African indications:

• Depression
• Anxiety disorders

Contraindications

XR Capsules and XR Tablets

• Hypersensitivity to the active ingredient or any of its excipients 
• Patients taking monoamine oxidase inhibitors (MAOIs)
• Patients who have discontinued treatment with an MAOI in less than 14 days
• Children under 18 years of age
• Pregnancy
• Breastfeeding

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Venlafaxine must be discontinued for at least 7 days before starting treatment with an MAOI. Severe adverse reactions have been reported when venlafaxine therapy is initiated soon after discontinuation of an MAOI and when an MAOI is initiated soon after discontinuation of venlafaxine

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Tablets

• Hypersensitivity to the active ingredient or any of its excipients
• Children under the age of 18 years
• Pregnancy
• Breastfeeding
• Concomitant use in patients taking monoamine oxidase inhibitors (MAOIs)

Cautions

• Renal impairment 
• Hepatic impairment 
• Elderly 
• History of suicidal related events
• Significant degree of suicidal ideation 
• Children and adolescents below 18 years
• Raised intraocular pressure 
• Poor cardiac function
• Hypertension
• Conditions which may be adversely affected by tachycardia
• Recent myocardial infarction
• Unstable heart disease
• QT prolongation or risk thereof
• Seizure disorders
• Volume depletion
• Bleeding diathesis
• History of bleeding disorders
  - Von Willebrand disease
  - Haemophilia A
  - Deficiency in F VIII
  - Haemophilia B
• Comorbid bleeding disorders
  - Multiple pregnancy
  - Gestational hypertension
  - Preeclampsia
• History or family history of bipolar disorder  
• History of aggression
• Abrupt withdrawal 
• Diabete mellitus
• Preexisting severe gastrointestinal narrowing
• Patients with dysphagia
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption

Forms avail. in SA and covered in this monograph: tab, extended release capsule (XR cap)

Major depressive episodes

• Oral (XR cap): Initial: 75mg, dly; Titrate by 75mg at intervals of at least 4 days; Maintenance: 75-375mg, dly; Max: 375mg/24hrs
• Oral (tab): 75-150mg/day, in 2-3 divided doses; Titrate by 50-75mg at intervals of at least 4 days; Maintenance: 75-375mg, in 2-3 divided doses; Max: 375mg/24hrs

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Antidepressive medicinal products should continue for at least 6 months following remission

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Generalised anxiety disorder
Social anxiety disorder

• Oral (XR cap): Initial: 75mg, dly; Titrate by 75mg at intervals of at least 4 days; Maintenance: 75-225mg, dly; Max: 225mg/24hrs

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Panic disorder

• Oral (XR cap): Initial: 37.5mg, dly for 7 days; Then titrate by 75mg at intervals of 2 weeks; Maintenance: 37.5-225mg, dly; Max: 225mg/24hrs

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Take with food

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Taper over at least 2 weeks if venlafaxine has been used for more than 6 weeks

Not established for use in children younger than 18 years (see Contraindications)

Pregnancy

• Contraindicated

Breastfeeding

• Contraindicated

Fertility

• Reduced fertility was observed in a study in which both male and female rats were exposed to O-desmethylvenlafaxine. The human relevance of this finding is unknown

Renal Impairment

• Caution; dose adjustment recommended

Hepatic Impairment

• Caution; dose adjustment recommended

Hepatic Impairment	Dose
Mild to moderate (Child-Pugh class A and B)	Reduce dose by 50%
Severe (Child-Pugh class C)	Reduce dose by ≥ 50%

Elderly

• Caution; no dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache 
• Abnormal dreams
• Decreased libido
• Dizziness
• Hypertonia
• Insomnia
• Nervousness
• Paresthesia
• Sedation
• Tremor
• Depersonalisation
• Apathy
• Hallucinations
• Myoclonus
• Agitation
• Impaired coordination and balance
• Akathisia
• Psychomotor restlessness
• Seizures 
• Mania
• Neuroleptic malignant syndrome 
• Serotonergic syndrome
• Delirium
• Extrapyramidal reactions 
• Suicidal ideation and behaviours
• Vertigo
• Aggression
• Asthenia 

Cardiovascular Disorders

• Hypertension
• Vasodilatation
• Palpitations
• Postural hypotension
• Syncope
• Tachycardia
• Hypotension
• QT prolongation
• Ventricular fibrillation
• Ventricular tachycardia

Respiratory Disorders

• Yawning
• Pulmonary eosinophilia

Gastrointestinal Disorders

• Nausea and vomiting
• Anorexia
• Constipation
• Bruxism
• Diarrhoea
• Pancreatitis
• Dry mouth
• Gastrointestinal haemorrhage

Hepatobiliary Disorders

• Abnormal hepatic function tests
• Hepatitis

Genitourinary Disorders

• Abnormal ejaculation and orgasm (males)
• Anorgasmia
• Erectile dysfunction 
• Impaired urination
• Menstrual disorders 
• Pollakiuria
• Abnormal orgasm (females)
• Urinary retention
• Urinary incontinence
• Urogenital

Endocrine and Metabolic Disorders

• Increased serum cholesterol 
• Weight loss
• Weight gain
• Hyponatraemia
• Syndrome of Inappropriate Antidiuretic Hormone Secretion 
• Increased prolactin 

Musculoskeletal Disorders

• Rhabdomyolysis

Skin and Subcutaneous Tissue Disorders

• Sweating 
• Rash
• Alopecia
• Erythema multiforme
• Toxic epidermal necrolysis
• Stevens-Johnson syndrome
• Pruritus
• Urticaria
• Photosensitivity

Immune, Blood and Lymphatic System Disorders

• Ecchymosis
• Mucous membrane bleeding
• Prolonged bleeding time
• Thrombocytopaenia
• Blood dyscrasias
• Angioedema
• Anaphylaxis

Sensory Disorders

• Abnormality of accommodation
• Mydriasis
• Visual disturbances
• Altered taste sensation
• Tinnitus
• Closed angle glaucoma

• Monoamine Oxidase Inhibitors
• Central nervous system active substances
• Selective serotonin reuptake inhibitors  
• Serotonin and noradrenalin reuptake inhibitors  
• Triptans
• Lithium  
• Sibutramine
• St. John's Wort
• Fentanyl and its analogues
• Tramadol
• Dextromethorphan
• Tapentadol
• Pethidine
• Methadone  
• Pentazocine
• Dopamine antagonists
• Alcohol
• QT prolonging agents 
• CYP3A4 inhibitors
• CYP2D6 inhibitors
• Lithium
• Antipsychotics
• Imipramine
• Metoprolol
• Indinavir
• Oral contraceptives
• Phentermine

• Blood pressure

Specific cases may require

• Mental status
• Ophthalmic examination
• Serum cholesterol
• ECG 
• Vital signs

Additional observations

• Blood loss
• Signs of anaemia
  - Fatigue
  - Shortness of breath
  - Chest pain
  - Lactation problems

Risk of postpartum haemorrhage (PPH)

• PPH is a leading cause of maternal mortality. Treatment with SSRIs and SNRIs within one month prior to birth may increase the risk of PPH
• Observational data indicate an increased risk of PPH following SSRI/ SNRI exposure within the month prior to delivery
• Healthcare professionals should be aware of the potential risk of PPH while making treatment decisions for prescribing SSRI/ SNRI towards the end of pregnancy
• Patients should be advised to inform their doctors before taking SSRI/ SNRI containing medicines if they have history of bleeding disorders (e.g von Willebrand disease, haemophilia A, deficiency in F VIII, and haemophilia B); and comorbid bleeding disorders (e.g multiple pregnancy, gestational hypertension or preeclampsia)

Therapy Assessment

• 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
• Longer-term treatment may also be appropriate for the prevention of recurrence of major depressive episodes (MDE)
• In most of the cases, the recommended dose in the prevention of MDE is the same as the one used during the current episode
• Antidepressive medicinal products should continue for at least six months following remission

Drug-laboratory Test Interactions

• False-positive urine immunoassay screening tests for phencyclidine (PCP) and amphetamine have been reported in patients taking venlafaxine 

Venlafaxine, and its active metabolite, O-desmethylvenlafaxine, inhibits the reuptake of serotonin and norepinephrine. It also inhibits reuptake of dopamine. It is not active at histaminergic, muscarinic, or alpha-1 adrenergic receptors.

Tablet 37.5mg

• Odiven (Zydus)

Tablet 75mg

• Odiven (Zydus)

Capsule XR 37.5mg

• Adco Venlafaxine XR (Adcock)
• Venlor XR (Cipla Medpro)

Capsule XR 75mg

• Adco Venlafaxine XR (Adcock)
• Efegen XR (Ranbaxy)
• Efexor XR (UpJohn) originator
• Sandoz Venlafaxine (Sandoz)
• Venlafaxine unicorn (Ranbaxy)
• Venlor XR (Cipla Medpro)

Capsule XR 150mg

• Adco Venlafaxine XR (Adcock)
• Efegen XR (Ranbaxy)
• Efexor XR (UpJohn) originator
• Sandoz Venlafaxine (Sandoz)
• Venlafaxine unicorn (Ranbaxy)
• Venlor XR (Cipla Medpro)