Desvenlafaxine

Registered South African indications:

• Major depressive disorder

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to venlafaxine hydrochloride
• Coadministration with a monoamine oxidase inhibitor (MAOI) including linezolid, or within at least 14 days of discontinuing treatment with an MAOI
• Children younger than 18 years of age
• Pregnancy
• Breastfeeding

• Moderate to severe renal impairment
• Moderate to severe hepatic impairment
• Cardiovascular disease
• Hypertension
• Cerebrovascular disease
• Lipid metabolism disorders
• Bleeding disorders
• History of bleeding disorders
  - Von Willebrand disease
  - Haemophilia A
  - Deficiency in F VIII
  - Haemophilia B
• Comorbid bleeding disorders
  - Multiple pregnancy
  - Gestational hypertension
  - Preeclampsia
• Seizure disorders
• History or family history of mania or hypomania
• Raised intraocular pressure
• Risk factors for closed angle glaucoma
• Volume depletion
• Abrupt withdrawal
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: fct, tab

South African registered indications and dosages

Major depressive disorder

• Oral (fct, tab): 50mg, once dly with or without food; Titrate at an interval of not less than 7 days; Max: 100mg/24hrs

Discontinuation of desvenlafaxine
Symptoms associated with the discontinuation of desvenlafaxine, other SNRIs and SSRIs have been reported. Monitor patients for these symptoms when discontinuing treatment. A gradual reduction in the dose, rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the medical practitioner may continue decreasing the dose but at a more gradual rate

Switching patients from other antidepressants to desvenlafaxine
Discontinuation symptoms have been reported when switching patients from other antidepressants, including venlafaxine, to desvenlafaxine. Tapering of the initial antidepressant may be necessary to minimise discontinuation symptoms

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

Pregnancy

South African recommendations

• Contraindicated
• Desvenlafaxine must not be administered to pregnant women. Safety during pregnancy has not been established. Observational data indicate an increased risk (less than 2-fold) of postpartum haemorrhage following SSRI/SNRI exposure within the month prior to birth
• Studies have demonstrated that desvenlafaxine crosses the human placenta. If desvenlafaxine is used until, or shortly before birth, discontinuation effects in the newborn may occur
• Complications, including the need for respiratory support, tube-feeding or prolonged hospitalisation, have been reported in neonates exposed to SNRIs or SSRIs late in the third trimester. Such complications can arise immediately upon delivery
• Patients should be advised to notify their doctor if they become pregnant or intend to become pregnant during therapy Observational data indicate an increased risk (less than 2-fold) of postpartum haemorrhage following SSRI/SNRI exposure within the month prior to birth

Breastfeeding

South African recommendations

• Contraindicated
• Desvenlafaxine must not be administered to lactating women. Safety during lactation have not been established
• Desvenlafaxine (O-desmethylvenlafaxine) is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue desvenlafaxine, taking into account the importance of the medicine to the mother

Fertility

South African recommendations

• No information available

• Mild: No dose adjustment recommended
• Moderate to severe: Caution; dose adjustment recommended 

• Child-Pugh A: No dose adjustment recommended
• Child-Pugh Class B and C: Caution; dose adjustment recommended
  Initial: 50mg daily; Max dose: 100mg/24hrs

• No dose adjustment recommended

Central Nervous System Disorders

• Dizziness
• Insomnia
• Drowsiness
• Fatigue
• Anxiety
• Abnormal dreams
• Jitteriness
• Depersonalisation
• Dystonia
• Vertigo
• Yawning
• Disturbances in attention
• Seizures

Cardiovascular Disorders

• Orthostatic hypotension
• Syncope
• Tachycardia
• Hypertension
• Coronary occlusion
• Ischaemic heart disease
• Myocardial infarction

Gastrointestinal Disorders

• Nausea and vomiting
• Xerostomia
• Constipation
• Decreased appetite
• Bruxism

Hepatobiliary Disorders

• Abnormal hepatic function tests
• Acute pancreatitis

Genitourinary Disorders

• Delayed ejaculation
• Failed ejaculation
• Male sexual disorder
• Proteinuria
• Erectile dysfunction
• Urinary retention
• Urinary hesitancy
• Anorgasmia

Endocrine and Metabolic Disorders

• Decreased libido
• Increased serum cholesterol 
• Increased LDL cholesterol
• Increased serum prolactin
• Increased weight
• Hot flushes

Musculoskeletal Disorders

• Tremor
• Stiffness
• Weakness

Skin and Subcutaneous Tissue Disorders

• Hyperhidrosis
• Alopecia
• Photosensitivity
• Rash
• Stevens-Johnson syndrome

Immune, Blood and Lymphatic System Disorders

• Angioedema

Sensory Disorders

• Blurred vision
• Mydriasis
• Tinnitus
• Closed angle glaucoma

• Serotonergic agents
• CYP3A4 inhibitors
• CYP2D6 substrates
• Alcohol
• Alpha agonists
• Beta agonists
• Dapoxetine
• Antiplatelet agents
• Iobenguane I 123
• Linezolid
• Monoamine oxidase inhibitors
• Methylene blue
• Metoclopramide
• Urokinase

• Renal function
• Blood pressure
• Serum lipids

Specific cases may require

• Intraocular pressure
• 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)

Desvenlafaxine succinate is the major active metabolite of venlafaxine. It is thought to derive its clinical effect through the inhibition of serotonin and norepinephrine reuptake, which potentiates the effect of these neurotransmitters.  

Film coated tablet 50mg

• Depven 50 XL (Cipla Medpro)

Film coated tablet 100mg

• Depven 100 XL (Cipla Medpro)

Tablet srt 50mg

• Deslafeks (Innovata Pharmaceuticals)
• Deslafore XR 50 (Adcock Ingram)
• Exlov XR (Pharma Dynamics)
• Exsira (Pfizer) originator

Tablet srt 100mg

• Deslafeks (Innovata Pharmaceuticals)
• Deslafore XR 100 (Adcock Ingram)
• Exlov XR (Pharma Dynamics)
• Exsira (Pfizer) originator