Durexin

Generic composition: Dosulepin

 General description

Durexin is formerly known as Dothiapen, belongs to Tricyclic antidepressants (TCAs) with anxiolytic effects.

Therapeutic category

• Tri-cyclic Anti-depressants

Dosage forms available

• DUREXIN 25mg Tablets

 Mechanism of action

Dosulepin is active in inhibiting the reuptake of noradrenaline, 5- hydroxytryptamine (5-HT) and dopamine. Dosulepin also reduces and/or down regulates central noradrenaline receptor numbers. It inhibits the uptake of 5-HT into the platelets. Dosulepin also has some central and peripheral anti-cholinergic and antihistaminic activity at standard dose levels.

Pharmacokinetics

Dosulepin is readily absorbed from small intestine, peak plasma concentration reaches in 2-3 hours, highly protein-bound, extensively metabolised in the liver and excreted primarily from urine. Dosulepin crosses blood-brain barrier, placenta and excreted in breast milk.

 Uses

• Major Depressive Disorders
• Neuropathic pain (Offlabel)

 Dose –

• Dosulepin to SSRI: gradually reduce the dose to 25mg – 50 mg / day then added SSRI at usual starting dose, and then slowly withdraw the remaining dosulepin over 5 – 7days.
• Dosulepin 25mg two to three times a day until using the dosulepin, this will reduce chances of side effects while it will be used to the dosulepin
• Dose start at 25 mg a day and be increased slowly to 75 mg a day for pain relief or preventing migraine.
• Adults: Initially 75 mg/day in divided doses or as a single dose at night, increasing to 150mg/day
• Elderly: 50-75mg daily initially.
• Children: Not recommended

 Side effects

Drowsiness, hyponatremia (esp in elderly), cardiotoxicity, postural hypotension, anticholinergic side effects (blurred vision, urinary retention, constipation), extra pyramidal side effects, arrhythmias, convulsions.

 Contraindications

• Recent myocardial infarction, any degree of heart block or other cardiac arrhythmias
• Mania
• Severe liver disease and hepatic dysfunction
• Hypersensitivity to dosulepin or to any of the excipients
• Epileptic patients as dosulepin decreases the seizure threshold
• Narrow angle glaucoma and prostatic hypertrophy
• Alcohol consumption due to CNS Depressant activity

Precautions

• Caution in elderly and patients susceptible for cardiovascular toxicity
• Suicidal tendency may be increased
• Caution in patients with history of mania or psychoses
• Renal impairment
• Gradual withdrawal recommended
• Diabetic patients as dosulepin may alter blood sugar levels
• Pregnancy; should be avoided unless compelling reason to administer.

Pregnancy category: C

Interactions

• MAOIs and SSRIs; concomitant administration should be avoided.
• Cardiovascular drugs (eg. quinidine), antiarrhythmics (eg. quinidine), calcium channel blockers (eg. diltiazem, verapamil), antihistamines (eg. astemizole and terfenadine), some antipsychotics (notably pimozide and sertindole), cisapride and sotalol; arrhythmias may precipitate.
• Antimuscarinic side effects may be enhanced by concurrent use with antimuscarinic drugs.
• Oral contraceptives may antagonise the antidepressant effect but side effects may be increased due to increased plasma concentrations of tricyclics.
• Diuretics; increased risk of postural hypotension
• It is advisable to review all antihypertensive therapy during treatment with tricyclic antidepressants.
• Anaesthetics given during tricyclic antidepressant therapy may increase the risk of arrhythmias and hypotension. If surgery is necessary, the anaesthetist should be informed that the patient is being so treated.
• Barbiturates and other enzyme inducers such as rifampicin; may increase the metabolism of tricyclic antidepressants and result in lowered plasma concentrations and reduced antidepressant response.

Advantages

• Fewer anticholinergic side effects of all TCAs.