Clofranil25 mg

Clofranil is a tricyclic antidepressant (TCA) with the following evidence-based uses:

Established/FDA-approved use

• Obsessive-Compulsive Disorder (OCD): Clofranil is indicated for the treatment of obsessions and compulsions in patients with OCD when these symptoms cause marked distress, are time-consuming, or significantly interfere with social or occupational functioning.

Guideline-supported / commonly used off-label uses

• Major depressive disorder (MDD): Clofranil is used off-label (and is an approved indication in some other countries) for depression, particularly when other antidepressants have failed, though it is not typically first-line due to its side-effect profile.
• Panic disorder with or without agoraphobia: used off-label in some treatment-resistant cases, based on limited trial evidence.
• Chronic pain / neuropathic pain syndromes: occasionally used off-label as an adjunct, consistent with other TCAs, though evidence is limited compared to amitriptyline.

Off-label uses should only be undertaken under specialist supervision after first-line options have been considered.

Each tablet/capsule contains Clomipramine Hydrochloride equivalent to the labeled strength of clomipramine base (commonly available as 10 mg, 25 mg, 50 mg, and 75 mg strengths). Inactive ingredients vary by manufacturer and formulation.

Clofranil is a dibenzazepine-derivative tricyclic antidepressant (TCA). It is chemically related to imipramine and is one of the most serotonin-selective agents within the TCA class, which underlies its particular efficacy in obsessive-compulsive disorder.

Clofranil is available in oral tablet and capsule formulations and is used under close medical supervision due to its cardiovascular and central nervous system side-effect profile, which is characteristic of tricyclic antidepressants.

Clofranil belongs to the Tricyclic Antidepressants (TCAs) class of drugs, specifically a dibenzazepine derivative with potent serotonin reuptake inhibition.

Clomipramine Hydrochloride and its active metabolite, desmethylclomipramine, inhibit the reuptake of serotonin and norepinephrine at the presynaptic neuronal membrane, increasing the concentration of these neurotransmitters in the synaptic cleft. Clomipramine Hydrochloride itself is a relatively potent and selective serotonin reuptake inhibitor compared to other TCAs, which is thought to explain its specific efficacy in OCD, while its metabolite contributes more norepinephrine reuptake inhibition.

Clomipramine Hydrochloride also has affinity for histaminergic (H1), cholinergic (muscarinic), and alpha-1 adrenergic receptors, accounting for its sedative, anticholinergic, and hypotensive side effects. It is extensively metabolized in the liver via the cytochrome P450 system (mainly CYP2D6 and CYP1A2/CYP3A4), with a plasma half-life of approximately 19-37 hours (and up to 54-77 hours for its active metabolite).

Clofranil is administered orally, preferably with food to minimize gastrointestinal irritation. Once a stable maintenance dose is reached, it may be given as a single bedtime dose to take advantage of its sedating effect and improve adherence. Tablets/capsules should be swallowed whole and not crushed or chewed unless the product labeling specifically permits it.

The following are well-established, clinically significant interactions with Clofranil:

• Monoamine oxidase inhibitors (MAOIs): concurrent use, or use within 14 days of stopping either drug, is contraindicated due to risk of serotonin syndrome and hypertensive crisis.
• Other serotonergic drugs (SSRIs, SNRIs, triptans, tramadol, linezolid, IV methylene blue, St. John's Wort): increased risk of serotonin syndrome; combine only with caution and close monitoring.
• CYP2D6 inhibitors (e.g., fluoxetine, paroxetine, quinidine, cimetidine): can significantly increase plasma levels of Clofranil, raising the risk of toxicity including cardiac and CNS effects; dose reduction may be needed.
• Other anticholinergic drugs (antihistamines, antipsychotics, antiparkinsonian agents): additive anticholinergic effects (dry mouth, constipation, urinary retention, confusion).
• CNS depressants (alcohol, benzodiazepines, opioids): additive sedation and respiratory depression risk.
• Drugs that prolong the QT interval or affect cardiac conduction (certain antiarrhythmics, antipsychotics): additive risk of arrhythmia, particularly important given the TCA class effect on cardiac conduction.
• Sympathomimetics (e.g., epinephrine): Clofranil may potentiate pressor effects; use with caution.

Side effects associated with Clofranil are generally consistent with the tricyclic antidepressant class and are often dose-related.

Very common (reported in a large proportion of patients)

• Dry mouth, constipation, and other anticholinergic effects
• Somnolence/drowsiness and fatigue
• Tremor and dizziness
• Nausea, dyspepsia, and weight gain
• Sexual dysfunction (notably ejaculatory failure in men, decreased libido)
• Excessive sweating

Less common but clinically important

• Orthostatic hypotension and tachycardia
• Blurred vision, urinary retention/hesitancy
• Weight gain, hyponatremia (particularly in elderly patients)

Serious (require prompt medical attention)

• Seizures, particularly at higher doses or with rapid dose increases
• Cardiac conduction abnormalities and arrhythmias
• Suicidal thinking or behavior, especially in patients under 25 years of age (see Precautions)
• Angle-closure glaucoma (acute eye pain, vision changes)
• Serotonin syndrome (when combined with other serotonergic agents)
• Rare severe skin reactions (e.g., DRESS syndrome)

Clofranil should be used during pregnancy only if clearly needed and if the potential benefit justifies the potential risk to the fetus; a physician must be consulted before use. Neonates whose mothers took tricyclic antidepressants, including Clofranil, late in the third trimester have developed withdrawal symptoms such as jitteriness, irritability, feeding difficulty, and, rarely, seizures — gradual tapering prior to delivery may be considered under medical guidance where feasible.

Clofranil and its active metabolite pass into breast milk. Because of the potential for adverse effects in the nursing infant, a decision should be made, in consultation with a physician, whether to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.

Boxed Warning: Suicidality

Antidepressants, including Clofranil, increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (under 25 years of age), particularly during the initial months of treatment or after dose changes. Patients of all ages should be monitored closely for clinical worsening, unusual behavior changes, and suicidality, and family members/caregivers should be advised of the need for close observation.

Cardiac conduction effects

Clofranil can cause dose-related changes in cardiac conduction (including QT prolongation) and arrhythmias, a risk shared by the TCA class and markedly increased in overdose. Caution is advised in patients with pre-existing cardiac disease, and an ECG should be considered before and during treatment in at-risk patients.

Seizures

Clofranil lowers the seizure threshold more than some other TCAs, particularly at higher doses or with rapid titration; use caution in patients with a seizure disorder or other risk factors for seizures.

Anticholinergic effects

Use with caution in patients with narrow-angle glaucoma, urinary retention or benign prostatic hyperplasia, and in the elderly, who are more sensitive to anticholinergic effects and at increased risk of falls, confusion, and cognitive impairment.

Discontinuation

Abrupt discontinuation after prolonged use may cause withdrawal-type symptoms (nausea, headache, malaise); dose should be tapered gradually under medical supervision rather than stopped suddenly.

Manic switch

May precipitate a manic or hypomanic episode in patients with underlying bipolar disorder; screen for bipolar disorder before initiating.

Overdose with Clofranil is particularly dangerous, even in relatively small amounts, due to its cardiotoxic and pro-convulsant effects, and is considered a medical emergency. Signs and symptoms may include cardiac arrhythmias and conduction block, severe hypotension, seizures, marked drowsiness progressing to coma, and severe anticholinergic effects (dilated pupils, dry mouth, urinary retention).

If overdose is suspected, seek immediate emergency medical attention or contact a poison control center right away. Treatment should be provided in a hospital setting with continuous cardiac monitoring; specific home treatment is not safe and should not be attempted.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Pediatric use

Clofranil is approved for use in children and adolescents aged 10-17 years for OCD, at doses up to 3 mg/kg/day or 200 mg/day (whichever is lower). Safety and efficacy in children under 10 years of age have not been established. Close monitoring for suicidality and cardiac effects is required, as in adults, and growth should be monitored during long-term use.

Elderly

Elderly patients are more sensitive to the anticholinergic, sedative, and cardiovascular effects of Clofranil; lower starting doses and slower titration are recommended, with maintenance doses generally not exceeding 75 mg/day unless closely supervised.

Renal impairment

No well-established dose adjustment guidelines exist; use with caution and at the lowest effective dose, with close clinical monitoring.

Hepatic impairment

Clofranil is extensively metabolized by the liver; use with caution and reduced doses in hepatic impairment, with close monitoring for toxicity.

Treatment duration for OCD with Clofranil should be individualized. An adequate trial typically requires at least 4-10 weeks at an optimized dose to assess response. If effective, treatment is often continued for a year or longer to prevent relapse, with periodic reassessment by the prescribing physician of the continued need for therapy. Discontinuation should always be via a gradual dose taper.

Tricyclic Antidepressant (TCA); Dibenzazepine derivative

Clomipramine Hydrochloride inhibits presynaptic reuptake of serotonin (and, via its active metabolite, norepinephrine), increasing synaptic concentrations of these neurotransmitters, which is believed to underlie its antidepressant and anti-obsessional effects. It also blocks histaminergic, cholinergic, and alpha-1 adrenergic receptors, which accounts for its characteristic side-effect profile.

C

Clofranil is indicated for OCD in children and adolescents aged 10-17 years, starting at 25 mg/day and titrated to a maximum of 3 mg/kg/day or 200 mg/day, whichever is lower. Safety and efficacy have not been established in children under 10 years of age. As with adults, pediatric patients require close monitoring for emergence or worsening of suicidal thoughts/behavior, particularly during the first weeks of treatment and after dose adjustments, as well as monitoring of growth and cardiac status during long-term therapy.