Clomipramine

Registered South African indications:

• Depression
• Cataplexy
• Obsessive-compulsive disorder

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients  
• Hypersensitivity to tricyclic antidepressants
• Elderly (≥75 or elderly with cardiac, prostate or ophthalmic pathologies)
• Recent myocardial infarction
• Congenital long QT syndrome
• Hypokalaemia
• Narrow-angle glaucoma
• Retention of urine
• Mania
• Coadministration with other antidepressants
• Coadministration with monoamine oxidase inhibitors or within 14 days of their use
• Coadministration with linezolid
• Coadministration with methylene blue 

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly (≥60-74 years)
• Cardiovascular insufficiency
• Atrioventricular block (grade 1-3)
• Dysrhythmias 
• Low seizure threshold
• Adrenal tumours
• Schizophrenia
• Bipolar disorder
• High risk of suicidal thoughts
• Hyperthyroidism
• Abrupt withdrawal
• Prolonged use 
• Concomitant use with contact lens
• Galactose intolerance
• Fructose intolerance
• Lactase deficiency
• Sucrase-isomaltase insufficiency 
• Glucose-galactose malabsorption
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: tab, slow release (SR) tab, inj

Depressive episodes
Recurrent depressive disorders
Major depression
Obsessive-compulsive syndromes

• Oral (tab): Initiate: 25mg, 8-12hrly; Titrate by 25mg at intervals of1-3 days; Maintenance: 50-100mg, dly; Max: 250mg/24hrs 
• Oral (SR tab): 75mg, dly
• IM: 25-50mg; Titrate by 25mg, dly; Maintenance: 100-150mg/24hrs
• IV infusion: Initial: 50-75mg over 1.5-3hrs; Treatment duration: 3-5 days after clinical improvement seen

The dosage should be built up gradually for the single bedtime dose, in order to ensure maximum tolerability

Transfer from parenteral to oral dosing as soon as clinical improvement seen

Infusion to be given with 250-500ml isotonic saline or glucose solution

Cataplexy accompanying narcolepsy

• Oral (tab): 25-75mg, dly

Paed. forms avail. in SA and covered in this monograph: tab

Obsessive-compulsive disorders

Younger than 5 years

• Not established for use

Older than 5 years

• Oral (tab): Initial: 25mg, dly; Titrate slowly over 2 weeks; Maintenance: 3mg/kg OR 100mg (whichever is less); Max: 3mg/kg OR 200mg (whichever is less)

Pregnancy

• Caution
• There is limited amount of data from the use of clomipramine in pregnant women that indicates a potential to harm the foetus or cause congenital malformation
• Neonates whose mothers had taken tricyclic antidepressants up until delivery have developed dyspnoea, lethargy, colic, irritability, hypotension or hypertension, tremor or spasms, during the first few hours or days
• Studies in animals have shown reproductive toxicity. Clomipramine is not recommended during pregnancy and in women of childbearing potential not using contraception

Breastfeeding

• Caution; not recommended
• Clomipramine passes into the breast milk in small quantities. Therefore breastfeeding mothers should be advised to withdraw the medication or cease breastfeeding

Renal Impairment

• Caution; no dose adjustment recommended

Hepatic Impairment

• Caution; no dose adjustment recommended

Elderly

• ≥60-74 years: Caution; dose adjustment recommended
  Limit use for clinical cases of depression and/or severe OCD
  Use with high caution; Max: 100mg/24hrs 
  Avoid SR preparations
• ≥75 years/elderly with cardiac, prostate or ophthalmic pathologies: Contraindicated

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Drowsiness
• Transient fatigue
• Restlessness
• Increased appetite
• Confusion
• Disorientation
• Hallucinations
• Anxiety states
• Agitation
• Sleep disturbances
• Mania
• Hypomania
• Aggressiveness
• Impaired memory
• Depersonalisation
• Aggravated depression
• Impaired concentration
• Insomnia
• Nightmares
• Yawning
• Activation of psychotic symptoms
• Dizziness
• Tremor
• Headache
• Myoclonus
• Delirium
• Speech disorders
• Paraesthesia
• Muscle weakness
• Muscle hypertonia
• Convulsions
• Ataxia
• EEG changes
• Hyperpyrexia
• Neuroleptic malignant syndrome
• Peripheral neuropathy
• Extrapyramidal symptoms 

Cardiovascular Disorders

• Sinus tachycardia
• Palpitations
• Postural hypotension
• ECG changes 
• Dysrhythmias
• Increased blood pressure
• Conduction disorders 

Gastrointestinal Disorders

• Nausea and vomiting
• Abdominal disorders
• Diarrhoea
• Anorexia
• Dry mouth
• Constipation

Hepatobiliary Disorders

• Increased transaminases
• Hepatitis
• Stomatitis

Genitourinary Disorders

• Urinary retention
• Disturbances of micturition

Endocrine and Metabolic Disorders

• Increased weight 
• Disturbances of libido and potency
• Galactorrhoea
• Breast enlargement
• Syndroms of inappropriate antidiuretic hormone secretion
• Sweating
• Hot flushes

Skin and Subcutaneous Tissue Disorders

• Allergic skin reactions
• Photosensitivity
• Pruritus
• Oedema
• Hair loss
• Local reactions after intravenous injections

Immune, Blood and Lymphatic System Disorders

• Allergic alveolitis
• Systemic anaphylactic
• Anaphylactoid reactions
• Leucopenia
• Agranulocytosis
• Thrombocytopenia
• Eosinophilia 
• Purpura

Sensory Disorders

• Taste disturbances
• Tinnitus
• Glaucoma
• Disorders of visual accommodation 
• Blurred vision
• Mydriasis

• Tricyclic antidepressants
• Electroconvulsive therapy
• Monoamine oxidase inhibitors
• Adrenergic neurone blockers
• Anticholinergic agents
• Alpha agonists
• Beta-agonists
• Central nervous system depressants
• Diuretics
• Selective serotonin reuptake inhibitors
• Abiraterone acetate 
• Serotonergic agents
• Sympathomimetic agents
• Neuroleptics
• CYP2D6 inhibitors
• CYP1A2 inhibitors
• CYP2C19 inhibitors
• CYP3A4 inhibitors
• CYP450 inducers
• CYP2D6 inducers 
• CYP1A2 inducers
• CYP2C19 inducers 
• CYP3A4 inducers

• Blood pressure 
• Hepatic function
• Full blood count

Specific cases may require:

• ECG 

Clomipramine has actions at several sites including alpha1 adrenolytic, anticholinergic, antihistaminic and antiserotonergic activities. The therapeutic activity of clomipramine is believed to be based on its ability to inhibit neuronal reuptake of serotonin, primarily, and also noradrenaline.

Tablet 10mg

• Anafranil (Novartis) originator
• Equinorm (Pharmacare)

Tablet 25mg

• Anafranil (Novartis) originator
• Clomidep (Ranbaxy)
• Equinorm (Pharmacare)
• Micro-Clomipramine (Micro)

Tablet SR 75mg

• Anafranil SR (Novartis) originator

Injection (per 2ml) 25mg

• Anafranil (Novartis) originator
• Micro-Clomipramine (Micro)