Imipramine

Registered South African indications: 

• Depression
• Behavioural disorders in children
• Nocturnal enuresis

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Severe hepatic impairment
• Porphyria
• Cross-sensitivity to other tricyclic antidepressants of the dibenzazepine group
• Heart block 
• Cardiac arrhythmias
• Recent myocardial infarction
• Narrow angle glaucoma
• Urine retention
• Mania
• Children < 6 years
• Coadministration with selective, reversible monoamine oxidase inhibitors

Cautions

• Pregnancy
• Breastfeeding
• Severe renal impairment
• Mild to moderate hepatic impairment
• Elderly
• Epilepsy and risk factors thereof
• Adrenal medulla tumours
• Panic disorders
• Hyperthyroidism
• Hypotension
• History of increased intraocular pressure
• History of narrow angle glaucoma
• Chronic constipation
• History of urinary retention
• Long term therapy
• Concomitant use of contact lenses
• Abrupt withdrawal
• Agitated patients
• Schizophrenia
• History of suicide-related events, or those exhibiting a significant degree of suicidal ideation
• May impair ability to drive and operate machinery
• Concomitant treatment with electroconvulsive therapy
• Hyponatraemia

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

Depression
- Outpatients

• Oral (tab): Initial: 25-75mg/day, in divided doses; Titrate stepwise to 150-200mg, dly; Maintenance: 50-100mg, dly

Depression
- Inpatients

• Oral (tab): Initial: 200-300mg/day, in divided doses; Maintenance: 100mg, dly

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

Nocturnal enuresis

Younger than 5 years

• Not established for use

Between 5-8 years

• Oral (tab): Initial: 20-30mg, dly, at night; Higher dosage should be reserved for poor clinical response at intervals of 1 week
• Body weight 18-25kg: Oral (tab): 0.9-1.2mg/kg, daily

Between 9-12 years

• Oral (tab): Initial: 25-50mg, dly, at night; Higher dosage should be reserved for poor clinical response at intervals of 1 week
• Body weight 28-39kg: Oral (tab): 0.9-1.3mg/kg, daily

Older than 12 years

• Oral (tab): Initial: 25-75mg, dly, at night; Higher dosage should be reserved for poor clinical response at intervals of 1 week

Dose should be given as a single dose after evening meal

For children subject to enuresis early on the night, part of the dose can be taken early afternoon

Once desired response is achieved, treatment should be continued for a further 1-3 months (with the lowest maintenance dose)

Pregnancy

• Caution
• There is no evidence of the safety of the drug in human pregnancy. There have been isolated reports of a possible connection between the use of tricyclic antidepressants and adverse effects (developmental disorders) on the foetus. Treatment with imipramine should be avoided during pregnancy unless the anticipated benefits justify the potential risk to the foetus. Neonates whose mothers had taken imipramine up until delivery have developed dyspnoea, lethargy, colic, irritability, hypotension or hypertension, tremor or spasms, during the first few hours or days. If possible, imipramine should be gradually withdrawn at least 7 weeks before the calculated date of confinement

Breastfeeding

• Caution; not recommended
• As imipramine is excreted in breast milk, it should not be administered to nursing mothers unless considered essential when the mother should be advised to cease breastfeeding

Renal Impairment

• Mild to moderate: No dose adjustment recommended
• Severe: Caution; no dose adjustment recommended

Hepatic Impairment

• Mild to moderate: Caution; no dose adjustment recommended
• Severe: Contraindicated

Elderly

• Caution; dose adjustment recommended
  Initial: 10mg, dly; Titrate up to 30-50mg, dly; Optimum dose should be reached in 10 days; Continue until the end of treatment

Porphyria Information

• Probably porphyrinogenic (PRP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Fatigue
• Drowsiness
• Restlessness
• Delirium
• Confusion
• Disorientation
• Hallucinations 
• Increased anxiety
• Agitation
• Sleep disturbances
• Labile mood
• Activation of psychotic symptoms
• Aggressiveness
• Paranoid delusion
• Suicidal ideation
• Suicidal behaviours
• Tremor
• Paraesthesia
• Headache
• Dizziness
• Epileptic seizures
• EEG changes
• Myoclonus
• Weakness
• Extrapyrimidal symptoms
• Ataxia
• Speech disorders
• Withdrawal symptoms
• Withdrawal in neonates

Cardiovascular Disorders

• Sinus tachycardia 
• ECG changes 
• Postural hypotension
• Cardiac arrhythmias 
• Severe hypotension 
• Arrhythmias
• Conduction disorders
• Palpitations
• Increased blood pressure
• Cardiac decompensation
• Peripheral vasospastic reactions

Gastrointestinal Disorders

• Dry mouth
• Constipation
• Paralytic ilius
• Nausea and vomiting
• Anorexia 
• Stomatitis
• Tongue lesions
• Abdominal disorders

Hepatobiliary Disorders

• Increased transaminases
• Impaired hepatic enzymes
• Hepatitis

Genitourinary Disorders

• Disturbance of micturition
• Disturbance of libido and potency

Endocrine and Metabolic Disorders

• Hot flushes
• Increased weight
• Enlarged mammary glands
• Galactorrhoea
• Syndrome of inappropriate antidiuretic hormone secretion
• Increase or decrease in blood sugar
• Decreased weight
• Hyponatraemia

Skin and Subcutaneous Tissue Disorders

• Oedema
• Photosensitivity
• Pruritus
• Petechiae
• Hair loss
• Sweating

Immune, Blood and Lymphatic System Disorders

• Allergic reactions
• Hypersensitivity
• Agranulocytosis
• Bone marrow depression
• Leucopenia
• Eosinophilia
• Thrombocytopenia 

Sensory Disorders

• Blurred vision
• Disturbance in visual accommodation
• Mydriasis
• Tinnitis

• Electroconvulsive therapy
• Thyroid therapy
• Monoamine oxidase inhibitors
• Selective serotonin reuptake inhibitors 
• Central nervous system depressants
• Alprazolam
• Disulfiram
• Neuroleptics
• Adrenergic neurone blockers
• Beta blockers
• Diuretics
• Alpha-2 adrenoceptor stimulants
• Anticoagulants
• Anticholinergic agents
• Sympathomimetic agents
• Quinidine
• Hepatic enzyme inducers
• Cimetidine
• Methylphenidate
• Oestrogens
• Antiviral agents
• Calcium channel blockers
• Nitrates
• Dopaminergic agents
• Centrally acting appetite suppressants
• Antineoplastic agents
• Analgesics
• Antiarrhythmics
• Muscle relaxants

• Vital signs
• Hepatic function

Specific cases may require:

• Dental examination
• ECG
• Full blood count
• Cardiac function (elderly)

Ability to Drive and Use Machines

Patients should be warned:

• That blurred vision, drowsiness and other CNS symptoms may occur
• Against possible hazards such as driving a car, operating machinery or doing anything which may require alertness or quick actions
• That alcohol or other drugs may potentiate these effects

Imipramine hydrochloride is a tricyclic antidepressant with weak antihistamine and anticholinergic properties. Its therapeutic activity is believed to be due to its ability to inhibit the reuptake of noradrenaline and serotonin into the respective neurones.

Tablet 10mg

• Ethipramine (Pharmacare)
• Tofranil (Pharmaco) originator

Tablet 25mg

• Ethipramine (Pharmacare)
• Tofranil (Pharmaco) originator