Imi

Uses

Depression: For the relief of symptoms of depression. Endogenous depression is more likely to be alleviated than other depressive states. One to three weeks of treatment may be needed before optimal therapeutic effects are evident.

Childhood Enuresis: May be useful as temporary adjunctive therapy in reducing enuresis in children aged 6 years and older, after possible organic causes have been excluded by appropriate tests. In patients having daytime symptoms of frequency and urgency, examination should include voiding cystourethrography and cystoscopy, as necessary. The effectiveness of treatment may decrease with continued drug administration.

Imi is also used to associated treatment for these conditions: Attention Deficit Hyperactivity Disorder (ADHD), Bulimia Nervosa, Enuresis, Major Depressive Disorder (MDD), Neuropathic Pain, Panic Disorder, Post Traumatic Stress Disorder (PTSD)

How Imi works

Imi works by inhibiting the neuronal reuptake of the neurotransmitters norepinephrine and serotonin . It binds the sodium-dependent serotonin transporter and sodium-dependent norepinephrine transporter reducing the reuptake of norepinephrine and serotonin by neurons. Depression has been linked to a lack of stimulation of the post-synaptic neuron by norepinephrine and serotonin . Slowing the reuptake of these neurotransmitters increases their concentration in the synaptic cleft, producing knock-on effects in protein kinase signalling which is thought to contribute to changes in neurotransmission and brain physiology which relieves symptoms of depression .

Dosage

Imi dosage

Depression: Initially up to 75 mg daily in divided doses increased gradually to 150-200 mg (up to 300 mg in hospital); up to 150 mg may be given as a single dose at bed time; elderly, initially 10 mg daily, increased gradually to 30-50 mg daily; child not recommended for depression.

Panic attack: Initially 10-25 mg/day, depending on how the medication is tolerated, raise the dose until the desired response is obtained. The daily doses required vary greatly from patient to patient, between 75-150 mg, if necessary it can be increased to 200 mg.Nocturnal enuresis (Child): 

• 7 years: 25 mg
• 8 to 11 years: 20-50 mg
• Over 11 years: 50-75 mg at bedtime; max. period of treatment (Including gradual withdrawal) is 3 months; full physical examination is required before further course.

Side Effects

Dry mouth, less sedation, blurred vision (disturbances of accommodation, increased intraocular pressure), constipation, nausea, difficulty with micturation; cardiovascular side-effects, sweating, tremors, rashes and hypersensitivity reaction (including urticaria & photosensitivity), behavioral disturbances (particularly in children) hypomania or mania (particularly in elderly), interference with sexual function; blood sugar changes, increased appetite, weight gain (occasionally weight loss).

Toxicity

The anticholinergic actvity of imipramine can produce dry mucous membranes, blurred vision, increased intraocular pressure, hyperthermia, constipation, adynamic ileus, urinary retention, delayed micturition, and dilation of the urinary tract .

Central nervous system and neuromuscular effects include drowsiness, lethargy, fatigue, agitation, excitement, nightmares, restlessness, insomnia, confusion, disturbed concentration, disorientation, delusions, and hallucinations.

Effects on the GI tract include anorexia, nausea and vomiting, diarrhea, abdominal cramps, increases in pancreatic enzymes, epigastric distress, stomatitis, peculiar taste, and black tongue.

Rarely agranulocytosis, thrombocytopenia, eosinophilia, leukopenia, and purpura have occured.

Infants whose mothers were receiving tricyclic antidepressants prior to delivery have experienced cardiac problems, irritability, respiratory distress, muscle spasms, seizures, and urinary retention.

Serotonin syndrome can occur when used in conjunction with other pro-serotonergic drugs.

LD₅₀/> Values

Rat - Oral 250 mg/kg - Intraperitoneal 79mg/kg - Subcutaneous 250 mg/kg - Intravenous 15.9 mg/kg

Mouse - Oral 188 mg/kg - Intraperitoneal 51.6 mg/kg - Subcutaneous 195 μg/kg - Intravenous 21 mg/kg

Human range of toxicity is considered to include single dosages greater than 5 mg/kg.

Precaution

Cardiac diseases (particularly with arrhythmias), history with epilepsy, pregnancy and breast feeding, elderly, hepatic impairment (avoid if severe), thyroid disease, psychoses, angle-closure glaucoma, history of urinary retention, concurrent electro-convulsive therapy. Drowsiness may affect performances of skilled tasks (e.g. driving), alcohol induced Imi effect.

Interaction

Imi should not be used in combination with Monoamine oxidase inhibitors (MAO), anticholinergic agents, antihypertensive agents, methylphenidate, levodopa, antipsychotic drug, cimetidine, barbiturates, and oral contraceptives.

Food Interaction

• Avoid alcohol.
• Avoid St. John's Wort.
• Do not take with bran and high fiber foods.
• Limit caffeine intake.
• Take with food.

Imi Alcohol interaction

[Moderate] GENERALLY AVOID:

Concomitant use of ethanol and a tricyclic antidepressant (TCA) may result altered TCA plasma levels and efficacy, and additive impairment of motor skills, especially driving skills.

Acute ethanol ingestion may inhibit TCA metabolism, while chronic ingestion of large amounts of ethanol may induce hepatic TCA metabolism.

Patients should be advised to avoid alcohol during TCA therapy.

Alcoholics who have undergone detoxification should be monitored for decreased TCA efficacy.

Dosage adjustments may be required.

Imi Drug Interaction

Major: duloxetine, duloxetine, escitalopram, escitalopramModerate: aripiprazole, aripiprazole, pregabalin, pregabalin, levothyroxine, levothyroxine, alprazolam, alprazolamUnknown: omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol

Imi Disease Interaction

Major: anticholinergic effects, cardiovascular disease, pheochromocytoma, acute myocardial infarction recovery, cardiovascular disease, depression, seizure disordersModerate: bone marrow suppression, diabetes, renal/liver disease, schizophrenia/bipolar disorder, tardive dyskinesia, acute alcohol intoxication, bipolar disorder screening, glaucoma, hyper/hypoglycemia, liver/renal disease, neutropenia, schizophrenia, thyroid disorders, urinary retention

Volume of Distribution

Imi has a high apparent volume of distribution of 10-20 L/kg . The drug is known to accumulate in the brain at concentrations 30-40 times that in systemic circulation.

Elimination Route

Rapidly and well absorbed (>95%) after oral administration . The primary site of absorption is the small intestine as the basic amine groups are ionized in the acidic environment of the stomach, preventing movement across tissues. Bioavailability ranges from 29-77% due to high inter-individual variability. Peak plasma concentration is usually attained 2-6 hours following oral administration. Absorption is unaffected by food.

Half Life

Imi has a mean half life of 12 h. Its active metabolite, desipramine has a mean half life of 22.5 h .

Clearance

Imi has a mean clearance of 1 L/h/kg. Its active metabolite, desipramine has a mean clearance of 1.8 L/h/kg .

Elimination Route

Imi is primarily excreted in the urine with less than 5% present as the parent compound

Pregnancy & Breastfeeding use

Pregnancy category D. Limited data suggest that imipramine is likely to be excreted in human breast milk. Known risk of damage to fetus.

Contraindication

Recent myocardial infarction, arrhythmias (particularly heart block), not indicated in manic phase, severe liver disease.

Acute Overdose

Children have been reported to be more sensitive than adults to an acute overdosage of imipramine. An acute overdose in infants or young children must be considered serious and potentially fatal.

Storage Condition

Store in a cool & dry place, protected from light and moisture. Keep all medicines out of the reach of children.

Innovators Monograph

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