Imipramine

Pronunciation: (im-IPP-ruh-meen)

Class: Tricyclic compound Imipramine Hydrochloride

Trade Names:

Tofranil

- Tablets 10 mg

- Tablets 25 mg

- Tablets 50 mg

Apo-Imipramine (Canada)

Imipramine Pamoate

Trade Names:

Tofranil-PM

- Capsules 75mg

- Capsules 100mg

- Capsules 125mg

- Capsules 150mg

Pharmacology

Inhibits reuptake of norepinephrine and, to a lesser degree, serotonin in CNS.

Pharmacokinetics

Absorption

T max is 2 to 4 h. Steady state is reached in 2 to 5 days.

Distribution

More than 90% is protein bound. Lipid soluble.

Metabolism

Significant first pass effect. Metabolism occurs in liver. Active metabolite is desipramine.

Elimination

The t ½ is 11 to 25 h.

Peak

2 to 4 weeks.

Indications and Usage

Relief of symptoms of depression; treatment of enuresis in children 6 yr and older.

Unlabeled Uses

Treatment of chronic pain, panic disorder, eating disorders (bulimia nervosa), and facilitation of cocaine withdrawal.

Contraindications

Hypersensitivity to any tricyclic antidepressant. Generally not to be given in combination with or within 14 days of treatment with MAO inhibitor or during acute recovery phase of MI; cross-sensitivity may occur among the dibenzazepines.

Dosage and Administration

Depression

Use parenterally only in patients who are not able or not willing to take oral medication. Give via IM route. Do not administer IV. Up to 100 mg/day in divided doses may be given IM. Switch to oral as soon as possible.

Adults

PO 100 to 300 mg/day, in divided doses or once daily at bedtime.

Elderly & Adolescents

PO 30 to 40mg/day; may increase up to 100 mg/day.

Children

PO 1.5 mg/kg/day in divided doses; up to maximum of 5 mg/kg/day.

Childhood Enuresis (6 yr)

PO 25 mg/day given 1 h before bedtime; if response unsatisfactory after 1 wk, may increase to 50 mg in children younger than 12 yr of age. Children older than 12 yr of age may receive 75 mg/night. Do not exceed 2.5 mg/kg/day.


Drug Interactions


Cimetidine metabolism of imipramine inhibited by cimetidine (increased plasma concentration)
Diltiazem plasma concentration of imipramine increased by diltiazem
Labetalol plasma concentration of imipramine increased by labetalol
Propranolol plasma concentration of imipramine increased by propranolol
Terbinafine plasma concentration of imipramine possibly increased by terbinafine
Thyroid Hormones effects of imipramine enhanced by thyroid hormones
Verapamil plasma concentration of imipramine increased by verapamil
Imipramine belongs to Antidepressants, Tricyclic and will have the following interactions:

Adrenaline (epinephrine) increased risk of hypertension and arrhythmias when tricyclics given with adrenaline (epinephrine) (but local anaesthetics with adrenaline appear to be safe)
Adrenergic Neurone Blockers tricyclics antagonise hypotensive effect of adrenergic neurone blockers
Alcohol increased sedative effect when tricyclics given with alcohol
Amiodarone increased risk of ventricular arrhythmias when tricyclics given with amiodarone —avoid concomitant use Amiodarone has a long half-life; there is a potential for drug interactions to occur for several weeks (or even months) after treatment with it has been stopped
Amprenavir side-effects of tricyclics possibly increased by amprenavir
Anaesthetics, General increased risk of arrhythmias and hypotension when tricyclics given with general anaesthetics See also Surgery and Long-term Medication, section 15.1
Antidepressants, SSRI plasma concentration of some tricyclics increased by SSRIs
Antiepileptics tricyclics antagonise anticonvulsant effect of antiepileptics (convulsive threshold lowered)
Antihistamines increased antimuscarinic and sedative effects when tricyclics given with antihistamines Sedative interactions apply to a lesser extent to the non-sedating antihistamines. Interactions do not generally apply to antihistamines used for topical action (including inhalation)
Antimuscarinics increased risk of antimuscarinic side-effects when tricyclics given with antimuscarinics Many drugs have antimuscarinic effects; concomitant use of two or more such drugs can increase side-effects such as dry mouth, urine retention, and constipation; concomitant use can also lead to confusion in the elderly. Interactions do not generally apply to antimuscarinics used by inhalation
Antipsychotics plasma concentration of tricyclics increased by antipsychotics —possibly increased risk of ventricular arrhythmias Increased risk of toxicity with myelosuppressive drugs
Anxiolytics and Hypnotics increased sedative effect when tricyclics given with anxiolytics and hypnotics
Apraclonidine avoidance of tricyclics advised by manufacturer of apraclonidine
Atomoxetine increased risk of ventricular arrhythmias when tricyclics given with atomoxetine
Baclofen tricyclics enhance muscle relaxant effect of baclofen
Barbiturates tricyclics antagonises anticonvulsant effect of barbiturates (convulsive threshold lowered), also metabolism of tricyclics possibly accelerated (reduced plasma concentration)
Brimonidine avoidance of tricyclics advised by manufacturer of brimonidine
Carbamazepine metabolism of tricyclics accelerated by carbamazepine (reduced plasma concentration and reduced effect)
Cimetidine plasma concentration of tricyclics possibly increased by cimetidine
Clonidine tricyclics antagonise hypotensive effect of clonidine , also increased risk of hypertension on clonidine withdrawal
Clozapine possibly increased antimuscarinic side-effects when tricyclics given with clozapine Avoid concomitant use of clozapine with drugs that have a substantial potential for causing agranulocytosis
Coumarins tricyclics may enhance or reduce anticoagulant effect of coumarins Change in patient's clinical condition, particularly associated with liver disease, intercurrent illness, or drug administration, necessitates more frequent testing. Major changes in diet (especially involving salads and vegetables) and in alcohol consumption may also affect anticoagulant control
Diltiazem plasma concentration of tricyclics possibly increased by diltiazem
Disopyramide increased risk of ventricular arrhythmias when tricyclics given with disopyramide
Disulfiram metabolism of tricyclics inhibited by disulfiram (increased plasma concentration)
Diuretics increased risk of postural hypotension when tricyclics given with diuretics
Entacapone caution with tricyclics advised by manufacturer of entacapone
Flecainide increased risk of ventricular arrhythmias when tricyclics given with flecainide
Lithium risk of toxicity when tricyclics given with lithium
MAOIs increased risk of hypertension and CNS excitation when tricyclics given with MAOIs , tricyclics should not be started until 2 weeks after stopping MAOIs (3 weeks if starting clomipramine or imipramine), also MAOIs should not be started for at least 1–2 weeks after stopping tricyclics (3 weeks in the case of clomipramine or imipramine) For interactions of reversible MAO-A inhibitors (RIMAs) see Moclobemide, and for interactions of MAO-B inhibitors see Rasagiline and Selegiline; the antibacterial Linezolid is a reversible, non-selective MAO inhibitor
Methylphenidate metabolism of tricyclics possibly inhibited by methylphenidate
Moclobemide after stopping tricyclics do not start moclobemide for at least 1 week
Moxifloxacin increased risk of ventricular arrhythmias when tricyclics given with moxifloxacin —avoid concomitant use
Nefopam side-effects possibly increased when tricyclics given with nefopam
Nicorandil tricyclics possibly enhance hypotensive effect of nicorandil
Nitrates tricyclics reduce effects of sublingual tablets of nitrates (failure to dissolve under tongue owing to dry mouth)
Noradrenaline (norepinephrine) increased risk of hypertension and arrhythmias when tricyclics given with noradrenaline (norepinephrine)
Oestrogens antidepressant effect of tricyclics antagonised by oestrogens (but side-effects of tricyclics possibly increased due to increased plasma concentration) Interactions of combined oral contraceptives may also apply to combined contraceptive patches; in case of hormone replacement therapy low dose unlikely to induce interactions
Opioid Analgesics sedative effects possibly increased when tricyclics given with opioid analgesics
Pentamidine Isetionate increased risk of ventricular arrhythmias when tricyclics given with pentamidine isetionate
Phenothiazines increased risk of antimuscarinic side-effects when tricyclics given with phenothiazines
Phenytoin plasma concentration of tricyclics possibly reduced by phenytoin
Pimozide increased risk of ventricular arrhythmias when tricyclics given with pimozide —avoid concomitant use
Primidone tricyclics antagonises anticonvulsant effect of primidone (convulsive threshold lowered), also metabolism of tricyclics possibly accelerated (reduced plasma concentration)
Procainamide increased risk of ventricular arrhythmias when tricyclics given with procainamide
Propafenone increased risk of arrhythmias when tricyclics given with propafenone
Rasagiline increased risk of CNS toxicity when tricyclics given with rasagiline Rasagiline is a MAO-B inhibitor
Rifampicin plasma concentration of tricyclics possibly reduced by rifampicin
Ritonavir plasma concentration of tricyclics possibly increased by ritonavir
Selegiline CNS toxicity reported when tricyclics given with selegiline Selegiline is a MAO-B inhibitor
Sibutramine increased risk of CNS toxicity when tricyclics given with sibutramine (manufacturer of sibutramine advises avoid concomitant use)
Sodium Oxybate increased risk of side-effects when tricyclics given with sodium oxybate
Sotalol increased risk of ventricular arrhythmias when tricyclics given with sotalol
Thyroid Hormones effects of tricyclics possibly enhanced by thyroid hormones
Tramadol increased risk of CNS toxicity when tricyclics given with tramadol
Verapamil plasma concentration of tricyclics possibly increased by verapamil
Imipramine belongs to Antidepressants and will have the following interactions:

Artemether with Lumefantrine avoidance of antidepressants advised by manufacturer of artemether/lumefantrine
Atomoxetine possible increased risk of convulsions when antidepressants given with atomoxetine


Adverse Reactions

Cardiovascular

Orthostatic hypotension; hypertension; tachycardia; palpitations; arrhythmias; ECG changes; stroke; heartblock; CHF.

CNS

Confusion; hallucinations; delusions; nervousness; restlessness; agitation; panic; insomnia; nightmares; mania; exacerbation of psychosis; drowsiness; dizziness; weakness; numbness; extrapyramidal symptoms; emotional lability; seizures; tremors.

Dermatologic

Rash; pruritus; photosensitivity reaction; dry skin; acne; itching.

EENT

Nasal congestion; tinnitus; conjunctivitis; mydriasis; blurred vision; increased IOP.

GI

Nausea; vomiting; anorexia; GI distress; diarrhea; flatulence; peculiar taste in mouth; dry mouth; constipation.

Genitourinary

Impotence; sexual dysfunction; nocturia; urinary frequency; UTI; vaginitis; cystitis; dysmenorrhea; amenorrhea; urinary retention and hesitancy.

Hematologic

Bone marrow depression including agranulocytosis; eosinophilia; purpura; thrombocytopenia; leukopenia.

Hepatic

Hepatitis; jaundice.

Metabolic

Elevation or depression of blood sugar.

Respiratory

Pharyngitis; rhinitis; sinusitis; laryngitis; coughing.

Miscellaneous

Breast enlargement.

Precautions

Pregnancy

Category D .

Lactation

Excreted in breast milk.

Children

Safety and efficacy of imipramine as temporary adjunctive therapy for nocturnal enuresis in pediatric patients younger than 6 yr have not been established; chronic use in patients 6yr and older has not been established. Do not exceed 2.5 mg/kg/day.

Special Risk Patients

Use with caution in patients with history of seizures, urinary retention, ureteral spasm, angle-closure glaucoma or increased IOP, conduction disorders, with hyperthyroid or those receiving thyroid medication, hepatic or renal impairment, schizophrenia or paranoia.

Hazardous Tasks

Patients should use caution while performing tasks requiring alertness.

Cardiovascular disorders

Use with extreme caution in patients with cardiovascular disorders. These patients require cardiac surveillance at all dose levels of the drug.
Overdosage

Symptoms

Confusion, agitation, hallucinations, seizures, status epilepticus, clonus, choreoathetosis, hyperactive reflexes, positive Babinski sign, coma, cardiac arrhythmias, renal failure, flushing, dry mouth, dilated pupils, hyperpyrexia.

Patient Information

* Warn patient of risk of seizure.
* Tell female patient to inform health care provider if becoming or intending to become pregnant.
* Explain that it may be several weeks before a response is noticed.
* Instruct patient to avoid intake of alcoholic beverages or other CNS depressants.
* Advise patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness.
* Caution patient to avoid exposure to sunlight and to use sunscreen or wear protective clothing to avoid photosensitivity reaction.
* Teach patient to avoid sudden position changes to prevent orthostatic hypertension.
* Inform patient that dizziness, dry mouth (suggest taking frequent sips of water, sucking on ice chips, or sugarless hard candy or chewing sugarless gum), drowsiness, or constipation may occur, but that these side effects often subside with time.
* Instruct patient to report all problems to health care provider, including dizziness, drowsiness, dry mouth, constipation, or weight gain.