Imipramine Hydrochloride
Name: Imipramine Hydrochloride
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- Imipramine Hydrochloride imipramine hydrochloride tablet
- Imipramine Hydrochloride names
Introduction
Dibenzazapine-derivative tricyclic antidepressant (TCA).a b f
Interactions for Imipramine Hydrochloride
Metabolized in the liver by various CYP isoenzymes (e.g., CYP1A2, CYP2C, CYP2D6, CYP3A4).c
Drugs Affecting Hepatic Microsomal Enzymes
Inhibitors of CYP2D6: Potential pharmacokinetic interaction (increased plasma imipramine concentrations).a b Consider imipramine dosage adjustment whenever a CYP2D6 inhibitor is added or discontinued.a b
Inducers of CYP2D6: Potential pharmacokinetic interaction (decreased plasma imipramine concentrations).a b Consider imipramine dosage adjustment whenever a CYP2D6 inducer is added or discontinued.a
Specific Drugs
| Drug | Interaction | Comments |
|---|---|---|
| Alcohol | Potentiates CNS depressant effects of alcohola b | Increased risks if overdose or suicide attempt occursa b |
| Antiarrhythmics: class 1C (e.g., flecainide, propafenone); quinidine | Potential for decreased imipramine metabolisma b | Monitor for TCA toxicity; dosage adjustment may be neededa b |
| Anticholinergic agents | Hyperthermia, particularly during hot weather, and paralytic ileusa b c | Use with caution; dosage adjustment may be neededc |
| Antipsychotics (e.g., phenothiazines) | Potential for decreased imipramine metabolisma b | |
| Barbiturates | Potential for increased imipramine metabolisma b | Dosage adjustment may be neededa b |
| Cimetidine | Potential for decreased imipramine metabolisma b | Monitor for TCA toxicity; dosage adjustment may be neededc |
| CNS depressants | Potentiates effects of CNS depressantsa b | Use with cautiona b |
| Hypotensive agents (e.g., clonidine, guanethidine) | Antagonizes antihypertensive effects of clonidine or guanethidinea b | Use with cautiona b |
| Levodopa | May interfere with levodopa absorption c | Monitor levodopa dosage carefullya |
| MAO inhibitors | Potentially life-threatening serotonin syndromea b | Concomitant use contraindicateda b Allow at least 14 days to elapse when switching to or from these drugsa b |
| Methylphenidate | Potential for decreased imipramine metabolisma b | Use with caution; decreased imipramine dosage may be requireda b |
| Phenytoin | Potential for increased imipramine metabolisma b | Dosage adjustment may be neededa b |
| SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) | Potential for decreased imipramine metabolism and increased plasma concentrationsa b | Use with caution; monitor for TCA toxicity; dosage adjustment may be neededa b Allow at least 5 weeks to elapse when switching from fluoxetinea b |
| Smoking | Possible decreased steady-state imipramine concentrationsg | |
| Sympathomimetic agents (e.g., amphetamines, epinephrine, isoproterenol, norepinephrine, phenylephrine) | Increased vasopressor, cardiac effectsc | Avoid concomitant usea b |
| Thyroid agents | Possible cardiac arrhythmiasc | Use with caution and under close supervisiona b |
Imipramine Hydrochloride Pharmacokinetics
Absorption
Bioavailability
Well absorbed from the GI tract following oral administration, with peak plasma concentrations usually attained within 1–2 hours.f
Bioavailability is approximately 43%.g
Onset
Antidepressant effect usually occurs within 1–3 weeks.a b
Food
Food does not affect absorption.g
Distribution
Extent
Widely distributed in the body.g
Imipramine and its active metabolite, desipramine, are distributed into milk100 101 in concentrations similar to those present in maternal plasma.101
Plasma Protein Binding
Approximately 60–96%.g
Elimination
Metabolism
Extensively metabolized in the liver via demethylation to pharmacologically active metabolite, desipramine, by various CYP isoenzymes (e.g., CYP1A2, CYP2D6, CYP3A4, CYP2C).c
Elimination Route
Excreted principally in urine as inactive metabolites within 24 hours (40%) and within 72 hours (70%); small amounts excreted in feces via biliary elimination.f
Half-life
Imipramine: 8–20 hours.f g
Desipramine: Up to 125 hours.f g
Special Populations
Alcoholics found to have a threefold greater intrinsic clearance of imipramine.g
Stability
Storage
Oral
CapsulesTight containers at <30°C.a b
TabletsTight containers at 15–30°C.a b
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
| Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
| Oral | Tablets | 10 mg* | Imipramine Hydrochloride Tablets | Par |
| Tofranil (with povidone) | Mallinckrodt | |||
| 25 mg* | Imipramine Hydrochloride Tablets | Par | ||
| Tofranil (with povidone) | Mallinckrodt | |||
| 50 mg* | Imipramine Hydrochloride Tablets | Par | ||
| Tofranil (with povidone) | Mallinckrodt | |||
| Tablets, film-coated | 10 mg* | Imipramine Hydrochloride Tablets | Sandoz, Mutual, United Research | |
| 25 mg* | Imipramine Hydrochloride Tablets | Sandoz, Mutual, United Research | ||
| 50 mg* | Imipramine Hydrochloride Tablets | Sandoz, Mutual, United Research |
| Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
| Oral | Capsules | equivalent to imipramine hydrochloride 75 mg | Tofranil-PM (with parabens) | Mallinckrodt |
| equivalent to imipramine hydrochloride 100 mg | Tofranil-PM (with parabens) | Mallinckrodt | ||
| equivalent to imipramine hydrochloride 125 mg | Tofranil-PM (with parabens) | Mallinckrodt | ||
| equivalent to imipramine hydrochloride 150 mg | Tofranil-PM (with parabens) | Mallinckrodt |