Imipramine Pamoate - Imipramine Pamoate capsule prescribing information
Suicidality and Antidepressant Drugs
Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of imipramine pamoate or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Imipramine pamoate is not approved for use in pediatric patients (see WARNINGS: Clinical Worsening and Suicide Risk , PRECAUTIONS: Information for Patients , and PRECAUTIONS: Pediatric Use ).
INDICATIONS AND USAGE
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.
DOSAGE AND ADMINISTRATION
The following recommended dosages for imipramine pamoate should be modified as necessary by the clinical response and any evidence of intolerance.
Initial Adult Dosage
Outpatients:
Therapy should be initiated at 75 mg/day. Dosage may be increased to 150 mg/day which is the dose level at which optimum response is usually obtained. If necessary, dosage may be increased to 200 mg/day.
Dosage higher than 75 mg/day may also be administered on a once-a-day basis after the optimum dosage and tolerance have been determined. The daily dosage may be given at bedtime. In some patients it may be necessary to employ a divided-dose schedule.
As with all tricyclics, the antidepressant effect of imipramine may not be evident for one to three weeks in some patients.
Hospitalized Patients:
Therapy should be initiated at 100 to 150 mg/day and may be increased to 200 mg/day. If there is no response after two weeks, dosage should be increased to 250 to 300 mg/day.
Dosage higher than 150 mg/day may also be administered on a once-a-day basis after the optimum dosage and tolerance have been determined. The daily dosage may be given at bedtime. In some patients it may be necessary to employ a divided-dose schedule.
As with all tricyclics, the antidepressant effect of imipramine may not be evident for one to three weeks in some patients.
Adult Maintenance Dosage:
Following remission, maintenance medication may be required for a longer period of time at the lowest dose that will maintain remission after which the dosage should gradually be decreased.
The usual maintenance dosage is 75 to 150 mg/day. The total daily dosage can be administered on a once-a-day basis, preferably at bedtime. In some patients it may be necessary to employ a divided-dose schedule.
In cases of relapse due to premature withdrawal of the drug, the effective dosage of imipramine should be reinstituted.
Adolescent and Geriatric Patients:
Therapy in these age groups should be initiated with imipramine pamoate tablets at a total daily dosage of 25 to 50 mg, since imipramine pamoate capsules are not available in these strengths. Dosage may be increased according to response and tolerance, but it is generally unnecessary to exceed 100 mg/day in these patients. Imipramine pamoate capsules may be used when total daily dosage is established at 75 mg or higher.
The total daily dosage can be administered on a once-a-day basis, preferably at bedtime. In some patients it may be necessary to employ a divided-dose schedule.
As with all tricyclics, the antidepressant effect of imipramine may not be evident for one to three weeks in some patients.
Adolescent and geriatric patients can usually be maintained at lower dosage. Following remission, maintenance medication may be required for a longer period of time at the lowest dose that will maintain remission after which the dosage should gradually be decreased.
The total daily maintenance dosage can be administered on a once-a-day basis, preferably at bedtime. In some patients it may be necessary to employ a divided-dose schedule.
In cases of relapse due to premature withdrawal of the drug, the effective dosage of imipramine should be reinstituted.
Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders
At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with imipramine pamoate. Conversely, at least 14 days should be allowed after stopping imipramine pamoate before starting an MAOI intended to treat psychiatric disorders (see CONTRAINDICATIONS ).
Use of Imipramine Pamoate With Other MAOIs, Such as Linezolid or Methylene Blue
Do not start imipramine pamoate in a patient who is being treated with linezolid or intravenous methylene blue because there is increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered (see CONTRAINDICATIONS ).
In some cases, a patient already receiving imipramine pamoate therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, imipramine pamoate should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with imipramine pamoate may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue (see WARNINGS ).
The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with imipramine pamoate is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use (see WARNINGS ).
CONTRAINDICATIONS
Monoamine Oxidase Inhibitors (MAOIs)
The use of MAOIs intended to treat psychiatric disorders with imipramine pamoate or within 14 days of stopping treatment with imipramine pamoate is contraindicated because of an increased risk of serotonin syndrome. The use of imipramine pamoate within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated (see WARNINGS and DOSAGE AND ADMINISTRATION ).
Starting imipramine pamoate in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome (see WARNINGS and DOSAGE AND ADMINISTRATION ).
Myocardial Infarction
The drug is contraindicated during the acute recovery period after a myocardial infarction.
Hypersensitivity to Tricyclic Antidepressants
Patients with a known hypersensitivity to this compound should not be given the drug. The possibility of cross-sensitivity to other dibenzazepine compounds should be kept in mind.
ADVERSE REACTIONS
Note: Although the listing which follows includes a few adverse reactions which have not been reported with this specific drug, the pharmacological similarities among the tricyclic antidepressant drugs require that each of the reactions be considered when imipramine is administered.
Cardiovascular: Orthostatic hypotension, hypertension, tachycardia, palpitation, myocardial infarction, arrhythmias, heart block, ECG changes, precipitation of congestive heart failure, stroke.
Psychiatric: Confusional states (especially in the elderly) with hallucinations, disorientation, delusions; anxiety, restlessness, agitation; insomnia and nightmares; hypomania; exacerbation of psychosis.
Neurological: Numbness, tingling, paresthesias of extremities; incoordination, ataxia, tremors; peripheral neuropathy; extrapyramidal symptoms; seizures, alterations in EEG patterns; tinnitus.
Anticholinergic: Dry mouth, and, rarely, associated sublingual adenitis; blurred vision, disturbances of accommodation, mydriasis; constipation, paralytic ileus; urinary retention, delayed micturition, dilation of the urinary tract.
Allergic: Skin rash, petechiae, urticaria, itching, photosensitization; edema (general or of face and tongue); drug fever; cross-sensitivity with desipramine.
Hematologic: Bone marrow depression including agranulocytosis; eosinophilia; purpura; thrombocytopenia.
Gastrointestinal: Nausea and vomiting, anorexia, epigastric distress, diarrhea; peculiar taste, stomatitis, abdominal cramps, black tongue.
Endocrine: Gynecomastia in the male; breast enlargement and galactorrhea in the female; increased or decreased libido, impotence; testicular swelling; elevation or depression of blood sugar levels; inappropriate antidiuretic hormone (ADH) secretion syndrome.
Other: Jaundice (simulating obstructive); altered liver function; weight gain or loss; perspiration; flushing; urinary frequency; drowsiness, dizziness, weakness and fatigue; headache; parotid swelling; alopecia; proneness to falling; hyponatremia.
Withdrawal Symptoms: Though not indicative of addiction, abrupt cessation of treatment after prolonged therapy may produce nausea, headache and malaise.
Postmarketing Experience
The following adverse drug reaction has been reported during post-approval use of imipramine pamoate. Because this reaction is reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate frequency.
Eye Disorders: Angle-closure glaucoma
DESCRIPTION
Imipramine Pamoate Capsules, USP are a tricyclic antidepressant, available as capsules for oral administration. The 75 mg, 100 mg, 125 mg, and 150 mg capsules contain imipramine pamoate, USP equivalent to 75 mg, 100 mg, 125 mg, and 150 mg of imipramine hydrochloride. Imipramine pamoate, USP is 5-[3-(dimethylamino)propyl]-10,11-dihydro-5 H -dibenz[b,f]azepine 4, 4'-methylenebis-(3-hydroxy-2-naphthoate) (2:1), and its structural formula is:
(C 19 H 24 N 2 ) 2 ●C 23 H 16 O 6 M.W. = 949.18
Imipramine pamoate, USP is a slightly yellow, crystalline powder. It is soluble in ethanol, in acetone, in ether, in chloroform, and in carbon tetrachloride, and is insoluble in water.
Inactive Ingredients: colloidal silicon dioxide, magnesium stearate, pregelatinized starch, sodium starch glycolate and talc.
Gelatin capsule shells contain FD&C Blue No. 1, FD&C Red No. 40, FD&C Yellow No. 6, gelatin, and titanium dioxide. The 100 mg capsules also contain FD&C Yellow No. 10. The 125 mg capsules also contain FD&C Yellow No. 5.
In addition to the ingredients listed above, each capsule contains iron oxide used in the black monogramming ink.
CLINICAL PHARMACOLOGY
The mechanism of action of imipramine is not definitely known. However, it does not act primarily by stimulation of the central nervous system. The clinical effect is hypothesized as being due to potentiation of adrenergic synapses by blocking uptake of norepinephrine at nerve endings.
HOW SUPPLIED
Imipramine Pamoate Capsules, USP
75 mg capsules are supplied as light caramel opaque cap and light caramel opaque body with “54 591” printed on the cap and body, containing a light yellow to yellow powder.
NDC 0054-0273-13: Bottle of 30 Capsules NDC 0054-0273-25: Bottle of 100 Capsules
100 mg capsules are supplied as light caramel opaque cap and rich yellow opaque body with “54 758” printed on the cap and body, containing a light yellow to yellow powder.
NDC 0054-0274-13: Bottle of 30 Capsules NDC 0054-0274-25: Bottle of 100 Capsules
125 mg capsules are supplied as light caramel opaque cap and ivory opaque body with “54 466” printed on the cap and body, containing a light yellow to yellow powder.
NDC 0054-0275-13: Bottle of 30 Capsules
150 mg capsules are supplied as light caramel opaque cap and light caramel opaque body with “54 161” printed on the cap and body, containing a light yellow to yellow powder.
NDC 0054-0276-13: Bottle of 30 Capsules NDC 0054-0276-25: Bottle of 100 Capsules
Storage
Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Dispense in a tight, child-resistant container as defined in the USP/NF.
