Imipramine Pamoate

Description

DESCRIPTION Imipramine pamoate capsules USP are a tricyclic antidepressant, available as capsules for oral administration. The 75-, 100-, 125-, and 150-mg capsules contain imipramine pamoate equivalent to 75, 100, 125, and 150 mg of imipramine hydrochloride. Imipramine pamoate is 5-[3-(dimethylamino)propyl]-10,11-dihydro- 5H -dibenz[b,f]azepine 4, 4'-methylenebis-(3-hydroxy-2-naphthoate) (2:1), and its structural formula is Imipramine Pamoate Imipramine pamoate is a fine, yellow, tasteless, odorless powder. It is soluble in ethanol, in acetone, in ether, in chloroform, and in carbon tetrachloride, and is insoluble in water. Inactive Ingredients. corn starch, FD and C blue 1, FD and C red 40, FD and C yellow 6, D and C yellow 10 (in 100 mg and 125 mg capsules), gelatin, magnesium stearate, sodium lauryl sulphate, talc and titanium dioxide. FDA approved dissolution specification differs from the USP dissolution specification. Imipramine Pamoate

What Is Imipramine Pamoate Used For?

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

DOSAGE AND ADMINISTRATION The following recommended dosages for imipramine pamoate capsules 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 Tofranil™, brand of imipramine hydrochloride 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...

Side Effects (Adverse Reactions)

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

Drug Interactions

Drug Interactions Drugs Metabolized by P450 2D6 - The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the Caucasian population (about 7% to 10% of Caucasians are so-called "poor metabolizers"); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8-fold increase in plasma AUC of the TCA). In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary). Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6. The plasma concentration of imipramine may increase when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decrease by concomitant administration with hepatic enzyme inducers (e.g., barbiturates, phenytoin), and adjustment of the dosage of imipramine may therefore be necessary. In occasional susceptible patients or in those receiving anticholinergic drugs (including antiparkinsonism agents) in addition, the atropine-like effects may become more pronounced (e.g., paralytic ileus). Close supervision and careful adjustment of...

Contraindications

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.

Pregnancy and Breastfeeding

Pregnancy Animal reproduction studies have yielded inconclusive results (see also ANIMAL PHARMACOLOGY AND TOXICOLOGY ). There have been no well-controlled studies conducted with pregnant women to determine the effect of imipramine on the fetus. However, there have been clinical reports of congenital malformations associated with the use of the drug. Although a causal relationship between these effects and the drug could not be established, the possibility of fetal risk from the maternal ingestion of imipramine cannot be excluded. Therefore, imipramine should be used in women who are or might become pregnant only if the clinical condition clearly justifies potential risk to the fetus.

Nursing Mothers Limited data suggest that imipramine is likely to be excreted in human breast milk. As a general rule, a woman taking a drug should not nurse since the possibility exists that the drug may be excreted in breast milk and be harmful to the child.

Overdosage

OVERDOSAGE Deaths may occur from overdosage with this class of drugs. Multiple drug ingestion (including alcohol) is common in deliberate tricyclic overdose. As the management is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment. Signs and symptoms of toxicity develop rapidly after tricyclic overdose. Therefore, hospital monitoring is required as soon as possible. Children have been reported to be more sensitive than adults to an acute overdosage of imipramine pamoate. An acute overdose of any amount in infants or young children, especially, must be considered serious and potentially fatal. Manifestations These may vary in severity depending upon factors such as the amount of drug absorbed, the age of the patient, and the interval between drug ingestion and the start of treatment. Critical manifestations of overdose include cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic toxicity. Other CNS manifestations may include drowsiness, stupor, ataxia, restlessness, agitation, hyperactive reflexes, muscle rigidity, athetoid and choreiform movements. Cardiac abnormalities may include tachycardia, and signs of congestive failure. Respiratory depression, cyanosis, shock, vomiting, hyperpyrexia, mydriasis, and diaphoresis may also be present. Management Obtain an ECG and immediately initiate cardiac monitoring. Protect the patient's airway, establish an intravenous line, and initiate gastric decontamination. A minimum of 6 hours of observation with cardiac monitoring and observation for signs of CNS or respiratory depression, hypotension, cardiac dysrhythmias and/or conduction blocks, and seizures is necessary. If signs of toxicity occur at any time during this period, extended monitoring is required. There are case reports of patients...

How Supplied

HOW SUPPLIED Imipramine Pamoate Capsules USP 75 mg are size "2" capsule with brown cap and brown body, imprinted with "LU" in black ink on cap and "U01" in black ink on body, containing pale yellow to yellow granular powder. They are supplied as follows: NDC 68180-314-06 Bottles of 30's Imipramine Pamoate Capsules USP 100 mg are size "1" capsule with brown cap and dark yellow body, imprinted with "LU" in black ink on cap and "U02" in black ink on body, containing pale yellow to yellow granular powder. They are supplied as follows: NDC 68180-315-06 Bottles of 30's Imipramine Pamoate Capsules USP 125 mg are size "1" capsule with brown cap and light yellow body, imprinted with "LU" in black ink on cap and "U03" in black ink on body, containing pale yellow to yellow granular powder. They are supplied as follows: NDC 68180-316-06 Bottles of 30's Imipramine Pamoate Capsules USP 150 mg are size "0" capsule with brown cap and brown body, imprinted with "LU" in black ink on cap and "U04" in black ink on body, containing pale yellow to yellow granular powder. They are supplied as follows: NDC 68180-317-06 Bottles of 30's Store at 20°C to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Dispense in tight container (USP) with a child-resistant closure.