DESIPRAMINE HYDROCHLORIDE (Page 3 of 4)

OVERDOSAGE

Deaths may occur from overdosage with this class of drugs. Overdose of desipramine has resulted in a higher death rate compared to overdoses of other tricyclic antidepressants. Multiple drug ingestion (including alcohol) is common in deliberate tricyclic antidepressant 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 antidepressant overdose; therefore, hospital monitoring is required as soon as possible. There is no specific antidote for desipramine overdosage.

Oral LD₅₀

The oral LD₅₀ of desipramine is 290 mg/kg in male mice and 320 mg/kg in female rats.

Manifestations of Overdosage

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 antidepressant toxicity. Early changes in the QRS complex include a widening of the terminal 40 msec with a rightward axis in the frontal plane, recognized by the presence of a terminal S wave in Lead 1 and AVL and an R wave in AVR.

Other signs of overdose may include: confusion, disturbed concentration, transient visual hallucinations, dilated pupils, agitation, hyperactive reflexes, stupor, drowsiness, muscle rigidity, vomiting, hypothermia, hyperpyrexia, or any of the symptoms listed under ADVERSE REACTIONS.

Management

Aggressive supportive care and serum alkalinization are the mainstays of therapy.

General. 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. Follow ECG, renal function, CPK, and arterial blood gasses as clinically indicated. There are case reports of patients succumbing to fatal dysrhythmias late after overdose; these patients had clinical evidence of significant poisoning prior to death, and most received inadequate gastrointestinal decontamination. Monitoring of plasma drug levels should not guide management of the patient.

Gastrointestinal Decontamination. Emesis is contraindicated. Activated charcoal should be administered to patients who present early after an overdose.

Cardiovascular. A maximal limb-lead QRS duration widening to greater than 100 msec is a significant indicator of toxicity, specifically for the risk of seizures and, eventually, cardiac dysrhythmias. Serum alkalinization with intravenous sodium bicarbonate and hyperventilation (as needed) should be instituted in patients manifesting significant toxicity such as QRS widening. Dysrhythmias despite adequate alkalemia may respond to overdrive pacing, beta-agonist infusions, and magnesium therapy. Type 1A and 1C antiarrhythmics are generally contraindicated (e.g., quinidine, disopyramide, and procainamide).

CNS. In patients with CNS depression, early intubation is advised because of the potential for abrupt deterioration. Seizures should be controlled with benzodiazepines. If these are ineffective or seizures recur, other anticonvulsants (eg, phenobarbital, propofol) may be used.

Psychiatric Follow-up. Since overdosage is often deliberate, patients may attempt suicide by other means during the recovery phase. Psychiatric referral may be appropriate.

Pediatric Management. The principles of management of child and adult overdosages are similar. It is strongly recommended that the physician contact the local poison control center for specific pediatric treatment.

DOSAGE AND ADMINISTRATION

Not recommended for use in children (see WARNINGS).

Lower dosages are recommended for elderly patients and adolescents. Lower dosages are also recommended for outpatients compared to hospitalized patients, who are closely supervised. Dosage should be initiated at a low level and increased according to clinical response and any evidence of intolerance. Following remission, maintenance medication may be required for a period of time and should be at the lowest dose that will maintain remission.

Usual Adult Dose

The usual adult dose is 100 to 200 mg per day. In more severely ill patients, dosage may be further increased gradually to 300 mg/day if necessary. Dosages above 300 mg/day are not recommended.

Dosage should be initiated at a lower level and increased according to tolerance and clinical response.

Treatment of patients requiring as much as 300 mg should generally be initiated in hospitals, where regular visits by the physician, skilled nursing care, and frequent electrocardiograms (ECGs) are available.

The best available evidence of impending toxicity from very high doses of desipramine hydrochloride is prolongation of the QRS or QT intervals on the ECG. Prolongation of the PR interval is also significant, but less closely correlated with plasma levels. Clinical symptoms of intolerance, especially drowsiness, dizziness, and postural hypotension, should also alert the physician to the need for reduction in dosage.

Initial therapy may be administered in divided doses or a single daily dose.

Maintenance therapy may be given on a once-daily schedule for patient convenience and compliance.

Adolescent and Geriatric Dose

The usual adolescent and geriatric dose is 25 to 100 mg daily.

Dosage should be initiated at a lower level and increased according to tolerance and clinical response to a usual maximum of 100 mg daily. In more severely ill patients, dosage may be further increased to 150 mg/day. Doses above 150 mg/day are not recommended in these age groups.

Initial therapy may be administered in divided doses or a single daily dose.

Maintenance therapy may be given on a once-daily schedule for patient convenience and compliance.

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 desipramine hydrochloride. Conversely, at least 14 days should be allowed after stopping desipramine hydrochloride before starting an MAOI intended to treat psychiatric disorders (see CONTRAINDICATIONS).

Use of desipramine hydrochloride With Other MAOI’s, Such as Linezolid or Methylene Blue:

Do not start desipramine hydrochloride 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 desipramine hydrochloride 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, Desipramine hydrochloride should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with desipramine hydrochloride 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 desipramine hydrochloride is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use (see WARNINGS).

HOW SUPPLIED

Desipramine hydrochloride tablets, USP for oral administration are available as:

10 mg: white to off white, rounded square shape, biconvex, coated tablets with ‘N6’ debossed on one side and plain on other side.

NDC 23155-578-01: Bottles of 100

25 mg: white to off white, round biconvex, coated tablets with ‘I86’ debossed on one side and plain on other side.

NDC 23155-579-01: Bottles of 100

50 mg: white to off white, round biconvex, coated tablets with ‘I82’ debossed on one side and plain on other side.

NDC 23155-580-01: Bottles of 100

75 mg: white to off white, round biconvex, coated tablets with ‘I83’ debossed on one side and plain on other side.

NDC 23155-581-01: Bottles of 100

100 mg: white to off white, round biconvex, coated tablets with ‘I84’ debossed on one side and plain on other side.

NDC 23155-582-01: Bottles of 100

150 mg: white to off white, round biconvex, coated tablets with ‘I85’ debossed on one side and plain on other side.

NDC 23155-583-25: Bottles of 50

Store at 20°-25°C (68°-77°F); [see USP Controlled Room Temperature]. Protect from excessive heat. Dispense in tight container with child-resistant closure.

Dispense with Medication Guide available at:www.avetpharma.com/product

Manufactured by:
USV Private Limited
Daman — 396210, India

Manufactured for:
Avet Pharmaceuticals Inc.
East Brunswick, NJ 088161.866.901.DRUG (3784)

Revised: 06/2023

Dispense with Medication Guide available at:www.avetpharma.com/product