デシプラミン

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. (L1712)

ADMIN OF TRICYCLIC ANTIDEPRESSANTS...WITH OR SHORTLY AFTER...MAO INHIBITORS HAS RESULTED IN SEVERE REACTIONS. ... OTHER INTERACTIONS INCL POTENTIATION OF CENTRAL DEPRESSANT DRUGS, BLOCKADE OF ANTIHYPERTENSIVE EFFECTS OF GUANETHIDINE, & AUGMENTATION OF PRESSOR EFFECTS OF SYMPATHOMIMETIC AMINES. /TRICYCLIC ANTIDEPRESSANTS/

Concurrent use /of thyroid hormones/ with tricyclic antidepressants may increase the therapeutic and toxic effects of both medications, possibly due to increased receptor sensitivity to catecholamines; toxic effects include cardiac arrhythmias and CNS stimulation. /Tricyclic antidepressants/

Concurrent use /of sympathomimetics/ with tricyclic antidepressants may potentiate cardiovascular effects possibly resulting in arrhythmias, tachycardia, or severe hypertension or hyperpyrexia; phentolamine can control the adverse reaction. Significant systemic absorption of ophthalmic epinephrine may also potentiate cardiovascular effects; also, local anesthetics with vasoconstrictors should be avoided or a minimal amount of the vasoconstrictor should be used with the local anesthetic. Concurrent use with tricyclic antidepressants may decrease the pressor effect of ephedrine and mephentermine. /Tricyclic antidepressants/

If significant systemic absorption occurs, concurrent use /of ophthalmic naphazoline, nasal or ophthalmic oxymetazoline, nasal or ophthalmic phenylephrine, or nasal xylometazoline/ with tricyclic antidepressants may potentiate pressor effects of these medications. /Tricyclic antidepressants/

For more Interactions (Complete) data for DESIPRAMINE (20 total), please visit the HSDB record page.

Liver test abnormalities have been reported to occur in up to 16% of patients being treated with tricyclic antidepressants, but elevations are uncommonly above 3 times the upper limit of normal. The aminotransferase abnormalities are usually mild, asymptomatic and transient, reversing even with continuation of medication and without dose adjustment. Rare instances of clinically apparent acute liver injury have been reported due to desipramine, but far fewer than have been reported with amitriptyline or imipramine. The onset of jaundice is usually within 1 to 8 weeks of starting the antidepressant, and the pattern of serum enzyme elevations can be either hepatocellular or cholestatic. Features suggestive of hypersensitivity (fever, rash, eosinophilia) are common, but rarely severe. Autoantibody formation is unusual. These features are typical of tricyclic antidepressant hepatotoxicity.

Desipramine has a broad toxic profile, including an increased risk of suicide, orthostatic hypotension, cardiac abnormalities, seizures, ocular crisis, and fractures. A short-term study demonstrated a significantly increased risk of suicide in children, adolescents, and young adults aged 24 and younger; this represents one of the most significant adverse effects to consider when prescribing desipramine. Orthostatic hypotension, likely due to alpha-1 receptor blockade, is a common reason for drug discontinuation. Reports describe cardiovascular adverse effects, including heart block, arrhythmias, and sudden death associated with desipramine. Clinicians should screen for conduction abnormalities, with particular attention to the QT interval and family history of cardiac disease, before prescribing desipramine.

Signs and Symptoms of Overdose

Desipramine is a tricyclic antidepressant (TCA) that selectively blocks reuptake of norepinephrine (noradrenaline) from the neuronal synapse. It also inhibits serotonin reuptake, but to a lesser extent compared to tertiary amine TCAs such as imipramine. Inhibition of neurotransmitter reuptake increases stimulation of the post-synaptic neuron. Chronic use of desipramine also leads to down-regulation of beta-adrenergic receptors in the cerebral cortex and sensitization of serotonergic receptors. An overall increase in serotonergic transmission likely confers desipramine its antidepressant effects. Desipramine also possesses minor anticholinergic activity, through its affinity for muscarinic receptors. TCAs are believed to act by restoring normal levels of neurotransmitters via synaptic reuptake inhibition and by increasing serotonergic neurotransmission via serotonergic receptor sensitization in the central nervous system.

MILD PARKINSONIAN SYNDROME...MAY BE SEEN IN SOME PT, PARTICULARLY OLDER PERSONS TAKING LARGE DOSES. ...HIGH DOSES...MAY PRODUCE GRAND MAL SEIZURES EVEN IN PT WITHOUT HISTORY OF CONVULSIONS. .../IT/ MAY PRODUCE ALLERGIC TYPE OF OBSTRUCTIVE JAUNDICE.../WHICH/ CLEARS WHEN DRUG IS DISCONTINUED. /IMIPRAMINE/

Effects of overdosage include agitation, hallucinations, hyperreflexia, hyperpyrexia, and convulsions. Both hypotension and hypertension also occur.

Benchmark Dataset for the Liver Toxicity Knowledge Base (LTKB)

desipramine

Norpramin®

Antidepressants

3

less-DILI-concern drugs

IN CATS UNDER ANESTHESIA IV INJECTION OF 4 TO 25 MG OF DESIPRAMINE HAS BEEN FOUND TO REDUCE SPONTANEOUS ACTIVITY OF RETINAL NEURONES. DOSES OF 5 TO 20 MG/KG INCR C-WAVE IN ELECTRORETINOGRAM, & DOSES OF 20 TO 35 MG/KG REDUCED B-WAVE...

DESPITE ITS CLINICAL ANTIDEPRESSANT EFFECTS, IMIPRAMINE PRODUCES DEPRESSION OF SPONTANEOUS MOTOR ACTIVITY IN LAB ANIMALS. ...IT ALSO...DECR BODY TEMP, & CAUSES ATAXIA. IT IMPAIRS BOTH ACQUISITION & PERFORMANCE OF CONDITIONED AVOIDANCE RESPONSES. /IMIPRAMINE/

IMIPRAMINE LOWERS BLOOD PRESSURE IN ANESTHETIZED DOGS & OBTUNDS VARIOUS CARDIOVASCULAR REFLEXES, INCL CAROTID OCCLUSION REFLEX, BEZOLD-JARISCH REFLEX, & POSTURAL RESPONSES. /IMIPRAMINE/

◉ Summary of Use during Lactation

◈ What is desipramine?

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

Antidepressant

For relief of symptoms in various depressive syndromes, especially endogenous depression. It has also been used to manage chronic peripheral neuropathic pain, as a second line agent for the management of anxiety disorders (e.g. panic disorder, generalized anxiety disorder), and as a second or third line agent in the ADHD management.