ジソピラミド

3.5

2.71

Breast Feeding; Lactation; Milk, Human; Antiarrhythmics

Pharmaceuticals

94.5-95 °C

94.5 - 95 °C

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P264, P270, P280, P301+P317, P318, P330, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 42 reports by companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

REACH registered substance: Disopyramide (EC: 223-110-2)

Disopyramide: Does not have an individual approval but may be used under an appropriate group standard

In clinical trials, disopyramide was associated with a low rate of serum aminotransferase and alkaline phosphatase elevations. Despite wide scale use, disopyramide has only rarely been linked to cases of clinically apparent liver injury. Two types of hepatic injury have been described. The first is an acute hepatocellular injury that arises within 1 to 3 days of starting disopyramide and resembles acute hepatic ischemia with marked early rises in serum aminotransferase levels (and LDH), with minimal increase in alkaline phosphatase and subsequent rise in serum bilirubin. The prothrombin time may be abnormal initially. The injury resolves rapidly and may relate to sudden worsening of congestive heart failure due to the myocardial depressant effects of disopyramide.

The most serious adverse reactions identified include hypotension and congestive heart failure. Common adverse reactions, which may be dose-dependent, are linked to the drug's anticholinergic properties. Although these effects can be transitory, they may also persist or become severe.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

disopyramide

DILI Positive

Oral

DOI:10.1016/j.drudis.2019.09.022

Disopyramide

14.0

59.2

The recommended dosage for most adults is 600 mg/day given in divided doses (150 mg every 6 hours). For patients whose body weight is less than 110 pounds (50 kg), the recommended dosage is 400 mg/day given in divided doses (100 mg every 6 hours).

Data used to generate the benchmarks include the following: Lowest Daily Dose (LDD): 600 mg/day, Lowest Therapeutic Dose (LTD): 7.5 mg/kg-day, and Screening Dose: 0.003 mg/kg-day.

31-Aug-15

C01BA03

C - Cardiovascular system

QC - Cardiovascular system

Disopyramide is an anti-arrhythmic drug indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia that are life-threatening. At therapeutic plasma levels, disopyramide shortens the sinus node recovery time, lengthens the effective refractory period of the atrium, and has a minimal effect on the effective refractory period of the AV node. Little effect has been shown on AV-nodal and His-Purkinje conduction times or QRS duration. However, prolongation of conduction in accessory pathways occurs.

Disopyramide is a Type 1A antiarrhythmic drug (ie, similar to procainamide and quinidine). It inhibits the fast sodium channels. In animal studies Disopyramide decreases the rate of diastolic depolarization (phase 4) in cells with augmented automaticity, decreases the upstroke velocity (phase 0) and increases the action potential duration of normal cardiac cells, decreases the disparity in refractoriness between infarcted and adjacent normally perfused myocardium, and has no effect on alpha- or beta-adrenergic receptors.

Hepatic

Disopyramide has known human metabolites that include N-Desisopropyldisopyramide.

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DISOPYRAMIDE

Established Pharmacologic Class [EPC] - Antiarrhythmic

Disopyramide is an Antiarrhythmic.

Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade.

A class of drugs that inhibit the activation of VOLTAGE-GATED SODIUM CHANNELS.

Nearly complete

In healthy men, about 50% of a given dose of disopyramide is excreted in the urine as the unchanged drug, about 20% as the mono-N-dealkylated metabolite and 10% as the other metabolites.