DIQTA 1.0: Drug-Induced QT Prolongation Atlas

AMISULPRIDE

DIR Classification Postmarketing Surveillance Drug Property Information Reference

DIR Classification

Classification:Moderate-DIQT concern

Severity Score:3.0

Description in Drug Labeling: View Full Labeling: SPL in DailyMed | PDF

WARNINGS AND PRECAUTIONS
QT Prolongation
BARHEMSYS causes dose- and concentration-dependent prolongation of the QT interval [see CLINICAL PHARMACOLOGY (12.2)]. The recommended dosage is 5 or 10 mg as a single intravenous dose infused over 1 to 2 minutes [see DOSAGE AND ADMINISTRATION (2.1)].
Avoid BARHEMSYS in patients with congenital long QT syndrome and in patients taking droperidol.
Electrocardiogram (ECG) monitoring is recommended in patients with pre-existing arrhythmias/cardiac conduction disorders; electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia); congestive heart failure; and in patients taking other medicinal products (e.g., ondansetron) or with other medical conditions known to prolong the QT interval [see DRUG INTERACTIONS (7.2)].
DRUG INTERACTIONS
Drugs Prolonging the QT Interval
BARHEMSYS causes dose- and concentration-dependent QT prolongation [see CLINICAL PHARMACOLOGY (12.2)]. To avoid potential additive effects, avoid use of BARHEMSYS in patients taking droperidol. ECG monitoring is recommended in patients taking other drugs known to prolong the QT interval (e.g., ondansetron) [see WARNINGS AND PRECAUTIONS (5.1)].
OVERDOSAGE
Doses of oral amisulpride (BARHEMSYS is not approved for oral dosing) above 1200 mg/day have been associated with adverse reactions related to dopamine-2 (D2) antagonism, in particular:
cardiovascular adverse reactions (e.g., prolongation of the QT interval, torsades de pointes, bradycardia and hypotension) [see WARNINGS AND PRECAUTIONS (5.1)].
neuropsychiatric adverse reactions (e.g., sedation, coma, seizures, and dystonic and extrapyramidal reactions).
ADVERSE REACTIONS
Postmarketing Experience
The following adverse reactions have been identified during postapproval chronic oral use of amisulpride outside of the United States (BARHEMSYS is not approved for oral dosing or chronic use). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and lymphatic system disorders: agranulocytosis
Cardiac disorders: bradycardia, torsades de pointes, ventricular tachycardia, prolonged QT by electrocardiogram
General disorders: neuroleptic malignant syndrome
Immune system disorders: angioedema, hypersensitivity, urticaria
Hepatic disorders: increased hepatic enzymes
Nervous system disorders: agitation, anxiety, dystonia, extrapyramidal disorder, seizure
Psychiatric disorders: confusional state, insomnia, somnolence
Vascular disorders: hypotension
CLINICAL PHARMACOLOGY
Pharmacodynamics
Cardiac Electrophysiology
In 40 healthy Caucasian and Japanese subjects, the maximum mean difference (95% upper confidence bound) in QTcF from placebo after baseline-correction (ΔΔQTcF) was 5.0 (7.1) milliseconds after a 2-minute intravenous infusion of 5 mg BARHEMSYS and 23.4 (25.5) milliseconds after an 8-minute intravenous infusion of 40 mg BARHEMSYS [see WARNINGS AND PRECAUTIONS (5.1)].
A significant exposure-response relationship was identified between amisulpride concentration and ΔΔQTcF. Using this exposure-response relationship, 10 mg BARHEMSYS infused intravenously over 1 min has a maximal predicted (95% upper prediction interval) ΔΔQTcF of 13.4 (15.1) milliseconds.
The recommended infusion rate is 1 to 2 minutes for 5 mg or 10 mg of BARHEMSYS [see DOSAGE AND ADMINISTRATION (2.1)].
PATIENT COUNSELING INFORMATION
QT Prolongation
Instruct patients to contact their healthcare provider immediately if they perceive a change in their heart rate, if they feel lightheaded, or if they have a syncopal episode [see WARNINGS AND PRECAUTIONS (5.1)].
[Drug Interactions]
Advise patients to report to their healthcare provider if they are taking drugs which prolong the QT interval [see WARNINGS AND PRECAUTIONS (5.1)].

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

QT Prolongation

24085

Other ADRs

362

38381225

Odds Ratio = 30.815

Drug Property Information

ATC Code(s):

N05AL05 - amisulpride

N05AL0 -
N05AL - Benzamides
N05A - ANTIPSYCHOTICS
N05 - PSYCHOLEPTICS
N - NERVOUS SYSTEM

Active Ingredient:AMISULPRIDE

Active Ingredient UNII:8110R61I4U

Drugbank ID:DB06288

PubChem Compound:2159

CTD ID:D000077582

PharmGKB:PA162565877

CAS Number:71675-85-9

Dosage Form(s):injection, solution

Route(s) Of Administrator:intravenous

Daily Dose:

400.0 mg/day N05AL05

Chemical Structure:

SMILE Code:
CCN1CCCC1CNC(=O)C1=CC(=C(N)C=C1OC)S(=O)(=O)CC

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