DIRA 1.0: Atlas of Drug-induced Rhabdomyolysis

FLUVOXAMINE MALEATE

DIR Classification Postmarketing Surveillance Drug Property Information Reference

DIR Classification

Classification:Less-DIR concern

Severity Score:1

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

WARNINGS AND PRECAUTIONS
Potential Thioridazine Interaction
The effect of fluvoxamine (25 mg b.i.d. for one week) on thioridazine steady-state concentrations was evaluated in 10 male inpatients with schizophrenia. Concentrations of thioridazine and its two active metabolites, mesoridazine and sulforidazine, increased three-fold following coadministration of fluvoxamine.
Thioridazine administration produces a dose-related prolongation of the QTc interval, which is associated with serious ventricular arrhythmias, such as torsades de pointes-type arrhythmias, and sudden death. It is likely that this experience underestimates the degree of risk that might occur with higher doses of thioridazine. Moreover, the effect of fluvoxamine may be even more pronounced when it is administered at higher doses.
Therefore, fluvoxamine and thioridazine should not be coadministered [see CONTRAINDICATIONS (4.1)].
[Potential Pimozide Interaction]
Pimozide is metabolized by the cytochrome P4503A4 isoenzyme, and it has been demonstrated that ketoconazole, a potent inhibitor of CYP3A4, blocks the metabolism of this drug, resulting in increased plasma concentrations of parent drug. An increased plasma concentration of pimozide causes QT prolongation and has been associated with torsades de pointes-type ventricular tachycardia, sometimes fatal. As noted below, a substantial pharmacokinetic interaction has been observed for fluvoxamine in combination with alprazolam, a drug that is known to be metabolized by CYP3A4. Although it has not been definitively demonstrated that fluvoxamine is a potent CYP3A4 inhibitor, it is likely to be, given the substantial interaction of fluvoxamine with alprazolam. Consequently, it is recommended that fluvoxamine not be used in combination with pimozide [see CONTRAINDICATIONS (4.1)].
[Post-Marketing Reports]
Voluntary reports of adverse reactions in patients taking fluvoxamine maleate that have been received since market introduction and are of unknown causal relationship to fluvoxamine maleate use include: acute renal failure, agranulocytosis, amenorrhea, anaphylactic reaction, angioedema, aplastic anemia, bullous eruption, Henoch-Schoenlein purpura, hepatitis, ileus, pancreatitis, porphyria, Stevens-Johnson syndrome, toxic epidermal necrolysis, vasculitis, and ventricular tachycardia (including torsades de pointes).
OVERDOSAGE
Commonly (greater than or equal to 5%) observed adverse events associated with fluvoxamine maleate overdose include gastrointestinal complaints (nausea, vomiting and diarrhea), coma, hypokalemia, hypotension, respiratory difficulties, somnolence, and tachycardia. Other notable signs and symptoms seen with fluvoxamine maleate overdose (single or multiple drugs) include bradycardia, ECG abnormalities (such as heart arrest, QT interval prolongation, first degree atrioventricular block, bundle branch block, and junctional rhythm), convulsions, dizziness, liver function disturbances, tremor, and increased reflexes.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

Rhabdomyolysis

42866

Other ADRs

2783

14114496

Odds Ratio = 5.443

Drug Property Information

ATC Code(s):

N06AB08 - fluvoxamine maleate

N06AB - Selective serotonin reuptake inhibitors
N06A - ANTIDEPRESSANTS
N06 - PSYCHOANALEPTICS
N - NERVOUS SYSTEM

Active Ingredient:fluvoxamine maleate

Active Ingredient UNII:5LGN83G74V

Drugbank ID:DB00176

PubChem Compound:3404

CAS Number:54739-18-3

Dosage Form(s):capsule, extended release

Route(s) Of Administrator:oral

Daily Dose:

100.0 mg/day N06AB08

Chemical Structure:

SMILE Code:
COCCCCC(=NOCCN)C1=CC=C(C=C1)C(F)(F)F

Reference

COHORT STUDY:

N/A

OTHER REFERENCE(S):

N/A

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