DIRA 1.0: Atlas of Drug-induced Rhabdomyolysis

DILTIAZEM HYDROCHLORIDE

DIR Classification Postmarketing Surveillance Drug Property Information Reference

DIR Classification

Classification:Moderate-DIR concern

Severity Score:3

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

PRECAUTIONS
Drug Interactions
Statins. Diltiazem is an inhibitor of CYP3A4 and has been shown to increase significantly the AUC of some statins. The risk of myopathy and rhabdomyolysis with statins metabolized by CYP3A4 may be increased with concomitant use of diltiazem. When possible, use a non-CYP3A4-metabolized statin together with diltiazem; otherwise, dose adjustments for both diltiazem and the statin should be considered along with close monitoring for signs and symptoms of any statin related adverse events.
In a healthy volunteer cross-over study (N=10), co-administration of a single 20 mg dose of simvastatin at the end of a 14 day regimen with 120 mg BID diltiazem SR resulted in a 5-fold increase in mean simvastatin AUC versus simvastatin alone. Subjects with increased average steady-state exposures of diltiazem showed a greater fold increase in simvastatin exposure. Computer-based simulations showed that at a daily dose of 480 mg of diltiazem, an 8- to 9-fold mean increase in simvastatin AUC can be expected. If co-administration of simvastatin with diltiazem is required, limit the daily doses of simvastatin to 10 mg and diltiazem to 240 mg.
In a ten-subject randomized, open label, 4-way cross-over study, co-administration of diltiazem (120 mg BID diltiazem SR for 2 weeks) with a single 20 mg dose of lovastatin resulted in 3- to 4-fold increase in mean lovastatin AUC and Cmax versus lovastatin alone. In the same study, there was no significant change in 20 mg single dose pravastatin AUC and Cmax during diltiazem coadministration. Diltiazem plasma levels were not significantly affected by lovastatin or pravastatin.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

Rhabdomyolysis

42821

Other ADRs

7187

14110092

Odds Ratio = 4.173

Drug Property Information

ATC Code(s):

C05AE03 - diltiazem hydrochloride

C05AE - Muscle relaxants
C05A - AGENTS FOR TREATMENT OF HEMORRHOIDS AND
C05 - VASOPROTECTIVES
C - CARDIOVASCULAR SYSTEM

C08DB01 - diltiazem hydrochloride

C08DB - Benzothiazepine derivatives
C08D - SELECTIVE CALCIUM CHANNEL BLOCKERS WITH DIRECT CARDIAC EFFECTS
C08 - CALCIUM CHANNEL BLOCKERS
C - CARDIOVASCULAR SYSTEM

Active Ingredient:diltiazem hydrochloride

Active Ingredient UNII:OLH94387TE

Drugbank ID:DB00343

PubChem Compound:39186

CAS Number:42399-41-7

Dosage Form(s):capsule, extended release

Route(s) Of Administrator:oral

Daily Dose:

240.0 mg/day C08DB01

Chemical Structure:

SMILE Code:
CC(=O)O[C@@H]1[C@@H](SC2=CC=CC=C2N(C1=O)CCN(C)C)C3=CC=C(C=C3)OC

Reference

COHORT STUDY:

N/A

OTHER REFERENCE(S):

N/A

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