DIRA 1.0: Atlas of Drug-induced Rhabdomyolysis

EZETIMIBE

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
Myopathy/Rhabdomyolysis
In clinical trials, there was no excess of myopathy or rhabdomyolysis associated with ZETIA compared with the relevant control arm (placebo or statin alone). However, myopathy and rhabdomyolysis are known adverse reactions to statins and other lipid-lowering drugs. In clinical trials, the incidence of creatine phosphokinase (CPK) >10 × ULN was 0.2% for ZETIA vs. 0.1% for placebo, and 0.1% for ZETIA coadministered with a statin vs. 0.4% for statins alone. Risk for skeletal muscle toxicity increases with higher doses of statin, advanced age (>65), hypothyroidism, renal impairment, and depending on the statin used, concomitant use of other drugs.
In post-marketing experience with ZETIA, cases of myopathy and rhabdomyolysis have been reported. Most patients who developed rhabdomyolysis were taking a statin prior to initiating ZETIA. However, rhabdomyolysis has been reported with ZETIA monotherapy and with the addition of ZETIA to agents known to be associated with increased risk of rhabdomyolysis, such as fibrates. ZETIA and any statin or fibrate that the patient is taking concomitantly should be immediately discontinued if myopathy is diagnosed or suspected. The presence of muscle symptoms and a CPK level >10 × the ULN indicates myopathy.
ADVERSE REACTIONS
The following serious adverse reactions are discussed in greater detail in other sections of the label:
- Liver enzyme abnormalities [see WARNINGS AND PRECAUTIONS (5.2)]
- Rhabdomyolysis and myopathy [see WARNINGS AND PRECAUTIONS (5.3)]
Post-Marketing Experience
Because the reactions below are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
The following additional adverse reactions have been identified during post-approval use of ZETIA:
Hypersensitivity reactions, including anaphylaxis, angioedema, rash, and urticaria; erythema multiforme; arthralgia; myalgia; elevated creatine phosphokinase; myopathy/rhabdomyolysis [see WARNINGS AND PRECAUTIONS (5.3)]; elevations in liver transaminases; hepatitis; abdominal pain; thrombocytopenia; pancreatitis; nausea; dizziness; paresthesia; depression; headache; cholelithiasis; cholecystitis.

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

Rhabdomyolysis

420

42492

Other ADRs

11578

14105701

Odds Ratio = 12.043

Drug Property Information

ATC Code(s):

C10BA02 - ezetimibe

C10BA - HMG CoA reductase inhibitors in combination with other lipid modifying agents
C10B - "LIPID MODIFYING AGENTS, COMBINATIONS"
C10 - LIPID MODIFYING AGENTS
C - CARDIOVASCULAR SYSTEM

C10BA05 - ezetimibe

C10BA - HMG CoA reductase inhibitors in combination with other lipid modifying agents
C10B - "LIPID MODIFYING AGENTS, COMBINATIONS"
C10 - LIPID MODIFYING AGENTS
C - CARDIOVASCULAR SYSTEM

C10BA06 - ezetimibe

C10BA - HMG CoA reductase inhibitors in combination with other lipid modifying agents
C10B - "LIPID MODIFYING AGENTS, COMBINATIONS"
C10 - LIPID MODIFYING AGENTS
C - CARDIOVASCULAR SYSTEM

C10AX09 - ezetimibe

C10AX - Other lipid modifying agents
C10A - "LIPID MODIFYING AGENTS, PLAIN"
C10 - LIPID MODIFYING AGENTS
C - CARDIOVASCULAR SYSTEM

Active Ingredient:ezetimibe

Active Ingredient UNII:EOR26LQQ24

Drugbank ID:DB00973

PubChem Compound:150311

CAS Number:163222-33-1

Dosage Form(s):tablet

Route(s) Of Administrator:oral

Daily Dose:

10.0 mg/day C10AX09

Chemical Structure:

SMILE Code:
C1=CC(=CC=C1[C@@H]2[C@H](C(=O)N2C3=CC=C(C=C3)F)CC[C@@H](C4=CC=C(C=C4)F)O)O

Reference

COHORT STUDY:

N/A

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