General

Canada-Approved Medicine

This monograph describes a medication approved for use in Canada by the Therapeutic Products Directorate, a division of Health Canada’s Health Products and Food Branch. The medication is not approved by the United States Food and Drug Administration; however, a similar formulation carrying a different generic or brand name might be available in the US.

Pronunciation:
bezz-uh-fibe-rate

Trade Name(s)

• Bezalip SR 

Ther. Class.

lipid-lowering agents

Pharm. Class.

fibric acid derivatives

Indications

• Use in conjunction with diet and other modalities in the treatment of hypercholesterolemia (Type IIa and IIb mixed hyperlipidemia, to decrease serum TG, LDL cholesterol and apolipoprotein B and increase HDL cholesterol, and apolipoprotein A).
• Treatment of adults with hypertriglyceridemia (Type IV and V hyperlipidemias) at risk of pancreatitis and other sequelae.

Action

Inhibits triglyceride synthesis.

Therapeutic Effect(s):

Lowered cholesterol and triglycerides, increased HDL, with decreased risk of pancreatitis and other sequelae.

Pharmacokinetics

Absorption: Well absorbed (100%) following oral administration.

Distribution: Unknown.

Metabolism and Excretion: 50% metabolized, 50% excreted unchanged in urine, remainder as metabolites. 3% excreted in feces.

Half-life: 1–2 hr.

TIME/ACTION PROFILE (blood levels)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity/photosensitivity to bezafibrate or other fibric acid or fibrate derivatives;
• Severe hepatic or renal impairment (CCr <60 mL/min), primary biliary cirrhosis, gallstone or gallbladder disease or hypoalbuminemia;
• OB:  Avoid use during pregnancy (discontinue several mo prior to conception);
• Lactation: Discontinue breastfeeding.

Use Cautiously in:

• History of liver disease;
• Doses >400 mg/day in conjunction with HMG CoA reductase inhibitors (statins) with any risk factors (renal impairment, infection, trauma, surgery, hormonal or electrolyte imbalance) ↑ risk for rhabdomyolysis;
• Geri:  Consider age-related ↓ in renal function; avoid in patients >70 yr;
• Pedi:  Limited experience in children at a dose of 10–20 mg/kg/day.

Adverse Reactions/Side Effects

CNS: dizziness, headache

GI: dyspepsia, flatulence, gastritis, ↓ appetite, abdominal distension, abdominal pain, cholestasis, constipation, diarrhea, nausea

GU: erectile dysfunction, renal failure

Derm: alopecia, photosensitivity reaction, pruritus, rash, urticaria

MS: muscle cramps, muscular weakness, myalgia, RHABDOMYOLYSIS

Misc: hypersensitivity reactions including anaphylaxis

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

• ↑ risk of bleeding with  oral anticoagulants ; ↓ dose of anticoagulant by 50% with frequent monitoring.
•  Cyclosporine  ↑ risk of severe myositis/rhabdomyolysis; combination therapy should be undertaken with caution.
• Concurrent use of  immunosuppressants  may ↑ risk of reversible renal impairment.
• ↑ risk of myopathy with  HMG CoA reductase inhibitors (statins) ; combination therapy should be undertaken with extreme caution and must be discontinued at the first signs of myopathy and should not be undertaken in the presence of predisposing factors including impaired renal function, severe infection, trauma, surgery, hormonal /electrolyte imbalance or ↑ alcohol intake.
• ↑ risk of serious hypoglycemia with  insulin  or  sulfonylureas.
• Concurrent use with  MAO inhibitors  may ↑ risk of hepatotoxicity.
•  Cholestyramine  and other  bile-acid sequestrants  may ↓ absorption; separate administration by ≥2 hr.
• Effectiveness may be ↓ by concurrent  estrogen.

Route/Dosage

PO (Adults): 400 mg once daily.

Availability

Sustained-release tablet: 400 mg

Assessment

• Obtain a diet history with regard to fat consumption. Before starting benzafibrate, every attempt should be made to obtain a normal triglyceride level with diet, exercise and weight loss.
• Assess for cholelithiasis. If gallbladder studies are indicated, and gallstones are found, discontinue therapy.

Lab Test Considerations:

• Monitor serum lipids prior to and periodically during therapy.
• Monitor AST and ALT serums periodically during therapy to assess for ↑ levels. Discontinue therapy if levels rise >3 times normal value.
• If patient develops muscle tenderness during therapy, monitor CPK levels. If CPK levels are markedly ↑ or myopathy occurs, discontinue therapy.

Implementation

• PO Administer without regard to meals.  DNC:  Swallow sustained-release tablets whole; do not crush, break, or chew.

Patient/Family Teaching

• Instruct the patient to take the medication as directed, and to not share medication. Missed doses should be taken as soon as remembered; do not double dose. Medication helps control but does not cure elevated serum triglyceride levels.
• Advise patient that medication should be taken in conjunction with diet restrictions of fat, cholesterol, carbohydrates, and alcohol, as well as an exercise regimen, and cessation of smoking.
• Instruct patient to notify health care professional of unexplained muscle pain or weakness, tiredness, fever, nausea, vomiting, abdominal pain.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any other Rx, OTC, or herbal products.
• Rep:  Advise females of reproductive potential to immediately notify health care professional if pregnancy is planned or suspected.
• Emphasize importance of follow-up appointments, and lab tests to evaluate effectiveness.

Evaluation/Desired Outcomes

• A decrease in serum triglyceride and LDL cholesterol levels.
• An increase in HDL levels.