Ezetimibe

Registered South African indications:

• Primary hypercholesterolaemia
  - Heterozygous familial hypercholesterolaemia
  - Non-familial hypercholesterolaemia
• Homozygous familial hypercholesterolaemia

Contraindications

• Hypersensitivity to the active ingredient of any of its excipients
• Pregnancy
• Breastfeeding
• Moderate to severe hepatic impairment (Child Pugh score≥7)
• Children younger than 10 years 
• Coadministration with a statin in patients with active liver disease or unexplained persistent elevations in serum transaminases

Cautions 

• Coadministration with ciclosporin
• Coadministration with warfarin
• Galactose intolerance
• Total lactase deficiency
• Glucose-galactose malabsorption

Forms avail. in SA and covered in this monograph: tab 

Primary hypercholesterolaemia, as adjunctive therapy to diet for the reduction of elevated total cholesterol and low-density lipoprotein cholesterol (Additional agent may be required)
- Heterozygous familial hypercholesterolaemia
- Non-familial hypercholesterolaemia
Homozygous familial hypercholesterolaemia, for the reduction of elevated total cholesterol and low-density lipoprotein cholesterol (Additional agent required)

• Oral (tab): 10mg, dly with or without food 

The patient should be on an appropriate lipid-lowering diet and weight loss program where indicated 

Dosing of ezetimibe should occur at least 2 hours before or 4 hours after administration of a bile acid sequestrant

Paed. forms avail. in SA and covered in this monograph: tab

Primary hypercholesterolaemia, as adjunctive therapy to diet for the reduction of elevated total cholesterol and low-density lipoprotein cholesterol (Additional agent may be required)
- Heterozygous familial hypercholesterolaemia
- Non-familial hypercholesterolaemia
Homozygous familial hypercholesterolaemia, for the reduction of elevated total cholesterol and low-density lipoprotein cholesterol (Additional agent required)

Younger than 10 years 

• Contraindicated

Older than 10 years

• See adult dosage

The patient should be on an appropriate lipid-lowering diet and weight loss program where indicated 

Dosing of ezetimibe should occur at least 2 hours before or 4 hours after administration of a bile acid sequestrant

Pregnancy

• Contraindicated
• Ezetimibe is contraindicated during pregnancy. No clinical data are available on the use of ezetimibe during pregnancy

Breastfeeding 

• Contraindicated
• Ezetimibe is contraindicated during breastfeeding
• Ezetimibe should not be used during breastfeeding. Studies on rats have shown that ezetimibe is secreted into breast milk. It is not known if ezetimibe is secreted into human breast milk

Fertility

• No clinical trial data are available on the effects of ezetimibe on human fertility. Ezetimibe had no effect on the fertility of male or female rats

Renal Impairment

• No dose adjustment recommended

Hepatic Impairment 

• Mild (Child Pugh score 5-6): No dose adjustment recommended 
• Moderate to severe (Child Pugh score≥7): Contraindicated

Elderly

• No dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings 

Central Nervous System Disorders

• Fatigue
• Dizziness
• Paraesthesia
• Depression
• Headache 
• Paraesthesia 

Cardiovascular Disorders

• Hypertension
• Hot flush
• Chest pain 
• Peripheral oedema

Respiratory Disorders

• Cough
• Dyspnoea

Gastrointestinal Disorders

• Abdominal pain
• Diarrhoea
• Flatulence
• Dyspepsia
• Gastrooesophageal reflux disease
• Nausea
• Pancreatitis
• Constipation
• Dry mouth
• Gastrititis 

Hepatobiliary Disorders

• Hepatitis
• Cholelithiasis
• Cholecystitis
• Increase in alanine aminotransferase
• Increase in aspartate aminotrasferase
• Increase in gamma-glutamyltransferase 
• Abnormal liver function test 

Endocrine and Metabolic Disorders

• Decreased appetite
• Increase in blood CPK 

Musculoskeletal Disorders

• Myopathy
• Rhabdomyolysis
• Arthralgia
• Muscle spasms
• Neck pain
• Myalgia 
• Back pain 
• Muscular weakness 
• Pain in extremity 

Skin and Subcutaneous Tissue Disorders

• Erythema multiforme
• Pruritis 
• Rash 
• Urticaria 

Immune, Blood and Lymphatic System Disorders

• Thrombocytopaenia
• Hypersensitivity reactions

• Cholestyramine
• Fibrates 
• Ciclosporin
• Warfarin
• Statins
• Antacids

None routine. Specific cases may require

• Hepatic function

•  The patient should be on an appropriate lipid-lowering diet and should continue on this diet during treatment with ezetimibe

Ezetimibe inhibits the intestinal absorption of cholesterol at the small intestine brush border, leading to a decrease in the delivery of intestinal cholesterol to the liver.  

Tablet 10mg

• Ezetimibe 10 Teva (Teva Pharmaceuticals)
• Ezetimibe 10 Unicorn (Sandoz SA)
• Ezetrol (MSD)
• Mezibe 10 (Ranbaxy Pharmaceuticals)
• Mibitez (Trinity Pharma)
• Nitasol (Trinity Pharma)
• Tactus 10mg (Sandoz SA)
• Toleze 10 (Adcock Ingram)
• Trezecol 10mg (Accord Healthcare)
• Tryzetor 10mg (Pharma Dynamics)
• Zytezo (Zydus Healthcare SA)

COMBINATION PREPARATIONS

Ezetimibe/ Simvastatin

Tablet 10/10mg

• Inegy (MSD) originator
• Mezibe Plus 10/10 (Ranbaxy Pharmaceuticals)

Tablet 10/20mg

• Inegy (MSD) originator
• Mezibe Plus 10/20 (Ranbaxy Pharmaceuticals)

Tablet 10/40mg

• Inegy (MSD) originator
• Mezibe Plus 10/40 (Ranbaxy Pharmaceuticals)