sorders: gynecomastia
General disorders and administration site conditions: chest pain; pain; peripheral oedema; pyrexia
Investigations: white blood cells urine positive
Injury, poisoning and procedural complications: tendinopathy, sometimes complicated by rupture
The following adverse events have been reported with some statins:
• sexual dysfunction
• exceptional cases of interstitial lung disease, especially with long term therapy (see section 4.4)
• diabetes mellitus: frequency will depend on the presence or absence of risk factors (fasting blood glucose ≥5.6 mmol/L, BMI>30kg/m2, raised triglycerides, history of hypertension)
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971, Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.
4.9 Overdose
ATOZET
In the event of an overdose, symptomatic and supportive measures should be employed. Liver function tests should be performed and serum CPK levels should be monitored.
Ezetimibe
In clinical studies, administration of ezetimibe, 50 mg/day to 15 healthy subjects for up to 14 days, or 40 mg/day to 18 patients with primary hyperlipidemia for up to 56 days, was generally well tolerated. A few cases of overdose have been reported; most have not been associated with adverse experiences. Reported adverse experiences have not been serious. In animals, no toxicity was observed after single oral doses of 5000 mg/kg of ezetimibe in rats and mice and 3000 mg/kg in dogs.
Atorvastatin
Due to extensive atorvastatin binding to plasma proteins, haemodialysis is not expected to significantly enhance atorvastatin clearance.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Lipid modifying agents, HMG-CoA reductase inhibitors in combination with other lipid modifying agents, ATC code: C10BA05
ATOZET (ezetimibe/atorvastatin) is a lipid-lowering product that selectively inhibits the intestinal absorption of cholesterol and related plant sterols and inhibits the endogenous synthesis of cholesterol.
Mechanism of action
ATOZET
Plasma cholesterol is derived from intestinal absorption and endogenous synthesis. ATOZET contains ezetimibe and atorvastatin, two lipid-lowering compounds with complementary mechanisms of action. ATOZET reduces elevated total cholesterol (total-C), LDL-C, apolipoprotein B (Apo B), triglycerides (TG), and non-high-density lipoprotein cholesterol (non-HDL-C), and increases high-density lipoprotein cholesterol (HDL-C) through dual inhibition of cholesterol absorption and synthesis.
Ezetimibe
Ezetimibe inhibits the intestinal absorption of cholesterol. Ezetimibe is orally active and has a mechanism of action that differs from other classes of cholesterol-reducing compounds (e.g., statins, bile acid sequestrants [resins], fibric acid derivatives, and plant stanols). The molecular target of ezetimibe is the sterol transporter, Niemann-Pick C1-Like 1 (NPC1L1), which is responsible for the intestinal uptake of cholesterol and phytosterols.
Ezetimibe |
