Source: Health Products Regulatory Authority (IE) Revision Year: 2023 Publisher: Organon Pharma (Ireland) Limited, 2 Dublin Landings, North Wall Quay North Dock, Dublin, D01 V4A3, Ireland
INEGY is indicated to reduce the risk of cardiovascular events (see section 5.1) in patients with coronary heart disease (CHD) and a history of acute coronary syndrome (ACS), either previously treated with a statin or not.
INEGY is indicated as adjunctive therapy to diet for use in patients with primary (heterozygous familial and non-familial) hypercholesterolaemia or mixed hyperlipidaemia where use of a combination product is appropriate:
INEGY is indicated as adjunctive therapy to diet for use in patients with HoFH. Patients may also receive adjunctive treatments (e.g. low-density lipoprotein [LDL] apheresis).
The patient should be on an appropriate lipid‑lowering diet and should continue on this diet during treatment with INEGY.
Route of administration is oral. The dosage range of INEGY is 10/10 mg/day through 10/80 mg/day in the evening. All dosages may not be available in all member states. The typical dose is 10/20 mg/day or 10/40 mg/day given as a single dose in the evening. The 10/80-mg dose is only recommended in patients with severe hypercholesterolaemia and at high risk for cardiovascular complications who have not achieved their treatment goals on lower doses and when the benefits are expected to outweigh the potential risks (see sections 4.4 and 5.1). The patient’s low-density lipoprotein cholesterol (LDL‑C) level, coronary heart disease risk status, and response to current cholesterol-lowering therapy should be considered when starting therapy or adjusting the dose.
The dose of INEGY should be individualised based on the known efficacy of the various dose strengths of INEGY (see section 5.1, Table 2) and the response to the current cholesterol-lowering therapy. Adjustments of dosage, if required, should be made at intervals of not less than 4 weeks. INEGY can be administered with or without food. The tablet should not be split.
In the cardiovascular events risk reduction study (IMPROVE-IT), the starting dose was 10/40 mg once a day in the evening. The 10/80-mg dose is only recommended when the benefits are expected to outweigh the potential risks.
The recommended starting dosage for patients with homozygous familial hypercholesterolaemia is INEGY 10/40 mg/day in the evening. The 10/80-mg dose is only recommended when the benefits are expected to outweigh the potential risks (see above; sections 4.3 and 4.4). INEGY may be used as an adjunct to other lipid-lowering treatments (e.g. LDL apheresis) in these patients or if such treatments are unavailable.
In patients taking lomitapide concomitantly with INEGY, the dose of INEGY must not exceed 10/40 mg/day (see sections 4.3, 4.4 and 4.5).
Dosing of INEGY should occur either ≥2 hours before or ≥4 hours after administration of a bile acid sequestrant.
In patients taking amiodarone, amlodipine, verapamil, diltiazem, or products containing elbasvir or grazoprevir concomitantly with INEGY, the dose of INEGY should not exceed 10/20 mg/day (see sections 4.4 and 4.5).
In patients taking lipid-lowering doses (≥1 g/day) of niacin concomitantly with INEGY, the dose of INEGY should not exceed 10/20 mg/day (see sections 4.4 and 4.5).
No dosage adjustment is required for elderly patients (see section 5.2).
Initiation of treatment must be performed under review of a specialist.
Adolescents ≥10 years (pubertal status: boys Tanner Stage II and above and girls who are at least one year post-menarche): The clinical experience in paediatric and adolescent patients (aged 10-17 years old) is limited. The recommended usual starting dose is 10/10 mg once a day in the evening. The recommended dosing range is 10/10 to a maximum of 10/40 mg/day (see sections 4.4 and 5.2).
Children <10 years: INEGY is not recommended for use in children below age 10 due to insufficient data on safety and efficacy (see section 5.2). The experience in pre-pubertal children is limited.
No dosage adjustment is required in patients with mild hepatic impairment (Child-Pugh score 5 to 6). Treatment with INEGY is not recommended in patients with moderate (Child-Pugh score 7 to 9) or severe (Child-Pugh score >9) liver dysfunction.(See sections 4.4 and 5.2.)
No modification of dosage should be necessary in patients with-mild renal impairment (estimated glomerular filtration rate ≥60 mL/min/1.73 m²). In patients with chronic kidney disease and estimated glomerular filtration rate <60 mL/min/1.73 m², the recommended dose of INEGY is 10/20 mg once a day in the evening (see sections 4.4, 5.1, and 5.2). Higher doses should be implemented cautiously.
INEGY is for oral administration. INEGY can be administered as a single dose in the evening.
In the event of an overdose, symptomatic and supportive measures should be employed. Co-administration of ezetimibe (1,000 mg/kg) and simvastatin (1,000 mg/kg) was well-tolerated in acute, oral toxicity studies in mice and rats. No clinical signs of toxicity were observed in these animals. The estimated oral LD50 for both species was ezetimibe ≥1,000 mg/kg/simvastatin ≥1,000 mg/kg.
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 hypercholesterolaemia for up to 56 days, was generally well tolerated. A few cases of overdosage 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 5,000 mg/kg of ezetimibe in rats and mice and 3,000 mg/kg in dogs.
A few cases of overdosage have been reported; the maximum dose taken was 3.6 g. All patients recovered without sequelae.
2 years.
Do not store above 30°C.
Blisters: Store in the original package in order to protect from moisture and light.
Bottles: Keep bottles tightly closed in order to protect from moisture and light.
White HDPE bottles with foil induction seals, white child-resistant polypropylene closure, and silica gel desiccant, containing 100 tablets.
Push-through blisters of opaque polychlorotrifluoroethylene/PVC sealed to vinyl coated aluminium in packs of 90 tablets.
Push-through blisters of opaque polychlorotrifluoroethylene/PVC sealed to vinyl coated aluminium in packs of 7, 10, 14, 28, 30, 50, 56, 84, 98, 100, or 300 tablets.
Unit dose push-through blisters of opaque polychlorotrifluoroethylene/PVC sealed to vinyl coated aluminium in packs of 30, 50, 100, or 300 tablets.
Not all pack sizes may be marketed.
No special requirements.
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