COMPOSITION: Each film-coated tablet contains
Active ingredients: Irbesartan: 150mg
Inactive ingredients: Povidone, Croscarmellose sodium, Microcrystalline cellulose , Maltose, Colloidal anhydrous silica, Magnesium stearate, Opadry Y-1-7000 White.
Irbesartan is a potent, orally active, selective angiotensin-II receptor (type AT1) antagonist. It is expected to block all actions of angiotensin-II mediated by the AT1 receptor, regardless of the source or route of synthesis of angiotensin-II. The selective antagonism of the angiotensin-II (AT1) receptors results in increases in plasma renin levels and angiotensin-II levels, and a decrease in plasma aldosterone concentration. Serum potassium levels are not significantly affected by irbesartan alone at the recommended doses. Irbesartan does not inhibit ACE (kininase-II), an enzyme which generates angiotensin-II and also degrades bradykinin into inactive metabolites. Irbesartan does not require metabolic activation for its activity.
After oral administration, irbesartan is well absorbed: studies of absolute bioavailability gave values of approximately 60-80%. Concomitant food intake does not significantly influence the bioavailability of irbesartan.
Plasma protein binding is approximately 96%, with negligible binding to cellular blood components. The volume of distribution is 53 – 93 litres. Following oral or intravenous administration of 14C irbesartan, 80-85% of the circulating plasma radioactivity is attributable to unchanged irbesartan.
Irbesartan is metabolised by the liver via glucuronide conjugation and oxidation. The major circulating metabolite is irbesartan glucuronide (approximately 6%).
Irbesartan exhibits linear and dose proportional pharmacokinetics over the dose range of 10 to 600 mg. A less than proportional increase in oral absorption at doses beyond 600 mg (twice the maximal recommended dose) was observed; the mechanism for this is unknown. Peak plasma concentrations are attained at 1.5 – 2 hours after oral administration. The total body and renal clearance are 157 – 176 and 3 – 3.5 ml/min, respectively. The terminal elimination half-life of irbesartan is 11 – 15 hours. Steady-state plasma concentrations are attained within 3 days after initiation of a once-daily dosing regimen. Limited accumulation of irbesartan (< 20%) is observed in plasma upon repeated once-daily dosing. In a study, somewhat higher plasma concentrations of irbesartan were observed in female hypertensive patients. However, there was no difference in the half-life and accumulation of irbesartan. No dosage adjustment is necessary in female patients. Irbesartan AUC and Cmax values were also somewhat greater in elderly subjects (≥ 65 years) than those of young subjects (18 – 40 years). However the terminal half-life was not significantly altered. No dosage adjustment is necessary in elderly patients.
Renal impairment: in patients with renal impairment or those undergoing haemodialysis, the pharmacokinetic parameters of irbesartan are not significantly altered. Irbesartan is not removed by haemodialysis.
Hepatic impairment: in patients with mild to moderate cirrhosis, the pharmacokinetic parameters of irbesartan are not significantly altered.
Studies have not been performed in patients with severe hepatic impairment.
Treatment of essential hypertension.
Treatment of renal disease in patients with hypertension and type 2 diabetes mellitus as part of an antihypertensive medicinal product regimen
POSOLOGY AND METHOD OF ADMINISTRATION
The usual recommended initial and maintenance dose is 150 mg once daily, with or without food. NACARDIO at a dose of 150 mg once daily generally provides a better 24 hour blood pressure control than 75 mg. However, initiation of therapy with 75 mg could be considered, particularly in haemodialysed patients and in the elderly over 75 years.
In patients insufficiently controlled with 150 mg once daily, the dose of NACARDIO can be increased to 300 mg, or other antihypertensive agents can be added. In particular, the addition of a diuretic such as hydrochlorothiazide has been shown to have an additive effect with NACARDIO
In hypertensive type 2 diabetic patients, therapy should be initiated at 150 mg irbesartan once daily and titrated up to 300 mg once daily as the preferred maintenance dose for treatment of renal disease.
Renal impairment: no dosage adjustment is necessary in patients with impaired renal function. A lower starting dose (75 mg) should be considered for patients undergoing haemodialysis .
Hepatic impairment: no dosage adjustment is necessary in patients with mild to moderate hepatic impairment.
Elderly patients: although consideration should be given to initiating therapy with 75 mg in patients over 75 years of age, dosage adjustment is not usually necessary for the elderly.
Hypersensitivity to the active substance, or to any of the excipients
Second and third trimesters of pregnancy
SPECIAL WARNINGS AND PRECAUTIONS FOR USE
Intravascular volume depletion: symptomatic hypotension, especially after the first dose, may occur in patients who are volume and/or sodium depleted by vigorous diuretic therapy, dietary salt restriction, diarrhoea or vomiting. Such conditions should be corrected before the administration of NACARDIO.
Renovascular hypertension: there is an increased risk of severe hypotension and renal insufficiency when patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney are treated with medicinal products that affect the renin-angiotensin-aldosterone system.
Renal impairment and kidney transplantation: when NACARDIO is used in patients with impaired renal function, a periodic monitoring of potassium and creatinine serum levels is recommended. There is no experience regarding the administration of NACARDIO in patients with a recent kidney transplantation.
Hypertensive patients with type 2 diabetes and renal disease: the effects of irbesartan both on renal and cardiovascular events were not uniform across all subgroups, in an analysis carried out in the study with patients with advanced renal disease.
Hyperkalaemia: as with other medicinal products that affect the renin-angiotensin-aldosterone system, hyperkalaemia may occur during the treatment with NACARDIO, especially in the presence of renal impairment, overt proteinuria due to diabetic renal disease, and/or heart failure. Close monitoring of serum potassium in patients at risk is recommended
Lithium: the combination of lithium and NACARDIO is not recommended
Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy: as with other vasodilators, special caution is indicated in patients suffering from aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy.
Primary aldosteronism: patients with primary aldosteronism generally will not respond to antihypertensive medicinal products acting through inhibition of the renin-angiotensin system. Therefore, the use of NACARDIO is not recommended.
INTERACTION WITH OTHER MEDICINAL PRODUCTS
Diuretics and other antihypertensive agents: other antihypertensive agents may increase the hypotensive effects of irbesartan; however NACARDIO has been safely administered with other antihypertensive agents, such as beta-blockers, long-acting calcium channel blockers, and thiazide diuretics. Prior treatment with high dose diuretics may result in volume depletion and a risk of hypotension when initiating therapy with NACARDIO
Potassium supplements and potassium-sparing diuretics: based on experience with the use of other medicinal products that affect the renin-angiotensin system, concomitant use of potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium or other medicinal products that may increase serum potassium levels (e.g. heparin) may lead to increases in serum potassium and is, therefore, not recommended
Lithium: reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin converting enzyme inhibitors. Similar effects have been very rarely reported with irbesartan so far. Therefore, this combination is not recommended. If the combination proves necessary, careful monitoring of serum lithium levels is recommended.
Non-steroidal anti-inflammatory drugs: when angiotensin II antagonists are administered simultaneously with non-steroidal anti-inflammatory drugs (i.e. selective COX-2 inhibitors, acetylsalicylic acid (>3g/day) and non-selective NSAIDs), attenuation of the antihypertensive effect may occur.
PREGNANCY AND LACTATION
The use of AIIRAs is not recommended during the first trimester of pregnancy The use of AIIRAs is contraindicated during the second and third trimester of pregnancy
Because no information is available regarding the use of NACARDIO during breast-feeding, NACARDIO is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES
No studies on the effects on the ability to drive and use machines have been performed. Based on its pharmacodynamic properties, irbesartan is unlikely to affect this ability. When driving vehicles or operating machines, it should be taken into account that dizziness or weariness may occur during treatment.
Very common: Hyperkalaemia* occurred more often in diabetic patients treated with irbesartan than with placebo.
Common: significant increases in plasma creatine kinase were commonly observed (1.7%) in irbesartan treated subjects. None of these increases were associated with identifiable clinical musculoskeletal events.
Nervous system disorders:
Common: dizziness, orthostatic dizziness*
Respiratory, thoracic and mediastinal disorders:
Uncommon: diarrhoea, dyspepsia/heartburn
Musculoskeletal and connective tissue disorders:
Common: musculoskeletal pain*
Common: orthostatic hypotension*
General disorders and administration site conditions:
Uncommon: chest pain
Inform doctors with side effects when using medicine
Experience in adults exposed to doses of up to 900 mg/day for 8 weeks revealed no toxicity. The most likely manifestations of overdose are expected to be hypotension and tachycardia; bradycardia might also occur from overdose. No specific information is available on the treatment of overdose with NACARDIO. The patient should be closely monitored, and the treatment should be symptomatic and supportive. Suggested measures include induction of emesis and/or gastric lavage. Activated charcoal may be useful in the treatment of overdose. Irbesartan is not removed by haemodialysis.
STORAGE: Store at temperature below 300C. Protect from sunlight and moisture.
SHELF-LIFE: 24 months from the manufacturing date.
HOW SUPPLIED: 2 blisters x 14 Tablets/Box.
- Keep all medicines out of the reach of children.
- Read carefully the leaflet before use.
- For further information, please contact your doctor.
- This drug is dispensed on prescription only.
Manufactured by: LABORATORIOS LESVI, S.L
Avda. Barcelona, 69 08970 Sant Joan Despí (Barcelona)- Spain
Product-licence holder: QUALIGEN, S.L
Avda. Barcelona, 69 08970 Sant Joan Despí (Barcelona)- Spain