Class: Angiotensin-II receptor antagonists, diuretic

Manufacturer: Sun Pharma Laboratories Ltd, 6-9 EPIP, Kartholi, Bari Brahmana, Jammu – 181 133. (J & K), India.

Dosage Form: Tablet

Similar Brands:

Uses:

Irovel H is indicated for the treatment of hypertension. The fixed dose combination is not indicated for the initial therapy.

Dosage:

A patient whose blood pressure is not adequately controlled with irbesartan monotherapy may be switched to Irovel H. The recommended dose of Irovel H is one tablet once daily or two tablets once daily. The largest incremental effect will likely be in the transition from monotherapy to 150/12.5mg. It takes 2-4 weeks for the blood pressure to stabilize after a change in the dose of irovel H.

More than two tablets once daily are not recommended. The maximum antihypertensive effect is attained about three weeks after initiation of therapy.

No dosage adjustment is necessary in elderly patients with hepatic impairment or mild to severe renal impairment.

Irovel H may be administered with other antihypertensive agents.

Irovel H may be administered with or without food.

Use in patients with renal impairment

The usual regimens of therapy with irovel H should be followed as long as the patients creatinine clearance is >30 ml/min. In patients with more severe renal impairment, loop diuretics are preffered to thiazides. Irovel H is not recommended.

Use in patients with hepatic impairment

No dosage adjustment is necessary in patients with hepatics impairment.

Side Effects:

Irbesartan/Hydrochlorothiazide.

No adverse effects peculiar to this combination have been observed. Adverse events are limited to those reported previously with Irbesartan and/or hydrochlorothiazide.

The side effects reported are dizziness, dose-related orthostasis, abdominal pain, dyspepsia, nausea, vomiting, headache, fatigue, influenza, myalgia, migraine, muscle pain, urticaria, pruritus,, rash and angioedema.

Serum potassium should be monitored, particularly in the elderly and patients with renal impairment. Elevations of ALT occurred rarely and usually resolved upon discontinuation of therapy.

Irbesartan

Irbesartan has been generally well tolerated in human studies. Adverse events reported are headache, sinus, abnormality, cough, pharyngitis, diarrhea, rhinitis, urinary tract infection, rash, anxiety/nervousness, and muscle cramp. However most side effects have been mild and transient in nature and have not required discontinuation of therapy. Rare cased of hypersensitivity reaction, occasionally severe (e.g. anaphylaxis), have been reported.

Hydrochlorothiazide

Weakness, pancreatitis, jaundice (intrahepatic cholestatic jaundice), cramping, gastric irritation, aplastic anaemia, agranulocytosis, leucopenia, hemolytic anemia, thrombocytopenia, photosensitivity, urticaria, necrotizing angiitis  (vasculitis and cutaneous vasculitis), fever, respiratory distress including pneumonia and pulmonary oedema, anaphylactic reactions, hyperglycemia, glycosuria, hyperuricaemia, muscle spasm, restlessness, renal failure, renal dysfunction, interstitial nephritis, erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis. Transient blurred vision and xanthopsia.

Warnings & Precautions:

Irbesartan and hydrochlorothiazide combination tablet:

The combination of Irbesartan and hydrochlorothiazide tablet had no effect on serum potassium. Higher doses of irbesartan ameliorated the hypokalaemic response to hydrochlorothiazide.

Hydrochlorothiazide

• Hypersensitivity reactions may occur in patients with or without history of allergy or bronchial asthma.
• Thiazides might exacerbate or activate systemic lupus erythematosus.
• Patients taking thiazide diuretics should be observed for hyponatraemia, hypercalcaemia, hypokalaemia and hypochloraemic alkalosis.
• As with all antihypertensive therapy, symptomatic hypotension might occur in some patients.
• Hyperglycaemia and hyperuricaemia might occur with thiazide diuretics.
• Lithium should not be given.

Hypotension in volume or salt depleted patients, impaired renal function, pregnancy and lactation.

Pregnancy & Lactation:

Consult your physician

Drug Interactions:

Irbesartan

No significant drug-drug pharmacokinetic or pharmacogynamic interactions have been found in interaction studies with hydrochlorothiazide, digoxin, warfarin, and nifedipine. In vitro studies show significant inhibition of the formation of oxidized irbesartan metabolites with the known cytochrome CYP 2C9 substrates/inhibitors sulphenazole, tolbutamide and nifedipine. Concomitant hydrochlorothiazide had no effect on irbesartan pharmacokinetics. Based on in vitro data, no interaction would be expected with drugs whose metabolism is dependant up cytochrome P450 isozymes.

Hydrochlorothiazide

Thiazides interact with alcohol, barbiturates, narcotics, anti-diabetic drugs, other antihypertensive drugs, cholestyramine and colestipol resins, corticosteroids, ACTH, pressor amines, skeletal muscle relaxants (non-depolarizing), lithium, NSAIDs.

Contraindications:

Hypersensitivity to the drug and any of the ingredients, Anuria, Sulphonamide-derived drugs.

Price: Ksh 2,550

Notes:

Mode of action

Irbesartan – angiotensin II is a potent vasoconstrictor formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE Kinase II). Angiotensin II is the principal pressor agent of the rennin-angotensin system (RAS) and also stimulates aldosterone synthesis and secretion by adrenal cortex, cardiac contraction, renal resorption of sodium, activity of sympathetic nervous system, and smooth muscle-cell growth.

Irbesartan is aspecific antagonist of AT, receptors with a much greater affinity (more than 8500-fold) for the AT, receptor than for the AT2receptor, and no agonist activity.

Hydrochlorothiazide – Hydrochlorothiazide is a thiazide diuretic. It affects the renal tubular mechanism of electrolyte re-absorption and directly increases excretion of sodium and chloride in approximately equal amounts. Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with consequent increase in plasma renin activity, increase in aldosterone secretion, increase in urinary potassium loss, and decrease in serum potassium. The renin aldosterone link is mediated by angiotensin II so co-administration of angiotensin II receptor antagonist tends to reverse the potassium loss associated with these diuretics.

Overdose

Irbesartan

No data are available in regard to over dosage humans. However, daily doses of 900mg for 8 weeks were well tolerated. The most  likely manifestations of over dosage are expected to be hypotension and tachycardia; bradycardia might occur from overdose. In managing overdose, consider the possibilities of multiple-drug interactions, drug-drug interactions, and unusual drug kinetics in the patient. Irbesartan in not removed by haemodialysis.

Hydrochlorothiazide

The most common signs and symptoms of overdose observed are those caused by electrolyte depletion (hypokalaemia, hypochloraemia, hyponatraemia) and dehydration resulting from excessive dieresis. If digitalis has also been administered, hypokalaemia may accentuate cardiac arrhythmias

Pack Size: 30s

Ref: PADPI0087