GIRAN H

Candesartan Cilexetil+ Hydrochlorothiazide

Description:

Giran H (Candesartan Cilexetil-Hydrochlorothiazide) combines an angiotensin II receptor blocker, Candesartan Cilexetil and a diuretic, Hydrochlorothiazide.

Composition:

Giran H Tablet: Each tablet contains Candesartan Cilexetil INN 8mg and Hydrochlorothiazide BP12.5 mg.

Pharmacology:

Candesartan Cilexetil is an ester prodrug that is hydrolysed in the body to the active form Candesartan during absorption from the gastrointestinal tract. Candesartan is angiotensin II receptor (type AT1) blocker. Candesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues (eg, vascular smooth muscle, adrenal gland).

Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. Indirectly, the diuretic action of hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in aldosterone secretion, increases in urinary potassium loss, and decreases in serum potassium. The renin-aldosterone link is mediated by angiotensin II, so coadministration of Candesartan tends to reverse the potassium loss associated with Hydrochlorothiazide.

Indication:

Giran H is indicated for the treatment of hypertension. This fixed dose combination is not indicated for initial therapy

Dosage and administration:

Initially 4 mg (2 mg in hepatic and renal impairment) once daily adjusted according to response; usual maintenance dose 8 mg once daily; max. 32 mg once daily. Doses larger than 32 mg do not appear to have a greater blood pressure lowering effect.

Hydrochlorothiazide is effective in doses of 12.5 to 50 mg once daily.

Contraindication:

Giran H is contraindicated in patients who are hypersensitive to any component of this product. Because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.

Drug interactions:

No significant drug interactions have been reported in studies of Candesartan Cilexetil given with other drugs such as glyburide, nifedifine, digoxin, warfarin, hydrochlorothiazide and oral contraceptives in healthy volunteers. Because candesartan is not metabolised by the cytochrome P450 system and has no effects on P450 enzymes, interactions with drugs that inhibit, or are metabolised by, those enzymes could not be expected.

Alcohol, barbiturates, or narcotics- Potentiation of orthostatic hypotension may occur. Antidiabetic drugs (oral agents and insulin)- Dosage adjustment of the antidiabetic drug may be required. Other antihypertensive drugs- Additive effect or potentiation. Cholestyramine and colestipol resins- Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Corticosteroids, ACTH- Intensified electrolyte depletion, particularly hypokalemia. Skeletal muscle relaxants, tubocurarine- Possible increased responsiveness to the muscle relaxant. Lithium -Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity. NSAID can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics.

Side-effects:

Adverse experiences have generally been mild and transient in nature. The overall incidence of adverse events reported with Giran H was comparable to placebo. In placebo-controlled trials that included 1089 patients treated with various combinations of candesartan cilexetil (doses of 2-32 mg) and hydrochlorothiazide (doses of 6.25-25 mg) and 592 patients treated with placebo, adverse events occurring in greater than 2% of patients treated with Giran H and that were more frequent for Giran H than placebo were upper respiratory tract infection (3.6% vs 3.0%), back pain (3.3% vs 2.4%), influenza-like symptoms (2.5% vs 1.9%), dizziness (2.9% vs 1.2%). The frequency of headache was greater than 2% (2.9%) in patients treated with Giran H but was less frequent than the rate in patients treated with placebo (5.2%).

Precautions:

In clinical trials of various doses of candesartan cilexetil and hydrochlorothiazide, the incidence of hypertensive patients who developed hypokalemia (serum potassium <3.5 mEq/L) was 2.5% versus 2.1% for placebo; the incidence of hyperkalemia (serum potassium >5.7 mEq/L) was 0.4% versus 1.0% for placebo. No patient receiving Giran H 16-12.5 mg or 32-12.5 mg was discontinued due to increases or decreases in serum potassium. Overall, the combination of candesartan cilexetil and hydrochlorothiazide had no clinically significant effect on serum potassium.

Use in pregnancy and lactation:

When pregnancy is detected, Candesartan Cilexetil should be discontinued as soon as possible. It should be not used in lactation.

Pediatric use:

Safety and effectiveness in pediatric patients have not been established.

Storage:

Store in a cool and dry place. Keep out of the reach of children

Packing:

Giran H Tablet: Each box contains 2×10's/3×10's/5×10's/10×10's tablets in blister pack.