ntrolled clinical studies of hypertension, 264 (15.6%) were 65 years and over, while 45 (2.7%) were 75 years and over. No overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. [See Clinical Pharmacology (12.3) and Clinical Studies (14).]
10 OVERDOSAGE
Irbesartan
No data are available in regard to overdosage in humans. However, daily doses of 900 mg for 8 weeks were well tolerated. The most likely manifestations of overdosage are expected to be hypotension and tachycardia; bradycardia might also occur from overdose. Irbesartan is not removed by hemodialysis.
To obtain up-to-date information about the treatment of overdosage, a good resource is a certified regional Poison Control Center. Telephone numbers of certified Poison Control Centers are listed in the Physicians’ Desk Reference (PDR). In managing overdose, consider the possibilities of multiple-drug interactions, drug-drug interactions, and unusual drug kinetics in the patient.
Laboratory determinations of serum levels of irbesartan are not widely available, and such determinations have, in any event, no established role in the management of irbesartan overdose.
Acute oral toxicity studies with irbesartan in mice and rats indicated acute lethal doses were in excess of 2000 mg/kg, about 25- and 50-fold the MRHD (300 mg) on a mg/m2 basis, respectively.
Hydrochlorothiazide
The most common signs and symptoms of overdose observed in humans are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias. The degree to which hydrochlorothiazide is removed by hemodialysis has not been established. The oral LD50 of hydrochlorothiazide is greater than 10 g/kg in both mice and rats.
11 DESCRIPTION
AVALIDE (irbesartan-hydrochlorothiazide) Tablets is a combination of an angiotensin II receptor antagonist (AT1 subtype), irbesartan, and a thiazide diuretic, hydrochlorothiazide (HCTZ).
Irbesartan is a non-peptide compound, chemically described as a 2-butyl-3-[p-(o-1H-tetrazol-5-ylphenyl)benzyl]-1,3-diazaspiro[4.4]non-1-en-4-one. Its empirical formula is C25H28N6O, and its structural formula is:
Irbesartan is a white to off-white crystalline powder with a molecular weight of 428.5. It is a nonpolar compound with a partition coefficient (octanol/water) of 10.1 at pH of 7.4. Irbesartan is slightly soluble in alcohol and methylene chloride and practically insoluble in water.
Hydrochlorothiazide is 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is C7H8ClN3O4S2 and its structural formula is:
Hydrochlorothiazide is a white, or practically white, crystalline powder with a molecular weight of 297.7. Hydrochlorothiazide is slightly soluble in water and freely soluble in sodium hydroxide solution.
AVALIDE is available for oral administration in tablets containing either 150 mg or 300 mg of irbesartan combined with 12.5 mg of hydrochlorothiazide or 300 mg of irbesartan combined with 25 mg hydrochlorothiazide. Inactive ingredients include: lactose monohydrate, microcrystalline cellulose, pregelatinized starch, croscarmellose sodium, ferric oxide red, ferric oxide yellow, silicon di
