Each tablet contains: Irbesartan, USP 150 mg and 300 mg, respectively.
Pharmacology: Mechanism of Action: Irbesartan is a nonpeptide angiotensin II antagonist that selectively blocks the binding of angiotensin II to the AT1, receptor. In the rennin-angiotensin system, angiotensin I is converted by angiotensin-converting enzyme (ACE) to form angiotensin II. Angiotensin II stimulates the adrenal cortex to synthesize and secrete Aldosterone, which decreases the excretion of sodium and increases the excretion of potassium. Angiotensin II also acts as a vasoconstrictor in vascular smooth muscle. Irbesartan, by blocking the binding of angiotensin II to the AT1 receptor, promotes vasodilation and decreases the effects of Aldosterone. The negative feedback regulation of angiotensin II on renin secretion also is inhibited, but the resulting rise in plasma renin concentrations and consequent rise in angiotensin II plasma concentrations do not counteract the blood pressure-lowering effect that occurs.
Pharmacokinetics: Absorption: Rapid and complete; average absolute bioavailability ranges from 60 to 80%. Food does not affect the bioavailability of Irbesartan.
Distribution: Volume of distribution (VolD)-53 to 93 liters. Irbesartan crosses the blood-brain barrier and placenta in low concentrations.
Protein binding: High (90%), primarily to albumin and alpha1-acid glycoprotein.
Biotransformation: Irbesartan is metabolized by glucuronide conjugation and oxidation. Following oral of radiolabeled Irbesartan, more than 80% of the circulating plasma radioactivity is attributed to unchanged Irbesartan. The primary metabolite is the inactive Irbesartan glucuronide conjugate and accounts for approximately 6% of circulating metabolites. The remaining oxidative metabolites are considered to be inactive. In vitro studies indicate that Irbesartan is oxidized primarily by the cytochrome P450 2C9 isoenzyme.
Half life: Elimination: 11 to 15 hours.
Time to peak concentration: 1.5 to 2 hours.
Elimination: Renal: Approximately 20%.
Fecal (biliary): Approximately 80%.
In dialysis: Irbesartan is not removable by hemodialysis.
Hypertension (treatment): Irbesartan is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive medications. It is used in the management of hypertension including the treatment of renal disease in hypertensive diabetic patients.
Oral: Usual adult dose: Hypertension: Initially 150 once a day. If blood pressure reduction is not adequate, the dosage may be increased up to 300 mg once a day. If blood pressure is not controlled by Irbesartan alone, a low dose of a diuretic. such as Hydrochlorothiazide. may be added. Patients not adequately controlled by the maximum Irbesartan dose of 300 mg once a day are unlikely to derive additional benefit from a higher dose. In patients who are volume- and/or salt-depleted, such as those treated vigorously with diuretics or on hemodialysis, a lower initial dose of 75 mg of Irbesartan is recommended.
Usual adult prescribing limits: 300 mg.
Usual pediatric dose: Safety and efficacy have not been established in children younger than 6 years of age.
Hypertension: Children 6 to 12 years of age: Initial dose of 75 mg once a day. Patients requiring further reduction in blood pressure should be titrated to 150 mg once a day.
Usual adolescent dose: Adolescents 13 to 16 years of age: Initial dose of 150 mg once daily.
Patients requiring further reduction in blood pressure should be titrated to 300 mg once a day.
Usual pediatric prescribing limits: Children: 150 mg daily.
Adolescents: 300 mg daily.
Clinical effects: Acute and/or chronic Bradycardia (slow heartbeat); hypotension (dizziness, lightheadedness, or fainting); tachycardia (fast heartbeat).
Treatment: Treatment should be symptomatic and supportive.
Supportive care: Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.
Except under special circumstances, this medication should not be used when the following medical problems exists: Hypersensitivity to Irbesartan.
Risk-benefit should be considered when the following medical problems exist: Congestive heart failure, severe (therapy with angiotensin receptor antagonists in these patients, who may be especially susceptible to changes in the renin-angiotensin-aldosterone system, has been associated with oliguria, azotemia, acute renal failure, and/or death).
Dehydration (sodium or volume depletion, due to excessive perspiration, vomiting, diarrhea, prolonged diuretic therapy, dialysis, or dietary salt restriction) (a reduction in salt or fluid volume may increase the risk of symptomatic hypotension).
Renal artery stenosis, unilateral or bilateral or; Renal function impairment (increase in serum creatinine or BUN concentrations have occurred in patients with unilateral or bilateral renal artery stenosis who were treated with ACE inhibitors and a similar effect may occur with Irbesartan treatment; therapy with angiotensin receptor-antagonists in patients susceptible to changes in the renin-angiotensin-aldosterone system, such as patients with severe congestive heart failure, has been associated with oliguria, progressive azotemia, acute renal failure, and/or death).
Carcinogenicity: No evidence of carcinogenicity was found in a 2-year study in male rats given Irbesartan in doses of up 500 mg per kg body weight (mg/kg) per day or in female rats given Irbesartan in doses of up to 1000 mg/kg per day or in mice given Irbesartan in doses of up to 1000 mg/kg per day In male and female rats, a 500 mg/kg dose represents 3 and 11 times, respectively, the maximum recommended human daily dose (MRHDD) Of 300 mg of Irbesartan. In female rats, a 1000 mg/kg dose represents approximately 21 times the MRHDD of 300 mg of Irbesartan. For male and female mice a 1000 mg/kg dose represents approximately 3 and 5 times, respectively, the MRHDD of 300 mg of Irbesartan.
Mutagenicity: Irbesartan was not found to be mutagenic in the Ames microbial test, rat hepatocyte DNA repair test, or V 79 mammalian-cell forward gene mutation assay.
Irbesartan was found to be negative for the induction of chromosomal aberrations in the in vivo human lymphocyte assay and in in vivo mouse micronucleus study.
Pediatrics: No information is available on the relationship of age to the effects of Irbesartan in pediatric patients younger than 6 years of age. Safety and efficacy have not been established in patients younger than 6 years of age. Infants exposed in utero to angiotensin II receptor antagonists should be observed closely for hypotension, oliguria, and hyperkalemia. Oliguria should be treated with support of blood pressure and renal perfusion. Dialysis or exchange transfusion may be necessary to reverse hypotension and/or substitute for disordered renal function.
Geriatrics: In subjects 65 to 80 years of age, Irbesartan elimination half-life is not significantly altered, but the area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax) values may be greater by 20 to 50% than those in subjects 18 to 40 years of age. No dosage adjustment is necessary in the elderly may experience greater sensitivity to the effects of Irbesartan.
Fertility: Irbesartan had no adverse effects on fertility or mating behavior of male and female rats given oral doses off 650 mg/kg per day. The ≤650 mg/kg dose of Irbesartan represents approximately five times the MRHDD of 300 mg.
Pregnancy: Fetal exposure to drugs that act directly on the renin-angiotensin system during the second and third trimesters can cause hypotension, reversible or irreversible renal failure, anuria, neonatal skull hypoplasia, and death in the fetus or neonate. Irbesartan should be discontinued as soon as possible when pregnancy is detected, unless no alternative therapy can be used. If medication is continued, serial ultrasound examinations should be performed to assess the intra-amniotic environment. Perinatal diagnostic tests, such as contraction-stress testing (CST), a nonstress test (NST), or biophysical profiling (BPP) also may be appropriate during the applicable week of pregnancy. FDA Pregnancy Category C (first trimester). FDA Pregnancy Category D (second and third trimester).
Breast-feeding: It is not known whether Irbesartan is distributed into breast milk. but Irbesartan and/or its metabolite(s) is distributed into the milk of lactating rats at a low concentration. Because of the potential for adverse effects in the nursing infant, Irbesartan should not be administered to nursing mothers.
Those indicating need medical attention: Incidence rare:
Hypotension (dizziness, light-headedness, or fainting)- usually seen in volume- or salt-depleted patients receiving high doses of a diuretic.
Note: Hypotension occurred in 0.4% of patients receiving Irbesartan in clinical trials.
Incidence not determined:
Observed clinical practice.
Angioedema (swelling on face, lips, throat, or tongue); hyperkalemia (confusion, irregular heartbeat, numbness or tingling in hands, feet, or lips, difficult breathing, or weakness or heaviness of legs)- has been rarely reported; jaundice (clay-colored stools, dark urine, itching, loss of appetite, stomach pain, yellow eyes or skin).
Those indicating need for medical attention only if they continue or are bothersome: Incidence less frequent:
Anxiety and/or nervousness; diarrhea; dizziness; dyspepsia (belching; heartburn; stomach discomfort); fatigue (unusual tiredness); headache; musculoskeletal pain (muscle or bone pain); upper respiratory infection (cold symptoms).
Incidence not determined:
Observed clinical practice.
Urticaria (hives or welts, itching, redness of skin, or skin rash).
Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.
Diuretics (concurrent use with Irbesartan may have additive hypotensive effects).
Medications that inhibit the cytochrome P450 2C9 isoenzyme or medications that are metabolized by cytochrome P450 2C9 (the isoenzyme responsible for Irbesartan metabolism), such as Tolbutamide (in vitro studies show that Irbesartan metabolism may be affected by medications that are metabolized by or inhibit the cytochrome P450 2C9 isoenzyme, although no clinically relevant interactions have been observed).
Store at temperatures not exceeding 30°C.
C09CA04 - irbesartan ; Belongs to the class of angiotensin II receptor blockers (ARBs). Used in the treatment of cardiovascular disease.
Irbez 150: Tab 150 mg x 3 x 10's.
Irbez 300: Tab 300 mg x 3 x 10's.