Irbesartan

Avapro treats hypertension alone or with other antihypertensive agents. Blood-pressure lowering reduces cardiovascular risk, principally stroke and myocardial infarction; targets and accompanying risk-factor treatment need an individualized current clinical plan.

The labeled nephropathy population has type 2 diabetes, hypertension, elevated serum creatinine and proteinuria above 300 mg/day. In that population irbesartan reduces progression measured by doubled creatinine or end-stage renal disease requiring dialysis or transplant. This is not an unrestricted indication for type 1 diabetic kidney disease, normotensive albuminuria or every form of CKD.

This profile covers selected oral single-agent tablets. Irbesartan/hydrochlorothiazide combinations have separate doses and precautions. The pediatric study did not show effective blood-pressure lowering in ages 6–16, and children below 6 were not studied; the study dose is not a pediatric prescribing recommendation.

Take orally with or without food; other antihypertensives can be combined when appropriate. Current Avapro labeling lists 150 and 300 mg unscored tablets, despite retaining the 75 mg initial-dose recommendation. The separately reviewed Macleods generic supplies a labeled 75 mg tablet; arrange the prescribed strength rather than assuming an Avapro 75 mg product or an approved split-tablet method.

No PK-based adjustment is required for mild to severe renal impairment unless also volume depleted; kidney function and potassium still require monitoring. Hemodialysis does not remove irbesartan. The hepatic data describe mild-to-moderate cirrhosis and no adjustment in that setting; do not infer a validated severe-hepatic-disease regimen. No automatic geriatric adjustment is required, but sensitivity, diuresis and comorbidity affect selection.

Hypersensitivity to a component is contraindicated. Do not combine aliskiren with irbesartan in patients with diabetes. In renal impairment (GFR below 60 mL/min), the interaction section advises avoiding aliskiren; this is distinct from the diabetes contraindication. Pregnancy carries the boxed stop instruction and is not listed as a separate §4 contraindication.

The current Avapro box warns of fetal toxicity: stop promptly when pregnancy is detected because medicines acting directly on the renin–angiotensin system can injure or kill the developing fetus. Pregnancy planning requires a replacement-treatment discussion.

Hypertension trials reported diarrhea, dyspepsia/heartburn and fatigue more often than placebo. In the diabetic-nephropathy trial, hyperkalemia and orthostatic symptoms were prominent; potassium above 6 mEq/L occurred in 18.6% versus 6.0% on placebo in that particular population. Postmarketing reports include angioedema, anaphylaxis, intestinal angioedema, hepatitis/jaundice, anemia, thrombocytopenia and hypoglycemia in diabetic patients; voluntary reports do not establish frequency.

Other potassium-raising medicines, potassium supplements and potassium-containing salt substitutes can produce severe hyperkalemia. Review the full list, including potassium-sparing diuretics, and monitor serum potassium. Use supplements or salt substitutes only with the treating clinician’s advice.

NSAIDs, including COX-2 inhibitors, may reduce antihypertensive benefit and worsen kidney function, especially with older age, diuresis, dehydration or renal impairment. Monitor renal function periodically when combined. Lithium levels and toxicity can rise; check lithium concentrations and clinical symptoms.

Combining an ARB with an ACE inhibitor or aliskiren increases hypotension, hyperkalemia and renal impairment without added benefit for most patients. Generally avoid combinations; if specifically warranted, closely monitor BP, renal function and electrolytes. Aliskiren is contraindicated with diabetes and should be avoided with GFR below 60 mL/min.

Avoid fetal exposure and stop promptly when pregnancy is detected; discuss safer alternatives before planned pregnancy. The label does not establish safety in the first trimester. Exposed infants require observation for hypotension, low urine output, hyperkalemia and renal impairment. Human milk and infant-effect data are absent; Avapro use during breastfeeding is not recommended.

No effective pediatric regimen is established in the selected label: the ages-6–16 trial did not show effective BP reduction, and age below 6 was not studied. Older trial participants showed no overall safety/effectiveness difference, but some may be more sensitive. No age-only adjustment is needed; monitor orthostasis, volume status and interacting medicines.

Mild-to-severe renal impairment does not itself require a PK dose reduction; volume depletion does call for the 75 mg start. The drug is not dialyzable, and dialysis alone is not a reason to invent a postdialysis replacement dose. Mild-to-moderate cirrhosis did not significantly alter PK; severe hepatic impairment lacks a separately validated regimen in this profile. Kidney decline and hyperkalemia may still require withholding or adjustment.

Irbesartan competitively blocks angiotensin II at AT1 receptors, reducing vasoconstrictor and aldosterone-secreting effects. It does not inhibit ACE or renin. Renin and circulating angiotensin II rise after receptor blockade, but do not overcome the BP effect.

Absolute oral bioavailability averages 60–80%; peak levels occur after 1.5–2 hours, with no important food effect. Protein binding is about 90%, terminal half-life 11–15 hours and steady state about 3 days. Glucuronidation and primarily CYP2C9 oxidation form mostly inactive metabolites. Drug/metabolites leave through bile/feces and urine; about 20% of radiolabeled dose is recovered in urine. Hemodialysis does not clear irbesartan.

Assess BP, orthostatic symptoms, volume status, serum potassium and renal function before and during therapy, especially after initiation, dose changes or added NSAIDs/potassium-raising drugs. Periodic renal monitoring is explicit for vulnerable patients. Follow proteinuria and renal progression when treating the labeled nephropathy population. The selected label supplies no universal BP target, lab interval or percentage-creatinine stop rule.

Discuss pregnancy plans and report pregnancy immediately so irbesartan can be discontinued promptly. Avoid unapproved potassium supplements or salt substitutes; discuss OTC NSAIDs and new prescriptions. Report marked dizziness/fainting, reduced urine or vomiting/diarrhea that causes dehydration. Emergency care is needed for airway/facial swelling or severe allergic symptoms.

Seek medical or Poison Control help for overdose. Hypotension and tachycardia are expected; bradycardia may also occur. Treatment is supportive and individualized; irbesartan is not removed by hemodialysis. Tolerability of high doses in studies does not increase the labeled 300 mg/day maximum.

Product

Avapro 150 mg film-coated tablet

Route

Oral; prescription only

Appearance

White to off-white oval; heart / 2872; unscored

Example package

30 tablets · NDC 0024-5851-30

Current Avapro supplies 150 mg (heart / 2872) and 300 mg (heart / 2873) tablets; the 300 mg 30-count bottle is NDC 0024-5852-30. The reviewed Macleods generic supplies 75, 150 and 300 mg, with ML 94, ML 95 and ML 96 respectively. Its 75 mg 30-count bottle is NDC 33342-047-07. Do not transfer these identifiers to another manufacturer or to irbesartan/hydrochlorothiazide combinations.

Avapro: store at 25°C (77°F), with excursions to 15–30°C (59–86°F). Selected Macleods generic: 20–25°C, with excursions to 15–30°C. Keep the dispensed product in its labeled container and out of children’s reach. No universal opened-bottle discard date or moisture instruction is stated for these selected labels.