Nepitan

Adult Heart Failure: The recommended starting dose is 49/51 mg orally twice daily. Double the dose after 2 to 4 weeks to the target maintenance dose of 97/103 mg twice daily, as tolerated by the patient.

Reduce the starting dose to 24/26 mg twice daily for:

• Patients not currently taking an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin II receptor blocker (ARB) or previously taking a low dose of these agents.
• Patients with severe renal impairment.
• Patients with moderate hepatic impairment.

Pediatric Heart Failure: Refer to Table 1 for the recommended dose for pediatric patients aged one year and older. Take the recommended dose orally twice daily. Adjust pediatric patient doses every 2 weeks, as tolerated by the patient.

Recommended Dose Titration-

Pediatric Patients Less than 40 kg:

• Starting: 1.6 mg/kg
• Second: 2.3 mg/kg
• Final: 3.1 mg/kg

Pediatric Patients At least 40 kg, less than 50 kg:

• Starting: 24/26 mg
• Second: 49/51 mg
• Final: 49/51 mg

Pediatric Patients At least 50 kg:

• Starting: 49/51 mg
• Second: 72/78 mg
• Final: 97/103 mg

The most common side effects are Angioedema, Hypotension, Impaired Renal Function, Hyperkalemia, Cough, Dizziness.

Limited data are available with regard to overdosage in human subjects with this tablet. In healthy volunteers, a single dose of this tablet 583 mg sacubitril/617 mg valsartan, and multiple doses of 437 mg sacubitril/463 mg valsartan (14 days) have been studied and were well tolerated. Hypotension is the most likely result of overdosage due to the blood-pressure-lowering effects of this tablet. Symptomatic treatment should be provided. This tablet is unlikely to be removed by hemodialysis because of high protein binding.

This tablet contains a neprilysin inhibitor, sacubitril, and an angiotensin receptor blocker, valsartan. This tablet inhibits neprilysin (neutral endopeptidase; NEP) via LBQ657, the active metabolite of the prodrug sacubitril, and blocks the angiotensin II type-1 (AT1 ) receptor via valsartan. The cardiovascular and renal effects of this tablet in heart failure patients are attributed to the increased levels of peptides that are degraded by neprilysin, such as natriuretic peptides, by LBQ657, and the simultaneous inhibition of the effects of angiotensin II by valsartan. Valsartan inhibits the effects of angiotensin II by selectively blocking the AT1 receptor, and also inhibits angiotensin II-dependent aldosterone release.

This tablet may cause angioedema and must not be used in patients with a known history of angioedema related to previous ACEi or ARB therapy and in patients with hereditary angioedema.

This tablet lowers blood pressure and may cause symptomatic hypotension. Closely monitor serum creatinine, and down-titrate or interrupt this tablet in patients who develop a clinically significant decrease in renal function. In patients with renal artery stenosis, monitor renal function.

Monitor serum potassium periodically and treat appropriately, especially in patients with risk factors for hyperkalemia such as severe renal impairment, diabetes, hypoaldosteronism, or a high potassium diet. Dosage reduction or interruption of this tablet may be required.