United States - English - NLM (National Library of Medicine)

novartis pharmaceuticals corporation - sacubitril (unii: 17erj0mkgi) (sacubitrilat - unii:spi5pbf81s), valsartan (unii: 80m03yxj7i) (valsartan - unii:80m03yxj7i) - sacubitril 24 mg - entresto is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. benefits are most clearly evident in patients with left ventricular ejection fraction (lvef) below normal. lvef is a variable measure, so use clinical judgment in deciding whom to treat [see clinical studies (14.1)] . entresto is indicated for the treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged one year and older. entresto reduces nt-probnp and is expected to improve cardiovascular outcomes. entresto is contraindicated: - in patients with hypersensitivity to any component - in patients with a history of angioedema related to previous ace inhibitor or arb therapy [see warnings and precautions (5.2)] - with concomitant use of ace inhibitors. do not administer within 36 hours of switching from or to an ace inhibitor [see drug interactions (7.1)] - with concomitant use of aliskiren in patients with diabetes [see drug interactions (7.1)] risk summary entresto can cause fetal harm when administered to a pregnant woman. use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death (see clinical considerations ). most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. in animal reproduction studies, entresto treatment during organogenesis resulted in increased embryo-fetal lethality in rats and rabbits and teratogenicity in rabbits (see data ). when pregnancy is detected, consider alternative drug treatment and discontinue entresto. however, if there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system, and if the drug is considered lifesaving for the mother, advise a pregnant woman of the potential risk to the fetus. the background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations fetal/neonatal adverse reactions oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension, and death. perform serial ultrasound examinations to assess the intra-amniotic environment. fetal testing may be appropriate, based on the week of gestation. patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. if oligohydramnios is observed, consider alternative drug treatment. closely observe neonates with histories of in utero exposure to entresto for hypotension, oliguria, and hyperkalemia. in neonates with a history of in utero exposure to entresto, if oliguria or hypotension occurs, support blood pressure and renal perfusion. exchange transfusions or dialysis may be required as a means of reversing hypotension and replacing renal function. data animal data entresto treatment during organogenesis resulted in increased embryo-fetal lethality in rats at doses greater than or equal to 49 mg sacubitril/51 mg valsartan/kg/day (less than or equal to 0.06 [lbq657, the active metabolite] and 0.72 [valsartan]-fold the maximum recommended human dose [mrhd] of 97/103 mg twice-daily on the basis of the area under the plasma drug concentration-time curve [auc]) and rabbits at doses greater than or equal to 5 mg sacubitril/5 mg valsartan/kg/day (2-fold and 0.03-fold the mrhd on the basis of valsartan and lbq657 auc, respectively). entresto is teratogenic based on a low incidence of fetal hydrocephaly, associated with maternally toxic doses, which was observed in rabbits at an entresto dose of greater than or equal to 5 mg sacubitril/5 mg valsartan/kg/day. the adverse embryo-fetal effects of entresto are attributed to the angiotensin receptor antagonist activity. pre- and postnatal development studies in rats at sacubitril doses up to 750 mg/kg/day (2.2-fold the mrhd on the basis of lbq657 auc) and valsartan at doses up to 600 mg/kg/day (0.86-fold the mrhd on the basis of auc) indicate that treatment with entresto during organogenesis, gestation and lactation may affect pup development and survival. risk summary there is no information regarding the presence of sacubitril/valsartan in human milk, the effects on the breastfed infant, or the effects on milk production. sacubitril/valsartan is present in rat milk (see data ). because of the potential for serious adverse reactions in breastfed infants from exposure to sacubitril/valsartan, advise a nursing woman that breastfeeding is not recommended during treatment with entresto. data following an oral dose (15 mg sacubitril/15 mg valsartan/kg) of [14 c] entresto to lactating rats, transfer of lbq657 into milk was observed. after a single oral administration of 3 mg/kg [14 c] valsartan to lactating rats, transfer of valsartan into milk was observed. the safety and effectiveness of entresto have been established for the treatment of heart failure in pediatric patients 1 year to less than 18 years. use of entresto was evaluated in a multinational, randomized, double-blind trial comparing entresto and enalapril in 375 patients aged 1 month to less than 18 years (entresto n = 187; enalapril n = 188) (panorama-hf) [see clinical studies (14.2)] . the safety profile in pediatric patients (1 year to less than 18 years) receiving entresto was similar to that seen in adult patients. limited safety and efficacy data in patients aged 1 month to less than 1 year were inadequate to support conclusions on safety and efficacy in this age group. juvenile animal toxicity data sacubitril given orally to juvenile rats from postnatal day (pnd) 7 to pnd 35 or pnd 70 (an age approximately equivalent to neonatal through pre-pubertal development or adulthood in humans) at doses greater than or equal to 400 mg/kg/day (approximately 2-fold the auc exposure to the active metabolite of sacubitril, lbq657, at an entresto pediatric clinical dose of 3.1 mg/kg twice daily) resulted in decreases in body weight, bone length, and bone mass. the decrease in body weight was transient from pnd 10 to pnd 20 and the effects for most bone parameters were reversible after treatment stopped. exposure at the no-observed-adverse-effect-level (noael) of 100 mg/kg/day was approximately 0.5-fold the auc exposure to lbq657 at the 3.1 mg/kg twice daily dose of entresto. the mechanism underlying bone effects in rats and the translatability to pediatric patients are unknown. valsartan given orally to juvenile rats from pnd 7 to pnd 70 (an age approximately equivalent to neonatal through adulthood in humans) produced persistent, irreversible kidney damage at all dose levels. exposure at the lowest tested dose of 1 mg/kg/day was approximately 0.2-fold the exposure at 3.1 mg/kg twice daily dose of entresto based on auc. these kidney effects in neonatal rats represent expected exaggerated pharmacological effects that are observed if rats are treated during the first 13 days of life. this period coincides with 36 weeks of gestation in humans, which could occasionally extend up to 44 weeks after conception in humans. in humans, nephrogenesis is thought to be complete around birth; however, maturation of other aspects of kidney function (such as glomerular filtration and tubular function) may continue until approximately 2 years of age. it is unknown whether post-natal use of valsartan before maturation of renal function is complete has long-term deleterious effects on the kidney. there were 4,143 and 3,971 heart failure patients 65 years of age and older in paradigm-hf and paragon-hf, respectively [see clinical studies (14)] . of the total number of entresto-treated patients, 2,087 (49.6%) and 1,995 (82.9%) were 65 years of age and older, while 786 (18.7%) and 1,100 (45.7%) were 75 years of age and older in paradigm-hf and paragon-hf, respectively. no overall differences in safety or effectiveness of entresto have been observed between patients 65 years of age and older and younger adult patients in either study. no relevant pharmacokinetic differences have been observed in elderly (≥ 65 years) or very elderly (≥ 75 years) patients compared to the overall population [see clinical pharmacology (12.3)] . no dose adjustment is required when administering entresto to patients with mild hepatic impairment (child-pugh a classification). half of the starting dose is recommended in adult and pediatric patients with heart failure and with moderate hepatic impairment (child-pugh b classification). the use of entresto in patients with severe hepatic impairment (child-pugh c classification) is not recommended, as no studies have been conducted in these patients [see dosage and administration (2.8) and clinical pharmacology (12.3)] . no dose adjustment is required in patients with mild (egfr 60 to 90 ml/min/1.73 m2 ) to moderate (egfr 30 to 60 ml/min/1.73 m2 ) renal impairment. half of the starting dose is recommended in adult and pediatric patients with heart failure and with severe renal impairment (egfr less than 30 ml/min/1.73 m2 ). [see dosage and administration (2.7), warnings and precautions (5.4) and clinical pharmacology (12.3)] . - entresto sprinkle contains oral pellets inside of a capsule. the capsule must be opened and the oral pellets inside must be sprinkled on soft food before you take or give entresto sprinkle. do not swallow the capsule or the empty capsule shells. - the capsule must be opened and the oral pellets inside must be sprinkled on soft food before you take or give entresto sprinkle. - do not swallow the capsule or the empty capsule shells. - do not chew or crush the oral pellets. - use all of the oral pellets in the capsule. do not use part of a capsule to try to prepare a dose. - do not take or give entresto sprinkle through a nasogastric tube (ng tube), gastrostomy tube (g tube), or other feeding tubes because it may clog the tube. - entresto sprinkle is available in 2 strengths: 6 mg/6 mg (sacubitril 6 mg and valsartan 6 mg) and 15 mg/16 mg (sacubitril 15 mg and valsartan 16 mg). - you can see the difference between the 2 strengths by the color of the capsule cap and the imprint on it. the capsule containing the 6 mg/6 mg strength has a white cap with the number “04” printed on it. the capsule containing the 15 mg/16 mg strength has a yellow cap with the number “10” printed on it. - the capsule containing the 6 mg/6 mg strength has a white cap with the number “04” printed on it. - the capsule containing the 15 mg/16 mg strength has a yellow cap with the number “10” printed on it. - check to make sure you have received the prescribed strength of entresto sprinkle before taking or giving the dose. - a clean small bowl, cup, or spoon to measure and hold the soft food that you or your child likes, such as applesauce, yogurt, or pudding. - bottle with capsules containing entresto sprinkle. - place the following items on a clean flat surface: a small bowl, cup or spoon with about 1 to 2 teaspoonfuls of soft food that you or your child likes for each capsule of entresto sprinkle prescribed (see figure b ). bottle with capsules containing entresto sprinkle. - a small bowl, cup or spoon with about 1 to 2 teaspoonfuls of soft food that you or your child likes for each capsule of entresto sprinkle prescribed (see figure b ). - bottle with capsules containing entresto sprinkle. - check that you have the right strength of entresto sprinkle. - hold the capsule upright (with the colored cap on top) so that the oral pellets are in the bottom of the capsule (figure c ). - hold the capsule over the soft food. - gently pinch the middle of the capsule and pull slightly to separate the 2 ends of the capsule (figure d ). take care not to spill the contents while opening the capsule. - check the capsule to make sure that you did not miss any oral pellets. tap the capsule to remove any remaining oral pellets. - repeat steps 4 and 5 if you need more than 1 capsule for the prescribed dose. - take or give the food with the oral pellets right away after adding the oral pellets (figure f ). - make sure that you or your child eat all of the food containing the oral pellets. - make sure that you or your child do not chew the oral pellets to avoid a change of taste. - throw away the empty shells of the capsule in the household trash (figure g ). - wash your hands and all the items used to take or give entresto sprinkle. - store entresto sprinkle at room temperature between 68°f to 77°f (20°c to 25°c). - protect entresto sprinkle from moisture. t2024-30

Australia - English - Department of Health (Therapeutic Goods Administration)

pharmacor pty ltd - sacubitril, quantity: 97.2 mg; valsartan, quantity: 102.8 mg - tablet, film coated - excipient ingredients: hyprolose; purified talc; microcrystalline cellulose; colloidal anhydrous silica; sodium starch glycollate type a; magnesium stearate; titanium dioxide; hypromellose; iron oxide yellow; iron oxide red; macrogol 4000; iron oxide black - pharmacor sacubitril/valsartan is indicated in adult patients for the treatment of chronic heart failure (nyha class ii-iv) with reduced ejection fraction.

Australia - English - Department of Health (Therapeutic Goods Administration)

pharmacor pty ltd - sacubitril, quantity: 97.2 mg; valsartan, quantity: 102.8 mg - tablet, film coated - excipient ingredients: magnesium stearate; purified talc; microcrystalline cellulose; colloidal anhydrous silica; hyprolose; sodium starch glycollate type a; titanium dioxide; hypromellose; iron oxide yellow; iron oxide red; macrogol 4000; iron oxide black - pharmacor sacubitril/valsartan is indicated in adult patients for the treatment of chronic heart failure (nyha class ii-iv) with reduced ejection fraction.

Australia - English - Department of Health (Therapeutic Goods Administration)

pharmacor pty ltd - sacubitril, quantity: 48.6 mg; valsartan, quantity: 51.4 mg - tablet, film coated - excipient ingredients: hyprolose; microcrystalline cellulose; colloidal anhydrous silica; sodium starch glycollate type a; purified talc; magnesium stearate; titanium dioxide; hypromellose; iron oxide yellow; macrogol 4000 - pharmacor sacubitril/valsartan is indicated in adult patients for the treatment of chronic heart failure (nyha class ii-iv) with reduced ejection fraction.

Australia - English - Department of Health (Therapeutic Goods Administration)

pharmacor pty ltd - sacubitril, quantity: 24.3 mg; valsartan, quantity: 25.7 mg - tablet, film coated - excipient ingredients: sodium starch glycollate type a; microcrystalline cellulose; magnesium stearate; purified talc; colloidal anhydrous silica; hyprolose; titanium dioxide; hypromellose; iron oxide yellow; iron oxide red; macrogol 4000; iron oxide black - pharmacor sacubitril/valsartan is indicated in adult patients for the treatment of chronic heart failure (nyha class ii-iv) with reduced ejection fraction.

Australia - English - Department of Health (Therapeutic Goods Administration)

novartis pharmaceuticals australia pty ltd - valsartan, quantity: 51.4 mg; sacubitril, quantity: 48.6 mg - tablet, film coated - excipient ingredients: purified talc; colloidal anhydrous silica; crospovidone; titanium dioxide; hypromellose; hyprolose; macrogol 4000; magnesium stearate; iron oxide red; microcrystalline cellulose; iron oxide yellow - entresto is indicated in adult patients for the treatment of chronic heart failure (nyha class ii-iv) with reduced ejection fraction.

Australia - English - Department of Health (Therapeutic Goods Administration)

novartis pharmaceuticals australia pty ltd - valsartan, quantity: 25.7 mg; sacubitril, quantity: 24.3 mg - tablet, film coated - excipient ingredients: colloidal anhydrous silica; crospovidone; iron oxide red; titanium dioxide; macrogol 4000; hypromellose; hyprolose; magnesium stearate; microcrystalline cellulose; iron oxide black; purified talc - entresto is indicated in adult patients for the treatment of chronic heart failure (nyha class ii-iv) with reduced ejection fraction.

Australia - English - Department of Health (Therapeutic Goods Administration)

novartis pharmaceuticals australia pty ltd - valsartan, quantity: 102.8 mg; sacubitril, quantity: 97.2 mg - tablet, film coated - excipient ingredients: colloidal anhydrous silica; iron oxide black; magnesium stearate; titanium dioxide; iron oxide red; purified talc; crospovidone; hypromellose; macrogol 4000; hyprolose; microcrystalline cellulose - entresto is indicated in adult patients for the treatment of chronic heart failure (nyha class ii-iv) with reduced ejection fraction.

Australia - English - Department of Health (Therapeutic Goods Administration)

pharmacor pty ltd - valsartan, quantity: 51.4 mg; sacubitril, quantity: 48.6 mg - tablet, film coated - excipient ingredients: hyprolose; sodium starch glycollate type a; colloidal anhydrous silica; microcrystalline cellulose; purified talc; magnesium stearate; titanium dioxide; hypromellose; iron oxide yellow; macrogol 4000 - pharmacor sacubitril/valsartan is indicated in adult patients for the treatment of chronic heart failure (nyha class ii-iv) with reduced ejection fraction.

Australia - English - Department of Health (Therapeutic Goods Administration)

pharmacor pty ltd - valsartan, quantity: 25.7 mg; sacubitril, quantity: 24.3 mg - tablet, film coated - excipient ingredients: hyprolose; colloidal anhydrous silica; sodium starch glycollate type a; purified talc; microcrystalline cellulose; magnesium stearate; titanium dioxide; hypromellose; iron oxide yellow; iron oxide red; macrogol 4000; iron oxide black - pharmacor sacubitril/valsartan is indicated in adult patients for the treatment of chronic heart failure (nyha class ii-iv) with reduced ejection fraction.