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

viona pharmaceuticals inc - ranolazine (unii: a6iez5m406) (ranolazine - unii:a6iez5m406) - ranolazine extended-release tablet is indicated for the treatment of chronic angina. ranolazine extended-release tablet may be used with beta-blockers, nitrates, calcium channel blockers, anti-platelet therapy, lipid-lowering therapy, ace inhibitors, and angiotensin receptor blockers. ranolazine is contraindicated in patients: - taking strong inhibitors of cyp3a [seedrug interactions (7.1)] - taking inducers of cyp3a [see drug interactions (7.1)] - with liver cirrhosis [see use in specific populations (8.6)] risk summary there are no available data on ranolazine use in pregnant women to inform any drug-associated risks. studies in rats and rabbits showed no evidence of fetal harm at exposures 4 times the maximum recommended human dose (mrhd) (see data). in the u.s. general population, the estimated background risk of major birth defects and of miscarriage of clinically recognized pregnancies is 2-4% and 15-20%, respectively. data animal data embryofetal toxicity studies were conducted in rats and ra

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

zydus lifesciences limited - ranolazine (unii: a6iez5m406) (ranolazine - unii:a6iez5m406) - ranolazine extended-release tablet is indicated for the treatment of chronic angina. ranolazine extended-release tablet may be used with beta-blockers, nitrates, calcium channel blockers, anti-platelet therapy, lipid-lowering therapy, ace inhibitors, and angiotensin receptor blockers. ranolazine is contraindicated in patients: - taking strong inhibitors of cyp3a [seedrug interactions (7.1)] - taking inducers of cyp3a [see drug interactions (7.1)] - with liver cirrhosis [see use in specific populations (8.6)] risk summary there are no available data on ranolazine use in pregnant women to inform any drug-associated risks. studies in rats and rabbits showed no evidence of fetal harm at exposures 4 times the maximum recommended human dose (mrhd) (see data). in the u.s. general population, the estimated background risk of major birth defects and of miscarriage of clinically recognized pregnancies is 2-4% and 15-20%, respectively. data animal data embryofetal toxicity studies were conducted in rats and ra

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

unichem pharmaceuticals (usa), inc. - ranolazine (unii: a6iez5m406) (ranolazine - unii:a6iez5m406) - ranolazine extended-release tablets are indicated for the treatment of chronic angina. ranolazine extended-release tablets may be used with beta-blockers, nitrates, calcium channel blockers, anti-platelet therapy, lipid-lowering therapy, ace inhibitors, and angiotensin receptor blockers. ranolazine is contraindicated in patients: - taking strong inhibitors of cyp3a [see drug interactions (7.1)] - taking inducers of cyp3a [see drug interactions (7.1)] - with liver cirrhosis [see use in specific populations (8.6)] risk summary there are no available data on ranolazine use in pregnant women to inform any drug-associated risks. studies in rats and rabbits showed no evidence of fetal harm at exposures 4 times the maximum recommended human dose (mrhd) (see data) . in the u.s. general population, the estimated background risk of major birth defects and of miscarriage of clinically recognized pregnancies is 2-4% and 15-20%, respectively. data animal data embryofetal toxicity studies were conducted in r

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

glenmark pharmaceuticals inc., usa - ranolazine (unii: a6iez5m406) (ranolazine - unii:a6iez5m406) - ranolazine extended-release tablets are indicated for the treatment of chronic angina. ranolazine extended-release tablets may be used with beta-blockers, nitrates, calcium channel blockers, anti-platelet therapy, lipid-lowering therapy, ace inhibitors, and angiotensin receptor blockers. ranolazine is contraindicated in patients: risk summary there are no available data on ranolazine use in pregnant women to inform any drug-associated risks. studies in rats and rabbits showed no evidence of fetal harm at exposures 4 times the maximum recommended human dose (mrhd) (see error! hyperlink reference not valid. ) . in the u.s. general population, the estimated background risk of major birth defects and of miscarriage of clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data animal data embryofetal toxicity studies were conducted in rats and rabbits orally administered ranolazine during organogenesis. in rats, decreased fetal weight and reduced ossification were observed at doses (corresponding to 4-fold the auc for the mrhd) that caused maternal weight loss. no adverse fetal effects were observed in either species exposed (auc) to ranolazine at exposures (auc) equal to the mrhd. risk summary there are no data on the presence of ranolazine in human milk, the effects on the breastfed infant, or the effects on milk production. however, ranolazine is present in rat milk [see use in specific populations (8.1)] . the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ranolazine and any potential adverse effects on the breastfed infant from ranolazine or from the underlying maternal condition. adult female rats were administered ranolazine orally from gestation day 6 through postnatal day 20. no adverse effects on pup development, behavior, or reproduction parameters were observed at a maternal dosage level of 60 mg/kg/day (equal to the mhrd based on auc). at maternally toxic doses, male and female pups exhibited increased mortality and decreased body weight, and female pups showed increased motor activity. the pups were potentially exposed to low amounts of ranolazine via the maternal milk. safety and effectiveness have not been established in pediatric patients. of the chronic angina patients treated with ranolazine in controlled studies, 496 (48%) were ≥65 years of age, and 114 (11%) were ≥75 years of age. no overall differences in efficacy were observed between older and younger patients. there were no differences in safety for patients ≥65 years compared to younger patients, but patients ≥75 years of age on ranolazine, compared to placebo, had a higher incidence of adverse events, serious adverse events, and drug discontinuations due to adverse events. in general, dose selection for an elderly patient should usually start at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease, or other drug therapy. ranolazine is contraindicated in patients with liver cirrhosis. in a study of cirrhotic patients, the cmax of ranolazine was increased 30% in cirrhotic patients with mild (child-pugh class a) hepatic impairment, but increased 80% in cirrhotic patients with moderate (child-pugh class b) hepatic impairment compared to patients without hepatic impairment. this increase was not enough to account for the 3-fold increase in qt prolongation seen in cirrhotic patients with mild to moderate hepatic impairment [see clinical pharmacology (12.2)] . a pharmacokinetic study of ranolazine in subjects with severe renal impairment (crcl <30 ml/min) was stopped when 2 of 4 subjects developed acute renal failure after receiving ranolazine extended-release tablets 500 mg twice daily for 5 days (lead-in phase) followed by 1000 mg twice a day (1 dose in one subject and 11 doses in the other). increases in creatinine, bun, and potassium were observed in 3 subjects during the 500 mg lead-in phase. one subject required hemodialysis, while the other 2 subjects improved upon drug discontinuation [see error! hyperlink reference not valid. ]. monitor renal function periodically in patients with moderate to severe renal impairment. discontinue ranolazine extended-release tablets if acute renal failure develops. in a separate study, cmax was increased between 40% and 50% in patients with mild, moderate, or severe renal impairment compared to patients with no renal impairment, suggesting a similar increase in exposure in patients with renal failure independent of the degree of impairment. the pharmacokinetics of ranolazine has not been assessed in patients on dialysis. heart failure (nyha class i to iv) had no significant effect on ranolazine pharmacokinetics. ranolazine had minimal effects on heart rate and blood pressure in patients with angina and heart failure nyha class i to iv. no dose adjustment of ranolazine is required in patients with heart failure. a population pharmacokinetic evaluation of data from angina patients and healthy subjects showed no effect of diabetes on ranolazine pharmacokinetics. no dose adjustment is required in patients with diabetes. ranolazine produces small reductions in hba1c in patients with diabetes, the clinical significance of which is unknown. ranolazine should not be considered a treatment for diabetes.

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

amneal pharmaceuticals llc - ranolazine (unii: a6iez5m406) (ranolazine - unii:a6iez5m406) - ranolazine extended-release tablets are indicated for the treatment of chronic angina. ranolazine extended-release tablets may be used with beta-blockers, nitrates, calcium channel blockers, anti-platelet therapy, lipid-lowering therapy, ace inhibitors and angiotensin receptor blockers. ranolazine is contraindicated in patients: - taking strong inhibitors of cyp3a [see drug interactions (7.1)] - taking inducers of cyp3a [see drug interactions (7.1)] - with liver cirrhosis [see use in specific populations (8.6)] risk summary there are no available data on ranolazine use in pregnant women to inform any drug-associated risks. studies in rats and rabbits showed no evidence of fetal harm at exposures 4 times the maximum recommended human dose (mrhd) (see data) . in the u.s. general population, the estimated background risk of major birth defects and of miscarriage of clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. data animal data embryofetal toxicity studies were conducted in rats and rabbits orally administered ranolazine during organogenesis. in rats, decreased fetal weight and reduced ossification were observed at doses (corresponding to 4-fold the auc for the mrhd) that caused maternal weight loss. no adverse fetal effects were observed in either species exposed (auc) to ranolazine at exposures (auc) equal to the mrhd. risk summary there are no data on the presence of ranolazine in human milk, the effects on the breastfed infant, or the effects on milk production. however, ranolazine is present in rat milk [see use in specific populations (8.1)] . the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ranolazine and any potential adverse effects on the breastfed infant from ranolazine or from the underlying maternal condition. adult female rats were administered ranolazine orally from gestation day 6 through postnatal day 20. no adverse effects on pup development, behavior, or reproduction parameters were observed at a maternal dosage level of 60 mg/kg/day (equal to the mhrd based on auc). at maternally toxic doses, male and female pups exhibited increased mortality and decreased body weight, and female pups showed increased motor activity. the pups were potentially exposed to low amounts of ranolazine via the maternal milk. safety and effectiveness have not been established in pediatric patients. of the chronic angina patients treated with ranolazine in controlled studies, 496 (48%) were ≥65 years of age and 114 (11%) were ≥75 years of age. no overall differences in efficacy were observed between older and younger patients. there were no differences in safety for patients ≥65 years compared to younger patients, but patients ≥75 years of age on ranolazine, compared to placebo, had a higher incidence of adverse events, serious adverse events and drug discontinuations due to adverse events. in general, dose selection for an elderly patient should usually start at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease, or other drug therapy. ranolazine is contraindicated in patients with liver cirrhosis. in a study of cirrhotic patients, the cmax of ranolazine was increased 30% in cirrhotic patients with mild (child-pugh class a) hepatic impairment, but increased 80% in cirrhotic patients with moderate (child-pugh class b) hepatic impairment compared to patients without hepatic impairment. this increase was not enough to account for the 3-fold increase in qt prolongation seen in cirrhotic patients with mild to moderate hepatic impairment [see clinical pharmacology (12.2)] . a pharmacokinetic study of ranolazine in subjects with severe renal impairment (crcl <30 ml/min) was stopped when 2 of 4 subjects developed acute renal failure after receiving ranolazine 500 mg twice daily for 5 days (lead-in phase) followed by 1000 mg twice a day (1 dose in one subject and 11 doses in the other). increases in creatinine, bun and potassium were observed in 3 subjects during the 500 mg lead-in phase. one subject required hemodialysis, while the other 2 subjects improved upon drug discontinuation [see warnings and precautions (5.2)] . monitor renal function periodically in patients with moderate to severe renal impairment. discontinue ranolazine if acute renal failure develops. in a separate study, cmax was increased between 40% and 50% in patients with mild, moderate, or severe renal impairment compared to patients with no renal impairment, suggesting a similar increase in exposure in patients with renal failure independent of the degree of impairment. the pharmacokinetics of ranolazine has not been assessed in patients on dialysis. heart failure (nyha class i to iv) had no significant effect on ranolazine pharmacokinetics. ranolazine had minimal effects on heart rate and blood pressure in patients with angina and heart failure nyha class i to iv. no dose adjustment of ranolazine is required in patients with heart failure. a population pharmacokinetic evaluation of data from angina patients and healthy subjects showed no effect of diabetes on ranolazine pharmacokinetics. no dose adjustment is required in patients with diabetes. ranolazine produces small reductions in hba1c in patients with diabetes, the clinical significance of which is unknown. ranolazine should not be considered a treatment for diabetes.

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

lupin pharmaceuticals, inc. - ranolazine (unii: a6iez5m406) (ranolazine - unii:a6iez5m406) - ranolazine extended-release tablets are indicated for the treatment of chronic angina. ranolazine extended-release tablets may be used with beta-blockers, nitrates, calcium channel blockers, anti-platelet therapy, lipid-lowering therapy, ace inhibitors, and angiotensin receptor blockers. ranolazine is contraindicated in patients: - taking strong inhibitors of cyp3a [see drug interactions (7.1)] - taking inducers of cyp3a [see drug interactions (7.1)] - with liver cirrhosis [see use in specific populations (8.6)] risk summary there are no available data on ranolazine extended-release tablets use in pregnant women to inform any drug-associated risks. studies in rats and rabbits showed no evidence of fetal harm at exposures 4 times the maximum recommended human dose (mrhd) (see data) . in the u.s. general population, the estimated background risk of major birth defects and of miscarriage of clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data animal data: embryofetal toxicity studies were conducted in rats and rabbits orally administered ranolazine during organogenesis. in rats, decreased fetal weight and reduced ossification were observed at doses (corresponding to 4-fold the auc for the mrhd) that caused maternal weight loss. no adverse fetal effects were observed in either species exposed (auc) to ranolazine at exposures (auc) equal to the mrhd. risk summary there are no data on the presence of ranolazine in human milk, the effects on the breastfed infant, or the effects on milk production. however, ranolazine is present in rat milk [see use in specific populations (8.1)] . the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ranolazine and any potential adverse effects on the breastfed infant from ranolazine or from the underlying maternal condition. adult female rats were administered ranolazine orally from gestation day 6 through postnatal day 20. no adverse effects on pup development, behavior, or reproduction parameters were observed at a maternal dosage level of 60 mg/kg/day (equal to the mhrd based on auc). at maternally toxic doses, male and female pups exhibited increased mortality and decreased body weight, and female pups showed increased motor activity. the pups were potentially exposed to low amounts of ranolazine via the maternal milk. safety and effectiveness have not been established in pediatric patients. of the chronic angina patients treated with ranolazine in controlled studies, 496 (48%) were ≥65 years of age, and 114 (11%) were ≥75 years of age. no overall differences in efficacy were observed between older and younger patients. there were no differences in safety for patients ≥65 years compared to younger patients, but patients ≥75 years of age on ranolazine, compared to placebo, had a higher incidence of adverse events, serious adverse events, and drug discontinuations due to adverse events. in general, dose selection for an elderly patient should usually start at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease, or other drug therapy. ranolazine is contraindicated in patients with liver cirrhosis. in a study of cirrhotic patients, the cmax of ranolazine was increased 30% in cirrhotic patients with mild (child-pugh class a) hepatic impairment, but increased 80% in cirrhotic patients with moderate (child-pugh class b) hepatic impairment compared to patients without hepatic impairment. this increase was not enough to account for the 3-fold increase in qt prolongation seen in cirrhotic patients with mild to moderate hepatic impairment [see clinical pharmacology (12.2)].   a pharmacokinetic study of ranolazine in subjects with severe renal impairment (crcl <30 ml/min) was stopped when 2 of 4 subjects developed acute renal failure after receiving ranolazine extended-release tablets 500 mg twice daily for 5 days (lead-in phase) followed by 1000 mg twice a day (1 dose in one subject and 11 doses in the other). increases in creatinine, bun, and potassium were observed in 3 subjects during the 500 mg lead-in phase. one subject required hemodialysis, while the other 2 subjects improved upon drug discontinuation [see warnings and precautions (5.2)] . monitor renal function periodically in patients with moderate to severe renal impairment. discontinue ranolazine extended-release tablets if acute renal failure develops. in a separate study, cmax was increased between 40% and 50% in patients with mild, moderate, or severe renal impairment compared to patients with no renal impairment, suggesting a similar increase in exposure in patients with renal failure independent of the degree of impairment. the pharmacokinetics of ranolazine has not been assessed in patients on dialysis. heart failure (nyha class i to iv) had no significant effect on ranolazine pharmacokinetics. ranolazine had minimal effects on heart rate and blood pressure in patients with angina and heart failure nyha class i to iv. no dose adjustment of ranolazine is required in patients with heart failure. a population pharmacokinetic evaluation of data from angina patients and healthy subjects showed no effect of diabetes on ranolazine pharmacokinetics. no dose adjustment is required in patients with diabetes. ranolazine produces small reductions in hba1c in patients with diabetes, the clinical significance of which is unknown. ranolazine should not be considered a treatment for diabetes.

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

sungen pharma llc - ranolazine (unii: a6iez5m406) (ranolazine - unii:a6iez5m406) - ranolazine extended-release tablets are indicated for the treatment of chronic angina. ranolazine extended-release tablets may be used with beta-blockers, nitrates, calcium channel blockers, anti-platelet therapy, lipid-lowering therapy, ace inhibitors, and angiotensin receptor blockers. ranolazine extended-release tablets are contraindicated in patients: - taking strong inhibitors of cyp3a [see drug interactions (7.1) ] - taking inducers of cyp3a [see drug interactions (7.1) ] - with liver cirrhosis [see use in specific populations (8.6) ] risk summary there are no available data on ranolazine extended-release tablets use in pregnant women to inform any drug-associated risks. studies in rats and rabbits showed no evidence of fetal harm at exposures 4 times the maximum recommended human dose (mrhd) (see data ) . in the u.s. general population, the estimated background risk of major birth defects and of miscarriage of clinically recognized pregnancies is 2-4% and 15-20%, respectively. data animal data embryofetal toxicity studies were conducted in rats and rabbits orally administered ranolazine during organogenesis. in rats, decreased fetal weight and reduced ossification were observed at doses (corresponding to 4-fold the auc for the mrhd) that caused maternal weight loss. no adverse fetal effects were observed in either species exposed (auc) to ranolazine at exposures (auc) equal to the mrhd. risk summary there are no data on the presence of ranolazine in human milk, the effects on the breastfed infant, or the effects on milk production. however, ranolazine is present in rat milk [see use in specific populations (8.1) ] . the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ranolazine extended-release tablets and any potential adverse effects on the breastfed infant from ranolazine extended-release tablets or from the underlying maternal condition. adult female rats were administered ranolazine orally from gestation day 6 through postnatal day 20. no adverse effects on pup development, behavior, or reproduction parameters were observed at a maternal dosage level of 60 mg/kg/day (equal to the mhrd based on auc). at maternally toxic doses, male and female pups exhibitedincreased mortality and decreased body weight, and female pups showed increased motor activity. the pups were potentially exposed to low amounts of ranolazine via the maternal milk. safety and effectiveness have not been established in pediatric patients. of the chronic angina patients treated with ranolazine extended-release tablets in controlled studies, 496 (48%) were ≥65 years of age, and 114 (11%) were ≥75 years of age. no overall differences in efficacy were observed between older and younger patients. there were no differences in safety forpatients ≥65 years compared to younger patients, but patients ≥75 years of age on ranolazine extended-release tablets, compared to placebo, had a higher incidence of adverse events, serious adverse events, and drug discontinuations due to adverse events. in general, dose selection for an elderly patient should usually start at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease, or other drug therapy. ranolazine extended-release tabletsare contraindicated in patients with liver cirrhosis. in a study of cirrhotic patients, the c max of ranolazine was increased 30% in cirrhotic patients with mild (child-pugh class a) hepatic impairment, but increased 80% in cirrhotic patients with moderate (child-pugh class b) hepatic impairment compared to patients without hepatic impairment. this increase was not enough to account for the 3-fold increase in qt prolongation seen in cirrhotic patients with mild to moderate hepatic impairment [see clinical pharmacology (12.2) ] . a pharmacokinetic study of ranolazine extended-release tablets in subjects with severe renal impairment (crcl<30 ml/min) was stopped when 2 of 4 subjects developed acute renal failure after receiving ranolazine extended-release tablets 500 mg twice daily for 5 days (lead-in phase) followed by 1000 mg twice a day (1 dose in one subject and 11 doses in the other). increases in creatinine, bun, and potassium were observed in 3 subjects during the 500 mg lead-in phase. one subject required hemodialysis, while the other 2 subjects improved upon drug discontinuation [see warnings and precautions (5.2) ] . monitor renal function periodically in patients with moderate to severe renal impairment. discontinue ranolazine extended-release tablets if acute renal failure develops. in a separate study, c max was increased between 40% and 50% in patients with mild, moderate, or severe renal impairment compared to patients with no renal impairment, suggesting a similar increase in exposure in patients with renal failure independent of the degree of impairment. the pharmacokinetics of ranolazine has not been assessed in patients on dialysis. heart failure (nyha class i to iv) had no significant effect on ranolazine pharmacokinetics. ranolazine extended-release tablets had minimal effects on heart rate and blood pressure in patients with angina and heart failure nyha class i to iv. no dose adjustment of ranolazine extended-release tablets is required in patients with heart failure. a population pharmacokinetic evaluation of data from angina patients and healthy subjects showed no effect of diabetes on ranolazine pharmacokinetics. no dose adjustment is required in patients with diabetes. ranolazine extended-release tablets produce small reductions in hba1c in patients with diabetes, the clinical significance of which is unknown. ranolazine extended-release tablets should not be considered a treatment for diabetes.

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

avkare - ranolazine (unii: a6iez5m406) (ranolazine - unii:a6iez5m406) - ranolazine extended-release tablets are indicated for the treatment of chronic angina. ranolazine extended-release tablets may be used with beta-blockers, nitrates, calcium channel blockers, anti-platelet therapy, lipid-lowering therapy, ace inhibitors, and angiotensin receptor blockers. ranolazine extended-release tablets are contraindicated in patients: - taking strong inhibitors of cyp3a [see drug interactions (7.1) ] - taking inducers of cyp3a [see drug interactions (7.1) ] - with liver cirrhosis [see use in specific populations (8.6) ] risk summary there are no available data on ranolazine extended-release tablets use in pregnant women to inform any drug-associated risks. studies in rats and rabbits showed no evidence of fetal harm at exposures 4 times the maximum recommended human dose (mrhd) (see data ) . in the u.s. general population, the estimated background risk of major birth defects and of miscarriage of clinically recognized pregnancies is 2-4% and 15-20%, respectively. data animal data embryofetal toxicity studies were conducted in rats and rabbits orally administered ranolazine during organogenesis. in rats, decreased fetal weight and reduced ossification were observed at doses (corresponding to 4-fold the auc for the mrhd) that caused maternal weight loss. no adverse fetal effects were observed in either species exposed (auc) to ranolazine at exposures (auc) equal to the mrhd. risk summary there are no data on the presence of ranolazine in human milk, the effects on the breastfed infant, or the effects on milk production. however, ranolazine is present in rat milk [see use in specific populations (8.1) ] . the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ranolazine extended-release tablets and any potential adverse effects on the breastfed infant from ranolazine extended-release tablets or from the underlying maternal condition. adult female rats were administered ranolazine orally from gestation day 6 through postnatal day 20. no adverse effects on pup development, behavior, or reproduction parameters were observed at a maternal dosage level of 60 mg/kg/day (equal to the mhrd based on auc). at maternally toxic doses, male and female pups exhibitedincreased mortality and decreased body weight, and female pups showed increased motor activity. the pups were potentially exposed to low amounts of ranolazine via the maternal milk. safety and effectiveness have not been established in pediatric patients. of the chronic angina patients treated with ranolazine extended-release tablets in controlled studies, 496 (48%) were ≥65 years of age, and 114 (11%) were ≥75 years of age. no overall differences in efficacy were observed between older and younger patients. there were no differences in safety forpatients ≥65 years compared to younger patients, but patients ≥75 years of age on ranolazine extended-release tablets, compared to placebo, had a higher incidence of adverse events, serious adverse events, and drug discontinuations due to adverse events. in general, dose selection for an elderly patient should usually start at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease, or other drug therapy. ranolazine extended-release tabletsare contraindicated in patients with liver cirrhosis. in a study of cirrhotic patients, the c max of ranolazine was increased 30% in cirrhotic patients with mild (child-pugh class a) hepatic impairment, but increased 80% in cirrhotic patients with moderate (child-pugh class b) hepatic impairment compared to patients without hepatic impairment. this increase was not enough to account for the 3-fold increase in qt prolongation seen in cirrhotic patients with mild to moderate hepatic impairment [see clinical pharmacology (12.2) ] . a pharmacokinetic study of ranolazine extended-release tablets in subjects with severe renal impairment (crcl<30 ml/min) was stopped when 2 of 4 subjects developed acute renal failure after receiving ranolazine extended-release tablets 500 mg twice daily for 5 days (lead-in phase) followed by 1000 mg twice a day (1 dose in one subject and 11 doses in the other). increases in creatinine, bun, and potassium were observed in 3 subjects during the 500 mg lead-in phase. one subject required hemodialysis, while the other 2 subjects improved upon drug discontinuation [see warnings and precautions (5.2) ] . monitor renal function periodically in patients with moderate to severe renal impairment. discontinue ranolazine extended-release tablets if acute renal failure develops. in a separate study, c max was increased between 40% and 50% in patients with mild, moderate, or severe renal impairment compared to patients with no renal impairment, suggesting a similar increase in exposure in patients with renal failure independent of the degree of impairment. the pharmacokinetics of ranolazine has not been assessed in patients on dialysis. heart failure (nyha class i to iv) had no significant effect on ranolazine pharmacokinetics. ranolazine extended-release tablets had minimal effects on heart rate and blood pressure in patients with angina and heart failure nyha class i to iv. no dose adjustment of ranolazine extended-release tablets is required in patients with heart failure. a population pharmacokinetic evaluation of data from angina patients and healthy subjects showed no effect of diabetes on ranolazine pharmacokinetics. no dose adjustment is required in patients with diabetes. ranolazine extended-release tablets produce small reductions in hba1c in patients with diabetes, the clinical significance of which is unknown. ranolazine extended-release tablets should not be considered a treatment for diabetes.

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

aurobindo pharma limited - ranolazine (unii: a6iez5m406) (ranolazine - unii:a6iez5m406) - ranolazine extended-release tablets are indicated for the treatment of chronic angina. ranolazine extended-release tablets may be used with beta-blockers, nitrates, calcium channel blockers, anti-platelet therapy, lipid-lowering therapy, ace inhibitors, and angiotensin receptor blockers. ranolazine extended-release tablets are contraindicated in patients: - taking strong inhibitors of cyp3a [see drug interactions (7.1)] - taking inducers of cyp3a [see drug interactions (7.1)] - with liver cirrhosis [see use in specific populations (8.6)] risk summary there are no available data on ranolazine extended-release tablets use in pregnant women to inform any drug-associated risks. studies in rats and rabbits showed no evidence of fetal harm at exposures 4 times the maximum recommended human dose (mrhd) (see data) . in the u.s. general population, the estimated background risk of major birth defects and of miscarriage of clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data animal data embryofetal toxicity studies were conducted in rats and rabbits orally administered ranolazine during organogenesis. in rats, decreased fetal weight and reduced ossification were observed at doses (corresponding to 4-fold the auc for the mrhd) that caused maternal weight loss. no adverse fetal effects were observed in either species exposed (auc) to ranolazine at exposures (auc) equal to the mrhd. risk summary there are no data on the presence of ranolazine in human milk, the effects on the breastfed infant, or the effects on milk production. however, ranolazine is present in rat milk [see use in specific populations (8.1)] . the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ranolazine extended-release tablets and any potential adverse effects on the breastfed infant from ranolazine extended-release tablets or from the underlying maternal condition. adult female rats were administered ranolazine orally from gestation day 6 through postnatal day 20. no adverse effects on pup development, behavior, or reproduction parameters were observed at a maternal dosage level of 60 mg/kg/day (equal to the mhrd based on auc). at maternally toxic doses, male and female pups exhibited increased mortality and decreased body weight, and female pups showed increased motor activity. the pups were potentially exposed to low amounts of ranolazine via the maternal milk. safety and effectiveness have not been established in pediatric patients. of the chronic angina patients treated with ranolazine extended-release tablets in controlled studies, 496 (48%) were ≥ 65 years of age, and 114 (11%) were ≥ 75 years of age. no overall differences in efficacy were observed between older and younger patients. there were no differences in safety for patients ≥ 65 years compared to younger patients, but patients ≥ 75 years of age on ranolazine extended-release tablets, compared to placebo, had a higher incidence of adverse events, serious adverse events, and drug discontinuations due to adverse events. in general, dose selection for an elderly patient should usually start at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease, or other drug therapy. ranolazine extended-release tablets are contraindicated in patients with liver cirrhosis. in a study of cirrhotic patients, the cmax of ranolazine was increased 30% in cirrhotic patients with mild (child-pugh class a) hepatic impairment, but increased 80% in cirrhotic patients with moderate (child-pugh class b) hepatic impairment compared to patients without hepatic impairment. this increase was not enough to account for the 3-fold increase in qt prolongation seen in cirrhotic patients with mild to moderate hepatic impairment [see clinical pharmacology (12.2)] . a pharmacokinetic study of ranolazine extended-release tablets in subjects with severe renal impairment (crcl < 30 ml/min) was stopped when 2 of 4 subjects developed acute renal failure after receiving ranolazine extended-release tablets 500 mg twice daily for 5 days (lead-in phase) followed by 1000 mg twice a day (1 dose in one subject and 11 doses in the other). increases in creatinine, bun, and potassium were observed in 3 subjects during the 500 mg lead-in phase. one subject required hemodialysis, while the other 2 subjects improved upon drug discontinuation [see warnings and precautions (5.2)] . monitor renal function periodically in patients with moderate to severe renal impairment. discontinue ranolazine extended-release tablets if acute renal failure develops. in a separate study, cmax was increased between 40% and 50% in patients with mild, moderate, or severe renal impairment compared to patients with no renal impairment, suggesting a similar increase in exposure in patients with renal failure independent of the degree of impairment. the pharmacokinetics of ranolazine has not been assessed in patients on dialysis. heart failure (nyha class i to iv) had no significant effect on ranolazine pharmacokinetics. ranolazine extended-release tablets had minimal effects on heart rate and blood pressure in patients with angina and heart failure nyha class i to iv. no dose adjustment of ranolazine extended-release tablets is required in patients with heart failure. a population pharmacokinetic evaluation of data from angina patients and healthy subjects showed no effect of diabetes on ranolazine pharmacokinetics. no dose adjustment is required in patients with diabetes. ranolazine extended-release tablets produce small reductions in hba1c in patients with diabetes, the clinical significance of which is unknown. ranolazine extended-release tablets should not be considered a treatment for diabetes.

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

cipla usa inc. - ranolazine (unii: a6iez5m406) (ranolazine - unii:a6iez5m406) - ranolazine extended-release tablets are indicated for the treatment of chronic angina. ranolazine extended-release tablets may be used with beta-blockers, nitrates, calcium channel blockers, anti-platelet therapy, lipid-lowering therapy, ace inhibitors, and angiotensin receptor blockers. ranolazine extended-release tablets are contraindicated in patients: - taking strong inhibitors of cyp3a [see drug interactions (7.1)] - taking inducers of cyp3a [see drug interactions (7.1)] - with liver cirrhosis [see use in specific populations (8.6)] risk summary there are no available data on ranolazine use in pregnant women to inform any drug-associated risks. studies in rats and rabbits showed no evidence of fetal harm at exposures 4 times the maximum recommended human dose (mrhd) (see data) . in the u.s. general population, the estimated background risk of major birth defects and of miscarriage of clinically recognized pregnancies is 2-4% and 15-20%, respectively. data animal data embryofetal toxicity s