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WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Use Of QUALAQUIN For Treatment Or Prevention Of Nocturnal Leg Cramps

QUALAQUIN may cause unpredictable serious and life-threatening hematologic reactions including thrombocytopenia and hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) in addition to hypersensitivity reactions, QT prolongation, serious cardiac arrhythmias including torsades de pointes, and other serious adverse events requiring medical intervention and hospitalization. Chronic renal impairment associated with the development of TTP, and fatalities have also been reported. The risk associated with the use of QUALAQUIN in the absence of evidence of its effectiveness for treatment or prevention of nocturnal leg cramps, outweighs any potential benefit in treating and/or preventing this benign, self-limiting condition.

Thrombocytopenia

Quinine-induced thrombocytopenia is an immune-mediated disorder. Severe cases of thrombocytopenia that are fatal or life threatening have been reported, including cases of HUS/TTP. Chronic renal impairment associated with the development of TTP has also been reported. Thrombocytopenia usually resolves within a week upon discontinuation of quinine. If quinine is not stopped, a patient is at risk for fatal hemorrhage. Upon re-exposure to quinine from any source, a patient with quinine-dependent antibodies could develop thrombocytopenia that is more rapid in onset and more severe than the original episode.

QT Prolongation And Ventricular Arrhythmias

QT interval prolongation has been a consistent finding in studies which evaluated electrocardiographic changes with oral or parenteral quinine administration, regardless of age, clinical status, or severity of disease. The maximum increase in QT interval has been shown to correspond with peak quinine plasma concentration. Quinine sulfate has been rarely associated with potentially fatal cardiac arrhythmias, including torsades de pointes, and ventricular fibrillation.

QUALAQUIN has been shown to cause concentration-dependent prolongation of the PR and QRS interval. At particular risk are patients with underlying structural heart disease and preexisting conduction system abnormalities, elderly patients with sick sinus syndrome, patients with atrial fibrillation with slow ventricular response, patients with myocardial ischemia or patients receiving drugs known to prolong the PR interval (e.g. verapamil) or QRS interval (e.g. flecainide or quinidine).

QUALAQUIN is not recommended for use with other drugs known to cause QT prolongation, including Class IA antiarrhythmic agents (e.g., quinidine, procainamide, disopyramide), and Class III antiarrhythmic agents (e.g., amiodarone, sotalol, dofetilide).

The use of macrolide antibiotics such as erythromycin should be avoided in patients receiving QUALAQUIN. Fatal torsades de pointes was reported in an elderly patient who received concomitant quinine, erythromycin, and dopamine. Although a causal relationship between a specific drug and the arrhythmia was not established in this case, erythromycin is a CYP3A4 inhibitor and has been shown to increase quinine plasma levels when used concomitantly. A related macrolide antibiotic, troleandomycin, has also been shown to increase quinine exposure in a pharmacokinetic study.

Quinine may inhibit the metabolism of certain drugs that are CYP3A4 substrates and are known to cause QT prolongation, e.g., astemizole, cisapride, terfenadine, pimozide, halofantrine and quinidine. Torsades de pointes has been reported in patients who received concomitant quinine and astemizole. Therefore, concurrent use of QUALAQUIN with these medications, or drugs with similar properties, should be avoided.

Concomitant administration of QUALAQUIN with the antimalarial drugs, mefloquine or halofantrine, may result in electrocardiographic abnormalities, including QT prolongation, and increase the risk for torsades de pointes or other serious ventricular arrhythmias. Concurrent use of QUALAQUIN and mefloquine may also increase the risk of seizures.

QUALAQUIN should also be avoided in patients with known prolongation of QT interval and in patients with clinical conditions known to prolong the QT interval, such as uncorrected hypokalemia, bradycardia, and certain cardiac conditions.

Concomitant Use Of Rifampin

Treatment failures may result from the concurrent use of rifampin with QUALAQUIN, due to decreased plasma concentrations of quinine, and concomitant use of these medications should be avoided.

Concomitant Use Of Neuromuscular Blocking Agents

The use of neuromuscular blocking agents should be avoided in patients receiving QUALAQUIN. In one patient who received pancuronium during an operative procedure, subsequent administration of quinine resulted in respiratory depression and apnea. Although there are no clinical reports with succinylcholine or tubocurarine, quinine may also potentiate neuromuscular blockade when used with these drugs.

Hypersensitivity

Serious hypersensitivity reactions reported with quinine sulfate include anaphylactic shock, anaphylactoid reactions, urticaria, serious skin rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis, angioedema, facial edema, bronchospasm, and pruritus.

A number of other serious adverse reactions reported with quinine, including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), thrombocytopenia, immune thrombocytopenic purpura (ITP), blackwater fever, disseminated intravascular coagulation, leukopenia, neutropenia, granulomatous hepatitis, and acute interstitial nephritis may also be due to hypersensitivity reactions.

QUALAQUIN should be discontinued in case of any signs or symptoms of hypersensitivity.

Atrial Fibrillation And Flutter

QUALAQUIN should be used with caution in patients with atrial fibrillation or atrial flutter. A paradoxical increase in ventricular response rate may occur with quinine, similar to that observed with quinidine. If digoxin is used to prevent a rapid ventricular response, serum digoxin levels should be closely monitored, because digoxin levels may be increased with use of quinine.

Hypoglycemia

Quinine stimulates release of insulin from the pancreas, and patients, especially pregnant women, may experience clinically significant hypoglycemia.

Patient Counseling Information

See FDA-approved patient labeling (Medication Guide)

Dosing Instructions

Patients should be instructed to:

• Take all of the medication as directed.
• Take no more of the medication than the amount prescribed.
• Take with food to minimize possible gastrointestinal irritation.

If a dose is missed, patients should also be instructed not to double the next dose. If more than 4 hours has elapsed since the missed dose, the patient should wait and take the next dose as previously scheduled.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenesis

Carcinogenicity studies of quinine have not been conducted.

Mutagenesis

Genotoxicity studies of quinine were positive in the Ames bacterial mutation assay with metabolic activation and in the sister chromatid exchange assay in mice. The sex-linked recessive lethal test performed in Drosophila, the in vivo mouse micronucleus assay, and the chromosomal aberration assay in mice and Chinese hamsters were negative.

Impairment of Fertility

Published studies indicate that quinine produces testicular toxicity in mice at a single intraperitoneal dose of 300 mg/kg corresponding to a dose of approximately 0.75 times the maximum recommended human dose (MRHD; 32 mg/kg/day) and in rats at an intramuscular dose of 10 mg/kg/day, 5 days/week, for 8 weeks corresponding to a daily dose of approximately 0.05 times the MRHD based on body surface area (BSA) comparisons. The findings include atrophy or degeneration of the seminiferous tubules, decreased sperm count and motility, and decreased testosterone levels in the serum and testes. There was no effect on testes weight in studies of oral doses of up to 500 mg/kg/day in mice and 700 mg/kg/day in rats (approximately 1.2 and 3.5 times the MRHD respectively based on BSA comparisons). In a published study in 5 men receiving 600 mg of quinine TID for one week, sperm motility was decreased and percent sperm with abnormal morphology was increased; sperm count and serum testosterone were unaffected.

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are extensive published data but few well-controlled studies of QUALAQUIN in pregnant women. Published data on over 1,000 pregnancy exposures to quinine did not show an increase in teratogenic effects over the background rate in the general population; however, the majority of these exposures were not in the first trimester. In developmental and reproductive toxicity studies, central nervous system (CNS) and ear abnormalities and increased fetal deaths occurred in some species when pregnant animals received quinine at doses about 1 to 4 times the human clinical dose. Quinine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

P. falciparum malaria carries a higher risk of morbidity and mortality in pregnant women than in the general population. Pregnant women with P. falciparum malaria have an increased incidence of fetal loss (including spontaneous abortion and stillbirth), preterm labor and delivery, intrauterine growth retardation, low birth weight, and maternal death. Therefore, treatment of malaria in pregnancy is important.

Hypoglycemia, due to increased pancreatic secretion of insulin, has been associated with quinine use, particularly in pregnant women.

Quinine crosses the placenta with measurable blood concentrations in the fetus. In 8 women who delivered live infants 1 to 6 days after starting quinine therapy, umbilical cord plasma quinine concentrations were between 1.0 and 4.6 mg/L (mean 2.4 mg/L) and the mean (±SD) ratio of cord plasma to maternal plasma quinine concentrations was 0.32 ± 0.14. Quinine levels in the fetus may not be therapeutic. If congenital malaria is suspected after delivery, the infant should be evaluated and treated appropriately.

A study from Thailand (1999) of women with P. falciparum malaria who were treated with oral quinine sulfate 10 mg/kg 3 times daily for 7 days at anytime in pregnancy reported no significant difference in the rate of stillbirths at > 28 weeks of gestation in women treated with quinine (10 of 633 women [1.6%]) as compared with a control group without malaria or exposure to antimalarial drugs during pregnancy (40 of 2201 women [1.8%]). The overall rate of congenital malformations (9 of 633 offspring [1.4%]) was not different for women who were treated with quinine sulfate compared with the control group (38 of 2201 offspring [1.7%]). The spontaneous abortion rate was higher in the control group (10.9%) than in women treated with quinine sulfate (3.5%) [OR = 3.1; 95% CI 2.1-4.7]. An epidemiologic survey that included 104 mother-child pairs exposed to quinine during the first 4 months of pregnancy, found no increased risk of structural birth defects was seen (2 fetal malformations [1.9%]). Rare and isolated case reports describe deafness and optic nerve hypoplasia in children exposed in utero due to maternal ingestion of high doses of quinine.

In animal developmental studies conducted in multiple animal species, pregnant animals received quinine by the subcutaneous or intramuscular route at dose levels similar to the maximum recommended human dose (MRHD; 32 mg/kg/day) based on body surface area (BSA) comparisons. There were increases in fetal death in utero in rabbits at maternal doses ≥ 100 mg/kg/day and in dogs at ≥ 15 mg/kg/day corresponding to dose levels approximately 0.5 and 0.25 times the MRHD respectively based on BSA comparisons. Rabbit offspring had increased rates of degenerated auditory nerve and spiral ganglion and increased rates of CNS anomalies such as anencephaly and microcephaly at a dose of 130 mg/kg/day corresponding to a maternal dose approximately 1.3 times the MRHD based on BSA comparison. Guinea pig offspring had increased rates of hemorrhage and mitochondrial change in the cochlea at maternal doses of 200 mg/kg corresponding to a dose level of approximately 1.4 times the MRHD based on BSA comparison. There were no teratogenic findings in rats at maternal doses up to 300 mg/kg/day and in monkeys at doses up to 200 mg/kg/day corresponding to doses approximately 1 and 2 times the MRHD respectively based on BSA comparisons.

In a pre-postnatal study in rats, an estimated oral dose of quinine sulfate of 20 mg/kg/day corresponding to approximately 0.1 times the MRHD based on BSA comparison resulted in offspring with impaired growth, lower body weights at birth and during the lactation period, and delayed physical development of teeth eruption and eye opening during the lactation period.

Labor And Delivery

There is no evidence that quinine causes uterine contractions at the doses recommended for the treatment of malaria. In doses several-times higher than those used to treat malaria, quinine may stimulate the pregnant uterus.

Nursing Mothers

There is limited information on the safety of quinine in breastfed infants. No toxicity was reported in infants in a single study where oral quinine sulfate (10 mg/kg every 8 hours for 1 to 10 days) was administered to 25 lactating women. It is estimated from this study that breastfed infants would receive less than 2 to 3 mg per day of quinine base ( < 0.4% of the maternal dose) via breast milk.

Although quinine is generally considered compatible with breastfeeding, the risks and benefits to infant and mother should be assessed. Caution should be exercised when administered to a nursing woman.

If malaria is suspected in the infant, appropriate evaluation and treatment should be provided. Plasma quinine levels may not be therapeutic in infants of nursing mothers receiving QUALAQUIN.

Pediatric Use

The safety and efficacy of QUALAQUIN in pediatric patients under the age of 16 has not been established.

Geriatric Use

Clinical studies of quinine sulfate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond to treatment differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Renal Impairment

Clearance of quinine is decreased in patients with severe chronic renal failure. The dosage and dosing frequency should be reduced.

Hepatic Impairment

In patients with severe hepatic impairment (Child-Pugh C), quinine oral clearance (CL/F) is decreased, volume of distribution (Vd/F) is increased, and half-life is prolonged, relative to subjects with normal liver function. Therefore, quinine is not indicated in patients with severe hepatic impairment and alternate therapy should be administered.

Close monitoring is recommended for patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment, as exposure to quinine may be increased relative to subjects with normal liver function.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Use Of QUALAQUIN For Treatment Or Prevention Of Nocturnal Leg Cramps

QUALAQUIN may cause unpredictable serious and life-threatening hematologic reactions including thrombocytopenia and hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP) in addition to hypersensitivity reactions, QT prolongation, serious cardiac arrhythmias including torsades de pointes, and other serious adverse events requiring medical intervention and hospitalization. Chronic renal impairment associated with the development of TTP, and fatalities have also been reported. The risk associated with the use of QUALAQUIN in the absence of evidence of its effectiveness for treatment or prevention of nocturnal leg cramps, outweighs any potential benefit in treating and/or preventing this benign, self-limiting condition.

Thrombocytopenia

Quinine-induced thrombocytopenia is an immune-mediated disorder. Severe cases of thrombocytopenia that are fatal or life threatening have been reported, including cases of HUS/TTP. Chronic renal impairment associated with the development of TTP has also been reported. Thrombocytopenia usually resolves within a week upon discontinuation of quinine. If quinine is not stopped, a patient is at risk for fatal hemorrhage. Upon re-exposure to quinine from any source, a patient with quinine-dependent antibodies could develop thrombocytopenia that is more rapid in onset and more severe than the original episode.

QT Prolongation And Ventricular Arrhythmias

QT interval prolongation has been a consistent finding in studies which evaluated electrocardiographic changes with oral or parenteral quinine administration, regardless of age, clinical status, or severity of disease. The maximum increase in QT interval has been shown to correspond with peak quinine plasma concentration. Quinine sulfate has been rarely associated with potentially fatal cardiac arrhythmias, including torsades de pointes, and ventricular fibrillation.

QUALAQUIN has been shown to cause concentration-dependent prolongation of the PR and QRS interval. At particular risk are patients with underlying structural heart disease and preexisting conduction system abnormalities, elderly patients with sick sinus syndrome, patients with atrial fibrillation with slow ventricular response, patients with myocardial ischemia or patients receiving drugs known to prolong the PR interval (e.g. verapamil) or QRS interval (e.g. flecainide or quinidine).

QUALAQUIN is not recommended for use with other drugs known to cause QT prolongation, including Class IA antiarrhythmic agents (e.g., quinidine, procainamide, disopyramide), and Class III antiarrhythmic agents (e.g., amiodarone, sotalol, dofetilide).

The use of macrolide antibiotics such as erythromycin should be avoided in patients receiving QUALAQUIN. Fatal torsades de pointes was reported in an elderly patient who received concomitant quinine, erythromycin, and dopamine. Although a causal relationship between a specific drug and the arrhythmia was not established in this case, erythromycin is a CYP3A4 inhibitor and has been shown to increase quinine plasma levels when used concomitantly. A related macrolide antibiotic, troleandomycin, has also been shown to increase quinine exposure in a pharmacokinetic study.

Quinine may inhibit the metabolism of certain drugs that are CYP3A4 substrates and are known to cause QT prolongation, e.g., astemizole, cisapride, terfenadine, pimozide, halofantrine and quinidine. Torsades de pointes has been reported in patients who received concomitant quinine and astemizole. Therefore, concurrent use of QUALAQUIN with these medications, or drugs with similar properties, should be avoided.

Concomitant administration of QUALAQUIN with the antimalarial drugs, mefloquine or halofantrine, may result in electrocardiographic abnormalities, including QT prolongation, and increase the risk for torsades de pointes or other serious ventricular arrhythmias. Concurrent use of QUALAQUIN and mefloquine may also increase the risk of seizures.

QUALAQUIN should also be avoided in patients with known prolongation of QT interval and in patients with clinical conditions known to prolong the QT interval, such as uncorrected hypokalemia, bradycardia, and certain cardiac conditions.

Concomitant Use Of Rifampin

Treatment failures may result from the concurrent use of rifampin with QUALAQUIN, due to decreased plasma concentrations of quinine, and concomitant use of these medications should be avoided.

Concomitant Use Of Neuromuscular Blocking Agents

The use of neuromuscular blocking agents should be avoided in patients receiving QUALAQUIN. In one patient who received pancuronium during an operative procedure, subsequent administration of quinine resulted in respiratory depression and apnea. Although there are no clinical reports with succinylcholine or tubocurarine, quinine may also potentiate neuromuscular blockade when used with these drugs.

Hypersensitivity

Serious hypersensitivity reactions reported with quinine sulfate include anaphylactic shock, anaphylactoid reactions, urticaria, serious skin rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis, angioedema, facial edema, bronchospasm, and pruritus.

A number of other serious adverse reactions reported with quinine, including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), thrombocytopenia, immune thrombocytopenic purpura (ITP), blackwater fever, disseminated intravascular coagulation, leukopenia, neutropenia, granulomatous hepatitis, and acute interstitial nephritis may also be due to hypersensitivity reactions.

QUALAQUIN should be discontinued in case of any signs or symptoms of hypersensitivity.

Atrial Fibrillation And Flutter

QUALAQUIN should be used with caution in patients with atrial fibrillation or atrial flutter. A paradoxical increase in ventricular response rate may occur with quinine, similar to that observed with quinidine. If digoxin is used to prevent a rapid ventricular response, serum digoxin levels should be closely monitored, because digoxin levels may be increased with use of quinine.

Hypoglycemia

Quinine stimulates release of insulin from the pancreas, and patients, especially pregnant women, may experience clinically significant hypoglycemia.

Patient Counseling Information

See FDA-approved patient labeling (Medication Guide)

Dosing Instructions

Patients should be instructed to:

• Take all of the medication as directed.
• Take no more of the medication than the amount prescribed.
• Take with food to minimize possible gastrointestinal irritation.

If a dose is missed, patients should also be instructed not to double the next dose. If more than 4 hours has elapsed since the missed dose, the patient should wait and take the next dose as previously scheduled.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenesis

Carcinogenicity studies of quinine have not been conducted.

Mutagenesis

Genotoxicity studies of quinine were positive in the Ames bacterial mutation assay with metabolic activation and in the sister chromatid exchange assay in mice. The sex-linked recessive lethal test performed in Drosophila, the in vivo mouse micronucleus assay, and the chromosomal aberration assay in mice and Chinese hamsters were negative.

Impairment of Fertility

Published studies indicate that quinine produces testicular toxicity in mice at a single intraperitoneal dose of 300 mg/kg corresponding to a dose of approximately 0.75 times the maximum recommended human dose (MRHD; 32 mg/kg/day) and in rats at an intramuscular dose of 10 mg/kg/day, 5 days/week, for 8 weeks corresponding to a daily dose of approximately 0.05 times the MRHD based on body surface area (BSA) comparisons. The findings include atrophy or degeneration of the seminiferous tubules, decreased sperm count and motility, and decreased testosterone levels in the serum and testes. There was no effect on testes weight in studies of oral doses of up to 500 mg/kg/day in mice and 700 mg/kg/day in rats (approximately 1.2 and 3.5 times the MRHD respectively based on BSA comparisons). In a published study in 5 men receiving 600 mg of quinine TID for one week, sperm motility was decreased and percent sperm with abnormal morphology was increased; sperm count and serum testosterone were unaffected.

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are extensive published data but few well-controlled studies of QUALAQUIN in pregnant women. Published data on over 1,000 pregnancy exposures to quinine did not show an increase in teratogenic effects over the background rate in the general population; however, the majority of these exposures were not in the first trimester. In developmental and reproductive toxicity studies, central nervous system (CNS) and ear abnormalities and increased fetal deaths occurred in some species when pregnant animals received quinine at doses about 1 to 4 times the human clinical dose. Quinine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

P. falciparum malaria carries a higher risk of morbidity and mortality in pregnant women than in the general population. Pregnant women with P. falciparum malaria have an increased incidence of fetal loss (including spontaneous abortion and stillbirth), preterm labor and delivery, intrauterine growth retardation, low birth weight, and maternal death. Therefore, treatment of malaria in pregnancy is important.

Hypoglycemia, due to increased pancreatic secretion of insulin, has been associated with quinine use, particularly in pregnant women.

Quinine crosses the placenta with measurable blood concentrations in the fetus. In 8 women who delivered live infants 1 to 6 days after starting quinine therapy, umbilical cord plasma quinine concentrations were between 1.0 and 4.6 mg/L (mean 2.4 mg/L) and the mean (±SD) ratio of cord plasma to maternal plasma quinine concentrations was 0.32 ± 0.14. Quinine levels in the fetus may not be therapeutic. If congenital malaria is suspected after delivery, the infant should be evaluated and treated appropriately.

A study from Thailand (1999) of women with P. falciparum malaria who were treated with oral quinine sulfate 10 mg/kg 3 times daily for 7 days at anytime in pregnancy reported no significant difference in the rate of stillbirths at > 28 weeks of gestation in women treated with quinine (10 of 633 women [1.6%]) as compared with a control group without malaria or exposure to antimalarial drugs during pregnancy (40 of 2201 women [1.8%]). The overall rate of congenital malformations (9 of 633 offspring [1.4%]) was not different for women who were treated with quinine sulfate compared with the control group (38 of 2201 offspring [1.7%]). The spontaneous abortion rate was higher in the control group (10.9%) than in women treated with quinine sulfate (3.5%) [OR = 3.1; 95% CI 2.1-4.7]. An epidemiologic survey that included 104 mother-child pairs exposed to quinine during the first 4 months of pregnancy, found no increased risk of structural birth defects was seen (2 fetal malformations [1.9%]). Rare and isolated case reports describe deafness and optic nerve hypoplasia in children exposed in utero due to maternal ingestion of high doses of quinine.

In animal developmental studies conducted in multiple animal species, pregnant animals received quinine by the subcutaneous or intramuscular route at dose levels similar to the maximum recommended human dose (MRHD; 32 mg/kg/day) based on body surface area (BSA) comparisons. There were increases in fetal death in utero in rabbits at maternal doses ≥ 100 mg/kg/day and in dogs at ≥ 15 mg/kg/day corresponding to dose levels approximately 0.5 and 0.25 times the MRHD respectively based on BSA comparisons. Rabbit offspring had increased rates of degenerated auditory nerve and spiral ganglion and increased rates of CNS anomalies such as anencephaly and microcephaly at a dose of 130 mg/kg/day corresponding to a maternal dose approximately 1.3 times the MRHD based on BSA comparison. Guinea pig offspring had increased rates of hemorrhage and mitochondrial change in the cochlea at maternal doses of 200 mg/kg corresponding to a dose level of approximately 1.4 times the MRHD based on BSA comparison. There were no teratogenic findings in rats at maternal doses up to 300 mg/kg/day and in monkeys at doses up to 200 mg/kg/day corresponding to doses approximately 1 and 2 times the MRHD respectively based on BSA comparisons.

In a pre-postnatal study in rats, an estimated oral dose of quinine sulfate of 20 mg/kg/day corresponding to approximately 0.1 times the MRHD based on BSA comparison resulted in offspring with impaired growth, lower body weights at birth and during the lactation period, and delayed physical development of teeth eruption and eye opening during the lactation period.

Labor And Delivery

There is no evidence that quinine causes uterine contractions at the doses recommended for the treatment of malaria. In doses several-times higher than those used to treat malaria, quinine may stimulate the pregnant uterus.

Nursing Mothers

There is limited information on the safety of quinine in breastfed infants. No toxicity was reported in infants in a single study where oral quinine sulfate (10 mg/kg every 8 hours for 1 to 10 days) was administered to 25 lactating women. It is estimated from this study that breastfed infants would receive less than 2 to 3 mg per day of quinine base ( < 0.4% of the maternal dose) via breast milk.

Although quinine is generally considered compatible with breastfeeding, the risks and benefits to infant and mother should be assessed. Caution should be exercised when administered to a nursing woman.

If malaria is suspected in the infant, appropriate evaluation and treatment should be provided. Plasma quinine levels may not be therapeutic in infants of nursing mothers receiving QUALAQUIN.

Pediatric Use

The safety and efficacy of QUALAQUIN in pediatric patients under the age of 16 has not been established.

Geriatric Use

Clinical studies of quinine sulfate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond to treatment differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Renal Impairment

Clearance of quinine is decreased in patients with severe chronic renal failure. The dosage and dosing frequency should be reduced.

Hepatic Impairment

In patients with severe hepatic impairment (Child-Pugh C), quinine oral clearance (CL/F) is decreased, volume of distribution (Vd/F) is increased, and half-life is prolonged, relative to subjects with normal liver function. Therefore, quinine is not indicated in patients with severe hepatic impairment and alternate therapy should be administered.

Close monitoring is recommended for patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment, as exposure to quinine may be increased relative to subjects with normal liver function.

Регистрационный номер:

ЛСР-001809/08

Торговое название препарата: Литэн Н

Международное непатентованное название (МНН): Лизиноприл +Гидрохлортиазид, 10мг+12,5 мг и 20 мг+12,5мг

Лекарственная форма:

таблетки

Состав:

Литэн Н 10 мг+12,5мг

Активные вещества: лизиноприла дигидрат 10,888 мг (соответственно лизиноприла10 мг) и гидрохлортиазида 12,5 мг
Вспомогательные вещества: кальция гидрофосфата дигидрат, маннитол, крахмал кукурузный, крахмал прежелатизированный, магния стеарат, тальк, кремния диоксида коллоидного безводного, железа оксид желтый C.I.77492,Е172
Литэн Н 20 мг+12,5 мг

Активные вещества: лизиноприла дигидрат 21,776 мг (соответственно лизиноприла 20 мг) и гидрохлортиазида 12,5 мг
Вспомогательные вещества: кальция гидрофосфата дигидрат, маннитол, крахмал кукурузный, крахмал прежелатизированный, магния стеарат, тальк, кремния диоксида коллоидного безводного, железа оксид желтый C.I.77492,Е172, железо оксид красный C.I.77491,Е172

Описание

Таблетки 10 мг+12,5мг

От светло-желтого до желтого цвета, шестиугольные таблетки с гладкой поверхностью, цельными краями и риской посередине.
Таблетки 20 мг+12,5мг

От бледно-розового до розового цвета шестиугольные таблетки с гладкой поверхностью и цельными краями и риской посередине.

Фармакотерапевтическая группа:

гипотензивное комбинированное средство (АПФ ингибитор + диуретик).

Код АТХ: С09ВА03

Фармакологическое действие

Фармакодинамика

Литэн Н — это комбинация ингибитора ангиотензин-превращающего фермента (лизиноприл) и диуретика (гидрохлортиазид). Обладает антигипертензивным и диуретическим действием.
Лизиноприл. Ингибитор АПФ, уменьшает образование ангиотензина II из ангиотензина I. Снижение содержание ангиотензина II ведет к прямому уменьшению выделения альдостерона. Уменьшает деградацию брадикинина и увеличивает синтез простагландина. Снижает общее периферическое сосудистое сопротивление, артериальное давление (АД), преднагрузку, давление легочных каппиллярах, вызывает увеличение минутного объема крови и повышение толерантности к нагрузкам у больных с сердечной недостаточностью. Расширяет артерии в большей степени, чем вены. Некоторые эффекты объясняются воздействием на тканевые ренин-ангиотензиновые системы. При длительном применении уменьшается гипертрофия миокарда и стенок артерий резистивного типа. Улучшает кровоснабжение ишемизированного миокарда. Ингибиторы АПФ удлиняют продолжительность жизни у больных хронической сердечной недостаточностью, замедляют прогрессирование дисфункции левого желудочка у больных, перенесших инфаркт миокарда без клинических проявлений сердечной недостаточности. Начало действия через 1 час, максимальный эффект определяется через 6 часов, длительность – 24 часа. При артериальной гипертензии эффект отмечается в первые дни после начала лечения, стабильное действие развивается через 1-2 месяца.
Гидрохлортиазид Тиазидный диуретик, диуретический эффект которого связан с нарушением реабсорбции ионов натрия, хлора, калия, магния, воды в дистальном отделе нефрона; задерживает выведение ионов кальция, мочевой кислоты. Обладает антигипертензивными свойствами; гипотензивное действие развивается за счет расширения артериол. Практически не оказывает влияние на нормальное артериальное давление. Диуретический эффект наступает через 1-2 часа, достигает максимума через 4 часа и продолжается 6-12 часов. Антигипертензивное действие наступает через 3-4 дня, но для достижения оптимального терапевтического эффекта может потребоваться 3-4 недели.
Лизиноприл и гидрохлортиазид, если применяются одновременно, оказывают аддитивный антигипертензивный эффект.

Показания к применению

• артериальная гипертензия (у больных, которым показана комбинированная терапия).

Противопоказания

Повышенная чувствительность к препарату, другим ингибиторам АПФ и производным сульфониламидов, анурия, выраженная почечная недостаточность (клиренс креатинина менее 30 мл/мин.), ангионевротический отек (в том числе и в анамнезе от применения ингибиторов АПФ), гемодиализ с использованием высокопроточных мембран, гиперкальциемия, гипонатриемия, порфирия, прекома, печеночная кома, сахарный диабет (тяжелые формы), беременность, период лактации, возраст до 18 лет (эффективность и безопасность не установлены).

С осторожностью: аортальный стеноз/гипертрофическая кардиомиопатия, двусторонний стеноз почечных артерий, стеноз артерии единственной почки с прогрессирующей азотемией, состояние после трансплантации почек, почечная недостаточность (клиренс креатинина менее 30 мл/мин.), первичный гиперальдостеронизм, артериальная гипотензия, гипоплазия костного мозга, гипонатриемия (повышенный риск развития артериальной гипотензии у пациентов, находящихся на малосолевой или бессолевой диете), состояния, сопровождающиеся снижением объема циркулирующей крови (в том числе диарея, рвота), заболевания соединительной ткани (системная красная волчанка, склеродермия), сахарный диабет, подагра, гиперурикемия, гиперкалиемия, ишемическая болезнь сердца, цереброваскулярная недостаточность, тяжелая хроническая сердечная недостаточность, печеночная недостаточность, пожилой возраст.

Способ применения и дозы

Принимать внутрь, один раз в сутки.
Артериальная гипертензия

По 1 таблетке Литэна Н 10 мг 1 раз в сутки. При необходимости дозу можно увеличить до Литэна Н 20 мг 1 раз в сутки.
Дозы при почечной недостаточности

У больных с клиренсом креатинина более 30 мл/мин и менее 80 мл/мин., препарат можно применять только после титрования дозы отдельных компонентов препарата. Рекомендованная начальная доза лизиноприла при не осложненной почечной недостаточности составляет 5-10 мг.
Предшествующая терапия диуретиками

Симптоматическая гипотензия может возникать после приема начальной дозы препарата. Такие случаи встречаются чаще у больных, у которых была потеря жидкости и электролитов вследствие предшествовавшего лечения диуретиками. Поэтому надо прекратить прием диуретиков за 2-3 дня до начала лечения Литэном Н (см. Особые указания).

Побочное действие

У большинства пациентов побочные явления были легкими и преходящими. Самыми частыми были: головокружение, головная боль.
Побочные явления, которые встречались реже:
Со стороны сердечно-сосудистой системы: выраженное снижение артериального давления, боль в груди, редко – ортостатическая гипотензия, тахикардия, брадикардия, появление симптомов сердечной недостаточности, нарушение атриовентрикулярной проводимости, инфаркт миокарда.
Со стороны пищеварительного тракта: тошнота, рвота, боли в животе, сухость во рту, диарея, диспепсия, анорексия, изменение вкуса, панкреатит, гепатит (гепатоцеллюлярный и холестатический), желтуха.
Со стороны нервной системы: лабильность настроения, нарушение концентрации внимания, парестезии, повышенная утомляемость, сонливость, судорожные подергивания мышц конечностей и губ, редко – астенический синдром, спутанность сознания.
Со стороны дыхательной системы – диспноэ, бронхоспазм, апноэ.
Со стороны кожных покровов – крапивница, потливость, выпадение волос, фотосенсибилизация.
Аллергические реакции: ангионевротический отек лица, конечностей, губ, языка, надгортанника и/или гортани (см. «Особые указания»), кожные высыпания, зуд, лихорадка, васкулит, положительные результаты на антинуклеарные антитела, повышение СОЭ, эозинофилия.
Со стороны органов кроветворения: лейкопения, тромбоцитопения, нейтропения, агранулоцитоз, анемия (снижение содержания гемоглобина, гематокрита, эритроцитопения).
Со стороны мочеполовой системы – уремия, олигурия/анурия, нарушение функции почек, острая почечная недостаточность, снижение потенции.
Лабораторные показатели: гиперкалиемия и/или гипокалиемия, гипонатриемия, гипомагниемия, гипохлоремия, гиперурикемия, гипергликемия, повышение уровня мочевины и креатинина, редко – повышение активности «печеночных» трансаминаз, гипербилибинемия, гиперхолестеринемия, гипертриглицеридемия, снижение толерантности к глюкозе.
Прочие: сухой кашель, артралгия/артрит, миалгия, нарушение развития почек плода, обострение подагры.

Передозировка

Симптомы: выраженное снижение АД.
Лечение: вызвать рвоту и/или промыть желудок, симптоматическая терапия, направленная на коррекцию дегидратации и нарушений водно-солевого баланса. При артериальной гипотензии вводить изотонический раствор. Контроль мочевины, креатинина и электролитов в сыворотке крови, а также диуреза.

Взаимодействие с другими лекарственными средствами

При одновременном применении:
с калийсберегающими диуретиками (спиронолактон, триамтерен, амилорид), препаратами калия, заменителями соли, содержащими калий – повышается риск развития гиперкалиемии, особенно у больных с нарушенной функцией почек;
с вазодилататорами, барбитуратами, фенотиазинами, трициклическими антидепрессантами, этанолом – усиление гипотензивного действия;
с нестероидными противовоспалительными препаратами (индометацин и др.), эстрогенами – снижение антигипертензивного действия лизиноприла;
с препаратами лития – замедление выведения лития из организма (усиление кардиотоксического и нейротоксического действия лития);
с антацидами и колестрамином — снижение всавывания в желудочно-кишечном тракте.
Усиливает нейротоксичность салицилатов, ослабляет действие пероральных гипогликемических средств, норэпинефрина, эпинефрина и противоподагрических средств, усиливает эффекты (включая побочные) сердечных гликозидов, действие периферических миорелаксантов, уменьшает выведение хинидина.
Уменьшает эффект пероральных контрацептивов.

Особые указания

Симптоматическая гипотензия

Чаще всего выраженное АД возникает при снижении объема циркулирующей крови, вызванной терапией диуретиками, уменьшением количества соли в пище, диализом, диареей или рвотой (см. «Взаимодействие с другими лекарственными средствами» и «Побочное действие»). У больных хронической сердечной недостаточностью с одновременной почечной недостаточностью или без нее, возможно развитие, симптоматической гипотензии. Она чаще выявляется у больных с тяжелыми формами сердечной недостаточности, как следствие применения больших доз диуретиков, гипонатриемии или нарушенной функции почек. У таких больных лечение надо начать под строгим контролем врача. Подобных правил надо придерживаться при назначении больным ишемической болезнью сердца, цереброваскулярной недостаточностью, у которых резкое снижение АД может привести к инфаркту миокарда или инсульту.
Транзиторная гипотензивная реакция не является противопоказанием для приема следующей дозы препарата.
Нарушение функции почек

У больных хронической сердечной недостаточностью, выраженное снижение АД после начала лечения ингибиторами АПФ может привести к дальнейшему ухудшению почечной функции.
Отмечены случаи острой почечной недостаточности.
У больных с двусторонним стенозом почечных артерий или стенозом артерии единственной почки, получавших АПФ ингибиторы, отмечалось повышение мочевины и креатинина в сыворотке крови, обычно обратимое после прекращения лечения. Чаще встречалось у больных почечной недостаточностью.
Повышенная чувствительность/Ангионевротический отек

Ангионевротический отек лица, конечностей, губ, языка, надгортанника и/или гортани отмечался редко у больных, лечившихся АПФ ингибиторами, включая лизиноприл, который может возникнуть в любой период лечения. В таком случае лечение лизиноприлом необходимо как можно скорее прекратить и за больным установить наблюдение до полной регрессии симптомов. В случаях, когда отек возник только на лице и губах, состояние чаще всего проходит без лечения, однако, возможно назначение антигистаминных препаратов.
Антиневротическй отек с отеком гортани может быть фатальным. Когда охвачены язык, надгортанник или гортань может произойти обструкция дыхательных путей, поэтому надо немедленно проводить соответствующую терапию (0,3-0,5 мл раствор эпинефрина (адреналина) 1:1000 подкожно) и/или меры по обеспечению проходимости дыхательных путей.
У больных, у которых в анамнезе уже был ангионевротический отек не связанный с предыдущим лечением ингибиторами АПФ, может быть повышен риск его развития во время лечения ингибитором АПФ (см. «Противопоказания»).
Кашель

При применении ингибитора АПФ отмечался кашель. Кашель сухой, длительный, который исчезает после прекращения лечения ингибитором АПФ. При дифференциальном диагнозе кашля, надо учитывать и кашель, вызванный применением ингибитора АПФ.
Больные, находящиеся на диализе

Анафилактическая реакция отмечена и у больных, подвергнутых гемодиализу с использованием диализных мембран с высокой проницаемостью, которые одновременно принимают ингибиторы АПФ. В таких случаях надо рассмотреть возможность применения другого типа мембраны для диализа или другого ангипертензивного средства.
Хирургия/Общая анестезия

При применении средств, снижающих АД, у больных при обширном хирургическом вмешательстве или во время общей анестезии, лизиноприл может блокировать образование ангиотензина II.
Выраженное снижение АД которое считают следствием этого механизма, можно устранить увеличением объема циркулирующей крови.
Перед хирургическим вмешательством (включая стоматологию) необходимо предупредить хирурга/анестезиолога о применении ингибиторов АПФ.
Калий в сыворотке

В некоторых случаях отмечалась гиперкалиемия.
Факторы риска для развития гиперкалиемии включают почечную недостаточность, сахарный диабет, прием препаратов калия или препаратов, вызывающих увеличение концентрации калия в крови (например, гепарин), особенно у больных с нарушением функцией почек.
У больных, у которых существует риск симптоматической гипотензии (находящихся на малосолевой или бессолевой диете) с или без гипонатриемии, а также у пациентов, которые получали высокие дозы диуретиков, вышеназванные состояния перед началом лечения необходимо скомпенсировать (потерю жидкости и солей).
Метаболические и эндокринные эффекты

Тиазидные диуретики могут влиять на толерантность к глюкозе, поэтому необходимо корректировать дозы противодиабетических лекарственных средств.
Тиазидные диуретики могут снижать выделения кальция с мочой и вызывать гиперкальциемию. Выраженная гиперкальциемия может быть симптомом скрытого гиперпаратиреоза, рекомендуется прекратить лечение тиазидными диуретиками до проведения теста по оценке функции паращитовидных желез.
В период лечения препаратом Литэн Н необходим регулярный контроль в плазме крови калия, глюкозы, мочевины, жиров и креатинина.
В период лечения не рекомендуется употреблять алкогольные напитки, так как алкоголь усиливает гипотензивное действие препарата.
Следует соблюдать осторожность при выполнении физических упражнений, жаркой погоде (риск развития дегидратации и чрезмерного снижения АД из-за снижения объема циркулирующей крови).

Влияние на способность управления транспортными средствами и механизмами

В период лечения следует воздержаться от вождения автотранспорта и занятий потенциально опасными видами деятельности, требующими повышенной концентрации внимания и быстроты психомоторных реакций, так как возможно головокружение, особенно в начале курса лечения.

Форма выпуска

Таблетки по 10мг + 12,5мг и 20мг + 12,5 мг
По 10 таблеток в блистер из ПВХ/алюминиевой фольги. По 2 или 3 блистера вместе с инструкцией по применению в картонной пачке.

Условия хранения

Хранить в сухом месте при температуре не выше 30°С. Хранить в недоступном для детей месте.
Срок годности 2 года.
Не использовать по истечении срока годности, указанного на упаковке.

Условия отпуска из аптек:

По рецепту

Производитель:

АО «Босналек», Сараево, ул. Юкичева 53, Босния и Герцеговина

Представительство в РФ:

117292, Москва, ул. Вавилова, дом 85, офис 3.

Форма выпуска, упаковка и состав
препарата Лимонтар^®

Limptar N

Limptar N is a cinchona alkaloid and a 4-methanolquinoline. It rapidly acts on blood schizontocide by interfering with lysosomal function or nucleic acid synthesis in the Plasmodia spp. It has no activity against exoerythrocytic forms.

Limptar N is used parenterally to treat life-threatening infections caused by chloroquine-resistant Plasmodium falciparum malaria. Limptar N acts as a blood schizonticide although it also has gametocytocidal activity against P. vivax and P. malariae. Because it is a weak base, it is concentrated in the food vacuoles of P. falciparum. It is thought to act by inhibiting heme polymerase, thereby allowing accumulation of its cytotoxic substrate, heme. As a schizonticidal drug, it is less effective and more toxic than chloroquine. However, it has a special place in the management of severe falciparum malaria in areas with known resistance to chloroquine.

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Uses

Limptar N Sulfate, is an antimalarial drug used only for treatment of uncomplicated Plasmodium falciparum malaria. Limptar N sulfate has been shown to be effective in geographical regions where resistance to chloroquine has been documented 

Limptar N Sulfate oral capsules are not approved for:

• Treatment of severe or complicated P. falciparum malaria.
• Prevention of malaria.
• Treatment or prevention of nocturnal leg cramps

Limptar N Dihydrochloride is used for the acute treatment of malaria. It may also be used in the treatment of Babesiosis in conjunction with clindamycin.

Limptar N is also used to associated treatment for these conditions: Malaria caused by Plasmodium falciparum

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How Limptar N works

The theorized mechanism of action for quinine and related anti-malarial drugs is that these drugs are toxic to the malaria parasite. Specifically, the drugs interfere with the parasite’s ability to break down and digest hemoglobin. Consequently, the parasite starves and/or builds up toxic levels of partially degraded hemoglobin in itself.

Limptar N

Trade Name	Limptar N
Availability	Prescription only
Generic	Quinine
Quinine Other Names	(8S,9R)-quinine, 6′-Methoxycinchonidine, Chinin, Chinine, Chininum, Quinina, Quinine
Related Drugs	doxycycline, clindamycin, hydroxychloroquine, Plaquenil, Cleocin
Type
Formula	C20H24N2O2
Weight	Average: 324.4168 Monoisotopic: 324.183778022
Protein binding	Approximately 70%
Groups	Approved
Therapeutic Class	Anti-malarial drugs
Manufacturer
Available Country	Germany
Last Updated:	June 22, 2022 at 11:59 pm

Structure

Table Of contents

• Limptar N
• Uses
• Dosage
• Side Effect
• Precautions
• Interactions
• Uses during Pregnancy
• Uses during Breastfeeding
• Accute Overdose
• Food Interaction
• Half Life
• Volume of Distribution
• Clearance
• Interaction With other Medicine
• Contradiction
• Storage

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Dosage

Limptar N dosage

Intravenous:

• Adult: Initially, 20 mg/kg to max 1.4 g over 4 hr with maintenance infusion started after 8 hr. Maintenance infusions: 10 mg/kg to max 700 mg over 4 hr 8 hrly. Loading dose should not be given if patient has received quinine, quinidine, halofantrine or mefloquine during the previous 24 hr.
• Child: ≤5 mg/kg/hr by slow IV infusion.

Oral:

• Adult: 648 mg given every 8 hr for 7 days.
• Child: ≥8 yr 10 mg/kg 8 hrly for 7 days.

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Should be taken with food. Take with food to minimise GI discomfort.

Reconstitutions

Dilute in NaCl 0.9% to a concentration of diHCl 60-100 mg/mL.

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Side Effects

Headache, nausea, disturbed vision, impaired hearing, tinnitus, abdominal pain, vomiting, diarrhoea, vertigo; flushing skin with intense pruritus, urticaria; fever, dyspnoea, agranulocytosis, palpitations, rashes; myalgia, muscle weakness, asthma, asthenia, disorientation, angioedema; haemoglobinuria; hypoprothrombinaemia, hypoglycaemia, hypotension, renal failure.

Toxicity

Limptar N is a documented causative agent of drug induced thrombocytopenia (DIT). Thrombocytopenia is a low amount of platelets in the blood. Limptar N induces production of antibodies against glycoprotein (GP) Ib-IX complex in the majority of cases of DIT, or more rarely, the platelet-glycoprotein complex GPIIb-IIIa. Increased antibodies against these complexes increases platelet clearance, leading to the observed thrombocytopenia.

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Precaution

Patients with cardiac conduction defects, heart block or AF. Pregnancy and lactation.

Interaction

Reduced renal clearance of amantadine. Reduced clearance with cimetidine. Increased anticoagulant effect of warfarin and other anticoagulants. Reduced plasma levels of ciclosporin. Increased plasma levels of digoxin. Increased risk of myopathy and rhabdomyolysis with atorvastatin. May enhance hypoglycaemic effects of oral antidiabetics.

Food Interaction

• Take with food. Food reduces irritation.

[Minor] Coadministration with grapefruit juice does not appear to affect the pharmacokinetics of quinine in a clinically relevant manner.

Although grapefruit juice is an inhibitor of CYP450 3A4 and quinine is metabolized by this pathway to its major metabolite, 3-hydroxyquinine, a study of ten healthy volunteers found no significant differences in quinine peak plasma concentration (Cmax), time to reach Cmax (Tmax), terminal elimination half-life, systemic exposure (AUC), or apparent oral clearance (Cl

Relative to the control period, the apparent renal clearance of quinine was markedly increased by 81% during treatment with half-strength grapefruit juice.

However, since renal clearance accounts for approximately 6% of the total clearance of quinine, this change would likely have minimal clinical impact.

The lack of a significant interaction is probably due to the fact that grapefruit juice primarily inhibits intestinal rather than hepatic CYP450 3A4, and quinine is not known to undergo significant presystemic metabolism as evidenced by its relatively high oral bioavailability (76% to 88%).

Nevertheless, excessive consumption of grapefruit juice and tonic water (which contains quinine) was suspected as the cause of torsade de pointes arrhythmia in a patient with a history of asymptomatic long QT syndrome.

Treatment with magnesium sulfate and metoprolol had no effect, but the arrhythmia resolved spontaneously 48 hours after discontinuation of the drinks.

Based on current data, moderate grapefruit juice consumption is probably safe for the majority of patients taking quinine.

Limptar N Drug Interaction

Moderate: fluticasone / salmeterol, duloxetine, budesonide / formoterol

Unknown: aspirin, diphenhydramine, calcium / vitamin d, celecoxib, rosuvastatin, omega-3 polyunsaturated fatty acids, fluticasone nasal, atorvastatin, pregabalin, esomeprazole, acetaminophen, levothyroxine, acetaminophen, cyanocobalamin, ascorbic acid, cholecalciferol, cetirizine

Limptar N Disease Interaction

Major: QT prolongation, G-6-PD deficiency, myasthenia gravis, ocular toxicity, thrombocytopenia, tinnitus

Moderate: liver impairment, renal impairment

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Volume of Distribution

• 1.43 ± 0.18 L/kg [Healthy Pediatric Controls]
• 0.87 ± 0.12 L/kg [P. falciparum Malaria Pediatric Patients]
• 2.5 to 7.1 L/kg [healthy subjects who received a single oral 600 mg dose]

Elimination Route

76 — 88%

Half Life

Approximately 18 hours

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Clearance

• 0.17 L/h/kg [healthy]
• 0.09 L/h/kg [patients with uncomplicated malaria]
• 18.4 L/h [healthy adult subjects with administration of multiple-dose activated charcoal]
• 11.8 L/h [healthy adult subjects without administration of multiple-dose activated charcoal]
• Oral cl=0.06 L/h/kg [elderly subjects]

Elimination Route

Limptar N is eliminated primarily via hepatic biotransformation. Approximately 20% of quinine is excreted unchanged in urine.

Pregnancy & Breastfeeding use

Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

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Contraindication

Hypersensitivity to quinine, mefloquine or quinidine. Patients with nocturnal leg cramps; prolonged QT interval, tinnitus or optic neuritis, myasthenia gravis, G6PD deficiency, haemolysis and who had suffered from blackwater fever. Concomitant use with ritonavir, mefloquine, rifampicin, class IA and class III antiarrhythmic agents, neuromuscular blocking agents, other drugs known to cause QT prolongation, and Al- and/or Mg-containing antacids.

Special Warning

Renal Impairment:

• Oral:Severe: Initially, 648 mg followed after 12 hr by maintenance doses of 324 mg 12 hrly.
• Intravenous: Severe: Reduce maintenance dose to 5-7 mg/kg of quinine salt 8 hrly.

Hepatic Impairment:

• Mild to moderate: No dosage adjustment needed.
• Intravenous: Severe: Reduce maintenance dose to 5-7 mg/kg of quinine salt 8 hrly.

Acute Overdose

Symptoms: GI effects, CNS disturbances, oculotoxicity, cardiotoxicity,; tinnitus, abdominal pain, diarrhoea, vertigo, pulmonary oedema, hypotension, sweating, flushing, nausea, vomiting, headache, slightly disturbed vision, deafness, vasodilatation and adult resp distress syndrome.

Management: Administer multiple dose of activated charcoal within 1 hr or perform gastric lavage. Symptomatic (e.g. maintaining BP, respiration and renal function, treating arrhythmias) and supportive treatment.

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Storage Condition

Store between 20-25° C. Protect from light.

Innovators Monograph

You find simplified version here Limptar N

FAQ

What is Limptar N used for?

Limptar N is used to treat malaria caused by Plasmodium falciparum. Plasmodium falciparum is a parasite that gets into the red blood cells in the body and causes malaria.

How safe is Limptar N?

Experts consider Limptar N safe to consume in small doses.The FDA also specify that manufacturers must place Limptar N on the label for consumers to easily see.

How does Limptar N work?

Limptar N works by killing the parasite or preventing it from growing.

What are the common side effects of Limptar N?

Common side effects of Limptar N are include:

• nausea.
• restlessness.
• difficulty hearing or ringing in the ears.
• confusion.
• nervousness.

Is Limptar N safe during pregnancy?

You should not avoid taking Limptar N  because you are pregnant. The risk of harm to you and your baby from malaria is likely to be far greater than any possible risk from taking quinine. There is no convincing scientific evidence that Limptar N is harmful to an unborn baby.

Is Limptar N safe during breastfeeding?

Because of the low levels of Limptar N in breastmilk, amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants. The dosage in milk is far below those required to treat an infant for malaria.

Can I drive after taking Limptar N?

Limptar N may cause blurred vision and may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert and able to see clearly. Do not use to treat any condition that has not been checked by your doctor.

When should be best taken of Limptar N?

Limptar N usually is taken with food three times a day (every 8 hours) for 3 to 7 days. Take Limptar N at around the same times every day.

How much Limptar N can I take daily?

Adults and children 16 years of age and older 648 milligrams (mg) (2 capsules) every 8 hours for 7 days. Children younger than 16 years of age Use and dose must be determined by your doctor.

How long does it take for Limptar N tablets to work?

A reduction in frequency of leg cramps may take up to 4 weeks to become apparent. Patients should be monitored closely during the early stages of treatment for adverse effects. After an initial trial of 4 weeks, treatment should be stopped if there is no benefit.

How long until Limptar N is out of my system?

The limit of sensitivity for quinine in urine, utilizing TLC, is approximately 0.2mg/mL. Laboratory experience indicates that Limptar N may be detected as long as 4 to 5 days after intake.

Can I take Limptar N for a long time?

Long-term off-label use of Limptar N, still prescribed to individuals with muscle cramps despite Food and Drug Administration warnings of adverse events, is associated with an increased risk of death.

When should I stop taking Limptar N?

Stop taking Limptar N and call your doctor at once if you have headache with chest pain and severe dizziness, fast or pounding heartbeats, unusual bruising or bleeding, signs of infection, severe lower back pain, or blood in your urine.

Is Limptar N bad for liver?

The hepatotoxicity of Limptar N is usually mild and resolves within 1 to 4 weeks of stopping. In many instances, jaundice and liver test abnormalities may worsen for a few days after stopping Limptar N, but fatalities have not been reported, and recovery is usually rapid.

Can I just stop taking Limptar N?

After an initial trial of 4 weeks, treatment should be stopped if there is no benefit. Treatment should be interrupted approximately every 3 months to reassess the benefit. In patients taking Limptar N long term, a trial discontinuation may be considered.

How often can I take Limptar N ?

Adults and children aged 12 years and over, 600mg every eight hours for 7 days.

Does Limptar N raise blood pressure?

This tea has been used in folk medicine to treat a variety of problems, and scientists have confirmed that it lowers blood pressure as well as cholesterol.

How does Limptar N work in the body?

brank works by killing the parasite or preventing it from growing.

Is Limptar N bad for heart?

Limptar N can cause serious side effects on your heart, kidneys, or blood cells.

Does Limptar N make me sleepy?

Limptar N may cause hypoglycemia.

What happens if I miss a dose of Limptar N?

Take the Limptar N of dose as soon as you remember. If you are more than 4 hours late for your dose, skip the missed dose and take the medicine at your next scheduled dose time. Do not take extra medicine to make up the missed dose.

Who should not take Limptar N?

You should not take Limptar N if you have a heart rhythm disorder called Long QT syndrome, a genetic enzyme deficiency called glucose-6-phosphate dehydrogenase deficiency, myasthenia gravis, optic neuritis (inflammation of the nerves in your eyes), if you have taken Limptar N in the past and it caused a blood cell disorder or severe bleeding.

What happen if I overdose on Limptar N?

Symptoms of overdose may include are sudden vision change, confusion, severe trouble hearing, fast/irregular heartbeat, fainting, slow/shallow breathing, seizures, inability to wake up (coma).