European Union - English - EMA (European Medicines Agency)

eigerbio europe limited - lonafarnib - progeria; laminopathies - other alimentary tract and metabolism products, - zokinvy is indicated for the treatment of patients 12 months of age and older with a genetically confirmed diagnosis of hutchinson-gilford progeria syndrome or a processing-deficient progeroid laminopathy associated with either a heterozygous lmna mutation with progerin-like protein accumulation or a homozygous or compound heterozygous zmpste24 mutation.

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

eiger biopharmaceuticals, inc. - lonafarnib (unii: iow153004f) (lonafarnib - unii:iow153004f) - zokinvy is indicated in patients 12 months of age and older with a body surface area (bsa) of 0.39 m2 and above: - to reduce the risk of mortality in hutchinson-gilford progeria syndrome (hgps) - for the treatment of processing-deficient progeroid laminopathies with either: heterozygous lmna mutation with progerin-like protein accumulation homozygous or compound heterozygous zmpste24 mutations - heterozygous lmna mutation with progerin-like protein accumulation - homozygous or compound heterozygous zmpste24 mutations limitations of use zokinvy is not indicated for other progeroid syndromes or processing-proficient progeroid laminopathies. based upon its mechanism of action, zokinvy would not be expected to be effective in these populations. zokinvy is contraindicated in patients taking: - strong cyp3a inhibitors [see drug interactions (7.1)] - strong or moderate cyp3a inducers [see drug interactions (7.1)] - midazolam [see drug interactions (7.2)] - lovastatin, simvastatin, or atorvastatin [see drug interactions (7.2)] risk summary based on findings from animal studies, zokinvy can cause embryofetal harm when administered to a pregnant woman. there are no human data on zokinvy use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. advise pregnant women of the risk to a fetus. in animal reproduction studies, oral administration of lonafarnib to pregnant rats during organogenesis produced embryo-fetal toxicity at exposures that were 1.2-times the human exposure at the recommended dose of 150 mg/m2 twice daily. in pregnant rabbits, oral administration of lonafarnib during organogenesis produced skeletal malformations and variations at exposures lower than the human exposure at 150 mg/m2 twice daily, and maternal toxicity at 26 times the human exposure at 150 mg/m2 twice daily (see data) . the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data animal data in an embryo-fetal development study in rats, oral administration of lonafarnib during organogenesis produced an increase in post-implantation loss (resorptions) and decreases in fetal body weight and number of live fetuses at 30 mg/kg/day (1.2 times the auc [area under the plasma concentration-time curve] in humans at the recommended dose of 150 mg/m2 twice daily). no effects on embryo-fetal development in rats were observed at systemic exposures lower than the human auc at 150 mg/m2 twice daily. in rabbits, oral administration of lonafarnib during organogenesis resulted in skeletal malformations and variations at systemic exposures lower than the human auc at the recommended dose of 150 mg/m2 twice daily, and maternal toxicity (body weight loss and abortion) at 120 mg/kg/day (26 times the human auc at 150 mg/m2 twice daily). no effects in offspring were observed in a pre- and postnatal development study in rats with maternal administration of up to 20 mg/kg/day orally (auc lower than the human auc at 150 mg/m2 twice daily) during organogenesis through lactation. risk summary there are no data on the presence of zokinvy in human milk, the effects on the breastfed infant, or the effects on milk production. lonafarnib is excreted in rat milk (see data) . when a drug is present in animal milk, it is likely that the drug will be present in human milk. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for zokinvy and any potential adverse effects of the breastfed infant from zokinvy or from the underlying maternal condition. data lonafarnib is excreted in milk following oral administration in lactating rats, with a mean milk to plasma concentration ratio of 1.5 at 12 hours. contraception zokinvy can cause embryo-fetal harm when administered to pregnant women [see use in specific populations (8.1)] . advise females of reproductive potential to use appropriate effective contraception during treatment with zokinvy. infertility based on findings in rats, zokinvy may reduce fertility in females and males of reproductive potential [see warnings and precautions (5.6), nonclinical toxicology (13.1)] . the safety and effectiveness of zokinvy for the treatment of hgps and processing-deficient progeroid laminopathies (with either heterozygous lmna mutation with progerin-like protein accumulation or homozygous or compound heterozygous zmpste24 mutations) have been established in pediatric patients 12 months of age and older. use of zokinvy for these indications is supported by adequate and well-controlled studies in pediatric patients 2 years of age and older [see clinical studies (14)] . the safety and effectiveness of zokinvy in pediatric patients less than 12 months of age have not been established. the safety and effectiveness of zokinvy for the treatment of hgps and processing-deficient progeroid laminopathies (with either heterozygous lmna mutation with progerin-like protein accumulation or homozygous or compound heterozygous zmpste24 mutations) have been established in adults. use of zokinvy in adults for these indications is based on adequate and well-controlled studies in pediatric patients 2 years of age and older [see clinical studies (14)] . instructions for use zokinvy™ (zo-kinvy) (lonafarnib) capsules, for oral use this instructions for use contains information on how to mix and give or take a dose of zokinvy if the capsules cannot be swallowed whole. read this instructions for use before you start giving or taking zokinvy and each time you get a refill. there may be new information. this information does not take the place of talking to your healthcare provider about you or your child’s medical condition or treatment supplies needed to prepare and give or take a dose of zokinvy   before mixing a dose of zokinvy, gather the following supplies: - the prescribed number of zokinvy capsules for you or your child’s dose. place the capsule or capsules on a clean flat surface. - either ora-blend sf, ora-plus, orange juice or applesauce for mixing. do not mix with juice that contains grapefruit or seville oranges. seville oranges may also be called bitter or sour oranges. - if mixing with ora-blend sf, ora-plus or orange juice: a clean medicine cup with 5 milliliter (ml) and 10 ml measurement levels, or if mixing with applesauce: a clean teaspoon. - clean cup(s) for each zokinvy capsule to be mixed. - a clean spoon for stirring the mixture. how to open zokinvy capsules and mix the capsule contents step 1: if mixing with ora-blend sf, ora-plus or orange juice: use a clean medicine cup to measure either 5 ml or 10 ml of ora-blend sf, ora-plus or orange juice. if mixing with applesauce: measure either 1 or 2 teaspoonfuls of applesauce. you can choose to use 5 ml or 10 ml of liquid or 1 or 2 teaspoonfuls of applesauce (see figure a). step 2: place the ora-blend sf, ora-plus, orange juice or applesauce measured in step 1 into a clean cup (see figure b). step 3: hold a zokinvy capsule above the clean cup containing the liquid or applesauce. hold the zokinvy capsule on both sides between your thumb and forefinger. gently twist and pull apart the capsule (see figure c). empty the contents of the capsule directly into the clean cup (see figure d). step 4: using a clean spoon, mix the zokinvy capsule contents well (see figure e) . if only 1 capsule is to be taken, skip to step 6 . if 2 capsules are to be taken, go to step 5 . step 5: if 2 capsules will be taken, repeat steps 1 through 4 for the second capsule. after completing the mixing process for the second capsule, the 2 servings can either be placed together in a single cup or remain in 2 serving cups for you or your child to take the full dose of zokinvy. after you finish, go to step 6 . step 6: give or take all of the zokinvy mixture with morning and evening meals within about 10 minutes of preparing. how should i store zokinvy? - store at room temperature between 68°f to 77°f (20°c to 25°c) keep zokinvy and all medicines out of reach of children. this instructions for use has been approved by the u.s. food and drug administration. manufactured for: eiger biopharmaceuticals, inc., 2155 park boulevard palo alto, ca 94306 ©2020 eiger biopharmaceuticals issued: 11/2020

Israel - English - Ministry of Health

neopharm ltd, israel - lonafarnib - hard gelatin capsules - lonafarnib 50 mg - lonafarnib - zokinvy is indicated in patients 12 months of age and older with a body surface area (bsa) of0.39 m2 and above:to reduce the risk of mortality in hutchinson-gilford progeria syndrome (hgps)• for the treatment of processing-deficient progeroid laminopathies with either:o heterozygous lmna mutation with progerin-like protein accumulationo homozygous or compound heterozygous zmpste24 mutationslimitations of usezokinvy is not indicated for other progeroid syndromes or processing-proficient progeroid laminopathies. based upon its mechanism of action, zokinvy would not be expected to be effective in these populations.

Israel - English - Ministry of Health

neopharm ltd, israel - lonafarnib - hard gelatin capsules - lonafarnib 75 mg - lonafarnib - zokinvy is indicated in patients 12 months of age and older with a body surface area (bsa) of0.39 m2 and above:to reduce the risk of mortality in hutchinson-gilford progeria syndrome (hgps)• for the treatment of processing-deficient progeroid laminopathies with either:o heterozygous lmna mutation with progerin-like protein accumulationo homozygous or compound heterozygous zmpste24 mutationslimitations of usezokinvy is not indicated for other progeroid syndromes or processing-proficient progeroid laminopathies. based upon its mechanism of action, zokinvy would not be expected to be effective in these populations.

Ireland - English - HPRA (Health Products Regulatory Authority)

bluefish pharmaceuticals ab - sorafenib tosilate - film-coated tablet - sorafenib

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

teva pharmaceuticals, inc. - sorafenib tosylate (unii: 5t62q3b36j) (sorafenib - unii:9zoq3tzi87) - sorafenib tablets are indicated for the treatment of patients with unresectable hepatocellular carcinoma (hcc). sorafenib tablets are indicated for the treatment of patients with advanced renal cell carcinoma (rcc). sorafenib tablets are indicated for the treatment of patients with locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (dtc) that is refractory to radioactive iodine treatment. - sorafenib tablets are contraindicated in patients with known severe hypersensitivity to sorafenib or any other component of sorafenib tablets. - sorafenib in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer [see warnings and precautions (5.8)] . risk summary based on findings from animal studies and its mechanism of action [see clinical pharmacology (12.1)] , sorafenib may cause fetal harm when administered to a pregnant woman. there are no available data in pregnant women to inform a drug-associated risk. in animal reproduction studies, o

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

mylan pharmaceuticals inc. - sorafenib tosylate (unii: 5t62q3b36j) (sorafenib - unii:9zoq3tzi87) - sorafenib tablets are indicated for the treatment of patients with unresectable hepatocellular carcinoma (hcc). sorafenib tablets are indicated for the treatment of patients with advanced renal cell carcinoma (rcc). sorafenib tablets are indicated for the treatment of patients with locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (dtc) that is refractory to radioactive iodine treatment. based on findings from animal studies and its mechanism of action [see clinical pharmacology (12.1)] , sorafenib may cause fetal harm when administered to a pregnant woman. there are no available data in pregnant women to inform a drug-associated risk. in animal reproduction studies, oral administration of sorafenib to pregnant rats and rabbits during the period of organogenesis resulted in embryo-fetal toxicities at maternal exposures that were significantly lower than human exposures at the recommended dose of 400 mg twice daily (see data) . advise pregnant women and females of reproductive potential of the potential risk to a fetus. the background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. in animal reproduction studies, sorafenib was teratogenic and induced embryo-fetal toxicity (including increased post-implantation loss, resorptions, skeletal retardations, and retarded fetal weight) when administered orally to pregnant rats and rabbits during the period of organogenesis. the effects occurred at doses considerably below the recommended human dose of 400 mg twice daily (approximately 500 mg/m2 /day on a body surface area basis). adverse intrauterine development effects were seen at doses > 0.2 mg/kg/day (1.2 mg/m2 /day) in rats and ≥ 0.3 mg/kg/day (≥ 3.6 mg/m2 /day) in rabbits. these doses result in exposures (auc) that are approximately 0.008 times the auc in patients at the recommended dose. there are no data on the presence of sorafenib or its metabolites in human milk, or its effects on the breast-fed child or on milk production. sorafenib was present in milk of lactating rats (see data) . because of the potential for serious adverse reactions in a breastfed child from sorafenib, advise women not to breastfeed during treatment with sorafenib and for 2 weeks after the last dose. following administration of radiolabeled sorafenib to lactating wistar rats, approximately 27% of the radioactivity was secreted into milk. the milk to plasma auc ratio was approximately 5:1. sorafenib may cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)] . verify the pregnancy status of females of reproductive potential prior to the initiation of sorafenib. advise females of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of sorafenib. based on genotoxicity and findings in animal reproduction studies, advise males with female partners of reproductive potential and pregnant partners to use effective contraception during treatment with sorafenib and for 3 months following the last dose of sorafenib [see use in specific populations (8.1), nonclinical toxicology (13.1)]. based on findings in animal studies, sorafenib may impair fertility in males of reproductive potential [see nonclinical toxicology (13.1)] . the safety and effectiveness of sorafenib have not been established in pediatric patients. repeat dosing of sorafenib to young and growing dogs resulted in irregular thickening of the femoral growth plate at daily sorafenib doses ≥ 600 mg/m2 (approximately 0.3 times the auc at the recommended human dose), hypocellularity of the bone marrow adjoining the growth plate at 200 mg/m2 /day (approximately 0.1 times the auc at the recommended human dose), and alterations of the dentin composition at 600 mg/m2 /day. similar effects were not observed in adult dogs when dosed for 4 weeks or less. in total, 59% of hcc patients treated with sorafenib were age 65 years or older and 19% were 75 and older. in total, 32% of rcc patients treated with sorafenib were age 65 years or older and 4% were 75 and older. no differences in safety or efficacy were observed between older and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. no dose adjustment is necessary for patients with mild, moderate or severe renal impairment who are not on dialysis. the pharmacokinetics of sorafenib have not been studied in patients who are on dialysis [see clinical pharmacology (12.3)]. no dose adjustment is necessary for patients with mild or moderate hepatic impairment. the pharmacokinetics of sorafenib have not been studied in patients with severe (child-pugh c) hepatic impairment [see clinical pharmacology (12.3)] .

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

dr.reddys laboratories inc - sorafenib tosylate (unii: 5t62q3b36j) (sorafenib - unii:9zoq3tzi87) - sorafenib tablets are indicated for the treatment of patients with unresectable hepatocellular carcinoma (hcc). sorafenib tablets are indicated for the treatment of patients with advanced renal cell carcinoma (rcc). sorafenib tablets are indicated for the treatment of patients with locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (dtc) that is refractory to radioactive iodine treatment. • sorafenib tablets are contraindicated in patients with known severe hypersensitivity to sorafenib or any other component of sorafenib tablets. • sorafenib tablets in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer [see warnings and precautions ( 5.8)]. risk summary based on findings from animal studies and its mechanism of action [see clinical pharmacology ( 12.1)] , sorafenib may cause fetal harm when administered to a pregnant woman. there are no available data in pregnant women to inform a drug-associated risk. in animal reproduction s

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

torrent pharmaceuticals limited - sorafenib (unii: 9zoq3tzi87) (sorafenib - unii:9zoq3tzi87) - sorafenib tablets are indicated for the treatment of patients with unresectable hepatocellular carcinoma (hcc). sorafenib tablets are indicated for the treatment of patients with advanced renal cell carcinoma (rcc). sorafenib tablets are indicated for the treatment of patients with locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (dtc) that is refractory to radioactive iodine treatment. •sorafenib tablets are contraindicated in patients with known severe hypersensitivity to sorafenib or any other component of sorafenib tablets. •sorafenib tablets in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer [see warnings and precautions ( 5.8 )] . based on findings from animal studies and its mechanism of action [see clinical pharmacology (12.1 )] , sorafenib may cause fetal harm when administered to a pregnant woman. there are no available data in pregnant women to inform a drug-associated risk. in animal reproduction studies, ora

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

golden state medical supply, inc. - sorafenib (unii: 9zoq3tzi87) (sorafenib - unii:9zoq3tzi87) - sorafenib tablets are indicated for the treatment of patients with unresectable hepatocellular carcinoma (hcc). sorafenib tablets are indicated for the treatment of patients with locally recurrent or metastatic, progressive,differentiated thyroid carcinoma (dtc) that is refractory to radioactive iodine treatment. sorafenib tablets are contraindicated in patients with known severe hypersensitivity to sorafenib or any other component of sorafenib tablets. sorafenib tablets in combination with carboplatin and paclitaxel are contraindicated in patients with squamous cell lung cancer [see warnings and precautions (5.8)]. risk summary based on findings from animal studies and its mechanism of action [see clinical pharmacology (12.1)], sorafenib tablets may cause fetal harm when administered to a pregnant woman. there are no available data in pregnant women to inform a drug-associated risk. in animal reproduction studies, oral administration of sorafenib to pregnant rats and rabbits during the period of organogenesis resulted in embryo-fetal toxicities at maternal exposures that were significantly lower than human exposures at the recommended dose of 400 mg twice daily (see data). advise pregnant women and females of reproductive potential of the potential risk to a fetus. the background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. data animal data in animal reproduction studies, sorafenib was teratogenic and induced embryo-fetal toxicity (including increased post-implantation loss, resorptions, skeletal retardations, and retarded fetal weight) when administered orally to pregnant rats and rabbits during the period of organogenesis. the effects occurred at doses considerably below the recommended human dose of 400 mg twice daily (approximately 500 mg/m2/day on a body surface area basis). adverse intrauterine development effects were seen at doses >0.2 .mg/kg/day (1.2 mg/m2/day) in rats and ≥0.3 mg/kg/day (≥3.6 mg/m2/day) in rabbits. these doses result in exposures (auc) that are approximately 0.008 times the auc in patients at the recommended dose. risk summary there are no data on the presence of sorafenib or its metabolites in human milk, or its effects on the breast-fed child or on milk production. sorafenib was present in milk of lactating rats (see data). because of the potential for serious adverse reactions in a breastfed child from sorafenib, advise women not to breastfeed during treatment with sorafenib and for 2 weeks after the last dose. data animal data following administration of radiolabeled sorafenib to lactating wistar rats, approximately 27% of the radioactivity was secreted into milk. the milk to plasma auc ratio was approximately 5:1. sorafenib tablets may cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)]. pregnancy testing verify the pregnancy status of females of reproductive potential prior to the initiation of sorafenib tablets. contraception females advise females of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of sorafenib tablets. males based on genotoxicity and findings in animal reproduction studies, advise males with female partners of reproductive potential and pregnant partners to use effective contraception during treatment with sorafenib tablets and for 3 months following the last dose of sorafenib tablets [see use in specific populations (8.1), nonclinical toxicology (13.1)]. infertility males based on findings in animal studies, sorafenib tablets may impair fertility in males of reproductive potential [see nonclinical toxicology (13.1)]. the safety and effectiveness of sorafenib tablets have not been established in pediatric patients. juvenile animal toxicity data repeat dosing of sorafenib to young and growing dogs resulted in irregular thickening of the femoral growth plate at daily sorafenib doses ≥600 mg/m2 (approximately 0.3 times the auc at the recommended human dose), hypocellularity of the bone marrow adjoining the growth plate at 200 mg/m2/day (approximately 0.1 times the auc at the recommended human dose), and alterations of the dentin composition at 600 mg/m2/day. similar effects were not observed in adult dogs when dosed for 4 weeks or less. in total, 59% of hcc patients treated with sorafenib tablets were age 65 years or older and 19% were 75 and older. no differences in safety or efficacy were observed between older and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. no dose adjustment is necessary for patients with mild, moderate or severe renal impairment who are not on dialysis. the pharmacokinetics of sorafenib have not been studied in patients who are on dialysis [see clinical pharmacology (12.3)].