الولايات المتحدة - الإنجليزية - NLM (National Library of Medicine)

actelion pharmaceuticals us, inc. - mechlorethamine (unii: 50d9xsg0vr) (mechlorethamine - unii:50d9xsg0vr) - mechlorethamine 0.012 g in 60 g - valchlor is an alkylating drug indicated for the topical treatment of stage ia and ib mycosis fungoides-type cutaneous t-cell lymphoma in patients who have received prior skin-directed therapy. the use of valchlor is contraindicated in patients with known severe hypersensitivity to mechlorethamine. hypersensitivity reactions, including anaphylaxis, have occurred with topical formulations of mechlorethamine. pregnancy category d [see warnings and precautions (5.5) ] risk summary mechlorethamine can cause fetal harm when administered to a pregnant woman. there are case reports of children born with malformations in pregnant women systemically administered mechlorethamine. mechlorethamine was teratogenic in animals after a single subcutaneous administration. if this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see warnings and precautions (5.5) ]. animal data mechlorethamine caused fetal malformat

الولايات المتحدة - الإنجليزية - NLM (National Library of Medicine)

actelion pharmaceuticals us, inc. - macitentan (unii: z9k9y9wmvl) (macitentan - unii:z9k9y9wmvl) - macitentan 10 mg - opsumit is an endothelin receptor antagonist (era) indicated for the treatment of pulmonary arterial hypertension (pah, who group i) to reduce the risks of disease progression and hospitalization for pah. effectiveness was established in a long-term study in pah patients with predominantly who functional class ii–iii symptoms treated for an average of 2 years. patients had idiopathic and heritable pah (57%), pah caused by connective tissue disorders (31%), and pah caused by congenital heart disease with repaired shunts (8%) [see clinical studies (14.1)] . opsumit may cause fetal harm when administered to a pregnant woman. opsumit is contraindicated in females who are pregnant. opsumit was consistently shown to have teratogenic effects when administered to animals. if opsumit is used during pregnancy, advise the patient of the potential risk to a fetus [see warnings and precautions (5.1) and use in specific populations (8.1)] . opsumit is contraindicated in patients with a history of a hypersensitivity reaction to macitentan or any component of the product [see adverse reactions (6.2)] . risk summary based on data from animal reproduction studies, opsumit may cause embryo-fetal toxicity, including birth defects and fetal death, when administered to a pregnant female and is contraindicated during pregnancy. there are risks to the mother and the fetus associated with pulmonary arterial hypertension in pregnancy [see clinical considerations] . there are limited data on opsumit use in pregnant women. macitentan was teratogenic in rabbits and rats at all doses tested. if this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient of the risk to a fetus [see contraindications (4.1)] . 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 2–4% and 15–20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk in patients with pulmonary arterial hypertension, pregnancy is associated with an increased rate of maternal and fetal morbidity and mortality, including spontaneous abortion, intrauterine growth restriction and premature labor. data animal data in both rabbits and rats, there were cardiovascular and mandibular arch fusion abnormalities. administration of macitentan to female rats from late pregnancy through lactation caused reduced pup survival and impairment of the male fertility of the offspring at all dose levels tested. risk summary there are no data on the presence of macitentan in human milk, the effects on the breastfed infant, or the effect on milk production. because of the potential for serious adverse reactions in breastfed infants from opsumit advise women not to breastfeed during treatment with opsumit. pregnancy testing verify the pregnancy status of females of reproductive potential prior to initiating opsumit, monthly during treatment and one month after stopping treatment with opsumit. the patient should contact her physician immediately for pregnancy testing if onset of menses is delayed or pregnancy is suspected. if the pregnancy test is positive, the physician and patient must discuss the risks to her, the pregnancy, and the fetus [see warnings and precautions (5.1), and dosage and administration (2.2) and contraindication (4.1)] . contraception female patients of reproductive potential must use acceptable methods of contraception during treatment with opsumit and for 1 month after treatment with opsumit. patients may choose one highly effective form of contraception (intrauterine devices (iud), contraceptive implants or tubal sterilization) or a combination of methods (hormone method with a barrier method or two barrier methods). if a partner's vasectomy is the chosen method of contraception, a hormone or barrier method must be used along with this method. counsel patients on pregnancy planning and prevention, including emergency contraception, or designate counseling by another healthcare provider trained in contraceptive counseling [see warnings and precautions (5.1)] . infertility based on findings in animals, opsumit may impair fertility in males of reproductive potential. it is not known whether effects on fertility would be reversible [see warnings and precautions (5.7), adverse reactions (6.1) and nonclinical toxicology (13.1)] . the safety and efficacy of opsumit in children have not been established. of the total number of subjects in the clinical study of opsumit for pah, 14% were 65 and over. no overall differences in safety or effectiveness were observed between these subjects and younger subjects.

الولايات المتحدة - الإنجليزية - NLM (National Library of Medicine)

actelion pharmaceuticals us, inc. - bosentan (unii: q326023r30) (bosentan anhydrous - unii:xul93r30k2) - bosentan anhydrous 62.5 mg - tracleer is indicated for the treatment of pulmonary arterial hypertension (pah) (who group 1): - in adults to improve exercise ability and to decrease clinical worsening. studies establishing effectiveness included predominantly patients with who functional class ii-iv symptoms and etiologies of idiopathic or heritable pah (60%), pah associated with connective tissue diseases (21%), and pah associated with congenital heart disease with left-to-right shunts (18%) [see clinical studies (14.1)] . - in pediatric patients aged 3 years and older with idiopathic or congenital pah to improve pulmonary vascular resistance (pvr), which is expected to result in an improvement in exercise ability. use of tracleer is contraindicated in females who are or may become pregnant. to prevent pregnancy, females of reproductive potential must use two reliable forms of contraception during treatment and for one month after stopping tracleer [see boxed warning, warnings and precautions (5.2), drug interactions (7.2), use in specific populations (8.1)] . co-administration of cyclosporine a and bosentan resulted in markedly increased plasma concentrations of bosentan. therefore, concomitant use of tracleer and cyclosporine a is contraindicated [see cytochrome p450 drug interactions (7.1)] . an increased risk of liver enzyme elevations was observed in patients receiving glyburide concomitantly with bosentan. therefore co-administration of glyburide and tracleer is contraindicated [see cytochrome p450 drug interactions (7.1)] . tracleer is contraindicated in patients who are hypersensitive to bosentan or any component of the product. observed reactions include drug reaction with eosinophilia and systemic symptoms (dress), anaphylaxis, rash, and angioedema [see adverse reactions (6.2), description (11)] . risk summary based on data from animal reproduction studies, tracleer may cause fetal harm, including birth defects and fetal death, when administered to a pregnant female and is contraindicated during pregnancy [see contraindications (4.1)] . there are limited data on tracleer use in pregnant women. in animal reproduction studies, oral administration of bosentan to pregnant rats at 2-times the maximum recommended human dose (mrhd) on a mg/m 2 basis caused teratogenic effects in rats, including malformations of the head, mouth, face, and large blood vessels [see animal data] . advise pregnant women of the potential risk to a fetus. 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 2–4% and 15–20%, respectively. data animal data bosentan was teratogenic in rats given oral doses two times the mrhd (on a mg/m 2 basis). in an embryo-fetal toxicity study in rats, bosentan showed dose-dependent teratogenic effects, including malformations of the head, mouth, face and large blood vessels. bosentan increased stillbirths and pup mortality at oral doses 2 and 10 times the mrhd (on a mg/m 2 basis). although birth defects were not observed in rabbits given oral doses of up to the equivalent of 10.5 g/day in a 70 kg person, plasma concentrations of bosentan in rabbits were lower than those reached in the rat. the similarity of malformations induced by bosentan and those observed in endothelin-1 knockout mice and in animals treated with other endothelin receptor antagonists indicates that embryo-fetal toxicity is a class effect of these drugs. risk summary data from a case report describe the presence of bosentan in human milk. there is insufficient information about the effects of bosentan on the breastfed infant and no information on the effects of bosentan on milk production. because of the potential for serious adverse reactions, such as fluid retention and hepatotoxicity, in breastfed infants from tracleer, advise women not to breastfeed during treatment with tracleer. pregnancy testing verify the pregnancy status of females of reproductive potential prior to initiating tracleer, monthly during treatment and one month after stopping treatment with tracleer. the patient should contact her physician immediately for pregnancy testing if onset of menses is delayed or pregnancy is suspected. if the pregnancy test is positive, the physician and patient must discuss the risks to her, the pregnancy, and the fetus. contraception drug interaction studies show that bosentan reduces serum levels of the estrogen and progestin in oral contraceptives. based on these findings, hormonal contraceptives (including oral, injectable, transdermal, and implantable contraceptives) may be less effective for preventing pregnancy in patients using tracleer and should not be used as a patient's only contraceptive method [see drug interactions (7.2)] . females of reproductive potential using tracleer must use two acceptable methods of contraception during treatment and for 1 month after treatment with tracleer. patients may choose one highly effective form of contraception (intrauterine devices (iud) or tubal sterilization) or a combination of methods (hormone method with a barrier method or two barrier methods). if a partner's vasectomy is the chosen method of contraception, a hormone or barrier method must be used along with this method. counsel patients on pregnancy planning and prevention, including emergency contraception, or designate counseling by another healthcare provider trained in contraceptive counseling [see boxed warning] . infertility males decreased sperm counts have been observed in patients receiving tracleer. based on these findings and findings in animals, tracleer may impair fertility in males of reproductive potential. it is not known whether effects on fertility would be reversible [see warnings and precautions (5.6), adverse reactions (6.1), nonclinical toxicology (13.1)] . the efficacy of tracleer in patients <18 years is supported by data from an uncontrolled trial in which 19 pediatric patients were treated with tracleer. in this study, cardiopulmonary hemodynamic improvements were similar to those seen in adults treated with tracleer [see pulmonary arterial hypertension (14.1)] . safety in pediatric patients is supported by data from 100 pediatric patients treated with tracleer for a median of 17 months [see clinical studies experience (6.1), pulmonary arterial hypertension (14.1)] . juvenile animal toxicity data in a juvenile rat toxicity study, rats were treated from day 4 postpartum to adulthood (day 69 postpartum). decreased body weights, absolute weights of testes and epididymides, and reduced number of sperm in epididymides were observed after weaning. no effect on testis histology or sperm morphology and function was seen. the noael was 4 times (at day 4 postpartum) and 2 times (day 69 postpartum) the human therapeutic exposure, respectively. no effects on general development, sensory, cognitive function and reproductive performance were detected at the highest dose tested in juvenile rats, 7 times the therapeutic exposure in children with pah. clinical studies of tracleer did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. because there is in vitro and in vivo evidence that the main route of excretion of bosentan is biliary, liver impairment could be expected to increase exposure (c max and auc) of bosentan. the pharmacokinetics of tracleer have not been evaluated in patients with severe liver impairment (child-pugh class c). in patients with moderate hepatic impairment (child-pugh class b), the systemic exposures to bosentan and its active metabolite increased significantly. tracleer should generally be avoided in patients with moderate or severe liver impairment. pharmacokinetics of bosentan were not altered in patients with mild impairment of hepatic function (child-pugh class a) [see dosage and administration (2.6), warnings and precautions (5.1), pharmacokinetics (12.3)] . the effect of renal impairment on the pharmacokinetics of bosentan is small and does not require dosing adjustment [see pharmacokinetics (12.3)] .

الولايات المتحدة - الإنجليزية - NLM (National Library of Medicine)

actelion pharmaceuticals us, inc. - non-medicated valchlor® demonstration gel does not contain mechlorethamine (the medicine in valchlor). the purpose of valchlor demonstration gel is to show healthcare providers and patients how to properly apply valchlor. this will also allow the user to experience the consistency of valchlor and how it may feel on the skin. this information does not take the place of talking to your healthcare provider about your condition or your treatment. how should valchlor demonstration gel be used? - use valchlor demonstration gel on clean and dry, healthy skin - if you take a bath or shower, be sure to use the gel after your skin is dry (at least 30 minutes after bathing or showering) how to use valchlor demonstration gel: some important do's and don'ts about valchlor demonstration gel: - when applying valchlor demonstration gel, avoid the eyes, mouth, and nose. - valchlor demonstration gel should only be used on healthy skin since it is non-medicated. - the 5g tube of valchlor demonstration gel is meant for single

الولايات المتحدة - الإنجليزية - NLM (National Library of Medicine)

actelion pharmaceuticals us, inc. - epoprostenol (unii: dcr9z582x0) (epoprostenol - unii:dcr9z582x0) - epoprostenol 500000 ng in 10 ml - veletri is indicated for the treatment of pulmonary arterial hypertension (pah) (who group 1) to improve exercise capacity. studies establishing effectiveness included predominantly patients with nyha functional class iii–iv symptoms and etiologies of idiopathic or heritable pah or pah associated with connective tissue diseases. a large study evaluating the effect of epoprostenol on survival in nyha class iii and iv patients with congestive heart failure due to severe left ventricular systolic dysfunction was terminated after an interim analysis of 471 patients revealed a higher mortality in patients receiving epoprostenol plus conventional therapy than in those receiving conventional therapy alone. the chronic use of veletri in patients with congestive heart failure due to severe left ventricular systolic dysfunction is therefore contraindicated. some patients with pulmonary hypertension have developed pulmonary edema during dose initiation, which may be associated with pulmonary veno-occlusive disease. vele

الولايات المتحدة - الإنجليزية - NLM (National Library of Medicine)

actelion pharmaceuticals us, inc. - iloprost (unii: jed5k35ygl) (iloprost - unii:jed5k35ygl) - iloprost 0.01 mg in 1 ml - ventavis is indicated for the treatment of pulmonary arterial hypertension (pah) (who group 1) to improve a composite endpoint consisting of exercise tolerance, symptoms (nyha class), and lack of deterioration. studies establishing effectiveness included predominately patients with nyha functional class iii–iv symptoms and etiologies of idiopathic or heritable pah (65%) or pah associated with connective tissue diseases (23%) [see clinical studies (14)] . none. risk summary limited published data from case series and case reports with ventavis in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. there are risks to the mother and fetus associated with pulmonary arterial hypertension (see clinical considerations) . in animal reproductive studies, administration of continuous intravenous iloprost to pregnant han-wistar rats during organogenesis at doses 2-times the recommended human dose on a mg/m2 basis resulted in adverse develo

الولايات المتحدة - الإنجليزية - NLM (National Library of Medicine)

actelion pharmaceuticals us, inc. - selexipag (unii: 5exc0e384l) (selexipag - unii:5exc0e384l) - selexipag 200 ug - uptravi is indicated for the treatment of pulmonary arterial hypertension (pah, who group i) to delay disease progression and reduce the risk of hospitalization for pah. effectiveness of uptravi tablets was established in a long-term study in pah patients with who functional class ii–iii symptoms. patients had idiopathic and heritable pah (58%), pah associated with connective tissue disease (29%), pah associated with congenital heart disease with repaired shunts (10%) [see clinical studies (14.1)] . hypersensitivity to the active substance or to any of the excipients. concomitant use of strong inhibitors of cyp2c8 (e.g., gemfibrozil) [see drug interactions (7.1) and clinical pharmacology (12.3)] . risk summary there are no adequate and well-controlled studies with uptravi in pregnant women. animal reproduction studies performed with selexipag showed no clinically relevant effects on embryofetal developmen

الولايات المتحدة - الإنجليزية - NLM (National Library of Medicine)

actelion pharmaceuticals us, inc. - miglustat (unii: adn3s497az) (miglustat - unii:adn3s497az) - miglustat 100 mg - zavesca is indicated as monotherapy for the treatment of adult patients with mild to moderate type 1 gaucher disease for whom enzyme replacement therapy is not a therapeutic option (e.g. due to allergy, hypersensitivity, or poor venous access). none. risk summary based on findings from animal reproduction studies, zavesca may cause fetal harm when administered to a pregnant woman. available data from postmarketing case reports with zavesca use in pregnancy are insufficient to assess a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. there are risks associated with symptomatic type i gaucher disease in pregnancy, including hepatosplenomegaly and thrombocytopenia (see clinical considerations). advise pregnant women of the potential risks to the fetus. in animal reproduction studies, miglustat was maternally toxic in rabbits at exposures near the expected human therapeutic dose and caused embryo-fetal toxicitie

الولايات المتحدة - الإنجليزية - NLM (National Library of Medicine)

actelion pharmaceuticals us, inc. - epoprostenol sodium (unii: 4k04iq1of4) (epoprostenol - unii:dcr9z582x0) - epoprostenol sodium 1500000 ng in 10 ml

الولايات المتحدة - الإنجليزية - NLM (National Library of Medicine)

actelion pharmaceuticals us, inc. - macitentan (unii: z9k9y9wmvl) (macitentan - unii:z9k9y9wmvl), tadalafil (unii: 742sxx0ict) (tadalafil - unii:742sxx0ict) - opsynvi is the combination of macitentan and tadalafil indicated for the chronic treatment of adults with pulmonary arterial hypertension (pah, who group i and who functional class (fc) ii–iii). individually, macitentan reduces the risk of clinical worsening events and hospitalization, and tadalafil improves exercise ability [see clinical studies (14.1)] . opsynvi may cause fetal harm when administered to a pregnant woman. opsynvi is contraindicated in females who are pregnant. macitentan was consistently shown to have teratogenic effects when administered to animals. if opsynvi is used during pregnancy, advise the patient of the potential risk to a fetus [see warnings and precautions (5.1) and use in specific populations (8.1)] . opsynvi is contraindicated in patients with a history of a hypersensitivity reaction to macitentan, tadalafil, or any component of the product. hypersensitivity reactions have been reported. stevens-johnson syndrome and exfoliative dermatitis have been reported with tadalafil [see adverse reactions (6.2)]. opsynvi is contraindicated in patients who are using any form of organic nitrate, either regularly or intermittently. do not use nitrates within 48 hours of the last dose of opsynvi. tadalafil potentiates the hypotensive effect of nitrates. this potentiation is thought to result from the combined effects of nitrates and tadalafil on the nitric oxide/cgmp pathway [see clinical pharmacology (12.2)]. coadministration of gc stimulators such as riociguat with opsynvi is contraindicated. tadalafil may potentiate the hypotensive effects of gc stimulators. risk summary based on data from animal reproduction studies, opsynvi is contraindicated during pregnancy. macitentan, a component of opsynvi, may cause embryo-fetal toxicity, including birth defects and fetal death, when administered to a pregnant female. the available data from opsynvi pharmacovigilance reports and published case reports on macitentan are insufficient to evaluate the potential risk of embryo-fetal toxicity. macitentan was teratogenic in rabbits and rats at all doses tested. available data from a randomized controlled trial, observational studies, and case series with tadalafil use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. in tadalafil animal reproduction studies, no adverse developmental effects were observed with oral administration of tadalafil to pregnant rats and mice during organogenesis at exposures 7 times the maximum recommended human dose (mrhd) of 40 mg/day (see data) . there are risks to the mother and the fetus associated with pah in pregnancy (see clinical considerations) . if this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise pregnant women of the potential risk to a fetus [see contraindications (4.1) and warnings and precautions (5.1)]. the background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk in patients with pah, pregnancy is associated with an increased rate of maternal and fetal morbidity and mortality, including heart failure, stroke, spontaneous abortion, intrauterine growth restriction, premature labor, and preterm birth. data animal data macitentan in both rabbits and rats, there were cardiovascular and mandibular arch fusion abnormalities. administration of macitentan to female rats from late pregnancy through lactation caused reduced pup survival and impairment of the male fertility of the offspring at all dose levels tested. tadalafil tadalafil and/or its metabolites cross the placenta, resulting in fetal exposure in rats. animal reproduction studies showed no evidence of teratogenicity, embryotoxicity, or fetotoxicity when tadalafil was given to pregnant rats or mice at unbound tadalafil exposures up to 7 times the exposure at the maximum recommended human dose (mrhd) of 40 mg/day during organogenesis based on auc. in one of two perinatal/postnatal developmental studies in rats, a reduction of postnatal pup survival was observed at dose levels of 60, 200 and 1000 mg/kg. the no-observed-effect-level (noel) for developmental toxicity was 30 mg/kg, which provided maternal exposure to unbound tadalafil concentrations approximately 5 times the exposure at the mrhd based on auc. signs of maternal toxicity occurred at doses greater than 200 mg/kg/day, which produced aucs greater than 8 times the exposure at the mrhd. surviving offspring had normal development and reproductive performance. risk summary there are no data on the presence of tadalafil, macitentan, and/or their metabolites in human milk, the effects on the breastfed infant, or the effect on milk production. tadalafil and/or its metabolites are present in the milk of lactating rats (see data) . when a drug is present in animal milk, it is likely that the drug will be present in human milk. because of the potential for serious adverse reactions in breastfed infants from opsynvi, advise women not to breastfeed during treatment with opsynvi. data tadalafil and/or its metabolites are present in the milk of lactating rats at concentrations approximately 2.4-times that found in the plasma. pregnancy testing verify the pregnancy status of females of reproductive potential prior to initiating opsynvi, monthly during treatment and one month after stopping treatment with opsynvi. the patient should contact her physician immediately for pregnancy testing if onset of menses is delayed or pregnancy is suspected. if the pregnancy test is positive, the physician and patient must discuss the risks to her, the pregnancy, and the fetus [see dosage and administration (2.2) and contraindications (4.1)]. contraception female patients of reproductive potential must use acceptable methods of contraception during treatment with opsynvi and for 1 month after treatment with opsynvi. patients may choose one highly effective form of contraception (intrauterine devices (iud), contraceptive implants or tubal sterilization) or a combination of methods (hormone method with a barrier method or two barrier methods). if a partner's vasectomy is the chosen method of contraception, a hormone or barrier method must be used along with this method. counsel patients on pregnancy planning and prevention, including emergency contraception, or designate counseling by another healthcare provider trained in contraceptive counseling [see warnings and precautions (5.1)] . infertility males macitentan based on findings in animals, macitentan may impair fertility in males of reproductive potential. it is not known whether effects on fertility would be reversible [see warnings and precautions (5.11), clinical pharmacology (12.2), and nonclinical toxicology (13.1)]. tadalafil based on the data from 3 studies in adult males, tadalafil decreased sperm concentrations in the study of 10 mg tadalafil for 6 months and the study of 20 mg tadalafil for 9 months. this effect was not seen in the study of 20 mg tadalafil taken for 6 months. there was no adverse effect of tadalafil 10 mg or 20 mg on mean concentrations of testosterone, luteinizing hormone or follicle stimulating hormone. the clinical significance of the decreased sperm concentrations in the two studies is unknown. there have been no studies evaluating the effect of tadalafil on fertility in men or women [see clinical pharmacology (12.2) and nonclinical toxicology (13.1)] . the safety and efficacy of opsynvi in children has not been established. of the total number of subjects in the clinical study of opsynvi for pah, 20% were 65 and over. no overall differences in safety or effectiveness were observed between these subjects and younger subjects. the use of opsynvi is not recommended in patients undergoing dialysis. avoid use of opsynvi in patients with severe renal impairment (creatinine clearance 15–29 ml/min) because of increased tadalafil exposure (auc), lack of clinical experience and the lack of ability to influence clearance by dialysis. for patients with mild (creatinine clearance 51–80 ml/min) to moderate (creatinine clearance 30–50 ml/min) renal impairment, the recommended dose should be consistent with the adult dosing [see dosage and administration (2.1) and clinical pharmacology (12.3)]. opsynvi was not studied in severe hepatic impairment patients defined as a model for end-stage liver disease score ≥19. opsynvi must not be initiated in patients with severe hepatic impairment, or clinically significant elevated hepatic aminotransferases (greater than 3 times the upper limit of normal at baseline (> 3 × uln). for patients with mild to moderate hepatic impairment (child pugh class a or b) the recommended dose should be consistent with the adult dosing see dosage and administration (2.1) [see warnings and precautions (5.3) and clinical pharmacology (12.3)].