Jungtinės Valstijos - anglų - NLM (National Library of Medicine)

chiesi usa, inc. - mannitol (unii: 3owl53l36a) (mannitol - unii:3owl53l36a) - bronchitol is indicated as add-on maintenance therapy to improve pulmonary function in adult patients 18 years and older with cystic fibrosis.  use bronchitol only for adults who have passed the bronchitol tolerance test [see dosage and administration (2.1)]. bronchitol is contraindicated in the following conditions: - hypersensitivity to mannitol or to any of the capsule components hypersensitivity to mannitol or to any of the capsule components - failure to pass the bronchitol tolerance test (btt) failure to pass the bronchitol tolerance test (btt) risk summary there are no adequate and well-controlled studies of bronchitol in pregnant women. the available data on bronchitol use in pregnant women are not sufficient to inform any drug-associated risks for major birth defects and miscarriage. based on animal reproduction studies, no evidence of structural alterations was observed when mannitol was administered to pregnant rats and mice during organogenesis at doses up to approximately 20 and 10 times, respectively, the maximum recommended daily inhalation dose (mrdid) in humans [see data ]. there are risks to the mother associated with cystic fibrosis in pregnancy [see clinial considerations]. bronchitol should be used during pregnancy only if the potential benefit justifies the potential risk to the mother and 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 united states general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk cystic fibrosis may increase the risk for preterm delivery. data animal data in animal reproduction studies, oral administration of mannitol to pregnant rats and mice during the period of organogenesis did not cause fetal structural alterations. the mannitol dose in rats and mice was approximately 20 and 10 times the maximum recommended human daily inhalation dose (mrdid) in humans, respectively, (on a mg/m2 basis at maternal doses of 1600 mg/kg/day in both species). risk summary it is not known whether bronchitol is excreted in human breast milk. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for bronchitol and any potential adverse effects on the breastfed child from bronchitol or from the underlying maternal condition. bronchitol is not indicated for use in children and adolescents. the safety and effectivenss of bronchitol have not been established in pediatric patients for cystic fibrosis. patients aged 6 years to 17 years were included in two 26-week, double-blind clinical trials (trials 2 and 3). in these trials, 154 patients under 18 years of age received bronchitol and 105 patients received control (50 mg inhaled mannitol). hemoptysis was reported in 12 of 154 (7.8%)  patients who received bronchitol and in 2 of 105 (1.9%) patients who received control. clinical trials of bronchitol did not include sufficient numbers of patients with cystic fibrosis who were 65 years of age and older to allow evaluation of safety and efficacy in this population. clinical trials of bronchitol did not include patients with hepatic or renal impairment. no specific dose recommendations for these patient populations are available. however, an increase in systemic exposure of mannitol can be expected in patients with renal impairment based on the kidney being its primary route of elimination. patient instructions for use bronchitol® (mannitol) inhalation powder for oral inhalation use this patient instructions for use contains information on how to take bronchitol .  7-day treatment pack - 140 capsules (14 blister packs) - 1 inhaler - prescribing information 4-week treatment pack - 560 capsules (56 blister packs) - 4 inhalers - prescribing information  important information you need to know before using bronchitol - do not use bronchitol until your healthcare provider has performed the bronchitol tolerance test (btt) and approved you for treatment.   this is to make sure you get the right treatment if you have a severe reaction. - for oral inhalation only - do not swallow bronchitol capsules. - use an inhaled short-acting bronchodilator 5 to 15 minutes before every dose of bronchitol - use bronchitol 2 times each day.  inhale through your mouth (oral inhalation) the capsule contents in 10 single bronchitol capsules: 1 time in the morning 1 time at least 2 to 3 hours before bedtime - 1 time in the morning - 1 time at least 2 to 3 hours before bedtime preparing to use bronchitol bronchitol is supplied to people in cartons containing 140 or 560 capsules in blister packs. supplies you will need to use bronchitol: - 1 blister pack - 1 inhaler - bronchodilator (and spacer for bronchodilator if needed) - sink or hand washing station use an inhaled bronchodilator 5 to15 minutes before using bronchitol (see figure a ). clean and dry hands well (see figure b ). inhaler use steps for inhalation of the contents of a single capsule: step 1 .  remove cap (see figure c ) step 2. twist open inhaler by turning the mouthpiece to the right. (see figure d ). step 3. take 1 capsule out of the blister pack and put it in the chamber.(see figure e ). do not place capsule into the mouthpiece of the inhaler. step 4. hold inhaler upright and turn the mouthpiece to the left until it locks in place. (see figure f ). step 5. push both piercing buttons at the same time. release both piercing buttons at the same time (see figure g ). step 6. breathe out (exhale) fully (see figure h ). do not breathe out into inhaler. step 7. close lips around the mouthpiece and take a steady deep breath in through your mouth. do not breathe through your nose. remove inhaler from mouth. hold breath for 5 seconds before exhaling, do not breathe out (exhale) into inhaler (see figure i ).   you should hear a rattling sound while breathing in. if you do not, tap bottom of inhaler firmly and repeat steps 6 and 7. step 8. open the inhaler by turning the cap to the right. if powder is left in capsule, repeat steps 6 and 7. after the capsule is empty, throw away. (see figure j ). step 9 . repeat steps 3 to 8 for all 10 capsules in 1 blister pack (see figure k ).   breathe in (inhale) contents of each capsule one after another until all 10 capsules in the blister pack are used. step 10. after inhaling contents of all 10 capsules, close mouthpiece and place cap on inhaler (see figure l ). step 11. continue using bronchitol for 7 days then throw away (discard) the inhaler (see figure m ). how should i store bronchitol? - store bronchitol at room temperature between 68°f to77°f (20°c to 25°c). - if your bronchitol capsules are stored at temperatures more than 86°f (30°c), throw them away. - do not freeze bronchitol. - do not refrigerate bronchitol. - keep bronchitol and all medicines out of the reach of children. cleaning your bronchitol inhaler. - your inhaler should give you the correct dose of medicine for 7 days without needing cleaning. however, if your inhaler does need cleaning: - make sure your inhaler is empty. - wash your inhaler in warm water with the mouthpiece open. - shake it until there are no large water droplets left in the inhaler. - leave it to dry in the air by laying it on its side with the mouthpiece open. - allow the inhaler to dry fully (or completely) after it has been washed. caring for your bronchitol inhaler. - keep your inhaler dry and always make sure your hands are completely dry before using it. - do not breathe or cough into your inhaler. - do not take your inhaler apart. - do not place a capsule directly into the mouthpiece of your inhaler. - do not leave a used capsule in your inhaler chamber. - use a new inhaler after 7 days. - if your inhaler breaks, call to your healthcare provider. for more information about bronchitol or how to use your inhaler, call 1-888-661-9260. manufactured by: pharmaxis ltd 20 rodborough road frenchs forest nsw 2086 australia manufactured for: chiesi usa, inc. cary, nc 27518 usa 1-888-661-9260 bronchitol is registered in the us patent and trademark office. this patient instructions for use has been approved by the u.s. food and drug administration. revised: 1/2024 ctbr-009-0817-00-spl-1

Jungtinės Valstijos - anglų - NLM (National Library of Medicine)

chiesi usa, inc. - pegunigalsidase alfa (unii: 8m7v7q6537) (pegunigalsidase alfa - unii:8m7v7q6537) - elfabrio is indicated for the treatment of adults with confirmed fabry disease. none. risk summary there are no available data on elfabrio use in pregnant females to evaluate a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes; however, as an enzyme replacement, elfabrio is not expected to cause adverse outcomes. animal reproduction studies have been conducted with pegunigalsidase alfa-iwxj in pregnant rats and rabbits. no adverse effects on embryofetal development were observed in pregnant rats intravenously administered pegunigalsidase alfa-iwxj twice per week at exposures up to 3.6 times that of the maximum recommended human dose (mrhd) (based on area under the concentration-time curve (auc)). maternal toxicity was observed in pregnant rabbits intravenously administered pegunigalsidase alfa-iwxj twice per week at doses that were ≥ 3.2 times the mrhd (based on human equivalent dose) [ see data ] . the estimated background risk of major birth defects and miscarriage in 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. there is a pregnancy safety study for elfabrio. if a patient becomes pregnant while receiving elfabrio, healthcare providers should report elfabrio exposure by calling 1-888-661-9260 or visiting https://chiesirarediseases.com/contact-us/medical-information-form. data animal data in an embryofetal development study in the rat, pegunigalsidase alfa-iwxj was administered during the period of organogenesis on gestation day 6, 9, 12, and 15. no maternal or fetal adverse effects were noted at exposures that were up to 3.6-fold greater than the recommended dose of 1 mg/kg every two weeks. in an embryofetal development study in the rabbit, administration of pegunigalsidase alfa-iwxj during the period of organogenesis on gestation day 6, 9, 12, 15, and 18, resulted in maternal toxicity, including maternal mortality, decreased body weight, and decreased feed consumption. these effects were observed at exposures that were ≥ 3.2-fold greater than the recommended dose of 1 mg/kg every two weeks. adverse embryofetal effects included abortion, increased late resorptions, number of does with resorptions, and increased post-implantation loss at exposures that were 6.5 fold greater than the recommended dose of 1 mg/kg every two weeks. decreased fetal body weight was observed at exposures that were ≥ 3.2 times greater than the recommended dose of 1 mg/kg every two weeks. there was no increase in fetal external, skeletal, or visceral malformations. risk summary there are no data on the presence of pegunigalsidase alfa-iwxj in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for elfabrio and any potential adverse effects on the breastfed infant from pegunigalsidase alfa-iwxj or from the underlying maternal condition. the safety and effectiveness of elfabrio have not been established in pediatric patients. clinical trials of elfabrio did not include patients 65 years of age and older to determine if they respond differently from younger adult patients. patients that received prior ert are more likely to have pre-existing anti-drug antibodies (ada) to pegunigalsidase alfa-iwxj which could be due to the ada cross-reactivity to pegunigalsidase alfa-iwxj by prior ert. when switching from other ert to elfabrio: - pre-existing ada may reduce the plasma pegunigalsidase alfa-iwxj concentrations, which may reduce elfabrio efficacy [see clinical pharmacology ( 12.2 , 12.6 ) ]. - the risk of elfabrio-related hypersensitivity and infusion-associated reactions may be increased in certain patients with pre-existing ada from prior ert [ see warnings and precautions ( 5.1 , 5.2 ) and adverse reactions ( 6.1 )] . consider monitoring clinical or pharmacodynamic responses (e.g., plasma lyso-gb3 levels) when switching from agalsidase beta to elfabrio, in patients with pre-existing ada. 

Jungtinės Valstijos - anglų - NLM (National Library of Medicine)

taro pharmaceuticals u.s.a., inc. - deferiprone (unii: 2bty8kh53l) (deferiprone - unii:2bty8kh53l) - deferiprone tablets are indicated for the treatment of transfusional iron overload in adult patients with thalassemia syndromes when current chelation therapy is inadequate. limitations of use - safety and effectiveness have not been established for the treatment of transfusional iron overload in patients with myelodysplastic syndrome or in patients with diamond blackfan anemia. pediatric use information is approved for chiesi usa, inc.'s ferriprox ® (deferiprone) tablets. however, due to chiesi usa, inc.'s marketing exclusivity rights, this drug product is not labeled with that information. deferiprone is contraindicated in patients with known hypersensitivity to deferiprone or to any of the excipients in the formulations. the following reactions have been reported in association with the administration of deferiprone: henoch-schönlein purpura; urticaria; and periorbital edema with skin rash [see adverse reactions (6.2)]. risk summary in animal reproduction studies, oral administration of deferiprone to pregnant rats and rabbits during organogenesis at doses 33% and 49%, respectively, of the maximum recommended human dose (mrhd) resulted in structural abnormalities, embryo-fetal mortality and alterations to growth (see data) . the limited available data from deferiprone use in pregnant women are insufficient to inform a drug-associated risk of major birth defects and miscarriage. based on evidence and developmental toxicity in animal studies, deferiprone can cause fetal harm when administered to a pregnant woman. advise pregnant women and females of reproductive potential 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 of miscarriage is 2 to 4% and 15 to 20%, respectively. data human data post-marketing data available from 39 pregnancies of deferiprone-treated patients and 10 pregnancies of partners of deferiprone-treated patients are as follows: of the 39 pregnancies in deferiprone-treated patients, 23 resulted in healthy newborns, 6 ended in spontaneous abortion, 9 had unknown outcomes, and 1 infant was born with anal atresia, nephroptosis, ventricular septal defect, hemivertebra and urethral fistula. of the 10 pregnancies in partners of deferiprone-treated patients, 5 resulted in healthy newborns, 1 resulted in a healthy newborn with slight hypospadias, 1 was electively terminated, 1 resulted in the intrauterine death of twins, and 2 had unknown outcomes. animal data during organogenesis, pregnant rats and rabbits received deferiprone at oral doses of 0, 30, 80 or 200 mg/kg/day, and 0, 10, 50, or 150 mg/kg/day, respectively. the daily dose was administered as two equal divided doses approximately 7 hours apart. doses of 200 mg/kg/day in rats and 150 mg/kg/day in rabbits, approximately 33% and 49% of the mrhd, respectively, resulted in increased post-implantation loss and reduced fetal weights in the presence of maternal toxicity (reduced maternal body weight and body weight gain in both rats and rabbits; abnormal large placenta at low incidence in rats). the 200 mg/kg/day dose in rats resulted in external, visceral and skeletal fetal malformations such as cranial malformations, cleft palate, limb malrotation, anal atresia, internal hydrocephaly, anophthalmia and fused bones. the dose of 150 mg/kg/day in rabbits resulted in external fetal malformations (partially opened eyes) and minor blood vessel and skeletal variations. in rats, malformations including micrognathia and persistent ductus arteriosus could be observed in the absence of maternal toxicity at doses equal to or greater than 30 and 80 mg/kg/day, approximately 5% and 13% of the mhrd, respectively. risk summary there is no information regarding the presence of deferiprone in human milk, the effects on the breastfed child, or the effects on milk production. because of the potential for serious adverse reactions in the breastfed child, including the potential for tumorigenicity shown for deferiprone in animal studies, advise patients that breastfeeding is not recommended during treatment with deferiprone, and for at least 2 weeks after the last dose. pregnancy testing pregnancy testing is recommended for females of reproductive potential prior to initiating deferiprone. contraception females deferiprone can cause embryo-fetal harm when administered to a pregnant woman [see use in specific populations (8.1)] . advise female patients of reproductive potential to use effective contraception during treatment with deferiprone and for at least 6 months after the last dose. males based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with deferiprone and for at least 3 months after the last dose [see nonclinical toxicology (13.1)] . safety and effectiveness of deferiprone tablets have not been established in pediatric patients with chronic iron overload due to blood transfusions who are less than 8 years of age. pediatric use information is approved for chiesi usa, inc.'s ferriprox® (deferiprone) tablets. however, due to chiesi usa, inc.'s marketing exclusivity rights, this drug product is not labeled with that information. clinical studies of deferiprone did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Jungtinės Valstijos - anglų - NLM (National Library of Medicine)

chiesi usa, inc. - clevidipine (unii: 19o2gp3b7q) (clevidipine - unii:19o2gp3b7q) - clevidipine 0.5 mg in 1 ml - cleviprex is indicated for the reduction of blood pressure when oral therapy is not feasible or not desirable. cleviprex is contraindicated in patients with allergies to soybeans, soy products, eggs, or egg products. cleviprex is contraindicated in patients with defective lipid metabolism such as pathologic hyperlipemia, lipoid nephrosis, or acute pancreatitis if it is accompanied by hyperlipidemia. cleviprex is contraindicated in patients with severe aortic stenosis because afterload reduction can be expected to reduce myocardial oxygen delivery. risk summary the available data based on post-marketing reports with cleviprex use in pregnant women are not sufficient to inform a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. there are risks to the mother and fetus associated with poorly controlled hypertension in pregnancy (see clinical considerations ). in animal studies, clevidipine was associated with increased incidences of intrauterine deaths, slightly red

Jungtinės Valstijos - anglų - NLM (National Library of Medicine)

chiesi usa, inc. - zileuton (unii: v1l22wve2s) (zileuton - unii:v1l22wve2s) - zileuton 600 mg - zyflo cr is indicated for the prophylaxis and chronic treatment of asthma in adults and children 12 years of age and older. zyflo cr is not indicated for use in the reversal of bronchospasm in acute asthma attacks.  therapy with zyflo cr can be continued during acute exacerbations of asthma. the use of zyflo cr is contraindicated in patients with: - active liver disease or persistent hepatic function enzyme elevations greater than or equal to 3 times the upper limit of normal (≥3×uln) [see warnings and precautions (5), and use in specific populations (8.7) ]. - a history of allergic reaction to zileuton or any of the ingredients of zyflo cr (e.g., rash, eosinophilia, etc.). information on specific populations is based on studies conducted with zileuton immediate-release tablets and is applicable to zyflo cr. risk summary there are no adequate human data on zyflo cr use in pregnant women to inform a drug associated risk. in animal studies, oral administration of zileuton to pregnant rats and rabbits during org

Jungtinės Valstijos - anglų - NLM (National Library of Medicine)

chiesi usa, inc. - nicardipine hydrochloride (unii: k5bc5011k3) (nicardipine - unii:cz5312222s) - nicardipine hydrochloride 0.2 mg in 1 ml

Jungtinės Valstijos - anglų - NLM (National Library of Medicine)

chiesi usa, inc. - elapegademase (unii: 9r3d3y0uhs) (elapegademase - unii:9r3d3y0uhs) - revcovi is indicated for the treatment of adenosine deaminase severe combined immune deficiency (ada-scid) in pediatric and adult patients. none. adequate and well-controlled studies with revcovi have not been conducted in pregnant women to inform a drug-associated risk. animal reproduction studies have not been conducted with revcovi. it is not known whether revcovi can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. all pregnancies have a risk of birth defect, loss, or other adverse outcomes. in the us 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. human no pregnancy was reported for any patients receiving revcovi. there are two reports of confirmed cases of successful pregnancy and delivery in ada-scid patients treated with adagen (the same class of enzyme replacement therapy used in the treatment of ada-scid). no teratogenic effects of adagen

Jungtinės Valstijos - anglų - NLM (National Library of Medicine)

chiesi usa, inc. - tobramycin (unii: vz8rrz51vk) (tobramycin - unii:vz8rrz51vk) - tobramycin 300 mg in 4 ml - bethkis is indicated for the management of cystic fibrosis patients with pseudomonas aeruginosa . safety and efficacy have not been demonstrated in patients under the age of six years, patients with fev1 less than 40% or greater than 80% predicted, or patients colonized with burkholderia cepacia [see clinical studies ( 14 )] . bethkis is contraindicated in patients with a known hypersensitivity to any aminoglycoside. risk summary aminoglycosides can cause fetal harm. published literature reports that use of streptomycin, an aminoglycoside, can cause total, irreversible, bilateral congenital deafness when administered to a pregnant woman [warnings and precautions ( 5.6 )] . although there are no available data on use of bethkis in pregnant women to be able to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, systemic absorption of tobramycin following inhaled administration is expected to be minimal [see clinical pharmacology ( 12.3 )] . there are risks

Jungtinės Valstijos - anglų - NLM (National Library of Medicine)

chiesi usa, inc. - velmanase alfa-tycv (unii: m91tg242p2) (velmanase alfa-tycv - unii:m91tg242p2) - lamzede is indicated for the treatment of non-central nervous system manifestations of alpha-mannosidosis in adult and pediatric patients. none. risk summary based on findings from animal reproduction studies, lamzede may cause embryo-fetal harm when administered to a pregnant female. in animal reproduction studies, major visceral malformations were observed in rats and rabbits when velmanase alfa-tycv was administered in pregnant rats and rabbits during the period of organogenesis. these malformations were observed in rats at the highest dose level, at exposures that were approximately 7-fold the recommended dose in patients of 1 mg/kg. malformations occurred at all dose levels in rabbits with the highest dose exposures approximately 2.5-fold the recommended patient dose of 1 mg/kg ( see data ) . there are no available data on lamzede use in pregnant females to evaluate a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. advise the pregnant female of the po

Jungtinės Valstijos - anglų - NLM (National Library of Medicine)

chiesi usa, inc. - lomitapide mesylate (unii: x4s83cp54e) (lomitapide - unii:82kub0583f) - juxtapid is indicated as an adjunct to a low-fat diet and other lipid-lowering treatments, including ldl apheresis where available, to reduce low-density lipoprotein cholesterol (ldl-c), total cholesterol (tc), apolipoprotein b (apo b), and non-high-density lipoprotein cholesterol (non-hdl-c) in patients with homozygous familial hypercholesterolemia (hofh). limitations of use - the safety and effectiveness of juxtapid have not been established in patients with hypercholesterolemia who do not have hofh, including those with heterozygous familial hypercholesterolemia (hefh). - the effect of juxtapid on cardiovascular morbidity and mortality has not been determined. juxtapid is contraindicated in the following conditions: - pregnancy [see warnings and precautions (5.3) and use in specific populations (8.1)] . - concomitant administration of juxtapid with moderate or strong cyp3a4 inhibitors, as this can increase juxtapid exposure [see warnings and precautions (5.6), drug interactions (7.1), and clinical pharmacology (12.3)]. - patients with moderate or severe hepatic impairment (based on child-pugh category b or c) and patients with active liver disease, including unexplained persistent elevations of serum transaminases [see warnings and precautions (5.1) and use in specific populations (8.7)] . pregnancy exposure registry there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to juxtapid during pregnancy. for additional information visit www.juxtapid.com or call the global lomitapide pregnancy exposure registry (per) at 1-877-902-4099. healthcare professionals are encouraged to call the per at 1-877-902-4099 to enroll patients who become pregnant during juxtapid treatment. risk summary based on findings from animal studies, juxtapid use is contraindicated in pregnancy since it may cause fetal harm [see contraindications (4), warnings and precautions (5.3)]. available human data are insufficient to draw conclusions about any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes. however, in animal reproduction studies, lomitapide was teratogenic in rats at clinically relevant exposures and in ferrets at exposures estimated to be less than human therapeutic exposure at 60 mg when administered during organogenesis, based on auc comparisons. embryo-fetal lethality was observed in rabbits at 6-times the maximum recommended human dose (mrhd) of 60 mg based on body surface area. if pregnancy is detected, discontinue juxtapid. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. data animal data oral gavage doses of 0.04, 0.4, or 4 mg/kg/day lomitapide given to pregnant rats from gestation day 6 through organogenesis were associated with fetal malformations at ≥2-times human exposure at the mrhd (60 mg) based on plasma auc comparisons. fetal malformations included umbilical hernia, gastroschisis, imperforate anus, alterations in heart shape and size, limb malrotations, skeletal malformations of the tail, and delayed ossification of cranial, vertebral and pelvic bones. oral gavage doses of 1.6, 4, 10, or 25 mg/kg/day lomitapide given to pregnant ferrets from gestation day 12 through organogenesis were associated with both maternal toxicity and fetal malformations at exposures that ranged from less than the human exposure at the mrhd to 5-times the human exposure at the mrhd. fetal malformations included umbilical hernia, medially rotated or short limbs, absent or fused digits on paws, cleft palate, open eye lids, low-set ears, and kinked tail. oral gavage doses of 0.1, 1, or 10 mg/kg/day lomitapide given to pregnant rabbits from gestation day 6 through organogenesis were not associated with adverse effects at systemic exposures up to 3-times the mrhd of 60 mg based on body surface area comparison. treatment at doses of ≥20 mg/kg/day, ≥6-times the mrhd, resulted in embryo-fetal lethality. pregnant female rats given oral gavage doses of 0.1, 0.3, or 1 mg/kg/day lomitapide from gestation day 7 through termination of nursing on lactation day 20 were associated with malformations at systemic exposures equivalent to human exposure at the mrhd of 60 mg based on auc. increased pup mortality occurred at 4-times the mrhd. risk summary there are no data on the presence of lomitapide in human or animal milk, effects on the breastfed infant or on milk production. because of the potential for serious adverse reactions, including hepatotoxicity, advise patients that breastfeeding is not recommended during treatment with juxtapid. pregnancy testing females of reproductive potential should have a negative pregnancy test before starting juxtapid. contraception based on animal studies, juxtapid may cause fetal harm when administered to pregnant women [see use in specific populations (8.1) ]. advise females of reproductive potential to use effective contraception during treatment with juxtapid and for two weeks after the final dose. the use of juxtapid may result in reduced efficacy of oral contraceptives if vomiting or diarrhea occurs. advise patients using oral contraceptives and who experience vomiting or diarrhea to use an effective alternative contraceptive method until 7 days after resolution of symptoms [see drug interactions (7.2)]. safety and effectiveness have not been established in pediatric patients. clinical studies of juxtapid did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients. other reported clinical experience has not identified differences in responses between the elderly and younger patients. in general, dosing for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. patients with end-stage renal disease receiving dialysis should not exceed 40 mg daily since lomitapide exposure in these patients increased approximately 50% compared with healthy volunteers. effects of mild, moderate, and severe renal impairment, including those with end-stage renal disease not yet receiving dialysis, on lomitapide exposure have not been studied. however, it is possible that patients with renal impairment who are not yet receiving dialysis may experience increases in lomitapide exposure exceeding 50% [see clinical pharmacology (12.3)] . patients with mild hepatic impairment (child-pugh a) should not exceed 40 mg daily since the lomitapide exposure in these patients increased approximately 50% compared with healthy volunteers. juxtapid is contraindicated in patients with moderate (child-pugh b) or severe (child-pugh c) hepatic impairment since the lomitapide exposure in patients with moderate hepatic impairment increased 164% compared with healthy volunteers [see contraindications (4) and clinical pharmacology (12.3)] .