Juxtapid
Lomitapide mesylate · Capsule · Oral
Uses
1 INDICATIONS AND USAGE JUXTAPID is indicated as an adjunct to a low-fat diet and exercise and other low density lipoprotein cholesterol (LDL-C) therapies to reduce LDL-C in adults and pediatric patients aged 2 years and older with homozygous familial hypercholesterolemia (HoFH). JUXTAPID is a microsomal triglyceride transfer protein inhibitor indicated as an adjunct to a low-fat diet and exercise and other low-density lipoprotein cholesterol (LDL-C) therapies, to reduce LDL-C in adult and pediatric patients aged 2 years and older with HoFH. ( 1 ).
Dosage and administration
Before treatment, measure ALT, AST, alkaline phosphatase, and total bilirubin; obtain a negative pregnancy test in females of reproductive potential; initiate a low-fat diet supplying <20% of energy from fat or less than 30 grams of fat, whichever is less. ( 2.1 ). The recommended initiation dosage is ( 2.2 ): 2 mg for patients aged 2 to 15 years. 5 mg for patients aged 16 years and older. Follow the titration schedule presented in Table 1 according to the patient's age. Select the dosage based on the recommended target LDL-C, safety, and tolerability ( 2.2 ). For pediatric patients, if a patient crosses over into the next age category, escalate the dose of JUXTAPID up to the maximum recommended dose applicable for the new age group ( 2.2 ). Measure transaminases prior to any dosage increase. If transaminases are abnormal, reduce or withhold dosing of JUXTAPID and monitor as recommended ( 5.1 ). Table 1: Recommended JUXTAPID Dosage and Titration Schedule Age group (years) JUXTAPID Dose 2 mg 5 mg 10 mg 20 mg 40 mg 60 mg W:Weeks; ---: Not a recommended dosage; 1 Maximum recommended dosage. 2 to 10 W 0 to 8 W 9 to 12 W 13 to 16 W 17 and beyond 1 --- --- 11 to 15 W 0 to 4 W 5 to 8 W 9 to 12 W 13 to 16 17 and beyond 1 --- 16 to 17 --- W 0 to 4 W 5 to 8 W 9 to 12 13 and beyond 1 --- 18 and older --- W 0 to 2 W 3 to 6 W 7 to 10 W 11 to 14 15 and beyond 1 Due to reduced absorption of fat-soluble vitamins/fatty acids: Take daily vitamin E [400 international units (IU) for patients aged 9 years and older, or 200 IU for patients aged 2 to 8 years old] and linoleic acid (200 mg), alpha-linolenic acid (210 mg), eicosapentaenoic acid (110 mg), and docosahexaenoic acid (80 mg) supplements ( 2.2 ). Take orally once daily, whole, with water and without food, at least 2 hours after evening meal. If unable to swallow intact capsule, patients may sprinkle capsule contents onto a tablespoon of apple sauce or mashed banana ( 2.3 ). Refer to the Full PI for dosage modifications based on elevated transaminases ( 2.5 ); in patients with end-stage renal disease on dialysis require dose adjustment ( 2.6 ), and in patients with baseline mild hepatic impairment require dose adjustment ( 2.7 ). 2.1 Prior to Initiation Before beginning treatment with JUXTAPID: Liver function tests: Measure transaminases (ALT, AST), alkaline phosphatase, and total bilirubin [see Warnings and Precautions (5.1) ] ; Pregnancy testing: Obtain a negative pregnancy test in females of reproductive potential prior to initiating treatment with JUXTAPID [see Contraindications (4) , Warnings and Precautions (5.3) , and Use in Specific Populations (8.1 , 8.3) ] ; Dietary counseling: Initiate a low-fat diet supplying <20% of energy from fat or less than 30 grams of fat, whichever is less [see Warnings and Precautions (5.5) ]. 2.2 Recommended Dosage Initiation Dosage The recommended initiation dosage is 2 mg for patients aged 2 to 15 years. 5 mg for patients aged 16 years and older. Dosage Titration Follow the titration schedule presented in Table 1 according to the patient's age. Select the dosage based on target LDL-C level recommended in current HoFH treatment guidance, safety, and tolerability. For pediatric patients, if a patient crosses over into the next age group, escalate the dosage of JUXTAPID to dosage recommended for the new age group. Measure transaminases prior to any dosage increase. If transaminases are abnormal, reduce or withhold dosing of JUXTAPID and monitor as recommended [see Warnings and Precautions (5.1) ] . Table 1: Recommended JUXTAPID Dosage and Titration Schedule Age Group JUXTAPID Dosage and Titration Schedule 2 mg 5 mg 10 mg 20 mg 40 mg 60 mg 2 to 10 years Weeks 0 to 8 Weeks 9 to 12 Weeks 13 to 16 Weeks 17 and beyond Maximum recommended dosage. Select the dosage based on target LDL-C level recommended in current HoFH treatment guidance, safety and tolerability. Not recommended Not recommended 11 to 15 years Weeks 0 to 4 Weeks 5 to 8 Weeks 9 to 12 Weeks 13 to 16 Weeks 17 and beyond Not recommended 16 to l7 years Not recommended Weeks 0 to 4 Weeks 5 to 8 Weeks 9 to 12 Weeks 13 and beyond Not recommended 18 years and older Not recommended Weeks 0 to 2 Weeks 3 to 6 Weeks 7 to 10 Weeks 11 to 14 Week 15 and beyond Maximum Recommended Dosage The maximum recommended dosage is: 20 mg for patients aged 2 to 10 years. 40 mg for patients aged 11 to 17 years. 60 mg for patients aged 18 years and older. Nutritional Supplementation To reduce the risk of developing a fat-soluble nutrient deficiency due to JUXTAPID's mechanism of action in the small intestine [see Warnings and Precautions (5.4) ] , administer JUXTAPID with daily nutritional supplements. See Table 2 for nutritional supplementation recommendations according to age. Table 2: Nutritional Supplementation Recommendations for Adult and Pediatric Patients Aged 2 Years and Older Receiving JUXTAPID Age Group Vitamin E Essential Fatty Acids 2 to 8 years 200 International Units (IU) (134 mg d-alpha-tocopherol or 90 mg dl-alpha-tocopherol) Linoleic acid: 200 mg Alpha-linolenic acid (ALA): 210 mg Eicosapentaenoic acid (EPA): 110 mg Docosahexaenoic acid (DHA): 80 mg 9 years and older 400 IU (268 mg d-alpha-tocopherol or 180 mg dl-alpha-tocopherol) 2.3 Administration Take JUXTAPID orally once daily with a glass of water, without food, at least 2 hours after the evening meal. Administration with food may increase the risk of gastrointestinal adverse reactions [see Warnings and Precautions (5.5) ]. Swallow JUXTAPID capsules whole: If a patient is unable to swallow the intact capsule(s), open the capsule(s) and sprinkle the contents on 1 tablespoon of apple sauce or mashed banana. For younger patients who require a smaller spoon for administration, sprinkle the capsule contents onto 1 tablespoon of apple sauce or mashed banana, and administer the entire amount using the smaller spoon.
Dosage forms and strengths
Capsules: 2 mg: Grey/grey hard gelatin capsule printed with black ink "A733" and "2 mg" 5 mg: Orange/orange hard gelatin capsule printed with black ink "A733" and "5 mg" 10 mg: Orange/white hard gelatin capsule printed with black ink "A733" and "10 mg" 20 mg: White/white hard gelatin capsule printed with black ink "A733" and "20 mg" 30 mg: Orange/yellow hard gelatin capsule printed with black ink "A733" and "30 mg" Capsules: 2 mg, 5 mg, 10 mg, 20 mg, and 30 mg ( 3 ).
Contraindications
4 CONTRAINDICATIONS 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 ( 4 ). Concomitant use with strong or moderate CYP3A4 inhibitors ( 4 ). Moderate or severe hepatic impairment or active liver disease including unexplained persistent abnormal liver function tests ( 4 ).
Warnings and precautions
Embryo-Fetal Toxicity: May cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception. Discontinue JUXTAPID if pregnancy detected ( 5.3 ). Gastrointestinal adverse reactions occur in 93% of adult and 72% of pediatric patients and could affect absorption of concomitant oral medications ( 5.5 ). 5.1 Risk of Hepatotoxicity JUXTAPID can cause elevations in transaminases and hepatic steatosis in adults and pediatric patients, as described below [see Warnings and Precautions (5.2) ] . JUXTAPID may induce steatohepatitis, which can progress to cirrhosis over several years. Clinical trials of JUXTAPID for HoFH would have been unlikely to detect this adverse outcome given their size and duration [see Clinical Studies (14) ] . Elevation of Transaminases Elevations in transaminases (ALT and/or AST) are associated with JUXTAPID. In the 78-week adult clinical trial, 10 (34%) of the 29 patients with HoFH had at least one elevation in ALT or AST ≥3 times ULN, and 4 (14%) of the patients had at least one elevation in ALT or AST ≥5 times ULN. There were no concomitant or subsequent clinically meaningful elevations in bilirubin, INR, or alkaline phosphatase [see Adverse Reactions (6.1) ]. No patients discontinued prematurely because of elevated transaminases. Among the 19 patients who subsequently enrolled in the adult HoFH extension trial, one discontinued because of increased transaminases that persisted despite several dose reductions, and one temporarily discontinued because of markedly elevated transaminases (ALT 24 times ULN, AST 13 times ULN) that had several possible causes, including a drug-drug interaction between JUXTAPID and the strong CYP3A4 inhibitor clarithromycin [see Drug Interactions (7.1) ]. In the 104-week open-label trial in pediatric patients aged 5 to 17 years with HoFH exposed to JUXTAPID, 6 (14%) of the 43 patients with HoFH had at least one elevation in ALT and/or AST ≥3 times ULN, including 2 (5%) patients who had at least one elevation in ALT ≥5 times ULN. No patients discontinued treatment because of increased transaminases, although some patients required dose interruptions or reductions for management of liver transaminase elevations. Monitoring of Transaminases Before initiating JUXTAPID and during treatment, monitor transaminases as recommended in Table 7. Table 7: Recommendations for Monitoring Transaminases TIME RECOMMENDATIONS Before initiating treatment Measure ALT, AST, alkaline phosphatase, and total bilirubin. If abnormal, consider initiating JUXTAPID only after an appropriate work-up and the baseline abnormalities have been explained or resolved. JUXTAPID is contraindicated in patients with moderate or severe hepatic impairment, or active liver disease, including unexplained persistent elevations of serum transaminases [see Contraindications (4) ] . During the first year Measure liver-related tests (ALT and AST, at a minimum) prior to each increase in dose or monthly, whichever occurs first. After the first year Measure liver-related tests (ALT and AST, at a minimum) at least every 3 months and before any increase in dose. At any time during treatment If transaminases are >1 and <3 times ULN, no dose modification is required. Continue routine monitoring of liver-related tests (once monthly during the first year of treatment and every 3 months thereafter). If transaminases are ≥3 times ULN, reduce or withhold dosing of JUXTAPID and monitor as recommended [see Dosage and Administration (2.5) ]. Discontinue JUXTAPID for persistent or clinically significant elevations. If transaminase elevations are accompanied by clinical symptoms of liver injury (such as nausea, vomiting, abdominal pain, fever, jaundice, lethargy, flu-like symptoms), increases in bilirubin ≥2 times ULN, or active liver disease, discontinue treatment with JUXTAPID and identify the probable cause. Hepatic Steatosis JUXTAPID increases hepatic fat, with or without concomitant increases in transaminases. Hepatic steatosis is a risk factor for progressive liver disease, including steatohepatitis and cirrhosis. The long-term consequences of hepatic steatosis associated with JUXTAPID treatment are unknown. During the HoFH clinical trial conducted in adults, the median absolute increase in hepatic fat was 6% after both 26 weeks and 78 weeks of treatment, from 1% at baseline, measured by magnetic resonance spectroscopy (MRS) [see Adverse Reactions (6.1) ]. Clinical data suggest that hepatic fat accumulation is reversible after stopping treatment with JUXTAPID, but whether histological sequelae remain is unknown, especially after long-term use; protocol scheduled liver biopsies were not performed in the adult clinical trial. In a phase 3 trial in pediatric patients, two patients (both aged 5 to 10 years) developed mild hepatic steatosis (as assessed by ultrasound), which resolved without specific medical interventions, other than the protocol specified follow-up ultrasounds and laboratory monitoring. Overall, the median absolute increase in hepatic fat was 4% after 24 weeks and 104 weeks, from 3% at baseline, measured by NMR. As with data from the adult patients, clinical pediatric data suggest that hepatic fat accumulation is reversible after stopping treatment with JUXTAPID, but whether histological sequelae remain is unknown, especially after long term use. Alcohol may increase levels of hepatic fat and induce or exacerbate liver injury. Drinking more than one alcoholic drink per day is not recommended for patients taking JUXTAPID. Exercise caution when using JUXTAPID with other medications known to have potential for hepatotoxicity, such as isotretinoin, amiodarone, acetaminophen (>4 g/day for ≥3 days/week), methotrexate, tetracyclines, and tamoxifen. The effect of concomitant administration of JUXTAPID with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Side effects
The following important adverse reactions have been observed and are discussed in detail in other sections of the label: Risk of hepatotoxicity [see Warnings and Precautions (5.1) ] Reduced absorption of fat-soluble vitamins, and serum fatty acids [see Warnings and Precautions (5.4) ] Gastrointestinal adverse reactions [see Warnings and Precautions (5.5) ] Most common adverse reactions in adult patients (incidence ≥10%) are diarrhea, nausea, dyspepsia, vomiting, and abdominal pain (6.1). Most common adverse reactions in pediatric patients aged 5 to 17 years old (incidence ≥15%) are abdominal pain, alanine aminotransferase increased, aspartate aminotransferase increased, diarrhea, and vomiting ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Chiesi Farmaceutici S.p.A. at 1-888-661-9260 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adults with HoFH One single-arm, open-label, 78-week trial has been conducted in 29 adult patients with HoFH, 23 of whom completed at least one year of treatment. The initial dosage of JUXTAPID was 5 mg daily, with titration up to 60 mg daily during an 18-week period based on safety and tolerability. In this trial, the mean age was 31 years (range, 18 to 55 years), 16 (55%) patients were male, 25 (86%) patients were White, 2 (7%) were Asian, 1 (3%) was Black or African American, and 1 (3%) was multi-racial [see Clinical Studies (14) ] . Five (17%) of the 29 patients discontinued treatment due to an adverse reaction. The adverse reactions that contributed to treatment discontinuations included diarrhea (2 patients; 7%) and abdominal pain, nausea, gastroenteritis, weight loss, headache, and difficulty controlling INR on warfarin (1 patient each; 3%). The most common adverse reactions were gastrointestinal, reported by 27 (93%) of 29 patients. Adverse reactions reported by ≥8 (28%) patients in the clinical trial included diarrhea, nausea, vomiting, dyspepsia, and abdominal pain. Other common adverse reactions, reported by 5 to 7 (17 to 24%) patients, included weight loss, abdominal discomfort, abdominal distension, constipation, flatulence, increased ALT, chest pain, influenza, nasopharyngitis, and fatigue. The adverse reactions reported in at least 10% of adult patients are presented in Table 8. Table 8: Adverse Reactions Reported in ≥10% of Patients in the Adult Clinical Trial ADVERSE REACTION N (%) Diarrhea 23 (79) Nausea 19 (65) Dyspepsia 11 (38) Abdominal pain 10 (34) Vomiting 10 (34) Chest pain 7 (24) Decreased weight 7 (24) Abdominal discomfort 6 (21) Abdominal distension 6 (21) Constipation 6 (21) Flatulence 6 (21) Influenza 6 (21) Fatigue 5 (17) Increased ALT 5 (17) Nasopharyngitis 5 (17) Back pain 4 (14) Gastroenteritis 4 (14) Pharyngolaryngeal pain 4 (14) Angina pectoris 3 (10) Defecation urgency 3 (10) Dizziness 3 (10) Fever 3 (10) Gastroesophageal reflux disease 3 (10) Headache 3 (10) Nasal congestion 3 (10) Palpitations 3 (10) Rectal tenesmus 3 (10) Adverse reactions of severe intensity were reported by 8 (28%) of 29 patients, with the most common being diarrhea (4 patients, 14%), vomiting (3 patients, 10%), increased ALT or hepatotoxicity (3 patients, 10%), and abdominal pain, distension, and/or discomfort (2 patients, 7%). Pediatric Patients with HoFH Aged 5 to 17 years A single-arm, open label, multinational, 104-week trial was conducted in 43 pediatric patients with HoFH aged 5 to 17 years. Thirty-nine of the patients completed the trial. The dose of JUXTAPID was escalated from an age-dependent starting dose to a maximum tolerated dose (MTD) as applicable to the pediatric age group and based on acceptable safety and tolerability criteria, in addition to LDL-C goals [see Dosage and Administration (2) and Clinical Studies (14) ] . Table 9: Adverse Reactions Reported in ≥10% of Pediatric Patients Aged 5 to 17 Years ADVERSE REACTION N (%) Elevated transaminases Grouped terms composed of several similar terms 23 (53) Abdominal pain 23 (53) Diarrhea 22 (51) Vomiting 12 (28) Decreased appetite 6 (14) Nausea 5 (12) Transaminase Elevations During the adult clinical trial, 10 (34%) of 29 patients had at least one elevation in ALT and/or AST ≥3 times ULN (see Table 10 ). No clinically meaningful elevations in total bilirubin or alkaline phosphatase were observed. Transaminases typically fell within one to four weeks of reducing the dose or withholding JUXTAPID. Among the 19 adult patients who enrolled in an extension trial following the adult clinical trial, one discontinued because of increased transaminases that persisted despite several dose reductions, and one temporarily discontinued because of markedly elevated transaminases (ALT 24 times ULN, AST 13 times ULN) that had several possible causes, including a drug-drug interaction between JUXTAPID and the strong CYP3A4 inhibitor clarithromycin [see Drug Interactions (7.1) ]. In the pediatric trial, 6 patients experienced elevations in ALT and/or AST ≥3 times ULN (see Table 10 ). No discontinuations occurred due to increased transaminases in the trial, although some patients required interrupting JUXTAPID or reducing the dose. Table 10: Patient Incidence of Transaminase Elevations During the Clinical Trials ADULTS Upper limits of normal (ULN) ranged from 33 to 41 international units/L for ALT and 36 to 43 international units/L for AST. N (%) PEDIATRIC PATIENTS AGED 5 TO 17 YEARS ULN ranged from 21 to 55 international units/L for ALT and 24 to 60 international units/L for AST, based on age and gender.
Drug interactions
7 DRUG INTERACTIONS CYP3A4 inhibitors increase exposure to lomitapide. Strong and moderate CYP3A4 inhibitors are contraindicated with JUXTAPID. Patients must avoid grapefruit juice ( 7.1 ). When administered with weak CYP3A4 inhibitors, the dose of JUXTAPID should be decreased by half. Follow the titration recommendations provided in the Full PI ( 7.2 ). Warfarin: Lomitapide increases plasma concentrations of warfarin. Monitor international normalized ratio (INR) regularly, especially with JUXTAPID dose adjustment ( 7.3 ). Simvastatin and lovastatin exposure increase with JUXTAPID. Limit dose when co-administered with JUXTAPID due to myopathy risk ( 7.4 ). P-glycoprotein (P-gp) Substrates: Consider dose reduction of P-gp substrate because of possible increased absorption with JUXTAPID ( 7.5 ). Bile Acid Sequestrants: Separate JUXTAPID dosing by at least 4 hours ( 7.6 ). 7.1 Moderate and Strong CYP3A4 Inhibitors A strong CYP3A4 inhibitor has been shown to increase lomitapide exposure approximately 27-fold [see Clinical Pharmacology (12.3) ] . Concomitant use of strong CYP3A4 inhibitors with JUXTAPID is contraindicated. Concomitant use of moderate CYP3A4 inhibitors has not been studied, but concomitant use with JUXTAPID is contraindicated since lomitapide exposure will likely increase significantly in the presence of these inhibitors. Avoid food or drinks containing grapefruit during JUXTAPID treatment [see Contraindications (4) , Warnings and Precautions (5.6) , and Clinical Pharmacology (12.3) ] . 7.2 Weak CYP3A4 Inhibitors Weak CYP3A4 inhibitors can increase lomitapide exposure approximately 2-fold [see Clinical Pharmacology (12.3) ] . When administered with weak CYP3A4 inhibitors, the dose of JUXTAPID should be decreased by half. Careful titration of JUXTAPID may then be considered based on LDL-C response and safety/tolerability to half the maximum recommended dosage except when co-administered with oral contraceptives only, in which case the maximum recommended JUXTAPID dosage is approximately two thirds of the maximum recommended dosage (Table 3) [see Dosage and Administration (2.4) , Warnings and Precautions (5.6) , and Clinical Pharmacology (12.3) ] . 7.3 Warfarin Lomitapide increases plasma concentrations of both R(+)-warfarin and S(-)-warfarin by approximately 30% and increases the INR 22%. Patients taking warfarin should undergo regular monitoring of INR, particularly after any changes in JUXTAPID dosage. The dose of warfarin should be adjusted as clinically indicated [see Warnings and Precautions (5.8) ] . 7.4 Simvastatin and Lovastatin The risk of myopathy, including rhabdomyolysis, with simvastatin and lovastatin monotherapy is dose-related. Lomitapide approximately doubles the exposure of simvastatin; therefore, the recommended dose of simvastatin should be reduced by 50% when initiating JUXTAPID [see Clinical Pharmacology (12.3) ] . While taking JUXTAPID, limit simvastatin dosage to 20 mg daily (or 40 mg daily for patients who have previously tolerated simvastatin 80 mg daily for at least one year without evidence of muscle toxicity). Refer to the simvastatin prescribing information for simvastatin dosing recommendations. Interaction between lovastatin and lomitapide has not been studied. However, the metabolizing enzymes and transporters responsible for the disposition of lovastatin and simvastatin are similar, suggesting that JUXTAPID may increase the exposure of lovastatin; therefore, reducing the dose of lovastatin should be considered when initiating JUXTAPID. 7.5 P-glycoprotein Substrates Lomitapide is an inhibitor of P-glycoprotein (P-gp). Coadministration of JUXTAPID with P-gp substrates may increase the absorption of P-gp substrates. Dose reduction of the P-gp substrate should be considered when used concomitantly with JUXTAPID. 7.6 Bile Acid Sequestrants JUXTAPID has not been tested for interaction with bile acid sequestrants. Administration of JUXTAPID and bile acid sequestrants should be separated by at least 4 hours since bile acid sequestrants can interfere with the absorption of oral medications.
Use in specific populations
Lactation: Breastfeeding not recommended ( 8.2 ). 8.1 Pregnancy Pregnancy Exposure There is a registry that monitors pregnancy outcomes in women exposed to JUXTAPID during pregnancy. For additional information visit www.JUXTAPID.com or call the Lomitapide Observational Worldwide Exposure Registry (LOWER) at 1-877-902-4099. Healthcare professionals are encouraged to call the LOWER 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. 8.2 Lactation 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. 8.3 Females and Males of Reproductive Potential 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) ]. 8.4 Pediatric Use The safety and effectiveness of JUXTAPID as an adjunct to other LDL-C lowering therapies for the treatment of HoFH have been established in pediatric patients aged 2 years and older. Use of JUXTAPID for this indication is supported by evidence from an open-label trial in adults; an open-label trial of 43 pediatric patients with HoFH aged 5 to 17 years old; and additional pharmacokinetic modeling and simulation data for pediatric patients aged 2 years and older. Adverse reactions reported in pediatric patients aged 5 to 17 years were similar to those reported in adults [see Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , and Clinical Studies (14) ] . The safety and effectiveness of JUXTAPID have not been established in pediatric patients younger than 2 years old. 8.5 Geriatric Use Clinical trials of JUXTAPID did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from 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. 8.6 Renal Impairment Patients with end-stage renal disease (eGFR <15 mL/min/1.73m 2 ) receiving hemodialysis, lomitapide exposure increased approximately 50% compared with healthy volunteers [see Clinical Pharmacology (12.3) ] . The maximum recommended dosage of JUXTAPID in patients with end-stage renal disease receiving hemodialysis is lower than in those with normal renal function [see Dosage and Administration (2.6) ].
Pregnancy
8.1 Pregnancy Pregnancy Exposure There is a registry that monitors pregnancy outcomes in women exposed to JUXTAPID during pregnancy. For additional information visit www.JUXTAPID.com or call the Lomitapide Observational Worldwide Exposure Registry (LOWER) at 1-877-902-4099. Healthcare professionals are encouraged to call the LOWER 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.
Pediatric use
8.4 Pediatric Use The safety and effectiveness of JUXTAPID as an adjunct to other LDL-C lowering therapies for the treatment of HoFH have been established in pediatric patients aged 2 years and older. Use of JUXTAPID for this indication is supported by evidence from an open-label trial in adults; an open-label trial of 43 pediatric patients with HoFH aged 5 to 17 years old; and additional pharmacokinetic modeling and simulation data for pediatric patients aged 2 years and older. Adverse reactions reported in pediatric patients aged 5 to 17 years were similar to those reported in adults [see Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , and Clinical Studies (14) ] . The safety and effectiveness of JUXTAPID have not been established in pediatric patients younger than 2 years old.
Geriatric use
8.5 Geriatric Use Clinical trials of JUXTAPID did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from 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.
Overdosage
There is no specific treatment in the event of overdose of JUXTAPID. In the event of overdose, the patient should be treated symptomatically, and supportive measures instituted as required. Liver-related tests should be monitored. Hemodialysis is unlikely to be beneficial given that lomitapide is highly protein-bound.
Description
11 DESCRIPTION JUXTAPID capsules contain lomitapide mesylate, a synthetic lipid-lowering agent for oral administration. The chemical name of lomitapide mesylate is N-(2,2,2-trifluoroethyl)-9-[4-[4-[[[4'a-(trifluoromethyl)[1,1'-biphenyl]-2-yl]carbonyl]amino]-1-piperidinyl]butyl]-9 H -fluorene-9-carboxamide, methanesulfonate salt. Its structural formula is: The empirical formula for lomitapide mesylate is C 39 H 37 F 6 N 3 O 2 ∙ CH 4 O 3 S and its molecular weight is 789.8. Lomitapide mesylate is a white to off-white powder that is slightly soluble in aqueous solutions of pH 2 to 5. Lomitapide mesylate is freely soluble in acetone, ethanol, and methanol; soluble in 2-butanol, methylene chloride, and acetonitrile; sparingly soluble in 1-octanol and 2-propanol; slightly soluble in ethyl acetate; and insoluble in heptane. Each JUXTAPID capsule contains lomitapide mesylate equivalent to 2, 5, 10, 20, or 30 mg lomitapide free base and the following inactive ingredients: pregelatinized starch, sodium starch glycolate, microcrystalline cellulose, lactose monohydrate, silicon dioxide and magnesium stearate. The capsule shells of all strengths contain gelatin and titanium dioxide; the 2 mg capsules contain black iron oxide; the 5 mg, 10 mg and 30 mg capsules also contain red iron oxide; and the 30 mg capsules also contain yellow iron oxide. The imprinting ink contains shellac, black iron oxide, and propylene glycol. Chemical Structure
Mechanism of action
12.1 Mechanism of Action JUXTAPID directly binds and inhibits microsomal triglyceride transfer protein (MTP), which resides in the lumen of the endoplasmic reticulum, thereby preventing the assembly of apo B-containing lipoproteins in enterocytes and hepatocytes. This inhibits the synthesis of chylomicrons and VLDL. The inhibition of the synthesis of VLDL leads to reduced levels of plasma LDL-C.
How supplied
How Supplied JUXTAPID strengths are available as follows: Capsule Strength Description Package Configuration NDC Number 2 mg Grey/grey hard gelatin capsule printed with black ink "A733" and "2 mg" Bottles of 28 capsules 10122-402-28 5 mg Orange/orange hard gelatin capsule printed with black ink "A733" and "5 mg" Bottles of 28 capsules 10122-405-28 10 mg Orange/white hard gelatin capsule printed with black ink "A733" and "10 mg" Bottles of 28 capsules 10122-410-28 20 mg White/white hard gelatin capsule printed with black ink "A733" and "20 mg" Bottles of 28 capsules 10122-420-28 30 mg Orange/yellow hard gelatin capsule printed with black ink "A733" and "30 mg" Bottles of 28 capsules 10122-430-28 Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (between 59°F and 86°F). Brief exposure to temperatures up to 40°C (104°F) may be tolerated provided the mean kinetic temperature does not exceed 25°C (77°F); however, such exposure should be minimized. Keep container tightly closed and protect from moisture.
Storage
Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (between 59°F and 86°F). Brief exposure to temperatures up to 40°C (104°F) may be tolerated provided the mean kinetic temperature does not exceed 25°C (77°F); however, such exposure should be minimized. Keep container tightly closed and protect from moisture.
Patient information
See FDA-approved labeling ( Medication Guide ) Patients or their caregiver(s) should be informed that a registry for patients taking JUXTAPID has been established to monitor and evaluate the long-term effects of JUXTAPID. Patients or their caregiver(s) are encouraged to participate in the registry and should be informed that their participation is voluntary. For information regarding the registry program visit www.JUXTAPID.com or call 1-877-902-4099. Advise patients of the following: Risk of Hepatotoxicity [see Warnings and Precautions (5.1) ] JUXTAPID can cause both elevations in transaminases and hepatic steatosis. Discuss with patients or their caregiver(s) about the importance of monitoring of liver-related tests before taking JUXTAPID, prior to each dose escalation, and periodically thereafter. Advise patients of the potential for increased risk of liver injury if alcohol is consumed while taking JUXTAPID. It is recommended that patients taking JUXTAPID limit consumption to not more than one alcoholic drink per day. JUXTAPID is commonly associated with nausea, vomiting, and abdominal pain. Advise patients or their caregiver(s) to promptly report these symptoms if they increase in severity, persist, or change in the character, as they might reflect liver injury. Patients or their caregiver(s) should also report any other symptoms of possible liver injury, including fever, jaundice, lethargy, or flu-like symptoms. JUXTAPID REMS Program [see Warnings and Precautions (5.2) ] JUXTAPID is only available through a restricted program called JUXTAPID REMS Program and therefore, JUXTAPID is only available from certified pharmacies that are enrolled in the program. Embryofetal Toxicity [see Warnings and Precautions (5.3) , Drug Interactions (7.2) , Use in Specific Populations (8.1 , 8.3) ] JUXTAPID is contraindicated in pregnancy since it may cause fetal harm. Advise female patients who become pregnant to discontinue JUXTAPID and inform their healthcare provider of a known or suspected pregnancy. Advise female patients of reproductive potential to use effective contraception during treatment with JUXTAPID and for two weeks after the final dose. Advise patients who are taking oral contraceptives and experience vomiting or diarrhea while taking JUXTAPID to use an effective alternative contraceptive method until 7 days after resolution of symptoms . Lactation [see Use in Specific Populations (8.2) ] Advise female patients not to breastfeed during treatment with JUXTAPID . Dietary Supplements [see Warnings and Precautions (5.4) ] Inform patients or their caregiver(s) that JUXTAPID may reduce the absorption of fat-soluble nutrients. Instruct patients or their caregiver(s) to take daily nutritional supplements that contain the dosages of vitamin E and essential fatty acids recommended in the Dosage and Administration Section (2.2) . Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.5) ] Inform patients or their caregiver(s) that gastrointestinal adverse reactions are common with JUXTAPID. These include, but are not limited to, diarrhea, nausea/vomiting, abdominal pain/discomfort, flatulence, and constipation. Advise patients or their caregiver(s) to adhere to low-fat diet supplying <20% of energy from fat or less than 30 grams of fat, whichever is less, to reduce the risk of gastrointestinal adverse reactions. Instruct patients or their caregiver(s) to stop JUXTAPID and contact their healthcare provider if severe diarrhea occurs or if they experience symptoms of volume depletion such as lightheadedness, decreased urine output, or tiredness. Inform patients or their caregiver(s) that taking JUXTAPID with food may adversely impact gastrointestinal tolerability; therefore, they should take JUXTAPID at least 2 hours after the evening meal, swallowing each capsule whole, with water. Inform patients or their caregiver(s) that if the patient is unable to swallow the intact capsule(s), the capsule(s) can be opened and the contents sprinkled on 1 tablespoon of apple sauce or mashed banana, which are fat free. For younger patients who require a smaller spoon for administration, inform the patient or their caregiver(s) to sprinkle the capsule content onto 1 tablespoon of apple sauce or mashed banana and administer the entire amount using the smaller spoon. Absorption of oral medications may be affected in patients who develop diarrhea or vomiting. For example, hormone absorption from oral contraceptives may be incomplete, warranting the use of additional contraceptive methods. Patients who develop these symptoms should seek advice from their healthcare provider. Drug Interactions [see Warnings and Precautions (5.6 , 5.7) and Drug Interactions (7) ] Instruct patients or their caregiver(s) to avoid food or drinks containing grapefruit during JUXTAPID treatment. Because multiple drug-drug interactions have been described with JUXTAPID, advise patients or their caregiver(s) to tell their healthcare provider(s) about all medications, nutritional supplements, and vitamins that they are taking or may be taking while taking JUXTAPID. Advise patients taking simvastatin or lovastatin that JUXTAPID may cause myopathy. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever. Missed Doses If a dose of JUXTAPID is missed, the normal dose should be taken at the usual time the next day. If dosing is interrupted for more than a week, tell patients or their caregiver(s) to contact their healthcare provider before restarting treatment.
Label text from the FDA structured product label by Chiesi USA, Inc. (revised Mar 30, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Lomitapide Mesylate in 7 products
Juxtapid NDC products (7)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 76431-110 | Lomitapide Mesylate 10 mg/1 Capsule | Amryt Pharmaceuticals DAC | NDA |
| 76431-120 | Lomitapide Mesylate 20 mg/1 Capsule | Amryt Pharmaceuticals DAC | NDA |
| 10122-402 | Lomitapide Mesylate 2 mg/1 Capsule | Chiesi USA, Inc. | NDA |
| 10122-405 | Lomitapide Mesylate 5 mg/1 Capsule | Chiesi USA, Inc. | NDA |
| 10122-410 | Lomitapide Mesylate 10 mg/1 Capsule | Chiesi USA, Inc. | NDA |
| 10122-420 | Lomitapide Mesylate 20 mg/1 Capsule | Chiesi USA, Inc. | NDA |
| 10122-430 | Lomitapide Mesylate 30 mg/1 Capsule | Chiesi USA, Inc. | NDA |
Frequently asked questions
What is Juxtapid used for?
1 INDICATIONS AND USAGE JUXTAPID is indicated as an adjunct to a low-fat diet and exercise and other low density lipoprotein cholesterol (LDL-C) therapies to reduce LDL-C in adults and pediatric patients aged 2 years and older with homozygous familial hypercholesterolemia (HoFH). JUXTAPID is a microsomal triglyceride transfer protein inhibitor indicated as an adjunct to a low-fat diet and…
What are the side effects of Juxtapid?
The following important adverse reactions have been observed and are discussed in detail in other sections of the label: Risk of hepatotoxicity [see Warnings and Precautions (5.1) ] Reduced absorption of fat-soluble vitamins, and serum fatty acids [see Warnings and Precautions (5.4) ] Gastrointestinal adverse reactions [see Warnings and Precautions (5.5) ] Most common adverse reactions in adult… See the full label for the complete list.
Who makes Juxtapid?
Juxtapid is listed by 2 labelers in the FDA NDC directory, including Amryt Pharmaceuticals DAC, Chiesi USA, Inc..