Juxtapid

2 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. Administer JUXTAPID at least 4 hours before or 4 hours after administration of a bile acid sequestrant [see Drug Interactions (7.6) ]. 2.4 Dosage Modifications for Cytochrome P450 3A4 Inhibitors Moderate or Strong Cytochrome P450 3A4 Inhibitors JUXTAPID is contraindicated with concomitant use of moderate and strong cytochrome P450 3A4 (CYP3A4) inhibitors [see Contraindications (4) and Drug Interactions (7.1) ]. Weak CYP3A4 Inhibitors (With or Without Oral Contraceptives) J UXTAPID Initiation in Patients Treated with a Stable Dosage of a Weak CYP3A4 Inhibitor: Follow the recommended dosage and titration schedule described in Table 1. Consider target LDL-C level, safety, and tolerability when selecting a maintenance dosage. Refer to the maximum recommended dose of JUXTAPID described in Table 3. Weak CYP3A4 Inhibitor Initiation in Patients Treated with a Stable Dosage of JUXTAPID: Decrease the dosage of JUXTAPID by half. The dosage of JUXTAPID may be further titrated according to target LDL-C level, safety, and tolerability, not to exceed the maximum recommended dose of JUXTAPID described in Table 3. Concomitant Oral contraceptive use Only JUXTAPID Initiation in Patients Treated with a Stable Dosage of an Oral Contraceptive: Follow the recommended dosage and titration schedule described in Table 1. Consider target LDL-C level, safety, and tolerability when selecting a maintenance dosage, not to exceed the maximum recommended dose of JUXTAPID described in Table 3. Oral contraceptive Initiation in Patients Treated with a Stable Dosage of JUXTAPID: Decrease the dose of JUXTAPID by one-third. The dosage of JUXTAPID may be further titrated according to target LDL-C level, safety, and tolerability, not to exceed the maximum recommended dose of JUXTAPID described in Table 3. Table 3: Recommended Maximum JUXTAPID Dosage with Concomitant Weak CYP3A4 inhibitor or an Oral Contraceptive Age group Maximum JUXTAPID Dosage Weak CYP3A4 inhibitor Oral Contraceptive Oral contraceptives are not indicated before menarche. 2 to 10 years 10 mg 15 mg 11 to 17 years 20 mg 30 mg 18 years and older 30 mg 40 mg 2.5 Dosage Modification Based on Elevated Transaminases Table 4 summarizes recommendations for dosage adjustment and monitoring for patients who develop elevated transaminases during treatment with JUXTAPID [see Warnings and Precautions (5.1) ]. Table 4: Dosage Adjustment and Monitoring for Patients with Elevated Transaminases ALT OR AST TREATMENT AND MONITORING RECOMMENDATIONS Recommendations based on an age and gender appropriate ULN. ≥3 times and <5 times ULN Confirm elevation with a repeat measurement within one week. If confirmed, reduce the dosage to the last tolerated dosage, and obtain additional liver-related tests if not already measured (such as alkaline phosphatase, total bilirubin, and INR). Repeat tests weekly and withhold dosing if there are signs of abnormal liver function (increase in bilirubin or INR), if transaminase levels rise above 5 times the ULN, or if transaminase levels do not fall below 3 times ULN within approximately 4 weeks. In these cases of persistent or worsening abnormalities, also investigate to identify the probable cause. If resuming JUXTAPID after transaminases resolve to <3 times ULN, consider reducing the dose to the last tolerated dosage, and monitor liver-related tests more frequently. ≥5 times ULN Withhold dosing, obtain additional liver-related tests if not already measured (such as alkaline phosphatase, total bilirubin, and INR), and investigate to identify the probable cause. If resuming JUXTAPID after transaminases resolve to <3 times ULN, reduce the dose to the last tolerated dosage, and monitor liver-related tests more frequently. 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 investigate to identify the probable cause [see Warnings and Precautions (5.1) ] . 2.6 Recommended Dosage in Patients with Renal Impairment The recommended dosage of JUXTAPID in patients with end-stage renal disease (eGFR <15 mL/min/1.73m 2 ) receiving hemodialysis is described in Table 5. JUXTAPID has not been studied in patients with mild, moderate, or severe renal impairment, including those with end stage renal disease not receiving dialysis [see Use in Specific Populations (8.6) ]. Table 5: Dosage Adjustment for Patients with End Stage Renal Disease Receiving Hemodialysis Age GROUP MAXIMUM RECOMMENDED DAILY DOSAGE 2 to 10 years 15 mg 11 to 17 years 30 mg 18 years and older 40 mg 2.7 Recommended Dosage in Patients with Baseline Hepatic Impairment JUXTAPID is contraindicated in 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 (5.6) ] . Table 6 summarizes the dosage adjustment for patients with baseline mild hepatic impairment (Child-Pugh A) [see Use in Specific Populations (8.7) ] . Table 6: Dosage Adjustment for Patients with Baseline Mild Hepatic Impairment AGE GROUP MAXIMUM RECOMMENDED DAILY DOSAGE 2 to 10 years 15 mg 11 to 17 years 30 mg 18 years and older 40 mg

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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).