Version May 2024
Lomitapide can cause elevations in transaminases. In the clinical trial, 34% of patients had at least 1 elevation in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 3 times the upper limit of normal (ULN) or higher. There were no concomitant clinically meaningful elevations of total bilirubin, international normalized ratio (INR), or alkaline phosphatase.
Lomitapide also increases hepatic fat, with or without concomitant increases in transaminases. The median absolute increase in hepatic fat was 6% after both 26 and 78 weeks of treatment, from 1% at baseline, measured by magnetic resonance spectroscopy (MRS). Hepatic steatosis associated with lomitapide treatment may be a risk factor for progressive liver disease, including steatohepatitis and cirrhosis.
Measure ALT, AST, alkaline phosphatase, and total bilirubin before initiating treatment and then ALT and AST regularly as recommended. During treatment, adjust the dose of lomitapide if the ALT or AST is 3 times the ULN or higher. Discontinue lomitapide for clinically significant liver toxicity.
Because of the risk of hepatotoxicity, lomitapide is available only through a restricted program under a risk evaluation and mitigation strategy (REMS) called the Juxtapid REMS program. Prescribe lomitapide only to patients with a clinical or laboratory diagnosis consistent with homozygous familial hypercholesterolemia (HoFH). The safety and effectiveness of lomitapide have not been established in patients with hypercholesterolemia who do not have HoFH.
Homozygous familial hypercholesterolemia (adjunctive agent):
Note:
Safety: Measure transaminases (ALT, AST), alkaline phosphatase, and total bilirubin prior to initiation and prior to any dose increase; obtain a negative pregnancy test in female patients of reproductive potential prior to beginning treatment (manufacturer's labeling).
Appropriate use: Refer patient to a lipid specialist prior to use. Consider for use in patients with baseline low-density lipoprotein cholesterol ≥190 mg/dL who have an inadequate response to statins with or without ezetimibe and PCSK9 inhibitors (ACC [Lloyd-Jones 2022]). To reduce development of fat-soluble nutrient deficiency, administer daily supplements containing vitamin E 400 units, linoleic acid ≥200 mg, alpha-linolenic acid (ALA) ≥210 mg, eicosapentaenoic acid (EPA) ≥110 mg, and docosahexaenoic acid (DHA) ≥80 mg. Initiate and maintain a low-fat diet supplying <20% of energy from fat (manufacturer's labeling).
Oral: Initial: 5 mg once daily; after ≥2 weeks of therapy, may increase to 10 mg once daily, as tolerated; then at ≥4-week intervals, may increase to 20 mg once daily, then to 40 mg once daily, and finally to a maximum dose of 60 mg/day as tolerated.
Dosage adjustment for concomitant therapy: Significant drug interactions exist requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Mild to severe impairment (not receiving dialysis): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, it is possible that patients with renal impairment not receiving dialysis may experience increases in lomitapide exposure exceeding 50%.
End stage renal disease (ESRD; receiving dialysis): Maximum dose: 40 mg/day
Mild impairment (Child-Pugh class A): Maximum dose: 40 mg/day
Moderate to severe impairment (Child-Pugh class B or C), active liver disease (including unexplained persistent transaminase elevations): Use is contraindicated.
Hepatotoxicity: Note: If transaminases are abnormal, reduce or withhold dose; monitor as recommended. If transaminase elevations are accompanied by clinical symptoms of liver injury (eg, nausea, vomiting, abdominal pain, fever, jaundice, lethargy, flu-like symptoms), increases in bilirubin ≥2 times ULN, or active liver disease, discontinue use and investigate for probable cause.
AST or ALT ≥ 3 to <5 times ULN: Confirm measurement (within 1 week); once confirmed, reduce dose and obtain additional liver function tests (LFTs) (eg, alkaline phosphatase, total bilirubin, and INR); repeat tests weekly and withhold subsequent doses if signs of abnormal liver function (eg, increased bilirubin or INR), if transaminases rise to >5 times ULN, or if they do not fall to <3 times ULN within ~4 weeks; investigate for probable cause. If resuming after transaminase resolution to <3 times ULN, consider reducing dose and monitor LFTs more frequently.
AST or ALT ≥ 5 times ULN: Withhold doses, obtain additional LFTs (eg, alkaline phosphatase, total bilirubin, and INR); investigate for probable cause. If resuming after transaminase resolution to <3 times ULN, reduce dose and monitor LFTs more frequently.
Persistent or clinically significant transaminase elevations: Discontinue use.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Cardiovascular: Chest pain (24%)
Gastrointestinal: Abdominal distension (21%; severe abdominal distension: ≤7%), abdominal distress (21%; severe abdominal distress: ≤7%), abdominal pain (34%; severe abdominal pain: ≤7%), constipation (21%), diarrhea (79%; severe diarrhea: 14%), dyspepsia (38%), flatulence (21%), gastroenteritis (14%), nausea (65%), vomiting (34%; severe vomiting: 10%) weight loss (24%)
Hepatic: Increased serum alanine aminotransferase (17%; ≥3 to <5 × ULN: 21%; ≥5 to <10 × ULN: 10%; ≥10 to <20 × ULN: 3%), increased serum aspartate aminotransferase (≥3 to <5 × ULN: 17%; ≥5 to <10 × ULN: 3%), liver steatosis (increase in hepatic fat >5%: 78%; >20% fat increase: 13%)
Infection: Influenza (21%)
Nervous system: Fatigue (17%)
Neuromuscular & skeletal: Back pain (14%)
Respiratory: Nasopharyngitis (17%), pharyngolaryngeal pain (14%)
1% to 10%:
Cardiovascular: Angina pectoris (10%), palpitations (10%)
Gastrointestinal: Bowel urgency (10%), gastroesophageal reflux disease (10%), rectal tenesmus (10%)
Hepatic: Severe hepatotoxicity (≤10%)
Nervous system: Dizziness (10%), headache (10%)
Respiratory: Nasal congestion (10%)
Miscellaneous: Fever (10%)
Postmarketing:
Dermatologic: Alopecia
Neuromuscular & skeletal: Myalgia
Pregnancy; coadministration with moderate or strong CYP3A4 inhibitors; moderate or severe hepatic impairment (Child-Pugh class B or C) and patients with active liver disease, including unexplained persistent elevations of serum transaminases.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to lomitapide or any component of the formulation; known significant, chronic bowel disease (eg, inflammatory bowel disease, malabsorption); concomitant administration of simvastatin >20 mg daily (concomitant use with simvastatin 40 mg daily is permitted in patients previously tolerant of simvastatin 80 mg daily for ≥1 year without evidence of myotoxicity); galactose intolerance, congenital lactase deficiency, or glucose-galactose malabsorption
Concerns related to adverse effects:
• Gastrointestinal events: Significant gastrointestinal events (eg, diarrhea, nausea, dyspepsia, vomiting) occur commonly during treatment. Severe diarrhea, leading to volume depletion requiring hospitalization, has been reported. Monitor patients susceptible to complications from diarrhea (eg, elderly, coadministration with drugs causing volume depletion or hypotension). Consider dosage reduction or withholding dose if severe diarrhea or symptoms of volume depletion (eg, lightheadedness, decreased urine output, tiredness) occur. Absorption of other oral medications may be affected in patients with diarrhea or vomiting. Adhering to a low-fat diet (<20% of energy from fat) and gradual titration of dosage may reduce the risk of gastrointestinal adverse events.
• Hepatotoxicity: [US Boxed Warning]: May cause transaminase elevations; elevations in ALT or AST ≥3 times upper limit of normal occurred during clinical trials (no clinically meaningful concomitant bilirubin, INR, or alkaline phosphatase elevation was observed). Lomitapide also increases hepatic fat, with or without concomitant transaminase elevations. Hepatic steatosis associated with lomitapide (reversible upon discontinuation) may be a risk factor for progressive liver disease including steatohepatitis and cirrhosis. Monitor hepatic function (ALT, AST, alkaline phosphatase and total bilirubin) prior to treatment; monitor ALT and AST regularly as recommended during treatment; dosage adjustment, withholding dose or discontinuation may be necessary; transaminases typically reduce within 1 to 4 weeks after reducing the dose or discontinuation. Discontinue use with persistent or clinically significant elevations. Alcohol ingestion may increase the risk of hepatic steatosis and induce or exacerbate liver injury; alcohol consumption should be limited to ≤1 drink/day. Use caution when administered concomitantly with other hepatotoxic medications (eg, acetaminophen [>4 g/day for ≥3 days/week], amiodarone, isotretinoin, methotrexate, tetracyclines, tamoxifen); may require more frequent monitoring of liver function tests. Concomitant administration with other LDL-lowering agents that also have the potential to increase hepatic fat is not recommended (has not been studied).
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with mild (Child-Pugh class A) hepatic impairment due to increased drug exposure; a reduced dose is recommended. Use is contraindicated in patients with moderate to severe (Child-Pugh class B or C) impairment or active liver disease including unexplained persistent elevations of serum transaminases. If abnormal liver function tests have been explained or resolved, consideration may be given to initiation of lomitapide. Monitor liver function as recommended.
• Renal impairment: Use with caution in patients with mild to severe renal impairment including end-stage renal disease (ESRD) not receiving dialysis (has not been studied); drug exposure may significantly increase. Use with caution in patients with ESRD receiving dialysis; a reduced dose is recommended.
Dosage form specific issues:
• Lactose: Contains lactose; avoid use in patients with hereditary galactose intolerance, congenital lactase deficiency, or glucose-galactose malabsorption; may result in diarrhea and malabsorption.
Other warnings/precautions:
• Fat-soluble vitamins: Lomitapide may reduce the absorption of fat-soluble nutrients (eg, vitamin E, linoleic acid, alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid); supplementation is recommended. Patients with chronic bowel or pancreatic diseases predisposed to malabsorption are at increased risk for deficiency.
• Limitations of use: [US Boxed Warning]: Prescribe lomitapide only to patients with a clinical or laboratory diagnosis consistent with HoFH. Safety and effectiveness have not been established in patients with hypercholesterolemia who do not have HoFH, including those with heterozygous familial hypercholesterolemia. The effect of lomitapide on cardiovascular morbidity and mortality has not been determined.
• REMS program: [US Boxed Warning]: Due to the risk for hepatotoxicity, access is restricted through a REMS program (Juxtapid REMS program). Only certified healthcare providers and pharmacies may prescribe and dispense lomitapide.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Juxtapid: 5 mg, 10 mg, 20 mg, 30 mg, 40 mg [DSC], 60 mg [DSC]
No
Capsules (Juxtapid Oral)
5 mg (per each): $2,284.69
10 mg (per each): $2,284.69
20 mg (per each): $2,284.69
30 mg (per each): $2,284.69
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Juxtapid: 5 mg, 10 mg, 20 mg
Oral: Administer with water and without food; administer at least 2 hours after the evening meal since administration with food may increase risk of gastrointestinal adverse effects. Swallow capsules whole (do not open, crush, dissolve, or chew).
Hazardous agent (NIOSH 2016 [group 3]).
Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage. NIOSH recommends single gloving for administration of intact tablets or capsules (NIOSH 2016). Assess risk to determine appropriate containment strategy (USP-NF 2017).
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/203858s017lbl.pdf#page=32, must be dispensed with this medication.
Homozygous familial hypercholesterolemia: Adjunct to a low-fat diet and other lipid-lowering treatments, including low-density lipoprotein (LDL) apheresis where available, to reduce low-density lipoprotein cholesterol (LDL-C), total cholesterol, apolipoprotein B (apo B), and non-high-density lipoprotein cholesterol (non-HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH).
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.
Substrate of CYP1A2 (minor), CYP2B6 (minor), CYP2C19 (minor), CYP2C8 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (weak)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alcohol (Ethyl): May enhance the hepatotoxic effect of Lomitapide. Management: Advise patients to limit alcohol consumption to 1 drink per day while receiving lomitapide. Risk D: Consider therapy modification
Aldesleukin: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Atorvastatin: Lomitapide may increase the serum concentration of Atorvastatin. Atorvastatin may increase the serum concentration of Lomitapide. Management: When the lomitapide dose is 10 mg daily or greater, reduce the lomitapide dose by 50% when combined with atorvastatin. No dose adjustment is required when the lomitapide dose is 5 mg daily. Risk D: Consider therapy modification
Bile Acid Sequestrants: May decrease the absorption of Lomitapide. Management: Administer lomitapide at least 4 hours before or after administration of a bile acid sequestrant. Risk D: Consider therapy modification
CarBAMazepine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
Ciprofloxacin (Systemic): May increase the serum concentration of Lomitapide. Risk X: Avoid combination
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Lomitapide. Risk X: Avoid combination
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Lomitapide. Risk X: Avoid combination
CYP3A4 Inhibitors (Weak): May increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider therapy modification
Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Risk C: Monitor therapy
Elranatamab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Epcoritamab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination
Estrogen Derivatives: May increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 40 mg/day. Risk D: Consider therapy modification
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone. Risk C: Monitor therapy
Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy
FLUoxetine: May increase the serum concentration of Lomitapide. Management: Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half with concurrent fluoxetine; the lomitapide dose may then be increased to a max adult dose of 30 mg/day (patients on lomitapide 5 mg/day may continue that dose). Risk D: Consider therapy modification
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Ginkgo Biloba: May increase the serum concentration of Lomitapide. Management: Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half with concurrent gingko biloba; the lomitapide dose may then be increased to a max adult dose of 30 mg/day (patients on lomitapide 5 mg/day may continue that dose). Risk D: Consider therapy modification
Glofitamab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Istradefylline: May increase the serum concentration of Lomitapide. Management: Decrease the initial dose of lomitapide by half in patients taking lomitapide 10 mg daily or more when used in combination with weak CYP3A4 inhibitors, including istradefylline (dose of 40 mg daily or more). The maximum dose of lomitapide is 30 mg daily. Risk D: Consider therapy modification
Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy
Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider therapy modification
Lovastatin: Lomitapide may increase the serum concentration of Lovastatin. Management: Consider reducing lovastatin doses during concomitant treatment with lomitapide, and monitor for signs and symptoms of muscle toxicity. Specific dosing recommendations are not presently available. Risk D: Consider therapy modification
Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam. Risk C: Monitor therapy
Mipomersen: Lomitapide may enhance the hepatotoxic effect of Mipomersen. Specifically, the risk of steatosis may be increased with this combination. Risk X: Avoid combination
Mosunetuzumab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Nilotinib: May increase the serum concentration of Lomitapide. Management: Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half with concurrent nilotinib; the lomitapide dose may then be increased to a max adult dose of 30 mg/day (patients on lomitapide 5 mg/day may continue that dose). Risk X: Avoid combination
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy
Nirogacestat: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination
Pacritinib: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination
RaNITIdine (Withdrawn from US Market): May increase the serum concentration of Lomitapide. Management: Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half with concurrent ranitidine; the lomitapide dose may then be increased to a max adult dose of 30 mg/day (patients on lomitapide 5 mg/day may continue that dose). Risk D: Consider therapy modification
Red Yeast Rice: Lomitapide may increase the serum concentration of Red Yeast Rice. Management: Consider reducing red yeast rice doses during concomitant treatment with lomitapide, and monitor for signs and symptoms of muscle toxicity. Specific dosing recommendations are not presently available. Risk D: Consider therapy modification
Ritlecitinib: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Simvastatin: Lomitapide may increase serum concentrations of the active metabolite(s) of Simvastatin. Lomitapide may increase the serum concentration of Simvastatin. Management: Reduce the recommended simvastatin dose by 50%. Generally, limit the maximum adult simvastatin dose to 20 mg/day. A 40 mg/day dose can be considered in patients who previously received 80 mg/day for at least a year without evidence of muscle toxicity. Risk D: Consider therapy modification
Sirolimus (Conventional): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a weak CYP3A4 inhibitor. Risk D: Consider therapy modification
Spironolactone: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Talquetamab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Teclistamab: May increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Ticagrelor: May increase the serum concentration of Lomitapide. Management: Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half with concurrent ticagrelor; the lomitapide dose may then be increased to a max adult dose of 30 mg/day (patients on lomitapide 5 mg/day may continue that dose). Risk D: Consider therapy modification
Tipranavir: May increase the serum concentration of Lomitapide. Risk X: Avoid combination
Treosulfan: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination
Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Risk C: Monitor therapy
Trofinetide: May increase the serum concentration of CYP3A4 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider therapy modification
Warfarin: Lomitapide may increase the serum concentration of Warfarin. Risk C: Monitor therapy
Zileuton: May increase the serum concentration of Lomitapide. Management: Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half with concurrent zileuton; the lomitapide dose may then be increased to a max adult dose of 30 mg/day (patients on lomitapide 5 mg/day may continue that dose). Risk D: Consider therapy modification
High-fat diets containing ≥20% of total calories from fat may increase the risk of gastrointestinal adverse reactions (eg, abdominal pain/discomfort, constipation, diarrhea, flatulence, and nausea/vomiting). Grapefruit juice may increase lomitapide plasma concentration. Absorption of fat-soluble nutrients may be reduced. Management: Avoid administering with high fat diets. Avoid grapefruit juice. Take recommended daily supplements of vitamin E, alpha-linolenic acid (ALA), linoleic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA).
Evaluate pregnancy status prior to use in females of reproductive potential. Women of reproductive potential should have a negative pregnancy test prior to therapy and effective contraception must be used during treatment and for 2 weeks after the final lomitapide dose. Dose adjustment may be required for women using oral contraceptives. In addition, females using oral contraceptives should also use an effective, alternate form of contraception for 7 days after the resolution of symptoms if nausea or diarrhea occur during lomitapide treatment.
Based on data from animal reproduction studies, in utero exposure to lomitapide may cause fetal harm. Use is contraindicated in pregnant women. Discontinue if pregnancy occurs during treatment.
Data collection to monitor pregnancy and infant outcomes following exposure to lomitapide is ongoing. Health care providers are encouraged to enroll women exposed to lomitapide during pregnancy in the Global Lomitapide Pregnancy Exposure Registry by calling 1-877-902-4099.
It is not known if lomitapide is present in breast milk.
Due to the potential for serious adverse reactions in the breastfeeding infant, breastfeeding is not recommended by the manufacturer.
ALT, AST, alkaline phosphatase, total bilirubin at baseline; pregnancy test in females of reproductive potential prior to initiation of therapy. Measure transaminases prior to any increase in dose or monthly (whichever occurs first) during the first year, and then at least every 3 months and prior to dosage increases (also see Dosage Adjustment for Toxicity)
Lomitapide directly binds to and inhibits microsomal triglyceride transfer protein (MTP) which is located in the lumen of the endoplasmic reticulum. MTP inhibition prevents the assembly of apo-B containing lipoproteins in enterocytes and hepatocytes resulting in reduced production of chylomicrons and VLDL and subsequently reduces plasma LDL-C concentrations.
Distribution: Mean Vd: 985-1292 L
Protein binding: 99.8% to plasma proteins
Metabolism: Primarily hepatic (extensive) through CYP3A4 to M1 and M3 (major [inactive in vitro] metabolites); CYP1A2, CYP2B6, CYP2C8, and CYP2C19 are also involved in metabolism to a minor degree.
Bioavailability: ~7%
Half-life elimination: 39.7 hours
Time to peak: ~6 hours
Excretion: Urine (53% to 60%; major component: M1 metabolite); feces (33% to 35%; major component: parent drug)
Altered kidney function: In patients with end-stage renal disease receiving dialysis, lomitapide exposure was increased by ~50% compared to healthy volunteers. The pharmacokinetics of lomitapide have not been evaluated in patients with mild to severe renal impairment not receiving dialysis; however, exposure exceeding 50% is possible.
Hepatic function impairment: In patients with mild hepatic impairment (Child-Pugh class A), lomitapide exposure was increased by ~50% compared to healthy volunteers. Lomitapide exposure was increased by 164% and Cmax was 361% higher in patients with moderate hepatic impairment compared to healthy volunteers.
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