Juxtapid 20mg Capsules
WARNING: This drug may cause liver problems in some patients. Blood tests will be needed to watch for any liver problems. Talk with the doctor. @ COMMON USES: It is used to lower cholesterol.
Drug Class
Lipid-lowering agent
Pharmacologic Class
Microsomal Triglyceride Transfer Protein (MTP) Inhibitor
Pregnancy Category
Category X
FDA Approved
Dec 2012
DEA Schedule
Not Controlled
Overview
What is this medicine?
Lomitapide is a medication used to lower very high cholesterol levels, specifically in people with a rare inherited condition called homozygous familial hypercholesterolemia (HoFH). It works by blocking a protein in your body that helps make 'bad' cholesterol (LDL-C). This helps reduce the amount of bad cholesterol in your blood.
How to Use This Medicine
Taking Your Medication
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided with your prescription and follow the instructions closely.
When taking your medication:
- Take it at least 2 hours after your evening meal.
- Do not take it with food, as it may cause stomach upset.
- Take it with a full glass of water.
- Swallow the tablet whole; do not chew, break, open, or dissolve it.
Storing and Disposing of Your Medication
To keep your medication effective and safe:
- Store it at room temperature in a dry place.
- Avoid storing it in a bathroom.
- Keep the lid tightly closed.
- Keep all medications in a safe place, out of the reach of children and pets.
Missing a Dose
If you miss a dose:
- Skip the missed dose and return to your regular dosing schedule.
- Do not take two doses at the same time or take extra doses.
- If you stop taking the medication for more than 1 week, consult with your doctor before restarting.
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided with your prescription and follow the instructions closely.
When taking your medication:
- Take it at least 2 hours after your evening meal.
- Do not take it with food, as it may cause stomach upset.
- Take it with a full glass of water.
- Swallow the tablet whole; do not chew, break, open, or dissolve it.
Storing and Disposing of Your Medication
To keep your medication effective and safe:
- Store it at room temperature in a dry place.
- Avoid storing it in a bathroom.
- Keep the lid tightly closed.
- Keep all medications in a safe place, out of the reach of children and pets.
Missing a Dose
If you miss a dose:
- Skip the missed dose and return to your regular dosing schedule.
- Do not take two doses at the same time or take extra doses.
- If you stop taking the medication for more than 1 week, consult with your doctor before restarting.
Lifestyle & Tips
- Follow a low-fat diet (less than 20% of total calories from fat) as prescribed by your doctor or dietitian. This is crucial to reduce gastrointestinal side effects and optimize treatment.
- Take the capsule whole with water at least 2 hours after your evening meal.
- Do not eat grapefruit or drink grapefruit juice while taking this medication.
- Take daily supplements of fat-soluble vitamins (A, D, E, K) and essential fatty acids as recommended by your doctor, as this medication can interfere with their absorption.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
5 mg orally once daily, increased gradually based on tolerability and LDL-C response
Dose Range:
5 - 60 mg
Condition-Specific Dosing:
homozygousFamilialHypercholesterolemia:
Initial 5 mg once daily, titrate every 2 weeks to 10 mg, then 20 mg, 40 mg, and maximum 60 mg once daily. Doses above 40 mg should be considered only if LDL-C goal is not met and tolerability is acceptable.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established (Safety and efficacy not established in pediatric patients)
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment needed (CrCl 50-80 mL/min)
Moderate:
No dose adjustment needed (CrCl 30-50 mL/min)
Severe:
Initial 5 mg once daily, maximum 40 mg once daily (CrCl <30 mL/min, non-dialysis dependent)
Dialysis:
Initial 5 mg once daily, maximum 40 mg once daily (Hemodialysis or peritoneal dialysis). Administer after dialysis on dialysis days.
Hepatic Impairment:
Mild:
Initial 5 mg once daily, maximum 40 mg once daily (Child-Pugh A)
Moderate:
Contraindicated (Child-Pugh B)
Severe:
Contraindicated (Child-Pugh C)
Pharmacology
Mechanism of Action
Lomitapide directly binds to and inhibits microsomal triglyceride transfer protein (MTP), which is located in the lumen of the endoplasmic reticulum. This inhibition prevents the assembly of apo B-containing lipoproteins (chylomicrons and VLDL) in enterocytes and hepatocytes, leading to reduced production of chylomicrons and VLDL, and subsequently reduced plasma LDL-C levels.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 7%
Tmax:
6 hours
FoodEffect:
High-fat meal delays Tmax by approximately 3 hours and reduces Cmax by approximately 50% but does not significantly affect AUC. Should be taken with water at least 2 hours after the evening meal.
Distribution:
Vd:
985 L
ProteinBinding:
Greater than 99%
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 39.5 hours
Clearance:
Not available
ExcretionRoute:
Approximately 59% in feces (primarily as metabolites), 33% in urine (primarily as metabolites)
Unchanged:
Less than 1% in urine
Pharmacodynamics
OnsetOfAction:
Within 2 weeks (initial LDL-C reduction)
PeakEffect:
Approximately 4-6 weeks for maximal LDL-C reduction at a given dose
DurationOfAction:
Sustained with continued dosing
Safety & Warnings
BLACK BOX WARNING
Hepatotoxicity: JUXTAPID can cause elevations in transaminases and hepatic steatosis. Liver function tests must be monitored regularly. JUXTAPID is contraindicated in patients with moderate or severe hepatic impairment or with active liver disease.
Side Effects
Serious Side Effects: Seek Medical Attention Immediately
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you experience any of the following symptoms, contact your doctor or seek medical help right away:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of liver problems, including:
+ Dark urine
+ Tiredness
+ Decreased appetite
+ Upset stomach or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Chest pain
Abnormal heartbeat
Flu-like symptoms
Severe diarrhea that requires hospitalization
Signs of dehydration, such as:
+ Severe dizziness or fainting
+ Inability to urinate or changes in urine output
+ Extreme fatigue
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to contact your doctor or seek medical help if you experience any of the following:
Stomach cramps
Bloating
Dizziness, tiredness, or weakness
Gas
Constipation
Heartburn
Weight loss
Back pain
Nose or throat irritation
* Headache
Common side effects of this medication include diarrhea, upset stomach, vomiting, and stomach pain. Following a low-fat diet may help reduce the likelihood of these side effects. If any of these side effects are severe, bothersome, or persistent, contact your doctor.
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects not mentioned here. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you experience any of the following symptoms, contact your doctor or seek medical help right away:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of liver problems, including:
+ Dark urine
+ Tiredness
+ Decreased appetite
+ Upset stomach or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Chest pain
Abnormal heartbeat
Flu-like symptoms
Severe diarrhea that requires hospitalization
Signs of dehydration, such as:
+ Severe dizziness or fainting
+ Inability to urinate or changes in urine output
+ Extreme fatigue
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to contact your doctor or seek medical help if you experience any of the following:
Stomach cramps
Bloating
Dizziness, tiredness, or weakness
Gas
Constipation
Heartburn
Weight loss
Back pain
Nose or throat irritation
* Headache
Common side effects of this medication include diarrhea, upset stomach, vomiting, and stomach pain. Following a low-fat diet may help reduce the likelihood of these side effects. If any of these side effects are severe, bothersome, or persistent, contact your doctor.
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects not mentioned here. If you have questions or concerns about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Signs of liver problems: unusual tiredness, loss of appetite, pain in the upper right side of your stomach, dark urine, yellowing of your skin or eyes (jaundice), itching.
- Severe or persistent diarrhea, nausea, vomiting, or stomach pain.
- Unusual bleeding or bruising (may indicate vitamin K deficiency).
- Vision problems, especially at night (may indicate vitamin A deficiency).
- Muscle weakness or tingling/numbness (may indicate vitamin E deficiency).
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following conditions to ensure safe treatment:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Describe the allergic reaction you experienced, including the symptoms that occurred.
If you have liver disease or elevated liver enzymes, as this may affect the medication's safety and efficacy.
If you have been diagnosed with problems digesting certain sugars, including lactose, glucose, or galactose, as this medication may contain these sugars.
If you have difficulty swallowing the medication whole, as it must not be crushed, chewed, or split.
If you are taking any other medications, including prescription and over-the-counter (OTC) drugs, natural products, or vitamins, that may interact with this medication. Certain medications, such as those used to treat HIV, infections, or depression, should not be taken with this drug. Your doctor or pharmacist can advise you on potential interactions.
If you are pregnant or plan to become pregnant, as this medication is not recommended during pregnancy. Do not take this medication if you are pregnant.
* If you are breastfeeding, as it is not recommended to breastfeed while taking this medication.
This list is not exhaustive, and it is crucial to discuss all your medications, health problems, and concerns with your doctor and pharmacist to ensure safe treatment. Do not start, stop, or change the dose of any medication without consulting your doctor first.
It is essential to inform your doctor about the following conditions to ensure safe treatment:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Describe the allergic reaction you experienced, including the symptoms that occurred.
If you have liver disease or elevated liver enzymes, as this may affect the medication's safety and efficacy.
If you have been diagnosed with problems digesting certain sugars, including lactose, glucose, or galactose, as this medication may contain these sugars.
If you have difficulty swallowing the medication whole, as it must not be crushed, chewed, or split.
If you are taking any other medications, including prescription and over-the-counter (OTC) drugs, natural products, or vitamins, that may interact with this medication. Certain medications, such as those used to treat HIV, infections, or depression, should not be taken with this drug. Your doctor or pharmacist can advise you on potential interactions.
If you are pregnant or plan to become pregnant, as this medication is not recommended during pregnancy. Do not take this medication if you are pregnant.
* If you are breastfeeding, as it is not recommended to breastfeed while taking this medication.
This list is not exhaustive, and it is crucial to discuss all your medications, health problems, and concerns with your doctor and pharmacist to ensure safe treatment. Do not start, stop, or change the dose of any medication without consulting your doctor first.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Regular blood tests will be necessary, as directed by your doctor, to monitor your condition. Be sure to follow the diet and exercise plan recommended by your doctor.
To avoid potential interactions, do not consume grapefruit or grapefruit juice while taking this medication. If you plan to drink alcohol, discuss this with your doctor first, and limit your intake to no more than one alcoholic drink per day.
When taking this medication, avoid taking colesevelam, colestipol, or cholestyramine within a 4-hour window before or after taking your dose. If you experience diarrhea or vomiting, oral medications may not be absorbed properly. This is particularly important if you are taking birth control pills, as you may need to use an additional form of contraception, such as a condom, for 7 days after the diarrhea or vomiting has stopped. If you have questions or concerns, consult your doctor.
Your doctor may recommend taking supplements like vitamin E and fatty acids while you are on this medication. Be sure to follow their instructions carefully.
If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects.
This medication can cause harm to an unborn baby. A pregnancy test will be performed before you start taking this medication to confirm that you are not pregnant. If you may become pregnant, you must use birth control while taking this medication and for a certain period after the last dose. Your doctor will advise you on how long to continue using birth control. If you become pregnant while taking this medication, contact your doctor immediately.
To avoid potential interactions, do not consume grapefruit or grapefruit juice while taking this medication. If you plan to drink alcohol, discuss this with your doctor first, and limit your intake to no more than one alcoholic drink per day.
When taking this medication, avoid taking colesevelam, colestipol, or cholestyramine within a 4-hour window before or after taking your dose. If you experience diarrhea or vomiting, oral medications may not be absorbed properly. This is particularly important if you are taking birth control pills, as you may need to use an additional form of contraception, such as a condom, for 7 days after the diarrhea or vomiting has stopped. If you have questions or concerns, consult your doctor.
Your doctor may recommend taking supplements like vitamin E and fatty acids while you are on this medication. Be sure to follow their instructions carefully.
If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects.
This medication can cause harm to an unborn baby. A pregnancy test will be performed before you start taking this medication to confirm that you are not pregnant. If you may become pregnant, you must use birth control while taking this medication and for a certain period after the last dose. Your doctor will advise you on how long to continue using birth control. If you become pregnant while taking this medication, contact your doctor immediately.
Overdose Information
Overdose Symptoms:
- Exacerbation of known adverse effects, particularly gastrointestinal symptoms (e.g., severe diarrhea, nausea, vomiting, abdominal pain) and potential for increased liver enzyme elevations.
What to Do:
There is no specific antidote for lomitapide overdose. Treatment should be symptomatic and supportive. Monitor liver function tests closely. Contact a poison control center immediately (e.g., 1-800-222-1222 in the US).
Drug Interactions
Contraindicated Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, telithromycin, nefazodone, ritonavir, lopinavir/ritonavir, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir, grapefruit juice)
Major Interactions
- Moderate CYP3A4 inhibitors (e.g., fluconazole, erythromycin, diltiazem, verapamil, aprepitant, fosamprenavir, imatinib, ciprofloxacin, cimetidine, ranitidine, amiodarone, dronedarone, ticagrelor, conivaptan, delavirdine, efavirenz, etravirine, posaconazole, voriconazole, crizotinib, idelalisib, cobicistat, stiripentol, enasidenib, ribociclib, sonidegib, tucatinib, vemurafenib, viloxazine, voxilaprevir)
- P-glycoprotein (P-gp) inhibitors (e.g., cyclosporine, amiodarone, verapamil, quinidine, diltiazem, clarithromycin, erythromycin, itraconazole, ketoconazole, ritonavir)
- Warfarin (increased INR)
- Simvastatin (increased simvastatin exposure)
- Atorvastatin (increased atorvastatin exposure)
Moderate Interactions
- Weak CYP3A4 inhibitors (e.g., cimetidine, fluoxetine, fluvoxamine, sertraline, ciprofloxacin, ethinyl estradiol, norethindrone)
- CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, phenobarbital, St. John's Wort) - may decrease lomitapide efficacy
- Bile acid sequestrants (may interfere with absorption, administer lomitapide at least 4 hours after sequestrant)
Minor Interactions
- Not specifically listed as minor, but caution with any drug metabolized by or affecting CYP3A4 or P-gp.
Monitoring
Baseline Monitoring
Liver function tests (ALT, AST, alkaline phosphatase, total bilirubin)
Rationale: To establish baseline liver function and identify pre-existing liver disease, as lomitapide can cause hepatotoxicity.
Timing: Prior to initiation of therapy
Lipid panel (LDL-C, HDL-C, Total Cholesterol, Triglycerides)
Rationale: To establish baseline lipid levels and confirm diagnosis of HoFH.
Timing: Prior to initiation of therapy
Pregnancy test
Rationale: Lomitapide is contraindicated in pregnancy (Category X).
Timing: Prior to initiation in females of reproductive potential
Routine Monitoring
Liver function tests (ALT, AST, alkaline phosphatase, total bilirubin)
Frequency: Monthly for the first year, then at least every 3 months thereafter, or as clinically indicated.
Target: Within normal limits
Action Threshold: If ALT or AST âĨ 3x ULN but < 5x ULN, reduce dose or interrupt treatment. If ALT or AST âĨ 5x ULN, discontinue treatment. If clinically significant symptoms of liver injury occur, discontinue treatment.
Lipid panel (LDL-C, HDL-C, Total Cholesterol, Triglycerides)
Frequency: Every 4-6 weeks during dose titration, then every 3-6 months or as clinically indicated once stable.
Target: Individualized LDL-C goal (typically <100 mg/dL or lower for HoFH patients)
Action Threshold: If LDL-C goal not met, consider dose increase if tolerated. If triglycerides are persistently elevated, assess for other causes.
INR (for patients on warfarin)
Frequency: More frequently after initiation or dose adjustment of lomitapide.
Target: Individualized therapeutic range
Action Threshold: Adjust warfarin dose as needed to maintain target INR.
Symptom Monitoring
- Signs and symptoms of liver injury (e.g., fatigue, anorexia, right upper quadrant abdominal pain, dark urine, jaundice, pruritus)
- Gastrointestinal adverse events (e.g., diarrhea, nausea, vomiting, dyspepsia, abdominal pain, constipation, flatulence)
- Symptoms of fat-soluble vitamin deficiency (e.g., night blindness, easy bruising, muscle weakness, neuropathy)
Special Patient Groups
Pregnancy
Lomitapide is contraindicated in pregnancy (Pregnancy Category X) due to potential for fetal harm based on its mechanism of action and animal studies. It can cause fetal malformations and embryo-fetal death.
Trimester-Specific Risks:
First Trimester:
High risk of fetal malformations and embryo-fetal death.
Second Trimester:
High risk of fetal malformations and embryo-fetal death.
Third Trimester:
High risk of fetal malformations and embryo-fetal death.
Lactation
Lomitapide is contraindicated during breastfeeding (Lactation Risk L5). It is unknown if lomitapide is excreted in human milk, but due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended.
Infant Risk:
High risk (L5 - Contraindicated)
Pediatric Use
Safety and efficacy have not been established in pediatric patients. Use is generally not recommended.
Geriatric Use
No overall differences in safety or effectiveness were observed between elderly (âĨ65 years) and younger patients, but greater sensitivity of some older individuals cannot be ruled out. No specific dose adjustment is required based on age alone, but monitor for adverse effects.
Clinical Information
Clinical Pearls
- Lomitapide is a highly specialized medication for a rare genetic disorder (HoFH) and should only be prescribed by physicians experienced in managing lipid disorders.
- Strict adherence to the low-fat diet is critical for both efficacy and to minimize severe gastrointestinal side effects.
- Regular and diligent monitoring of liver function tests is paramount due to the Black Box Warning for hepatotoxicity. Patients must be educated on symptoms of liver injury.
- Patients must take fat-soluble vitamin and essential fatty acid supplements due to the drug's mechanism of action affecting fat absorption.
- Due to significant drug interactions, especially with CYP3A4 inhibitors, a thorough medication review is essential before and during therapy.
Alternative Therapies
- Evinacumab (Evkeeza) - Angiopoietin-like 3 (ANGPTL3) inhibitor
- Alirocumab (Praluent) / Evolocumab (Repatha) - PCSK9 inhibitors (often used in combination with lomitapide or as alternatives if not tolerated/effective)
- Apheresis (LDL apheresis) - Mechanical removal of LDL-C from blood
- Other lipid-lowering agents (e.g., high-dose statins, ezetimibe) - typically used in combination with lomitapide, not as alternatives for HoFH alone.
Cost & Coverage
Average Cost:
Price varies significantly, typically >$10,000 per 30 capsules
Insurance Coverage:
Specialty Tier (requires prior authorization, often with strict criteria for HoFH diagnosis and failure of other therapies)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe use, never share your medication with others or take someone else's medication. This medication is accompanied by a Medication Guide, which provides crucial information. Please read this guide carefully and review it again whenever you receive a refill. If you have any questions or concerns about this medication, consult your doctor, pharmacist, or healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. Be prepared to provide details about the overdose, including the substance taken, the amount, and the time it occurred.