Juxtapid 5mg 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-modifying 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?
Juxtapid is a medication used to lower very high cholesterol levels in people with a rare inherited condition called Homozygous Familial Hypercholesterolemia (HoFH). It works by blocking a protein in your liver and gut that helps make cholesterol, which reduces the amount of 'bad' cholesterol (LDL-C) in your blood.
How to Use This Medicine
Taking Your Medication Correctly
To ensure you 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 maintain the effectiveness and safety of your medication:
- 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 location, 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 one week, consult your doctor before restarting.
To ensure you 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 maintain the effectiveness and safety of your medication:
- 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 location, 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 one week, consult your doctor before restarting.
Lifestyle & Tips
- Follow a low-fat diet as prescribed by your doctor or dietitian. This is crucial to reduce gastrointestinal side effects and optimize treatment.
- Take the medication on an empty stomach, at least 2 hours after your evening meal and at least 3 hours before bedtime.
- Avoid consuming grapefruit or grapefruit juice while taking this medication, as it can increase the levels of Juxtapid in your body.
- Take fat-soluble vitamin supplements (A, D, E, K) and essential fatty acid supplements as recommended by your doctor, as this medication can interfere with their absorption.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
Initial: 5 mg orally once daily. Titrate gradually based on tolerability and liver enzyme monitoring.
Dose Range:
5 - 60 mg
Condition-Specific Dosing:
Homozygous Familial Hypercholesterolemia (HoFH):
Initial: 5 mg once daily. Titrate to 10 mg, 20 mg, 40 mg, and then 60 mg once daily at intervals of at least 2 weeks, based on tolerability and liver enzyme monitoring. Max dose: 60 mg/day.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established (safety and efficacy not established in patients <12 years of age)
Adolescent:
Initial: 5 mg orally once daily for patients 12 years and older with HoFH. Titrate as per adult dosing, up to a maximum of 60 mg once daily.
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment required.
Moderate:
No dose adjustment required.
Severe:
No dose adjustment required (CrCl <30 mL/min), but caution is advised due to limited data.
Dialysis:
No dose adjustment required, but caution is advised due to limited data.
Hepatic Impairment:
Mild:
Initial dose 5 mg once daily. Max dose 40 mg once daily. Monitor LFTs closely.
Moderate:
Contraindicated.
Severe:
Contraindicated.
Pharmacology
Mechanism of Action
Lomitapide is a microsomal triglyceride transfer protein (MTP) inhibitor. It binds to and inhibits MTP, which is located in the lumen of the endoplasmic reticulum. This inhibition prevents the assembly of apolipoprotein B (apoB)-containing lipoproteins in enterocytes and hepatocytes. This leads to a reduction in the synthesis of chylomicrons and very low-density lipoprotein (VLDL), thereby reducing plasma levels of LDL-C.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 7%
Tmax:
6 hours (range 3-12 hours)
FoodEffect:
Food significantly reduces absorption (AUC and Cmax reduced by approximately 50% and 40% respectively when taken with a high-fat meal). Should be taken on an empty stomach.
Distribution:
Vd:
Approximately 985 L
ProteinBinding:
>99%
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 39.5 hours
Clearance:
Not available
ExcretionRoute:
Fecal (approximately 59%), Renal (approximately 33%)
Unchanged:
Less than 2% (feces), less than 1% (urine)
Pharmacodynamics
OnsetOfAction:
Lipid-lowering effects observed within weeks of initiation and dose titration.
PeakEffect:
Maximal LDL-C reduction typically achieved after reaching stable maintenance dose.
DurationOfAction:
Effects persist as long as treatment is continued.
Safety & Warnings
BLACK BOX WARNING
JUXTAPID can cause elevations in liver enzymes and hepatic steatosis. Because of the risk of hepatotoxicity, JUXTAPID is available only through a restricted program called the JUXTAPID REMS Program.
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 notice 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 discuss any concerns with your doctor. If you experience any of the following side effects, contact your doctor or seek medical help if they bother you or persist:
Stomach cramps
Bloating
Dizziness, tiredness, or weakness
Gas
Constipation
Heartburn
Weight loss
Back pain
Nose or throat irritation
Headache
Diarrhea
Upset stomach
Vomiting
* Stomach pain
A low-fat diet may help reduce the likelihood of experiencing these side effects. If any of these side effects are severe, bothersome, or persistent, contact your doctor for guidance.
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 or report them to the FDA at 1-800-332-1088 or https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice 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 discuss any concerns with your doctor. If you experience any of the following side effects, contact your doctor or seek medical help if they bother you or persist:
Stomach cramps
Bloating
Dizziness, tiredness, or weakness
Gas
Constipation
Heartburn
Weight loss
Back pain
Nose or throat irritation
Headache
Diarrhea
Upset stomach
Vomiting
* Stomach pain
A low-fat diet may help reduce the likelihood of experiencing these side effects. If any of these side effects are severe, bothersome, or persistent, contact your doctor for guidance.
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 or report them to the FDA at 1-800-332-1088 or 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 stomach or bowel problems: severe diarrhea, nausea, vomiting, stomach pain, constipation.
- Unusual bleeding or bruising (may indicate Vitamin K deficiency).
- Vision problems or night blindness (may indicate Vitamin A deficiency).
- Bone pain or muscle weakness (may indicate Vitamin D 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 difficulties 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 provide guidance 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 conditions, and concerns with your doctor and pharmacist to ensure safe treatment. Do not start, stop, or modify 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 difficulties 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 provide guidance 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 conditions, and concerns with your doctor and pharmacist to ensure safe treatment. Do not start, stop, or modify 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 minimize potential interactions, avoid consuming grapefruit and 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, do not take colesevelam, colestipol, or cholestyramine within 4 hours before or after taking your dose. If you experience diarrhea or vomiting, please note that oral medications, including birth control pills, may not be absorbed properly. As a precaution, if you are taking birth control pills, use an additional form of birth control, such as a condom, for 7 days after the diarrhea or vomiting has stopped. If you have any questions or concerns, consult your doctor.
Your doctor may recommend taking certain supplements, such as vitamin E and fatty acids, while you are on this medication. It is crucial to follow your doctor's instructions regarding these supplements.
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 conducted 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 specified period after the last dose. Your doctor will advise you on the duration of birth control use. If you become pregnant while taking this medication, contact your doctor immediately.
To minimize potential interactions, avoid consuming grapefruit and 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, do not take colesevelam, colestipol, or cholestyramine within 4 hours before or after taking your dose. If you experience diarrhea or vomiting, please note that oral medications, including birth control pills, may not be absorbed properly. As a precaution, if you are taking birth control pills, use an additional form of birth control, such as a condom, for 7 days after the diarrhea or vomiting has stopped. If you have any questions or concerns, consult your doctor.
Your doctor may recommend taking certain supplements, such as vitamin E and fatty acids, while you are on this medication. It is crucial to follow your doctor's instructions regarding these supplements.
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 conducted 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 specified period after the last dose. Your doctor will advise you on the duration of birth control use. If you become pregnant while taking this medication, contact your doctor immediately.
Overdose Information
Overdose Symptoms:
- Exacerbation of known adverse effects, particularly gastrointestinal symptoms (nausea, vomiting, diarrhea, 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).
Drug Interactions
Contraindicated Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, telithromycin, nefazodone, ritonavir, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir)
Major Interactions
- Moderate CYP3A4 inhibitors (e.g., fluconazole, erythromycin, diltiazem, verapamil, aprepitant, grapefruit juice)
- P-glycoprotein (P-gp) inhibitors (e.g., cyclosporine, dronedarone, amiodarone, verapamil, quinidine)
- Warfarin (increased INR)
- Simvastatin (increased simvastatin exposure)
- Atorvastatin (increased atorvastatin exposure)
- Ezetimibe (increased ezetimibe exposure)
- Bile acid sequestrants (administer lomitapide at least 4 hours after bile acid sequestrants)
Moderate Interactions
- Weak CYP3A4 inhibitors (e.g., cimetidine, fluvoxamine)
- Other lipid-lowering agents (additive effects on liver enzymes and GI side effects)
Minor Interactions
- Not many specific minor interactions listed, general caution with other medications.
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 treatment.
Lipid panel (LDL-C, HDL-C, Total Cholesterol, Triglycerides)
Rationale: To establish baseline lipid levels and assess treatment efficacy.
Timing: Prior to initiation of treatment.
Pregnancy test (for females of reproductive potential)
Rationale: Lomitapide is contraindicated in pregnancy.
Timing: Prior to initiation of treatment.
Routine Monitoring
Liver function tests (ALT, AST, alkaline phosphatase, total bilirubin)
Frequency: Monthly for the first year of treatment, then at least every 3 months thereafter, or as clinically indicated.
Target: ALT/AST < 3x ULN (Upper Limit of Normal)
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 liver injury (e.g., jaundice, symptoms of liver dysfunction) occurs, discontinue treatment.
Lipid panel (LDL-C)
Frequency: Every 3-6 months, or as needed to assess response and guide dose titration.
Target: Individualized based on treatment goals for HoFH.
Action Threshold: Assess response and consider dose adjustments or alternative therapies if target not met.
INR (International Normalized Ratio) for patients on warfarin
Frequency: More frequent monitoring (e.g., weekly) when initiating or adjusting lomitapide dose.
Target: Therapeutic range for warfarin.
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 pain, dark urine, jaundice, pruritus)
- Gastrointestinal symptoms (e.g., diarrhea, nausea, vomiting, dyspepsia, abdominal pain, constipation)
- Symptoms of fat-soluble vitamin deficiency (e.g., vision changes, easy bruising, bone pain)
Special Patient Groups
Pregnancy
Lomitapide is contraindicated in pregnancy due to potential for fetal harm. It is a Category X drug. Females of reproductive potential must use effective contraception during treatment and for at least 2 weeks after the last dose.
Trimester-Specific Risks:
First Trimester:
High risk of fetal harm, including potential for teratogenicity.
Second Trimester:
High risk of fetal harm.
Third Trimester:
High risk of fetal harm.
Lactation
Lomitapide is contraindicated during breastfeeding. 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
Approved for patients 12 years and older with HoFH. Safety and efficacy not established in patients younger than 12 years of age. Dosing for adolescents 12+ is similar to adults, with careful titration and monitoring.
Geriatric Use
No specific dose adjustment is required based on age. However, elderly patients may be more susceptible to adverse effects, particularly gastrointestinal issues. Monitor closely for adverse reactions and liver function.
Clinical Information
Clinical Pearls
- Lomitapide is a highly specialized medication for Homozygous Familial Hypercholesterolemia (HoFH) and is part of a REMS program due to hepatotoxicity risk.
- Strict adherence to a low-fat diet (<20% of total calories from fat) is critical to minimize gastrointestinal side effects and optimize efficacy.
- Always take on an empty stomach, at least 2 hours after the evening meal and at least 3 hours before bedtime.
- Regular and frequent monitoring of liver enzymes (ALT, AST) is mandatory, especially during the first year of treatment and dose titration.
- Patients require supplementation with fat-soluble vitamins (A, D, E, K) and essential fatty acids due to the drug's mechanism of action.
- Counsel patients on the importance of contraception due to the drug's teratogenic potential.
- Be aware of numerous drug interactions, especially with CYP3A4 inhibitors and P-gp inhibitors, which can significantly increase lomitapide exposure and toxicity.
Alternative Therapies
- Evinacumab (Evkeeza) - Angiopoietin-like 3 (ANGPTL3) inhibitor
- Evinacumab-dgnb (Evkeeza) - Angiopoietin-like 3 (ANGPTL3) inhibitor
- Alirocumab (Praluent) - PCSK9 inhibitor
- Evolocumab (Repatha) - PCSK9 inhibitor
- Inclisiran (Leqvio) - siRNA targeting PCSK9
- Apheresis (LDL apheresis)
- Statins (high-intensity)
- Ezetimibe
- Bile acid sequestrants
Cost & Coverage
Average Cost:
Highly variable, typically >$10,000 - $20,000+ per 30 capsules (5mg, 10mg, 20mg, 40mg, 60mg)
Insurance Coverage:
Specialty Tier / Tier 4-5 (requires prior authorization, step therapy, and often limited to HoFH diagnosis)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure your safety, never share your medication with others or take someone else's medication. This medication is accompanied by a Medication Guide, which is a crucial patient fact sheet. Please read it carefully and review it again whenever you receive a refill. If you have any questions or concerns about this medication, we encourage you to discuss them with your doctor, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide detailed information about the overdose, including the substance taken, the amount, and the time it occurred.