Trikafta 100mg/50mg/75mg Tablets
WARNING: This drug can cause severe liver problems. Liver problems leading to a liver transplant and sometimes death have happened in people with and without a history of liver disease. Liver problems have happened within 1 to 15 months after this drug was started.If you have liver problems or raised liver enzymes, talk with your doctor. This drug may not be right for you. Have your liver function checked as you have been told by your doctor.Call your doctor right away if you have signs of liver problems like dark urine, tiredness, decreased appetite, upset stomach or stomach pain, light- colored stools, throwing up, or yellow skin or eyes. @ COMMON USES: It is used to treat cystic fibrosis.
Drug Class
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Modulator
Pharmacologic Class
CFTR Potentiator and CFTR Correctors
Pregnancy Category
Not assigned (Pregnancy Registry available)
FDA Approved
Oct 2019
DEA Schedule
Not Controlled
Overview
What is this medicine?
Trikafta is a medicine for people with cystic fibrosis (CF) who have specific genetic mutations. It works by helping the protein that is faulty in CF to work better, which can improve lung function and reduce other CF symptoms. It's a combination of three different medicines that work together.
How to Use This Medicine
Taking Your Medication Correctly
To get the most benefit from your medication, it's essential to follow your doctor's instructions carefully. Read all the information provided with your medication and follow the instructions closely. Take your medication with fatty foods, such as those made with butter or oils, or foods that contain eggs, peanut butter, cheeses, nuts, meats, or whole milk. If you're unsure what types of foods are considered fatty, consult with your doctor.
Swallow your medication whole, without chewing, breaking, or crushing it. Note that this medication comes in two different colored tablets, and it's crucial to understand when to take each one. If you have any questions, consult with your pharmacist.
Continue taking your medication as directed by your doctor or healthcare provider, even if you're feeling well.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, avoiding the bathroom. Keep all medications in a safe location, out of the reach of children and pets. Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. If you're unsure about the best way to dispose of your medication, consult with your pharmacist. You may also want to check if there are drug take-back programs in your area.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if you miss the morning dose by more than 6 hours, take the missed dose as soon as you remember and skip the evening dose. If you miss the evening dose by more than 6 hours, skip the missed dose and resume your regular schedule. Do not take two doses at the same time or take extra doses.
To get the most benefit from your medication, it's essential to follow your doctor's instructions carefully. Read all the information provided with your medication and follow the instructions closely. Take your medication with fatty foods, such as those made with butter or oils, or foods that contain eggs, peanut butter, cheeses, nuts, meats, or whole milk. If you're unsure what types of foods are considered fatty, consult with your doctor.
Swallow your medication whole, without chewing, breaking, or crushing it. Note that this medication comes in two different colored tablets, and it's crucial to understand when to take each one. If you have any questions, consult with your pharmacist.
Continue taking your medication as directed by your doctor or healthcare provider, even if you're feeling well.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, avoiding the bathroom. Keep all medications in a safe location, out of the reach of children and pets. Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. If you're unsure about the best way to dispose of your medication, consult with your pharmacist. You may also want to check if there are drug take-back programs in your area.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if you miss the morning dose by more than 6 hours, take the missed dose as soon as you remember and skip the evening dose. If you miss the evening dose by more than 6 hours, skip the missed dose and resume your regular schedule. Do not take two doses at the same time or take extra doses.
Lifestyle & Tips
- Take Trikafta with fat-containing food (e.g., eggs, butter, peanut butter, cheese, whole milk, meat, or nutritional supplements) to help your body absorb the medicine properly.
- Take doses approximately 12 hours apart (morning and evening).
- Do not eat or drink grapefruit or Seville oranges (or products containing them) while taking Trikafta, as they can increase the amount of medicine in your body.
- Continue with other prescribed CF treatments, including airway clearance techniques and other medications, unless otherwise instructed by your doctor.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
Not applicable for this specific strength (100mg/50mg/75mg). Adult dosing is Elexacaftor 200mg/Tezacaftor 100mg/Ivacaftor 150mg (2 tablets) in the morning and Ivacaftor 150mg (1 tablet) in the evening.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
For patients aged 6 years to less than 12 years: One tablet (elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg) orally in the morning and one tablet (ivacaftor 75 mg) orally in the evening. Both doses should be taken approximately 12 hours apart with fat-containing food.
Adolescent:
Not applicable for this specific strength (100mg/50mg/75mg). Adolescent dosing (≥12 years) is Elexacaftor 200mg/Tezacaftor 100mg/Ivacaftor 150mg (2 tablets) in the morning and Ivacaftor 150mg (1 tablet) in the evening.
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment required.
Moderate:
No dose adjustment required.
Severe:
Use with caution. Consider dose reduction if eGFR <30 mL/min/1.73 m² or end-stage renal disease (ESRD). For patients 6 to <12 years, reduce morning dose to 1 tablet (elexacaftor 50 mg/tezacaftor 25 mg/ivacaftor 37.5 mg) and evening dose to 1 tablet (ivacaftor 37.5 mg).
Dialysis:
Not studied. Use with caution. Consider dose reduction as for severe impairment.
Hepatic Impairment:
Mild:
No dose adjustment required (Child-Pugh A).
Moderate:
Reduce dose. For patients 6 to <12 years, reduce morning dose to 1 tablet (elexacaftor 50 mg/tezacaftor 25 mg/ivacaftor 37.5 mg) and evening dose to 1 tablet (ivacaftor 37.5 mg).
Severe:
Not recommended unless benefits outweigh risks. If used, reduce dose significantly. For patients 6 to <12 years, reduce morning dose to 1 tablet (elexacaftor 50 mg/tezacaftor 25 mg/ivacaftor 37.5 mg) once daily or every other day, and evening dose to 1 tablet (ivacaftor 37.5 mg) once daily or every other day, with careful monitoring.
Pharmacology
Mechanism of Action
Trikafta is a combination of three CFTR modulators: Elexacaftor and Tezacaftor are CFTR correctors, and Ivacaftor is a CFTR potentiator. Elexacaftor and tezacaftor work synergistically to increase the amount of mature CFTR protein at the cell surface by correcting the folding and trafficking defects of the F508del-CFTR protein. Ivacaftor then potentiates the function of this corrected CFTR protein by increasing the probability of channel opening at the cell surface, leading to increased chloride transport.
Pharmacokinetics
Absorption:
Bioavailability:
Well absorbed; enhanced by fat-containing food. Absolute bioavailability not precisely quantified for the combination.
Tmax:
Elexacaftor: ~6 hours; Tezacaftor: ~8 hours; Ivacaftor: ~4 hours (after single dose with food).
FoodEffect:
Administration with fat-containing food significantly increases exposure (AUC and Cmax) of all three components.
Distribution:
Vd:
Elexacaftor: ~100 L; Tezacaftor: ~100 L; Ivacaftor: ~100 L (apparent volume of distribution).
ProteinBinding:
Elexacaftor: ~99%; Tezacaftor: ~99%; Ivacaftor: ~99% (highly protein bound).
CnssPenetration:
Limited data, but generally considered low due to high protein binding and P-gp efflux.
Elimination:
HalfLife:
Elexacaftor: ~23 hours; Tezacaftor: ~159 hours; Ivacaftor: ~9 hours (after single dose).
Clearance:
Not readily available for the combination; primarily hepatic clearance.
ExcretionRoute:
Primarily fecal excretion (87% for elexacaftor, 79% for tezacaftor, 87% for ivacaftor).
Unchanged:
Minimal unchanged drug excreted in urine or feces.
Pharmacodynamics
OnsetOfAction:
Clinical benefits (e.g., FEV1 improvement) observed within 2-4 weeks.
PeakEffect:
Maximal FEV1 improvement typically observed within 4 weeks and sustained with continued treatment.
DurationOfAction:
Sustained with daily dosing due to long half-lives of components, particularly tezacaftor.
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
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
Severe dizziness or fainting
Changes in vision
Other Possible Side Effects
Like all medications, this drug can cause side effects. Although 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 or any other unusual symptoms that bother you or persist, contact your doctor for advice:
Headache
Symptoms of a common cold
Diarrhea or constipation
Stomach pain
Flu-like symptoms
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, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
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
Severe dizziness or fainting
Changes in vision
Other Possible Side Effects
Like all medications, this drug can cause side effects. Although 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 or any other unusual symptoms that bother you or persist, contact your doctor for advice:
Headache
Symptoms of a common cold
Diarrhea or constipation
Stomach pain
Flu-like symptoms
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, consult 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:
- Yellowing of skin or eyes (jaundice)
- Dark urine
- Pain or discomfort in the upper right stomach area
- Loss of appetite
- Nausea or vomiting
- Unusual tiredness or weakness
- Blurred vision or other changes in vision (especially in children)
- Headache, dizziness, or feeling lightheaded (signs of high blood pressure)
Before Using This Medicine
Before taking this medication, it is essential to inform your doctor about the following:
Any allergies you have, including allergies to this drug, any of its components, or other substances, such as foods or medications. Be sure to describe the symptoms you experienced as a result of the allergy.
Any medications you are currently taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins, that may interact with this medication. Certain medications used to treat conditions like HIV, infections, and seizures should not be taken with this drug. However, this is not an exhaustive list of all potential interacting medications.
* All of your health problems, as they may affect the safety of taking this medication.
It is crucial to consult with your doctor and pharmacist to ensure that it is safe to take this medication with all of your existing medications and health conditions. Do not initiate, discontinue, or modify the dosage of any medication without first consulting your doctor to avoid potential interactions or adverse effects.
Any allergies you have, including allergies to this drug, any of its components, or other substances, such as foods or medications. Be sure to describe the symptoms you experienced as a result of the allergy.
Any medications you are currently taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins, that may interact with this medication. Certain medications used to treat conditions like HIV, infections, and seizures should not be taken with this drug. However, this is not an exhaustive list of all potential interacting medications.
* All of your health problems, as they may affect the safety of taking this medication.
It is crucial to consult with your doctor and pharmacist to ensure that it is safe to take this medication with all of your existing medications and health conditions. Do not initiate, discontinue, or modify the dosage of any medication without first consulting your doctor to avoid potential interactions or adverse effects.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Before engaging in activities that require alertness, such as driving, wait until you understand how this drug affects you. Regularly undergo blood tests and lung function assessments as directed by your doctor. Additionally, avoid consuming grapefruit and grapefruit juice while taking this medication.
In children, this drug has been associated with the development of cataracts. Therefore, it is crucial to undergo an eye examination before initiating treatment and periodically while taking this medication. Discuss any concerns with your doctor. If you are using hormone-based birth control and experience a rash, consult your doctor promptly.
If you are pregnant, planning to become pregnant, or are breastfeeding, inform your doctor. It is necessary to discuss the potential benefits and risks of this medication to both you and your baby to make an informed decision.
In children, this drug has been associated with the development of cataracts. Therefore, it is crucial to undergo an eye examination before initiating treatment and periodically while taking this medication. Discuss any concerns with your doctor. If you are using hormone-based birth control and experience a rash, consult your doctor promptly.
If you are pregnant, planning to become pregnant, or are breastfeeding, inform your doctor. It is necessary to discuss the potential benefits and risks of this medication to both you and your baby to make an informed decision.
Overdose Information
Overdose Symptoms:
- Symptoms of overdose are not well established but may include exaggerated adverse effects such as elevated liver enzymes, rash, or gastrointestinal disturbances.
What to Do:
Call 1-800-222-1222 (Poison Control Center) immediately. Supportive care and symptomatic treatment should be provided. Monitor vital signs and liver function.
Drug Interactions
Contraindicated Interactions
- Strong CYP3A inducers (e.g., rifampin, carbamazepine, phenobarbital, phenytoin, St. John's Wort)
Major Interactions
- Strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin, ritonavir, cobicistat, grapefruit juice)
- Moderate CYP3A inducers (e.g., efavirenz, etravirine, bosentan, modafinil, nafcillin)
Moderate Interactions
- Moderate CYP3A inhibitors (e.g., fluconazole, erythromycin, diltiazem, verapamil, aprepitant, ciprofloxacin)
- CYP3A substrates (e.g., midazolam, triazolam, alprazolam, cyclosporine, tacrolimus, sirolimus)
- P-glycoprotein (P-gp) substrates (e.g., digoxin, dabigatran)
Minor Interactions
- Not specifically listed as minor for Trikafta; most interactions are significant due to CYP3A metabolism.
Monitoring
Baseline Monitoring
Liver Function Tests (ALT, AST, bilirubin)
Rationale: Risk of elevated transaminases and hepatic injury.
Timing: Prior to initiating treatment.
Ophthalmologic examination (slit lamp)
Rationale: Risk of non-congenital lens opacities (cataracts), especially in pediatric patients.
Timing: Prior to initiating treatment (for pediatric patients).
Blood Pressure
Rationale: Risk of elevated blood pressure.
Timing: Prior to initiating treatment.
Routine Monitoring
Liver Function Tests (ALT, AST, bilirubin)
Frequency: Every 3 months during the first year of treatment, then annually.
Target: Within normal limits.
Action Threshold: Interrupt treatment if ALT or AST >5x ULN or >3x ULN with bilirubin >2x ULN. Resume at reduced dose or discontinue based on resolution.
Ophthalmologic examination (slit lamp)
Frequency: Annually (for pediatric patients).
Target: No new or worsening lens opacities.
Action Threshold: Consider discontinuation if clinically significant cataracts develop.
Blood Pressure
Frequency: Periodically during treatment.
Target: Within normal limits for age.
Action Threshold: Manage hypertension as clinically indicated.
FEV1 (For efficacy monitoring)
Frequency: As per standard CF care guidelines.
Target: Improvement or stabilization of lung function.
Action Threshold: Not a direct action threshold for drug adjustment, but indicates treatment effectiveness.
Symptom Monitoring
- Signs and symptoms of liver injury (e.g., nausea, vomiting, abdominal pain, fatigue, anorexia, dark urine, jaundice)
- Visual changes or blurred vision (especially in pediatric patients)
- Headache, dizziness, or other signs of elevated blood pressure
Special Patient Groups
Pregnancy
There is a pregnancy exposure registry for Trikafta. Data from this registry and postmarketing reports have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Use during pregnancy should be based on a careful assessment of the benefits and risks.
Trimester-Specific Risks:
First Trimester:
No specific increased risk identified from available data.
Second Trimester:
No specific increased risk identified from available data.
Third Trimester:
No specific increased risk identified from available data.
Lactation
Elexacaftor, tezacaftor, and ivacaftor are present in human milk. There are no data on the effects of Trikafta on the breastfed infant or on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Trikafta and any potential adverse effects on the breastfed infant from Trikafta or from the underlying maternal condition. Monitor breastfed infants for adverse reactions (e.g., elevated liver enzymes, rash).
Infant Risk:
Low to moderate risk. Monitor infant for potential adverse effects.
Pediatric Use
Approved for patients aged 2 years and older with at least one F508del mutation. Dosing varies by age group (2-5 years, 6-11 years, ≥12 years). Pediatric patients require baseline and annual ophthalmologic exams due to risk of cataracts. Liver function monitoring is also crucial.
Geriatric Use
Clinical studies did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. No specific dose adjustment is recommended based on age alone, but consider age-related decreases in hepatic, renal, or cardiac function and concomitant disease or other drug therapy.
Clinical Information
Clinical Pearls
- Trikafta is a highly effective CFTR modulator for eligible patients, significantly improving lung function and quality of life.
- Strict adherence to taking the medication with fat-containing food is crucial for optimal absorption and efficacy.
- Patients and caregivers should be educated on the importance of regular liver function monitoring and reporting any signs of liver injury.
- Due to significant drug interactions, especially with CYP3A inhibitors and inducers, a thorough medication review is essential before and during treatment.
- The high cost of Trikafta necessitates careful consideration of insurance coverage and patient assistance programs.
Alternative Therapies
- Kalydeco (ivacaftor - for specific gating mutations)
- Standard CF therapies (e.g., bronchodilators, mucolytics, antibiotics, nutritional support)
Cost & Coverage
Average Cost:
Highly variable, typically >$300,000 - $350,000 annually per year
Insurance Coverage:
Specialty Tier (requires prior authorization, often subject to high co-pays or co-insurance)
General Drug Facts
If your symptoms or health problems do not improve or worsen over time, it is essential to contact your doctor for further evaluation and guidance. To ensure your safety and the effectiveness of your treatment, never share your medication with others or take someone else's medication.
This medication is accompanied by a Medication Guide, which provides crucial information about its safe and effective use. It is essential to read this guide carefully when you first receive your medication and each time your prescription is refilled. If you have any questions or concerns about your medication, do not hesitate 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 reporting the incident, be prepared to provide detailed information about the overdose, including the name of the medication taken, the amount consumed, and the time it occurred.
This medication is accompanied by a Medication Guide, which provides crucial information about its safe and effective use. It is essential to read this guide carefully when you first receive your medication and each time your prescription is refilled. If you have any questions or concerns about your medication, do not hesitate 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 reporting the incident, be prepared to provide detailed information about the overdose, including the name of the medication taken, the amount consumed, and the time it occurred.