Trikafta 50mg/25mg/37.5mg 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 Correctors
Pregnancy Category
Not 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 to you 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 the tablets whole; do not chew, break, or crush them. 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 to you 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 the tablets whole; do not chew, break, or crush them. 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.
- Do not eat or drink grapefruit or grapefruit juice while taking Trikafta, as it can increase the levels of the medicine in your body and lead to side effects.
- Take your morning and evening doses approximately 12 hours apart.
- Do not stop taking Trikafta without talking to your doctor, as your symptoms may worsen.
- Maintain regular follow-up appointments and blood tests as advised by your doctor.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
Morning dose: Two tablets (Elexacaftor 100mg/Tezacaftor 50mg/Ivacaftor 75mg) taken orally. Evening dose: One tablet (Ivacaftor 150mg) taken orally. Both doses should be taken approximately 12 hours apart with fat-containing food.
Condition-Specific Dosing:
Note:
The specified tablet strength (50mg/25mg/37.5mg) is part of the pediatric dosing regimen for patients 6-11 years of age. The adult dose uses different strength tablets.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
For patients 6 to less than 12 years of age: Morning dose: Two tablets (Elexacaftor 50mg/Tezacaftor 25mg/Ivacaftor 37.5mg) taken orally. Evening dose: One tablet (Ivacaftor 75mg) taken orally. Both doses should be taken approximately 12 hours apart with fat-containing food. For patients 2 to less than 6 years of age: Morning dose: Two tablets (Elexacaftor 40mg/Tezacaftor 20mg/Ivacaftor 25mg) taken orally. Evening dose: One tablet (Ivacaftor 50mg) taken orally. Both doses should be taken approximately 12 hours apart with fat-containing food.
Adolescent:
For patients 12 years of age and older: Same as adult dosing.
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment required.
Moderate:
No dose adjustment required.
Severe:
For patients with severe renal impairment (eGFR <30 mL/min/1.73 m2) or end-stage renal disease (ESRD): Morning dose: Two tablets (Elexacaftor 100mg/Tezacaftor 50mg/Ivacaftor 75mg) on Day 1, then one tablet (Elexacaftor 100mg/Tezacaftor 50mg/Ivacaftor 75mg) on Day 3, and then one tablet (Elexacaftor 100mg/Tezacaftor 50mg/Ivacaftor 75mg) twice weekly (e.g., Monday and Thursday). Evening dose: One tablet (Ivacaftor 150mg) on Day 1, then one tablet (Ivacaftor 150mg) on Day 3, and then one tablet (Ivacaftor 150mg) twice weekly (e.g., Monday and Thursday).
Dialysis:
Not studied in patients on dialysis. Dose adjustment for severe impairment applies.
Hepatic Impairment:
Mild:
Child-Pugh A: No dose adjustment required.
Moderate:
Child-Pugh B: Morning dose: Two tablets (Elexacaftor 100mg/Tezacaftor 50mg/Ivacaftor 75mg) on Day 1, then one tablet (Elexacaftor 100mg/Tezacaftor 50mg/Ivacaftor 75mg) twice weekly (e.g., Monday and Thursday). Evening dose: One tablet (Ivacaftor 150mg) on Day 1, then one tablet (Ivacaftor 150mg) twice weekly (e.g., Monday and Thursday).
Severe:
Child-Pugh C: Not recommended unless the benefits outweigh the risks. If used, the dose should be further reduced. Consult prescribing information for specific guidance.
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 most common CFTR mutation, F508del. Ivacaftor then enhances the function of the CFTR protein at the cell surface by increasing the probability of the channel opening, leading to increased chloride transport.
Pharmacokinetics
Absorption:
Bioavailability:
Not directly determined, but absorption is increased when taken with fat-containing food.
Tmax:
Elexacaftor: approximately 6 hours; Tezacaftor: approximately 8 hours; Ivacaftor: approximately 4 hours.
FoodEffect:
Administration with fat-containing food significantly increases the absorption of all three components (Elexacaftor, Tezacaftor, and Ivacaftor).
Distribution:
Vd:
Elexacaftor: 104 L; Tezacaftor: 107 L; Ivacaftor: 353 L (apparent volumes of distribution).
ProteinBinding:
Elexacaftor: >99%; Tezacaftor: >99%; Ivacaftor: >99%.
CnssPenetration:
Limited data, but not expected to be significant due to high protein binding and P-gp efflux.
Elimination:
HalfLife:
Elexacaftor: approximately 25 hours; Tezacaftor: approximately 159 hours; Ivacaftor: approximately 9 hours.
Clearance:
Not available (complex multi-component drug).
ExcretionRoute:
Primarily fecal (Elexacaftor, Tezacaftor, Ivacaftor and their metabolites).
Unchanged:
Minimal unchanged drug excreted in urine or feces.
Pharmacodynamics
OnsetOfAction:
Improvement in FEV1 observed within 2 weeks.
PeakEffect:
Peak improvement in FEV1 typically observed by Week 4.
DurationOfAction:
Sustained effect with continued daily dosing.
Note:
Pharmacodynamic effects are measured by improvements in lung function (FEV1) and sweat chloride levels.
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 or seek immediate 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 symptoms that bother you or do not go away, contact your doctor:
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. 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 or seek immediate 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 symptoms that bother you or do not go away, contact your doctor:
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. 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:
- Signs of liver problems: yellowing of skin or eyes (jaundice), dark urine, pain in the upper right side of your stomach, nausea, vomiting, unusual tiredness, loss of appetite.
- Vision changes: blurred vision, seeing halos around lights, difficulty seeing at night, or any new or worsening eye problems (especially in children).
- Rash or other allergic reactions.
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:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
Any medications you are currently taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins. This is crucial because certain medications, such as those used to treat HIV, infections, seizures, and other conditions, may interact with this drug and should not be taken concurrently.
Please note that this is not an exhaustive list of all medications or health conditions that may interact with this drug.
To ensure your safety, it is vital to discuss all of your medications and health conditions with your doctor and pharmacist. This includes:
All prescription and OTC medications
Natural products
Vitamins
* Any health problems you are experiencing
Before starting, stopping, or changing the dose of any medication, including this one, you must consult with your doctor to confirm that it is safe to do so. This will help prevent any potential interactions or adverse effects.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
Any medications you are currently taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins. This is crucial because certain medications, such as those used to treat HIV, infections, seizures, and other conditions, may interact with this drug and should not be taken concurrently.
Please note that this is not an exhaustive list of all medications or health conditions that may interact with this drug.
To ensure your safety, it is vital to discuss all of your medications and health conditions with your doctor and pharmacist. This includes:
All prescription and OTC medications
Natural products
Vitamins
* Any health problems you are experiencing
Before starting, stopping, or changing the dose of any medication, including this one, you must consult with your doctor to confirm that it is safe to do so. This will help prevent any 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. As directed by your doctor, regularly undergo blood tests and lung function assessments to monitor your condition. 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 breast-feeding, 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 breast-feeding, 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:
- No specific symptoms of overdose have been identified in clinical trials. Symptoms would likely be an exaggeration of known side effects, such as liver enzyme elevations.
What to Do:
In case of suspected overdose, contact a poison control center immediately or seek emergency medical attention. General supportive measures should be instituted, including monitoring of vital signs and observation of the patient's clinical status. Call 1-800-222-1222 (Poison Control).
Drug Interactions
Contraindicated Interactions
- Strong CYP3A inducers (e.g., rifampin, carbamazepine, phenobarbital, phenytoin, St. John's Wort) due to significant decrease in Trikafta exposure, leading to loss of efficacy.
Major Interactions
- Strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, posaconazole, voriconazole, clarithromycin, telithromycin, indinavir, lopinavir, ritonavir, nelfinavir, saquinavir, grapefruit juice) due to significant increase in Trikafta exposure, requiring dose reduction.
- Moderate CYP3A inducers (e.g., bosentan, efavirenz, etravirine, modafinil, nafcillin) due to decreased Trikafta exposure, potentially reducing efficacy.
- CYP3A substrates (e.g., midazolam, triazolam, certain immunosuppressants like cyclosporine, tacrolimus, sirolimus, everolimus; certain calcium channel blockers like amlodipine, diltiazem, verapamil; certain statins like simvastatin, lovastatin) due to potential for increased exposure of the substrate.
Moderate Interactions
- Moderate CYP3A inhibitors (e.g., fluconazole, erythromycin, diltiazem, verapamil, ciprofloxacin) due to increased Trikafta exposure, requiring careful monitoring or dose adjustment.
- P-glycoprotein (P-gp) substrates (e.g., digoxin) due to potential for increased exposure of the substrate.
- Warfarin: Potential for altered INR; monitor closely.
Minor Interactions
- Not specifically categorized as minor, but caution with any drug metabolized by CYP3A.
Monitoring
Baseline Monitoring
Liver Function Tests (ALT, AST, bilirubin)
Rationale: To establish baseline liver health and detect potential hepatotoxicity, which is a known adverse effect.
Timing: Prior to initiating treatment.
Ophthalmic Examination
Rationale: To establish baseline ocular health, especially in pediatric patients, due to reports of cataracts in pediatric patients treated with ivacaftor-containing regimens.
Timing: Prior to initiating treatment in pediatric patients.
Routine Monitoring
Liver Function Tests (ALT, AST, bilirubin)
Frequency: Every 3 months during the first year of treatment, and annually thereafter.
Target: Within normal limits.
Action Threshold: If ALT or AST >5x ULN, or >3x ULN with bilirubin >2x ULN, consider dose interruption and further evaluation. If persistent elevations, consider permanent discontinuation.
Ophthalmic Examination
Frequency: Annually in pediatric patients.
Target: No new or worsening cataracts.
Action Threshold: If cataracts are observed, continued treatment should be weighed against the risks.
Clinical Response (e.g., FEV1, sweat chloride, weight)
Frequency: Regularly as per clinical practice.
Target: Improvement or stabilization of CF symptoms and lung function.
Action Threshold: Lack of clinical response may prompt re-evaluation of diagnosis or adherence.
Symptom Monitoring
- Signs and symptoms of liver injury (e.g., nausea, vomiting, abdominal pain, fatigue, anorexia, dark urine, jaundice, scleral icterus)
- Visual changes or symptoms of cataracts (e.g., blurred vision, glare, difficulty with night vision), especially in pediatric patients.
Special Patient Groups
Pregnancy
There are no adequate and well-controlled studies of Trikafta in pregnant women. Use during pregnancy should only be considered if the potential benefit justifies the potential risk to the fetus. Animal studies have shown some adverse effects at high doses.
Trimester-Specific Risks:
First Trimester:
Risk cannot be ruled out. Limited human data.
Second Trimester:
Risk cannot be ruled out. Limited human data.
Third Trimester:
Risk cannot be ruled out. Limited human data.
Lactation
It is not known whether Trikafta components are excreted in human milk. Due to the potential for serious adverse reactions in breastfed infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Infant Risk:
Risk cannot be ruled out. Potential for adverse effects on the infant.
Pediatric Use
Approved for patients 2 years of age and older. Dosage adjustments are based on age. Ophthalmic examinations are recommended at baseline and annually in pediatric patients due to reports of cataracts.
Geriatric Use
Clinical studies of Trikafta did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. 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
- Always take Trikafta with fat-containing food to maximize absorption and efficacy.
- Strictly avoid grapefruit and grapefruit juice due to significant drug interaction.
- Regular monitoring of liver function tests is crucial, especially during the first year of treatment.
- Pediatric patients require regular eye exams due to the risk of cataracts.
- Trikafta is a highly effective treatment for eligible CF patients, significantly improving lung function and quality of life.
- Adherence is critical for optimal outcomes; emphasize consistent daily dosing.
Alternative Therapies
- Kalydeco (Ivacaftor) - for specific CFTR mutations responsive to potentiator monotherapy.
- Standard CF therapies (e.g., mucolytics, bronchodilators, antibiotics, nutritional support, airway clearance techniques) which are often continued in conjunction with CFTR modulators.
Cost & Coverage
Average Cost:
Highly variable, typically > $300,000 - $350,000 USD per year 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 issues persist or worsen, it is essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication.
This medication is accompanied by a Medication Guide, a patient fact sheet that provides crucial information. It is vital to read this guide carefully and review it again whenever your prescription is refilled. If you have any questions or concerns about this medication, consult your doctor, pharmacist, or other healthcare provider for clarification.
In the event of a suspected overdose, immediately contact your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide detailed information, including the name of the medication taken, the quantity, and the time it occurred.
This medication is accompanied by a Medication Guide, a patient fact sheet that provides crucial information. It is vital to read this guide carefully and review it again whenever your prescription is refilled. If you have any questions or concerns about this medication, consult your doctor, pharmacist, or other healthcare provider for clarification.
In the event of a suspected overdose, immediately contact your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide detailed information, including the name of the medication taken, the quantity, and the time it occurred.