Elexacaftor-Tezacaftor-Ivacaftor

Elexacaftor-Tezacaftor-Ivacaftor is a prescription medication used for the treatment of cystic fibrosis (CF) in people aged 12 years and older who have at least one copy of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

• Elexacaftor-Tezacaftor-Ivacaftor is available under the following different brand names: Trikafta

Common side effects of Elexacaftor-Tezacaftor-Ivacaftor include:

• Headache
• Diarrhea
• Upper respiratory tract infection (common cold) including stuffy and runny nose
• Stomach (abdominal) pain
• Inflamed sinuses
• Increase in liver enzymes
• Increase in a certain blood enzyme called creatine phosphokinase
• Rash
• Flu (influenza)
• Increase in blood bilirubin

Serious side effects of Elexacaftor-Tezacaftor-Ivacaftor include:

• Pain or discomfort in the upper right stomach (abdominal) area
• Nausea or vomiting
• Yellowing of the skin or the white part of the eyes
• Dark, amber-colored urine
• Loss of appetite

Rare side effects of Elexacaftor-Tezacaftor-Ivacaftor include:

• None 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out. 

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Fixed-dose tablet co-packaged with ivacaftor tablet

• 100 mg/50 mg/75 mg plus ivacaftor 150 mg

Cystic Fibrosis

Adult dosage

• 2 fixed-dose tablets (elexacaftor 100 mg, tezacaftor 50 mg, and ivacaftor 75 mg) orally every morning and 1 ivacaftor 150-mg tablet orally every evening; approximately 12 hours apart

Pediatric dosage

• Below 6 years:
  • Not Established
• 6 to below 12 years:
  • Below 30 kg: 2 tablets each containing 50 mg elexacaftor/ 25 mg tezacaftor/ 37.5 mg ivacaftor every morning and 1 ivacaftor 75-mg tab orally every evening approximately 12 hours apart
  • Above 30 kg: 2 tablets each containing 100 mg elexacaftor/ 50 mg tezacaftor/ 75 mg ivacaftor every morning and 1 ivacaftor 150-mg tab orally every evening approximately 12 hours apart
• Above 12 years
  • 2 fixed-dose tablets (elexacaftor 100 mg, tezacaftor 50 mg, and ivacaftor 75 mg) orally evening morning and 1 ivacaftor 150-mg tablet orally every evening approximately 12 hours apart

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Elexacaftor-Tezacaftor-Ivacaftor has severe interactions with the following drug
  • lonafarnib
• Elexacaftor-Tezacaftor-Ivacaftor has serious interactions with at least 58 other drugs.
• Elexacaftor-Tezacaftor-Ivacaftor has moderate interactions with at least 216 other drugs.
• Elexacaftor-Tezacaftor-Ivacaftor has minor interactions with the following drugs
  • acetazolamide
  • anastrozole
  • cyclophosphamide
  • larotrectinib

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Elexacaftor-Tezacaftor-Ivacaftor?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Elexacaftor-Tezacaftor-Ivacaftor?”

Cautions

• Noncongenital lens opacities were reported with ivacaftor-containing regimens; other risk factors were present in some cases (e. g, corticosteroid use, radiation exposure); a possible risk attributable to treatment with ivacaftor cannot be excluded
• Hormonal contraceptives may play a role in the occurrence of rash; for patients taking hormonal contraceptives who develop a rash, consider interrupting therapy and hormonal contraceptives; following the resolution of the rash, consider resuming therapy without the hormonal contraceptives; if the rash does not recur, resumption of hormonal contraceptives can be considered
• Elevated transaminases and hepatic injury
  • Elevated liver transaminases and bilirubin levels were observed; liver failure leading to transplantation was reported in a patient with cirrhosis and portal hypertension while receiving treatment
  • Avoid use in patients with pre-existing advanced liver disease (. g, as evidenced by cirrhosis, portal hypertension, ascites, hepatic encephalopathy) unless benefits are expected to outweigh risks; if used in these patients, they should be closely monitored after initiation of treatment
  • In some instances, transaminase elevations have been associated with concomitant elevations in total bilirubin and/or international normalized ratio (INR) and have resulted in patients being hospitalized for intervention, including patients without a history of pre-existing liver disease
  • Measure levels before initiating, every 3Months during the first year, and annually thereafter; consider more frequent monitoring for those with a history of the hepatic disease; interrupt dosing for significant elevations
• Drug interaction overview
  • CYP3A inhibitors or inducers
    • Coadministration with moderate or strong CYP3A inhibitors increases systemic exposure of lumacaftor/tezacaftor/ivacaftor; dosage adjustment is required if coadministered
    • Coadministration with strong CYP3A inducers is not recommended; ivacaftor systemic exposure is significantly decreased and exposure to lumacaftor and tezacaftor is expected to decrease if coadministered with a strong CYP3A inducer
    • Potential for lumacaftor/tezacaftor/ivacaftor to affect other drugs
    • Ivacaftor may inhibit CYP2C9; monitor INR if coadministered with warfarin; caution with other CYP2C9 substrates (.g, glimepiride, glipizide)
  • Coadministration of ivacaftor or tezacaftor/ivacaftor with digoxin, a sensitive P-GP substrate, increased digoxin AUC by 1.3-fold, consistent with weak inhibition of P-GP by ivacaftor
  • Elexacaftor and its active metabolite (M23-ELX) inhibit uptake by OATP1B1 and OATP1B3 in vitro; coadministration may increase exposures of drugs that are substrates of these transporters (.g, statins, glyburide, nateglinide, repaglinide)

Pregnancy and Lactation

• Human data are limited and incomplete from clinical trials on the use of lumacaftor/tezacaftor/ivacaftor or its components in pregnant women to inform a drug-associated risk
• Although there are no animal reproduction studies with the concomitant administration of lumacaftor, tezacaftor, and ivacaftor, separate reproductive and developmental studies were conducted with each active component in pregnant rats and rabbits
• Lactation
  • No data are available regarding the presence of elexacaftor, tezacaftor, or ivacaftor in human milk, the effects on the breastfed infant, or the effects on milk production.
  • Elexacaftor, tezacaftor, and ivacaftor are excreted into the milk of lactating rats