Vanzacaftor-Tezacaftor-Deutivacaftor

Vanzacaftor-Tezacaftor-Deutivacaftor is a combination medication indicated for the treatment of cystic fibrosis in patients aged 6 years and older who have at least one F508del mutation or another responsive mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

• Vanzacaftor-Tezacaftor-Deutivacaftor is available under the following different brand names: Alyftrek.

Common side effects of Vanzacaftor-Tezacaftor-Deutivacaftor include:

• cough
• mouth or throat pain
• pain or swelling of your nose or throat (nasopharyngitis) 
• flu (influenza)
• tiredness
• upper respiratory tract infection (common cold) including stuffy and runny nose 
• increase in liver enzymes
• rash
• headache 
• sinus congestion 

Serious side effects of Vanzacaftor-Tezacaftor-Deutivacaftor include:

• serious allergic reaction symptoms include rash or hives, tightness of the chest or throat difficulty breathing light-headedness or dizziness
• abnormality of the eye lens (cataract)

Rare side effects of Vanzacaftor-Tezacaftor-Deutivacaftor 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, coordination loss, 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 and pediatric dosage

Tablet

• 4 mg/20 mg/ 50 mg
• 10 mg/50 mg/125 mg

Cystic fibrosis

Adult dosage

• Vanzacaftor 20 mg/tezacaftor 100 mg/deutivacaftor 250 mg orally daily

Pediatric dosage

• Children younger than 6 years: Safety and efficacy not established
• Children aged between 6 to 12 years
  • Weighing less than 40 kg: Vanzacaftor 12 mg/tezacaftor 60 mg/deutivacaftor 150 mg orally daily
  • Weighing 40 kg and more: Vanzacaftor 20 mg/tezacaftor 100 mg/deutivacaftor 250 mg orally daily
• Children aged 12 years and older
• Any weight: Vanzacaftor 20 mg/tezacaftor 100 mg/deutivacaftor 250 mg orally daily

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.

• Vanzacaftor-Tezacaftor-Deutivacaftor has severe interactions with no other drugs
• Vanzacaftor-Tezacaftor-Deutivacaftor has serious interactions with at least 34 other drugs
• Vanzacaftor-Tezacaftor-Deutivacaftor has moderate interactions with at least 60 other drugs
• Vanzacaftor-Tezacaftor-Deutivacaftor has minor interactions with the following drugs:
  • acetazolamide
  • anastrozole
  • cyclophosphamide
  • drospirenone
  • 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 the products you use. 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, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Vanzacaftor-Tezacaftor-Deutivacaftor?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Vanzacaftor-Tezacaftor-Deutivacaftor?”

Cautions

• Hypersensitivity reactions
  • May cause hypersensitivity, including anaphylaxis
  • Hypersensitivity reactions reported during postmarketing surveillance for another drug that contains the same or similar active ingredients
  • Discontinue the drug if signs or symptoms of serious hypersensitivity reactions develop and initiate appropriate treatment; weigh benefits with risks before resuming therapy
• Discontinued or interrupted treatment
  • Consider benefits and risks before using in patients who discontinued or interrupted elexacaftor-, tezacaftor-, or ivacaftor-containing drugs due to adverse reactions
  • If prescribed, closely monitor for adverse reactions as clinically appropriate
• Cataracts
  • Cases of noncongenital lens opacities reported in pediatric patients treated with drugs containing ivacaftor (ivacaftor is like deutivacaftor)
  • Although other risk factors were present (e.g., corticosteroid use, exposure to radiation) in some cases, a possible risk attributable to ivacaftor treatment cannot be excluded
  • Baseline and follow-up ophthalmological examinations recommended in pediatric patients
• Drug interaction overview
  • Vanzacaftor, tezacaftor, and deutivacaftor are substrates of CYP3A
  • Tezacaftor and deutivacaftor are P-gp inhibitors
  • Vanzacaftor and deutivacaftor are BCRP inhibitors (in vitro)
  • Deutivacaftor is a CYP2C9 inhibitor (in vitro)
  • Strong or moderate CYP3A inhibitors
  • Modify Vanzacaftor-Tezacaftor-Deutivacaftor dose
  • Coadministration with strong or moderate CYP3A inhibitors increases systemic exposures of Vanzacaftor, tezacaftor, and deutivacaftor, which may increase the risk of adverse effects
  • Strong or moderate CYP3A inducers
    • Avoid
    • Coadministration with strong or moderate CYP3A inducers decreases systemic exposures of Vanzacaftor, tezacaftor, and deutivacaftor, which may reduce efficacy
  • CYP2C9 substrates
    • Monitor
    • Caution is advised if coadministered with CYP2C9 substrates
    • Monitor INR more frequently if coadministered with warfarin
  • P-gp and BCRP substrates
    • Monitor
    • Unless otherwise recommended in P-gp or BCRP substrate prescribing information, monitor more frequently for adverse reactions if coadministered with substrates where minimal concentration changes may lead to serious adverse reactions

Pregnancy and Lactation

• Data are unavailable data on use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes
• Lactation
  • There are no data on the presence of vanzacaftor, tezacaftor, or deutivacaftor or their metabolites in human milk, its effects on breastfed infants, or milk production
  • Vanzacaftor and tezacaftor are excreted into the milk of lactating female rats
  • Deutivacaftor has not been evaluated; however, ivacaftor is excreted into the milk of lactating female rats
  • Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug and any potential adverse effects on breastfed children from the drug or underlying maternal condition