Tezacaftor-Ivacaftor

Tezacaftor-Ivacaftor is a prescription medication used  for cystic fibrosis (CF) in patients who are homozygous for the F508del mutation or who have at least 1 mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive to Tezacaftor-Ivacaftor based on in vitro data and/or clinical evidence.

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

Common side effects of Tezacaftor-Ivacaftor include:

• headache
• nausea
• stuffy nose
• dizziness

Serious side effects of Tezacaftor-Ivacaftor include:

• high liver enzymes in the blood
• pain or discomfort in the upper right stomach (abdominal) area
• yellowing of your skin or the white part of the eyes
• loss of appetite
• nausea or vomiting
• dark, amber-colored urine

Rare side effects of 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, 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

Copackaged tablets

• Copackaged as a fixed-dose combination tablet of tezacaftor 50mg and ivacaftor 75mg PLUS a separate ivacaftor 75mg tablet.
• Copackaged as a fixed-dose combination tablet of tezacaftor 100mg and ivacaftor 150mg PLUS a separate ivacaftor 150mg tablet.

Cystic fibrosis

Adult dosage

• Morning dose: One Tezacaftor-Ivacaftor 100-mg/150-mg fixed-dose tablet orally.
• Evening dose: One ivacaftor 150-mg tablet orally.
• Administer morning and evening doses approximately 12 hours apart.

Pediatric dosage

• Children aged younger than 6 years: Safety and efficacy not established
• Children aged between 6 and 12 years and weighing less than 30 kg
• Morning dose: One Tezacaftor-Ivacaftor 50-mg/75-mg fixed-dose tablet orally.
• Evening dose: One ivacaftor 75-mg tablet orally.
  • Administer morning and evening doses approximately 12 hours apart
• Children aged 6 years and older and weighing 30 kg and more
• Morning dose: One Tezacaftor-Ivacaftor 100-mg/150-mg fixed-dose tablet orally.
• Evening dose: One ivacaftor 150-mg tablet orally.
  • Administer morning and evening doses 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, healthcare provider, or pharmacist first.

• Tezacaftor-Ivacaftor has severe interactions with the following drug:
  • lonafarnib
• Tezacaftor-Ivacaftor has serious interactions with at least 62 other drugs
• Tezacaftor-Ivacaftor has moderate interactions with at least 218 other drugs
• 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 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 Tezacaftor-Ivacaftor?”

Long-Term Effects

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

Cautions

• Ivacaftor may elevate liver transaminases; assess ALT and AST before initiating, every 3 months during the first year, and annually thereafter; monitor more frequently in patients with a history of elevated transaminases, when transaminases are significantly elevated (eg, ALT/AST above 5× ULN, ALT/AST above 3× ULN with bilirubin above 2× ULN), interrupt dosing and closely monitor until the abnormalities resolve.
• Non-congenital lens opacities reported in pediatric patients with ivacaftor; baseline and follow-up ophthalmological examinations are recommended before initiating.
• Drug interaction overview
  • CYP3A inducers
    • Avoid coadministration with strong CYP3A inducers.
    • Coadministration with strong CYP3A inducers is not recommended, owing to significantly decreased systemic exposure to ivacaftor, which may reduce therapeutic effectiveness.
    •  (eg, Rifampin decreases ivacaftor AUC by 89%)
    • Tezacaftor exposures can also be expected to decrease significantly.
  • CYP3A inhibitors
    • Strong and moderate CYP3A inhibitors significantly increase tezacaftor and ivacaftor systemic exposure; dosage regimen modifications are required if coadministered.
    • Coadministration with itraconazole, a strong CYP3A inhibitor, increased tezacaftor AUC by 4-fold and ivacaftor by 15.6-fold.
  • P-gp substrates
    • Coadministration with digoxin, a sensitive P-gp substrate, increased digoxin exposure by 1.3-fold, consistent with weak inhibition of P-gp by ivacaftor.
    • When used concomitantly with digoxin or other substrates of P-gp with a narrow therapeutic index (eg, cyclosporine, everolimus, sirolimus, tacrolimus), appropriate monitoring should be used.

Pregnancy and Lactation

• There are limited and incomplete human data from clinical trials and postmarketing reports on the use of tezacaftor and ivacaftor in pregnant women to inform a drug-associated risk.
• Lactation
  • Unknown if distributed in human breast milk.
  • Both tezacaftor and ivacaftor are excreted into the milk of lactating 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 the breastfed infant from the drug or the underlying maternal condition.