Select a medication above to begin.
Alyftrek
vanzacaftor/ tezacaftor/ deutivacaftor
Black Box Warnings .
Hepatotoxicity
elevated transaminases observed during tx; serious and potentially fatal drug-induced hepatic injury and hepatic failure reported with elexacaftor/tezacaftor/ivacaftor; hepatic injury reported within 1-15mo of elexacaftor/tezacaftor/ivacaftor tx start; monitor LFTs before tx start, then qmo x6mo, then q3mo x12mo, then at least q12mo, or if hepatic disease history, elevated baseline LFTs, or elevated LFTs history with elexacaftor, tezacaftor, or ivacaftor-containing product consider monitoring more frequently; interrupt tx if significant LFT elevations or if hepatic injury signs/symptoms occur, consider hepatologist referral, and monitor closely until resolution; if abnormalities resolve, only restart tx if benefit outweighs risk with closer monitoring; avoid use in patients with severe hepatic impairment; in patients with moderate hepatic impairment, use not recommended or may use with close monitoring
Adult Dosing .
Dosage forms: TAB: 10 mg/50 mg/125 mg
cystic fibrosis
- [2 tabs (vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg) PO qd (1 dose = vazacaftor 20 mg/tezacaftor 100 mg/deutivacaftor 250 mg)]
- Info: for patients with at least one F508del-CFTR mutation or vanzacaftor/tezacaftor/deutivacaftor-responsive CFTR gene mutation; give with fat-containing food
renal dosing
- [see below]
- eGFR >30: no adjustment; eGFR <30: not defined
- HD/PD: not defined
hepatic dosing
- [see below]
- Child-Pugh Class A or B: no adjustment; Child-Pugh Class C: avoid use; Info: caution advised if Child-Pugh Class A or B
Peds Dosing .
- Dosage forms: TAB: 4 mg/20 mg/50 mg, 10 mg/50 mg/125 mg
cystic fibrosis
- [6-11 yo, <40 kg]
- Dose: 3 tabs (vanzacaftor 4 mg/tezacaftor 20 mg/deutivacaftor 50 mg) PO qd (1 dose = vanzacaftor 12 mg/tezacaftor 60 mg/deutivacaftor 150 mg); Info: for patients with at least one F508del-CFTR mutation or vanzacaftor/tezacaftor/deutivacaftor-responsive CFTR gene mutation; give with fat-containing food
- [6-11 yo, >40 kg]
- Dose: 2 tabs (vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg) PO qd (1 dose = vazacaftor 20 mg/tezacaftor 100 mg/deutivacaftor 250 mg); Info: for patients with at least one F508del-CFTR mutation or vanzacaftor/tezacaftor/deutivacaftor-responsive CFTR gene mutation; give with fat-containing food
- [12 yo and older]
- Dose: 2 tabs (vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg) PO qd (1 dose = vazacaftor 20 mg/tezacaftor 100 mg/deutivacaftor 250 mg); Info: for patients with at least one F508del-CFTR mutation or vanzacaftor/tezacaftor/deutivacaftor-responsive CFTR gene mutation; give with fat-containing food
renal dosing
- [see below]
- eGFR >30: no adjustment; eGFR <30: not defined
- HD/PD: not defined
hepatic dosing
- [see below]
- Child-Pugh Class A or B: no adjustment; Child-Pugh Class C: avoid use; Info: caution advised if Child-Pugh Class A or B
Contraindications / Cautions .
- hepatic impairment, Child-Pugh Class C
- caution: hepatic impairment, Child-Pugh Class A-B
- caution: elevated LFTs history with prior elexacaftor/tezacaftor/ivacaftor use
- caution: baseline LFTs elevated
- caution: hepatic disease history
- caution: hypersensitivity to drug or ingredient
- caution: hypervitaminosis A
Drug Interactions .
Overview
vanzacaftor/tezacaftor/deutivacaftor
CFTR facilitator/potentiator
- CYP3A4 substrate
- CYP2C9 inhibitor, weak
- BCRP inhibitor
- P-gp inhibitor, weak
- drug interactions apply only to Alyftrek (vanzacaftor/tezacaftor/deutivacaftor); see other products for potentially relevant interactions
Contraindicated
- colchicine
Avoid/Use Alternative
- alpelisib
- apalutamide
- apixaban
- bosentan
- butalbital
- carbamazepine
- cenobamate
- cladribine oral
- dabigatran
- dabrafenib
- efavirenz
- encorafenib
- ensartinib
- enzalutamide
- etravirine
- fexinidazole
- fosamprenavir
- fosphenytoin
- grapefruit
- ivosidenib
- lopinavir/ritonavir
- lorlatinib
- lumacaftor/ivacaftor
- mavacamten
- methadone
- mitapivat
- mitotane
- modafinil
- nafcillin
- neratinib
- pacritinib
- pazopanib
- pentobarbital
- pexidartinib
- phenobarbital
- phenytoin
- pralsetinib
- primidone
- relugolix
- repotrectinib
- rifabutin
- rifampin
- rifapentine
- rivaroxaban
- sirolimus albumin-bound
- sotorasib
- St. John's wort
- topotecan
- venetoclax
Monitor/Modify Tx
- adagrasib
- afatinib
- aficamten
- aprepitant
- atazanavir
- atorvastatin
- avacopan
- berotralstat
- celecoxib
- ceritinib
- chloramphenicol
- clarithromycin
- clofazimine
- cobicistat
- conivaptan
- crizotinib
- cyclosporine
- danazol
- darunavir
- deuruxolitinib
- diclofenac
- digoxin
- diltiazem
- dronedarone
- duvelisib
- edoxaban
- enfortumab vedotin
- erythromycin
- everolimus
- fedratinib
- fluconazole
- fluvastatin
- glimepiride
- idelalisib
- imatinib
- irinotecan
- isavuconazonium
- itraconazole
- ketoconazole
- lapatinib
- lefamulin
- lenacapavir
- letermovir
- levoketoconazole
- lonafarnib
- mavorixafor
- methotrexate
- mifepristone
- mitoxantrone
- morphine
- nefazodone
- nelfinavir
- netupitant
- nilotinib
- nirogacestat
- pitavastatin
- posaconazole
- pravastatin
- quinidine (antiarrhythmic)
- ranolazine
- ribociclib
- rilzabrutinib
- riociguat
- ritonavir
- rosuvastatin
- simvastatin
- sirolimus
- tacrolimus
- talazoparib
- tenofovir alafenamide
- tenofovir disoproxil
- tipranavir
- torsemide
- tucatinib
- ubrogepant
- verapamil
- voriconazole
- warfarin
Caution Advised
- armodafinil
- artemether/lumefantrine
- belzutifan
- bexarotene
- brigatinib
- clobazam
- danshen
- darolutamide
- dexamethasone
- dicloxacillin
- echinacea
- elafibranor
- elagolix
- enasidenib
- eslicarbazepine acetate
- felbamate
- garlic
- ginkgo
- ginseng, Asian
- glecaprevir
- glycerol phenylbutyrate
- griseofulvin
- meropenem
- mobocertinib
- naldemedine
- nevirapine
- odevixibat
- olutasidenib
- omaveloxolone
- oxcarbazepine
- perampanel
- pibrentasvir
- pioglitazone
- prednisone
- rufinamide
- sarilumab
- seladelpar
- stiripentol
- sulfasalazine
- sunvozertinib
- suzetrigine
- tazemetostat
- tecovirimat
- telotristat ethyl
- tocilizumab
- topiramate
- tovorafenib
- vaborbactam
- vamorolone
- vemurafenib
- vinblastine
- vorasidenib
- zanubrutinib
Adverse Reactions .
Serious Reactions
- hepatotoxicity
- hepatic impairment
- hypersensitivity reaction
- anaphylaxis
- intracranial HTN
- cataracts (peds patients)
Common Reactions
- cough
- nasopharyngitis
- URI
- headache
- oropharyngeal pain
- influenza
- fatigue
- ALT incr.
- rash
- AST incr.
- sinus congestion
Safety/Monitoring .
Monitoring Parameters
LFTs before tx start, then qmo x6mo, then q3mo x12mo, then at least q12mo, or if hepatic disease history, elevated baseline LFTs, or elevated LFTs history with elexacaftor, tezacaftor, or ivacaftor-containing product consider monitoring more frequently; ophthalmic exam at baseline, then periodically in peds patients
Pregnancy/Lactation .
Pregnancy
Clinical Summary
weigh risk/benefit during pregnancy; no human data available; no known risk of teratogenicity based on animal data at 0.2-30x MRHD
Lactation
Clinical Summary
weigh risk/benefit while breastfeeding; no human data available to assess risk of infant harm or effects on milk production
Pharmacology .
Metabolism: for vanzacaftor: liver; CYP450: 3A4/5 substrate; for tezacaftor: liver extensively; CYP450: 3A4/5 substrate; Info: active metabolite; for deutivacaftor: liver; CYP450: 3A4/5 substrate
Excretion: for vanzacaftor: feces 91.6% (minimally unchanged), urine 0.5%; Half-life: 92.8h; for tezacaftor: feces 72%, urine 14% (<1% unchanged); Half-life: 22.5h; for deutivacaftor: unknown; Half-life: 19.2h
Subclass: Cystic Fibrosis
Mechanism of Action
for vanzacaftor: facilitates cellular processing of mutant CFTR protein, including F508del-CFTR, increasing amount of functional CFTR protein delivered to cell surfaces; for tezacaftor: facilitates cellular processing of mutant CFTR protein, including F508del-CFTR, increasing amount of functional CFTR protein delivered to cell surfaces; for deutivacaftor: potentiates mutant CFTR protein, increasing chloride channel open probability and chloride transport
Formulary .
No Formulary Selected
Join Now to View Patient Handouts!
Create a FREE epocrates Online account to access patient medication instructions. Your patients and caregivers will appreciate you printing these friendly handouts, available in English and Spanish. Each handout addresses common concerns such as how to take the medication, and possible side effects.
Current Members: Sign In.
Pill Pictures
Join Now to View Pill Pictures!
Create a FREE epocrates Online account to access full-color images of medications within the drug monograph.
Current Members: Sign In.