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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 w/ elexacaftor/tezacaftor/ivacaftor; hepatic injury reported w/in 1-15mo of elexacaftor/tezacaftor/ivacaftor tx start; monitor LFTs before tx start, then qmo x6mo, then q3mo x12mo, then at least q12mo or consider more frequently if hepatic dz hx, baseline LFTs elevated, or elevated LFT hx w/ elexacaftor-, tezacaftor-, or ivacaftor-containing products; interrupt tx if significant LFT elevations or if hepatic injury s/sx occur, consider hepatologist referral, and monitor closely until resolution; if abnormalities resolve, only restart tx if benefit outweighs risk w/ closer monitoring; avoid use in pts w/ severe hepatic impairment; in pts w/ moderate hepatic impairment, use not recommended or may use w/ close monitoring
Adult Dosing .
Dosage forms: convenience pack
Special Note
- [convenience pack components]
- Info: 7-day pack contains vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg tab x14
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 pts w/ at least one F508del-CFTR mutation or vanzacaftor/tezacaftor/deutivacaftor-responsive CFTR gene mutation; give w/ 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: convenience pack
Special Note
- [6-11 yo, <40 kg convenience pack components]
- Info: 7-day pack contains vanzacaftor 4 mg/tezacaftor 20 mg/deutivacaftor 50 mg tab x21
- [6-11 yo, >40 kg convenience pack components]
- Info: 7-day pack contains vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg tab x14
- [12 yo and older convenience pack components]
- Info: 7-day pack contains vanzacaftor 10 mg/tezacaftor 50 mg/deutivacaftor 125 mg tab x14
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 pts w/ at least one F508del-CFTR mutation or vanzacaftor/tezacaftor/deutivacaftor-responsive CFTR gene mutation; give w/ 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 pts w/ at least one F508del-CFTR mutation or vanzacaftor/tezacaftor/deutivacaftor-responsive CFTR gene mutation; give w/ 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 pts w/ at least one F508del-CFTR mutation or vanzacaftor/tezacaftor/deutivacaftor-responsive CFTR gene mutation; give w/ 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 hx w/ prior elexacaftor/tezacaftor/ivacaftor use
- caution: baseline LFTs elevated
- caution: hepatic dz hx
- caution: hypersensitivity to drug or ingredient
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
- futibatinib
- 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
- 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
- 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
- olutasidenib
- omaveloxolone
- oxcarbazepine
- perampanel
- pibrentasvir
- pioglitazone
- prednisone
- rufinamide
- sarilumab
- seladelpar
- somatropin
- stiripentol
- sulfasalazine
- suzetrigine
- tazemetostat
- tecovirimat
- telotristat ethyl
- tocilizumab
- topiramate
- tovorafenib
- vaborbactam
- vamorolone
- vemurafenib
- vinblastine
- vorasidenib
- zanubrutinib
Adverse Reactions .
Serious Reactions
- hepatotoxicity
- hepatic impairment
- hypersensitivity rxn
- anaphylaxis
- cataracts (peds pts)
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 consider more frequently if hepatic dz hx, elevated baseline LFTs, or elevated LFT hx w/ elexacaftor, tezacaftor, or ivacaftor-containing products; ophthalmic exam at baseline, then periodically in peds pts
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
vanzacaftor and tezacaftor facilitate cellular processing of mutant CFTR protein, incl. F508del-CFTR, increasing amt of functional CFTR protein delivered to cell surfaces; deutivacaftor potentiates mutant CFTR protein, increasing chloride channel open probability and chloride transport
Formulary .
No Formulary Selected
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