Deutivacaftor (1 brand name, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- ALYFTREK
Boxed Warning
Elevated transaminases have been observed in patients treated with ALYFTREK. Cases of serious and potentially fatal drug-induced liver injury and liver failure were reported in patients who were taking a fixed-dose combination drug containing elexacaftor, tezacaftor, and ivacaftor, which contains the same or similar active ingredients as ALYFTREK. Liver injury has been reported within the first month of therapy and up to 15 months following initiation of elexacaftor/tezacaftor/ivacaftor [see Warnings and Precautions (5.1) and Adverse Reactions (6)]. Assess liver function tests (ALT, AST, alkaline phosphatase, and bilirubin) in all patients prior to initiating ALYFTREK, every month during the first 6 months of treatment, then every 3 months for the next 12 months, then at least annually thereafter. Consider more frequent monitoring for patients with a history of liver disease or elevated liver function tests at baseline [see Dosage and Administration (2.1), Warnings and Precautions (5.1), Adverse Reactions (6), and Use in Specific Populations (8.7)]. Interrupt ALYFTREK for significant elevations in liver function tests or in the event of signs or symptoms of liver injury. Consider referral to a hepatologist. Follow patients closely with clinical and laboratory monitoring until abnormalities resolve. If abnormalities resolve, resume treatment only if the benefit is expected to outweigh the risk. Closer monitoring is advised after resuming ALYFTREK [see Warnings and Precautions (5.1)]. ALYFTREK should not be used in patients with severe hepatic impairment (Child-Pugh Class C). ALYFTREK is not recommended in patients with moderate hepatic impairment (Child-Pugh Class B) and should only be considered when there is a clear medical need, and the benefit outweighs the risk. If used, monitor patients closely [see Dosage and Administration (2.4), Warnings and Precautions (5.1), Adverse Reactions (6), Use in Specific Populations (8.7), and Clinical Pharmacology (12.3)].
Indications and Usage
ALYFTREK is indicated for the treatment of cystic fibrosis (CF) in adult and pediatric patients 6 years of age and older who have a clinical diagnosis of CF and who have at least one variant in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is either responsive based on clinical and/or in vitro data (see Table 5) or results in production of CFTR protein [see Clinical Pharmacology (12.1)]. If the patient’s genotype is unknown, an FDA-cleared CF genetic test should be used to confirm the presence of at least one variant in the CFTR gene that is either responsive based on clinical and/or in vitro data or results in production of CFTR protein.
Contraindications
None.
Adverse Reactions
The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Drug-Induced Liver Injury and Liver Failure [see Warnings and Precautions (5.1)] Hypersensitivity Reactions, Including Anaphylaxis [see Warnings and Precautions (5.2)] Patients Who Discontinued or Interrupted Elexacaftor-, Tezacaftor-, or Ivacaftor-Containing Drugs Due to Adverse Reactions [see Warnings and Precautions (5.3)] Intracranial Hypertension [see Warnings and Precautions (5.4)] Neuropsychiatric Events, Including Suicidal Thoughts and Behaviors [see Warnings and Precautions (5.5)] Cataracts [see Warnings and Precautions (5.8)]
Mechanism of Action
Vanzacaftor and tezacaftor bind to different sites on the CFTR protein and have an additive effect in facilitating the cellular processing and trafficking of select mutant forms of CFTR (including F508del-CFTR) to increase the amount of CFTR protein delivered to the cell surface compared to either molecule alone. Deutivacaftor potentiates the channel open probability (or gating) of the CFTR protein at the cell surface. The combined effect of vanzacaftor, tezacaftor and deutivacaftor is increased quantity and function of CFTR at the cell surface, resulting in increased CFTR activity as measured both by CFTR-mediated chloride transport in vitro and by sweat chloride in patients with CF.
Overdosage
Treatment of overdosage consists of general supportive measures including monitoring of vital signs and observation of the clinical status.