Impact of genetic variation on response to therapy
The SmPC for mavacamten states that patients with CYP2C19 poor metaboliser phenotype may have increased mavacamten exposures that can lead to increased risk of systolic dysfunction compared to normal metabolisers. The AUCinf is 241% times higher, and the peak plasma concentration is 47% higher in CYP2C19 poor metabolisers, compared to normal metabolisers. Terminal half-life is 6 to 9 days in CYP2C19 normal metabolisers and 23 days for CYP2C19 poor metabolisers.
Testing recommendations
The SmPC for mavacamten states that before initiation of treatment patients should be genotyped for CYP2C19 to determine the appropriate dose.
Therapeutic recommendations
Treatment should be initiated and managed under the supervision of a physician experienced in the management of patients with cardiomyopathy.
Consult the SmPC for detailed information on the response measures, assessment schedule, interactions and dose titration.
CYP2C19 metaboliser status unknown
- If treatment initiation occurs prior to determination of CYP2C19 phenotype, patients should follow dosing instructions for poor metabolisers until CYP2C19 phenotype is determined.
- Dose modifications are required with concomitant use of medicines that inhibit or induce CYP2C19 or CYP3A4.
- Consult the SmPC.
CYP2C19 Ultra-rapid metabolisers
Some examples of CYP2C19 genotypes include: *17/*17
- The recommended starting dose is 5 mg orally once daily.
- The maximum dose is 15 mg once daily.
- Dose modifications are required with concomitant use of medicines that inhibit or induce CYP2C19 or CYP3A4.
- Following initiation, the patient should be assessed for clinical response and treatment titrated according to the manufacturer’s recommendations.
- Consult the SmPC.
CYP2C19 Rapid metabolisers
Some examples of CYP2C19 genotypes include: *1/*17
- The recommended starting dose is 5 mg orally once daily.
- The maximum dose is 15 mg once daily.
- Dose modifications are required with concomitant use of medicines that inhibit or induce CYP2C19 or CYP3A4.
- Following initiation, the patient should be assessed for clinical response and treatment titrated according to the manufacturer’s recommendations.
- Consult the SmPC.
CYP2C19 Normal metaboliser status
Some examples of CYP2C19 genotypes include: *1/*1
- The recommended starting dose is 5 mg orally once daily.
- The maximum dose is 15 mg once daily.
- Dose modifications are required with concomitant use of medicines that inhibit or induce CYP2C19 or CYP3A4.
- Following initiation, the patient should be assessed for clinical response and treatment titrated according to the manufacturer’s recommendations.
- Consult the SmPC.
CYP2C19 Intermediate metabolisers
Some examples of CYP2C19 genotypes include: *1/*2, *1/*3, *2/*17, *3/*17
- The recommended starting dose is 5 mg orally once daily.
- The maximum dose is 15 mg once daily.
- Dose modifications are required with concomitant use of medicines that inhibit or induce CYP2C19 or CYP3A4.
- Following initiation, the patient should be assessed for clinical response and treatment titrated according to the manufacturer’s recommendations.
- Consult the SmPC.
CYP2C19 Poor metabolisers
Some examples of CYP2C19 genotypes include: *2/*2, *3/*3, *2/*3
- The recommended starting dose is 2.5 mg orally once daily.
- The maximum dose is 5 mg once daily.
- Dose modifications are required with concomitant use of medicines that inhibit or induce CYP2C19 or CYP3A4.
- Following initiation, the patient should be assessed for clinical response and treatment titrated according to the manufacturer’s recommendations.
- Consult the SmPC.
Further information
Mavacamten is extensively metabolised, primarily through CYP2C19 (74%), CYP3A4 (18%), and CYP2C9 (7.6%). In CYP2C19 intermediate, normal, rapid and ultra‑rapid metabolisers metabolism is expected to be driven through all three pathways, primarily through CYP2C19, and to a lesser extent by CYP3A4. In CYP2C19 poor metabolisers, metabolism is mostly by CYP3A4. CYP2C19 inhibitors/inducers and CYP3A4 inhibitors/inducers may thus affect the clearance of mavacamten and increase/decrease mavacamten plasma concentration, and this will depend on the CYP2C19 phenotype. Consult the SmPC for a full list of drug interactions.
References
Bristol Myers Squibb Pharmaceuticals Ltd (2024) Camzyos 10mg hard capsules SmPC. Available at: https://www.medicines.org.uk/emc/product/15029/smpc (Accessed online 15 April 2025).
