Interactions : אינטראקציות

7           DRUG INTERACTIONS
7.1         Potential for Other Drugs to Affect Plasma Concentrations of CAMZYOS Mavacamten is primarily metabolized by CYP2C19 and to a lesser extent by CYP3A4 and CYP2C9. Inducers and inhibitors of CYP2C19 and moderate to strong inhibitors or inducers of CYP3A4 may affect the exposures of mavacamten [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)]. (See Table 1)


Table 1:       Established and Potentially Significant Pharmacokinetic Drug Interactions with CAMZYOS
Impact of Other Drugs on CAMZYOS

Moderate to Strong CYP2C19 Inhibitors or Strong CYP3A4 Inhibitors
Concomitant use with a moderate to strong CYP2C19 or a strong CYP3A4 inhibitor increases mavacamten exposure, which may increase the risk of Clinical Impact heart failure due to systolic dysfunction [see Contraindications (4), Warnings and Precautions (5.2), Clinical Pharmacology (12.3)].
Concomitant use with a moderate to strong CYP2C19 inhibitor or a strong Prevention or Management
CYP3A4 inhibitor is contraindicated.

Moderate to Strong CYP2C19 Inducers or Moderate to Strong CYP3A4 Inducers Concomitant use with a moderate to strong CYP2C19 inducer or a moderate to strong CYP3A4 inducer decreases mavacamten exposure, which may reduce CAMZYOS’ efficacy [see Clinical Pharmacology (12.3)]. The risk Clinical Impact            of heart failure due to systolic dysfunction may increase with discontinuation of these inducers as the levels of induced enzyme normalizes [see Contraindications (4) and Warnings and Precautions
(5.2)].
Concomitant use of a moderate to strong CYP2C19 inducer or a moderate Prevention or Management to strong CYP3A4 inducer is contraindicated.

Weak CYP2C19 Inhibitors or Moderate CYP3A4 Inhibitors
Concomitant use with a weak CYP2C19 inhibitor or a moderate CYP3A4
Clinical Impact            inhibitor increases mavacamten exposure, which may increase the risk of adverse drug reactions [see Warnings and Precautions (5.2)].
Initiate CAMZYOS at the recommended starting dosage of 5 mg orally once daily in patients who are on stable therapy with a weak CYP2C19 inhibitor or a moderate CYP3A4 inhibitor.
Reduce dose of CAMZYOS by one level (i.e., 15 to 10 mg, 10 to 5 mg, or Prevention or Management   5 to 2.5 mg) in patients who are on CAMZYOS treatment and intend to initiate a weak CYP2C19 inhibitor or a moderate CYP3A4 inhibitor. Avoid initiation of concomitant weak CYP2C19 and moderate CYP3A4 inhibitors in patients who are on stable treatment with 2.5 mg of CAMZYOS because a lower dose is not available [see Dosage and Administration (2.2)].


7.2         Potential for CAMZYOS to Affect Plasma Concentrations of Other Drugs Certain CYP3A4, CYP2C9, and CYP2C19 Substrates
Mavacamten is an inducer of CYP3A4, CYP2C9, and CYP2C19. Concomitant use with CYP3A4, CYP2C9, or CYP2C19 substrates may reduce plasma concentration of these drugs [see Clinical Pharmacology (12.3)]. Closely monitor when CAMZYOS is used with concomitant CYP3A4, CYP2C9 or CYP2C19 substrates unless otherwise recommended in the Prescribing Information.
Certain Combined Hormonal Contraceptives (CHC)
Progestin and ethinyl estradiol are CYP3A4 substrates. Concomitant use of CAMZYOS may decrease exposures of certain progestins [see Clinical Pharmacology (12.3)], which may lead to contraceptive failure. CHCs containing a combination of ethinyl estradiol and norethindrone may be used with mavacamten, but if other CHCs are used, advise patients to add nonhormonal contraception (such as condoms) during concomitant use and for 4 months after the last dose of CAMZYOS.
7.3         Drugs That Reduce Cardiac Contractility
Expect additive negative inotropic effects of CAMZYOS and other drugs that reduce cardiac contractility.
Avoid concomitant use of CAMZYOS in patients on disopyramide, ranolazine, verapamil with a beta blocker, or diltiazem with a beta blocker as these medications and combinations increase the risk of left ventricular systolic dysfunction and heart failure symptoms and clinical experience is limited [see Warnings and Precautions (5.1)].
If concomitant therapy with a negative inotrope is initiated, or if the dose of a negative inotrope is increased, monitor LVEF closely until stable doses and clinical response have been achieved.