Wirkstoffe & Arzneimittelsicherheit

Gegenanzeigen · Camzyos

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HOS-147592 · Präparat HOS-099694

▪ Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. ▪ During pregnancy and in women of childbearing potential not using effective contraception (see sections 4.4 and 4.6). ▪ Concomitant treatment with strong CYP3A4 inhibitors in patients with CYP2C19 poor metaboliser phenotype and undetermined CYP2C19 phenotype (see sections 4.2, 4.4 and 4.5). ▪ Concomitant treatment with the combination of a strong CYP2C19 inhibitor and a strong CYP3A4 inhibitor (see section 4.5).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Camzyos

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HOS-147593 · Präparat HOS-099694

Pharmacodynamic interactions

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Wechselwirkungen · Camzyos

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HOS-147594 · Präparat HOS-099694

If treatment with a new negative inotrope is initiated or if the dose of a negative inotrope is increased in a patient receiving mavacamten, close medical supervision with monitoring of LVEF should be provided until stable doses and clinical response have been achieved (see sections 4.2 and 4.4).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Camzyos

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HOS-147595 · Präparat HOS-099694

9 Pharmacokinetic interactions

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Camzyos

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HOS-147596 · Präparat HOS-099694

Effect of other medicinal products on mavacamten In CYP2C19 intermediate, normal, rapid and ultra-rapid metabolisers, mavacamten is primarily metabolised by CYP2C19 and to a lesser extent by CYP3A4. In CYP2C19 poor metabolisers, metabolism is mostly by CYP3A4 (see section 5.2). 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. All clinical drug-drug interaction studies mainly enrolled CYP2C19 normal metabolisers and no CYP2C19 poor metabolisers were included in the assessment of the drug-drug interaction and therefore the effect of co-administration of CYP2C19 and CYP3A4 inhibitors with mavacamten in CYP2C19 poor metabolisers is not completely certain. Recommendations for dose modification and/or additional monitoring of patients initiating or discontinuing treatment with, or changing the dose of, concomitant medicinal products that are inhibitors of CYP2C19 or CYP3A4 or inducers of CYP2C19 or CYP3A4 are provided in table 2.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Camzyos

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HOS-147597 · Präparat HOS-099694

Strong CYP2C19 plus strong CYP3A4 inhibitors Co-administration of mavacamten with the combination of a strong CYP2C19 and a strong CYP3A4 inhibitor is contra-indicated (see section 4.3).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Camzyos

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HOS-147598 · Präparat HOS-099694

CYP2C19 inhibitors The effect of a moderate and strong CYP2C19 inhibitor on the PK of mavacamten was not investigated in a clinical drug-drug interaction study. The effect of a strong CYP2C19 inhibitor (e.g., ticlopidine) will be similar to the effect of the CYP2C19 poor metabolising status (see table 1). Co-administration of mavacamten with a weak CYP2C19 inhibitor (omeprazole) resulted in a 48% increase in mavacamten AUCinf with no effect on Cmax in CYP2C19 normal metabolisers. Intermittent administration of a CYP2C19 inhibitor (such as omeprazole or esomeprazole) is not recommended (see section 4.4).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): esomeprazole (HOS-087944) ticlopidine (HOS-087946) omeprazole (HOS-085912)

Wechselwirkungen · Camzyos

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HOS-147601 · Präparat HOS-099694

CYP3A4 inhibitors The effect of strong CYP3A4 inhibitors on the PK of mavacamten was not investigated in a clinical drug-drug interaction study. Co-administration of mavacamten with a strong CYP3A4 inhibitor (itraconazole) in CYP2C19 normal metabolisers is expected to result in an increase in mavacamten plasma concentration of up to 59% and 40% in AUC0-24 and Cmax, respectively. Co-administration of mavacamten with a moderate CYP3A4 inhibitor (verapamil) in CYP2C19 normal metabolisers resulted in an increase in mavacamten plasma concentration of 16% and 52% in AUCinf and Cmax, respectively. This change was not considered clinically significant.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): itraconazole (HOS-084516) verapamil (HOS-090602)

Wechselwirkungen · Camzyos

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HOS-147602 · Präparat HOS-099694

CYP2C19 and CYP3A4 inducers No clinical interaction studies were conducted to investigate the effect of concomitant administration with a strong CYP3A4 and CYP2C19 inducer. Co-administration of mavacamten with a strong inducer of both CYP2C19 and CYP3A4 (e.g., rifampicin) is expected to significantly affect the pharmacokinetics (PK) of mavacamten and leads to reduced efficacy and therefore co-administration with strong inducers of both CYP2C19 and CYP3A4 is not recommended. If discontinuing concomitant treatment with a strong inducer of CYP2C19 or CYP3A4 increase clinical assessments and mavacamten dose should be reduced (see section 4.2).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Wechselwirkungen · Camzyos

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HOS-147603 · Präparat HOS-099694

10 Table 2: Dose modification/monitoring of mavacamten with concomitant medicinal products

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Wechselwirkungen · Camzyos

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HOS-147604 · Präparat HOS-099694

Concomitant CYP2C19 poor metaboliser phenotype* CYP2C19 intermediate, medicinal product normal, rapid and ultra-rapid metaboliser phenotype Inhibitors Combined use of a Contra-indicated (see section 4.3) Contra-indicated (see strong CYP2C19 section 4.3) inhibitor and a strong CYP3A4 inhibitor Strong CYP2C19 No dose adjustment. Monitor LVEF 4 weeks Initiate mavacamten at a dose of inhibitor (e.g., later, and then resume the patient’s monitoring 2.5 mg. ticlopidine, fluconazole, and titration schedule (see section 4.2). The dose should be reduced from fluvoxamine) 15 mg to 5 mg and from 10 mg If CYP2C19 phenotype has not yet been and 5 mg to 2.5 mg or pause determined: treatment if on 2.5 mg. No adjustment of the starting dose of 2.5 mg Monitor LVEF 4 weeks later, is needed. and then resume the patient’s The dose should be reduced from 5 mg to monitoring and titration schedule 2.5 mg or pause treatment if on 2.5 mg. (see section 4.2). Monitor LVEF 4 weeks later, and then resume the patient’s monitoring and titration schedule (see section 4.2). Strong CYP3A4 Contra-indicated (see section 4.3) No dose adjustment. Monitor inhibitor (e.g., LVEF 4 weeks later, and then clarithromycin, resume the patient’s monitoring itraconazole, and titration schedule (see ketoconazole, section 4.2). voriconazole, ritonavir, cobicistat, ceritinib, idelalisib, tucatinib) Moderate CYP2C19 No dose adjustment. Monitor LVEF 4 weeks No adjustment of the starting inhibitor (e.g., later, and then resume the patient’s monitoring dose of 5 mg is needed. fluconazole, fluoxetine, and titration schedule. Adjust mavacamten Initiating or increasing the dose omeprazolea) dose based on clinical assessment (see of a moderate inhibitor while on section 4.2). mavacamten treatment: Dose should be reduced by one If CYP2C19 phenotype has not yet been dose level or pause treatment if determined: on 2.5 mg. Monitor LVEF No adjustment of the starting dose of 2.5 mg 4 weeks later, and then resume is needed. the patient’s monitoring and The dose should be reduced from 5 mg to titration schedule (see 2.5 mg or pause treatment if on 2.5 mg. section 4.2). Monitor LVEF 4 weeks later, and then resume the patient’s monitoring and titration schedule. Adjust mavacamten dose based on clinical assessment (see section 4.2). Moderate CYP3A4 If on medication when starting mavacamten, No dose adjustment. Monitor inhibitor (e.g., no adjustment of the starting dose of 2.5 mg is LVEF 4 weeks later, and then erythromycin, grapefruit needed. resume the patient’s monitoring juice, verapamil, and titration schedule (see diltiazem) Initiating or increasing the dose of a moderate section 4.2). inhibitor while on mavacamten treatment: If patients are receiving a 5 mg dose of mavacamten, their dose should be reduced to 2.5 mg or if on 2.5 mg pause treatment for 4 weeks. Monitor LVEF 4 weeks later, and then resume the patient’s monitoring and titration schedule (see section 4.2).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): ceritinib (HOS-086215) diltiazem (HOS-086288) ketoconazole (HOS-084513) cobicistat (HOS-088111) voriconazole (HOS-084524) itraconazole (HOS-084516) fluconazole (HOS-087945) clarithromycin (HOS-084517) erythromycin (HOS-084514) fluoxetine (HOS-085946) ritonavir (HOS-084521) fluvoxamine (HOS-085908) tucatinib (HOS-145562) ticlopidine (HOS-087946) idelalisib (HOS-116811) verapamil (HOS-090602)

Wechselwirkungen · Camzyos

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HOS-147609 · Präparat HOS-099694

11 Concomitant CYP2C19 poor metaboliser phenotype* CYP2C19 intermediate, medicinal product normal, rapid and ultra-rapid metaboliser phenotype Weak CYP2C19 No dose adjustment. Monitor LVEF 4 weeks Initiating or increasing the dose inhibitor (e.g., later, and then resume the patient’s monitoring of a weak inhibitor while on cimetidine, citalopram, and titration schedule. Adjust mavacamten mavacamten treatment: omeprazolea, dose based on clinical assessment (see Monitor LVEF 4 weeks later, esomeprazole) section 4.2). and subsequently resume the patient’s monitoring and titration schedule. Adjust mavacamten dose based on clinical assessment (see section 4.2). Weak CYP3A4 inhibitor If on medication when starting mavacamten, Initiating or increasing the dose (e.g., cimetidine, no adjustment of the starting dose of 2.5 mg is of a weak inhibitor while on esomeprazole, needed. mavacamten treatment: omeprazole, No dose adjustment. Monitor pantoprazole) Initiating or increasing the dose of weak LVEF 4 weeks later, and then inhibitor while on mavacamten treatment: resume the patient’s monitoring If patients are receiving a 5 mg dose of and titration schedule. Adjust mavacamten, their dose should be reduced to mavacamten dose based on 2.5 mg or if on 2.5 mg pause treatment for clinical assessment (see 4 weeks. section 4.2). Monitor LVEF 4 weeks later, and then resume the patient’s monitoring and titration schedule (see section 4.2). Inducers Strong CYP2C19 Initiating or increasing the dose of strong Initiating or increasing the dose inducer and strong inducer while on mavacamten treatment: of strong inducer while on CYP3A4 inducer (e.g., Monitor LVOT gradient and LVEF 4 weeks mavacamten treatment: rifampicin, apalutamide, later. Adjust mavacamten dose based on Monitor LVOT gradient and enzalutamide, mitotane, clinical assessment and then resume the LVEF 4 weeks later. Adjust phenytoin, patient’s monitoring and titration schedule mavacamten dose based on carbamazepine, (see section 4.2). The maximum dose is 5 mg. clinical assessment and then efavirenz, St. John’s resume the patient’s monitoring wort) Discontinuing or decreasing the dose of and titration schedule (see strong inducer while on mavacamten section 4.2). treatment: Decrease mavacamten dose from 5 mg to Discontinuing or decreasing the 2.5 mg or pause treatment if on 2.5 mg. dose of strong inducer while on Monitor LVEF 4 weeks later, and then resume mavacamten treatment: the patient’s monitoring and titration schedule Decrease mavacamten by one (see section 4.2). dose level when on doses 5 mg or higher. Maintain mavacamten dose when on 2.5 mg. Monitor LVEF 4 weeks later, and then resume the patient’s monitoring and titration schedule (see section 4.2).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): citalopram (HOS-087802) esomeprazole (HOS-087944) cimetidine (HOS-085835) carbamazepine (HOS-085618) apalutamide (HOS-086212) pantoprazole (HOS-085167) mitotane (HOS-112479) efavirenz (HOS-087947) phenytoin (HOS-084531) enzalutamide (HOS-116829) omeprazole (HOS-085912)

Wechselwirkungen · Camzyos

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HOS-147612 · Präparat HOS-099694

12 Concomitant CYP2C19 poor metaboliser phenotype* CYP2C19 intermediate, medicinal product normal, rapid and ultra-rapid metaboliser phenotype Moderate or weak No dose adjustment. Monitor LVEF 4 weeks Initiating the dose of moderate CYP2C19 inducer (e.g., later, and then resume the patient’s monitoring or weak inducer while on letermovir, and titration schedule. Adjust mavacamten mavacamten treatment: norethindrone, dose based on clinical assessment (see Monitor LVOT gradient and prednisone) section 4.2). LVEF 4 weeks later. Adjust mavacamten dose based on clinical assessment and then resume the patient’s monitoring and titration schedule (see section 4.2).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): letermovir (HOS-090621) norethindrone (HOS-088136) prednisone (HOS-084526)

Wechselwirkungen · Camzyos

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HOS-147615 · Präparat HOS-099694

Discontinuing a moderate or weak inducer while on mavacamten treatment: Decrease mavacamten by one dose level when on doses 5 mg or higher. Maintain mavacamten dose when on 2.5 mg. Monitor LVEF 4 weeks later, and then resume the patient’s monitoring and titration schedule. Adjust mavacamten dose based on clinical assessment (see section 4.2). Moderate or weak Initiating or increasing the dose of moderate No dose adjustment. Monitor CYP3A4 inducer (e.g., or weak inducer while on mavacamten LVEF 4 weeks later, and then phenobarbital, treatment: resume the patient’s monitoring primidone) Monitor LVOT gradient and LVEF 4 weeks and titration schedule. Adjust later. Adjust mavacamten dose based on mavacamten dose based on clinical assessment and then resume the clinical assessment (see patient’s monitoring and titration schedule section 4.2). (see section 4.2).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): phenobarbital (HOS-085617) primidone (HOS-090551)

Wechselwirkungen · Camzyos

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HOS-147616 · Präparat HOS-099694

Discontinuing or decreasing the dose of moderate or weak inducer while on mavacamten treatment: Decrease mavacamten dose to 2.5 mg or pause treatment if on 2.5 mg. Monitor LVEF 4 weeks later, and then resume the patient’s monitoring and titration schedule (see section 4.2). * Includes patients for whom the CYP2C19 phenotype has not yet been determined. a Omeprazole is considered a weak CYP2C19 inhibitor at a dose of 20 mg once daily and a moderate CYP2C19 inhibitor at a total daily dose of 40 mg.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): omeprazole (HOS-085912)

Wechselwirkungen · Camzyos

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HOS-147617 · Präparat HOS-099694

Effect of mavacamten on other medicinal products Mavacamten in vitro data suggest a potential induction of CYP3A4. Co-administration of a 17-day course of mavacamten at clinical relevant exposures in CYP2C19 normal, rapid and ultra-rapid metabolisers did not decrease the exposure to ethinyl oestradiol and norethindrone, which are the components of typical oral contraceptives and substrates for CYP3A4. Furthermore, co-administration of a 16-day course of mavacamten in CYP2C19 normal metabolisers, at clinical relevant exposures, resulted in a 13% decrease in midazolam plasma concentration. This change was not considered clinically significant.

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

RxNorm-Namen im Text (wörtliche Treffer, Rolle nicht bewertet): norethindrone (HOS-088136) midazolam (HOS-086167)

Nebenwirkungen · Camzyos

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HOS-147618 · Präparat HOS-099694

Summary of the safety profile

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Nebenwirkungen · Camzyos

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HOS-147619 · Präparat HOS-099694

The most commonly reported adverse reactions with mavacamten are dizziness (17%), dyspnoea (12%), systolic dysfunction (5%) and syncope (5%).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.

Nebenwirkungen · Camzyos

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HOS-147620 · Präparat HOS-099694

Tabulated list of adverse reactions

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Nebenwirkungen · Camzyos

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HOS-147621 · Präparat HOS-099694

Adverse reactions reported in patients treated with mavacamten in two phase 3 studies (EXPLORER- HCM and VALOR-HCM) are tabulated below. A total of 179 patients received a daily dose of either 2.5 mg, 5 mg, 10 mg or 15 mg of mavacamten. The median treatment duration for patients receiving mavacamten was 30.1 weeks (range: 1.6 to 40.3 weeks).

Originalpassage; keine automatisch abgeleitete Schwere, Häufigkeit oder Kausalität. Auch verneinte Befunde und nicht untersuchte Kombinationen bleiben sichtbar.