Boxed Warnings
Camzyos reduces left ventricular ejection fraction (LVEF).
Prior to and during treatment with Camzyos regular clinical and echocardiogram monitoring are required to appropriately titrate and maintain the optimal patient dose.
Initiation of Camzyos in patients with LVEF < 55% is not recommended. Interrupt Camzyos if LVEF is < 50% at any visit (see Section 4.2 Dose and Method of Administration; Section 4.4 Special Warnings and Precautions for Use).
Concomitant use of Camzyos with certain cytochrome P450 inhibitors or discontinuation of certain cytochrome P450 inducers may increase the risk of heart failure due to systolic dysfunction; therefore, the use of Camzyos is contraindicated with the following (see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use):
moderate to strong CYP2C19 inhibitors or strong CYP3A4 inhibitors;
moderate to strong CYP2C19 inducers or moderate to strong CYP3A4 inducers.
1 Name of Medicine
Mavacamten.
2 Qualitative and Quantitative Composition
Each 2.5 mg hard capsule contains 2.5 mg mavacamten.
Each 5 mg hard capsule contains 5 mg mavacamten.
Each 10 mg hard capsule contains 10 mg mavacamten.
Each 15 mg hard capsule contains 15 mg mavacamten.
For the full list of excipients, see Section 6.1 List of Excipients.
3 Pharmaceutical Form
Hard capsule (capsule).
Camzyos 2.5 mg capsules. Light purple opaque cap imprinted with "2.5 mg" in black, and white opaque body imprinted with "Mava" in black, both in radial direction. Capsule size: 2.
Camzyos 5 mg capsules. Yellow opaque cap imprinted with "5 mg" in black, and white opaque body imprinted with "Mava" in black, both in radial direction. Capsule size: 2.
Camzyos 10 mg capsules. Pink opaque cap imprinted with "10 mg" in black, and white opaque body imprinted with "Mava" in black, both in radial direction. Capsule size: 2.
Camzyos 15 mg capsules. Gray opaque cap imprinted with "15 mg" in black, and white opaque body imprinted with "Mava" in black, both in radial direction. Capsule size: 2.
4 Clinical Particulars
4.9 Overdose
Human experience of overdose with Camzyos is limited. Camzyos has been given as a single dose of up to 144 mg in patients with HCM. There was one serious adverse reaction of vasovagal reaction, hypotension, and asystole lasting 38 seconds reported at that dose. In healthy subjects, doses of up to 25 mg have been administered for up to 25 days. Three out of 8 participants treated at the 25 mg dose level experienced 20% or greater reductions in LVEF. Systolic dysfunction is the most likely result of overdosage of Camzyos.
Management of overdose. If warranted, treatment of overdose with Camzyos consists of discontinuation of Camzyos treatment as well as medically supportive measures to maintain hemodynamic status (e.g. initiation of inotropic support with adrenergic agents), including close monitoring of vital signs and LVEF and management of the clinical status of the patient. Early administration of activated charcoal may be considered in case of mavacamten overdose to reduce absorption although has not been specifically studied. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via a nasogastric tube, once the airway is protected.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).
5 Pharmacological Properties
5.3 Preclinical Safety Data
Genotoxicity. Mavacamten was not found to be genotoxic in a reverse mutation bacterial test (Ames test), a human in vitro lymphocyte clastogenicity assay, or a rat in vivo micronucleus assay.
Carcinogenicity. There was no evidence of carcinogenicity at the highest mavacamten doses tested in a 6-month rasH2 transgenic mouse study or a 2-year rat study. Exposures (AUC) in mice were up to 3-fold higher compared to the MRHD, while exposures (AUC) in rats were up to 0.2-fold compared to the maximum recommended human dose (MRHD).
Animal toxicology. The safety of mavacamten has been evaluated in rats and dogs dosed for up to 6 and 9 months, respectively. Noted toxicities, including echocardiographic findings of reduced systolic performance and cardiac dilation, death, due to heart failure, and, in rats, increased heart weights likely secondary to cardiac hypertrophy in response to decreased contractility, were consistent with the mavacamten mechanism of action and primary pharmacological activity. Other findings included cardiac osseous metaplasia in rats and QTc prolongation in dogs. Plasma exposures (AUC) at the no observed adverse effect level NOAEL in rats and dogs respectively are lower than those in humans at the MRHD.
6 Pharmaceutical Particulars
6.7 Physicochemical Properties
Chemical structure. The chemical name of mavacamten is 3-(1-methylethyl)-6- [[(1S)-1-phenylethyl]amino]-2,4(1H,3H)-pyrimidinedione.
The IUPAC Name is 6-[[(1S)-1-phenylethyl]amino]- 3-propan-2-yl-1H-pyrimidine-2,4-dione.
The molecular formula is C15H19N3O2, and the molecular weight is 273.33 g/mol.
The chemical structure is:
https://stagingapi.mims.com/au/public/v2/images/fullchemgif/CSMAVACA.gif CAS number. 1642288-47-8.
Mavacamten is a white to off-white powder that is practically insoluble in water and aqueous buffers, sparingly soluble in methanol and ethanol, and freely soluble in dimethyl sulfoxide and N-methyl-2-pyrrolidone.
7 Medicine Schedule (Poisons Standard)
Schedule 4 - Prescription Only Medicine.
Summary Table of Changes
https://stagingapi.mims.com/au/public/v2/images/fulltablegif/CAMZYOST.gif
