What are the precautions for combining Avmapki and Faczynja?

In clinical studies of the combination of Avmapki and Faczynja in the treatment of recurrent low-grade serous ovarian cancer (LGSOC), warnings and precautions such as eye toxicity, severe skin toxicity, hepatotoxicity, rhabdomyolysis, and embryo-fetal toxicity have emerged. Discontinue and resume at reduced dose upon recovery, or permanently discontinue based on severity.

1. Eye toxicity:Avmapki-Faczynja combination can cause adverse ocular reactions, including visual impairment and vitreoretinal disease. Common ocular adverse reactions are visual impairment, dry eye, orbital/periorbital edema, and vitreous floaters.

Refer patients to a qualified eye care professional for a comprehensive eye examination at baseline, before Cycle 2, every three cycles thereafter, and as clinically indicated. For any new or worsening eye signs or symptoms, refer the patient to an eye care professional immediately. Monitor for ocular adverse reactions and, depending on the severity and duration of the ocular adverse reactions, suspend, reduce, or permanently discontinue Avmapki-Faczynja combination preparation.

2. Severe skin toxicity: including severe adverse skin reactions (scars). Cases of acute generalized exanthematous pustulosis, erythema multiforme, and drug reactions with eosinophilia and systemic symptoms have also been reported in clinical trials. The most common skin toxicities are rash, acneiform dermatitis, dry skin, pruritus, and photosensitivity.

Patients can use topical corticosteroids (for the face, scalp, neck, upper chest, and upper back) and systemic oral antibiotics under the guidance of a doctor to prevent adverse skin reactions. These drugs are started at the beginning of the Avmapki-Faczynja combination pack and used for at least the first two treatment cycles. Limit unnecessary sun exposure and wear sunscreen (Sun Protection Factor[SPF] ≥ 30) every day. Monitor for skin toxicity and suspend, reduce dose, or permanently discontinue Avmapki-Faczynja combination based on severity and persistence.

3. Hepatotoxicity: In clinical studies, increases in AST, bilirubin, ALT and alkaline phosphatase have occurred. Increased blood bilirubin may be due to defatinib inhibiting the enzyme responsible for metabolism (uridine diphosphate glucuronosyltransferase [UGT] 1A1) and transport (organic anion transporting polypeptide [OATP] 1B1/1B3) of bilirubin. Monitor liver-related laboratory values u200bu200bbefore the start of each cycle, on Day 15 of the first four cycles, and as clinically indicated. Depending on the severity and duration of these adverse reactions, suspend, reduce the dose, or permanently discontinue Avmapki-Faczynja combination.

4. Rhabdomyolysis: Avmapki-Faczynja combination can lead to an increase in creatine phosphokinase (CPK), and some patients may experience myalgia. Monitor CPK before the start of each cycle, on day 15 of the first four cycles, and as clinically indicated. If CPK is elevated, evaluate the patient for rhabdomyolysis or other causes. Depending on the severity and duration of the adverse reaction, withhold, reduce, or permanently discontinue the Avmapki-Faczynja combination.

5. Embryo-fetal toxicity: According to the mechanism of action, pregnant women taking Avmapki-Faczynja compound preparation may cause harm to the fetus. Inhibition of either molecular pathway is associated with embryo-fetal abnormalities and lethality in animals. Inform pregnant women and women of reproductive potential of the potential risks to the fetus.

Advise females of reproductive potential to use effective contraception during treatment with Avmapki-Faczynja combination and for 1 month after the last dose. Advise male patients with a female partner of reproductive potential to use effective contraception during treatment with Avmapki-Faczynja combination and for 4 months after the last dose.

Reference materials:https://www.verastem.com/pdf/avmapki-faczynja-co-pack-full-prescribing-information.pdf