Drug Interactions between Kisqali Femara Co-Pack and samarium sm 153 lexidronam

GENERALLY AVOID: Theoretical concerns exist that chemotherapeutic agents and other bone marrow depressants may potentiate the myelosuppressive effects of samarium sm 153 lexidronam. In clinical trials, white blood cell and platelet counts decreased to a nadir of approximately 40% to 50% of baseline in 95% of patients within three to five weeks after administration of samarium sm 153 lexidronam, and tended to return to pretreatment levels by eight weeks. The potential for additive bone marrow toxicity with myelotoxic treatments including chemotherapy or external beam radiation has not been studied.

MANAGEMENT: The manufacturer recommends avoiding concomitant use of samarium sm 153 lexidronam with chemotherapy or external beam radiation therapy unless benefits are anticipated to outweigh the risks. Moreover, samarium sm 153 lexidronam should not be given after either of these treatments until there has been time for adequate marrow recovery. Caution and close monitoring of bone marrow function are advisable if coadministration with other myelotoxic agents is required. Patients should be advised to contact their physician if they develop signs and symptoms of myelosuppression such as pallor, dizziness, fatigue, lethargy, fainting, unusual bleeding or bruising, or signs of infection such as fever, chills, diarrhea, sore throat, muscle aches, shortness of breath, blood in phlegm, weight loss, red or inflamed skin, body sores, and pain or burning during urination.

MONITOR: Coadministration with ribociclib may increase the plasma concentrations and pharmacologic effects of drugs that are substrates of CYP450 3A4. The proposed mechanism is decreased clearance due to ribociclib-mediated inhibition of CYP450 3A4 metabolism. In healthy study subjects, administration of midazolam, a sensitive CYP450 3A4 substrate, with multiple 400 mg daily doses of ribociclib increased the midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) by 2.1-fold and 3.8-fold, respectively, compared to midazolam administered alone. When given at a clinically relevant dose of 600 mg daily, ribociclib is predicted to increase midazolam Cmax and AUC by 2.4-fold and 5.2-fold, respectively.

MANAGEMENT: Caution is advised when ribociclib is used concomitantly with drugs that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever ribociclib is added to or withdrawn from therapy.