Drug Interactions between alemtuzumab and Kisqali Femara Co-Pack

MONITOR CLOSELY: The use of alemtuzumab with other immunosuppressive or antineoplastic agents may increase the risk of infections. Alemtuzumab reduces T and B lymphocytes, but the extent and duration of the reduction is expected to differ based on the dose and indication. Alone, alemtuzumab may cause severe and prolonged myelosuppression, lymphopenia, and rarely, fatal autoimmune cytopenias. Serious, sometimes fatal opportunistic infections have been reported, and the risk may theoretically increase when coadministered with other immunosuppressive therapy. Agents that may be significantly myelo- or immunosuppressive include antineoplastic agents, radiation, zidovudine, linezolid, some antirheumatic agents, high dosages of corticosteroids or adrenocorticotropic agents (greater than 10 mg/day to 1 mg/kg/day, whichever is less, of prednisone or equivalent for more than 2 weeks), and long-term topical or inhaled corticosteroids.

MANAGEMENT: Caution is advised if alemtuzumab must be used in patients who have recently received or are receiving treatment with other immunosuppressive or antineoplastic drugs, and vice versa. Some authorities consider the combination of alemtuzumab (marketed under the brand name Lemtrada) to be contraindicated in patients receiving antineoplastic or immunosuppressive therapies. Close clinical and laboratory monitoring should be completed as recommended by the manufacturer. The product labeling should be consulted for recommendations on anti-infective prophylaxis to minimize the risks of serious opportunistic infections; as well as, for dosing adjustments and discontinuation recommendations should other toxicities or adverse effects occur. Some authorities recommend that alemtuzumab, marketed under the brand name Campath, not be given within 3 weeks of other chemotherapeutic agents. Since higher dosages are associated with an increased incidence of pancytopenia, the manufacturer of this dosage form of alemtuzumab recommends that single doses not exceed 30 mg and cumulative weekly doses not exceed 90 mg.

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.