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Guaifenesin; Phenylephrine: (Average) CNS-stimulating actions of caffeine can be additive with other CNS stimulants or psychostimulants like phenylephrine; caffeine ought to be avoided or used cautiously. Extreme caffeine ingestion (through medicines, supplements or beverages including espresso, green tea, other teas, guarana, colas) might contribute to side effects like nervousness, irritability, insomnia, or tremor.
Ibrutinib: (Major) If coadministered with ciprofloxacin, scale back the ibrutinib dose to 280 mg/day PO for the treatment of B-cell malignancies. Resume ibrutinib on the earlier dose if ciprofloxacin is discontinued. Provoke ibrutinib on the really useful dose of 420 mg/day PO for the remedy of chronic graft-versus-host disease. Monitor patients for ibrutinib toxicity (e.g., hematologic toxicity, bleeding, infection); interruption of ibrutinib therapy or a dose reduction could also be needed in patients who develop extreme toxicity. Ibrutinib is a CYP3A4 substrate; ciprofloxacin is a moderate CYP3A4 inhibitor. When ibrutinib was administered with multiple doses of another reasonable CYP3A4 inhibitor, the Cmax and AUC values of ibrutinib have been increased by 3.4-fold and 3-fold, respectively.
Canagliflozin; Metformin: (Average) Concomitant administration of metformin and ketoconazole could improve metformin exposure and increase the risk for lactic acidosis. If these medicine are given together, monitor for indicators of metformin toxicity; metformin dose adjustments may be wanted. Metformin is a human multidrug and toxic extrusion (MATE) and OCT2 substrate and ketoconazole is a MATE and OCT2 inhibitor. MATE and OCT2 inhibitors might decrease metformin elimination by blocking renal tubular secretion.