Drug Interactions between Effervescent Pain Relief and ponatinib

MONITOR CLOSELY: Coadministration of ponatinib and drugs that interfere with platelet function or coagulation may potentiate the risk of bleeding complications. Treatment with ponatinib is associated with severe, sometimes fatal hemorrhage including cerebral and gastrointestinal hemorrhage. In clinical trials, hemorrhagic events occurred in 24% of patients treated with ponatinib, and serious events occurred in 5% of patients. The incidence of serious bleeding events was higher in patients with accelerated phase or blast phase chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). Most hemorrhagic events occurred in patients with grade 4 thrombocytopenia.

MANAGEMENT: Concomitant use of other medications that interfere with platelet function or coagulation should be considered cautiously in patients treated with ponatinib. Close clinical and laboratory observation for bleeding complications is recommended during therapy. The INR should be monitored more frequently during coadministration of warfarin. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

MONITOR: Agents that cause urinary alkalinization can reduce serum salicylate concentrations in patients receiving anti-inflammatory dosages of aspirin or other salicylates. The mechanism involves reduction in salicylate renal tubular reabsorption due to increased urinary pH, resulting in increased renal salicylate clearance especially above urine pH of 7. This interaction is sometimes exploited in the treatment of salicylate toxicity.

MANAGEMENT: Patients treated chronically with urinary alkalinizers and large doses of salicylates (i.e. 3 g/day or more) should be monitored for potentially diminished or inadequate analgesic and anti-inflammatory effects, and the salicylate dosage adjusted if necessary.

Coadministration with drugs that elevate the gastric pH such as proton pump inhibitors, H2-receptor antagonists, and antacids may decrease the oral bioavailability of ponatinib and reduce its concentrations in plasma. The aqueous solubility of ponatinib has been shown to be pH-dependent, with higher pH resulting in decreased solubility. However, in a drug interaction study in healthy volunteers, coadministration of ponatinib after multiple doses of lansoprazole resulted in a minor reduction in ponatinib Cmax but no change in overall systemic exposure (AUC) compared to ponatinib administered alone. Therefore, ponatinib may be coadministered with medicines that increase gastric pH without dose adjustment or separation of administration.