Drug Interactions between caffeine / pheniramine / phenylephrine / sodium citrate / sodium salicylate and Refludan

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.

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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.

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GENERALLY AVOID: Theoretically, salicylates may potentiate the effects of anticoagulants and increase the risk of bleeding. Salicylates interfere with the action of vitamin K and induce a dose-dependent alteration in hepatic synthesis of coagulation factors VII, IX and X, occasionally increasing the prothrombin time. While these effects are generally slight for most salicylates (except aspirin) at recommended dosages, they may be of clinical significance when combined with the inhibitory effects of anticoagulants on the clotting cascade. Moreover, salicylates are known to cause dose-related gastrointestinal bleeding, which may be complicated by anticoagulant therapy.

MANAGEMENT: Until further data are available, products containing salicylates, especially if given chronically or in high dosages, should preferably be avoided in patients receiving anticoagulants. Close clinical and laboratory observation for bleeding complications is recommended if concurrent therapy is necessary. The same precaution should be observed with the use of salicylate-related agents such as salicylamide because of their structural and pharmacological similarities. Ambulatory 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. Patients should also be counseled to avoid any other over-the-counter salicylate products.

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