Drug Interaction Report

CONTRAINDICATED: Coadministration of antiplatelet therapy during the first 3 months of treatment with abrocitinib may increase the risk of bleeding with thrombocytopenia. Treatment with abrocitinib was associated with a transient, dose-dependent decrease in platelet count with the maximum decrease occurring at a median of 24 days after continuous administration of abrocitinib 200 mg/day. Recovery of platelet count (40% recovery) occurred by 12 weeks without discontinuation of the treatment. This interaction does not apply for low-dose aspirin (81 mg/day or less).

MANAGEMENT: Antiplatelet drugs, except for low-dose aspirin (81 mg/day or less), during the first 3 months of treatment with abrocitinib are considered contraindicated.

MONITOR: Chronic administration of antacids may reduce serum salicylate concentrations in patients receiving large doses of aspirin or other salicylates. The mechanism involves reduction in salicylate renal tubular reabsorption due to urinary alkalinization by antacids, resulting in increased renal salicylate clearance. In three children treated with large doses of aspirin for rheumatic fever, serum salicylate levels declined 30% to 70% during coadministration with a magnesium and aluminum hydroxide antacid. Other studies have found similar, albeit less dramatic results. Antacids reportedly have no effect on the oral bioavailability of aspirin in healthy adults. However, administration of antacids containing either aluminum and magnesium hydroxide or calcium carbonate two hours before aspirin dosing led to reduced absorption of aspirin in uremic patients.

MANAGEMENT: Patients treated chronically with antacids (or oral medications that contain antacids such as didanosine buffered tablets or pediatric oral solution) 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.

MONITOR: Chronic administration of antacids may reduce serum salicylate concentrations in patients receiving large doses of aspirin or other salicylates. The mechanism involves reduction in salicylate renal tubular reabsorption due to urinary alkalinization by antacids, resulting in increased renal salicylate clearance. In three children treated with large doses of aspirin for rheumatic fever, serum salicylate levels declined 30% to 70% during coadministration with a magnesium and aluminum hydroxide antacid. Other studies have found similar, albeit less dramatic results. Antacids reportedly have no effect on the oral bioavailability of aspirin in healthy adults. However, administration of antacids containing either aluminum and magnesium hydroxide or calcium carbonate two hours before aspirin dosing led to reduced absorption of aspirin in uremic patients.

MANAGEMENT: Patients treated chronically with antacids (or oral medications that contain antacids such as didanosine buffered tablets or pediatric oral solution) 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.

MONITOR: Chronic administration of antacids may reduce serum salicylate concentrations in patients receiving large doses of aspirin or other salicylates. The mechanism involves reduction in salicylate renal tubular reabsorption due to urinary alkalinization by antacids, resulting in increased renal salicylate clearance. In three children treated with large doses of aspirin for rheumatic fever, serum salicylate levels declined 30% to 70% during coadministration with a magnesium and aluminum hydroxide antacid. Other studies have found similar, albeit less dramatic results. Antacids reportedly have no effect on the oral bioavailability of aspirin in healthy adults. However, administration of antacids containing either aluminum and magnesium hydroxide or calcium carbonate two hours before aspirin dosing led to reduced absorption of aspirin in uremic patients.

MANAGEMENT: Patients treated chronically with antacids (or oral medications that contain antacids such as didanosine buffered tablets or pediatric oral solution) 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.

GENERALLY AVOID: The concomitant administration of aluminum-containing products (e.g., antacids and phosphate binders) and citrates may significantly increase serum aluminum concentrations, resulting in toxicity. Citrates or citric acid are contained in numerous soft drinks, citrus fruits, juices, and effervescent and dispersible drug formulations. Citrates enhance the gastrointestinal absorption of aluminum by an unknown mechanism, which may involve the formation of a soluble aluminum-citrate complex. Various studies have reported that citrate increases aluminum absorption by 4.6- to 50-fold in healthy subjects. Patients with renal insufficiency are particularly at risk of developing hyperaluminemia and encephalopathy. Fatalities have been reported. Patients with renal failure or on hemodialysis may also be at risk from soft drinks and effervescent and dispersible drug formulations that contain citrates or citric acid. It is unknown what effect citrus fruits or juices would have on aluminum absorption in healthy patients.

MANAGEMENT: The concomitant use of aluminum- and citrate-containing products and foods should be avoided by renally impaired patients. Hemodialysis patients should especially be cautioned about effervescent and dispersible over-the-counter remedies and soft drinks. Some experts also recommend that healthy patients should separate doses of aluminum-containing antacids and citrates by 2 to 3 hours.

ADJUST DOSING INTERVAL: The administration of aluminum-containing antacids with enteral nutrition may result in precipitation, formation of bezoars, and obstruction of feeding tubes. The proposed mechanism is the formation of an insoluble complex between the aluminum and the protein in the enteral feeding. Several cases of esophageal plugs and nasogastric tube obstructions have been reported in patients receiving high-protein liquids and an aluminum hydroxide-magnesium hydroxide antacid or an aluminum hydroxide antacid.

MANAGEMENT: Some experts recommend that antacids should not be mixed with or given after high protein formulations, that the antacid dose should be separated from the feeding by as much as possible, and that the tube should be thoroughly flushed before administration.

ADJUST DOSING INTERVAL: Administration with food may increase the absorption of calcium. However, foods high in oxalic acid (spinach or rhubarb), or phytic acid (bran and whole grains) may decrease calcium absorption.

MANAGEMENT: Calcium may be administered with food to increase absorption. Consider withholding calcium administration for at least 2 hours before or after consuming foods high in oxalic acid or phytic acid.

MONITOR: Smoking during treatment with abrocitinib may increase the risk of major adverse cardiovascular events (MACE) and the risk of developing malignancies. During abrocitinib clinical studies, current or past smokers had an additional increased risk of overall malignancies. Also, abrocitinib may increase patients' risk of MACE, including myocardial infarction, stroke, and cardiovascular death.

Administration of abrocitinib with high-fat, high-calorie food increased abrocitinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 29% and 26%, respectively, and prolonged the time to reach Cmax by 2 hours. These changes are not considered clinically relevant.

MANAGEMENT: Caution is advised if abrocitinib is prescribed to current or past smokers. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur. The manufacturer recommends discontinuing abrocitinib in patients that have experienced a myocardial infarction or stroke. Abrocitinib may be taken with or without food.

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.