Drug Interaction Report

MONITOR: Pentamidine may interfere with the therapeutic effects of insulin and other antidiabetic agents. The use of pentamidine has been associated with disturbances in blood glucose homeostasis due to direct toxic effects on beta cells of the pancreas. Hypoglycemia, which may be severe and/or prolonged, as well as hyperglycemia and insulin-dependent diabetes mellitus, the latter of which may be irreversible, have been reported. The onset of pentamidine-induced hypoglycemia generally varied from 5 to 7 days after start of therapy to several days after therapy stops. In some cases, hyperglycemia and progression to diabetes followed, although these effects have occurred independently also. Pancreatic toxicity has been reported with both parenteral use and, less frequently, oral inhalation of pentamidine. The risk appears to be related to total cumulative dosage and prior therapy with the drug, particularly within the last 3 months. Renal impairment also appears to be a risk factor.

MANAGEMENT: Blood glucose should be monitored closely during and after pentamidine therapy in patients receiving insulin or other antidiabetic agents, especially if they are elderly or have renal impairment. Patients should learn to recognize the symptoms of hypoglycemia such as headache, dizziness, drowsiness, nervousness, confusion, tremor, hunger, weakness, perspiration, palpitation, and tachycardia. If hypo- or hyperglycemia occur during pentamidine therapy, patients should initiate appropriate remedial therapy immediately and contact their physician. Dosage adjustments may be required if an interaction is suspected.

ADJUST DOSING INTERVAL: Pramlintide slows gastric emptying and may delay the absorption of concomitantly administered oral medications. In a pharmacokinetic study of 24 patients with type 2 diabetes, coadministration with pramlintide (120 mcg) decreased the peak plasma concentration (Cmax) of acetaminophen (1000 mg) by 29% and increased its time to peak plasma concentration (Tmax) based on the time of acetaminophen administration relative to pramlintide injection. Pramlintide significantly increased acetaminophen Tmax (range 48 to 72 minutes) when acetaminophen was administered simultaneously with or up to 2 hours following pramlintide injection, but it had negligible effect when acetaminophen was administered 1 to 2 hours before pramlintide injection.

MANAGEMENT: When rapid onset of a concomitantly administered oral medication is critical to its effectiveness, the medication should be administered at least 1 hour before or 2 hours after pramlintide injection.