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.

MONITOR: Glucagon-like peptide-1 (GLP-1) receptor agonists and dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists can delay gastric emptying, which may impact the absorption of concomitantly administered oral medications. Mild to moderate decreases in plasma concentrations of coadministered drugs have been demonstrated in pharmacokinetic studies for some GLP-1 receptor agonists (e.g., exenatide, lixisenatide), but not others. According to the prescribing information, liraglutide did not affect the absorption of several orally administered drugs to any clinically significant extent, including acetaminophen, atorvastatin, digoxin, griseofulvin, lisinopril, and an oral contraceptive containing ethinyl estradiol-levonorgestrel. Likewise, no clinically relevant effect on absorption was observed for concomitantly administered oral drugs studied with albiglutide (digoxin, ethinyl estradiol-norethindrone, simvastatin, warfarin), dulaglutide (acetaminophen, atorvastatin, digoxin, ethinyl estradiol-norelgestromin, lisinopril, metformin, metoprolol, sitagliptin, warfarin), or semaglutide (atorvastatin, digoxin, ethinyl estradiol-levonorgestrel, metformin, warfarin). The impact of dual GLP-1 and GIP receptor agonist tirzepatide on gastric emptying was reported to be dose- and time-dependent, with the greatest effect observed after a single 5 mg dose but diminished after subsequent doses. When acetaminophen was administered following a single 5 mg dose of tirzepatide, acetaminophen peak plasma concentration (Cmax) was decreased by 50% and its median time to peak plasma concentration (Tmax) delayed by 1 hour. However, no significant impact on acetaminophen Cmax and Tmax was observed after 4 consecutive weekly doses of tirzepatide (5 mg/5 mg/8 mg/10 mg), and the overall exposure (AUC) of acetaminophen was unaffected. Tirzepatide at lower doses of 0.5 mg and 1.5 mg also had minimal effects on acetaminophen exposure.

MANAGEMENT: Although no specific dosage adjustment of concomitant medications is generally recommended based on available data, potential clinical impact on some oral medications cannot be ruled out, particularly those with a narrow therapeutic index or low bioavailability, those that depend on threshold concentrations for efficacy (e.g., antibiotics), and those that require rapid gastrointestinal absorption (e.g., hypnotics, analgesics). Pharmacologic response to concomitantly administered oral medications should be monitored more closely following initiation, dose adjustment, or discontinuation of a GLP-1 receptor agonist or a dual GLP-1 and GIP receptor agonist.