3. Drug-Drug Interactions

Patient profiles will be assessed to identify those drug regimens, which may result in clinically significant drug-drug interactions. Drug-drug interactions considered clinically relevant for pramlintide are summarized in Table 2. Only those drug-drug interactions identified as clinical significance level 1 or those considered life-threatening which have not yet been classified will be reviewed.

Table 2. Pramlintide Drug-Drug Interactions^1,2

Target Drug	Interacting Drug	Interaction	Recommendation	Clinical Significance Level*
antidiabetic agents	somatostatin analogues (SAs) (e.g., octreotide, pasireotide)	concurrent use may impair glucose regulation as SAs inhibit insulin and glucagon secretion; substantially increased blood glucose levels may result	monitor closely for changes in blood glucose control before and throughout SA therapy; adjust antidiabetic doses as needed	moderate
pramlintide	alpha glucosidase inhibitors (e.g., acarbose, miglitol)	alpha glucosidase inhibitors slow nutritive absorption; adjunctive administration may potentiate pramlintide pharmacologic effects, increasing potential for additional blood glucose reductions and risk of hypoglycemia	concurrent administration not recommended by manufacturer	major
pramlintide	medications that slow gastrointestinal motility (e.g., tricyclic antidepressants, opiates, antimuscarinics, diphenoxylate)	adjunctive administration may enhance pramlintide pharmacologic effects, increasing potential for additional blood glucose reductions and risk of hypoglycemia	concurrent administration not recommended by manufacturer	2-major (CP)
pramlintide	insulin	adjunctive use may increase hypoglycemia risk; pramlintide pharmacokinetic parameters altered if mixed in same syringe with insulins	reduce mealtime insulin doses to minimize hypoglycemia; do not mix together; give as separate injections	2-major (CP)
pramlintide	oral medications with hypoglycemic effects (e.g., oral antidiabetic agents, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, disopyramide, fibric acid derivatives, salicylates, sulfonamide antibiotics)	concomitant administration may result in enhanced hypoglycemic pharmacologic and adverse effects	monitor blood glucose levels closely and adjust dosages as necessary if drug combination required to minimize excessive hypoglycemia and associated adverse events	moderate (DrugReax) 3-moderate (CP)