Pioglitazone and metformin and Repaglinide interaction

Hypoglycemia: Consider a lower dose of insulin or insulin secretagogue to reduce risk of hypoglycemia when used in combination with ACTOPLUS MET.

Congestive Heart Failure Pioglitazone, like other thiazolidinediones, can cause dose-related fluid retention when used alone or in combination with other antidiabetic medications and is most common when pioglitazone is used in combination with insulin.

Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues Insulin and insulin secretagogues, such as sulfonylureas, are known to cause hypoglycemia.

Therefore, a lower dosage of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with ACTOPLUS MET [see Drug Interactions (7.6 , 7.7) ] .

Use of insulin secretagogues or insulin use may increase the risk for hypoglycemia and may require dose reduction.

Factors which may increase the risk of hypoglycemia include changes in meal pattern (e.g., macronutrient content), changes in level of physical activity, changes to co-administered medication [see Drug Interactions (7) ] , and concomitant use with other antidiabetic agents.

Drugs That May Decrease the Blood Glucose Lowering Effect of Repaglinide Tablets Intervention: Repaglinide tablets dose increases and increased frequency of glucose monitoring may be required when co-administered.

CYP2C8 and CYP3A4 Inducers and Drugs That May Decrease the Blood Glucose Lowering Effect of repaglinide tablets : Co-administration may require repaglinide tablets dose increases and increased frequency of glucose monitoring ( 7 )

Examples: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, nonsteroidal anti-inflammatory agents (NSAIDs), pentoxifylline, pramlintide, propoxyphene, salicylates, somatostatin analogs (e.g., octreotide), and sulfonamide antibiotics.