Insulin icodec

Table 3 includes clinically significant drug interactions with Awiqli. Table 3: Clinically Significant Drug Interactions with Awiqli Drugs That May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analogs (e.g., octreotide), and sulfonamide antibiotics, glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose co-transporter 2 (SGLT-2) inhibitors.

Intervention: Dose reductions and increased frequency of glucose monitoring may be required when Awiqli is co-administered with these drugs. Drugs That May Decrease the Blood Glucose Lowering Effect of Awiqli Drugs: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. Intervention: Dose increases and increased frequency of glucose monitoring may be required when Awiqli is co-administered with these drugs.

Drugs That May Increase or Decrease the Blood Glucose Lowering Effect of Awiqli Drugs: Alcohol, beta-blockers, clonidine, and lithium salts.Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia. Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when Awiqli is co-administered with these drugs. Drugs That May Blunt Signs and Symptoms of Hypoglycemia Drugs: Beta-blockers, clonidine, guanethidine, and reserpine Intervention: Increased frequency of glucose monitoring may be required when Awiqli is co-administered with these drugs.

• Drugs that may increase the risk of hypoglycemia : antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), sulfonamide antibiotics, GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors.

( 7 ) • Drugs that may decrease the blood glucose lowering effect : atypical antipsychotics, corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. ( 7 ) • Drugs that may increase or decrease the blood glucose lowering effect : Alcohol, beta-blockers, clonidine, lithium salts, and pentamidine. ( 7 ) • Drugs that may blunt the signs and symptoms of hypoglycemia : beta-blockers, clonidine, guanethidine, and reserpine. ( 7 )

8.1 Pregnancy Risk Summary There are no available data with Awiqli in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see Clinical Considerations] . Rats and rabbits were exposed to insulin icodec-abae in animal reproduction studies during organogenesis. No adverse developmental effects were observed in rats or rabbits at exposures approximately equal to human exposure at a dose of 230 U/week [see Data] .

The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with an HbA 1c >7 and has been reported to be as high as 20-25% in women with an HbA 1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Clinical Considerations Disease-associated Maternal and/or Embryo/fetal Risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, still birth, and macrosomia related morbidity. Data Animal Data Insulin icodec-abae was investigated in studies covering the periods of embryo-fetal development and pre- and post-natal development in rats and the period of embryo-fetal development in rabbits.

In these studies, insulin icodec-abae did not cause adverse effects on embryo-fetal development when given subcutaneously at up to 10 U/kg/day in rats and 3 U/kg/day in rabbits, resulting in exposures comparable to human exposure (AUC) at a human subcutaneous dose of 230 U/week. Maternal deaths and abortions were observed in rabbits at human exposures secondary to maternal hypoglycemia. In a pre- and postnatal developmental study in rats where insulin icodec-abae was given by the subcutaneous route at doses up to

8.3 U/kg/day (from Gestation Day 6 through Lactation Day 20), maternal and pup mortality occurred during the lactation period at exposures approximately equal to human exposures, which were secondary to maternal hypoglycemia.