HUMULIN R (insulin regular, human)

There are 0 contraindications.

There are 1 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Hypoglycemic disorder

There are 3 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Disease of liver
Hypokalemia
Kidney disease with reduction in glomerular filtration rate (GFr)

There are 4 severe adverse reactions.

More Frequent	Less Frequent
Hypoglycemic disorder	None.

Rare/Very Rare
Anaphylaxis Edema Hypokalemia

There are 3 less severe adverse reactions.

More Frequent	Less Frequent
Injection site sequelae Weight gain	Lipodystrophy

Rare/Very Rare
None.

While available studies cannot definitely establish the absence of risk, published data from retrospective studies, open-label, randomized, parallel studies and meta-analyses over decades have not established an association with insulin human injection use during pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes. There is limited available data on the use of insulin human dry powder for inhalation in pregnant women; data are insufficient to determine drug-associated risks for adverse developmental outcomes. All available studies have methodological limitations, including lack of blinding, unclear methods or randomization, and small sample size.

Animal reproduction studies have not been performed with insulin human for injection. In animal reproduction studies with insulin human dry powder for inhalation, there were no adverse developmental outcomes with subcutaneous administration of carrier particles (vehicle without insulin) to pregnant rats during organogenesis at doses 21 times the human exposure at a daily dose of 99 mg, based on AUC. There are risks to the mother and fetus associated with poorly controlled diabetes mellitus in pregnancy.

Poorly controlled diabetes mellitus in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes mellitus in pregnancy increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity.

Available data from published literature suggests that exogenously administered human insulin is distributed into human milk. There are no adverse effects reported in breast-fed infants in the literature. There are no data on the effects of exogenous human insulin products on milk production.

There are no data on the presence of insulin human dry powder for inhalation in human milk, the effects on the breast-fed infant, or the effects on milk production; carrier particles administered subcutaneously are present in rat milk at approximately 10% of the maternal exposure. Based on the results of the rat study, it is highly likely that both insulin human and the carrier particles are distributed into human milk. Potential adverse effects that are related to inhalation administration of insulin human are unlikely to be associated with potential exposure through breast milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for insulin human and any potential adverse effects on the breast-fed child from insulin human or the underlying maternal condition.

The effect of age on the pharmacokinetics and pharmacodynamics of insulin human has not been established. Elderly patients may be at increased risk of hypoglycemia due to co-morbid disease states and concomitant medications. Caution should be exercised with using insulin human regular U-500 in geriatric patients; in geriatric patients, the initial dosage, dose increments, and maintenance dosage should be conservative to avoid hypoglycemia.

In clinical trials, 18 of 1285 patients (1.4%) with type 1 diabetes mellitus and 151 of 635 patients (24%) with type 2 diabetes mellitus treated with insulin human (Novolin(R) R) were >=65 years of age. Conclusions are limited regarding the efficacy and safety in patients >=65 years of age. In clinical trials with insulin human dry powder for inhalation, 671 patients (12%) were >=65 years of age, of which 42 (0.8%) were >=75 years of age.

In these studies, 381 (13%) of insulin human dry powder for inhalation-treated patients were >=65 years of age, of which 20 (0.7%) were >=75 years of age. No overall differences in effectiveness with insulin human dry powder for inhalation have been observed between patients >=65 years of age and younger adult patients. Clinical studies with insulin human dry powder for inhalation did not include sufficient numbers of patients 65 years of age and older to determine whether there were differences in safety between these and younger patients.