Insul

Approved Indications:

• Type 1 Diabetes Mellitus: For glycemic control in patients who require exogenous insulin to maintain normal blood glucose levels due to absolute insulin deficiency.
• Type 2 Diabetes Mellitus: For patients whose blood glucose cannot be adequately controlled by diet, exercise, and oral hypoglycemic agents alone and who need insulin for optimal glucose control.
• Gestational Diabetes Mellitus: May be used when dietary measures and exercise fail to maintain adequate glucose control during pregnancy, under close medical supervision.
• Perioperative and Acute Illness Hyperglycemia: For temporary insulin therapy during surgery, major illness, or stress conditions in patients with diabetes.
• Diabetic Ketoacidosis (DKA) and Hyperosmolar Hyperglycemic State (HHS): Regular Insulin is indicated for intravenous use in acute hyperglycemic emergencies; NPH is not used for acute management but may be reintroduced to maintain basal insulin needs afterward.

Important Off-Label or Clinically Accepted Uses:

• Hospitalized Patients: For managing hyperglycemia in hospitalized non-critically ill patients when blood glucose is not adequately controlled by oral agents or basal-only regimens.

General Dosage Principles:

• Insulin dosing is individualized based on patient-specific factors, frequent blood glucose monitoring, carbohydrate intake, and clinical status.
• Typical total daily insulin requirement: 0.4–1.0 units/kg/day, adjusted per glycemic targets.

Adults:

• When given as premixed insulin (commonly 70% NPH + 30% Regular Insulin), the total daily dose is usually split into two injections daily: one before breakfast and one before the evening meal.
• Dose adjustments are made based on self-monitoring of blood glucose or continuous glucose monitoring results.
• More frequent adjustments may be needed in response to changes in diet, activity, stress, or concomitant illness.

Pediatrics:

• Safe and effective under close supervision. Pediatric dosing follows similar weight-based calculations with careful titration to avoid hypoglycemia.
• Frequent monitoring and caregiver education are essential.

Elderly:

• Use lower initial doses and adjust cautiously due to increased risk of hypoglycemia and reduced counterregulatory response.

Special Groups (Renal/Hepatic Impairment):

• Reduced insulin requirements may be needed due to decreased clearance and increased sensitivity; close monitoring and careful dose titration are required.

Administration Route:

• Subcutaneous injection only for premixed or NPH-containing preparations.
• Regular Insulin alone may be administered intravenously for DKA or other emergencies.
• Rotate injection sites within the same region to minimize lipodystrophy.
• Usual injection sites: abdomen (preferred for consistency of absorption), upper arm, thigh, or buttocks.

Frequency & Duration:

• Administer premixed insulins generally twice daily before meals.
• Dosing schedules may be adjusted based on meal patterns and blood glucose targets.

Regular Insulin Human is a short-acting recombinant human insulin that lowers blood glucose by binding to insulin receptors on cell surfaces, primarily in muscle and adipose tissue, facilitating glucose uptake and storage while suppressing hepatic glucose production. Isophane Insulin Human (NPH) is an intermediate-acting insulin that combines insulin with protamine and zinc, delaying absorption and extending its duration of action. Together in premixed formulations, Regular Insulin controls postprandial glucose spikes while NPH Insulin provides basal insulin coverage between meals and overnight, helping maintain stable fasting and pre-meal glucose levels.

Absorption:

• Regular Insulin has an onset of action of about 30 to 60 minutes after subcutaneous injection.
• NPH Insulin starts acting within 1 to 2 hours due to its protamine content, which slows absorption.

Distribution:

• Widely distributed in extracellular fluid; does not cross the blood-brain barrier in significant amounts but crosses the placenta in small amounts if levels are high.

Metabolism:

• Primarily metabolized in the liver and kidneys by insulinase enzymes. Also partially degraded in muscle tissue.

Excretion:

• Metabolites and small amounts of unchanged insulin are excreted in the urine.

Onset, Peak, Duration:

• Regular Insulin: Onset 30–60 minutes, peak effect 2–4 hours, duration 6–8 hours.
• NPH Insulin: Onset 1–2 hours, peak 4–12 hours, duration 12–18 hours.
• The combination provides both rapid and sustained glucose control when dosed appropriately.

Pregnancy:

• FDA Pregnancy Category B (traditional classification). Human insulin does not cross the placenta in significant amounts when used within normal therapeutic ranges. Insulin is the standard treatment for diabetes during pregnancy when needed, with careful dose adjustment throughout pregnancy due to changing insulin requirements.

Lactation:

• Insulin is not significantly excreted in human milk and does not affect lactation. Safe for use in breastfeeding mothers. Blood glucose should be monitored closely postpartum as insulin requirements may change.

• Therapeutic Class: Human recombinant insulin.
• Subclass: Short-acting insulin (Regular) plus intermediate-acting insulin (NPH) in a premixed combination.

• Known hypersensitivity to human insulin or any formulation excipients.
• Hypoglycemia — insulin must never be administered during an episode of low blood sugar.

• Hypoglycemia Risk: The most frequent and serious risk; patients must be educated on early signs and corrective actions.
• Dose Adjustments: Needed during acute illness, surgery, stress, or significant changes in physical activity or diet.
• Injection Technique: Incorrect technique may cause erratic absorption; rotate sites to prevent lipodystrophy.
• Mixing Rules: Premixed insulins must not be mixed with other insulins or diluted.
• Renal or Hepatic Dysfunction: May reduce insulin clearance and increase risk of hypoglycemia.
• Beta-blockers: May mask hypoglycemia symptoms; monitor carefully.
• Monitor blood glucose and HbA1c regularly to ensure treatment goals are met and avoid both hyper- and hypoglycemia.

Common Side Effects:

• Hypoglycemia (mild to severe, may occur if dose exceeds requirements, meals are skipped, or physical activity is increased without adjustment).
• Local injection site reactions, including redness, swelling, or pain.
• Weight gain due to anabolic effects and increased glucose storage.

Serious or Rare Side Effects:

• Severe hypoglycemia leading to confusion, seizures, or loss of consciousness.
• Allergic reactions, including rash, itching, or very rarely systemic reactions like anaphylaxis.
• Lipodystrophy (lipoatrophy or lipohypertrophy) from repeated injections in the same site.

Timing:

• Hypoglycemia is most likely at peak insulin action.
• Local reactions generally appear soon after injection and resolve spontaneously.

Drugs that increase insulin’s effect and risk of hypoglycemia:

• Oral antidiabetic drugs, ACE inhibitors, beta-blockers (mask hypoglycemia warning signs), MAO inhibitors, salicylates, some antidepressants.

Drugs that decrease insulin’s effect (risk of hyperglycemia):

• Corticosteroids, some diuretics, oral contraceptives, thyroid hormones, sympathomimetic agents.

Alcohol:

• Can enhance insulin’s hypoglycemic effect and mask warning symptoms.

Metabolism Pathways:

• No significant CYP450 involvement, as insulin is metabolized by insulinase enzymes.

• The American Diabetes Association (ADA) and WHO continue to include human insulins as core therapies for type 1 and type 2 diabetes, especially where cost or availability limits the use of analog insulins.
• Recent guidance favors patient-tailored approaches: premixed insulins are acceptable for patients with predictable meal schedules but may be less flexible than basal-bolus regimens or insulin analogs.
• Emphasis remains on patient education for self-monitoring, injection technique, and recognizing hypoglycemia.

• Store unopened vials and pens at 2°C to 8°C (36°F to 46°F).
• Do not freeze. If accidentally frozen, discard the product.
• Protect from direct heat and light.
• Once opened, keep at room temperature (below 30°C) and use within 28 days.
• NPH Insulin is naturally cloudy — roll the vial or pen gently to mix before each injection; do not shake vigorously.
• Inspect the solution before use. Do not use if it contains lumps or clumps or if the Regular Insulin appears cloudy.