Humulin R

Dosage for Insulin Human must be highly individualized based on the patient's metabolic needs, blood glucose monitoring results, and glycemic goals.

• Type 1 Diabetes: The typical total daily insulin requirement ranges from 0.5 to 1.0 units/kg/day. This is usually split between basal insulin (NPH) and mealtime insulin (Regular).
• Type 2 Diabetes: Healthcare providers may start with a conservative dose, such as 0.1 to 0.2 units/kg/day or 10 units of basal insulin at bedtime, adjusting based on fasting glucose levels.
• Intravenous Administration: In cases of Diabetic Ketoacidosis (DKA), Regular Insulin Human may be administered as a continuous infusion, typically starting at 0.1 units/kg/hour.

Insulin Human is approved for use in pediatric patients with both Type 1 and Type 2 Diabetes. Dosing is weight-based and must account for the child's growth stage, pubertal status, and activity levels. During puberty, insulin requirements may increase significantly (up to 1.5 units/kg/day) due to growth hormone-induced insulin resistance. Careful monitoring by a pediatric endocrinologist is essential.

Renal Impairment

The kidneys play a major role in the clearance of insulin. In patients with renal impairment (decreased GFR), the half-life of Insulin Human may be prolonged. Healthcare providers typically reduce the dose to prevent prolonged hypoglycemia. A 25% reduction may be considered when GFR is 10-50 mL/min, and a 50% reduction when GFR is below 10 mL/min.

Hepatic Impairment

The liver is the primary site of insulin metabolism. Patients with hepatic impairment may have reduced gluconeogenic capacity and altered insulin clearance, necessitating frequent blood glucose monitoring and potential dose reductions.

Elderly Patients

Older adults are at a higher risk for hypoglycemia due to age-related declines in renal function and potential cognitive impairment. Dosing should be conservative, and targets may be less stringent to avoid the dangers of severe low blood sugar.

1. 1Preparation: Always check the vial or pen for the correct type of insulin and expiration date. Regular insulin should be clear; NPH should be uniformly cloudy after gentle rolling (do not shake).
2. 2Injection Sites: Inject subcutaneously into the abdomen, thigh, upper arm, or buttocks. Rotate sites within the same region to reduce the risk of lipodystrophy (thickening of the skin).
3. 3Timing: Regular Human Insulin should be injected approximately 30 minutes before a meal. NPH is typically given once or twice daily.
4. 4Mixing: If mixing NPH and Regular in one syringe, always draw the Regular (clear) insulin first to avoid contaminating the vial with protamine.
5. 5Storage: Unopened vials should be refrigerated (36°F–46°F). Opened vials may be kept at room temperature for up to 28–42 days (depending on the brand) but should be kept away from direct heat and light.

If you miss a dose of Insulin Human, check your blood glucose level immediately. Consult the specific plan provided by your doctor. Generally, if it is close to the time of your next meal, your doctor may advise you to take your regular mealtime dose. Never double the dose to "catch up," as this can lead to severe hypoglycemia.

An overdose of Insulin Human leads to hypoglycemia. Symptoms range from mild (sweating, tremors, hunger) to severe (seizure, coma, death).

• Mild/Moderate: Consume 15 grams of fast-acting carbohydrates (e.g., 4 oz juice, glucose tablets). Recheck in 15 minutes.
• Severe: If the patient is unconscious, emergency medical services must be called. Glucagon (injection or nasal spray) should be administered by a trained caregiver.

> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose without medical guidance. Regular blood glucose monitoring is the only way to ensure your dose is correct.

• Hypoglycemia (Low Blood Sugar): This is the most frequent side effect. Patients may experience shakiness, sweating, rapid heartbeat (tachycardia), dizziness, and intense hunger. If not treated, it can lead to confusion and loss of consciousness.
• Injection Site Reactions: Redness, swelling, or itching at the site of injection. These are usually transient and resolve as the body adjusts to the medication.
• Weight Gain: As insulin improves glucose uptake and utilization, calories that were previously lost in the urine (glycosuria) are now stored, which can lead to weight gain if diet is not managed.
• Peripheral Edema: Some patients experience temporary fluid retention and swelling in the ankles or feet when starting insulin therapy or after significant improvements in glycemic control.

• Lipodystrophy: This includes lipohypertrophy (thickening of fat tissue) or lipoatrophy (thinning of fat tissue) at the injection site. This occurs most often when injection sites are not rotated properly and can interfere with insulin absorption.
• Visual Changes: Rapid changes in blood glucose levels can cause temporary swelling of the lens in the eye, leading to blurred vision. This typically resolves once glucose levels stabilize.
• Pruritus (Itching): Generalized itching may occur as a mild allergic response to the insulin or the preservatives (like metacresol) in the formulation.

• Systemic Allergic Reactions: Rare but severe reactions can occur, characterized by a generalized rash, shortness of breath, wheezing, hypotension (low blood pressure), and fast pulse.
• Hypokalemia: Insulin causes a shift of potassium from the blood into the cells. In some patients, this can lead to dangerously low blood potassium levels, which may cause muscle weakness or heart rhythm disturbances.
• Insulin Antibodies: In very rare cases, the body may develop antibodies to the human insulin protein, which can lead to insulin resistance or localized skin reactions.

> Warning: Stop taking Insulin Human and call your doctor immediately if you experience any of these.

• Severe Hypoglycemia: Characterized by seizures, extreme confusion, or loss of consciousness. This is a medical emergency.
• Anaphylaxis: Symptoms include swelling of the face, tongue, or throat, severe difficulty breathing, and a sudden drop in blood pressure.
• Heart Failure Symptoms: If used in combination with certain other medications (like TZDs), insulin can worsen heart failure. Seek help for sudden shortness of breath, rapid weight gain, or severe swelling.
• Severe Hypokalemia: Symptoms include extreme muscle cramps, paralysis, or palpitations (feeling like your heart is skipping beats).

With prolonged use, the most significant long-term concern is the management of lipohypertrophy. If patients continue to inject into thickened areas of skin, insulin absorption becomes unpredictable, leading to unexplained fluctuations in blood sugar. Additionally, chronic over-insulinization in Type 2 Diabetes without lifestyle modification can contribute to metabolic syndrome progression and further weight gain.

While injectable Insulin Human does not carry a general Black Box Warning, the inhaled form of Insulin Human (e.g., Afrezza) carries a FDA Black Box Warning for Acute Bronchospasm.

• Summary: Acute bronchospasm has been observed in patients with asthma and COPD using inhaled insulin. Inhaled insulin is contraindicated in patients with chronic lung disease. Before starting inhaled insulin, a thorough medical history, physical examination, and lung function tests (FEV1) are required to identify potential lung disease.

Report any unusual symptoms to your healthcare provider. Consistent monitoring and reporting of side effects are crucial for safe diabetes management.

Insulin Human is a high-alert medication, meaning it has a significant risk of causing harm if used incorrectly. The primary safety concern is hypoglycemia. Patients must be educated on the symptoms of low blood sugar and the "Rule of 15" for treatment. Patients should never share insulin pens or needles, even if the needle is changed, as this poses a risk for the transmission of bloodborne pathogens like HIV and hepatitis.

As noted in the side effects section, there are no FDA black box warnings for standard injectable Insulin Human. However, the inhaled version (Afrezza) carries a warning for acute bronchospasm in patients with chronic lung disease. Patients using inhaled insulin must undergo spirometry testing (FEV1) at baseline, at 6 months, and annually thereafter.

• Hypoglycemia Risk: Any change in insulin strength, manufacturer, type, or method of administration may result in the need for a change in dosage. Changes should be made under close medical supervision.
• Hypersensitivity: Severe, life-threatening, generalized allergy, including anaphylaxis, can occur. If a reaction is suspected, discontinue use and seek emergency care.
• Hypokalemia: All insulin products cause a shift in potassium levels. Use with caution in patients at risk for low potassium, such as those using potassium-lowering medications (e.g., diuretics).
• Fluid Retention and Heart Failure: Concomitant use of PPAR-gamma agonists (like pioglitazone) with insulin has been associated with fluid retention and heart failure. Patients should be monitored for signs of heart failure.

Regular monitoring is required to ensure the safety and efficacy of Insulin Human:

• Self-Monitoring of Blood Glucose (SMBG): Patients should check their blood sugar multiple times daily, especially before meals, at bedtime, and when exercising.
• Hemoglobin A1c: Typically measured every 3 to 6 months to assess long-term glycemic control.
• Renal Function: Periodic testing of serum creatinine and GFR, as insulin clearance changes with kidney function.
• Potassium Levels: Especially in patients at risk for hypokalemia or those receiving intravenous insulin.

The ability to concentrate and react may be impaired as a result of hypoglycemia. Patients should be advised to take precautions to avoid hypoglycemia while driving. This is particularly important in those who have reduced or absent awareness of the warning symptoms of hypoglycemia.

Alcohol inhibits the liver's ability to release glucose (gluconeogenesis) and can significantly increase the risk of delayed hypoglycemia. Patients should be extremely cautious and discuss alcohol consumption with their healthcare provider. If alcohol is consumed, it should be taken with food.

Insulin Human should never be discontinued abruptly, especially in patients with Type 1 Diabetes, as this will lead to rapid-onset hyperglycemia and life-threatening Diabetic Ketoacidosis (DKA). Any changes to the insulin regimen must be directed by a healthcare professional.

> Important: Discuss all your medical conditions with your healthcare provider before starting Insulin Human. Ensure your family and close contacts know how to recognize and treat hypoglycemia.

There are no absolute drug-drug contraindications where Insulin Human cannot be used, as it is a necessary hormone. However, it is contraindicated during episodes of hypoglycemia. Using insulin when blood sugar is already low can be fatal.

• Thiazolidinediones (TZDs): Drugs like pioglitazone and rosiglitazone, when combined with insulin, increase the risk of fluid retention and congestive heart failure. Healthcare providers monitor for edema and weight gain.
• Beta-Blockers: Medications like metoprolol or propranolol can mask the autonomic symptoms of hypoglycemia, such as tremors and palpitations. Sweating is often the only symptom that remains unmasked.
• Clonidine and Reserpine: Similar to beta-blockers, these can mask the warning signs of low blood sugar.

• Drugs that Increase Hypoglycemic Effect: Certain medications can enhance the blood-sugar-lowering effect of insulin, increasing the risk of hypoglycemia. These include:
• Oral antidiabetic agents (e.g., Sulfonylureas)
• ACE inhibitors (e.g., Lisinopril)
• Angiotensin II receptor blockers
• MAO inhibitors
• Salicylates (e.g., Aspirin in high doses)
• Sulfonamide antibiotics
• Drugs that Decrease Hypoglycemic Effect: Certain medications can raise blood sugar, requiring an increase in the Insulin Human dose. These include:
• Corticosteroids (e.g., Prednisone)
• Atypical antipsychotics (e.g., Olanzapine, Clozapine)
• Estrogens and Progestogens (Oral contraceptives)
• Thiazide diuretics

• Carbohydrate Intake: The timing and amount of carbohydrate consumption directly interact with the efficacy of Insulin Human. Consistent carbohydrate counting is often recommended.
• Alcohol: As mentioned, alcohol increases the risk of severe hypoglycemia by inhibiting hepatic glucose production.

• Fenugreek, Ginseng, and Aloe Vera: Some studies suggest these may have mild glucose-lowering effects, which could theoretically increase the risk of hypoglycemia when combined with insulin.
• Chromium: Often taken for metabolic health, it may enhance insulin sensitivity and require dose adjustments.
• St. John's Wort: While primarily known for CYP interactions, its effect on glucose is minimal, but patients should always report its use.

Insulin Human does not typically interfere with common laboratory tests, but it will obviously affect blood glucose and C-peptide measurements. Exogenous insulin will suppress C-peptide levels in healthy individuals or those with remaining beta-cell function.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking. Even over-the-counter cold medicines containing decongestants can raise blood sugar levels.

• Hypoglycemia: Insulin Human must never be administered during an active episode of hypoglycemia. Doing so will exacerbate the condition and may lead to coma or death.
• Hypersensitivity: Patients with a known systemic allergy to Insulin Human or any of the excipients (such as metacresol, glycerin, or protamine in NPH) should not use the product. Anaphylaxis is a rare but absolute contraindication for the specific formulation involved.
• Chronic Lung Disease (Inhaled Form Only): Inhaled Insulin Human is absolutely contraindicated in patients with asthma, COPD, or other chronic lung conditions due to the risk of acute bronchospasm.

• Hypokalemia: Since insulin shifts potassium into the cells, patients with pre-existing untreated hypokalemia should be stabilized before high-dose insulin therapy is initiated to prevent cardiac arrhythmias.
• Renal and Hepatic Impairment: While not a contraindication to use, these conditions require extreme caution and significant dose adjustments because the risk of severe, prolonged hypoglycemia is greatly increased.

While Insulin Human is identical to endogenous insulin, patients who have had allergic reactions to animal-derived insulins (porcine or bovine) in the past may still react to the preservatives or stabilizing agents used in recombinant human insulin. However, true cross-reactivity with the human insulin protein itself is exceptionally rare.

> Important: Your healthcare provider will evaluate your complete medical history, including any history of lung disease or allergies, before prescribing Insulin Human.

Insulin Human is the preferred treatment for managing both pre-existing diabetes and gestational diabetes during pregnancy. It does not cross the placenta. Maintaining tight glycemic control is critical, as poorly controlled diabetes during pregnancy increases the risk of congenital malformations, macrosomia (large baby), and stillbirth. Insulin requirements typically decrease in the first trimester and increase significantly during the second and third trimesters. According to the FDA, Insulin Human is generally considered safe for use during pregnancy (formerly Category B).

Insulin Human is a natural component of breast milk. Exogenous insulin does not pass into breast milk in significant quantities, and even if it did, it would be degraded in the infant's digestive tract. Breastfeeding mothers may find that their insulin requirements decrease because the process of milk production consumes glucose. Healthcare providers will monitor the mother's glucose levels closely during the postpartum period.

Insulin Human is safe and effective for use in children. However, the risk of hypoglycemia is a major concern, particularly in young children who may not be able to communicate symptoms. Treatment regimens in children must be flexible enough to account for irregular eating habits and varying physical activity. Pediatric patients are also more susceptible to the effects of growth hormone and other counter-regulatory hormones that fluctuate during puberty.

In patients over 65, the risk of hypoglycemia is higher due to potential declines in kidney function and the presence of other medical conditions (polypharmacy). The symptoms of hypoglycemia may also be less obvious in the elderly. The American Diabetes Association suggests that for older adults with multiple chronic illnesses or cognitive impairment, less stringent A1c goals (e.g., <8.0%) may be appropriate to minimize the risk of dangerous falls and cardiovascular events related to low blood sugar.

As the GFR declines, the kidney's ability to clear insulin decreases. This leads to an increase in the circulating half-life of Insulin Human. Patients with Stage 4 or 5 Chronic Kidney Disease (CKD) often require significantly lower doses of insulin than those with normal renal function. Close monitoring is required during dialysis, as glucose levels can shift rapidly.

In patients with cirrhosis or other forms of hepatic impairment, the liver's ability to store glycogen and produce glucose (gluconeogenesis) is compromised. This makes these patients highly susceptible to hypoglycemia. Additionally, the liver's role in degrading insulin is reduced, further increasing the risk. Dosing must be conservative and frequently reassessed.

> Important: Special populations require individualized medical assessment. Always inform your specialist about any changes in your health status, such as new kidney or liver diagnoses.

Insulin Human is a recombinant version of the endogenous hormone produced by the pancreatic beta cells. Its primary molecular target is the insulin receptor (IR), a disulfide-linked heterotetramer. Upon binding, it activates the tyrosine kinase activity of the receptor, leading to the recruitment and phosphorylation of Insulin Receptor Substrates (IRS-1 through IRS-4). This activates the PI3K-Akt pathway, which is responsible for the translocation of GLUT4 glucose transporters to the plasma membrane, primarily in muscle and adipose tissue. This increases glucose uptake and lowers blood sugar. Additionally, insulin activates the MAPK pathway, which regulates cell growth and protein synthesis.

• Onset of Action: For Regular Insulin, onset is 30–60 minutes. For NPH, it is 1–2 hours.
• Peak Effect: Regular insulin peaks at 2–4 hours; NPH peaks at 4–10 hours.
• Duration: Regular insulin lasts 5–8 hours; NPH lasts 12–18 hours.
• Dose-Response: The relationship is generally linear, but absorption becomes more erratic at very high doses due to the size of the subcutaneous depot.

| Parameter | Value |

|---|---|

| Bioavailability | Varies by site (Abdomen > Arm > Thigh) |

| Protein Binding | Negligible (binds to specific receptors) |

| Half-life | 5–10 minutes (IV); hours (SC due to absorption) |

| Tmax | 2–4 hours (Regular SC) |

| Metabolism | Hepatic (50%), Renal, and Muscle |

| Excretion | Renal (primary) |

• Molecular Formula: C257H383N65O77S6
• Molecular Weight: Approximately 5808 Daltons
• Structure: Two polypeptide chains: an A-chain (21 amino acids) and a B-chain (30 amino acids) linked by two interchain disulfide bridges. There is also one intrachain disulfide bridge on the A-chain.
• Solubility: Soluble in water; Regular insulin is formulated at a neutral pH (7.0–7.8).

Insulin Human is the foundational member of the Insulin [EPC] class. It is distinguished from insulin analogs (like Lispro or Glargine) because its amino acid sequence is identical to that of naturally occurring human insulin. It remains a gold-standard therapy due to its predictability and lower cost compared to many newer analogs.