Insulin Isophane Human (NPH insulin)
Medicine Type :
Allopathy
Allopathy
Prescription Type:
Prescription Required
Prescription Required
Approval :
DCGI (Drugs Controller General of India)
DCGI (Drugs Controller General of India)
Schedule
Schedule H
Schedule H
Pharmacological Class:
Intermediate-acting insulin, Therapy Class:
Antidiabetic Agent, Approved Countries
The United States, Canada, the United Kingdom, France, Japan, Germany and Australia.
Insulin Isophane Human is an Anti-diabetic Agent belonging to the pharmacological class of Intermediate-acting insulin.
NPH (Neutral Protamine Hagedorn) insulin is a synonym for insulin isophane human. It is FDA-approved for the management of both type 1 and type 2 diabetes in adults and children.
Insulin Isophane Human is absorbed subcutaneously and distributed systemically. It undergoes metabolism primarily in the liver and kidneys. The elimination occurs through urine and, to a lesser extent, through the liver.
The most common side effect of Insulin Isophane in humans is low blood sugar levels (hypoglycemia).
Insulin Isophane Human is available in the form of injectable suspension.
The molecule is available in the United States, Canada, the United Kingdom, France, Japan, Germany and Australia.
Insulin Isophane Human is an Anti-diabetic Agent belonging to the pharmacological class of Intermediate-acting insulin.
Insulin regulates the metabolism of glucose as its primary function. Except for the brain and liver, insulin facilitates the glucose absorption and amino acids into muscle and fatty tissues. Moreover, it plays an anabolic function by promoting the production of proteins, fatty acids, and glycogen. Insulin prevents the liver's process of gluconeogenesis. The insulin receptor (IR) interacts with insulin, a heterotetrameric protein with two transmembrane beta units and two extracellular alpha units. Tyrosine kinase activity inherent to the receptor's beta subunit is stimulated when insulin binds to the alpha subunit of IR. Numerous intracellular substrates, including Cbl, APS, Shc, Gab 1, and insulin receptor substrates (IRS) proteins, can be autophosphorylated and phosphorylated by the attached receptor. The downstream signalling molecules Akt and PI3 kinase are activated due to these activated proteins. Akt controls the functions of protein kinase C (PKC) and glucose transporter 4 (GLUT4), two enzymes essential to metabolism and catabolism.
Insulin Isophane Human duration of action typically occurs approximately ranging from 14 to 24 hours.
The Data of Tmax of Insulin Isophane Human is not established.
The Cmax of Insulin Isophane Human data is not established.
Insulin Isophane Human is available in the form of injectable suspension.
Injectable suspension: To use the Insulin Isophane Human injectable suspension, prepare the dose, identify an injection site, disinfect it, administer the insulin subcutaneously, and cautiously dispose of the needle. For proper use, adhere to the doctor's recommendations.
The physician determines the exact dosage and timing based on the patient's needs and blood sugar levels.
- Insulin Isophane Human controls blood sugar levels in individuals with diabetes mellitus.
- It is used to improve the glycemic, reducing the risk of complications associated with uncontrolled blood sugar levels.
In Treatment of diabetes mellitus
To regulate blood sugar levels, insulin isophane is typically taken with other diabetic medications. It takes the place of the insulin that the body would generally manufacture. This facilitates the entry of glucose into the body's fat and muscle cells, which may be used as fuel. It also lowers the liver's synthesis of glucose.
To effectively manage diabetes, the blood glucose levels must be reduced. Controlling blood sugar levels will lower the likelihood of any of the severe complications of diabetes, including kidney damage, eye damage, nerve problems, and amputation of limbs. The risk of cardiac disease and stroke can be decreased with proper diabetes management. Individuals can live longer if they take this medication consistently and follow a healthy diet and exercise routine.
- Insulin Isophane Human is indicated for treating type 1 diabetes mellitus, where the body does not produce insulin.
- It is also used in type 2 diabetes mellitus when oral antidiabetic medications are not sufficient.
- It may sometimes be indicated for gestational diabetes during pregnancy.
Parenterally: Insulin Isophane Human is available as an injection suspension that can be administered parenterally. Crystalline NPH insulin is administered subcutaneously, avoiding intramuscular or intravenous routes. It is available in a two-phase solution, often combined with rapid-acting insulin. Subcutaneous injection in the abdomen ensures quicker absorption. NPH can be included in premixed formulations with regular insulin without affecting potency. Exercise, massage, and local heat increase absorption. Adequate mixing of NPH insulin pens for complete resuspension is necessary. A once or twice-daily regimen is standard, typically morning, evening, or bedtime for the premixed formulations, covering 70 to 75% NPH insulin.
The dosage and duration of treatment should be as per the treating physician's clinical judgment.
Injectable suspension: 100units/mL (3mL), 100units/mL (10mL)
Insulin Isophane Human is available in the form of injectable suspension.
Dose Adjustment in Adult Patients:
Type 1 Diabetes Mellitus
In divided doses, 0.5–1 units/kg/day SC is the usual daily maintenance range; nonobese individuals may need 0.4–0.6 units/kg/day, and obese individuals may need 0.8–1.2 units/kg/day.
Type 2 Diabetes Mellitus
Initial dosage recommendations: 0.2 units/kg/day
Morning
Give two-thirds of the regular dose of SC in the morning.
The regular insulin to NPH insulin ratio is 1:2.
At night
Give a third of the recommended daily dose of SC insulin.
Regular insulin to NPH insulin ratio: 1:1
Dosing Considerations
Human insulin dosages are always expressed in USP units and must be carefully adjusted to achieve the best results based on blood and urine glucose testing findings.
Regular blood glucose monitoring ought to be the basis for dose modifications.
To attain proper glycemic control, make adjustments.
Blood sugar patterns (>3 days)
Observe a consistent pattern over three days to assess blood sugar levels, comparing readings simultaneously each day. Calculate the range and median for each time slot and consider daily eating and activity patterns to understand blood glucose fluctuations comprehensively.
Blood glucose adjustments
When adjusting insulin, focus on one dose at a time, prioritizing correcting hypoglycemia and addressing the highest blood sugars. If all readings are elevated, start by correcting morning fasting blood glucose. Opt for small incremental changes in insulin doses, such as 1-2 units for type 1 diabetes and 2-3 units for type 2 diabetes, to ensure careful and controlled adjustments.
Sliding scales
To determine exact insulin dosages, a variety of sliding scales are available. These scales are typically designed for regular blood glucose monitoring, usually carried out every four hours (q4hr). Usually, sliding scale coverage begins when blood glucose levels are higher than 11 mmol/L (200 mg/dL). Modifications are made to the basal insulin dose initially, with possible upward modifications to the sliding scale doses if continuous coverage is necessary every 4 hours for 24 hours.
Insulin Isophane Human should be used in treating Diabetes Mellitus, along with appropriate nutritional limits.
While taking Insulin Isophane Human, maintain regular meal schedules with balanced macronutrient content to help stabilize blood sugar levels.
Patients should be cautious about their carbohydrate intake and aim for a well-balanced distribution of macronutrients.
Limit or avoid the intake of alcohol as it can interfere with blood sugar regulation.
Consume foods with a lower glycemic index to help stabilize blood sugar levels.
Be cautious about the risk of low blood sugar, particularly when combined with other diabetes medications that can cause hypoglycemia. Always carry a source of fast-acting glucose (like glucose tablets) to raise blood sugar if needed.
It is advised to stay hydrated, maintain a rich, balanced diet with appropriate carbohydrate intake, and consume plenty of vegetables, whole grains, fruits, and lean proteins to help manage your overall health and blood sugar levels effectively.
The dietary restriction should be individualized as per patient requirements.
Insulin Isophane Human may be contraindicated in the following conditions:-
In cases of hypersensitivity reactions, NPH insulin should not be used. Individuals may develop hypersensitivity to any pharmaceutical product or the formulation of insulin. It is possible to develop allergic reactions to various allergens or additives, including protamine, zinc, and metal-cresol. The patient might experience pruritis, followed by erythema and a generalized rash. Patients who experience severe hypoglycemia episodes regularly should not take NPH insulin. Hypoglycemia may be fatal in some instances.
- Never share an Insulin Isophane Human syringe with another patient, even when the needle is replaced.
- Modifications to the Insulin Regimen: Monitor blood sugar levels more frequently and carry out under strict physician supervision.
- Hypoglycemia: This condition could be fatal. In patients with renal or hepatic impairment, hypoglycemia unawareness, changes in insulin dosage, use of glucose-lowering medicines, meal patterns, and physical activity, check blood sugar levels and increase the frequency of such checks.
- Excessive sensitivity: The reactions could be fatal. Insulin Isophane Human should be stopped. If necessary, monitor and treat.
- Hypokalemia: This condition could be fatal. Patients at risk for hypokalemia should have their potassium levels checked and treated as necessary.
- Use of Thiazolidinediones (TZDs) concurrently with fluid retention and heart failure: Monitor for indications of heart failure and, should one arise, think about lowering the dosage or stopping the medication.
Alcohol Warning
It is unsafe to consume Insulin Isophane Human with alcohol.
Breast Feeding Warning
Safe to use during breastfeeding.
Pregnancy Warning
Generally considered safe to use during pregnancy.
Food Warning
Limit Alcohol consumption, and avoid heavy or high-fat meals.
The adverse reactions related to Insulin Isophane human can be categorized as follows:
- Common Adverse Effects: Hypoglycemia (low blood sugar), Injection site reactions (e.g., redness, swelling, itching)
- Less Common Adverse effects: Lipodystrophy, Weight gain, Peripheral oedema (swelling in extremities)
- Rare Adverse Effects: Severe allergic reactions, Insulin resistance, Skin thickening or pitting at the injection site
Reports on Postmarketing
Localized cutaneous amyloidosis
The clinically relevant drug interactions of Insulin Isophane Human are briefly summarized here.
- Increase the Risk of Hypoglycemia: When co-administered with anti-diabetic agents, salicylates, sulfonamide antibiotics, monoamine oxidase inhibitors, fluoxetine, disopyramide, fibrates, propoxyphene, pentoxifylline, ACE inhibitors, angiotensin II receptor blocking agents, and somatostatin analogues (e.g., octreotide), the risk of hypoglycemia associated with Insulin Isophane Human use may be increased. Insulin Isophane Human coadministration of these medications may necessitate dose modification and more frequent glucose monitoring.
- Drugs that could decrease the lowering effect of blood glucose: When corticosteroids, isoniazid, niacin, estrogens, oral contraceptives, phenothiazines, danazol, diuretics, sympathomimetic agents (e.g., terbutaline, albuterol, and adrenaline), somatropin, atypical antipsychotics, glucagon, protease inhibitors, and thyroid hormones are administered together, the glucose-lowering effect of insulin isophane human may be lessened. When Insulin Isophane Human is taken with certain medications, dosage adjustments and more frequent glucose checks may be necessary.
- That May Alter the Effect of Lowering Blood Glucose: Coadministration of insulin isophane human with beta-blockers, clonidine, lithium salts, and alcohol may enhance or decrease the medication's ability to control blood sugar. Hypoglycemia brought on by pentamidine may occasionally be followed by hyperglycemia. Insulin Isophane Human coadministration of these medications may necessitate dose modification and more frequent glucose monitoring.
- Drugs that May Blunt Hypoglycemia Signs and Symptoms: When beta-blockers, clonidine, guanethidine, and reserpine are provided in addition to insulin isophane human, hypoglycemia signs and symptoms may be decreased.
- The most common side effects of Insulin Isophane in humans are:
- Hypoglycemia is a low blood sugar level.
- Gaining weight and experiencing hand or foot oedema.
- Itchy, slightly rash skin; or
- Thickening or hollowing of the skin at the site where injection was given.
- Pregnancy
Pregnancy Category B: Could be acceptable. Either no danger has been shown by animal research, but human studies have yet to be conducted, or some risk has been shown by animal studies but not by human studies.
Human insulin use during pregnancy has not been linked to significant congenital disabilities, miscarriages, or unfavourable maternal or fetal outcomes, according to data from published studies conducted over decades; however, poorly controlled diabetes during pregnancy carries risks for both the mother and the fetus, and animal reproduction studies have not been completed.
Maternal risks for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm birth, stillbirth, and delivery problems are increased in cases of poorly controlled diabetes during pregnancy. Severe hyperglycemia increases the chance of serious birth abnormalities, stillbirth, and morbidity associated with macrosomia in fetuses.
- Nursing mothers
The available information from published literature suggests that exogenous human insulin products are transferred into human milk; there is no information on adverse reactions in breastfed infants reported in the literature; additionally, there is no information on how exogenous human insulin products affect milk production. The benefits of breastfeeding for development and health should be taken into account, along with the mother's clinical need for therapy and any potential adverse effects on the breastfed child from medication or an underlying maternal condition.
- Pediatric Use
Dose Adjustment in Pediatric Patients
<12 years: No proven efficacy or safety
> 12 years old: Use adult dosage range; the recommended amount is 0.5–1 unit/kg/day SC; during growth spurts, adolescents should typically maintain a daily content of ≤1.2 units/kg/day.
Dosing considerations
Human insulin dosages must be carefully adjusted to produce the best results based on blood and urine glucose testing findings. Human insulin dosages are always expressed in USP units.
- Geriatric Use
It has yet to be investigated how ageing affects the pharmacokinetics and pharmacodynamics of isophane in humans. Due to co-morbid conditions and polypharmacy, elderly patients using any form of insulin, particularly insulin isophane human, may be more at risk for hypoglycemia.
Dose Adjustment in Kidney Impairment Patients:
Patients with renal impairment may need more frequent adjustments to the dosage of Insulin Isophane and human and more regular blood glucose monitoring due to an increased risk of hypoglycemia.
Dose Adjustment in Hepatic Impairment Patients:
Patients with hepatic impairment may need more frequent adjustments to the dosage of Insulin Isophane and human and more regular blood glucose testing due to their higher risk of hypoglycemia.
Signs and Symptoms
The physician should be vigilant about the knowledge pertaining to identifying and treating overdosage of Insulin Isophane Human.
Overconsumption of Insulin Isophane Human may cause hypoglycemia and hypokalemia.
Management
There is no specific antidote or treatment for excessive intake of Insulin Isophane Human. However, immediate medical attention is essential. Insulin Isophane Human should be terminated immediately when an overdose is suspected or if any unusual symptoms occur after intake.
Management typically involves supportive measures like intravenous fluids, fluid replacement to prevent dehydration, and symptomatic treatment such as antiemetic medications for nausea and vomiting.
Mild hypoglycemia can be treated with fast-acting carbohydrates or oral glucose.
Intramuscular/subcutaneous glucagon or concentrated intravenous glucose may treat more severe episodes accompanied by coma, seizure, or neurologic impairment.
Maintain a healthy lifestyle through proper nutritional diet, regular physical activity, and stress management. These factors can help improve blood sugar control and reduce the risk of hypoglycemia.
Pharmacodynamics:
The pancreatic beta cells naturally create the hormone insulin. Following meals, insulin spikes are added to a basal insulin level in non-diabetic persons. The metabolic shifts when the body moves from a postabsorptive to an absorptive state are caused by postprandial insulin surges. Insulin increases DNA replication and protein synthesis by stimulating amino acid uptake by the liver, muscle, and adipose tissue. It also blocks the catabolism of energy stores, promotes energy storage via glycogenesis, and alters the activity of numerous enzymes involved in glycogen synthesis and glycolysis. A necessary component of growth hormone, insulin stimulates growth and processes, including DNA synthesis, cell division, and protein synthesis.
Pharmacokinetics:
Absorption
The drug is well absorbed when administered intramuscularly, subcutaneously, or intraperitoneally. It exhibits an onset of action within 1-1.5 hours, with a peak effect between 4-12 hours and a duration of 14-24 hours. The peak plasma time is observed at 6-10 hours after administration.
Distribution
The drug exhibits minimal protein binding, with approximately 5% binding to serum-binding proteins. Additionally, it has a low volume of distribution (Vd) at 0.15 L/kg.
Metabolism
Insulin is mainly absorbed and metabolized by the liver, kidney, muscle, and adipocytes; the liver is the primary organ responsible for insulin clearance.
Protein-bound: 5% (not bound to serum binding protein, but present as a monomer in plasma)
Elimination
The actual half-life cannot be reliably determined from the terminal slope of the concentration versus time curve due to the absorption-rate limited kinetics of insulin mixtures. Insulin Isophane Human (0.4 unit/kg) was administered subcutaneously to healthy participants, with a mean apparent half-life of roughly 4.4 hours (1-84 hours).
Excretion: Urine
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- Grunberger G, Chen L, Rodriguez A, Tinahones FJ, Jacober SJ, Bue-Valleskey J; IMAGINE 6 Investigators. A randomized clinical trial of basal insulin Registro vs NPH in insulin-naïve patients with type 2 diabetes: the IMAGINE 6 trial. Diabetes Obes Metab. 2016 Oct;18 Suppl 2:34-42. doi: 10.1111/dom.12743. PMID: 27723225.
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- Pramming S, Lauritzen T, Thorsteinsson B, Johansen K, Binder C. Absorption of soluble and isophane semi-synthetic human and porcine insulin in insulin-dependent diabetic subjects. Acta Endocrinol (Copenh). 1984 Feb;105(2):215-20. doi: 10.1530/acta.0.1050215. PMID: 6364670.
- https://www.ncbi.nlm.nih.gov/books/NBK549860/
- https://www.ema.europa.eu/en/
- https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/018781s181lbl.pdf
Published on: 9 Nov 2023 9:51 AM GMT
