Isophane (NPH) + Human Insulin

Insulin Isophane (NPH) + Human Insulin is an Anti-diabetic Agent belonging to the pharmacological class of intermediate-acting and fast-acting insulin.

Insulin Isophane (NPH) + Human Insulin is approved for treating diabetes mellitus. It manages high blood sugar levels in individuals with diabetes, aiding glucose regulation and preventing associated complications.

Insulin Isophane (NPH) and Human Insulin are injected subcutaneously, enabling absorption into the bloodstream. They mimic endogenous insulin actions, regulating glucose. Their distribution occurs systemically to tissues. Metabolism primarily involves degradation in the liver and kidneys. They are eliminated via urine and metabolic breakdown.

The common side effects of Insulin Isophane (NPH) + Human Insulin include low blood sugar levels (hypoglycemia), injection site reactions, cold sweats, anxiety, shakiness, hunger, rapid heartbeat, headache, and nervousness.

Insulin Isophane (NPH) + Human Insulin is available as a suspension for injection (Prefilled pen).

Insulin Isophane (NPH) + Human Insulin is available in the United States, Canada, the United Kingdom, Germany, France and Australia.

Insulin Isophane (NPH) + Human Insulin is an Anti-diabetic Agent belonging to the pharmacological class of intermediate-acting and fast-acting insulin.

Insulin Isophane: Insulin regulates the metabolism of glucose as its primary function. Except for the brain and liver, insulin facilitates glucose absorption and amino acids into muscle and fatty tissues. Moreover, it plays an anabolic role 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 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.

Human Insulin: Insulin generally controls glucose metabolism by increasing the absorption of glucose and amino acids into muscle and fat tissues—apart from the liver and brain. Moreover, it suppresses liver gluconeogenesis and promotes the production of proteins, fats, and glycogen. As a result of binding to the insulin receptor (IR), tyrosine kinase activity is activated, which phosphorylates substrates such as IRS proteins, starts signalling cascades such as PI3 kinase/Akt, and modifies glucose transporter 4 (GLUT4), protein kinase C (PKC), among other metabolic processes.

Synergistic Benefits: When human insulin + insulin isophane (NPH) are combined, they provide synergistic benefits for treating diabetes. While human insulin imitates the body's natural insulin action and helps with glucose consumption, the NPH component provides intermediate-acting insulin, which helps to regulate blood sugar levels between meals. Because of this synergy, glycemic regulation can be more thorough and consistent throughout the day, improving diabetes management and lowering the risk of complications for those with the disease.

Insulin Isophane (NPH) + Human Insulin is available as a suspension for injection(Prefilled pen).

Prefilled pen: To use the insulin glargine prefilled pen, identify the injection site, disinfect it, attach a new needle, prepare the pen, dial the dose, inject, 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 (NPH) + Human Insulin can be used in the following health conditions:

Insulin Isophane: In treating diabetes mellitus by regulating 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.

Human Insulin: Human insulin effectively manages diabetes by substituting the body's natural insulin, facilitating glucose entry into muscle and fat cells for energy. Additionally, it reduces glucose production in the liver, regulating blood sugar levels and preventing complications associated with uncontrolled glucose in the bloodstream.

Dual benefits: When human insulin is combined with insulin isophane (NPH), glucose can be effectively controlled in treating diabetes. Its prolonged action helps to keep blood sugar levels stable during the day and between meals. By lowering the risk of complications caused by uncontrolled blood sugar levels, this combination helps avoid hyperglycemia. It provides dose schedule flexibility, which improves patient adherence and helps people with diabetes manage their blood sugar levels more steadily.

Indicated to aid patients with diabetes mellitus improve their glycemic control.

Insulin Isophane (NPH) + Human Insulin cannot be used for basal versus prandial dose changes because the ratios of short-acting and intermediate-acting insulins are fixed.

Parenterally: Insulin Isophane (NPH) + Human Insulin is a suspension for injectable solution (prefilled pen) that can be administered parenterally, preferably subcutaneously once or twice daily within 15 minutes before or immediately after a meal. Before administering Insulin Isophane (NPH) + Human Insulin, visually check for discoloration or particles. To prevent lipodystrophy, subcutaneously injected in the buttocks, upper arm, thigh, or abdomen, switching sites each time. Avoid intravenous or intramuscular use and refrain from using insulin pumps. Avoid combining Insulin Isophane (NPH) + Human Insulin with other diluents or insulin substitutes. If a dose is missed, it should be taken with the following main meal and then continue the regular dosing schedule; taking an extra amount to compensate for the missed one is not recommended.

The dosage and duration of treatment should be as per the treating physician's clinical judgment.

Insulin Isophane (NPH) + Human Insulin is available as a suspension for injection.

Dosage Adjustment for Adult Patients

Initial dose

Moderate or lower ketones: 0.5 U/kg/day SC

Large ketones: 0.7 U/kg/day SC

Usually, intermediate- or long-acting insulin is administered at 50–75% of the entire daily amount.

Use this combination product if the NPH (isophane) to regular dosage ratio is 2:1.

Initial dosage; adjust based on blood glucose levels

Starting dose: split doses of 0.5–1 units/kg per day

Usually, intermediate- or long-acting insulin is administered at 50–75% of the entire daily amount.

Use this combination product if the NPH (isophane) to regular dosage ratio is 2:1.

Give two-thirds of the daily insulin SC.

Regular insulin to NPH (isophane) ratio: 1:2

Administer 1/3 of the daily insulin SC.

Insulin Isophane (NPH) + Human Insulin should be used in treating diabetes mellitus, along with appropriate dietary restrictions.

While taking Insulin Isophane (NPH) + Human Insulin, maintain an appropriate diet, primarily focusing on regulating carbohydrate intake and consuming a balanced and healthy meal plan. Limit or avoid excessive sugary foods and drinks significantly impacting blood glucose levels. Patients should avoid excessive alcohol consumption to reduce the risk of hypoglycemia and dehydration. Adequate fluid intake is essential to mitigate the potential for decreased blood pressure.

While taking this combination, it is advised to stay hydrated, consume a rich-balanced diet low in saturated fats and cholesterol—and drink plenty of vegetables, whole grains, fruits, and lean proteins in meals.

The dietary restriction should be individualized as per patient requirements.

Insulin Isophane (NPH) + Human Insulin may be contraindicated in the following conditions:-

Insulin Isophane (NPH) + Human Insulin FlexPens and syringes should never be shared by patients, even if the needle is replaced.

Hypokalemia: This condition could be fatal. Patients at risk for hypokalemia should have their potassium levels checked and treated as needed.

The adverse reactions related to Insulin Isophane (NPH) + Human Insulin can be categorized as: -

Localized cutaneous amyloidosis.

The most common side effects of Insulin Isophane (NPH) + Human Insulin include:

Insulin Isophane (NPH) + Human Insulin should be prudent in the following population group.

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.

Poorly treated diabetes during pregnancy carries dangers for the mother and fetus; no research on animal reproduction has been done. The extant literature, spanning several decades, has failed to establish a correlation between the use of human insulin during pregnancy and noteworthy congenital disabilities, miscarriage, or unfavorable outcomes for either the mother or the fetus.

Maternal risk factors for poorly managed diabetes during pregnancy include hypertension, spontaneous abortions, preterm birth, stillbirth, and delivery difficulties. Uncontrolled diabetes raises the chance of significant birth abnormalities, stillbirth, and morbidity associated with macrosomia in the fetus.

The available information from published literature indicates that exogenous human insulin products are transferred into human milk; there is no information on the adverse reactions observed in breastfed infants in the literature, nor is there information on the effects of exogenous human insulin products on milk production; the benefits of breastfeeding for development and health should be taken into account in conjunction with the mother's clinical need for therapy and any potential adverse effects on the breastfed child from medication or an underlying maternal condition.

Combining human insulin with insulin isophane (NPH) is advisable to help pediatric diabetic patients with their glycemic management. To lower the risk of hypoglycemia, pediatric patients' insulin isophane (NPH) + human insulin dosages must be individualized depending on their metabolic needs and frequent blood glucose monitoring.

Initial dose

Moderate or lower ketones: 0.5 U/kg/day SC

Large ketones: 0.7 U/kg/day SC

Increased quantity may be required during growth spurts.

Usually, intermediate- or long-acting insulin is administered at 50–75% of the entire daily amount.

Use this combination product if the NPH (isophane) to regular dosage ratio is 2:1.

There is no sufficient scientific evidence regarding the use and safety in hepatic impairment patients. Due to their increased risk of hypoglycemia, people with renal impairment may require more frequent blood glucose checks and insulin isophane (NPH) + human insulin dose changes.

There is no sufficient scientific evidence regarding the use and safety in hepatic impairment patients. Due to their increased risk of hypoglycemia, people with renal impairment may require more frequent blood glucose checks and insulin isophane (NPH) + human insulin dose changes.

The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Insulin Isophane (NPH) + Human Insulin.

Overconsumption of Insulin Isophane (NPH) + Human Insulin could lead to severe hypoglycemia, dehydration, kidney dysfunction, electrolyte imbalances, and gastrointestinal distress such as nausea and vomiting.

No specific antidote or treatment exists for excessive Insulin Isophane (NPH) + Human Insulin intake. However, immediate medical attention is essential. Insulin Isophane (NPH) + Human Insulin should be terminated immediately when an overdose is In cases of overdose, close medical attention is crucial. Insulin Isophane (NPH) + Human Insulin should be discontinued if an overdose is suspected or if unusual symptoms occur after ingestion. Activated charcoal or gastric lavage may also be considered if the overdose is detected shortly after ingestion to reduce absorption.

Patients may require supportive care to address the overdose's various effects. This may include providing fluids and electrolytes to correct dehydration and electrolyte imbalances. For severe hypoglycemia, treatment with glucose or other appropriate interventions may be needed.

In severe overdoses, mainly if acute kidney injury is present, hemodialysis may be considered to remove excess Human Insulin from the bloodstream.

Insulin Isophane: 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 the synthesis of protein 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.

Human Insulin: The onset and duration of Insulin Isophane (NPH) + Human Insulin action can vary widely among individuals. Subcutaneous administration at 0.05 to 0.4 units/kg starts within 10 to 75 minutes, peaks at around 3 hours (range: 20 minutes to 7 hours), and lasts about 8 hours (range: 3 to 14 hours). Higher doses can prolong the effect up to approximately 18 hours. Intravenous use at 0.1 to 0.2 units/kg starts within 10 to 15 minutes and lasts about 4 hours (2 to 6 hours).

Insulin Isophane: The drug is 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.

Human Insulin: In healthy subjects receiving subcutaneous Human Insulin doses from 0.05 to 0.4 units/kg, peak serum levels occurred within 36 to 150 minutes. For type 1 diabetes patients given a single 12-unit amount (approximately 0.15 units/kg), median peak levels appeared around 2 hours. Administered to healthy obese subjects, 50 to 100 units doses extended grades to 3 hours. Bioavailability ranges from 48% to 89% in 0.1 to 0.3 unit/kg doses.

Insulin Isophane: 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.

Human Insulin: When Human Insulin is administered intravenously at doses of 0.1 or 0.2 unit per kg, the mean volume of distribution ranges between 0.32 to 0.67 L per kg.

Insulin Isophane: Insulin is mainly absorbed and metabolized by the liver, kidney, muscle, and adipocytes; the liver is the primary organ responsible for insulin clearance.

Human Insulin: The liver is the primary organ involved in eliminating insulin, with the kidney, muscle, and adipocytes being the main sites of insulin uptake and breakdown.

Insulin Isophane: The actual half-life cannot be reliably determined from the terminal slope of the concentration versus the 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).

Human Insulin: After subcutaneously administering Human Insulin in the 0.05-0.4 unit/kg range, the median apparent half-life is around 1.5 hours (40 minutes-7 hours). With higher subcutaneous doses (50 and 100 units) in healthy obese subjects, the mean apparent half-life was approximately 3.6 hours (range 1.6-8.6 hours). Intravenous administration resulted in a mean half-life of about 20 minutes at a 0.1 unit per kg dose and 1 hour at a 0.2 unit per kg dose.

In diabetes treatment, balanced glucose regulation ensures sustained glucose management while providing a steady and balanced effect that maintains blood sugar levels throughout the day.