insulin NPH

Insulin NPH is a type of insulin used to improve glycemic control in adult and pediatric patients with diabetes types I and II. Insulin NPH is a human insulin suspension produced in labs using DNA recombinant technology. Neutral protamine Hagedorn (NPH) is a protein obtained from fish and added to insulin to slow down its absorption and prolong the effects. Animal insulins were used in the past, but currently, the only type of insulin available in the U.S. is human insulin which is structurally identical to natural human insulin.

Insulin, released by the pancreas after a meal, regulates the metabolism of carbohydrates, fats and proteins absorbed from food. Reduced insulin secretion or faulty functioning of insulin results in diabetes, a metabolic disorder that impairs the ability of the cells to absorb glucose for energy, resulting in high blood glucose levels (hyperglycemia). Dysfunction of insulin affects the entire body and can damage all organs, particularly, nerves, kidneys and eyes.

Insulin stimulates the uptake of glucose from blood by all the internal organs, most importantly, the liver, skeletal muscles and fat cells (adipose tissue). In the liver, insulin promotes storage of energy by stimulating conversion of glucose into glycogen and inhibiting glycogen breakdown. It also promotes the synthesis of fatty acids in the liver which are released into the bloodstream for cellular conversion into energy.

In the skeletal muscles, insulin promotes protein and glycogen synthesis, and uptake of glucose and amino acids, the building blocks of proteins. Insulin also promotes energy storage in adipose tissue by stimulating the breakdown of triglycerides into free fatty acids, reducing circulating triglyceride levels in the blood. Insulin level in nondiabetic individuals typically rises after a meal and decreases when blood glucose levels drop to base level.

Insulin is the mainstay treatment for type I diabetes, and it is used for treating type II diabetes when the glucose levels cannot be managed with diet, weight loss, exercise and oral medications. Most patients with type II diabetes ultimately become insulin-deficient with the progression of disease, and will require insulin therapy. Many patients with type II diabetes also develop insulin resistance, so insulin therapy is individualized based on each patient’s condition.

The types of human insulin used to treat diabetes are categorized by the time taken for onset, peak and duration of insulin effects. Insulin NPH is an intermediate-acting insulin with onset of effect within one or two hours, peak effect in four to 10 hours, and duration of effects for 12-18 hours. The NPH in the insulin suspension slows down insulin absorption and also turns it cloudy. Insulin NPH is administered subcutaneously with needles or pre-filled pens.

• Do not administer insulin NPH to patients:
  • With hypersensitivity to any component of insulin NPH
  • During episodes of hypoglycemia
• Insulin NPH should be administered subcutaneously. Do not administer as an intramuscular or intravenous injection.
• Insulin NPH is an intermediate-acting insulin. Do not use in circumstances that require rapid-acting insulin.
• Train patients to self-administer insulin NPH and advise them to never share their delivery devices, to avert the risk of bloodborne infections.
• Repeated insulin injections into the same areas can cause skin thickening or depression (lipodystrophy) or abnormal protein clumping in the skin (cutaneous amyloidosis). Injecting in these areas can reduce insulin absorption and result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) may result in hypoglycemia.
• Insulin requirements may change with certain conditions. Monitor glycemic control and adjust insulin regimen appropriately. Insulin requirement may decrease with nausea, vomiting, diarrhea, malabsorption, hypothyroidism and impaired kidney or liver function, and may increase with hyperthyroidism, fever, trauma, infection, or surgery.
• Changes in insulin strength, type, manufacturer or mode of administration can affect glycemic control and cause hyperglycemia or hypoglycemia. Insulin regimen changes should be made under close medical supervision with increased frequency of blood glucose monitoring.
• Hypoglycemia is the most common adverse effect of all insulin therapies, including insulin NPH.
  • Hypoglycemia can happen suddenly and symptoms differ in patients and may change over time in the same patient.
  • Hypoglycemia can affect concentration ability and reaction time and put the patient and others at risk when engaging in hazardous activities.
  • Severe hypoglycemia can cause seizure, unconsciousness, temporary or permanent brain damage, and even death.
  • Changes in meal pattern, physical activity and co-administered medications can increase the risk for hypoglycemia.
  • Patients with impaired liver or kidney function have a higher risk for hypoglycemia.
  • Patients with long-standing diabetes, diabetic nerve disease (neuropathy), recurrent hypoglycemia, or patients taking beta-blockers may have reduced awareness of hypoglycemic symptoms.
  • Blood glucose monitoring should be performed more frequently in patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia.
  • Patients and caregivers must be educated to self-monitor glucose levels, recognize and manage hypoglycemia.
• Insulin NPH can cause severe, life-threatening, generalized allergic reactions including anaphylaxis. Discontinue insulin NPH if allergic reactions occur, treat appropriately and monitor the patient until symptoms resolve. Do not use in patients who have had previous hypersensitivity reactions to insulin NPH.
• Insulin causes shift of potassium into the cells and can lead to low blood potassium (hypokalemia), which, if untreated, can cause respiratory paralysis and life-threatening irregular ventricular rhythm (ventricular arrhythmia) and death. Monitor potassium levels in patients at risk for hypokalemia, including patients taking potassium-lowering medications or medications sensitive to potassium concentrations.
• Concurrent use with thiazolidinediones, a class of oral antidiabetic drugs known as peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention and increase the risk for heart failure. Closely monitor such patients for symptoms and if the patient develops heart failure, treat appropriately and consider discontinuation or dose reduction of PPAR-gamma agonist.

Common side effects of insulin NPH include:

• Low blood glucose levels (hypoglycemia)
• Low blood potassium (hypokalemia)
• Hypersensitivity reactions including:
  • Severe allergic reaction (anaphylaxis)
• Injection site reactions including:
  • Erythema
  • Itching (pruritus)
  • Local swelling (edema)
  • Depression in skin tissue (lipoatrophy)
  • Thickening of skin tissue (lipohypertrophy)
  • Localized cutaneous amyloidosis
• Peripheral edema
• Weight gain
• Anti-insulin antibody development
• Transitory refraction disorder in the eye
• Transient worsening of diabetic retinopathy
• Acute painful peripheral neuropathy

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Injectable suspension

• 100 units/mL (3 mL)
• 100 units/mL (10 mL)
• 3 mL Humulin N KwikPen (prefilled)
• 3 mL single-patient-use Novolin N FlexPen

Adult and Pediatric:

Type 1 Diabetes Mellitus

Suggested guidelines for beginning dose

• Usual daily maintenance range is 0.5-1 unit/kg/day subcutaneous (SC) in divided doses; non-obese may require 0.4-0.6 unit/kg/day; obese may require 0.8-1.2 units/kg/day

Type 2 Diabetes Mellitus

Suggested guidelines for beginning dose: 0.2 unit/kg/day

Morning

• Give two thirds of daily insulin SC
• Ratio of regular insulin to NPH insulin 1:2

Evening

• Give one third of daily insulin SC
• Ratio of regular insulin to NPH insulin 1:1

Dosing Considerations

• Dosage of human insulin, which is always expressed in USP units, must be based on the results of blood and urine glucose tests and must be carefully individualized to optimal effect
• Dose adjustments should be based on regular blood glucose testing
• Adjust to achieve appropriate glucose control

Blood sugar patterns (longer than 3 days)

• Look for consistent pattern in blood sugars for longer than 3 days
• For the same time each day: Compare blood glucose level
• For each time of day: Calculate blood glucose range
• Calculate median blood glucose
• Consider eating and activity patterns during day

Blood glucose adjustments

• Adjust only 1 insulin dose at a time
• Correct hypoglycemia first
• Correct highest blood sugars next
• If all blood sugars are high (within 2.75 mmol/L [50 mg/dL]): Correct morning fasting blood glucose first
• Change insulin doses in small increments: Type 1 diabetes (1-2 unit change); type 2 diabetes (2-3 unit change)

Sliding scales

• Many sliding scales exist to determine exact insulin dose based on frequent blood glucose monitoring
• Commonly written for q4hr blood glucose test
• Sliding scale coverage usually begins after blood glucose is above 11 mmol/L (200 mg/dL)
• If coverage is needed every 4 hours x 24 hours, then base insulin dose is adjusted first; sliding scale doses may be adjusted upwards as well

Administration

• Administer within 15 minutes before a meal or immediately after a meal

Overdose

• Insulin NPH overdose can cause severe hypoglycemia and hypokalemia.
• Mild hypoglycemia can be treated with oral glucose and appropriate adjustments in drug dosage, meal patterns and exercise, as required.
• Severe hypoglycemic episodes with coma, seizure or neurologic impairment may be treated with concentrated intravenous glucose or intramuscular or subcutaneous injection of glucagon. Sustained carbohydrate intake and observation of the patient may be required to prevent recurrence of hypoglycemia.
• Hypokalemia should be corrected with appropriate supplemental potassium.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of insulin NPH include:
  • pramlintide
• Serious interactions of insulin NPH include:
  • ethanol
  • macimorelin
• Insulin NPH has moderate interactions with at least 127 other drugs.
• Insulin NPH has minor interactions with at least 77 other drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• There are no animal reproductive studies or adequate and well-controlled studies on insulin NPH use in pregnant women. Good glycemic control before conception and throughout pregnancy in patients with diabetes or history of gestational diabetes is essential for maternal and fetal health.
• Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, stillbirth and delivery complications, and fetal risks for birth defects and abnormally large growth (macrosomia).
• Insulin requirements may decrease during the first trimester, increase during second and third trimesters, and rapidly reduce after delivery. Glucose levels should be carefully monitored and insulin regimens appropriately adjusted in pregnant women.
• Natural insulin is present in breastmilk, however, it is not known if insulin NPH is excreted in breastmilk. Orally ingested insulin is degraded in the gastrointestinal tract.
• There are no reports of adverse effects on the breastfed infant from exposure to insulin in breastmilk.
• Good glucose control supports lactation in nursing mothers with diabetes, however, dosage adjustments of insulin may be required.

• Never share your pen, needles, syringes or other insulin NPH delivery devices with others even with changed needles, and never use those used by others.
• Administer your insulin NPH injection exactly as prescribed and instructed. Any regimen change must be done only under your physician’s supervision.
• Rotate your injection sites and do not inject into areas of skin that have scars, pits, lumps, scales, or are tender or bruised.
• Always check labels before every injection to avoid errors of mix-up with other insulin products.
• Blood glucose levels and insulin requirements can change with change in activity levels, during illness, emotional disturbances, or with other stressors. Learn to monitor glucose levels, and to recognize symptoms of hyperglycemia and hypoglycemia.
• If you frequently experience hypoglycemia, always carry sweets such as hard candy for immediate use and seek medical help if symptoms don’t resolve.
• Hypoglycemia can impair concentration ability and reaction time, be cautious about activities such as driving and operating heavy machinery.
• Report to your physician immediately if you experience any hypersensitivity reactions.
• Avoid drinking alcohol, it may increase or decrease the effect of insulin NPH.
• Store insulin NPH and insulin delivery devices safely out of reach of children.
• In case of overdose, seek medical help immediately or contact Poison Control.