Insulin Injection, Isophane (Porcine) (Hypurin NPH Insulin, Pork)

1. Health Canada Product Monograph — Insulin Injection, Isophane (Porcine)

• Insulin injection, isophane (porcine) is used to treat insulin-dependent diabetes mellitus in patients already using an animal-derived insulin.
• It is also used in new patients with insulin-dependent diabetes who cannot tolerate recombinant human insulin or whose diabetes is not adequately controlled by it.
• It is suited to patients who need a depot (reservoir) insulin of medium duration to cover longer gaps between meals.

• There are no adequate, well-controlled studies of insulin injection, isophane (porcine) in pregnant women, so it should be used during pregnancy only under medical supervision.
• Insulin requirements often decrease in early pregnancy but typically increase in the second and third trimesters, so blood glucose should be checked frequently by an experienced diabetes physician.
• Insulin requirements may decrease again after delivery, sometimes unpredictably, so blood glucose should be monitored closely after birth.
• Congenital abnormalities are more common in babies born to mothers with diabetes than to mothers without diabetes, making good glucose control especially important.

• It is not known whether insulin injection, isophane (porcine) passes into human breast milk.
• There are no adequate, well-controlled studies in breastfeeding women, so it should be used with caution while nursing.
• Breastfeeding mothers may need adjustments to their insulin dose and diet.

• Older adults with diabetes are more likely to have severe, rapid-onset episodes of low blood sugar (hypoglycemia).
• The usual early warning symptoms of low blood sugar may be reduced or absent in older adults, making regular blood glucose monitoring especially important.

• There is limited experience using insulin injection, isophane (porcine) in children younger than 6 years of age.
• It should be used in children under 6 only if clearly needed and under careful medical supervision, since its safety has not been established in this age group.

• The dose of insulin injection, isophane (porcine) is individualized for each patient by their physician, based on regular blood glucose monitoring.
• It is usually given by subcutaneous injection, but may be given intramuscularly if necessary, which produces a faster and shorter-lasting effect; it must never be given intravenously.
• After subcutaneous injection, onset of action occurs within about 2 hours, with peak effect between 6 and 12 hours, and an overall duration of 18 to 24 hours.
• It may be mixed in the same syringe with Hypurin Regular Insulin, Pork, drawing up the regular insulin first and injecting immediately after mixing.
• Dose adjustments are often needed when a patient's diet, activity level, illness, or life stage changes, and patients switching from another insulin product may need a different dose.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• Overdose with insulin injection, isophane (porcine) causes hypoglycemia (low blood sugar).
• Symptoms can include yawning, hunger, pale skin, restlessness, weakness, sweating, trembling, confusion, anxiety, and irritability.
• More severe overdose can cause numbness of the nose, mouth, fingers, or toes, blurred or double vision, slurred speech, difficulty concentrating, drowsiness, convulsions, and, if untreated, collapse, coma, or irreversible brain damage.
• Low blood potassium (hypokalemia) can also occur with insulin overdose.
• Mild hypoglycemia is treated with oral glucose or sugar and rest.
• Moderately severe hypoglycemia is treated with an injection of glucagon, followed by oral carbohydrate once the patient has recovered enough to eat safely.
• Patients who are unconscious or who do not respond to glucagon require an intravenous injection of dextrose in a medical setting.

• Low blood sugar (hypoglycemia) is the most common side effect of insulin injection, isophane (porcine).
• Weight gain may occur with insulin therapy.
• Low blood potassium (hypokalemia) may occur.
• Stinging, warmth, or a burning sensation at the injection site may occur.
• Redness, itching, or swelling (local allergic reaction) at the injection site may occur.
• Changes in the fatty tissue at injection sites (lipodystrophy), causing lumps or dimpling, may occur.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Severe low blood sugar can cause loss of consciousness, coma, or death if not treated promptly.
• Severe high blood sugar (hyperglycemia), if untreated, can progress to diabetic ketoacidosis or coma, which can be fatal.
• Generalized allergic reactions can cause hives, rash over the whole body, shortness of breath, wheezing, nausea, or a drop in blood pressure.
• Severe angioedema (swelling beneath the skin) is a rare reaction, occurring most often when insulin therapy is first started.
• Anaphylaxis, a severe whole-body allergic reaction, can occur rarely.
• Allergic reactions to the preservatives phenol or m-cresol, or to the zinc or protamine in the formulation, may occur.
• Nerve pain (neuropathic pain) can occur when blood sugar is brought under control too quickly.
• Seek urgent medical attention for confusion, loss of consciousness, seizures, or signs of a severe allergic reaction such as difficulty breathing or facial swelling.

• Use with caution in patients with liver disease, since insulin requirements may fall.
• Use with caution in patients with severe kidney impairment, since insulin requirements may fall and the body's ability to recover from low blood sugar may be reduced.
• Use with caution in patients with disease of the adrenal, pituitary, or thyroid glands, or with coeliac disease, since insulin requirements may change.
• Use with caution in patients switching from another insulin product or another animal or human insulin, since the early warning symptoms of low blood sugar may be less noticeable.
• Use with caution in patients with insulin resistance associated with lipid disorders, high blood pressure, or heart disease, who often require higher insulin doses.
• Use with caution during illness, infection, surgery, emotional stress, or puberty, since insulin needs can change quickly during these times.
• Use with caution in patients whose blood flow to injection sites is increased by heat, such as a hot bath, sunbathing, or sauna use, since this can speed insulin absorption and raise the risk of low blood sugar.
• Use with caution when driving or operating machinery, since low or high blood sugar can impair concentration and reaction time.

• Contraindicated in patients currently showing signs of hypoglycemia (low blood sugar).
• Contraindicated in patients with known hypersensitivity to porcine insulin or to any ingredient in the formulation.
• Contraindicated for intravenous administration under any circumstances.

• Corticosteroids, thyroid hormone replacement, diazoxide, and thiazide or loop diuretics can increase insulin requirements.
• Antipsychotics such as chlorpromazine and sympathomimetic agents can increase insulin requirements.
• Smoking may reduce the blood-sugar-lowering effect of insulin.
• ACE inhibitors, anabolic steroids, and testosterone can lower insulin requirements and increase the risk of hypoglycemia.
• Moderate to large amounts of alcohol, especially binge drinking, can lower insulin requirements and increase the risk of hypoglycemia.
• NSAIDs and salicylates, including large doses of aspirin, can enhance insulin's blood-sugar-lowering effect.
• Antiarrhythmic drugs such as disopyramide and quinidine can increase the risk of hypoglycemia.
• Antidepressants such as monoamine oxidase inhibitors, fluoxetine, and amitriptyline can increase the risk of hypoglycemia.
• The blood-pressure medicine guanethidine can lower insulin requirements.
• Antimalarial drugs such as chloroquine or quinine can increase the risk of hypoglycemia.
• Octreotide, fibrates, mebendazole, and high-dose intravenous pentoxifylline can lower insulin requirements.
• Tetracycline antibiotics such as oxytetracycline can lower insulin requirements.
• Clonidine and beta-blockers can mask the early warning signs of hypoglycemia and may raise or lower insulin requirements.
• The calcium channel blocker nifedipine can occasionally impair glucose tolerance.
• Cyclophosphamide, isoniazid, gemfibrozil, and oral contraceptives can raise or lower insulin requirements.
• Thiazolidinediones (TZDs) such as pioglitazone or rosiglitazone should not be combined with insulin therapy, due to an increased risk of heart failure and fluid retention (edema).

• Insulin injection, isophane (porcine) is given by injection, not by mouth, so food does not affect its absorption in the way it would for an oral medication.
• Because it lowers blood sugar for an extended period, meals and snacks must still be timed to match its intermediate duration of action; skipping meals increases the risk of low blood sugar, particularly several hours after the injection.

• Insulin injection, isophane (porcine) is intermediate-acting, with effects peaking 6 to 12 hours after injection and lasting 18 to 24 hours, so it is typically given once or twice daily on a fixed schedule.
• The exact timing relative to meals and other insulin doses should follow the individualized schedule set by the prescribing physician.

• Store unopened vials of insulin injection, isophane (porcine) refrigerated at 2C to 8C; do not freeze.
• Once a vial is in use, it may be kept at room temperature and should be used within 28 days, then discarded.
• Do not use a vial if its contents have been frozen or contain lumps that do not disperse when mixed.
• Gently roll or invert the vial before each use to re-suspend the insulin evenly, since it settles into a white suspension on standing.
• Each vial should be used by only one patient, and needles or syringes should never be shared.

• Insulin injection, isophane (porcine) is an intermediate-acting insulin used to control blood sugar in people with insulin-dependent diabetes.
• Monitor your blood sugar regularly as directed and know the warning signs of both low and high blood sugar.
• Never share insulin vials, needles, or syringes with another person, and always carry a fast-acting sugar source in case of a low blood sugar episode.