Insulin Isophane, Human Biosynthetic (rDNA Origin) (Humulin N)

1. Health Canada Product Monograph — Insulin Isophane, Human Biosynthetic (rDNA Origin)

• Insulin isophane, human biosynthetic (rDNA origin) is used to treat patients with diabetes mellitus who require insulin.
• It provides intermediate-duration background insulin coverage and is not used for emergencies such as diabetic coma or precoma, or for patients undergoing surgery, where a fast-acting regular insulin is used instead.
• Patients switching to it from an animal-source insulin can generally use the same dose and schedule at first, though some adjustment may be needed.

• Insulin isophane, human biosynthetic (rDNA origin) may be used during pregnancy when clinically needed, and good glucose control is essential for a healthy pregnancy.
• Insulin requirements usually decrease during the first trimester and increase during the second and third trimesters.
• Blood sugar should ideally be well controlled before conception and monitored closely throughout pregnancy.

• Breastfeeding mothers with diabetes taking insulin isophane, human biosynthetic (rDNA origin) may need adjustments to their insulin dose or diet.
• Adequate, well-controlled studies during breastfeeding have not been conducted.

• Insulin isophane, human biosynthetic (rDNA origin) may be used in older adults when clinically needed.
• Older adults may have less pronounced early warning symptoms of low blood sugar, so extra care with monitoring is advised.

• Insulin isophane, human biosynthetic (rDNA origin) may be used in children and adolescents when clinically needed.

• The dose of insulin isophane, human biosynthetic (rDNA origin) is determined by the physician according to each patient's individual requirements.
• It is a suspension and must be given only by subcutaneous injection, into the upper arms, thighs, buttocks, or abdomen, rotating sites so the same spot is not used more than about once a month.
• It must never be given intravenously and must not be used to treat diabetic coma.
• Patients switching from an animal-source insulin can generally start at the same dose, though some require an adjustment either right away or gradually over several weeks.
• It may be mixed with Humulin R (regular insulin) in the same syringe to meet individual needs, as directed by a physician.

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

• Overdose with insulin isophane, human biosynthetic (rDNA origin) causes hypoglycemia (low blood sugar), also called an insulin reaction.
• It can be brought on by taking too much insulin, missing or delaying a meal, unusually hard exercise before a meal, illness such as vomiting or diarrhea, or other changes in the body's need for insulin.
• Early symptoms usually include hunger, nervousness, sweating, and a fast heartbeat, with headache, confusion, drowsiness, blurred or double vision, or numbness of the lips, nose, or fingers possible as it progresses.
• Beta-blocker medicines can mask the usual warning symptoms of hypoglycemia.
• A patient who can swallow safely should be given fast-acting sugar or fruit juice by mouth.
• A patient unable to take sugar by mouth, or who is unconscious, requires intravenous dextrose or an injection of glucagon given in a medical setting.

• Low blood sugar (hypoglycemia) is the most common side effect of insulin isophane, human biosynthetic (rDNA origin).
• Redness, swelling, or itching (local allergic reaction) at the injection site may occur.
• Changes in the fatty tissue at injection sites, including lipoatrophy (dimpling) or lipohypertrophy (thickened, lumpy skin), may occur.
• Localized skin lumps from a build-up of protein (cutaneous amyloidosis) may occur at injection sites used repeatedly without rotation.

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.
• Uncontrolled high blood sugar, especially in type 1 diabetes, can progress to diabetic ketoacidosis or coma, which can be fatal.
• Generalized allergic reactions can cause a whole-body rash with itching, shortness of breath, wheezing, a fast pulse, or a drop in blood pressure, and severe cases can be life-threatening.
• Insulin antibodies can rarely develop and, in very rare cases, cause either insulin resistance (hyperglycemia) or unexpected low blood sugar.
• Injecting repeatedly into an area of lipodystrophy or cutaneous amyloidosis can cause unpredictable blood sugar swings, including sudden hyperglycemia or hypoglycemia if the injection site is changed.
• Seek urgent medical attention for confusion, loss of consciousness, seizures, or any signs of a severe allergic reaction such as difficulty breathing or facial swelling.

• Use with caution in patients with liver impairment, since insulin requirements may decrease.
• Use with caution in patients with kidney impairment, since insulin requirements may decrease.
• Use with caution in patients switching from another type, brand, or species of insulin, since the early warning symptoms of hypoglycemia may be less noticeable.
• Use with caution in patients with a long duration of diabetes, diabetic nerve disease, very tightly controlled blood sugar, or psychiatric illness, since hypoglycemia warning signs may be reduced.
• Use with caution in patients taking beta-blockers, since these can mask the warning signs of low blood sugar.
• Use with caution during illness, infection, stress, or major changes in diet or activity, since insulin needs can change quickly.
• Use with caution in patients with a history of systemic allergy to pork, beef, or other insulin, since they may also react to human insulin.
• Use with caution when driving or operating machinery, since low or high blood sugar can impair concentration and reaction time.

• Contraindicated during episodes of hypoglycemia (low blood sugar).
• Contraindicated in patients with hypersensitivity to human insulin or any ingredient in the formulation, unless given as part of a supervised desensitization program.
• Contraindicated for intravenous administration or for treatment of diabetic coma.

• Oral antidiabetic medicines, salicylates, sulfa antibiotics, monoamine oxidase inhibitor antidepressants, beta-blockers, alcohol, ACE inhibitors, angiotensin II receptor blockers, and anabolic steroids can decrease insulin requirements and raise the risk of hypoglycemia.
• Oral contraceptives, thiazide diuretics, corticosteroids, thyroid hormone replacement, sympathomimetic drugs, and danazol can increase insulin requirements.
• The seizure medicine phenytoin (diphenylhydantoin) can reduce insulin's blood-sugar-lowering effect.
• Diuretics can increase, decrease, or have no effect on insulin requirements, depending on the individual.
• Thiazolidinediones (TZDs) such as pioglitazone or rosiglitazone should not be combined with insulin therapy due to an increased risk of heart failure and swelling.
• Hormones that naturally oppose insulin's effect, such as growth hormone, corticotropin, glucocorticoids, thyroid hormone, and glucagon, can raise blood sugar and reduce insulin's effect.
• Conditions such as acromegaly, Cushing's syndrome, hyperthyroidism, and pheochromocytoma can complicate diabetes control by altering insulin needs.

• Insulin isophane, human biosynthetic (rDNA origin) is given by injection, not by mouth, so food does not affect its absorption the way it would for an oral medication.
• Because it works over an intermediate duration, an excess of insulin relative to food intake, such as skipping a meal, can cause hypoglycemia, so meals should be planned around the insulin schedule.

• Insulin isophane, human biosynthetic (rDNA origin) has a slower onset than regular insulin and an intermediate duration of action, generally lasting from about 16 to 24 hours, so it is typically given once or twice daily on a fixed schedule.
• The most satisfactory injection time is usually before breakfast, but the exact timing should follow the individualized schedule set by the prescribing physician.

• Before first use, store insulin isophane, human biosynthetic (rDNA origin) in the refrigerator at 2C to 8C; do not freeze it or expose it to direct sunlight.
• Once in use, vials, cartridges, or prefilled pens may be kept at room temperature, below 25C and away from heat and light, and should be discarded 28 days after first use.
• Do not use if the suspension shows clumps that do not mix in, or particles that stick to the vial and give it a frosted appearance.
• Cartridges and prefilled pens must never be refilled or shared between patients, even if the needle is changed.

• Insulin isophane, human biosynthetic (rDNA origin) is an intermediate-acting insulin used to control blood sugar in people with diabetes who need insulin.
• Monitor your blood sugar regularly, know the early warning signs of low and high blood sugar, and rotate your injection sites.
• Never share insulin needles, cartridges, or pens with another person, and always carry a fast-acting sugar source in case of a low blood sugar episode.