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Humulin N Side Effects

Generic Name: insulin isophane

Note: This page contains information about the side effects of insulin isophane. Some of the dosage forms included on this document may not apply to the brand name Humulin N.

Not all side effects for Humulin N may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to insulin isophane: pens

Other dosage forms:

Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Redness, swelling, itching, or mild pain at the injection site.

Seek medical attention right away if any of these SEVERE side effects occur while taking insulin isophane (the active ingredient contained in Humulin N)

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; wheezing; muscle pain); change in skin to thick or thin where the injection was given; changes in vision; chills; confusion; dizziness; drowsiness; fainting; fast or irregular heartbeat; headache; loss of consciousness; mood changes; seizures; shortness of breath; slurred speech; swelling of the hands, ankles, or feet; tremor; trouble breathing; trouble concentrating; unusual hunger; unusual sweating; weakness.

For Healthcare Professionals

Applies to insulin isophane: subcutaneous suspension


Frequency not reported: Sodium retention and edema[Ref]

Insulin may cause sodium retention and edema, especially with intensified insulin therapy. Combination use with thiazolidinediones has resulted in fluid retention which has led to or exacerbated heart failure.[Ref]


Long-term use of insulin can cause lipodystrophy at the site of repeated insulin injections. Lipodystrophy includes lipohypertrophy (thickening of adipose tissue) and lipoatrophy (thinning of adipose tissues).[Ref]

Uncommon (0.1% to 1%): Lipodystrophy[Ref]


The most common adverse reactions reported with this insulin include hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, weight gain, and edema.[Ref]


Hypersensitivity side effects have included both local and systemic reactions. These reactions are becoming rare (less than 1% of patients) due to the use of purer forms of pork insulin or biosynthetic human insulin. Local reactions have presented as erythema, swelling, heat, or subcutaneous nodules. They usually occurred within the first two weeks of therapy and then disappear. True allergy to insulin has been rare, and sensitization was usually associated with specific animal proteins in bovine and less pure forms of porcine insulins.[Ref]

Uncommon (0.1% to 1%): Local reactions such as redness, swelling, or itching at the injection site
Very rare (less than 0.01%): Anaphylactic reactions[Ref]


Frequency not reported: Formation of anti-insulin antibodies[Ref]

Increases in titers of anti-insulin antibodies that react with human insulin have been observed; some data indicates the increase is transient. The clinical significance of these antibodies is unknown; it does not appear to cause deterioration in glycemic control.[Ref]


Very common (10% or more): Hypoglycemia
Rare (less than 0.1%): Insulin resistance
Frequency not reported: Hypokalemia, hyperglycemia, diabetic ketoacidosis, hyperosmolar hyperglycemic non-ketotic syndrome, hypomagnesemia, hypophosphatemia[Ref]

Hypoglycemia is the most common adverse reaction of all insulin therapies. The timing of hypoglycemia generally reflects the time-action profile of the administered insulin, however, the time action profile of any insulin may vary considerably in different individuals or at different times in the same individual depending on dose, site of injection, blood supply, temperature, and physical activity. Other factors such as changes in food intake (timing of meals, amount or type of food) and concomitant medications will also affect the risk of hypoglycemia.

Hypokalemia, which is due to a shift in potassium from the extracellular to the intracellular space, occurs with all insulins. Hypokalemia and hypomagnesemia has been reported, particularly in patients treated for diabetic ketoacidosis (DKA). Insulin increases the intracellular transport of phosphate, which often results in hypophosphatemia during treatment of DKA. In situations in which not enough insulin is available to control blood glucose, hyperglycemia, diabetic ketoacidosis, and hyperosmolar hyperglycemic non-ketotic syndrome may occur.[Ref]


Frequency not reported: Transitory, reversible ophthalmologic refraction disorder, worsening diabetic neuropathy[Ref]

Transitory, reversible ophthalmologic refraction disorder and worsening of diabetic retinopathy has been reported with insulin initiation and glucose control intensification. Over the long-term, improved glycemic control decreases the risk for diabetic neuropathy.[Ref]


Injection site reactions including pain, redness, hives, inflammation, bruising, swelling, and itching have occurred. These usually resolve in a few days to a few weeks; rotation of the injection site reduces the risk of these reactions developing.[Ref]

Common (1% to 10%): Injection site hypertrophy
Frequency not reported: Injection site reactions[Ref]

Nervous system

Frequency not reported: Acute painful peripheral neuropathy[Ref]

Acute painful peripheral neuropathy has been reported with insulin initiation and glucose control intensification. Over the long-term, improved glycemic control decreases the risk for neuropathy.[Ref]


Frequency not reported: Weight gain[Ref]

Weight gain can occur with insulin use; it is believed to be due to the anabolic effects of insulin and the decrease in glycosuria.[Ref]


1. "Product Information. Humulin N (insulin isophane)." Lilly, Eli and Company, Indianapolis, IN.

2. Cerner Multum, Inc. "Australian Product Information." O 0

3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0

4. "Product Information. NovoLIN N (insulin isophane (NPH))." Novo Nordisk Pharmaceuticals Inc, Princeton, NJ.

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