Humulin R U-500 Kwikpen

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

Applies to insulin isophane: subcutaneous suspension, subcutaneous suspension pen-injector

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of low potassium levels like muscle pain or weakness, muscle cramps, or a heartbeat that does not feel normal.
• Change in eyesight.
• A burning, numbness, or tingling feeling that is not normal.
• Very bad dizziness or passing out.
• Mood changes.
• Seizures.
• Slurred speech.
• Swelling in the arms or legs.
• Very bad irritation where the shot was given.
• Change in skin to thick or thin where the shot was given.
• Low blood sugar may occur. Signs may be dizziness, headache, feeling sleepy, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating. Call the doctor right away if any of these signs occur. Follow what you have been told to do if low blood sugar occurs. This may include taking glucose tablets, liquid glucose, or some fruit juices.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Irritation where the shot is given.
• Weight gain.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Applies to insulin isophane: subcutaneous suspension

Frequency not reported: Sodium retention and edema

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.

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).

Uncommon (0.1% to 1%): Lipodystrophy

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

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.

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

Frequency not reported: Formation of anti-insulin antibodies

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.

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

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.

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

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.

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.

Common (1% to 10%): Injection site hypertrophy

Frequency not reported: Injection site reactions

Frequency not reported: Acute painful peripheral neuropathy

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.

Frequency not reported: Weight gain

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