Note: This document contains side effect information about insulin regular. Some dosage forms listed on this page may not apply to the brand name Humulin R U-500 KwikPen.

Applies to insulin regular: solution.

Serious side effects

Along with its needed effects, insulin regular (the active ingredient contained in Humulin R U-500 KwikPen) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking insulin regular:

Incidence not known

• Anxiety
• blurred vision
• chest tightness
• chills
• cold sweats
• confusion
• cool, pale skin
• cough
• decreased urine
• depression
• difficulty with swallowing
• dizziness
• dry mouth
• fast heartbeat
• flushing or redness of the skin
• headache
• hives, itching, or rash
• increased hunger
• increased thirst
• irregular heartbeat
• loss of appetite
• muscle pain or cramps
• nausea
• nightmares
• numbness or tingling in the hands, feet, or lips
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• seizures
• shakiness
• slurred speech
• sweating
• swelling
• unusual tiredness or weakness
• unusually warm skin

Other side effects

Some side effects of insulin regular may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Incidence not known

• Bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
• redistribution or accumulation of body fat

For Healthcare Professionals

Applies to insulin regular: injectable solution, intravenous solution, subcutaneous solution.

Ocular

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]

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

Dermatologic

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

Hypersensitivity

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

Postmarketing reports: Severe, life-threatening, generalized allergy, including anaphylaxis^[Ref]

Hypersensitivity reactions have included both local and systemic reactions. Anaphylaxis has been reported. Local reactions have presented as erythema, local edema, and pruritus at the injection site. Most minor reactions to insulin at the injection site resolve in a few days to a few weeks. In some instances these reactions have been caused by other factors such as irritants in a skin cleansing agent or poor injection technique. Localized reactions have been reported with metacresol, which is an excipient in many insulin products.

Generalized allergy to insulin may present as a whole body rash, dyspnea, wheezing, hypotension, tachycardia, or diaphoresis.^[Ref]

Immunologic

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]

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

Cardiovascular

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]

General

Adverse reactions reported with this insulin include hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, weight gain, and edema^[Ref]

Metabolic

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

Postmarketing reports: Weight gain^[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.

Weight gain has been reported and has been attributed to the anabolic effects of insulin and the decrease in glucosuria.^[Ref]

Local

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

Frequency not reported: Injection site reactions^[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]

Nervous system

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: Acute painful peripheral neuropathy^[Ref]

Other

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 glucosuria.^[Ref]