Humulin R (Concentrated) U-500

Follow your doctor's directions if you miss a dose. To prevent missed doses, keep insulin on hand at all times. Get your prescription refilled before you run out of medicine completely.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Insulin overdose can cause life-threatening hypoglycemia. Symptoms include drowsiness, confusion, blurred vision, numbness or tingling in your mouth, trouble speaking, muscle weakness, clumsy or jerky movements, seizure (convulsions), or loss of consciousness.

Get emergency medical help if you have signs of insulin allergy: redness or swelling where an injection was given, itchy skin rash over the entire body, trouble breathing, fast heartbeats, feeling like you might pass out, or swelling in your tongue or throat.

Call your doctor at once if you have:

• fluid retention--weight gain, swelling in your hands or feet, feeling short of breath; or

• low potassium--leg cramps, constipation, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling, muscle weakness or limp feeling.

Common side effects may include:

• low blood sugar;

• itching, mild skin rash; or

• thickening or hollowing of the skin where you injected the medicine.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Many other medicines can affect your blood sugar, and some medicines can increase or decrease the effects of insulin. Some drugs can also cause you to have fewer symptoms of hypoglycemia, making it harder to tell when your blood sugar is low. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using. This includes prescription and over-the-counter medicines, vitamins, and herbal products.

Applies to insulin regular: injection solution

Along with its needed effects, insulin regular (the active ingredient contained in Humulin R U-500 (Concentrated)) 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:

• Anxiety
• blurred vision
• chills
• cold sweats
• confusion
• convulsions
• 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
• tightness in the chest
• unusual tiredness or weakness
• unusually warm skin

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:

• 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

Applies to insulin regular: injectable solution, subcutaneous solution

Ocular

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]

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[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[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]

Local

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]

Other

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]

Frequency not reported: Weight gain[Ref]

Some side effects of Humulin R U-500 (Concentrated) may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.