Humulin R U-500 Kwikpen

Last updated on RxList: 2/11/2019
Humulin R U-500 Kwikpen Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Last reviewed on RxList 2/11/2019

Humulin R U-500 (insulin human injection) is a concentrated human insulin indicated to improve glycemic control in adults and children with diabetes mellitus requiring more than 200 units of insulin per day. Common side effects of Humulin R U-500 include:

  • low blood sugar (hypoglycemia),
  • allergic reactions,
  • injection site reactions
    • bruising,
    • pain,
    • bleeding,
    • redness,
    • bumps,
    • swelling,
    • discoloration,
    • itching,
    • warmth
  • a hard lump,
  • changes in distribution of body fat (lipodystrophy),
  • itching,
  • rash,
  • weight gain, and
  • swelling of extremities

Humulin R U-500 is available as a KwikPen or multiple dose vial. The dose of Humulin R U-500 is individualized based on metabolic needs, blood glucose monitoring results and glycemic control goal. Humulin R U-500 is administered subcutaneously two or three times daily 30 minutes before a meal. Humulin R U-500 may interact with antidiabetic agents, ACE inhibitors, angiotensin II receptor blockers (ARBs), disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors (MAOIs), pentoxifylline, pramlintide, propoxyphene, salicylates, somatostatin analogs, "sulfa" drugs, atypical antipsychotics, corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens, protease inhibitors, somatropin, sympathomimetic agents, thyroid hormones, alcohol, beta-blockers, clonidine, lithium salts, pentamidine, guanethidine, and reserpine. Tell your doctor all medications and supplements you use. Tell your doctor if you are pregnant or plan to become pregnant before using Humulin R U-500; careful monitoring of glucose control is essential during pregnancy. Humulin R U-500 passes into breast milk but is not expected to harm nursing infants. Women with diabetes who are lactating may require adjustments in their insulin dose. Consult your doctor before breastfeeding.

Our Humulin R U-500 (insulin human injection), for Subcutaneous Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

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.


Diabetes is defined best as... See Answer
Humulin R U-500 Kwikpen Consumer Information

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.

Read the entire detailed patient monograph for Humulin R U-500 Kwikpen (Insulin Human Injection for Subcutaneous Use)


Diabetes: What Raises and Lowers Your Blood Sugar Level? See Slideshow
Humulin R U-500 Kwikpen Professional Information


The following adverse reactions are discussed elsewhere:

The following additional adverse reactions have been identified during post-approval use of HUMULIN R U-500. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or to establish a causal relationship to drug exposure.


Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including HUMULIN R U-500 [see WARNINGS AND PRECAUTIONS].

Allergic Reactions

Severe, life-threatening, generalized allergy, including anaphylaxis, generalized skin reactions, rash, angioedema, bronchospasm, hypotension, and shock may occur with any insulin, including HUMULIN R U-500 and may be life threatening [see WARNINGS AND PRECAUTIONS].


Long-term use of insulin, including HUMULIN R U-500, can cause lipodystrophy at the site of repeated insulin injections. Lipodystrophy includes lipohypertrophy (thickening of adipose tissue) and lipoatrophy (thinning of adipose tissue) and may affect insulin absorption. Rotate insulin injections sites within the same region to reduce the risk of lipodystrophy [see DOSAGE AND ADMINISTRATION].

Injection Site Reactions

Patients taking HUMULIN R U-500 may experience injection site reactions, including injection site hematoma, pain, hemorrhage, erythema, nodules, swelling, discoloration, pruritus, warmth, and injection site mass.

Weight Gain

Weight gain can occur with insulin therapy, including HUMULIN R U-500, and has been attributed to the anabolic effects of insulin.

Peripheral Edema

Insulin, including HUMULIN R U-500, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.


As with all therapeutic proteins, insulin administration may cause anti-insulin antibodies to form. The presence of antibodies that affect clinical efficacy may necessitate dose adjustments to correct for tendencies toward hyper- or hypoglycemia.

The incidence of antibody formation with HUMULIN R U-500 is unknown.

Read the entire FDA prescribing information for Humulin R U-500 Kwikpen (Insulin Human Injection for Subcutaneous Use)

© Humulin R U-500 Kwikpen Patient Information is supplied by Cerner Multum, Inc. and Humulin R U-500 Kwikpen Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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