Humulin R
(insulin, regular, human)Humulin R Prescribing Information
HUMULIN R is indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus.
Important Administration Instructions
- Always check the insulin label before administration to confirm the correct insulin product is being used [see Warnings and Precautions ].
- Inspect HUMULIN R visually before use. It should appear clear and colorless. Do not use HUMULIN R if particulate matter or coloration is seen.
Route of Administration
Subcutaneous Injection
- Inject HUMULIN R subcutaneously approximately 30 minutes before meals into the thigh, upper arm, abdomen, or buttocks.
- Rotate injection sites within the same region from one injection to the next to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis [see Warnings and Precautions and Adverse Reactions ].
- HUMULIN R may be diluted with Sterile Diluent for HUMULIN R for subcutaneous injection ONLY under medical supervision.
- Dilute one part HUMULIN R to nine parts diluent to yield a concentration one-tenth that of HUMULIN R (equivalent to U-10).
- Dilute one part HUMULIN R to one part diluent to yield a concentration one-half that of HUMULIN R (equivalent to U-50).
- Diluted HUMULIN R may be used for 28 days when stored at 41°F (5°C) or for 14 days when stored at 86°F (30°C).
Intravenous Administration
- Administer HUMULIN R intravenously ONLY under medical supervision with close monitoring of blood glucose and potassium levels to reduce the risk of hypoglycemia and hypokalemia [see Warnings and Precautions ].
- For intravenous use, HUMULIN R should be used at concentrations from 0.1 unit/mL to 1 unit/mL in infusion systems containing 0.9% Sodium Chloride Injection.
- Intravenous infusion bags prepared with HUMULIN R are stable when stored in a refrigerator (36° to 46°F [2° to 8°C]) for 48 hours and then may be used at room temperature for up to an additional 48 hours.
Dosing Instructions
- Individualize and adjust the dosage of HUMULIN R based on the route of administration, the patient's metabolic needs, blood glucose monitoring results, and glycemic control goal.
- HUMULIN R given by subcutaneous injection should generally be used in regimens with an intermediate- or long-acting insulin.
- During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions ].
- Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (e.g., macronutrient content or timing of food intake), changes in renal or hepatic function, or during acute illness [see Warnings and Precautions , Use in Specific Populations ].
- Dosage adjustment may be needed when changing from another insulin to HUMULIN R [see Warnings and Precautions ].
Dosage Adjustment due to Drug Interactions
- Dosage adjustment may be needed when HUMULIN R is co-administered with certain drugs [see Drug Interactions ].
Instructions for Mixing with Other Insulins for Subcutaneous Injection
- Do not mix HUMULIN R with insulin preparations other than HUMULIN N.
- To mix HUMULIN R and HUMULIN N, draw HUMULIN R into the syringe first. Inject immediately after mixing.
Injection: 100 units/mL (U-100), clear and colorless solution available as:
- 10 mL multiple-dose vial
- 3 mL multiple-dose vial
Pregnancy
Risk Summary
Available data from published studies over decades have not established an association with human insulin use during pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data). There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations). Animal reproduction studies were not performed.
The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with a HbA1c >7% and has been reported to be as high as 20-25% in women with a HbA1c >10%. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Clinical Considerations
Disease-associated maternal and/or embryo/fetal risk
Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity.
Data
Human Data
While available studies cannot definitively establish the absence of risk, published data from retrospective studies, open-label, randomized, parallel studies and meta-analyses over decades have not established an association with human insulin use during pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes. All available studies have methodological limitations, including lack of blinding, unclear methods or randomization, and small sample size.
Lactation
Risk Summary
Available data from published literature suggests that exogenous human insulin products, including HUMULIN R, are transferred into human milk. There are no adverse reactions reported in breastfed infants in the literature. There are no data on the effects of exogenous human insulin products, including HUMULIN R on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for HUMULIN R and any potential adverse effects on the breastfed child from HUMULIN R or from the underlying maternal condition.
Pediatric Use
HUMULIN R is indicated to improve glycemic control in pediatric patients with diabetes mellitus.
The dosage of HUMULIN R must be individualized in pediatric patients based on metabolic needs and frequent monitoring of blood glucose to reduce the risk of hypoglycemia [see Dosage and Administration , Warnings and Precautions ].
Geriatric Use
The effect of age on the pharmacokinetics and pharmacodynamics of HUMULIN R has not been studied. Elderly patients using HUMULIN R may be at increased risk of hypoglycemia due to co-morbid disease [see Warnings and Precautions ].
Renal Impairment
The effect of renal impairment on the pharmacokinetics and pharmacodynamics of HUMULIN R has not been studied. Patients with renal impairment are at increased risk of hypoglycemia and may require more frequent HUMULIN R dose adjustment and more frequent blood glucose monitoring [see Warnings and Precautions ].
Hepatic Impairment
The effect of hepatic impairment on the pharmacokinetics and pharmacodynamics of HUMULIN R has not been studied. Patients with hepatic impairment are at increased risk of hypoglycemia and may require more frequent HUMULIN R dose adjustment and more frequent blood glucose monitoring [see Warnings and Precautions ].
HUMULIN R is contraindicated:
- during episodes of hypoglycemia [see Warnings and Precautions ]
- in patients with hypersensitivity to HUMULIN R or any of its excipients [see Warnings and Precautions ]
Never Share Needles or Syringes between Patients
Patients using HUMULIN R vials must never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.
Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen
Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) may affect glycemic control and predispose to hypoglycemia [see Warnings and Precautions ] or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to an unaffected area) has been reported to result in hypoglycemia [see Adverse Reactions ].
Make any changes to a patient's insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. For patients with type 2 diabetes, adjustments in concomitant anti-diabetic medications may be needed.
Hypoglycemia
Hypoglycemia is the most common adverse reaction of all insulins, including HUMULIN R. Severe hypoglycemia can cause seizures, may lead to unconsciousness, may be life threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place the patient and others at risk in situations where these abilities are important (e.g., driving or operating other machinery).
Hypoglycemia can happen suddenly and symptoms may differ in each patient and change over time in the same patient. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic neuropathy, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers) [see Drug Interactions ], or in patients who experience recurrent hypoglycemia.
Risk Factors for Hypoglycemia
The risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is highest when the glucose lowering effect of the insulin is maximal. As with all insulins, the glucose lowering effect time course of HUMULIN R may vary in different individuals or at different times in the same individual and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature [see Clinical Pharmacology ].
Other factors which may increase the risk of hypoglycemia include changes in meal pattern (e.g., macronutrient content or timing of meals), changes in level of physical activity, or changes to concomitant drugs [see Drug Interactions ]. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia [see Use in Specific Populations ].
Risk Mitigation Strategies for Hypoglycemia
Patients and caregivers must be educated to recognize and manage hypoglycemia. Self-monitoring of blood glucose plays an essential role in the prevention and management of hypoglycemia. In patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended.
Hypoglycemia Due to Medication Errors
Accidental mix-ups between insulin products have been reported. To avoid medication errors between HUMULIN R and other insulins, instruct patients to always check the insulin label before each injection.
Hypersensitivity Reactions
Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with HUMULIN R [see Adverse Reactions ]. If hypersensitivity reactions occur, discontinue HUMULIN R; treat per standard of care and monitor until symptoms and signs resolve. HUMULIN R is contraindicated in patients who have had a hypersensitivity reaction to HUMULIN R or its excipients.
Hypokalemia
All insulins, including HUMULIN R, cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia if indicated (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentrations).
Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists
Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention, when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients treated with insulin, including HUMULIN R, and a PPAR-gamma agonist should be observed for signs and symptoms of heart failure. If heart failure develops, it should be managed according to current standards of care, and discontinuation or dose reduction of the PPAR-gamma agonist must be considered.