April 29, 2016
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Novolin R

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Novolin R




Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Administration

Subcutaneous injection of Novolin R should be followed by a meal. Patients should wait approximately 30 minutes after injection before starting the meal [see DOSAGE AND ADMINISTRATION].

Any change of insulin dose should be made cautiously and only under medical supervision. Changing from one insulin product to another or changing the insulin strength may result in the need for a change in dosage. As with all insulin preparations, the time course of Novolin R action may vary in different individuals or at different times in the same individual and is dependent on many conditions, including dosage, the site of injection, local blood supply, temperature, and physical activity. Patients who change their level of physical activity or meal plan may require adjustment of insulin dosages. Insulin requirements may be altered during illness, emotional disturbances, or other stresses.

Hypoglycemia

Hypoglycemia is the most common adverse reaction of all insulin therapies, including Novolin R. Severe hypoglycemia may lead to unconsciousness, convulsions, temporary or permanent impairment of brain function or death. Severe hypoglycemia requiring the assistance of another person, parenteral glucose infusion, and glucagon administration has been observed in clinical trials with insulin, including trials with Novolin R.

The timing of hypoglycemia usually reflects the time-action profile of the administered insulin formulations [see CLINICAL PHARMACOLOGY]. Other factors such as changes in food intake (e.g., amount of food or timing of meals), injection site, exercise, and concomitant medications may also alter the risk of hypoglycemia [see DRUG INTERACTIONS]. As with all insulins, use caution in patients with hypoglycemia unawareness and in patients who may be predisposed to hypoglycemia (e.g., patients who are fasting or have erratic food intake, pediatric patients, and the elderly). The patient's ability to concentrate and react may be impaired as a result of hypoglycemia. This may present a risk in situations where these abilities are especially important, such as driving or operating other machinery.

Rapid changes in serum glucose concentrations may induce symptoms of hypoglycemia in patients with diabetes, regardless of the glucose value. Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions, such as longstanding diabetes, diabetic neuropathy, use of medications such as beta-blockers, or intensified glycemic control [see DRUG INTERACTIONS]. These situations may result in severe hypoglycemia (and, possibly, loss of consciousness) prior to the patient's awareness of hypoglycemia. Intravenously administered insulin has a more rapid onset of action than subcutaneously administered insulin, requiring more close monitoring for hypoglycemia.

Hypokalemia

All insulins, including Novolin R, cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia that, if left untreated, may cause respiratory paralysis, ventricular arrhythmia, and death. Use caution in patients who may be at risk for hypokalemia (e.g., patients using potassium-lowering medications and patients taking medications sensitive to serum potassium concentrations). Monitor glucose and potassium frequently when Novolin R is administered intravenously.

Hyperglycemia, Diabetic Ketoacidosis, And Hyperosmolar Hyperglycemic Non-Ketotic Syndrome

Hyperglycemia, diabetic ketoacidosis, or hyperosmolar hyperglycemic non-ketotic syndrome may develop in patients who take less insulin than needed to control blood glucose. These conditions can be precipitated by illness, infection, dietary indiscretion, or omission or improper administration of the prescribed insulin dose.

Renal Or Hepatic Impairment

As with other insulins, the dose requirements for Novolin R may be reduced in patients with renal or hepatic impairment.

Hypersensitivity And Allergic Reactions

Local Reactions

As with other insulins, patients may experience redness, swelling, or itching at the site of injection of Novolin R. These reactions usually resolve in a few days to a few weeks, but in some occasions, may require discontinuation of Novolin R. In some instances, these reactions may be related to factors other than insulin, such as irritants in a skin cleansing agent or poor injection technique. Localized reactions and generalized myalgias have been reported with the use of metacresol, which is an excipient in Novolin R.

Systemic Reactions

Severe, life-threatening, generalized allergy, including anaphylaxis may occur with any insulin, including Novolin R. Generalized allergy to insulin may manifest as a whole body rash (including pruritus), dyspnea, wheezing, hypotension, tachycardia, or diaphoresis.

Mixing Of Insulins

If Novolin R is mixed with NPH human insulin, Novolin R should be drawn into the syringe first and the mixture should be injected immediately after mixing. Insulin mixtures should not be administered intravenously.

Antibody Production

Increases in titers of anti-insulin antibodies that react with human insulin have been observed in patients treated with Novolin R. Data from a 12-month controlled trial in patients with type 1 diabetes suggest that the increase in these antibodies is transient. The clinical significance of these antibodies is not known but does not appear to cause deterioration in glycemic control or necessitate increases in insulin dose.

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, particularly when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients treated with insulin, including NOVOLIN 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.

Patient Counseling Information

See FDA-Approved Patient Labeling (Patient Information and Instructions for Use)

Instructions For All Patients

Maintenance of normal or near-normal glucose control is a treatment goal in diabetes mellitus and has been associated with a reduction in some diabetic complications. Patients should be informed about potential risks and benefits of Novolin R therapy including possible adverse reactions. Patients should also be offered continued education and advice on insulin therapies, injection technique, lifestyle management, regular glucose monitoring, periodic glycosylated hemoglobin testing, recognition and management of hypo-and hyperglycemia, adherence to meal planning, complications of insulin therapy, timing of dose, instruction in the use of injection devices, and proper storage of insulin. Patients should be informed that frequent, patient-performed blood glucose measurements are needed to achieve optimal glycemic control and avoid both hyper-and hypoglycemia.

The patient's ability to concentrate and react may be impaired as a result of hypoglycemia. This may present a risk in situations where these abilities are especially important, such as driving or operating other machinery. Patients who have frequent hypoglycemia or reduced or absent warning signs of hypoglycemia should be advised to use caution when driving or operating machinery. Female patients should be advised to tell their physician if they intend to become, or if they become pregnant.

Patients should be instructed to always carefully check that they are administering the correct insulin to avoid medication errors between Novolin R and other insulins. Patients should check the label for the drug name Novolin R, the enlarged R letter, and the blue horizontal bar. If a prescription for Novolin R is needed, it should be written clearly to avoid confusion with other insulin products.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Standard 2-year carcinogenicity studies in animals have not been performed to evaluate the carcinogenic potential of Novolin R.

Novolin R is not mutagenic in the following in vitro tests: The chromosomal aberration assay in human lymphocytes, the micronucleus assay in mouse polychromatic erythrocytes, and the mutation frequency assay in Chinese hamster cells.

Standard reproduction and teratology studies in animals, including fertility assessments have not been conducted with Novolin R.

Use In Specific Populations

Pregnancy

Pregnancy Category B: All pregnancies have a background risk of birth defects, loss, or other adverse outcome regardless of drug exposure. This background risk is increased in pregnancies complicated by hyperglycemia and may be decreased with good glycemic control. It is essential for patients with diabetes or a history of gestational diabetes to maintain good glycemic control before conception and throughout pregnancy. Insulin requirements may decrease during the first trimester, generally increase during the second and third trimesters, and rapidly decline after delivery. Careful monitoring of glucose control is important during pregnancy in patients with diabetes. Therefore, women should be advised to tell their healthcare provider if they intend to become, or if they become, pregnant while taking Novolin R.

No reproductive toxicity studies have been performed with Novolin R.

Nursing Mothers

It is unknown whether Novolin R is excreted in breast milk. Small amounts of human insulin are secreted into breast milk, the significance of which is not known. Use of Novolin R is compatible with breastfeeding, but insulin doses may need to be adjusted because lactation can reduce insulin requirements.

Pediatric Use

The safety and effectiveness of subcutaneous injections of Novolin R have been established in pediatric patients (ages 2 to18 years) with type 1 diabetes [see Clinical Studies]. Novolin R has not been studied in pediatric patients younger than 2 years of age. Novolin R has not been studied in pediatric patients with type 2 diabetes.

In general, pediatric patients with type 1 diabetes are more susceptible to hypoglycemia than adult patients with type 1 diabetes. As in adults, the dosage of Novolin R must be individualized in pediatric patients based on metabolic needs and frequent monitoring of blood glucose [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].

Geriatric Use

In 3 controlled clinical trials 18 of 1285 patients (1.4%) with type 1 diabetes treated with Novolin R and insulin aspart were ≥ 65 years of age. In 4 controlled clinical trials 151 of 635 patients (24%) with type 2 diabetes were ≥ 65 years of age. Therefore, conclusions are limited regarding the efficacy and safety of Novolin R in patients ≥ 65 years of age, particularly in patients with type 1 diabetes. Pharmacokinetic/pharmacodynamic studies to assess the effect of age on Novolin R have not been performed.

Use caution in patients with advanced age, due to the potential for decreased renal function in this population [see WARNINGS AND PRECAUTIONS].

This monograph has been modified to include the generic and brand name in many instances.

Last reviewed on RxList: 2/23/2016

Warnings
Precautions

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