Human Insulin

FDA Drug Information • Also known as: Novolin 70/30, Novolin N, Novolin R

Brand Names: Novolin 70/30, Novolin N, Novolin R
Drug Class: Insulin [EPC]
Route: SUBCUTANEOUS
Dosage Form: INJECTION, SOLUTION
Product Type: HUMAN OTC DRUG

Description

11 DESCRIPTION Insulin isophane human is produced by recombinant DNA technology, utilizing Saccharomyces cerevisiae (baker’s yeast) as the production organism. Insulin isophane human is a suspension of crystals produced from combining human insulin and protamine sulfate under appropriate conditions for crystal formation. The amino acid sequence of insulin isophane human is identical to human insulin and has the empirical formula C 257 H 383 N 65 O 77 S 6 and a molecular weight of 5808 Da. Figure 1: Structural formula of human insulin NOVOLIN N (insulin isophane human) injectable suspension is an intermediate acting human insulin. It is a sterile, white and cloudy suspension that contains insulin isophane human suspension (NPH) for subcutaneous use. Each milliliter of Novolin N contains 100 units of insulin human, dibasic sodium phosphate (1.9 mg), glycerin (16 mg), metacresol (1.5 mg), phenol (0.65 mg), protamine sulfate (approximately 0.35 mg), zinc (33.5 mcg for the vial or 33.2 mcg for the FlexPen), and Water for Injection. Hydrochloric acid 2N and sodium hydroxide 2N may be added to adjust the pH. The pH is 7.1 to 7.5. Structural Formula Novolin R

What Is Human Insulin Used For?

1 INDICATIONS AND USAGE NOVOLIN N is indicated to improve glycemic control in adults and pediatric patients with diabetes mellitus. NOVOLIN N is an intermediate-acting human insulin indicated to improve glycemic control in adults and pediatric patients with diabetes mellitus. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION

See Full Prescribing Information for important administration instructions. ( 2.1 )

Inject subcutaneously in abdominal wall, thigh, upper arm, or buttocks and rotate injection sites to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. ( 2.1 )

Individualize and adjust dosage based on metabolic needs, blood glucose monitoring results and glycemic control goal. ( 2.2 )

Administer NOVOLIN N once or twice daily. ( 2.2 )

In patients with type 1 diabetes, NOVOLIN N should generally be used in regimens that include a short-acting insulin. ( 2.2 )

NOVOLIN N can be mixed with NOVOLIN R. ( 2.4 ) 2.1 Important Administration Instructions

Always check insulin labels before administration [see Warnings and Precautions ( 5.4 )].

NOVOLIN N is a suspension that must be resuspended immediately before use. Resuspension is easier when the insulin has reached room temperature.

To resuspend vial, roll the vial gently in your hands in a horizontal position 10 times until the suspension appears uniformly white and cloudy. Inject immediately.

To resuspend FlexPen, gently move the pen up and down 20 times so the glass ball moves from one end of the cartridge to the other until the suspension appears uniformly white and cloudy. Inject immediately.

Inspect NOVOLIN N visually before use. Do not use NOVOLIN N if discoloration or particulate matter is seen.

Administer NOVOLIN N by subcutaneous injection in the abdominal wall, thigh, upper arm, or buttocks.

Rotate the injection site 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 ( 5.2 ), Adverse Reactions ( 6 )] .

During changes to a patient’s insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions ( 5.2 )] .

Do not administer NOVOLIN N intravenously and do not use in an insulin infusion pump. 2.2 Dosage Information

Individualize and adjust the dosage of NOVOLIN N based on the individual's metabolic needs, blood glucose monitoring results and glycemic control goal.

Administer NOVOLIN N once or twice daily.

In patients with type 1 diabetes, NOVOLIN N should generally be used in regimens that include a short-acting insulin.

Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), changes in renal or hepatic function or during acute illness [see Warnings and Precautions ( 5.2 , 5.3 ) and Use in Specific Populations ( 8.6 , 8.7 )].

Dosage adjustment may be needed when switching from another insulin to NOVOLIN N [see Warnings and Precautions ( 5.2 )]. 2.3 Dosage Adjustment due to Drug Interactions

Dosage adjustment may be needed when NOVOLIN N is co-administered with certain drugs [see Drug Interactions ( 7 )] . 2.4 Instructions...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following adverse reactions are also discussed elsewhere in the labeling:

Hypoglycemia [see Warnings and Precautions ( 5.3 )]

Hypoglycemia Due to Medication Errors [see Warnings and Precautions ( 5.4 )]

Hypersensitivity Reactions [see Warnings and Precautions ( 5.5 )]

Hypokalemia [see Warnings and Precautions ( 5.6 )] Adverse Reactions from Clinical Studies or Postmarketing Reports The following additional adverse reactions have been identified during clinical studies or from postmarketing reports with use of NOVOLIN N. Because some of 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. Adverse reactions associated with insulin initiation and glucose control intensification Intensification or rapid improvement in glucose control has been associated with a transitory, reversible ophthalmologic refraction disorder, worsening of diabetic retinopathy, and acute painful peripheral neuropathy. Over the long-term, improved glycemic control decreases the risk of diabetic retinopathy and neuropathy. Hypersensitivity reactions Severe, life-threatening, generalized allergy, including anaphylaxis. Hypoglycemia Hypoglycemia is the most commonly observed adverse reaction in NOVOLIN N. Hypokalemia NOVOLIN N can cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Injection site reactions NOVOLIN N can cause local injection site reactions including redness, swelling, or itching at the site of injection. These reactions usually resolve in a few days to a few weeks, but in some occasions, may require discontinuation. Localized reactions and generalized myalgias have been reported with the use of metacresol, which is an excipient in NOVOLIN N. Lipodystrophy Administration of insulin subcutaneously, including NOVOLIN N, has resulted in lipoatrophy (depression in the skin) or lipohypertrophy (enlargement or thickening of tissue) [see Dosage and Administration ( 2.1 )] in some patients. Localized Cutaneous Amyloidosis Localized cutaneous amyloidosis at the injection site has occurred. Hyperglycemia has been reported with repeated insulin injections into areas of localized cutaneous amyloidosis; hypoglycemia has been reported with a sudden change to an unaffected injection site. Medication Errors Medication errors in which other insulins have been accidentally substituted for NOVOLIN N have been identified during postapproval use. Peripheral edema Insulins, including NOVOLIN N, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy. Weight gain Weight gain can occur with insulins including NOVOLIN N, and has been attributed to the anabolic effects of insulin and the decrease in glucosuria. Immunogenicity As with all therapeutic proteins, insulin administration may cause anti-insulin antibodies to form. The incidence of antibody formation with NOVOLIN N is unknown. Adverse reactions observed with NOVOLIN N include hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, weight gain and edema. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk Inc. at 1-800-727-6500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions

7 DRUG INTERACTIONS Table 1: Clinically Significant Drug Interactions with NOVOLIN N Drugs that May Increase the Risk of Hypoglycemia Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analog (e.g., octreotide), and sulfonamide antibiotics Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when NOVOLIN N is co-administered with these drugs. Drugs that May Decrease the Blood Glucose Lowering Effect of NOVOLIN N Drugs: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones. Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when NOVOLIN N is co-administered with these drugs. Drugs that May Increase or Decrease the Blood Glucose Lowering Effect of NOVOLIN N Drugs: Alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia. Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when NOVOLIN N is co-administered with these drugs. Drugs that May Blunt Signs and Symptoms of Hypoglycemia Drugs: Beta-blockers, clonidine, guanethidine, and reserpine Intervention: Increased frequency of glucose monitoring may be required when NOVOLIN N is co-administered with these drugs.

Drugs that Affect Glucose Metabolism: Adjustment of insulin dosage may be needed. ( 7 )

Antiadrenergic Drugs (e.g., beta-blockers, clonidine, guanethidine, and reserpine): Signs and symptoms of hypoglycemia may be reduced or absent. ( 5.3 , 7 )

Contraindications

4 CONTRAINDICATIONS NOVOLIN N is contraindicated:

During episodes of hypoglycemia [see Warnings and Precautions ( 5.3 )]

In patients who have hypersensitivity reactions to NOVOLIN N or any of its excipients [see Warnings and Precautions ( 5.5 )]

During episodes of hypoglycemia ( 4 )

Hypersensitivity to NOVOLIN N or any of its excipients ( 4 )

Pregnancy and Breastfeeding

8.1 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 HbA 1c >7 and has been reported to be as high as 20-25% in women with a HbA 1c >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 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 of randomization, and small sample size.

Overdosage

10 OVERDOSAGE Excess insulin administration may cause hypoglycemia and hypokalemia. Mild episodes of hypoglycemia usually can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or exercise may be needed. More severe episodes with coma, seizure, or neurologic impairment can be treated with intramuscular or subcutaneous glucagon or intravenous glucose. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery. Hypokalemia must be corrected appropriately [see Warnings and Precautions ( 5.3 , 5.6 )] .

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Product: 50090-6565 NDC: 50090-6565-0 3 mL in a SYRINGE, PLASTIC / 5 in a CARTON

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.