Novolin R Injection 100 Units/mL U-100 (10 ml vial)

Novolin R is a fast acting insulin called insulin regular, and is a humane derived hormone. It lowers blood glucose (sugar) levels in the treatment of diabetes. Novolin R is designed to start taking effect quicker than some other insulin's and lasts approximately 8 hours. Some veterinarians may prescribe Novolin R If your pet has been diagnosed with diabetes.

Indications

Novolin R is indicated for subcutaneous administration for the treatment of patients with diabetes mellitus, for the control of hyperglycemia. Treatment with Novolin R is as an adjunct to diet and exercise for lowering blood glucose in patients with Type 1 diabetes or in patients with Type 2 diabetes for whom oral antidiabetic therapy is inadequate.

Novolin R may be administered intravenously under proper medical supervision in a clinical setting for glycemic control.

Active Ingredients:

Insulin Human

Inactive Ingredients:

glycerol, metacresol, zinc, water for injection, hydrochloric acid and sodium hydroxide.

View Novolin R Drug Facts Sheet.

Important Administration Instructions

Always check insulin labels before administration [see Warnings and Precautions]

• Inspect NOVOLIN R visually before use. It should appear clear and colorless. Do not use NOVOLIN R if particulate matter or coloration is seen.
• Use of NOVOLIN R in insulin pumps is not recommended because of the risk of precipitation.

Route of Administration

Subcutaneous Administration

• Inject NOVOLIN R subcutaneously approximately 30 minutes prior to the start of a meal into the abdominal area, buttocks, thigh, or the upper arm.
• 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 (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)].

Intravenous Administration

• Administer NOVOLIN 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 (5.3, 5.6) and How Supplied/Storage and Handling (16.2)].
• Dilute NOVOLIN R to concentrations from 0.05 unit/mL to 1 unit/mL insulin in infusion systems using polypropylene infusion bags. NOVOLIN R is stable in infusion fluids such as 0.9% sodium chloride, 5% dextrose, or 10% dextrose with 40 mmol/L potassium chloride.

Dosage Information

• Individualize and adjust the dosage of NOVOLIN R based on route of administration, the individual's metabolic needs, blood glucose monitoring results and glycemic control goal.
• NOVOLIN R given by subcutaneous injection should generally be used in regimens that include an intermediate or long-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 R [see Warnings and Precautions (5.2)].

Contraindications

NOVOLIN R is contraindicated:

• During episodes of hypoglycemia
• In patients with hypersensitivity to NOVOLIN R or any of its excipients

Warnings & Precautions

Never Share a NOVOLIN R FlexPen or Syringe between Patients

NOVOLIN R FlexPen must never be shared between patients, even if the needle is changed. Patients using NOVOLIN 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 (5.3)] 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 (6)].

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, dosage adjustments of concomitant anti-diabetic products may be needed.

Hypoglycemia

Hypoglycemia is the most common adverse reaction of all insulins, including NOVOLIN 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 an individual 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 individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers) [see Drug Interactions (7)], 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 insulin preparations, the glucose lowering effect time course of NOVOLIN 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 (12.2)]. 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 co-administered medication [see Drug Interactions (7)]. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia [see Use in Specific Populations (8.6, 8.7)].

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 at higher risk for hypoglycemia and 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 NOVOLIN R and other insulin products have been reported. To avoid medication errors between NOVOLIN R and other insulins, instruct patients to always check the insulin label before each injection.

Hypersensitivity and Allergic Reactions

Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with NOVOLIN R. Generalized allergy to insulin may manifest as a whole body rash (including pruritus), dyspnea, wheezing, hypotension, tachycardia, or diaphoresis. If hypersensi-tivity reactions occur, discontinue NOVOLIN R; treat per standard of care and monitor until symptoms and signs resolve. NOVOLIN R is contraindicated in patients who have had hypersensitivity reactions to insulin human injection or its excipients [see Contraindications (4)].

Hypokalemia

All insulins, including NOVOLIN 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 concentration).

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.

Adverse Reactions

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

• Hypoglycemia [see Warnings and Precautions (5.3)]
• 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 R. 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 commonlyobserved adverse reaction in NOVOLIN R.

Hypokalemia

NOVOLIN R can cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia.

Injection site reactions

NOVOLIN R 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 R.

Lipodystrophy

Administration of insulin subcutaneously, including NOVOLIN R, has resulted in lipoatrophy (depression in the skin) or lipohyper-trophy (enlargement or thickening of tissue) [see Dosage and Administration (2.2)] 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 R have been identified during postapproval use.

Peripheral edema

Insulins, including NOVOLIN R, 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 insulin therapies, including NOVOLIN R, and has been attributed to the anabolic effects of insulin and the decrease in glucosuria.

Immunogenicity

As with all therapeutic peptides, insulin administration may cause anti-insulin antibodies to form. Increases in titers of anti-insulin antibodies that react with human insulin have been observed in patients treated with NOVOLIN R.

Patient Instructions For Use Novolin R

Please read the following Instructions for Use carefully before using your Novolin R 10 mL vial and each time you get a refill. You should read the instructions in this manual even if you have used an insulin 10 mL vial before. There may be new information.

Before starting, gather all of the supplies that you will need to use for preparing and giving your insulin injection.

Never re-use syringes and needles.

How should I use the Novolin R vial?

1. Check to make sure that you have the correct type of insulin. This is especially important if you use different types of insulin.
2. Look at the vial and the insulin. The insulin should be clear and colorless. The tamper-resistant cap should be in place before the first use. If the cap had been removed before your first use of the vial, or if the insulin is cloudy, colored, or contains any particles, do not use it and call Novo Nordisk at 1-800-727-6500.
3. Wash your hands with soap and water. Clean your injection site with an alcohol swab and let the injection site dry before you inject. Talk with your healthcare provider about how to rotate injection sites and how to give an injection.
4. If you are using a new vial, pull off the tamper-resistant cap. Wipe the rubber stopper with an alcohol swab.
5. Do not roll or shake the vial. Shaking right before the dose is drawn into the syringe may cause bubbles or foam. This can cause you to draw up the wrong dose of insulin.
6. Pull back the plunger on the syringe until the black tip reaches the marking for the number of units you will inject.
7. Push the needle through the rubber stopper of the vial.
8. Push the plunger all the way in to force air into the vial.
9. Turn the vial and syringe upside down and slowly pull the plunger back to a few units beyond the correct dose.
10. If there are any air bubbles, tap the syringe gently with your finger to raise the air bubbles to the top. Then slowly push the plunger to the marking for your correct dose. This process should move any air bubbles present in the syringe back into the vial.
11. Check to make sure you have the right dose of Novolin R in the syringe.
12. Pull the syringe out of the vial's rubber stopper.
13. Novolin R can be injected under the skin (subcutaneously) of your stomach area, buttocks, upper legs (thighs), or upper arms. Change (rotate) your injection sites within the area you choose for each dose to reduce your risk of getting lipodystrophy (pits in skin or thickened skin) and localized cutaneous amyloidosis (skin with lumps) at the injection sites. For each injection, change (rotate) your injection site within the area of skin that you use. Do not use the same injection site for reach injection. Do not inject where the skin has pits, is thickened, or has lumps. Do not inject where the skin is tender, bruised, scaly or hard, or into scars or damaged skin. Your healthcare provider should tell you if you need to pinch the skin before and while inserting the needle. This can vary from patient to patient so it is important to ask your healthcare provider if you did not receive instructions on pinching the skin. Insert the needle into the skin. Press the plunger of the syringe to inject the insulin. When you are finished injecting the insulin, pull the needle out of your skin. You may see a drop of Novolin R at the needle tip. This is normal and has no effect on the dose you just received. If you see blood after you take the needle out of your skin, press the injection site lightly with a piece of gauze or an alcohol wipe. Do not rub the area.
14. After your injection, do not recap the needle. Place used syringes, needles and used insulin vials in a disposable puncture-resistant sharps container, or some type of hard plastic or metal container with a screw on cap such as a detergent bottle or coffee can.
15. Ask your healthcare provider about the right way to throw away used syringes and needles. There may be state or local laws about the right way to throw away used syringes and needles. Do not throw away used needles and syringes in household trash or recycle.

How should I mix Novolin R with NPH insulin?

Different insulins should be mixed only under instruction from a healthcare provider. Do not mix Novolin R with any other type of insulin except NPH insulin. Novolin R should be mixed with NPH insulin right before use. When you are mixing Novolin R insulin with NPH insulin, always draw the Novolin R (clear) insulin into the syringe first.

1. Add together the total number of units of NPH and Novolin R that you need to inject. Your total dose of medicine to inject will be the amount of NPH and Novolin R in the syringe after drawing up both insulins. For example, if you need 5 units of NPH and 2 units of Novolin R, the total dose of insulin in the syringe would be 7 units.

Preparing your NPH and Novolin® R insulins for injection:

2. Roll the NPH vial between your hands until all of the liquid in the vial is cloudy.
3. Pull the plunger of the syringe down so that the dark end is lined up to the number of units needed for your NPH insulin. This will draw into the syringe the same amount of air as the NPH dose needed.
4. Put the needle through the rubber stopper of the cloudy NPH insulin bottle. After you inject the air into the NPH vial, remove the needle from the vial but do not withdraw any of the NPH insulin. Putting air in the bottle makes it easier to draw the insulin out of the bottle.
5. Pull the plunger of the syringe down to the number of units needed for your Novolin R insulin. After you draw the air into the syringe, inject the air into the Novolin R vial.

Drawing up and mixing your NPH and Novolin R insulins for injection:

6. With the needle in place, turn the clear insulin vial of Novolin R upside down and slowly pull the plunger back to a few units beyond the right dose of Novolin R. The tip of the needle must be in the Novolin R liquid to get the full dose and not an air dose.
7. Check the syringe for air bubbles. If you see air bubbles, tap the syringe gently with your finger to raise the air bubbles to the top. Then slowly push the plunger to the marking for your correct dose. This process should move any air bubbles in the syringe back into the vial.
8. After withdrawing the needle from the Novolin R vial, insert the needle into the NPH vial.
9. Turn the NPH vial upside down with the syringe and needle still in the vial. Slowly pull the plunger back to withdraw your NPH dose.

Remember the total dose of medicine in the syringe should be your total dose of NPH and Novolin R insulins. (See Step 1 under "How should I mix Novolin R with NPH insulin?")

10. Inject your insulin right away otherwise it might not work properly.

How should I store Novolin R?

• Do not freeze Novolin R. Do not use Novolin R if it has been frozen.
• Keep Novolin R away from heat or light.
• All unopened vials
• Store unopened Novolin R vials in the refrigerator at 36°F to 46°F (2°C to 8°C).
• Unopened vials may be used until the expiration date printed on the label, if they have been stored in the refrigerator.
• Unopened vials should be thrown away after 42 days, if they are stored at room temperature below 77°F (25°C).
• After vials have been opened
• Opened Novolin R vials can be stored at room temperature below 77°F (25°C). Do not refrigerate.
• Throw away all opened Novolin R vials after 42 days, even if they still have insulin left in them.

This Patient Instructions for Use has been approved by the Food and Drug Administration.