Insulin Detemir

Dosage Forms & Strengths

injectable solution

• 100 units/mL (10mL vial)

prefilled syringe

• 100 units/mL (3mL FlexTouch)

Type I or II Diabetes Mellitus

Once daily dosage: Administer SC with evening meal or at bedtime

Twice daily dosage: Administer SC with morning meal and either with evening meal, at bedtime, or 12 hr after the morning dose

Initial dose

• Type 1 diabetes: Approximately one third of the total daily insulin requirements SC; rapid-acting or short-acting, premeal insulin should be used to satisfy the remainder of the daily insulin requirements; usual daily maintenance range is 0.5-1 unit/kg/day in divided doses; nonobese may require 0.4-0.6 unit/kg/day; obese may require 0.6-1.2 units/kg/day
• Type 2 diabetes inadequately controlled on oral medication: 10 units/day SC (or 0.1-0.2 unit/kg/day) in evening or divided q12hr
• Type 2 diabetes inadequately controlled on GLP-1 receptor agonist: 10 units/day SC given once daily in evening
• Subsequently adjust dose based on blood glucose measurements

Conversion from other insulins

• If converting from insulin glargine: Change can be accomplished on a unit-to-unit basis
• If converting from NPH insulin: Change can be accomplished on a unit-to-unit basis; however, some patients with type 2 diabetes may require more insulin detemir than NPH insulin
• Closely monitor blood glucose during transition and in the initial weeks thereafter; concurrent rapid-acting or short-acting insulins or other concomitant antidiabetic treatment may require dose adjustment

Dosing Considerations

Dosage of human insulin, which is always expressed in USP units, must be based on the results of blood and urine glucose tests and must be carefully individualized to optimal effect

Dose adjustments should be based on regular blood glucose testing

Adjust to achieve appropriate glucose control

Dose adjustments

• Look for consistent pattern in blood sugars for >3 days
• Same time each day: Compare blood glucose level with previous levels that occurred at that time of day
• For each time of day: Calculate blood glucose range
• Calculate median blood glucose
• Consider eating and activity patterns during the day

Rate of dose adjustments

• Adjust only 1 insulin dose at a time
• Correct hypoglycemia first
• Correct highest blood sugars next
• If all blood sugars are high (within 2.75 mmol/L [50 mg/dL]): Correct morning fasting blood glucose first
• Change insulin doses in small increments: Type 1 diabetes (1-2 U change); type 2 diabetes (resistant to diet, exercise; 2-3 U change)

Sliding scales

• Many sliding scales exist to determine exact insulin dose based on frequent blood glucose monitoring
• Commonly written for q4hr blood glucose test
• Sliding scale coverage usually begins after blood glucose >11 mmol/L (200 mg/dL)
• If coverage is needed q4hr for 24 hr, then base insulin dose is adjusted first; sliding scale doses may be adjusted upwards as well

Dosage Forms & Strengths

injectable solution

• 100 units/mL (10mL vial)

prefilled syringe

• 100 units/mL (3mL FlexTouch)

Type 1 Diabetes Mellitus

<2 years: Safety and efficacy not established

≥2 years: Approximately one-third of the total daily insulin requirements SC; rapid-acting or short-acting, premeal insulin should be used to satisfy the remainder of the daily insulin requirements; usual daily maintenance range in adolescents is ≤1.2 units/kg/day during growth spurts

Dosing Considerations

Dosage of human insulin, which is always expressed in USP units, must be based on the results of blood and urine glucose tests and must be carefully individualized to optimal effect

Conversion from other insulins

• Change from basal insulin to insulin detemir can be done on a unit-to-unit basis (then adjust to achieve glycemic targets)
• Monitor closely during growth spurts and adjust dose accordingly

LEVEMIR®
(LEV–uh-mere)
(insulin detemir [rDNA origin] injection)

Do not share your Levemir® FlexTouch® with other people, even if the needle has been changed. You may give other people a serious infection, or get a serious infection from them.

What is Levemir®?

• Levemir® is a man-made insulin that is used to control high blood sugar in adults and children with diabetes mellitus.
• Levemir® is not meant for use to treat diabetic ketoacidosis.

Who should not take Levemir®?

Do not take Levemir® if you:

• have an allergy to Levemir® or any of the ingredients in Levemir®.

Before taking Levemir®, tell your healthcare provider about all your medical conditions including, if you are:

• pregnant, planning to become pregnant, or are breastfeeding.
• taking new prescription or over-the-counter medicines, vitamins, or herbal supplements.

Before you start taking Levemir®, talk to your healthcare provider about low blood sugar and how to manage it.

How should I take Levemir®?

• Read the Instructions for Use that come with your Levemir®.
• Take Levemir®exactly as your healthcare provider tells you to.
• Know the type and strength of insulin you take. Do not change the type of insulin you take unless your healthcare provider tells you to. The amount of insulin and the best time for you to take your insulin may need to change if you take different types of insulin.
• Check your blood sugar levels. Ask your healthcare provider what your blood sugars should be and when you should check your blood sugar levels.
• Do not reuse or share your needles or syringes with other people. You may give other people a serious infection, or get a serious infection from them.
• Never inject Levemir® into a vein or muscle.

What should I avoid while taking Levemir®?

While taking Levemir® do not:

• Drive or operate heavy machinery, until you know how Levemir® affects you.
• Drink alcohol or use prescription or over-the-counter medicines that contain alcohol.

What are the possible side effects of Levemir®?

Levemir® may cause serious side effects that can lead to death, including:

Low blood sugar (hypoglycemia). Signs and symptoms that may indicate low blood sugar include:

• dizziness or light-headedness
• blurred vision
• anxiety, irritability, or mood changes
• sweating
• slurred speech
• hunger
• confusion
• shakiness
• headache
• fast heart beat

Your insulin dose may need to change because of:

• change in level of physical activity or exercise
• increased stress
• change in diet
• weight gain or loss
• illness

Other common side effects of Levemir® may include:

• Reactions at the injection site, itching, rash, serious allergic reactions (whole body reactions), skin thickening or pits at the injection site (lipodystrophy), weight gain, and swelling of your hands and feet.

Get emergency medical help if you have:

• trouble breathing, shortness of breath, fast heartbeat, swelling of your face, tongue, or throat, sweating, extreme drowsiness, dizziness, confusion.

These are not all the possible side effects of Levemir®. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of Levemir®.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask your pharmacist or healthcare provider for information about Levemir®that is written for health professionals. Do not use Levemir®for a condition for which it was not prescribed. Do not give Levemir®to other people, even if they have the same symptoms that you have. It may harm them.

What are the ingredients in Levemir®?

Active Ingredient: insulin detemir (rDNA origin)

Inactive Ingredients: zinc, m-cresol, glycerol, phenol, disodium phosphate dihydrate, sodium chloride and water for injection. Hydrochloric acid or sodium hydroxide may be added.

Patient Instructions For Use

LEVEMIR® 10 mL vial

Please read the following Instructions for use carefully before using your LEVEMIR® 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.

How should I use the LEVEMIR® 10 mL vial?

Using the 10 mL 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 LEVEMIR® insulin should be clear and colorless. The tamper-resistant cap should be in place before the first use. If the cap has been removed before your first use of the vial, or if the insulin is cloudy or colored, Do not use the insulin and return it to your pharmacy.

3. Wash your hands with soap and water.

4. If you are using a new vial, pull off the tamper-resistant cap.

Before each use, wipe the rubber stopper with an alcohol wipe.

5. Do not roll or shake the vial. Shaking the vial 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. The insulin should be used only if it is clear and colorless.

6. Pull back the plunger on your syringe until the black tip reaches the marking for the number of units you will inject.

7. Push the needle through the rubber stopper into the vial.

8. Push the plunger all the way in. This inserts 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 that you need.

10. If there are air bubbles, tap the syringe gently with your finger to raise the air bubbles to the top of the needle. Then slowly push the plunger to the correct unit marking for your dose.

11. Check to make sure you have the right dose of LEVEMIR® in the syringe.

12. Pull the syringe out of the vial.

13. Inject your LEVEMIR® right away as instructed by your healthcare provider.

How should I inject LEVEMIR® with a syringe?

If you clean your injection site with an alcohol swab, 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.

1. Pinch your skin between two fingers, push the needle into the skinfold, using a dart-like motion and push the plunger to inject the insulin under your skin. The needle will be straight in.

2. Keep the needle under your skin for at least 6 seconds to make sure you have injected all the insulin. After you pull the needle from your skin you may see a drop of Levemir® at the needle tip. This is normal and has no effect on the dose you just received.

3. If blood appears after you pull the needle from your skin, press the injection site lightly with an alcohol swab. Do not rub the area.

4. After each injection, remove the needle without recapping and dispose of it in a puncture-resistant container. Used syringes, needles, and lancets should be placed in sharps containers (such as red biohazard containers), hard plastic containers (such as detergent bottles), or metal containers (such as an empty coffee can). Such containers should be sealed and disposed of properly.

Read before first use

Instructions for Use

Levemir®
(LEV–uh-mere)

FlexTouch® Pen
(insulin detemir [rDNA origin] injection)

• Do not share your Levemir® FlexTouch® Pen with other people, even if the needle has been changed. You may give other people a serious infection, or get a serious infection from them.
• Levemir® FlexTouch® Pen (“Pen”) is a prefilled disposable pen containing 300 units of U-100 Levemir® (insulin detemir [rDNA origin] injection) insulin. You can inject from 1 to 80 units in a single injection.
• This Pen is not recommended for use by the blind or visually impaired without the assistance of a person trained in the proper use of the product.

Supplies you will need to give your Levemir® injection:

Levemir® FlexTouch® Pen

• a new NovoFine®, NovoFine® Plus, or NovoTwist® needle
• alcohol swab
• 1 sharps container for throwing away used Pens and needles. See “Disposing of used Levemir® FlexTouch® Pens and needles” at the end of these instructions.

Preparing your Levemir® FlexTouch® Pen:

• Wash your hands with soap and water.
• Before you start to prepare your injection, check the Levemir® FlexTouch® Pen label to make sure you are taking the right type of insulin. This is especially important if you take more than 1 type of insulin.
• Levemir® should look clear and colorless. Do not use Levemir® if it is thick, cloudy, or is colored.
• Do not use Levemir® past the expiration date printed on the label or 42 days after you start using the Pen.
• Always use a new needle for each injection to help ensure sterility and prevent blocked needles. Do not reuse or share your needles with other people. You may give other people a serious infection, or get a serious infection from them.

NovoFine®

Figure A

Step 1:

• Pull Pen cap straight off (See Figure B).

Figure B

Step 2:

• Check the liquid in the Pen (See Figure ). Levemir® should look clear and colorless. Do not use it if it looks cloudy or colored.

Figure C

Step 3:

• Select a new needle.
• Pull off the paper tab from the outer needle cap (See Figure D).

Figure D

Step 4:

• Push the capped needle straight onto the Pen and twist the needle on until it is tight (See Figure E).

Figure E

Step 5:

• Pull off the outer needle cap. Do not throw it away (See Figure F).

Figure F

Step 6:

• Pull off the inner needle cap and throw it away (See Figure G).

Figure G

Priming your Levemir® FlexTouch® Pen:

Step 7:

• Turn the dose selector to select 2 units (See Figure H).

Figure H

Step 8:

• Hold the Pen with the needle pointing up. Tap the top of the Pen gently a few times to let any air bubbles rise to the top (See Figure I).

Figure I

Step 9:

• Hold the Pen with the needle pointing up. Press and hold in the dose button until the dose counter shows “0”. The “0” must line up with the dose pointer.
• A drop of insulin should be seen at the needle tip (See Figure J).
  • If you do not see a drop of insulin, repeat steps 7 to 9, no more than 6 times.
  • If you still do not see a drop of insulin, change the needle and repeat steps 7 to 9.

Figure J

Selecting your dose:

Step 10:

• Turn the dose selector to select the number of units you need to inject. The dose pointer should line up with your dose (See Figure K).
  • If you select the wrong dose, you can turn the dose selector forwards or backwards to the correct dose.
  • The even numbers are printed on the dial.
  • The odd numbers are shown as lines.

Figure K

• The Levemir® FlexTouch® Pen insulin scale will show you how much insulin is left in your Pen (See Figure L).

Figure L

• To see how much insulin is left in your Levemir® FlexTouch® Pen:
  • Turn the dose selector until it stops. The dose counter will line up with the number of units of insulin that is left in your Pen. If the dose counter shows 80, there are at least 80 units left in your Pen.
  • If the dose counter shows less than 80, the number shown in the dose counter is the number of units left in your Pen.

Giving your injection:

• Inject your Levemir® exactly as your healthcare provider has shown you. Your healthcare provider should tell you if you need to pinch the skin before injecting.
• Levemir® can be injected under the skin (subcutaneously) of your stomach area (abdomen), upper legs (thighs) or upper arms.
• For each injection, change (rotate) your injection site within the area of skin that you use. Do not use the same injection site for each injection.

Step 11:

• Choose your injection site and wipe the skin with an alcohol swab. Let the injection site dry before you inject your dose (See Figure M).

Figure M

Step 12:

• Insert the needle into your skin (See Figure N).
  • Make sure you can see the dose counter. Do not cover it with your fingers, this can stop your injection. 

Figure N

Step 13:

• Press and hold down the dose button until the dose counter shows “0” (See Figure O).

Figure O

• The “0” must line up with the dose pointer. You may then hear or feel a click.
• Keep the needle in your skin after the dose counter has returned to “0” and slowly count to 6 (See Figure P).
  • When the dose counter returns to “0”, you will not get your full dose until 6 seconds later.
  • If the needle is removed before you count to 6, you may see a stream of insulin coming from the needle tip.
  • If you see a stream of insulin coming from the needle tip you will not get your full dose. If this happens you should check your blood sugar levels more often because you may need more insulin.

Figure P

Step 14:

• Pull the needle out of your skin (See Figure Q).
  • 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 swab. Do not rub the area.

Figure Q

Step 15:

• Carefully remove the needle from the Pen and throw it away (See Figure R).

Figure R

• Do not recap the needle. Recapping the needle can lead to needle stick injury.
• If you do not have a sharps container, carefully slip the needle into the outer needle cap (See Figure S). Safely remove the needle and throw it away as soon as you can.
  • Do not store the Pen with the needle attached. Storing without the needle attached helps prevent leaking, blocking of the needle, and air from entering the Pen.

Figure S

Step 16:

• Replace the Pen cap by pushing it straight on (See Figure T).

Figure T

After your injection:

• You can put your used Levemir® FlexTouch® Pen and needles in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles and Pens in your household trash.
• If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:
  • made of a heavy-duty plastic
  • can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out
  • upright and stable during use
  • leak-resistant
  • properly labeled to warn of hazardous waste inside the container
• When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. Do not reuse or share your needles or syringes with other people. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/ safesharpsdisposal.
• Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.

How should I store my Levemir® FlexTouch® Pen?

• Store unused Levemir® FlexTouch® Pens in the refrigerator at 36°F to 46°F (2°C to 8°C).
• Store the Pen you are currently using out of the refrigerator below 86°F.
• Do not freeze Levemir®. Do not use Levemir® if it has been frozen.
• Keep Levemir® away from heat or light.
• Unused Pens may be used until the expiration date printed on the label, if kept in the refrigerator.
• The Levemir® FlexTouch® Pen you are using should be thrown away after 42 days, even if it still has insulin left in it.

General Information about the safe and effective use of Levemir®.

• Keep Levemir® FlexTouch® Pens and needles out of the reach of children.
• Always use a new needle for each injection.
• Do not share your Levemir® FlexTouch® Pen or needles with other people. You may give other people a serious infection, or get a serious infection from them.

Do not take insulin detemir if:

• Your blood sugar is too low (hypoglycemia).
• You are allergic to anything in insulin detemir.

While using insulin detemir you should avoid alcohol. Alcohol, including beer and wine, may affect your blood sugar when you take insulin detemir.

You may have difficulty concentrating or reacting if you have low blood sugar (hypoglycemia). Be careful when you drive a car or operate machinery. Ask your doctor if it is alright to drive if you often have:

• low blood sugar
• decreased or no warning signs of low blood sugar

Follow your doctor's directions if you miss a dose of insulin. It is important to keep insulin detemir on hand at all times. Get your prescription refilled before you run out of medicine completely.

Insulin is a hormone that works by lowering levels of glucose (sugar) in the blood. Insulin detemir is a long-acting insulin that starts to work several hours after injection and keeps working evenly for 24 hours.

Insulin detemir is used to improve blood sugar control in adults and children with diabetes mellitus.

Insulin detemir is used to treat type 2 diabetes in adults.

Insulin detemir is also used to treat type 1 diabetes in adults and children who are at least 2 years old.

Insulin detemir may also be used for purposes not listed in this medication guide.

Usual Adult Dose for Diabetes Type 1:

Dose should be individualized based on clinical response; this basal insulin should be used in regimens with short-acting insulin

Initial dose: One-third the total daily insulin requirement subcutaneously once a day or in divided doses twice a day
-Once daily dosing should be administered with the evening meal or at bedtime; twice daily dosing should be given morning and evening; the evening dose may be given with dinner, at bedtime, or 12 hours after the morning dose
Maintenance dose: Adjust according to metabolic needs, blood glucose measurements, and glycemic goals

Conversion from Other Insulin Therapies: Insulin glargine and NPH insulin can be converted on a unit to unit basis; closely monitor blood glucose during the transition and in the initial weeks thereafter, the dose and frequency of short-acting insulin may need to be adjusted.

Comments:
-The initial total daily insulin requirement in insulin naive patients is generally 0.2 to 0.4 units of insulin per kilogram of body weight.

Use: To improve glycemic control in patients with type 1 diabetes mellitus.

Usual Adult Dose for Diabetes Type 2:

Dose should be individualized based on clinical response

-Insulin-naive: Initial dose: 10 units (or 0.1 to 0.2 units/kg) subcutaneously once a day or in divided doses twice a day
-For patients inadequately controlled on a GLP-1 receptor agonist: Initial dose: 10 units subcutaneously once a day
-Maintenance dose: Adjust according to metabolic needs, blood glucose measurements, and glycemic goals

Conversion from Other Insulin Therapies: Insulin glargine and NPH insulin can be converted on a unit to unit basis; however, some patients may require more insulin detemir than NPH insulin.

Comments:
-Once daily dosing should be administered with the evening meal or at bedtime; twice daily dosing should be given morning and evening; the evening dose may be given with dinner, at bedtime, or 12 hours after the morning dose.
-When changing treatment regimens, the dose and frequency of short-acting insulins and/or doses of any other anti-diabetic drugs may need to be adjusted.
-Closely monitor blood glucose during periods of transition and in the initial weeks thereafter.

Use: To improve glycemic control in patients with type 2 diabetes mellitus.

Usual Pediatric Dose for Diabetes Type 1:

Age: 2 years or older:
-Dose should be individualized based on clinical response; this basal insulin should be used in regimens with short-acting insulin

Initial dose: One-third the total daily insulin requirement subcutaneously once a day or in divided doses twice a day
-Once daily dosing should be administered with the evening meal or at bedtime; twice daily dosing should be given morning and evening; the evening dose may be given with dinner, at bedtime, or 12 hours after the morning dose
Maintenance dose: Adjust according to metabolic needs, blood glucose measurements, and glycemic goals

Conversion from Other Insulin Therapies: Insulin glargine and NPH insulin can be converted on a unit to unit basis; closely monitor blood glucose during the transition and in the initial weeks thereafter, the dose and frequency of short-acting insulin may need to be adjusted.

Comments:
-The initial total daily insulin requirement in insulin naive patients is generally 0.2 to 0.4 units of insulin per kilogram of body weight.

Use: To improve glycemic control in pediatric patients 2 years or older with type 1 diabetes mellitus.

Administration

Administer by sub-Q injection.1 18 Do not administer IV or IM or via insulin infusion pump.1 6 17

IV administration may cause severe hypoglycemia; prolonged duration of action dependent on sub-Q injection.a

Do not mix with any other insulin.1 6 7 17 18

Inspect visually prior to administration and use only if solution appears clear and colorless.a

Sub-Q Administration

Administer by sub-Q injection once or twice daily using a conventional insulin syringe, an injection pen (i.e., FlexPen or Innolet), or a PenFill cartridge-compatible insulin delivery device.8 18 a Use FlexPen and PenFill devices only with NovoFine needles.8 a

Consult labeling accompanying the injection device for proper assembly, administration, and care of injection pens and devices.1 8 18

Administer into thigh, abdominal wall, or upper arm.1 Follow a planned rotation of injection sites within an injection area.1

Once-daily regimen: Administer the daily dose with the evening meal or at bedtime.1 7 Has been administered once daily in the morning† in patients with type 2 diabetes mellitus.18 21

Twice-daily regimen: Administer the first dose in the morning and the second dose after the evening meal, at bedtime, or 12 hours after the morning dose.1 3 7

Dosage

Dosage of insulin detemir is expressed in terms of USP units.1 b

Individualize dosage based on blood glucose determinations to obtain optimum therapeutic effect.1 Glucose monitoring is recommended for all patients with diabetes mellitus.1

Closely monitor blood glucose concentrations during insulin initiations and transitions and in the initial weeks thereafter.1 Adjust dosage and timing of insulins and/or other concomitant antidiabetic agents as needed to achieve glycemic goals.1 18

Make any dosage change cautiously and only under medical supervision.1 If insulin therapy is changed (e.g., strength, timing of dosing, manufacturer, type, or method of administration), may require adjustments in dosage of insulin detemir or concomitant antidiabetic agents.1 2 a

May require insulin dosage adjustment if patient changes usual physical activity or meal plan, or during times of illness, emotional disturbances, or stress.1

Pediatric Patients

Children ≥6 years of age: Long duration of action; use alone as a basal insulin (e.g., insulin-naive patients) or concomitantly with a shorter-acting (“bolus”) insulin (e.g., insulin aspart, insulin human) to provide more optimal postprandial glycemic control.1 7 No specific dosage recommendations by manufacturer.a When used in a meal-related sub-Q insulin regimen, basal insulin requirements (e.g., insulin detemir) usually comprise 40–60% of the total daily insulin dosage, with the remainder given preprandially as rapid- or short-acting insulin.

Children ≥6 years of age: Initial total daily insulin dosages generally range from 0.2–1 unit/kg.

Children ≥6 years of age, from combination therapy of intermediate- or long-acting and short- or rapid-acting insulin: Initial dosage of insulin detemir is identical (unit-for-unit basis) to the dosage of the longer-acting insulin.1

Children ≥6 years of age, from basal insulin only: Initial dosage of insulin detemir is identical (unit-for-unit basis) to the dosage of the basal insulin.1

Adults

Long duration of action; use alone as a basal insulin (e.g., insulin-naive patients) or concomitantly with a shorter-acting (“bolus”) insulin (e.g., insulin aspart, insulin human) to provide more optimal postprandial glycemic control.1 7 When used in a meal-related sub-Q insulin regimen, basal insulin requirements (e.g., insulin detemir) usually comprise 40–60% of the total daily insulin dosage, with the remainder given preprandially as rapid- or short-acting insulin.

Type 1: Initial total daily insulin dosages generally range from 0.2–1 unit/kg.

Type 2, inadequately controlled on oral antidiabetic agents: Initial dosage is 0.1–0.2 units/kg once daily in the evening or 10 units once or twice daily.1

From combination therapy of intermediate- or long-acting and short- or rapid-acting insulin: Initial dosage of insulin detemir is identical (unit-for-unit basis) to the dosage of the longer-acting insulin.1

From basal insulin only: Initial dosage of insulin detemir is identical (unit-for-unit basis) to the dosage of the basal insulin.1

Some type 2 patients may require a higher dosage of insulin detemir than isophane insulin human.1 4

Special Populations

Hepatic Impairment

Dosage adjustment may be required in severe hepatic impairment (Child-Pugh grade C); carefully monitor blood glucose concentrations and adjust dosage as necessary.1 6 18 (See Hepatic Impairment under Cautions and also see Special Populations under Pharmacokinetics.)

Renal Impairment

Dosage adjustments may be required; carefully monitor blood glucose concentrations and adjust dosage as necessary.1 (See Renal Impairment under Cautions and also see Special Populations under Pharmacokinetics.)

Geriatric Patients

Conservative initial dosage, dose increments, and maintenance dosage recommended to avoid hypoglycemia.1 (See Geriatric Use under Cautions and also see Special Populations under Pharmacokinetics.)

Lactation

Dosage adjustments may be required.1 (See Specific Populations under Cautions.)

Many drugs affect glucose metabolism; if such drugs are used concomitantly, may require insulin dosage adjustment and careful monitoring.a

Specific Drugs

• Regulates glucose metabolism.a

• Binds insulin receptors to lower blood glucose by increasing cellular uptake of glucose into skeletal muscle and fat; inhibits hepatic glucose production, lipolysis and proteolysis and increases protein synthesis.a

• Longer duration of action and less intrapatient variability in blood glucose concentrations than with isophane insulin human.1 2 4 5 7 9 11

• Provide copy of manufacturer’s patient information.1

• Provide information regarding the potential risks and advantages of insulin detemir therapy.1

• Importance of strict adherence to manufacturer’s instructions regarding use and proper storage of vials and injection devices (e.g., PenFill cartridges, FlexPen, InnoLet). a

• Importance of providing instructions on safe disposal of needles.1 8

• Provide instructions regarding self-monitoring of blood glucose concentrations.a c

• Provide instructions regarding adherence to meal planning, regular physical exercise, periodic hemoglobin A1c (HbA1c) monitoring, and management of hypoglycemia and hyperglycemia.a

• Importance of changing insulin dosage with caution and only under medical supervision. a c Discuss potential for alterations in insulin requirements in special situations (e.g., illness, concomitant agents that alter glycemic control, travel, emotional disturbances, other stresses).a Discuss potential for alterations in insulin requirements as a result of changes in physical activity, missed doses, or inadvertent administration of incorrect doses.a

• Importance of administering insulin detemir either once daily with the evening meal or at bedtime; or twice daily, administered in the morning and after the evening meal, at bedtime, or 12 hours after the morning dose.1

• Importance of not mixing insulin detemir with other insulins or solutions.1 c Importance of using insulin detemir only if solution is clear and colorless with no visible particles.1

• Importance of informing clinicians of the development of skin reactions (redness, itching, or swelling) at injection site.a

• Importance of informing clinicians of the development of generalized hypersensitivity reactions (trouble with shortness of breath, whole body rash, fast heartbeat, sweating).c

• Inform patient that use of alcohol may increase risk of hypoglycemia.c

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.a c

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 c

• Importance of informing patients of other important precautionary information.1 (See Cautions.)

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Subcutaneous:

Levemir: 100 units/mL (10 mL) [contains metacresol, phenol]

Solution Pen-injector, Subcutaneous:

Levemir FlexPen: 100 units/mL (3 mL [DSC]) [contains metacresol, phenol]

Levemir FlexTouch: 100 units/mL (3 mL) [contains metacresol, phenol]

• Insulin, Long-Acting

3 to 4 hours; Peak effect: 3 to 9 hours (Plank 2005)

Time to Peak

Plasma: 6 to 8 hours

AUC and Cmax were higher by 10% and 24%, respectively, in children (6 to 12 y of age) compared with adolescents and adults.

Hypersensitivity to insulin detemir or any component of the formulation

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy

Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Beta-Blockers: May enhance the hypoglycemic effect of Insulin. Exceptions: Levobunolol; Metipranolol. Monitor therapy

DPP-IV Inhibitors: May enhance the hypoglycemic effect of Insulin. Management: Consider a decrease in insulin dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Consider therapy modification

Edetate CALCIUM Disodium: May enhance the hypoglycemic effect of Insulin. Monitor therapy

Edetate Disodium: May enhance the hypoglycemic effect of Insulin. Monitor therapy

GLP-1 Agonists: May enhance the hypoglycemic effect of Insulin. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Avoid the use of lixisenatide in patients receiving both basal insulin and a sulfonylurea. Exceptions: Liraglutide. Consider therapy modification

Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Monitor therapy

Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Liraglutide: May enhance the hypoglycemic effect of Insulin. Management: If liraglutide is used for the treatment of diabetes (Victoza), consider insulin dose reductions. The combination of liraglutide and insulin should be avoided if liraglutide is used exclusively for weight loss (Saxenda). Consider therapy modification

MAO Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Metreleptin: May enhance the hypoglycemic effect of Insulin. Management: Insulin dosage adjustments (including potentially large decreases) may be required to minimize the risk for hypoglycemia with concurrent use of metreleptin. Monitor closely. Consider therapy modification

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Pioglitazone: May enhance the adverse/toxic effect of Insulin. Specifically, the risk for hypoglycemia, fluid retention, and heart failure may be increased with this combination. Management: If insulin is combined with pioglitazone, dose reductions should be considered to reduce the risk of hypoglycemia. Monitor patients for fluid retention and signs/symptoms of heart failure. Consider therapy modification

Pramlintide: May enhance the hypoglycemic effect of Insulin. Management: Upon initiation of pramlintide, decrease mealtime insulin dose by 50% to reduce the risk of hypoglycemia. Monitor blood glucose frequently and individualize further insulin dose adjustments based on glycemic control. Consider therapy modification

Prothionamide: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Quinolone Antibiotics: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolone Antibiotics may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy

Rosiglitazone: Insulin may enhance the adverse/toxic effect of Rosiglitazone. Specifically, the risk of fluid retention, heart failure, and hypoglycemia may be increased with this combination. Avoid combination

Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

SGLT2 Inhibitors: May enhance the hypoglycemic effect of Insulin. Management: Consider a decrease in insulin dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

-Daily insulin requirements may be higher during illness, stress, pregnancy, in obese patients, trauma, during concurrent use with medications having hyperglycemic effects, or after surgery
-Daily insulin requirements may be lower with exercise, weight loss, calorie restricted diets, or during concurrent use of medications having hypoglycemic effects.

Supplemental doses may be prescribed during illness
Patients with type 2 diabetes receiving oral medications may be switched to insulin therapy temporarily.

Dosage adjustments may be required when the brand, type, or species of insulin is changed; oral antidiabetic treatment may need to be adjusted as well.

Exogenous insulins, including the newer biosynthetic insulins (i.e. aspart, detemir, glargine, glulisine, lispro) appear to be excreted into breast milk. Insulin is a protein that is inactivated if taken by mouth. If absorbed, it would be destroyed in the digestive tract of the infant. Lactation onset occurs later in women with type 1 diabetes, and there is an even greater delay in those with poor glucose control. However, once established lactation persists. Insulin requirements are generally lower in women who breastfeed, most likely due to glucose being used for milk production.

Use is considered acceptable; caution is recommended. Excreted into human milk: Yes Comments: Women who are breastfeeding may require adjustments in insulin dose and diet.