How to Switch Between Insulin Products
How to Switch Between Insulin Products
How to Switch Between Insulin Products
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Detail-Document #251005<br />
−This Detail-Document accompanies the related article published in−<br />
PHARMACIST’S LETTER / PRESCRIBER’S LETTER<br />
Oc<strong>to</strong>ber 2009 ~ Volume 25 ~ Number 251005<br />
<strong>How</strong> <strong>to</strong> <strong>Switch</strong> <strong>Between</strong> <strong>Insulin</strong> <strong>Products</strong><br />
<strong>Switch</strong>ing insulins should always be done with prescriber approval and close moni<strong>to</strong>ring. Advise patients <strong>to</strong> closely moni<strong>to</strong>r blood glucose levels<br />
after switching insulins. If switching between human insulin brands (e.g., Humulin R <strong>to</strong> Novolin R, Humulin N <strong>to</strong> Novolin N, or Humulin R/N or<br />
Novolin R/N <strong>to</strong> “s<strong>to</strong>re brand” R/N), keep the number of units each day the same. <strong>How</strong>ever, because these brands are not AB rated you may need <strong>to</strong><br />
contact the prescriber for approval <strong>to</strong> switch between brands. See our Comparison of <strong>Insulin</strong>s chart for meal timing, onset, peak, duration of action,<br />
and other information. Also see our algorithm Initiation and Adjustment of <strong>Insulin</strong> Regimens for Type 2 Diabetes.<br />
NPH <strong>to</strong> Long-acting<br />
NPH <strong>to</strong> insulin detemir (Levemir)<br />
Clinical Scenario Recommendation/Comments<br />
• Convert unit-per-unit. 1<br />
• Some patients on basal-bolus insulin may require more Levemir<br />
than NPH. 1<br />
• Give Levemir once daily, or divided twice daily if necessary for<br />
control. 1<br />
• Do not mix Levemir with other insulins. 1<br />
NPH <strong>to</strong> insulin glargine (Lantus) • NPH once daily: convert unit-per-unit and give once daily. 2<br />
• NPH twice daily: reduce daily dose by 20% and give once<br />
daily. 2<br />
• Do not mix Lantus with other insulins. 2<br />
Long-acting <strong>to</strong> NPH<br />
<strong>Insulin</strong> detemir (Levemir) <strong>to</strong> NPH • Convert unit-per-unit. 3<br />
• Give NPH at bedtime or split twice daily (e.g., 50:50 or 2/3 in<br />
AM and 1/3 before dinner or at bedtime). 3,4,5<br />
<strong>Insulin</strong> glargine (Lantus) <strong>to</strong> NPH • Convert unit-per-unit. 3<br />
• Give NPH at bedtime or split twice daily (e.g., 50:50 or 2/3 in<br />
AM and 1/3 before dinner or at bedtime). 3,4,5<br />
Copyright © 2009 by Therapeutic Research Center<br />
Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, S<strong>to</strong>ck<strong>to</strong>n, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249<br />
www.pharmacistsletter.com ~ www.prescribersletter.com<br />
More. . .
Long-acting <strong>to</strong> long-acting<br />
<strong>Insulin</strong> detemir (Levemir) <strong>to</strong> insulin glargine (Lantus)<br />
<strong>Insulin</strong> glargine (Lantus) <strong>to</strong> insulin detemir (Levemir)<br />
Clinical Scenario Recommendation/Comments<br />
Regular <strong>to</strong> rapid-acting<br />
Regular human insulin (Humulin, Novolin) <strong>to</strong> rapid-acting insulin analog<br />
(insulin aspart [Novolog], insulin glulisine [Apidra], insulin lispro<br />
[Humalog])<br />
Rapid-acting <strong>to</strong> regular<br />
<strong>Insulin</strong> aspart (Novolog), insulin glulisine (Apidra), or insulin lispro<br />
(Humalog) <strong>to</strong> regular human insulin (Humulin, Novolin)<br />
Rapid-acting <strong>to</strong> rapid-acting<br />
<strong>Insulin</strong> aspart (Novolog), insulin glulisine (Apidra) or insulin lispro<br />
(Humalog) <strong>to</strong> <strong>Insulin</strong> aspart (Novolog), insulin glulisine (Apidra) or<br />
insulin lispro (Humalog)<br />
More. . .<br />
Copyright © 2009 by Therapeutic Research Center<br />
Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, S<strong>to</strong>ck<strong>to</strong>n, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249<br />
www.pharmacistsletter.com ~ www.prescribersletter.com<br />
(Detail-Document #251005: Page 2 of 4)<br />
• Convert unit-per-unit. 2<br />
• Give once daily, or divided twice daily if necessary for control. 15<br />
• Do not mix Lantus with other insulins. 2<br />
• Convert unit-per-unit. 1,6<br />
• Give once daily, or divided twice daily if necessary for control. 1<br />
• A higher daily dose may be needed, especially if divided twice<br />
daily. 14<br />
• Do not mix Levemir with other insulins. 1<br />
• Convert unit-per-unit. 3,7,8,9<br />
• Rapid-acting insulin analogs have a faster onset of action and a<br />
shorter duration of action than human regular insulin. Give rapid<br />
acting insulin analogs about 10 minutes before meals or with<br />
meals. See Comparison of <strong>Insulin</strong>s for specifics of meal<br />
timing. 10<br />
• Convert unit-per-unit. 3,7,8,9<br />
• Rapid-acting insulin analogs have a faster onset of action and a<br />
shorter duration of action than human regular insulin. Give<br />
regular insulin about 30 minutes before meals. See Comparison<br />
of <strong>Insulin</strong>s for specifics of meal timing. 10<br />
• Convert unit-per-unit. 3,7,8,9,11<br />
• Give rapid-acting insulin analogs about 10 minutes before meals<br />
or with meals. See Comparison of <strong>Insulin</strong>s for specifics of meal<br />
timing. 10
Clinical Scenario Recommendation/Comments<br />
Premixed <strong>to</strong> premixed<br />
Premixed NPH/regular insulin (Humulin 70/30, Novolin 70/30) <strong>to</strong><br />
Premixed protamine/rapid-acting analog (insulin lispro protamine/insulin<br />
lispro [Humalog Mix 75/25], insulin aspart protamine/insulin aspart<br />
[Novolog Mix70/30])<br />
Premixed protamine/rapid-acting analog (insulin lispro protamine/insulin<br />
lispro [Humalog Mix 75/25], insulin aspart protamine/insulin aspart<br />
[Novolog Mix70/30]) <strong>to</strong> premixed NPH/regular insulin (Humulin 70/30,<br />
Novolin 70/30)<br />
Premixed NPH/regular insulin (Humulin 50/50) <strong>to</strong> insulin lispro/insulin<br />
lispro protamine (Humalog Mix 50/50)<br />
More. . .<br />
Copyright © 2009 by Therapeutic Research Center<br />
Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, S<strong>to</strong>ck<strong>to</strong>n, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249<br />
www.pharmacistsletter.com ~ www.prescribersletter.com<br />
(Detail-Document #251005: Page 3 of 4)<br />
• Convert unit-per-unit. 3,12,13<br />
• Premixed insulin analogs have a faster onset of action but similar<br />
duration of action compared <strong>to</strong> human premixed insulin. Give<br />
insulin analogs about 10 minutes before meals or with meals. See<br />
Comparison of <strong>Insulin</strong>s for specifics of meal timing. 10<br />
• Convert unit-per-unit. 3,12,13<br />
• Premixed insulin analogs have a faster onset of action but similar<br />
duration of action compared <strong>to</strong> human premixed insulin. Give<br />
human premixed insulins (Humulin 70/30, Novolin 70/30) about<br />
30 minutes before meals. See Comparison of <strong>Insulin</strong>s for<br />
specifics of meal timing. 10<br />
• Convert unit-per-unit. 1<br />
• Give Humalog 50/50 about 10 minutes before meals or with<br />
meals. See Comparison of <strong>Insulin</strong>s for specifics of meal timing. 10<br />
• Humulin 50/50 insulin is being discontinued due <strong>to</strong> declining<br />
usage. Humulin 50/50 insulin is expected <strong>to</strong> be unavailable as of<br />
April 2010 (see http://www.humalog.com/pdf/humulindiscontinued.pdf).<br />
Users of this document are cautioned <strong>to</strong> use their own professional judgment and consult any other necessary or appropriate sources prior <strong>to</strong> making clinical<br />
judgments based on the content of this document. Our edi<strong>to</strong>rs have researched the information with input from experts, government agencies, and national<br />
organizations. Information and Internet links in this article were current as of the date of publication.
Project Leader in preparation of this Detail-<br />
Document: Melanie Cupp, Pharm.D., BCPS<br />
References<br />
1. Product information for Levemir. Novo Nordisk Inc.<br />
Prince<strong>to</strong>n, NJ 08540. May 2007.<br />
2. Product information for Lantus. Sanofi-Aventis U.S.<br />
LLC. Bridgewater, NJ 08807. March 2007.<br />
3. U.S. Food and Drug Administration. Information<br />
regarding insulin s<strong>to</strong>rage and switching between<br />
products in an emergency.<br />
http://www.fda.gov/Drugs/EmergencyPreparedness/<br />
ucm085213.htm. (Accessed September 7, 2009).<br />
4. Carlise BA, Kroon LA, Koda-Kimble MA. Diabetes<br />
mellitus. In: Koda-Kimble MA, Young LY, Kradjan<br />
WA, Guglielmo BJ, edi<strong>to</strong>rs. Applied therapeutics:<br />
the clinical use of drugs. 8 th edition. Philadelphia,<br />
PA: Lippincott Williams & Wilkins; 2005.<br />
5. American College of Physicians Diabetes Care<br />
Guide.<br />
http://diabetes.acponline.org/cus<strong>to</strong>m_resources/ACP<br />
_DiabetesCareGuide_Ch08.pdf?dbp. (Accessed<br />
September 9, 2009).<br />
6. Hall DL, Drab SR, Havrilla PL. Advances in diabetes<br />
therapy: rapid and long-acting insulin analogs. Drug<br />
Topics continuing education. September 28, 2006.<br />
http://drug<strong>to</strong>pics.modernmedicine.com/drug<strong>to</strong>pics/dat<br />
a/articlestandard/drug<strong>to</strong>pics/402006/376897/article.<br />
pdf (Accessed September 7, 2009).<br />
(Detail-Document #251005: Page 4 of 4)<br />
7. Product information for Humalog. Eli Lilly and<br />
Company. Indianapolis, IN 46285. March 2009.<br />
8. Product information for Apidra. Sanofi-Aventis U.S.<br />
LLC. Bridgewater, NJ 08807. February 2009.<br />
9. Product information for Novolog. Novo Nordisk Inc.<br />
Prince<strong>to</strong>n, NJ 08540. July 2009.<br />
10. Comparison of insulins. Pharmacist's<br />
Letter/Prescriber's Letter 2006;22(9):220910.<br />
11. United States Department of Veterans Affairs.<br />
Pharmacy Benefits Management Services.<br />
Recommendations for converting from insulin lispro<br />
<strong>to</strong> insulin aspart. January 2005.<br />
http://www.pbm.va.gov/Clinical%20Guidance/Therap<br />
eutic%20Interchange%20Guidance/<strong>Insulin</strong>%20lispro<br />
%20<strong>to</strong>%20<strong>Insulin</strong>%20aspart%20conversion.pdf<br />
(Accessed September 7, 2009).<br />
12. Product information for Novolog Mix 70/30. Novo<br />
Nordisk Inc. Prince<strong>to</strong>n, NJ 08540. March 2008.<br />
13. Product information for Humalog Mix 75/25. Eli Lilly<br />
and Company. Indianapolis, IN 46285. March 2009.<br />
14. Rosens<strong>to</strong>ck J, Davies M, Home PD, et al. A<br />
randomized, 52-week, treat-<strong>to</strong>-target trial comparing<br />
insulin detemir with insulin glargine when<br />
administered as add-on <strong>to</strong> glucose-lowering drugs in<br />
insulin-naïve people with type 2 diabetes.<br />
Diabe<strong>to</strong>logia 2008;51:408-16.<br />
15. DeVries JH, Nattrass M, Pieber TR. Refining basal<br />
insulin therapy: what have we learned in the age of<br />
analogues? Diabetes Metab Res Rev 2007;23:441-<br />
54.<br />
Cite this Detail-Document as follows: <strong>How</strong> <strong>to</strong> switch between insulin products. Pharmacist’s Letter/Prescriber’s<br />
Letter 2009;25(10):251005.<br />
Evidence and Advice You Can Trust…<br />
3120 West March Lane, P.O. Box 8190, S<strong>to</strong>ck<strong>to</strong>n, CA 95208 ~ TEL (209) 472-2240 ~ FAX (209) 472-2249<br />
Copyright © 2009 by Therapeutic Research Center<br />
Subscribers <strong>to</strong> Pharmacist’s Letter and Prescriber’s Letter can get Detail-Documents, like this one, on any<br />
<strong>to</strong>pic covered in any issue by going <strong>to</strong> www.pharmacistsletter.com or www.prescribersletter.com
Detail-Document #241101<br />
−This Detail-Document accompanies the related article published in−<br />
PHARMACIST’S LETTER / PRESCRIBER’S LETTER<br />
November 2008 ~ Volume 24 ~ Number 241101<br />
Initiation and Adjustment of <strong>Insulin</strong> Regimens for Type 2 Diabetes 1,2,3<br />
Note: <strong>Insulin</strong> therapy should be individualized according <strong>to</strong> blood sugar values, A1c, diet, medications, lifestyle, etc.<br />
Diagnosis of Type 2 Diabetes<br />
A1c > 7% (eAG > 154 mg/dL)<br />
Assess current therapy<br />
Lifestyle change Monotherapy usually with metformin<br />
Metformin Add sulfonylurea if A1c < 8.5%, add insulin if A1c > 8.5%<br />
Combination oral therapy** Failure <strong>to</strong> control blood sugar*<br />
Motivated patient<br />
Willing <strong>to</strong> frequently moni<strong>to</strong>r High fasting, high postprandial glucose<br />
blood sugars<br />
Start/intensify insulin therapy<br />
Oral medications controlling<br />
postprandial glucose, but high fasting<br />
glucose. Good for timid insulin users.<br />
Premixed insulin daily or BID (doses harder<br />
Basal insulin with rapid-acting<br />
<strong>to</strong> adjust since fixed combination)<br />
Basal insulin (intermediate<br />
mealtime insulin (~4 doses/day) or long-acting) once daily<br />
• Example of initial insulin regimen<br />
o 10 units NPH or 0.2 units/kg at bedtime<br />
Failure <strong>to</strong> control blood sugar*<br />
o 10 units glargine or 0.2 units/kg once daily<br />
o<br />
o<br />
10 units detemir or 0.2 units/kg once daily<br />
10 units mealtime premixed insulin once or twice daily<br />
(prebreakfast and/or predinner)<br />
Once daily basal insulin with rapid-acting<br />
mealtime insulin<br />
• Twice daily provides better glucose control in most patients<br />
• Pioglitazone or exenatide + metformin in select patients** 3<br />
• Rosiglitazone NOT recommended 3<br />
• Consider insulin as initial therapy in severe hyperglycemia<br />
(plasma glucose levels >250 mg/dL), random glucose levels<br />
consistently >300 mg/dL, or an A1c >10%)<br />
• Failure <strong>to</strong> control blood sugar*=A1c>7%, eAG>154 mg/dL<br />
• S<strong>to</strong>p sulfonylurea, pioglit, or exenatide when start insulin 3<br />
Failure <strong>to</strong> control blood sugar*<br />
Add rapid-acting insulin before meals where postprandial<br />
hyperglycemia occurs OR premixed insulin daily or BID<br />
Failure <strong>to</strong> control blood sugar*<br />
Copyright © 2008 by Therapeutic Research Center<br />
Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, S<strong>to</strong>ck<strong>to</strong>n, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249<br />
www.pharmacistsletter.com ~ www.prescribersletter.com<br />
Types of <strong>Insulin</strong><br />
Rapid-acting insulin: lispro<br />
(Humalog), aspart (NovoLog),<br />
glulisine (Apidra)<br />
Regular short-acting insulin:<br />
Humulin R, Novolin R<br />
Intermediate-acting (basal) insulin:<br />
NPH (Humulin N, Novolin N)<br />
Long-acting (basal) insulin:<br />
glargine (Lantus),<br />
detemir (Levemir)<br />
Premixed insulin:<br />
Rapid acting: NovoLog Mix 70/30,<br />
Humalog Mix75/25 or 50/50<br />
Short-acting: Humulin 70/30 or 50/50<br />
Novolin 70/30<br />
More. . .
Users of this document are cautioned <strong>to</strong> use their own<br />
professional judgment and consult any other necessary<br />
or appropriate sources prior <strong>to</strong> making clinical<br />
judgments based on the content of this document. Our<br />
edi<strong>to</strong>rs have researched the information with input from<br />
experts, government agencies, and national<br />
organizations. Information and Internet links in this<br />
article were current as of the date of publication.<br />
Project Leader in preparation of this Detail-<br />
Document: Neeta Bahal O’Mara, Pharm.D., BCPS<br />
(Detail-Document #241101: Page 2 of 2)<br />
References<br />
1. Hirsch IB, Bergenstal RM, Parkin CG, et al. A realworld<br />
approach <strong>to</strong> insulin therapy in primary care<br />
practice. Clin Diabetes 2005;23:78-86.<br />
2. Nathan DM, Buse JB, Davidson MB, et al.<br />
Management of hyperglycemia in type 2 diabetes: a<br />
consensus algorithm for the initiation and adjustment<br />
of therapy. Diabetes Care 2006;29:1963-72.<br />
3. Nathan DM, Buse JB, Davidson MB, et al.<br />
Management of hyperglycemia in type 2 diabetes: A<br />
consensus algorithm for the initiation and adjustment<br />
of therapy. Diabetes Care (Dec) 2008;31:1-11.<br />
Cite this Detail-Document as follows: <strong>Insulin</strong> use in patients with type 2 diabetes. Pharmacist’s Letter/Prescriber’s<br />
Letter 2008;24(11):241101.<br />
Evidence and Advice You Can Trust…<br />
3120 West March Lane, P.O. Box 8190, S<strong>to</strong>ck<strong>to</strong>n, CA 95208 ~ TEL (209) 472-2240 ~ FAX (209) 472-2249<br />
Copyright © 2008 by Therapeutic Research Center<br />
Subscribers <strong>to</strong> Pharmacist’s Letter and Prescriber’s Letter can get Detail-Documents, like this one, on any<br />
<strong>to</strong>pic covered in any issue by going <strong>to</strong> www.pharmacistsletter.com or www.prescribersletter.com
Rapid-acting<br />
Detail-Document #220910<br />
−This Detail-Document accompanies the related article published in−<br />
PHARMACIST’S LETTER / PRESCRIBER’S LETTER<br />
September 2006 ~ Volume 22 ~ Number 220910<br />
Comparison of <strong>Insulin</strong>s<br />
―Based on U.S. product information―(Last modified December 2008)<br />
—Information for the non-insulin agents, Byetta and Symlin, is located at the end of the chart—<br />
<strong>Insulin</strong> Lispro Solution <strong>Insulin</strong> Aspart Solution <strong>Insulin</strong> Glulisine<br />
Brand, Maker Humalog 19 Eli Lilly NovoLog, 20 Novo Nordisk Apidra, 21,30 Aventis<br />
Availability All are prescription.<br />
Description Human insulin analog (rDNA)<br />
Onset 16 15 <strong>to</strong> 30 minutes 10 <strong>to</strong> 20 minutes 10 <strong>to</strong> 15 minutes 22<br />
Peak 16 30 minutes <strong>to</strong> 2.5 hours 1 <strong>to</strong> 3 hours 1 <strong>to</strong> 1.5 hours 22<br />
Duration 16 3 <strong>to</strong> 6.5 hours 3 <strong>to</strong> 5 hours 3 <strong>to</strong> 5 hours 22<br />
Administration FDA-labeled for SC injection and SC infusion (NovoLog approved for IV infusion in clinical settings).<br />
Meal timing Give SC injection within 15 minutes before or immediately after<br />
meals. 1<br />
Give pump bolus immediately before meal. 6<br />
Give 5 <strong>to</strong> 10 minutes before meals. Give SC injection within 15<br />
minutes before or within 20<br />
min. after starting a meal. 21<br />
Formulations 100 units/mL. 10 mL vials, 3 mL cartridge and disposable pen. 100 units/mL. 10 mL vials, 3 mL cartridge<br />
(latex-free), 24 100 units/mL. 10 mL vials,<br />
3 mL disposable FlexPen. 3 mL cartridge<br />
Appearance<br />
1, 10<br />
Clear<br />
Compatibility • Can mix with NPH or ultralente (draw lispro in<strong>to</strong> syringe first<br />
and inject immediately). 19<br />
• Mixture with NPH (Humulin N) stable in vials for 28 days at<br />
room temperature and refrigeration (prefilled syringes stable for<br />
14 days refrigerated). 35<br />
• Can mix with NPH (draw aspart in<strong>to</strong><br />
syringe first and inject immediately after<br />
mixing).<br />
• Can mix with Lilly diluent <strong>to</strong> dilutions of 1:2 (U-50) or 1:10<br />
(U-10). Diluted solutions stable for 28 days at<br />
5° C (41° F) and 14 days at 30° C (86° F).<br />
• Do not mix with glargine (see note under Lantus).<br />
• Discard pump insulin if exposed <strong>to</strong> >37° C.<br />
16<br />
• No data on mixing with regular, lente, or<br />
ultralente. 24<br />
• Can mix with NPH only<br />
(draw glulisine in<strong>to</strong> syringe<br />
first and inject<br />
immediately).<br />
• Discard pump insulin if exposed <strong>to</strong> >37° C.<br />
• Do not mix with glargine (see note under<br />
Lantus).<br />
21<br />
Stability of in- Vial, cartridge, pen: 28 days<br />
Vial, cartridge, pen: 28 days<br />
use products at External pump: 48 hours for most parts; 7 days for 3 mL External pump: 48 hours.<br />
room temp cartridge in D-TRON or D-TRON plus.<br />
24<br />
Vial, cartridge: 28 days.<br />
External pump: 48 hours. 1<br />
AWP $80.35/10 mL vial<br />
$83.71/10 mL vial<br />
$80.87/10 mL vial<br />
$156.18/5 of 3 mL cartridge<br />
$155.52/5 of 3 mL cartridge<br />
$162.68/5 of 3 mL cartridge<br />
$161.69/5 of 3 mL pen<br />
$161.73/5 of 3 mL FlexPen<br />
Copyright © 2006 by Therapeutic Research Center<br />
Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, S<strong>to</strong>ck<strong>to</strong>n, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249<br />
www.pharmacistsletter.com ~ www.prescribersletter.com<br />
More. . .
More. . .<br />
Copyright © 2006 by Therapeutic Research Center<br />
Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, S<strong>to</strong>ck<strong>to</strong>n, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249<br />
www.pharmacistsletter.com ~ www.prescribersletter.com<br />
(Detail-Document #220910: Page 2 of 12)<br />
Short-acting (ie, Regular insulin)<br />
Brand, maker Humulin R, Eli Lilly Novolin R, Novo Nordisk Iletin II Regular, 25 Eli Lilly*<br />
Species Human (rDNA) Human (rDNA) Pork<br />
Availability Non-prescription (except 500 units/mL Humulin R).<br />
Onset<br />
As of July 2005, Lilly will discontinue Iletin II Regular; s<strong>to</strong>ck depletion expected by end of 2005.<br />
16 30 <strong>to</strong> 60 minutes; onset more rapid with human than pork.<br />
Peak 16 1 <strong>to</strong> 5 hours; peak may be more rapid with human than pork.<br />
Duration 16 6 <strong>to</strong> 10 hours; longer with pork than human. May be longer with U-500. 4 <strong>to</strong> 12 hours<br />
Administration SC, IM, IV (unlabeled).<br />
500 units/mL SC only.<br />
SC, IM, IV. 39 SC, IV (unlabeled), but not IM.<br />
Meal timing SC injection: 30 minutes before meals. 1 Pump bolus: 20 <strong>to</strong> 30 minutes before a meal. 6<br />
Formulations 100 units/mL: 10 mL vial.<br />
100 units/mL: 10 mL vial, 3 mL cartridge, 100 units/mL. 10 mL vial.<br />
500 units/mL: 20 mL vial.<br />
3 mL Innolet.<br />
Appearance Clear and colorless. 1<br />
Compatibility • Can mix with NPH; use immediately or s<strong>to</strong>re for future use. 1 Mixture in vials stable at<br />
room temperature for 1 month, refrigera<strong>to</strong>r for 3 months, but must consider possibility of<br />
microbial contamination. 16,36<br />
• Mixing with lente/ultralente can delay onset of regular; may not reach binding<br />
equilibrium for 24 hours. Per ADA, mix with lente only if patient already stabilized on<br />
regimen. Standardize interval between mixing & injecting (either immediately or ≥24<br />
1, 5, 6<br />
hours after mixing).<br />
• Humulin R stable for 1 month at room temp after dilution with Lilly insulin diluent. 18<br />
• Do not mix with glargine.<br />
• Can mix with Water for Injection or 0.9% Sodium Chloride for Injection for use in SC<br />
infusion pump. Use within 24 hours. 16<br />
• Can mix with Iletin II Lente if<br />
administered immediately. 6<br />
• Can mix with NPH. 5<br />
• Can mix with ultralente. 5<br />
• Do not mix with glargine.<br />
• Diluent no longer available for<br />
Iletin II Regular. 18<br />
Stability of in- Vial: 28 days<br />
use products at<br />
room<br />
temperature<br />
42<br />
Vial: 30 days 43<br />
Vial: 28 days<br />
3 mL cartridge & Innolet: 28 days<br />
42<br />
AWP $36.19/10 mL vial (U-100)<br />
$37.71/10 mL vial<br />
$47.98/10 mL vial<br />
$219.46/20 mL vial (U-500)<br />
$119.34/5 of 3 mL cartridge<br />
$80.28/5 of 3 mL Innolet<br />
Discontinued
Intermediate-acting<br />
Lente (<strong>Insulin</strong> zinc suspension; contains zinc and<br />
acetate buffers) 5<br />
More. . .<br />
Copyright © 2006 by Therapeutic Research Center<br />
Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, S<strong>to</strong>ck<strong>to</strong>n, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249<br />
www.pharmacistsletter.com ~ www.prescribersletter.com<br />
(Detail-Document #220910: Page 3 of 12)<br />
NPH (Isophane insulin suspension; contains zinc and protamine) 5<br />
Brand, maker Humulin L, Lilly Novolin N, Novo Nordisk Humulin N, 25 Lilly Iletin II NPH, 25 Lilly<br />
Species Human Human Human Pork<br />
Availability Non-prescription.<br />
As of July 2005, Lilly will discontinue Humulin L and Iletin II NPH; s<strong>to</strong>ck depletion expected by end of 2005.<br />
Onset 16 1 <strong>to</strong> 3 hours 1 <strong>to</strong> 2 hours; onset more rapid with human than pork<br />
Peak 16 6 <strong>to</strong> 14 hours 6 <strong>to</strong> 14 hours<br />
Duration 16 16 <strong>to</strong> 24 hours 16 <strong>to</strong> 24+ hours; duration of human < pork<br />
Administration SC only. 16 Re-suspend before injection. 6 SC only. 16 Re-suspend before injection. 6<br />
Meal timing • Inject within 15 minutes before meals when NPH mixed with rapid-acting insulin. 1<br />
• Usually injected 30 minutes before meals when mixed with regular. 1<br />
• Individualize based on blood glucose. 8<br />
Formulations 100 units/mL. 10 mL vial. 100 units/mL. 10 mL<br />
vial, 3 mL cart, 3 mL<br />
100 units/mL. 10<br />
mL vial, 3 mL<br />
cartridge.<br />
100 units/mL. 10 mL<br />
vial.<br />
Appearance<br />
Innolet.<br />
Cloudy 1<br />
Compatibility • Do not mix with regular insulin unless patient<br />
stabilized on regimen (delays onset of regular<br />
insulin). Standardize interval between mixing and<br />
injecting (either immediately or at least 24 hours<br />
after mixing). 1, 5 Mix with Iletin II regular<br />
immediately before injecting. 6<br />
• Can mix with ultralente. 5<br />
• Do not mix with NPH or glargine. 1<br />
• Diluent no longer available for Humulin L. 18<br />
• Can mix with aspart or lispro. 5 Draw up rapid-acting insulin first and<br />
inject immediately. 24 (See additional stability information in lispro<br />
section).<br />
• Can mix with regular. Draw up regular insulin first; can be used<br />
immediately or s<strong>to</strong>red for future use. 1 Mixture in vials stable at room<br />
temperature for 1 month and in refrigera<strong>to</strong>r for 3 months. 5<br />
• Lilly NPH products stable for 1 month at room temperature after<br />
6, 18<br />
dilution with Lilly insulin diluent.<br />
1, 5<br />
• Do not mix with lente, ultralente, or glargine.<br />
Room temp Vial: 28 days<br />
stability, in-use<br />
products<br />
42 Vial: 30 days 43<br />
Vial: 28 days<br />
3 mL cart, Innolet: 14<br />
days<br />
42<br />
Vial: 28 days<br />
3 mL pen: 14 days<br />
42<br />
AWP $29.85/10 mL vial<br />
$37.71/10 mL vial $36.19/10 mL vial $47.98/10 mL vial<br />
Discontinued<br />
$119.44/5 of 3 mL cart $119.43/5 of 3 mL Discontinued<br />
$80.28/5 of 3 mL Innolet pens
Long-acting<br />
More. . .<br />
Copyright © 2006 by Therapeutic Research Center<br />
Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, S<strong>to</strong>ck<strong>to</strong>n, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249<br />
www.pharmacistsletter.com ~ www.prescribersletter.com<br />
(Detail-Document #220910: Page 4 of 12)<br />
<strong>Insulin</strong> glargine solution Ultralente (Extended insulin zinc suspension) <strong>Insulin</strong> Detemir solution<br />
Brand, maker Lantus, 12 Aventis Humulin U, Lilly Levemir, 34 Novo Nordisk<br />
Availability Prescription only. Non-prescription. Will be discontinued;<br />
expect s<strong>to</strong>ck depletion by end of 2005.<br />
Prescription only.<br />
Species Human insulin analog (rDNA) Human (rDNA) Human insulin analog (rDNA)<br />
Onset 16 1.1 hours 4 <strong>to</strong> 6 hours 0.8 <strong>to</strong> 2 hours (dose-dependent) 39<br />
Peak 16 No significant peak 8 <strong>to</strong> 20 hours Relatively flat<br />
Duration 16 24 hours 24 <strong>to</strong> 28 hours with 0.5 units/kg; somewhat<br />
dose-dependent. 6<br />
Dose-dependent; 12 hours for 0.2<br />
units/kg, 20 hours for 0.4 units/kg, up <strong>to</strong><br />
24 hours. Binds <strong>to</strong> albumin.<br />
Administration • Once daily SC at same time each day. • Re-suspend before injection.<br />
• Give equivalent dose of Lantus after<br />
conversion from once daily human<br />
NPH/lente; reduce Lantus dose by 20%<br />
after twice daily NPH.<br />
• No need <strong>to</strong> shake before administration.<br />
• Low pH may cause pain at injection site.<br />
6<br />
• Give SC once or twice daily. Give<br />
• SC injection only.<br />
once-daily dose at evening meal or hs.<br />
Give equivalent dose of Levemir after<br />
conversion from another basal insulin. 34<br />
• Type 2 diabetes: Some pts may need<br />
higher doses of Levemir than NPH.<br />
<strong>Insulin</strong>-naïve pts with poor control on<br />
PO drugs: 0.1-0.2 units/kg once daily in<br />
evening or 10 units once/ twice daily. 34<br />
Meal timing Not applicable. • Inject within 15 minutes before meals if mixed<br />
with rapid-acting insulin. 1<br />
• Usually injected 30 minutes before meals if<br />
mixed with regular. 1<br />
• Evening dose can be given at dinner or<br />
hs. In twice-daily regimens, it can also<br />
be given 12 h after morning dose. 34<br />
Formulations 100 units/mL. 10 mL vial, 3 mL cart for 100 units/mL. 10 mL vial. 100 units/mL. 10 mL vial,<br />
Opticlik.<br />
3 mL disposable FlexPen.<br />
Appearance Clear 1 Cloudy 1 Clear 14<br />
Compatibility • Do not mix with other insulins; diluent has<br />
low pH (4). 1<br />
Note: In initial studies, mixing glargine with<br />
lispro or aspart did not affect glycemic<br />
control. The mixture was cloudy. 13,40<br />
• Can mix with insulin lispro (inject within 5<br />
minutes), regular (standardize time from mixing<br />
<strong>to</strong> injecting), or lente. 4, 5 Do not mix with NPH. 1<br />
• Mixture with lente stable at room temp for 1<br />
month, refrigerated for 3 months. 26<br />
• Diluent no longer available for Humulin U. 18<br />
Do not mix with other insulins or<br />
diluent. Mixing with Levemir reduced<br />
levels of insulin aspart substantially. 34<br />
Has neutral pH (7.4). 2,34<br />
Room temp 10 mL vial: 28 days<br />
10 mL vial: 28 days<br />
stability, in-use 3 mL cartridge: 28 days<br />
products<br />
42 10 mL vial, 3 mL FlexPen: 42 days. Inuse<br />
vials can be refrigerated; other forms<br />
cannot. 43<br />
AWP $80.21/10 mL vial; $163.44/5 of 3 mL cart $29.85/10 mL vial (Discontinued) $83.70/10 mL vial; $161.69/5 FlexPen
<strong>Insulin</strong> Mixtures (Information for Humalog Mix 50/50 is at the end of this chart)<br />
30% insulin aspart,<br />
70% insulin aspart<br />
protamine<br />
Novolog Mix 70/30 28<br />
25% insulin lispro,<br />
75% insulin lispro<br />
protamine<br />
Humalog Mix 75/25 27<br />
70% NPH,<br />
30% regular<br />
More. . .<br />
Copyright © 2006 by Therapeutic Research Center<br />
Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, S<strong>to</strong>ck<strong>to</strong>n, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249<br />
www.pharmacistsletter.com ~ www.prescribersletter.com<br />
(Detail-Document #220910: Page 5 of 12)<br />
50% NPH,<br />
50% regular<br />
Brand,<br />
Humulin 70/30<br />
Maker Novo Nordisk Eli Lilly<br />
25<br />
Novolin 70/30<br />
Eli Lilly<br />
25<br />
Humulin 50/50<br />
Novo Nordisk<br />
Eli Lilly<br />
Availability Prescription only Non-prescription<br />
Species Human insulin analog (rDNA) Human (rDNA)<br />
Onset 10 <strong>to</strong> 20 minutes 39 Faster than Humulin 70/30 30 <strong>to</strong> 60 minutes 7 30 <strong>to</strong> 60 minutes 7 30 <strong>to</strong> 60 minutes 7<br />
Peak Mean 2.4 hours Mean 2.6 hours<br />
Mean 4.4 hours 2 <strong>to</strong> 12 hours Mean 3.3 hours<br />
Range 1 <strong>to</strong> 4 hours Range 1 <strong>to</strong> 6.5 hours Range 1.5 <strong>to</strong> 16 hours<br />
Range 2 <strong>to</strong> 5.5<br />
hours<br />
Duration Effective: 15 <strong>to</strong> 18 Up <strong>to</strong> 24 hours (similar <strong>to</strong> Effective: 10 <strong>to</strong> 16<br />
hours<br />
Humulin 70/30).<br />
hours<br />
Max: Up <strong>to</strong> 24 hours<br />
9<br />
Max: Up <strong>to</strong> 18 <strong>to</strong> 24<br />
hours 9<br />
Effective: 10 <strong>to</strong> 16<br />
hours 9<br />
Max: Up <strong>to</strong> 18 <strong>to</strong> 24<br />
hours 9<br />
Effective: 10 <strong>to</strong> 16<br />
hours 9<br />
Max: Up <strong>to</strong> 18 <strong>to</strong><br />
24 hours 9<br />
Administration SC only. Re-suspend before injection. 6<br />
Meal timing • Give within 15 minutes of a meal.<br />
• Individualize based on blood glucose. 8<br />
• Give approx. 30 minutes before meals. 1<br />
• Individualize based on blood glucose. 8<br />
Formulations 100 units/mL. 10 mL 100 units/mL. 10 mL vial, 3 100 units/mL. 10 mL 100 units/mL. 10 mL 100 units/mL. 10<br />
vial, 3 mL cart, 3 mL mL disposable pen vial,<br />
vial, 3 mL cartridge, 3 mL vial<br />
disposable FlexPen<br />
3 mL disposable pen mL Innolet<br />
Appearance Cloudy<br />
Compatibility • Do not mix with other insulins. • Humalog Mix 75/25, Humulin 70/30, and Humulin 50/50 stable for 1 month at room<br />
temperature after dilution with Lilly insulin diluent. 18<br />
Stability of in- Vial: 28 days Vial: 28 days<br />
Vial: 28 days Vial: 30 days<br />
use products at Pen: 14 days<br />
Pen: 10 days<br />
Pen: 10 days<br />
room temp 3 mL cart: 14 days<br />
43<br />
Vial: 28 days<br />
3 mL cart, Innolet: 10<br />
days<br />
Cost $83.71/10 mL vial $80.35/10 mL vial $36.19/10 mL vial $37.71/10 mL vial $36.19/10 mL vial<br />
$155.52/5 of 3 mL $161.69/5 of 3 mL pen $119.43/10 of 3 mL $119.44/5 of 3 mL cart<br />
cart<br />
pen<br />
$80.28/5 of 3 mL<br />
$161.73/5 of 3 mL pen<br />
Innolet
<strong>Insulin</strong> Administration Devices<br />
Device<br />
Manufacturer<br />
Au<strong>to</strong>pen Classic<br />
AN3810 and AN3800<br />
Owen Mumford<br />
800-421-6936<br />
www.owenmumford.com<br />
Lilly pens<br />
Eli Lilly<br />
800-545-5979<br />
www.lillydiabetes.com<br />
(See next pg. for<br />
HumaPen<br />
Memoir/Luxura)<br />
Innolet<br />
Novo Nordisk<br />
www.innolet-us.com<br />
Levemir FlexPen<br />
Novo Nordisk<br />
www.insulindevice.com<br />
NovoLog FlexPen<br />
Novo Nordisk<br />
NovoLog Mix 70/30<br />
FlexPen<br />
Novo Nordisk<br />
Description Dosage range<br />
and precision<br />
Reusable<br />
pen<br />
Prefilled<br />
disposable<br />
pen<br />
Prefilled<br />
disposable<br />
device<br />
Prefilled<br />
disposable<br />
pen<br />
Prefilled<br />
disposable<br />
pen<br />
Prefilled<br />
disposable<br />
pen<br />
1-21 units in 1unit<br />
increments<br />
or 2-42 units in<br />
2-unit<br />
increments<br />
1-60 units in 1unit<br />
increments<br />
1-50 units in 1unit<br />
increments<br />
1-60 units in 1unit<br />
increments<br />
1-60 units in 1unit<br />
increments<br />
1-60 units in 1unit<br />
increments<br />
<strong>Insulin</strong> Used S<strong>to</strong>rage &<br />
stability of<br />
3 mL cartridges<br />
from Lilly or CP<br />
Pharmaceuticals<br />
3 mL with:<br />
Humalog 75/25<br />
Humalog 50/50<br />
Humalog<br />
Humulin N<br />
Humulin 70/30<br />
3 mL with:<br />
Novolin N<br />
Novolin 70/30<br />
Novolin R<br />
3 mL with<br />
Levemir<br />
3 mL with<br />
NovoLog<br />
3 mL with<br />
NovoLog Mix<br />
70/30<br />
in-use pens<br />
According <strong>to</strong><br />
insulin cartridge<br />
specifications<br />
Room temp for:<br />
10 days<br />
10 days<br />
28 days<br />
14 days<br />
10 days<br />
Room temp for:<br />
14 days<br />
10 days<br />
28 days<br />
42 days at room<br />
temperature<br />
28 days at room<br />
temperature<br />
14 days at room<br />
temperature<br />
More. . .<br />
Copyright © 2006 by Therapeutic Research Center<br />
Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, S<strong>to</strong>ck<strong>to</strong>n, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249<br />
www.pharmacistsletter.com ~ www.prescribersletter.com<br />
(Detail-Document #220910: Page 6 of 12)<br />
AWP Comments<br />
$40 Au<strong>to</strong>matic side injection but<strong>to</strong>n.<br />
Comes with Unifine Pentip needles<br />
(1/2” or 5/16”, both 29 G), but can<br />
use other needles. Cannot easily<br />
correct “over-dialed” dose without<br />
losing insulin.<br />
$161.69<br />
for 5 pens<br />
Humalog<br />
$119.43<br />
for 5 pens<br />
Humulin<br />
$62.95/5<br />
of 3 mL<br />
dosers<br />
$161.69<br />
for 5 pens<br />
$161.73<br />
for 5 pens<br />
$161.73<br />
for 5 pens<br />
Can use with 28 G BD pen needles or<br />
equivalent. Has magnifying dose<br />
window. Also additional magnifier<br />
that snaps on the pen. Humalog<br />
products are prescription only.<br />
Uses NovoFine or BD pen needles.<br />
Has large dosage dial and numbers.<br />
Audible clicks. a Dial dose up/down<br />
for dose correction. Resets <strong>to</strong> zero<br />
after shot.<br />
Uses NovoFine or BD pen needles.<br />
Large window. Audible clicks. a Dial<br />
dose up/down for dose correction.<br />
Resets <strong>to</strong> zero after shot.<br />
Uses NovoFine or BD pen needles.<br />
Large window. Audible clicks. a Dial<br />
dose up/down for dose correction.<br />
Resets <strong>to</strong> zero after shot.<br />
Uses NovoFine or BD pen needles.<br />
Large window. Audible clicks. a Dial<br />
dose up/down for dose correction.<br />
Resets <strong>to</strong> zero after shot.
Device<br />
Manufacturer<br />
NovoPen 3<br />
Novo Nordisk<br />
NovoPen Junior<br />
Novo Nordisk<br />
OptiClik<br />
Aventis<br />
www.opticlik.com<br />
HumaPen Memoir<br />
Eli Lilly<br />
www.humalog.com/patient<br />
/humapen_memoir.jsp<br />
HumaPen Luxura HD<br />
Eli Lilly<br />
Description Dosage range<br />
and precision<br />
Reusable<br />
pen<br />
Reusable<br />
pen<br />
Reusable<br />
pen<br />
Reusable<br />
pen with<br />
memory<br />
Reusable<br />
pen<br />
2-70 units in 1unit<br />
increments<br />
1-35 units in ½<br />
unit increments<br />
1-80 units in 1<br />
unit increments<br />
1-60 units in 1unit<br />
increments<br />
1-30 units in ½unit<br />
increments<br />
(after 1st unit)<br />
<strong>Insulin</strong> Used S<strong>to</strong>rage &<br />
stability of<br />
3 mL Novo<br />
Nordisk PenFill<br />
cartridges<br />
(Novolin N, R,<br />
70/30, NovoLog,<br />
NovoLog Mix<br />
70/30)<br />
3 mL Novo<br />
Nordisk PenFill<br />
cartridges<br />
(Novolin N, R,<br />
70/30, NovoLog,<br />
NovoLog Mix<br />
70/30)<br />
3 mL Lantus<br />
cartridges<br />
3 mL Apidra<br />
cartridges<br />
3 mL Humalog<br />
cartridges only,<br />
from Lilly<br />
3 mL Humalog<br />
cartridges only,<br />
from Lilly<br />
in-use pens<br />
Room temperature;<br />
duration according<br />
<strong>to</strong> specific<br />
cartridge<br />
Room temperature;<br />
duration according<br />
<strong>to</strong> specific<br />
cartridge<br />
28 days at room<br />
temperature. Allow<br />
cartridge <strong>to</strong> reach<br />
room temperature<br />
(1-2 hours) before<br />
using in pen.<br />
28 days at room<br />
temperature per<br />
Humalog cartridge<br />
specifications<br />
28 days at room<br />
temperature per<br />
Humalog cartridge<br />
specifications<br />
More. . .<br />
Copyright © 2006 by Therapeutic Research Center<br />
Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, S<strong>to</strong>ck<strong>to</strong>n, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249<br />
www.pharmacistsletter.com ~ www.prescribersletter.com<br />
(Detail-Document #220910: Page 7 of 12)<br />
AWP Comments<br />
$12.50<br />
(pen)<br />
$37.49<br />
(pen)<br />
Uses Novofine or BD pen needles.<br />
Can add PenMate attachment <strong>to</strong> hide<br />
needle and au<strong>to</strong>inject.<br />
Uses NovoFine or BD pen needles.<br />
Can add PenMate attachment <strong>to</strong> hide<br />
needle and au<strong>to</strong>inject.<br />
Free Do not s<strong>to</strong>re in the refrigera<strong>to</strong>r, as<br />
that may damage electronics inside<br />
the pen body. If the pen<br />
malfunctions, the insulin can be<br />
drawn from the cartridge and<br />
$100<br />
($45 with<br />
coupon)<br />
N/A<br />
(product<br />
avail April<br />
2007)<br />
Chart is based on U.S. product labeling.<br />
Further information on insulin pens available online at: http://www.lifeclinic.com/focus/diabetes/supply_syringes.asp;<br />
http://www.childrenwithdiabetes.com/d_06_360.htm; http://www.childrenwithdiabetes.com/d_06_361.htm.<br />
a Patients should not rely on clicking sound as a means of determining the dose.<br />
injected.<br />
Do not refrigerate. Battery operated.<br />
Do not refrigerate.<br />
—Continue <strong>to</strong> the next page for information about Humalog Mix 50/50, Byetta, and Symlin—
Inhalation <strong>Insulin</strong><br />
Brand (Generic)<br />
Maker<br />
Exubera, 37,38<br />
(Recombinant<br />
human insulin),<br />
Pfizer.<br />
Product<br />
Discontinued<br />
Onset Peak Duration Administration Meal timing Formulation Stability (in-use at<br />
room temperature)<br />
10 <strong>to</strong> 20 30 <strong>to</strong> 90 6 hours Oral inhalation Within 10 1 mg, 3 mg unit U.D. blister: 3<br />
minutes minutes<br />
minutes of dose blisters months after opening<br />
meal ingestion<br />
foil overwrap<br />
<strong>Insulin</strong> Mixture-Disposable Pen Only<br />
Humalog Mix<br />
50/50 46<br />
(<strong>Insulin</strong> lispro<br />
50%, insulin<br />
lispro protamine<br />
50%),<br />
Human insulin<br />
analog (rDNA),<br />
Eli Lilly.<br />
Prescription only<br />
Faster<br />
than<br />
Humulin<br />
50/50<br />
Mean-<br />
2.3 hrs<br />
Range-<br />
0.8 <strong>to</strong><br />
4.8 hrs<br />
Similar <strong>to</strong><br />
Humulin<br />
50/50<br />
SC only.<br />
Resuspend<br />
before injection.<br />
Give within 15<br />
min. of a meal.<br />
Individualize<br />
based on blood<br />
glucose<br />
100 U/mL,<br />
3 mL disposable<br />
pen<br />
More. . .<br />
Copyright © 2006 by Therapeutic Research Center<br />
Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, S<strong>to</strong>ck<strong>to</strong>n, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249<br />
www.pharmacistsletter.com ~ www.prescribersletter.com<br />
(Detail-Document #220910: Page 8 of 12)<br />
AWP<br />
$140.00 (Combo<br />
Pack 12)<br />
$175.00 (Combo<br />
Pack 15)<br />
$187.50 (Kit)<br />
Pen: 10 days $161.69/5 of 3 mL<br />
pen<br />
Misc. Non-insulin Injectable Agents<br />
Brand (Generic)<br />
Maker<br />
Therapeutic Class Administration Meal Timing Formulation Stability (in-use) AWP<br />
Byetta (exenatide) 44<br />
Amylin.<br />
Prescription only.<br />
www.amylin.com<br />
Symlin<br />
(pramlintide) 45<br />
Amylin.<br />
Prescription only<br />
www.amylin.com<br />
Incretin mimetic Subcutaneous<br />
injection<br />
Synthetic amylin<br />
analogue<br />
Subcutaneous<br />
injection<br />
Within 60 minute<br />
period before<br />
morning and evening<br />
meals<br />
Immediately before<br />
meals containing<br />
>250 Kcal or<br />
>30 gm of<br />
carbohydrate<br />
5 mcg per dose, 60<br />
doses, 1.2 mL<br />
prefilled pen<br />
10 mcg per dose, 60<br />
doses, 2.4 mL<br />
prefilled pen<br />
0.6 mg per mL,<br />
5 mL vials<br />
S<strong>to</strong>re unused pen in<br />
refrigera<strong>to</strong>r. After 1 st<br />
use, may be kept at<br />
room temperature<br />
(up <strong>to</strong> 77ºF) for up <strong>to</strong><br />
30 days. Discard<br />
after 30 days.<br />
Discard 28 days after<br />
first use. May be<br />
refrigerated or kept<br />
at room temperature.<br />
$194.78 (1.2 mL)<br />
$228.59 (2.4 mL)<br />
$107.34
<strong>Insulin</strong>s<br />
Lead author: Jill Allen, Pharm.D., BCPS<br />
(Detail-Document #220910: Page 9 of 12)<br />
<strong>Insulin</strong>s are categorized in the tables above according <strong>to</strong> their onset and duration of action: rapid-, short-,<br />
intermediate-, long-acting, and premixtures of rapid or short-acting insulin combined with intermediateacting<br />
insulin. A second table also provides information about insulin pens and other administration<br />
devices.<br />
Availability. The new insulin analogs and U-500 insulin are available by prescription only. Other<br />
insulins are available OTC, but a prescription may be required for insurance company reimbursement.<br />
Type. Species of insulin available in the U.S. will soon be limited <strong>to</strong> human insulins and human insulin<br />
analogs. Years ago, beef insulins were removed from the U.S. market because of a theoretical concern<br />
for transmission of bovine spongiform encephalopathy (mad cow disease). For information on obtaining<br />
beef insulin from other countries, go <strong>to</strong> http://www.fda.gov/cder/drug/beefandporkinsulin/ default.htm. In<br />
July 2005, Lilly announced the discontinuation of it’s pork insulins (Iletin II regular and NPH), with the<br />
expectation that s<strong>to</strong>ck will be depleted by the end of the year. 29 Demand for these products has declined<br />
in recent years and recombinant human insulin products are easier <strong>to</strong> manufacture. The dose is usually<br />
similar when converting from animal <strong>to</strong> human insulin. Consider reducing the initial human insulin dose<br />
by 10% <strong>to</strong> 20% in patients receiving more than 100 units per day of animal insulin. 33 Lilly will also<br />
discontinue two long-acting human insulins, Humulin L (lente) and Humulin U (ultralente), with s<strong>to</strong>ck<br />
depletion also expected by the end of 2005. 29<br />
A recent statement from the International Diabetes Federation concludes that, in the absence of strong<br />
evidence favoring one species of insulin over another, patients should not be converted <strong>to</strong> a different<br />
species unless it has a clear advantage for the patient. 31 Since all insulins have slightly different<br />
properties, a particular patient may better <strong>to</strong>lerate one species of insulin better than another. In the past,<br />
anecdotal reports raised concern that human insulins might have a higher risk of hypoglycemia, but this<br />
concern has not been supported by further clinical research. 31<br />
Onset, peak, duration. The tables above compare the onset, peak, and duration of action of insulin<br />
formulations after subcutaneous injection. These values are approximate since many fac<strong>to</strong>rs can affect<br />
the pharmacokinetics of insulin. 1 Rapid-acting insulin analogs (insulins lispro, aspart, and glulisine) have<br />
small modifications <strong>to</strong> the insulin amino acid sequence that makes them dissociate in<strong>to</strong> monomers more<br />
quickly after subcutaneous injection. This allows more rapid absorption in<strong>to</strong> the systemic circulation.<br />
There is also less variability in absorption with rapid-acting insulin analogs than regular insulin. 3 Rapidacting<br />
analogs may provide better postprandial glucose control and less nocturnal hypoglycemia than<br />
31, 32<br />
regular insulin, but it is unclear that these benefits translate in<strong>to</strong> long-term improvements in outcome.<br />
After SC injection, intermediate- and long-acting insulin molecules aggregate in<strong>to</strong> hexamers (groups of<br />
six molecules) at the injection site. They slowly dissociate in<strong>to</strong> dimers and monomers which are absorbed<br />
in<strong>to</strong> the systemic circulation. <strong>Insulin</strong> detemir is acylated (linked <strong>to</strong> a fatty acid chain). This promotes<br />
hexamer formation and reversible binding <strong>to</strong> albumin after it reaches the bloodstream. 2 This helps<br />
prolong it’s duration of action. The time-action profile of insulin detemir is less variable than NPH. 2<br />
This may reduce the risk of hypoglycemia and weight gain. 3 Interindividual variability is less with insulin<br />
glargine than with NPH and ultralente. 4 <strong>Insulin</strong> lispro protamine and NPH insulin have similar<br />
pharmacokinetic profiles. 5 Newer basal insulins, like insulin glargine, reduce nocturnal hypoglycemia.<br />
<strong>How</strong>ever, it is unclear whether this benefit improves long-term glycemic control. 31<br />
More. . .<br />
Copyright © 2006 by Therapeutic Research Center<br />
Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, S<strong>to</strong>ck<strong>to</strong>n, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249<br />
www.pharmacistsletter.com ~ www.prescribersletter.com
(Detail-Document #220910: Page 10 of 12)<br />
Administration. <strong>Insulin</strong> suspensions should be gently shaken before each injection. Pens and<br />
cartridges of insulin suspensions should be rolled and tipped back and forth ten <strong>to</strong> 20 times <strong>to</strong> re-suspend<br />
the insulin and then primed before each injection. 6, 7 <strong>Insulin</strong> mixtures or dilutions should not be used in<br />
external pumps.<br />
Meal timing. The American Diabetes Association (ADA) recommends that rapid-acting insulin analogs<br />
(alone or with intermediate- or long-acting insulin) be injected within 15 minutes before or immediately<br />
after a meal. 1 It may be helpful <strong>to</strong> give the dose after a meal in young children who are unreliable eaters. 8<br />
Regular insulin is usually given 30 minutes before meals. Meal-timing for premixed formulations is<br />
based on whether the mixture contains rapid-acting or regular insulin. In one algorithm, the interval<br />
between injecting insulin and starting a meal depends on blood glucose moni<strong>to</strong>ring. For regular insulin,<br />
the interval is 20 <strong>to</strong> 30 minutes for a blood glucose of 65 <strong>to</strong> 150 mg/dL, 30 <strong>to</strong> 45 minutes for >150 <strong>to</strong> 250<br />
mg/dL, and 50 <strong>to</strong> 60 minutes for >250 mg/dL. <strong>Insulin</strong> lispro can be injected immediately before meals<br />
when blood glucose is 65 <strong>to</strong> 150 mg/dL. The interval between injecting and eating is 10 <strong>to</strong> 20 minutes for<br />
>150 <strong>to</strong> 250 mg/dL, and 20 <strong>to</strong> 30 minutes for >250 mg/dL. 8 A more detailed algorithm is outlined in the<br />
ADA’s book, Intensive Diabetes Management. 9<br />
Formulations and delivery devices. All insulins are available in 10 mL vials (U-100; 100 units/mL).<br />
The only exception is U-500 (500 units/mL) regular human insulin (20 mL vial), which is available from<br />
Lilly by prescription only for patients who require more than 200 units/day. 5 Some formulations are<br />
available in prefilled disposable pens or reusable pens with disposable insulin cartridges. These products,<br />
reviewed in a table above, are for SC injection. Although they may be more expensive than vials, they<br />
can make insulin administration simpler, more convenient, and less error-prone than withdrawing insulin<br />
from a vial and injecting with a syringe. Injections with an insulin pen may also be less painful; the<br />
needles are small and are not dulled by the withdrawal of insulin from a vial <strong>to</strong> syringe. Jet injec<strong>to</strong>rs<br />
(such as AdvantaJet, Medi-Jec<strong>to</strong>r, and Vitajet) avoid the use of needles, cost approximately $250-$500,<br />
weigh about 8 oz, and require frequent cleaning. 10, 11 Exubera, approved January 2006, was the first<br />
insulin formulation <strong>to</strong> be administered by oral inhalation. In Oc<strong>to</strong>ber 2007, due <strong>to</strong> poor acceptance by<br />
patients and prescribers, Pfizer announced it would be discontinuing sales of Exubera.<br />
Appearance. Patients and clinicians should check the appearance of an insulin before using it. Rapid-<br />
and short-acting insulins and insulin glargine should be clear; the others should be cloudy. 1, 5 Warn<br />
patients that insulin glargine can be mistaken for a shorter-acting insulin because it looks clear.<br />
Compatibility. Human and pork insulins can probably be mixed, but there is no reason <strong>to</strong> do so. 6<br />
There is no information on the compatibility between Novolin and Humulin insulins; incompatibility<br />
could result from differences in buffering agents between the two product lines. When mixed with<br />
another insulin, a rapid- or short-acting insulin should be drawn up in the syringe first in order <strong>to</strong> maintain<br />
clarity in the vial. The manufacturer recommends against mixing insulin glargine with other insulins. In<br />
an animal study, mixing it with regular insulin delayed the onset and peak of regular insulin. 12 A<br />
preliminary study in 14 diabetics found no effect on glycemic control when insulin glargine was mixed<br />
with lispro or aspart. The mixture did turn cloudy. 13 Pramlintide (Symlin), a synthetic amylin analog, is<br />
administered by SC injection. The manufacturer recommends against mixing pramlintide with insulin. 14<br />
<strong>How</strong>ever, a recent study found that mixing it with short- or long-acting insulin in the same syringe before<br />
SC injection did not affect the pharmacokinetics of either agent or change glucose pharmacodynamics. 15<br />
Although some insulin mixtures are chemically stable under refrigeration for up <strong>to</strong> three months, the<br />
possibility of microbial contamination must be considered. 16<br />
A diluent is not available for Novo Nordisk insulins.<br />
More. . .<br />
Copyright © 2006 by Therapeutic Research Center<br />
Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, S<strong>to</strong>ck<strong>to</strong>n, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249<br />
www.pharmacistsletter.com ~ www.prescribersletter.com<br />
17 In the past, there were three Lilly diluents. Now, a<br />
single diluent is available (call 317-276-1610) for use with Humalog and Humalog 75/25 or 70/30;<br />
Humulin R, N, 70/30 and 50/50; Iletin II pork NPH and U-500. 18 It cannot be used for Humulin L or R, or
(Detail-Document #220910: Page 11 of 12)<br />
Regular Iletin II pork insulin. Opened vials of diluent and most diluted insulins are stable for one month<br />
at room temperature. 6 Diluted Humalog is stable at room temperature for 14 days. 19<br />
Stability. Unopened insulin products should be s<strong>to</strong>red in the refrigera<strong>to</strong>r (36 <strong>to</strong> 46˚ F; 2 <strong>to</strong> 8˚ C) with the<br />
exception of packaged Exubera unit dose blisters (s<strong>to</strong>red at room temperature, 25ºC [77ºF]). Once the<br />
s<strong>to</strong>pper or seal has been punctured by a needle, the product is considered <strong>to</strong> be “open” or “in-use.” In-use<br />
insulin vials are usually kept at room temperature (59 <strong>to</strong> 86˚ F; 15 <strong>to</strong> 30˚ C) <strong>to</strong> make injections less<br />
painful. At room temperature, opened vials are stable for about 28 days (Levemir is the exception at 42<br />
days). The duration of stability at room temperature varies for other insulin products. In-use insulin pens<br />
and cartridges should be s<strong>to</strong>red at room temperature. For Exubera, once the foil overwrap is opened (inuse),<br />
the unit dose blisters should be s<strong>to</strong>red at room temperature and used within three months. [Note:<br />
Exubera has been discontinued.]<br />
Users of this document are cautioned <strong>to</strong> use their own<br />
professional judgment and consult any other necessary<br />
or appropriate sources prior <strong>to</strong> making clinical<br />
judgments based on the content of this document. Our<br />
edi<strong>to</strong>rs have researched the information with input from<br />
experts, government agencies, and national<br />
organizations. Information and Internet links in this<br />
article were current as of the date of publication.<br />
References<br />
1. American Diabetes Association. <strong>Insulin</strong><br />
administration. Diabetes Care 2004;27 (suppl<br />
1):S106-S107. Available online at:<br />
http://care.diabetesjournals.org/cgi/content/full/27/su<br />
ppl_1/s106. (Accessed June 6, 2005).<br />
2. Goldman-Levine JD, Lee KW. <strong>Insulin</strong> detemir -- A<br />
new basal insulin analog. Ann Pharmacother<br />
2005;39:502-7.<br />
3. Hirsch IB. <strong>Insulin</strong> analogues. N Engl J Med<br />
2005;352:174-83.<br />
4. Lepore M, Pampanelli S, Fanelli C, et al.<br />
Pharmacokinetics and pharmacodynamics of<br />
subcutaneous injection of long-acting human insulin<br />
analog glargine, NPH insulin, and ultralente human<br />
insulin and continuous subcutaneous infusion of<br />
insulin lispro. Diabetes 2000;49:2142-8.<br />
5. American Pharmaceutical Association. APhA special<br />
report: New approaches <strong>to</strong> insulin therapy for<br />
diabetics. Washing<strong>to</strong>n, DC; 2001.<br />
6. Eli Lilly & Company. Personal communication. 2002.<br />
7. Jehle PM, et al. Inadequate suspension of neutral<br />
protamine Hagedorn (NPH) insulin in pens. Lancet<br />
1999;354:1604-7.<br />
8. American Diabetes Association. Medical<br />
management of type 1 diabetes. 3rd ed: Available<br />
online at: http://s<strong>to</strong>re.diabetes.org/; 1998.<br />
9. American Diabetes Association. Intensive diabetes<br />
management. 2nd ed: Available online at:<br />
http://s<strong>to</strong>re.diabetes.org/; 1998.<br />
10. Guthrie DW, Guthrie RA. Methods of insulin delivery.<br />
Excerpt from Diabetes Sourcebook. Available online<br />
at: www.my.webmd.com. Accessed September 9,<br />
2002.<br />
11. American Diabetes Association. Resource Guide<br />
2005, Diabetes Forecast. Available online at:<br />
http://www.diabetes.org/diabetes-forecast/resourceguide.jsp.<br />
(Accessed June 4, 2005).<br />
12. Aventis Pharmaceuticals. Lantus (insulin glargine [r<br />
DNA origin] injection) package insert. Kansas City,<br />
MO; 2004.<br />
13. Kaplan W, Rodriguez LM, Smith OE, et al. Effects of<br />
mixing glargine and short-acting insulin analogs in<br />
glucose control. Diabetes Care 2004;27:2739-40.<br />
14. Amylin Pharmaceuticals. Symlin (pramlintide<br />
acetate) injection package insert. San Diego, CA:<br />
2005.<br />
15. Weyer C, Fineman MS, Strobel S, et al. Properties of<br />
pramlintide and insulin upon mixing. Am J Health<br />
Syst Pharm 2005;62:816-22.<br />
16. McEvoy GK, edi<strong>to</strong>r. AHFS Drug Information.<br />
Bethesda: American Society of Health-System<br />
Pharmacists; 2002.<br />
17. American Society of Health-System Pharmacists.<br />
Drug products with limited availability. Available<br />
online at: http://www.ashp.org/shortage/availabilitynotices.cfm.<br />
(Accessed June 9. 2005).<br />
18. Eli Lilly & Company. Personal communication. 2005.<br />
19. Eli Lilly and Company. Humalog package insert.<br />
Indianapolis, IN: 2004.<br />
20. Novo Nordisk Pharmaceuticals. NovoLog package<br />
insert. Prince<strong>to</strong>n, NJ 08540. Oc<strong>to</strong>ber 2005.<br />
21. Aventis Pharmaceuticals. Apidra (insulin glulisine)<br />
injection package insert. Kansas City, MO:<br />
December 2005.<br />
22. Retnakaran R, Zinman B. Using insulin effectively in<br />
the management of diabetes. Endocrinology Rounds.<br />
Available online at:<br />
http://www.endocrinologyrounds.ca/crus/endocdneng<br />
_060704.pdf. (Accessed June 8, 2005).<br />
23. European Agency for the Evaluation of Medicinal<br />
<strong>Products</strong>. Levemir product information. Available<br />
online at:<br />
http://www.emea.eu.int/humandocs/Humans/EPAR/l<br />
evemir/levemir.htm. (Accessed June 3, 2005).<br />
24. Novo Nordisk Pharmaceuticals. Personal<br />
communication. 2002.<br />
25. Physicians' Desk Reference Electronic Library.<br />
Montvale: Medical Economics Company; 2001.<br />
26. Olin B, edi<strong>to</strong>r. Facts and Comparisons. St. Louis:<br />
Facts and Comparisons, Inc; 2000.<br />
More. . .<br />
Copyright © 2006 by Therapeutic Research Center<br />
Pharmacist’s Letter / Prescriber’s Letter ~ P.O. Box 8190, S<strong>to</strong>ck<strong>to</strong>n, CA 95208 ~ Phone: 209-472-2240 ~ Fax: 209-472-2249<br />
www.pharmacistsletter.com ~ www.prescribersletter.com
27. Eli Lilly. Humalog Mix 75/25 package insert.<br />
Indianapolis, IN; 2004.<br />
28. Novo Nordisk Pharmaceuticals. Novolog Mix 70/30<br />
package insert. Prince<strong>to</strong>n, NJ: 2004.<br />
29. Eli Lilly, Discontinuation of Humulin U Ultralente<br />
(Human insulin [rDNA origin] extended zinc<br />
suspension) and Humulin L Lente (human insulin<br />
[rDNA origin]. Available online at www.fda.gov.<br />
(Accessed July 12, 2005).<br />
30. Pray WS, Pray JJ. New products for patients with<br />
diabetes. US Pharmacist. Available online at:<br />
http://www.medscape.com/viewarticle/494672.<br />
(Accessed July 14, 2005).<br />
31. International Diabetes Federation. Position<br />
statement: Animal, Human, and Analogue <strong>Insulin</strong>s.<br />
Available online at: http://www.idf.org. (Accessed<br />
July 14, 2005).<br />
32. Plank J, Siebenhofer A, Berghold A, et al. Systematic<br />
review and meta-analysis of short-acting insulin<br />
analogues in patients with diabetes mellitus. Arch<br />
Intern Med 2005;165:1337-44.<br />
33. Eli Lilly Medical Communications. Humulin:<br />
Transferring patients from animal-source <strong>to</strong> human<br />
recombinant insulin. Written communication. July 14,<br />
2005.<br />
34. Novo Nordisk Pharmaceuticals. Levemir (insulin<br />
detemir [rDNA origin] injection) package insert.<br />
Prince<strong>to</strong>n, NJ: 2005.<br />
35. Personal communication. Humalog—mixing with<br />
other insulins. Lilly Medical Information.<br />
Indianapolis, IN 46285. July 2005.<br />
36. Personal communication. Humulin—activity,<br />
stability, and s<strong>to</strong>rage of extemporaneously mixed<br />
doses. Lilly Medical Information. Indianapolis, IN<br />
46285. July 2005.<br />
(Detail-Document #220910: Page 12 of 12)<br />
37. Odegard PS, Capoccia KL. Inhaled insulin: Exubera.<br />
Ann Pharmacother 2005;39:843-53.<br />
38. Product information for Exubera. Pfizer. New York,<br />
NY 10017. January 2006.<br />
39. Personal communication. A. Moses, M.D. May 30,<br />
2006. Novo Nordisk. Prince<strong>to</strong>n, NJ 08540.<br />
40. Fiallo-Scharer R, Horner B, McFann K, et al. Mixing<br />
rapid-acting insulin analogues with insulin glargine in<br />
children with type 1 diabetes mellitus. J Pediatr<br />
2006;148:481-4.<br />
41. Anon. <strong>Insulin</strong> delivery. American Diabetes<br />
Association 2006 Resource guide. Pgs RG23-39.<br />
42. Anon. Frequently asked questions: how do I s<strong>to</strong>re<br />
my insulin? http://www.lillydiabetes.com/product<br />
/insulin_faqs.jsp?reqNavId=5.10. (Accessed August<br />
14, 2006).<br />
43. Anon. S<strong>to</strong>rage and stability of Novo Nordisk insulin<br />
products. July 24, 2006. Novo Nordisk. Prince<strong>to</strong>n,<br />
NJ 08540.<br />
44. Product information for Byetta. Amylin<br />
Pharmaceuticals. San Diego, CA 92121. February<br />
2007.<br />
45. Product information for Symlin. Amylin<br />
Pharmaceuticals. San Diego, CA 92121. June<br />
2005.<br />
46. Product information for Humalog Mix 50/50. Eli Lilly.<br />
Indianapolis, IN 46285. January 2006.<br />
Cite this Detail-Document as follows: Comparison of insulins. Pharmacist’s Letter/Prescriber’s Letter<br />
2006;22(9):220910.<br />
Evidence and Advice You Can Trust…<br />
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Copyright © 2006 by Therapeutic Research Center<br />
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