"Miriam E. Tucker
Medscape Medical News
The U.S. Food and Drug Administration (FDA) will now require a "for single patient use only" warning on all multidose pen devices used for injectable diabetes medications.
Humalog Mix 50-50
The primary activity of insulin, including Humalog Mix50/50, is the regulation of glucose metabolism. In addition, all insulins have several anabolic and anti-catabolic actions on many tissues in the body. In muscle and other tissues (except the brain), insulin causes rapid transport of glucose and amino acids intracellularly, promotes anabolism, and inhibits protein catabolism. In the liver, insulin promotes the uptake and storage of glucose in the form of glycogen, inhibits gluconeogenesis, and promotes the conversion of excess glucose into fat.
Insulin lispro, the rapid-acting component of Humalog Mix50/50, has been shown to be equipotent to Regular human insulin on a molar basis. One unit of Humalog® has the same glucose-lowering effect as one unit of Regular human insulin, but its effect is more rapid and of shorter duration.
Studies in nondiabetic subjects and patients with type 1 (insulin-dependent) diabetes demonstrated that Humalog, the rapid-acting component of Humalog Mix50/50, is absorbed faster than Regular human insulin (U-100). In nondiabetic subjects given subcutaneous doses of Humalog ranging from 0.1 to 0.4 U/kg, peak serum concentrations were observed 30 to 90 minutes after dosing. When nondiabetic subjects received equivalent doses of Regular human insulin, peak insulin concentrations occurred between 50 to 120 minutes after dosing. Similar results were seen in patients with type 1 diabetes.
Figure 1: Serum
Immunoreactive Insulin (IRI) Concentrations, After Subcutaneous Injection of
Humalog Mix50/50 or Humulin 50/50 in Healthy Nondiabetic Subjects.
Humalog Mix50/50 has two phases of absorption. The early phase represents insulin lispro and its distinct characteristics of rapid onset. The late phase represents the prolonged action of insulin lispro protamine suspension. In 30 healthy nondiabetic subjects given subcutaneous doses (0.3 U/kg) of Humalog Mix50/50, peak serum concentrations were observed 45 minutes to 13.5 hours (median, 60 minutes) after dosing (see Figure 1). In patients with type 1 diabetes, peak serum concentrations were observed 45 minutes to 120 minutes (median, 60 minutes) after dosing. The rapid absorption characteristics of Humalog are maintained with Humalog Mix50/50 (see Figure 1).
Direct comparison of Humalog Mix50/50 and Humulin 50/50 was not performed. However, a cross-study comparison shown in Figure 1 suggests that Humalog Mix50/50 has a more rapid absorption than Humulin 50/50.
Radiolabeled distribution studies of Humalog Mix50/50 have not been conducted. However, the volume of distribution following injection of Humalog is identical to that of Regular human insulin, with a range of 0.26 to 0.36 L/kg.
Human metabolism studies of Humalog Mix50/50 have not been conducted. Studies in animals indicate that the metabolism of Humalog, the rapid-acting component of Humalog Mix50/50, is identical to that of Regular human insulin.
Humalog Mix50/50 has two absorption phases, a rapid and a prolonged phase, representative of the insulin lispro and insulin lispro protamine suspension components of the mixture. As with other intermediate-acting insulins, a meaningful terminal phase half-life cannot be calculated after administration of Humalog Mix50/50 because of the prolonged insulin lispro protamine suspension absorption.
Studies in nondiabetic subjects and patients with diabetes demonstrated that Humalog has a more rapid onset of glucose-lowering activity, an earlier peak for glucose-lowering, and a shorter duration of glucose-lowering activity than Regular human insulin. The early onset of activity of Humalog Mix50/50 is directly related to the rapid absorption of Humalog. The time course of action of insulin and insulin analogs, such as Humalog (and hence Humalog Mix50/50), may vary considerably in different individuals or within the same individual. The parameters of Humalog Mix50/50 activity (time of onset, peak time, and duration) as presented in Figures 2 and 3 should be considered only as general guidelines. The rate of insulin absorption and consequently the onset of activity is known to be affected by the site of injection, exercise, and other variables (see General under PRECAUTIONS).
In a glucose clamp study performed in 30 nondiabetic subjects, the onset of action and glucose-lowering activity of Humalog, Humalog Mix50/50, Humalog® Mix75/25™, and insulin lisproprotamine suspension (NPL component) were compared (see Figure 2). Graphs of mean glucoseinfusion rate versus time showed a distinct insulin activity profile for each formulation. The rapid onset of glucose-lowering activity characteristic of Humalog was maintained in Humalog Mix50/50.
Direct comparison between Humalog Mix50/50 and Humulin 50/50 was not performed. However, a cross-study comparison shown on Figure 3 suggests that Humalog Mix50/50 has a duration of activity that is similar to Humulin 50/50.
Figure 2: Glucose Infusion
Rates (A Measure of Insulin Activity) After Injection of Humalog, Humalog
Mix50/50, Humalog Mix75/25, or Insulin Lispro Protamine Suspension (NPL
Component) in 30 Nondiabetic Subjects.
Figure 3: Insulin Activity
After Subcutaneous Injection of Humalog Mix50/50 and Humulin 50/50 in
Figures 2 and 3 represent insulin activity profiles as measured by glucose clamp studies in healthy nondiabetic subjects.
Figure 2 shows the time activity profiles of Humalog, Humalog Mix75/25, Humalog Mix50/50, and insulin lispro protamine suspension (NPL component).
Figure 3 is a comparison of the time activity profiles of Humalog Mix50/50 (see Figure 3a) andof Humulin 50/50 (see Figure 3b) from two different studies.
Age and Gender — Information on the effect of age on the pharmacokinetics of Humalog Mix50/50 is unavailable. Pharmacokinetic and pharmacodynamic comparisons between men and women administered Humalog Mix50/50 showed no gender differences. In large Humalog clinical trials, sub-group analysis based on age and gender demonstrated that differences between Humalog and Regular human insulin in postprandial glucose parameters are maintained across sub-groups.
Smoking — The effect of smoking on the pharmacokinetics and pharmacodynamics of Humalog Mix50/50 has not been studied.
Pregnancy — The effect of pregnancy on the pharmacokinetics and pharmacodynamics of Humalog Mix50/50 has not been studied.
Obesity — The effect of obesity and/or subcutaneous fat thickness on the pharmacokinetics and pharmacodynamics of Humalog Mix50/50 has not been studied. In large clinical trials, which included patients with Body Mass Index up to and including 35 kg/m2, no consistent differences were observed between Humalog and Humulin® R with respect to postprandialglucose parameters.
Renal Impairment — The effect of renal impairment on the pharmacokinetics and pharmacodynamics of Humalog Mix50/50 has not been studied. In a study of 25 patients with type 2 diabetes and a wide range of renal function, the pharmacokinetic differences between Humalog and Regular human insulin were generally maintained. However, the sensitivity of the patients to insulin did change, with an increased response to insulin as the renal function declined. Careful glucose monitoring and dose reductions of insulin, including Humalog Mix50/50, may be necessary in patients with renal dysfunction.
Hepatic Impairment — Some studies with human insulin have shown increased circulating levels of insulin in patients with hepatic failure. The effect of hepatic impairment on the pharmacokinetics and pharmacodynamics of Humalog Mix50/50 has not been studied. However, in a study of 22 patients with type 2 diabetes, impaired hepatic function did not affect the subcutaneous absorption or general disposition of Humalog when compared with patients withno history of hepatic dysfunction. In that study, Humalog maintained its more rapid absorptionand elimination when compared with Regular human insulin. Careful glucose monitoring and dose adjustments of insulin, incl uding Humalog Mix50/50, may b e necessary in patients with hepatic dysfunction.
Last reviewed on RxList: 3/26/2013
This monograph has been modified to include the generic and brand name in many instances.
Additional Humalog Mix 50-50 Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find tips and advances in treatment.