İHALE DÜNYASI
İHALE DÜNYASI
Humalog (R) Mix75/25TM [75% insulin lispro protamine suspension and 25% insulin lispro injection, (rDNA origin)] is a mixture of insulin lispro solution, a rapid-acting blood glucose-lowering agent and insulin lispro protamine suspension, an intermediate-acting blood glucose-lowering agent. Chemically, insulin lispro is Lys(B28), Pro(B29) human insulin analog, created when the amino acids at positions 28 and 29 on the insulin B-chain are reversed. Insulin lispro is synthesized in a special non-pathogenic laboratory strain of Escherichia coli bacteria that has been genetically altered to produce insulin lispro. Insulin lispro protamine suspension (NPL component) is a suspension of crystals produced from combining insulin lispro and protamine sulfate under appropriate conditions for crystal formation. Insulin lispro has the following primary structure: Insulin lispro has the empirical formula C 257 H 383 N 65 O 77 S 6 and a molecular weight of 5808, both identical to that of human insulin. Humalog Mix75/25 vials and Pens contain a sterile suspension of insulin lispro protamine suspension mixed with soluble insulin lispro for use as an injection. Each milliliter of Humalog Mix75/25 injection contains insulin lispro 100 units, 0.28 mg protamine sulfate, 16 mg glycerin, 3.78 mg dibasic sodium phosphate, 1.76 mg Metacresol, zinc oxide content adjusted to provide 0.025 mg zinc ion, 0.715 mg phenol, and Water for Injection. Humalog Mix75/25 has a pH of 7.0 to 7.8. Hydrochloric acid 10% and/or sodium hydroxide 10% may have been added to adjust pH. Primary Structure
Humalog Mix75/25, a mixture of 75% insulin lispro protamine suspension and 25% insulin lispro injection, (rDNA origin), is indicated in the treatment of patients with diabetes mellitus for the control of hyperglycemia. Humalog Mix75/25 has a more rapid onset of glucose-lowering activity compared with Humulin 70/30 while having a similar duration of action. This profile is achieved by combining the rapid onset of Humalog with the intermediate action of insulin lispro protamine suspension.
Table 1: Summary of Pharmacodynamic Properties of Insulin Products (Pooled Cross-Study Comparison) Insulin Products Dose, U/kg Time of Peak Activity, Hours After Dosing Percent of Total Activity Occurring in the First 4 Hours Humalog 0.3 2.4 (0.8 - 4.3) 70% (49 - 89%) Humulin R 0.32 (0.26 - 0.37) 4.4 (4.0 - 5.5) 54% (38 - 65%) Humalog Mix75/25 0.3 2.6 (1.0 - 6.5) 35% (21 - 56%) Humulin 70/30 0.3 4.4 (1.5 - 16) 32% (14 - 60%) Humalog Mix50/50 0.3 2.3 (0.8 - 4.8) 45% (27 - 69%) Humulin 50/50 0.3 3.3 (2.0 - 5.5) 44% (21 - 60%) NPH 0.32 (0.27 - 0.40) 5.5 (3.5 - 9.5) 14% (3.0 - 48%) NPL component 0.3 5.8 (1.3 - 18.3) 22% (6.3 - 40%) Humalog Mix75/25 is intended only for subcutaneous administration. Humalog Mix75/25 should not be administered intravenously. Dosage regimens of Humalog Mix75/25 will vary among patients and should be determined by the healthcare provider familiar with the patient's metabolic needs, eating habits, and other lifestyle variables. Humalog 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. Humalog Mix75/25 has a similar glucose-lowering effect as compared with Humulin 70/30 on a unit for unit basis. The quicker glucose-lowering effect of Humalog is related to the more rapid absorption rate of insulin lispro from subcutaneous tissue. Humalog Mix75/25 starts lowering blood glucose more quickly than Regular human insulin, allowing for convenient dosing immediately before a meal (within 15 minutes). In contrast, mixtures containing Regular human insulin should be given 30 to 60 minutes before a meal. The rate of insulin absorption and consequently the onset of activity are known to be affected by the site of injection, exercise, and other variables. As with all insulin preparations, the time course of action of Humalog Mix75/25 may vary considerably in different individuals or within the same individual. Patients must be educated to use proper injection techniques. Humalog Mix75/25 should be inspected visually before use. Humalog Mix75/25 should be used only if it appears uniformly cloudy after mixing. Humalog Mix75/25 should not be used after its expiration date.
Humalog Mix75/25 is contraindicated during episodes of hypoglycemia and in patients sensitive to insulin lispro or any of the excipients contained in the formulation.
Clinical studies comparing Humalog Mix75/25 with human insulin mixtures did not demonstrate a difference in frequency of adverse events between the two treatments. Adverse events commonly associated with human insulin therapy include the following: Body as a Whole - allergic reactions ( see PRECAUTIONS ). Skin and Appendages - injection site reaction, lipodystrophy, pruritus, rash. Other - hypoglycemia ( see WARNINGS and PRECAUTIONS ).
Humalog differs from Regular human insulin by its rapid onset of action as well as a shorter duration of activity. Therefore, the dose of Humalog Mix75/25 should be given within 15 minutes before a meal. Hypoglycemia is the most common adverse effect associated with the use of insulins, including Humalog Mix75/25. As with all insulins, the timing of hypoglycemia may differ among various insulin formulations. Glucose monitoring is recommended for all patients with diabetes. Any change of insulin should be made cautiously and only under medical supervision. Changes in insulin strength, manufacturer, type (e.g., Regular, NPH, analog), species, or method of manufacture may result in the need for a change in dosage.
Insulin requirements may be increased by medications with hyperglycemic activity such as corticosteroids, isoniazid, certain lipid-lowering drugs (e.g., niacin), estrogens, oral contraceptives, phenothiazines, and thyroid replacement therapy. Insulin requirements may be decreased in the presence of drugs that increase insulin sensitivity or have hypoglycemic activity, such as oral antidiabetic agents, salicylates, sulfa antibiotics, certain antidepressants (monoamine oxidase inhibitors), angiotensin-converting-enzyme inhibitors, angiotensin II receptor blocking agents, beta-adrenergic blockers, inhibitors of pancreatic function (e.g., octreotide), and alcohol. Beta-adrenergic blockers may mask the symptoms of hypoglycemia in some patients.