Full Prescribing Info Contents Description Action Indications/Uses Dosage/Direction for Use Overdosage Contraindications Special Precautions Use In Pregnancy & Lactation Adverse Reactions Drug Interactions Caution For Usage Storage Patient Counseling Information MIMS Class ATC Classification Regulatory Classification Presentation/Packing Full Prescribing Info Contents Human insulin (recombinant DNA origin) consists of dissolved insulin 30%, isophane insulin 70%. Description Insulin human, rDNA (produced by recombinant DNA technology in Saccharomyces cerevisiae). 1 ml contains 100 IU of insulin human. One IU (International Unit) corresponds to 0.035 mg of anhydrous human insulin. Mixtard is a mixture of dissolved insulin and isophane (NPH) insulin. Mixtard 30 consists of 30% dissolved insulin and 70% isophane insulin. Mixtard 30: 1 vial contains 10 ml equivalent to 1,000 IU. Mixtard 30 Penfill: 1 cartridge contains 3 ml equivalent to 300 IU. Excipients/Inactive Ingredients: Zinc chloride, glycerol, metacresol, phenol, disodium phosphate dihydrate, sodium hydroxide/hydrochloric acid (for pH adjustment), protamine sulphate and water for injections. Action Pharmacotherapeutic group: Drugs used in diabetes. Insulins and analogues for injection, intermediate- or long-acting combined with fast-acting, insulin (human). ATC code: A10AD01. Pharmacology: Pharmacodynamics: The blood glucose lowering effect of insulin is due to the facilitated uptake of glucose following binding of insulin to receptors on muscle and fat cells and to the simultaneous inhibition of glucose output from the liver. Mixtard is a dual-acting insulin. Onset of action is within ½ hour, reaches a maximum effect within 2-8 hours and the entire duration of action is up to 24 hours. Pharmacokinetics: Insulin in the blood stream has a half-life of a few minutes. Consequently, the time-action profile of an insulin preparation is determined solely by its absorption characteristics. This process is influenced by several factors (e.g. insulin dosage, injection route and site, thickness of subcutaneous fat, type of diabetes). The pharmacokinetics of insulin products are therefore affected by significant intra- and inter-individual variation. Absorption: The absorption profile is due to the product being a mixture of insulin products with fast and protracted absorption respectively. The maximum plasma concentration of the fast-acting insulin is reached within 1.5-2.5 hours after subcutaneous administration. Distribution: No profound binding to plasma proteins, except circulating insulin antibodies (if present) has been observed. Metabolism: Human insulin is reported to be degraded by insulin protease or insulin-degrading enzymes and possibly protein disulfide isomerase. A number of cleavage (hydrolysis) sites on the human insulin molecule have been proposed; none of the metabolites formed following the cleavage are active. Elimination: The terminal half-life is determined by the rate of absorption from the subcutaneous tissue. The terminal half-life (t½) is therefore a measure of the absorption rather than of the elimination per se of insulin from plasma (insulin in the blood stream has a t½ of a few minutes). Trials have indicated a t½ of about 5-10 hours. Toxicology: Preclinical safety data: Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction. Indications/Uses Treatment of diabetes mellitus.