Insulin Aspart Biphasic

Insulin Aspart Biphasic is used for: Diabetes mellitus

Subcutaneous Diabetes Mellitus Combination rapid-onset (faster than regular insulin) and intermediate-acting insulins in fixed dose Typical daily insulin requirements range between 0.5-1 unit/kg Dose regimen varies among patients depending on metabolic needs; Administer SC q12hr (ie, before breakfast and evening meal); each dose intended to cover 2 meals or a meal and snack Dosing Considerations: Insulin naive patients: For patients with type 2 diabetes, the recommended starting dose of Insulin Aspart 30/70 is 6 Units at breakfast and 6 Units at dinner (evening meal). Insulin Aspart 30/70 can also be initiated once daily with 12 units at dinner (evening meal). How to intensify: Insulin Aspart 30/70 can be intensified from once daily to twice daily. When using Insulin Aspart 30/70 once daily, it is generally recommended to move to twice daily when reaching 30 units by splitting the dose into equal breakfast and dinner doses. From Insulin Aspart 30/70 twice daily to thrice daily: If twice daily dosing with Insulin Aspart 30/70 results in recurrent daytime hypoglycaemic episodes, the morning dose can be split into morning and lunchtime doses. The dinner doses remain unchanged. How to adjust the dose: - Adjust the dose of Insulin Aspart 30/70 on the basis of the lowest pre-meal blood glucose level from the three previous days - Dose adjustment can be made once a week until target HbA1c is reached - The dose should not be increased if hypoglycemia occurred within three days - Adjustment of dose may be necessary if patients undertake increased physical activity, change their usual diet or during concomitant illness The following titration guideline is recommended for dose adjustments: Pre-meal blood glucose level Dose adjustment < 4.4 mmol/l < 80 mg/dl - 2 units 4.4 – 6.1 mmol/l 80 – 110 mg/dl 0 6.2 – 7.8 mmol/l 111 – 140 mg/dl + 2 units 7.9 – 10 mmol/l 141 – 180 mg/dl + 4 units > 10 mmol/l > 180 mg/dl + 6 units

Safety and efficacy not established

Renal impairment: Dose adjustments may be needed.

Administer subcutaneously in the upper arm, thigh or abdominal wall. A subcutaneous injection into the abdominal wall results in a faster absorption than from other injection sites.

Hypoglycaemia.Hypersensitivity to any of the components.

Rapid changes in serum glucose may induce symptoms of hypoglycemia Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions (eg, long duration of diabetes, diabetic nerve disease, use of beta-blockers or intensified diabetes control) Caution in conditions with decreased insulin requirements (eg, diarrhea, nausea, vomiting, malabsorption, hypothyroidism, renal impairment, hepatic impairment) Caution in conditions with increased insulin requirements (eg, fever, hyperthyroidism, trauma, infection, surgery) May cause a shift in potassium from extracellular to intracellular space, possibly leading to hypokalemia; caution when coadministered with potassium-lowering drugs or conditions that may decrease potassium Frequent glucose monitoring and insulin dose reduction may be required with renal or hepatic impairment; not recommended during periods of rapidly declining renal or hepatic function because of risk for prolonged hypoglycemia

Pregnancy Available information from published randomized controlled trials during second trimester of pregnancy have not reported association with insulin aspart and major birth defects or adverse maternal or fetal outcomes Poorly controlled diabetes in pregnancy increases maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications; poorly controlled diabetes increases fetal risk for major birth defects, still birth, and macrosomia related morbidity Animal data In animal reproduction studies, administration of subcutaneous insulin aspart to pregnant rats and rabbits during period of organogenesis did not cause adverse developmental effects at exposures 8-times and equal to human subcutaneous dose of 1 unit/kg/day, respectively; pre- and post-implantation losses and visceral/skeletal abnormalities were seen at higher exposures, which are considered secondary to maternal hypoglycemia; these effects were similar to those observed in rats administered regular human insulin Lactation There are no data on presence of insulin in human milk, effects on breastfed infant, or on milk production; one small published study reported that exogenous insulin, including insulin aspart, was present in human milk; however, there is insufficient information to determine effects of insulin aspart on breastfed infant; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy, and any potential adverse effects on breastfed infant from drug, or from underlying maternal condition

Reduce insulin requirements w/ oral hypoglycemics, octreotide, MAOIs, nonselective ?-adrenergic blockers, ACE inhibitors, salicylates, alcohol, anabolic steroids & sulfonamides; increase insulin requirements w/ OCs, thiazides, glucocorticoids, thyroid hormones, sympathomimetics & danazol. ?-blocking agents may mask the symptoms of hypoglycaemia. Alcohol may intensify & prolong the glucose lowering effect of insulin.

Side effects of Insulin Aspart Biphasic : >10% Hypoglycemia (47-69%) Headache (12-35%) Influenza-like symptoms (12-13%) 1-10% Headache (9%) Dyspepsia (9%) Diarrhea (7-8%) Back pain (7%) Pharyngitis (6-7%) Frequency Not Defined Insulin resistance Lipodystrophy Lipohypertrophy Local allergic reaction Hypokalemia Weight gain Peripheral edema

Insulin Aspart Biphasic is a biphasic suspension of soluble insulin aspart (rapid-acting human insulin analogue) and protamine-crystallised insulin aspart (intermediate-acting human insulin analogue). The blood glucose lowering effect of Insulin Aspart Biphasic 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. Soluble insulin aspart which has a rapid onset of action, thus allowing it to be given closer to a meal (within zero to 10 minutes of the meal) when compared to soluble human insulin. The crystalline phase consists of protamine-crystallised insulin aspart, which has an activity profile similar to that of human NPH insulin. When Insulin Aspart Biphasic is injected subcutaneously, the onset of action will occur within 10 to 20 minutes of injection. The maximum effect is exerted between 1 and 4 hours after injection. The duration of action is up to 24 hours.