Acilog Mix30% + 70%

Acilog Mix is a premixed suspension combining rapid-acting insulin aspart with intermediate-acting protamine-crystallised insulin aspart. It is indicated for the treatment of diabetes mellitus in patients who require insulin to control hyperglycaemia.

Established/Approved Uses

• To improve glycaemic control in adults and children with type 1 diabetes mellitus (as part of a basal-bolus or premixed insulin regimen, typically together with a longer-acting basal insulin where required).
• To improve glycaemic control in adults with type 2 diabetes mellitus, either alone or in combination with oral antidiabetic agents when oral therapy alone no longer provides adequate control.

Guideline-Supported / Practical Use

• As a twice-daily (or occasionally once- or thrice-daily) premixed regimen for patients who prefer a simpler injection schedule than a full basal-bolus regimen, particularly in resource-limited settings.

Acilog Mix is not a substitute for regular insulin during diabetic ketoacidosis or for intravenous use; it is intended for subcutaneous injection only.

Each mL of Biphasic Insulin Aspart [rDNA] suspension for injection contains 100 IU of insulin aspart (recombinant DNA origin), present as 30% soluble insulin aspart and 70% protamine-crystallised insulin aspart (the biphasic 30/70 mix is the most common marketed ratio). Other formulation ratios (e.g. 50/50, 70/30) may be available depending on the brand.

Excipients typically include glycerol, phenol, metacresol, zinc chloride, sodium hydrogen phosphate dihydrate, sodium chloride, protamine sulfate, and water for injection, with hydrochloric acid/sodium hydroxide for pH adjustment.

Acilog Mix is a biosynthetic, premixed insulin analogue suspension manufactured using recombinant DNA technology. It combines a rapid-acting fraction (soluble insulin aspart) that begins lowering blood glucose within 10-20 minutes, with an intermediate-acting fraction (protamine-crystallised insulin aspart) that provides a longer, more sustained glucose-lowering effect.

This dual-action profile is designed to cover both the immediate post-meal rise in blood glucose and the background insulin requirement between meals, in a single injection.

Acilog Mix belongs to the class of premixed (biphasic) insulin analogues, under the broader therapeutic category of antidiabetic agents/insulins used for the management of diabetes mellitus.

Biphasic Insulin Aspart [rDNA] acts on specific insulin receptors on cell membranes (particularly in liver, muscle, and adipose tissue) to lower blood glucose by:

• Stimulating peripheral glucose uptake by muscle and fat cells.
• Inhibiting hepatic glucose output (gluconeogenesis and glycogenolysis).
• Promoting protein synthesis and inhibiting lipolysis and proteolysis.

Insulin aspart differs from human insulin by a single amino acid substitution (proline replaced by aspartic acid at position B28), which reduces self-association and allows faster absorption after subcutaneous injection compared with regular human insulin. In Biphasic Insulin Aspart [rDNA], the soluble (rapid-acting) fraction provides a quick onset of action (approximately 10-20 minutes), peaking at 1-4 hours, while the protamine-crystallised (intermediate-acting) fraction dissolves more slowly, extending the glucose-lowering effect for up to 24 hours.

Acilog Mix should be injected subcutaneously 10-20 minutes before a meal, or as directed, into the abdomen, thigh, buttock, or upper arm, with rotation of injection sites. The suspension must be resuspended immediately before use until it appears uniformly white and cloudy. It must never be administered intravenously or used in insulin infusion pumps.

Several medicines can affect blood glucose control when used with Acilog Mix, requiring dose adjustment and closer monitoring.

Drugs That May Increase the Glucose-Lowering Effect (Increased Hypoglycaemia Risk)

• Oral antidiabetic agents, ACE inhibitors, disopyramide, fibrates, fluoxetine, MAO inhibitors, pentoxifylline, propoxyphene, salicylates, and sulfonamide antibiotics.

Drugs That May Reduce the Glucose-Lowering Effect (Increased Hyperglycaemia Risk)

• Corticosteroids, danazol, diuretics (thiazides), sympathomimetics, isoniazid, niacin, oral contraceptives/estrogens, phenothiazines, protease inhibitors, atypical antipsychotics, and thyroid hormones.

Drugs With Variable Effect

• Beta-blockers, clonidine, lithium salts, and alcohol may either potentiate or weaken the glucose-lowering effect of Acilog Mix; beta-blockers in particular may mask the warning symptoms of hypoglycaemia (such as tremor and palpitations), so patients on beta-blockers require extra vigilance.

Acilog Mix must not be mixed with other insulin products in the same syringe or pen.

The most common and clinically important adverse effect of Acilog Mix is hypoglycaemia, which can occur with any insulin therapy and may be severe if not promptly treated.

Very Common

• Hypoglycaemia (symptoms include sweating, palpitations, tremor, hunger, confusion, and in severe cases, seizure or loss of consciousness).

Common

• Injection-site reactions (redness, swelling, itching) - usually mild and transient.
• Lipodystrophy (lipohypertrophy or lipoatrophy) at repeated injection sites.
• Peripheral oedema, particularly when starting insulin therapy or intensifying glucose control.
• Weight gain.

Uncommon/Rare

• Generalised hypersensitivity/allergic reactions, including urticaria and, rarely, anaphylaxis.
• Refraction disorders (temporary blurred vision) at the start of insulin therapy due to rapid changes in blood glucose.

Pregnancy: Insulin, including Acilog Mix, is generally the preferred treatment for diabetes during pregnancy because good glycaemic control is important for maternal and fetal outcomes. However, Acilog Mix should be used only under close medical supervision, as insulin requirements typically fall in the first trimester and rise during the second and third trimesters. Use only if clearly needed and if the potential benefit justifies the potential risk; consult a physician before use in pregnancy.

Lactation: It is not known whether insulin aspart is excreted in human breast milk in clinically relevant amounts, but insulin is not expected to harm a breastfed infant since it is a protein that is digested in the infant's gastrointestinal tract. Breastfeeding mothers using Acilog Mix may need adjustment of insulin dose and diet; consult a physician.

Careful, individualised dose titration and regular blood glucose self-monitoring are essential during treatment with Acilog Mix.

• Hypoglycaemia: The principal risk of Acilog Mix; patients and caregivers should be educated on recognising early symptoms and on prompt treatment (e.g. oral glucose). Omitting meals, unplanned strenuous exercise, alcohol intake, or dose errors increase this risk.
• Hyperglycaemia and ketoacidosis: Inadequate dosing, missed doses, illness, or infection can lead to hyperglycaemia and, in type 1 diabetes, diabetic ketoacidosis, which is a medical emergency.
• Renal or hepatic impairment: May alter insulin clearance and requirements; more frequent monitoring and dose adjustment are recommended (see Dosage and Administration).
• Hypokalaemia: Insulin therapy can shift potassium into cells, causing hypokalaemia, particularly in patients with poor glycaemic control; monitor potassium levels where clinically indicated.
• Do not interchange between different insulin products, brands, or concentrations without medical guidance, as this can lead to dosing errors and severe hypoglycaemia or hyperglycaemia.
• Injection site rotation: Rotate injection sites within the same region to reduce the risk of lipodystrophy, which can affect insulin absorption.
• Concurrent illness, changes in diet, or physical activity require reassessment of the Acilog Mix dose in consultation with a physician.
• Beta-blockers and certain other medicines may mask the symptoms of hypoglycaemia (see Interactions).
• Acilog Mix must be resuspended immediately before injection and administered subcutaneously only - never intravenously or in an insulin pump.

An overdose of Acilog Mix relative to food intake, physical activity, or metabolic need can cause hypoglycaemia, which may be mild or severe.

• Mild hypoglycaemia can usually be treated promptly with oral glucose, sugary drinks, or fast-acting carbohydrates.
• Severe hypoglycaemia (with confusion, seizure, or unconsciousness) is a medical emergency - seek immediate medical attention or contact emergency services. Glucagon injection or intravenous glucose administered by a trained person or healthcare provider may be required, followed by close observation and further carbohydrate intake to prevent recurrence.

Do not attempt to manage severe hypoglycaemia or overdose at home without professional guidance; contact a physician, hospital, or poison control service immediately.

Unopened Acilog Mix: Store in a refrigerator at 2°C to 8°C (36°F to 46°F), away from the freezer compartment or cooling elements. Do not freeze; discard if it has been frozen.

In-use (opened) Acilog Mix: May be kept at room temperature (below 30°C), away from direct heat and light, for a limited period as specified by the manufacturer (commonly up to 4 weeks for vials/cartridges; consult the product leaflet for pen devices, which may have a shorter in-use period and should not be refrigerated once in use). Always keep out of reach of children.

Pediatric Use

Acilog Mix may be used in children with type 1 diabetes mellitus under specialist supervision, with individualised weight-based titration. Safety and efficacy in children under 2 years of age have not been established.

Elderly (Geriatric) Use

Clinical experience in patients 65 years and older is limited. Elderly patients, particularly those with renal or hepatic impairment or cardiovascular disease, should be started at the lower end of the dosing range with cautious, gradual titration due to increased risk of hypoglycaemia and its complications.

Renal Impairment

Insulin requirements may be reduced; monitor blood glucose closely and adjust dose accordingly.

Hepatic Impairment

Insulin requirements may be reduced due to decreased gluconeogenesis and insulin metabolism; monitor blood glucose closely and adjust dose accordingly.

Acilog Mix is generally used long-term as part of chronic diabetes management, since diabetes mellitus is a lifelong condition requiring ongoing glycaemic control. The specific regimen, dose, and duration are determined and periodically reassessed by the treating physician based on blood glucose control, HbA1c targets, and the patient's clinical status.

Biphasic Insulin Aspart [rDNA] is classified under: Insulins and analogues - Premixed (biphasic) insulin analogue for injection.

Biphasic Insulin Aspart [rDNA] lowers blood glucose by binding to insulin receptors on target cells, promoting glucose uptake into muscle and adipose tissue and suppressing hepatic glucose production. Its rapid-acting soluble component provides prompt post-prandial glucose control, while its intermediate-acting protamine-crystallised component provides a sustained basal-like effect between meals, giving a combined biphasic action profile from a single injection.

Category B (as per legacy FDA pregnancy categories applied to insulin aspart products)

Acilog Mix can be used in children and adolescents with type 1 diabetes mellitus, under the close supervision of a pediatric specialist, with individualised dosing based on body weight, growth, diet, and physical activity. Safety and efficacy have not been established in children below 2 years of age. Parents/caregivers should be trained in recognising and managing hypoglycaemia in the child.