Premixed Human Insulin 70 30

Premixed human insulin 70 30 is a cloudy suspension of 70% NPH insulin and 30% regular insulin, given subcutaneously twice daily before breakfast and the evening meal. It is the cheapest premixed insulin and widely used in public facilities, mainly in type 2 diabetes. It needs fixed meal times and snacks because its NPH component peaks 4 to 8 hours after injection.

Classification. Premixed human insulin; 30% soluble (regular) insulin and 70% isophane (NPH) insulin. Vials and pens of 100 units/mL (U100). Other ratios exist, such as 50 50 and 80 20.

Mechanism. Binds the insulin receptor, increasing glucose uptake, suppressing hepatic glucose output and ketogenesis, and driving potassium into cells. The regular fraction covers the meal and the NPH fraction covers the following hours.

Pharmacodynamics. Onset 30 to 60 minutes; two peaks, the first at 2 to 4 hours (regular) and the second at 4 to 8 hours (NPH); duration up to 16 to 24 hours.

Pharmacokinetics. Absorption varies with site, exercise and mixing. Cleared by the liver and kidney.

Type 2 diabetes, adults, starting.

• Start 10 units subcutaneously twice daily, 30 minutes before breakfast and before the evening meal; or 0.2 to 0.3 unit/kg/day divided equally. Use 6 units twice daily in older adults.
• When changing from basal insulin, give about half of the previous daily dose before each of the two meals; when changing from NPH plus regular insulin, give the same total daily dose.

Titration.

• Adjust the morning dose by the pre-evening meal glucose and the evening dose by the fasting glucose, by 2 units every 3 days (4 units if glucose is over 10 mmol/L), to a target of 4 to 7 mmol/L before meals.
• Reduce the dose by 10 to 20% after any hypoglycaemia. No fixed maximum; over about 1 unit/kg/day, or recurrent hypoglycaemia, change to a basal-bolus regimen.

Type 1 diabetes. Not advised where a basal-bolus regimen with separate insulins is available. Where it is the only option, use it with strict meal timing and snacks, and expect poorer control and more hypoglycaemia.

Pregnancy. Used when other options are unavailable; fixed ratios make it hard to match changing needs.

Children. Not usually used; a basal-bolus or split regimen with separate insulins is preferred.

Adjustments.

• Kidney: reduce dose by about 25% when eGFR is 10 to 50 and about 50% when under 10, adjusted to glucose.
• Liver: reduce dose in cirrhosis and acute liver failure.
• Older adults: start at the lower dose and use less strict targets.
• Weight: dose by weight at the start of treatment.

Contraindications. Hypoglycaemia; hypersensitivity to insulin or protamine (rare).

Hypoglycaemia. The main risk, particularly mid-morning, mid-afternoon and at night when meals are late or skipped. Treat glucose under 4 mmol/L (70 mg/dL) with 15 to 20 g fast oral glucose and recheck at 15 minutes. For severe hypoglycaemia give intravenous glucose 10% 150 to 200 mL over 15 minutes, or glucagon 1 mg intramuscularly or subcutaneously (0.5 mg for children under 25 kg).

Other serious adverse effects.

• Weight gain; lipohypertrophy at repeated injection sites with erratic absorption; rotate sites.
• Rare insulin allergy and injection site reactions; fluid retention with pioglitazone.
• Not for intravenous use or for ketoacidosis.

Common prescribing errors.

• Not resuspending the vial or pen, which gives wrong early and late doses.
• Giving the premixed insulin when a patient cannot eat at regular times.
• Using a syringe that does not match the vial concentration, or confusing units with millilitres.
• Confusing the premixed pen with the basal or rapid-acting pen.

Major interactions.

• Increased hypoglycaemia: sulphonylureas, ACE inhibitors, fibrates, fluoxetine, monoamine oxidase inhibitors, salicylates, alcohol.
• Reduced effect: corticosteroids, thiazides, atypical antipsychotics, oestrogen-containing contraceptives, protease inhibitors, thyroid hormones.
• Beta-blockers mask hypoglycaemia symptoms.
• Pioglitazone and insulin together: fluid retention and heart failure.

Special groups.

• Pregnancy: compatible but inflexible; needs rise from the second trimester and fall sharply after delivery.
• Breastfeeding: compatible; needs fall in lactation.
• Children: not usually used.
• Older adults: need steady meals; high risk of hypoglycaemia between meals; relax targets.
• Kidney impairment: reduce doses; prolonged action.
• Liver impairment: reduce doses.
• East Africa: usually the most available and affordable insulin regimen where two daily injections suit patients with fixed routines. Patients fasting during Ramadan need a split of the dose (full dose at sunset, reduced dose before dawn). Unopened vials keep in a fridge (2 to 8 degrees Celsius); an in-use vial or pen keeps at room temperature up to 25 degrees Celsius for 28 days; protect from direct sunlight and never freeze.

Formulation and preparation. Cloudy white suspension. Roll the vial or pen gently between the palms 10 times and tip it up and down until evenly cloudy; do not shake. Use U100 syringes with U100 vials. Do not mix with other insulins.

Subcutaneous administration. Inject 30 minutes before the meal into the abdomen (morning) or thigh (evening); rotate sites. Eat a snack between meals and at bedtime. Never give intravenously.

Baseline. Capillary glucose, HbA1c, eGFR, hypoglycaemia history, meal pattern.

Monitoring.

• Pre-breakfast, pre-evening meal and bedtime capillary glucose during titration; occasional 3 a.m. glucose when nocturnal hypoglycaemia is suspected.
• HbA1c every 3 months.
• eGFR at least annually.

Dose reduction and stopping. Reduce the dose by 10 to 20% after any hypoglycaemia without a clear cause. Change to a basal-bolus regimen when meals are irregular, hypoglycaemia recurs or total dose is high.

Referral and escalation. Admit severe hypoglycaemia (observe at least 24 hours after large doses), ketoacidosis or glucose over 25 mmol/L (450 mg/dL) with illness.