Insulin (Human) R
Indications
Insulin (Human) R is used for:
Diabetic ketoacidosis, Diabetes mellitus
Adult Dose
Subcutaneous
Type 1 Diabetes Mellitus
Initial: 0.2-0.4 units/kg/day SC divided q8hr or more frequently
Maintenance: 0.5-1 unit/kg/day SC divided q8hr or more frequently; in insulin-resistant patients (eg, due to obesity), substantially higher daily insulin may be required
Approximately 50-75% of the total daily insulin requirements are given as intermediate- or long-acting insulin administered in 1-2 injections; rapid- or short-acting insulin should be used before or at mealtimes to satisfy the remainder balance of the total daily insulin requirements
Type 2 Diabetes Mellitus
Type 2 diabetes inadequately controlled by diet, exercise, or oral medication:
Initial: 0.2-0.4 units/kg/day SC divided q8hr-q12hr
Intramuscular
Diabetic ketoacidosis
Adult: As soluble insulin, initial loading dose of 20 units, followed by 6 units/hr until blood glucose drops to 10 mmol/l, when the dose is given 2 hrly.
Intravenous
Diabetic ketoacidosis
Adult: As soluble insulin, given in concentration of 1 unit/ml using an infusion pump: Initially infuse at a rate of 6 units/hr, double or quadruple the rate if blood glucose concentration do not decrease by about 5 mmol/l/hr.
If blood glucose concentrations have decreased to 10 mmol/l, reduce the infusion rate to 3 units/hr and continue with 5% glucose to prevent hypoglycaemia, until the patient can eat orally.
Do not stop the insulin infusion before SC insulin is started. Ensure adequate fluid replacement and include potassium chloride in the infusion to prevent insulin-induced hypokalaemia.
Hyperkalemia
5-10 units IV insulin in 50 mL D50W (25 g) infused over 15-30 min
When combined with NPH/Intermediate acting insulin:
Morning
Give two thirds of daily insulin SC
Ratio of regular insulin to NPH insulin 1:2
Evening
Give one third of daily insulin SC
Ratio of regular insulin to NPH insulin 1:1
Dosing Considerations
Dosage of human insulin, must be based on the results of blood and urine glucose tests and must be carefully individualized to optimal effect
Dose adjustments should be based on regular blood glucose testing
Adjust to achieve appropriate glucose control
Hepatic impairment: Dosage reduction may be needed.
Child Dose
Subcutaneous
Type 1 Diabetes Mellitus
Initial: 0.2-0.4 unit/kg/day SC divided q8hr or more frequently
Maintenance: 0.5-1 unit/kg/day SC divided q8hr or more frequently; in insulin-resistant patients (eg, due to obesity), substantially higher daily insulin may be required
Adolescents: May require up to 1.5 mg/kg/day during puberty
The average total daily insulin requirement for prepubertal children varies from 0.7-1 unit/kg/day but may be much lower
Renal Dose
Renal impairment: Dose adjustments may be needed.
Administration
Administer within 15 minutes before a meal or immediately after a meal.
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.
Contra Indications
Hypoglycaemia.Hypersensitivity to any of the components.
Precautions
Pregnancy (insulin requirements tend to fall during the 1st trimester, increase during the 2nd and 3rd) and lactation. Caution with decreased insulin requirements: Diarrhea, nausea/vomiting, malabsorption, hypothyroidism, renal impairment, hepatic impairment
Hypokalemia may occur
Use with caution in renal and hepatic impairment (dosage requirements may be reduced)
Caution with increased insulin requirements: Fever, hyperthyroidism, trauma, infection, surgery
Lactation: Safe to use while breastfeeding
Pregnancy-Lactation
Pregnancy
Available data from published studies over decades have not established association with human insulin use during pregnancy and major birth defects, miscarriage or adverse maternal or fetal outcomes
There are risks to mother and fetus associated with poorly controlled diabetes in pregnancy; animal reproduction studies were not performed
Clinical considerations
Poorly controlled diabetes in pregnancy increases maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, stillbirth, and delivery complications; poorly controlled diabetes increases fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity
Lactation
Available data from published literature suggests that exogenous human insulin products, are transferred into human milk; there are no adverse reactions reported in breastfed infants in the literature; there are no data on effects of exogenous human insulin products, on milk production
Consider developmental and health benefits of breastfeeding along with the mother’s clinical need for therapy, and any potential adverse effects on breastfed infant from drug, or from underlying maternal condition
Interactions
Possible absence of hypoglycaemic warning symptoms with beta-blockers. Decreased hypoglycaemic effect with corticosteroids, danazol, diazoxide, diuretics, glucagon, isoniazid, phenothiazine derivatives, somatropin, sympathomimetic agents, thyroid hormones, oestrogens, progestins (e.g. in oral contraceptives), protease inhibitors and atypical antipsychotic (e.g. olanzapine and clozapine). Increased hypoglycaemic effect with oral antidiabetic agents, ACE inhibitors, disopyramide, fibrates, fluoxetine, MAOIs, pentoxifylline, propoxyphene, salicylates and sulfonamide antibiotics. Decreased insulin resistance with octreotide and lanreotide. Increased risk of wt gain and peripheral oedema with pioglitazone, rosiglitazone. Decreased effect of sermorelin.
Adverse Effects
Side effects of Insulin (Human) R :
Allergic reactions. Injection site reaction, lipodystrophy, pruritus, rash, lipoatrophy, hypokalaemia, blurred vision. Hypoglycaemia, insulin resistance.
Headache, Influenza-like symptoms, Dyspepsia, Diarrhea, Back pain, Pharyngitis,
Mechanism of Action
Insulin lowers blood glucose levels. It regulates carbohydrate, protein and fat metabolism by inhibiting hepatic glucose production and lipolysis, and enhancing peripheral glucose disposal. The various insulin formulations are classified according to their durations of action after SC Inj. They are divided into short-, intermediate-, or long-acting insulin. Soluble insulin (also known as 'neutral insulin' or 'regular insulin') is a short-acting preparation.
To extend the duration of action of insulin, preparations are formulated as suspensions in 2 methods. The 1st method involves complexing insulin with a protein so that it is slowly released, e.g. protamine zinc insulin (contains an excess of protamine) and isophane insulin (or NPH insulin which contains equal amounts of protamine and insulin). An alternative method is particle size modification e.g. insulin zinc suspensions. While all the formulations can be admin by SC inj, most by IM inj, only soluble insulin can be admin by IV. Compared to SC inj, IM admin usually has a faster onset of action, with a shorter duration of action.