Insulin Zinc

Registered South African indications:

• Diabetes mellitus

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypoglycaemia

Cautions

• Severe renal impairment or ESRD
• Severe hepatic impairment
• Elderly
• Transferring to another type or brand of insulin
• Changing from animal (especially bovine insulin) to human insulin
• Well-controlled diabetes
• Longstanding diabetes
• Concomitant infections
• Emotional stress
• Accidental or surgical trauma
• Puberty
• Increased physical activity
• Change in the usual diet

Forms avail. in SA and covered in this monograph: inj

Insulin-dependent diabetes mellitus 

• See link: General prescribing points on the principles of insulin dosing

Under no circumstances should insulin zinc be administered intravenously

The healthcare professional should determine the dosage of insulin zinc according to the requirements of the patient

See Additional Prescribing Points

No information available

Pregnancy

• Safe
• It is essential to maintain good control of the diabetic patient throughout pregnancy and, therefore diabetic patients should be advised to inform their doctor if they are pregnant or contemplating pregnancy
• During pregnancy, insulin requirements usually decrease during the first trimester and increase during the second and third trimesters
• The human pregnancy experience with regular insulin (with or without zinc) demonstrates that the risk of the embryo or foetal harm is low, if it exists at all
• As with all insulins, the primary concern is severe maternal hypoglycaemia
• It is not known if all insulin products cross the human placenta. Human insulin does not cross the placenta in clinically significant amounts
• Several reports have described the use of regular insulin in human pregnancy. These reports concluded that the insulin analogue had maternal efficacy and safety were similar to other insulins. No embryo-foetal adverse effects related to the drug were observed

Breastfeeding

• Compatible
• Insulin is a naturally-occurring constituent of the blood and is excreted into breast milk
• In a study, milk samples were obtained from breastfeeding mothers, the results showed that insulin, both endogenous and exogenous, are actively transported from the blood into milk and is protected from degradation and, presumably, has a functional or developmental role in the infant
• No metabolic effects of ingested insulin zinc on the breastfed newborn/infant are anticipated since insulin, as a peptide is digested into amino acids in the human gastrointestinal tract
• Breastfeeding women may require adjustments in insulin dose and diet

Fertility

• No information available

Renal impairment

• eGFR >30-89 ml/min/1.73m²: No dose adjustment recommended
• eGFR <29 ml/min/1.73m² or ESRD: Caution; dose adjustment recommended
  Reduce recommended dose by 20-40%. Monitor glucose target and renal function
• Patients on haemodialysis: No dose adjustment recommended

Hepatic impairment

• Mild to moderate (Child-Pugh Classes A & B): No dose adjustment recommended 
• Severe (Child-Pugh Class C): Caution; dose adjustment recommended
  Adjust insulin dose according to blood glucose target

Elderly

• Caution; dose adjustment recommended
  Reduce the initial recommended dose by 10%-20%. Conservative initial recommended dose is required to avoid risk for hypoglycaemia
• Severe hypoglycaemia: Caution; dose adjustment recommended
  Dosage reductions of 25%-50% have been recommended in these cases
  Control of geriatric patient's blood glucose needs to be individualised
  Avoid intensive glucose control (risk for hypoglycaemia and CVS-related mortality)

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Prohibited - At all times

Endocrine and Metabolic Disorders

• Hypoglycaemia
  - Headache
  - Visual disturbances
  - Hunger
  - Sweating
  - Palpitations
  - Anxiety
  - Tremor
  - Confusion
  - Convulsions
  - Coma

Skin and Subcutaneous Tissue Disorders

• Urticaria
• Injection site lipohypertrophy
• Injection site reactions
  - Erythema
  - Itching

Immune, Blood and Lymphatic System Disorders

• Generalised hypersensitivity reactions
• Anaphylactic reactions

Others

• Angioedema

• Angiotensin converting enzyme (ACE) inhibitors
• Enalapril
• Alcohol
• Anabolic steroids
• Aspirin
• Beta-blockers (may also mask the warning signs of hypoglycaemia)
• Disopyramide
• Fenfluramine
• Guanethidine
• Monoamine oxidase inhibitors (MAOIs)
• Selegiline
• Mebendazole
• Octreotide
• Tetracyclines
• Amitriptyline
• Chlordiazepoxide
• Chlorpromazine
• Calcium channel blockers
• Diltiazem
• Nifedipine
• Corticosteroids 
• Diazoxide
• Lithium
• Thiazide diuretics
• Thyroid hormones
• Cyclophosphamide
• Isoniazid
• Oral contraceptives

• Blood glucose testing
• Urine testing for ketones

General warnings

• Insulin zinc suspension should look uniformly milky after gently shaking
• If a deposit of solid particles remains on the bottom or wall of the cartridge/vial or if there are clumps floating in the insulin after the cartridge/vial has been rotated or carefully shaken, do not use
• If the insulin zinc suspension is clear and remains clear after the cartridge/vial is rotated or carefully shaken, it should also not be used

Method of administration

• Insulin zinc should only be administered via subcutaneous or intramuscular injection
• Appropriate sites for subcutaneous injection are the upper arm, thigh, buttock, or abdomen
• The injection site should not be massaged after injection
• Since lipohypertrophy is associated with repeated injections at the same site, the site of the subcutaneous injection should be rotated
• Patients should use a syringe marked for use with an insulin preparation that contains 100 units per ml, since use of an incorrect syringe could lead to dosage errors
• The patient should be educated regarding the use of proper injection techniques

Mixing of insulin

• Many insulin regimens involve the use of short-acting soluble insulin together with intermediate-acting insulin or a mixed insulin zinc suspension
• On the advice of a physician, short-acting insulins may be mixed with insulin zinc, usually twice daily
• The shorter-acting insulin should be drawn into the syringe first to prevent the longer-acting insulin zinc contaminating the vial
• It is recommended that patients inject immediately after mixing
• Such mixtures must not be administered intravenously

Administration using 10 ml vials and conventional insulin syringes

1. Wash hands
2. Remove the protective plastic cap on the vial
3. Use alcohol to wipe the exposed rubber top of the vial
4. Use the specified syringe needle, push the plunger right into the syringe and turn the vial and syringe upside down
5. Draw back on the plunger slowly to withdraw the correct dose of insulin zinc, while simultaneously avoiding drawing air into the syringe
6. To avoid clogging the needle, inject the required amount of insulin zinc promptly

Hypoglycaemia

• Hypoglycaemia in a conscious and cooperative patient is treated by administering sugar or glucose orally
• In cases of hypoglycaemic coma:
  - Up to 50 ml of a 50% solution of glucose should be administered intravenously or,
  - Glucagon 0.5-1.0 mg should be administered subcutaneously, intramuscularly or intravenously

Storage instructions

• Store in a refrigerator between 2^oC - 8^oC
• Do not freeze
• Protect from light

Insulin zinc is a suspension of large, zinc-containing crystals that have been precipitated in an acetate buffer that dissolve slowly after subcutaneous injection to release biosynthetic insulin. Biosynthetic insulin replaces the insufficient secretion of insulin by the β-cells of the pancreas to regulate glucose metabolism.

Injection (per ml) 100u

• Biosulin L (Dezzo Pharma)