Insulin Lispro/ Insulin Lispro Protamine

Registered South African indications:

• Diabetes mellitus

Contraindications

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

Cautions

• Breastfeeding
• Severe renal impairment
• Severe hepatic impairment
• Elderly
• Hyperglycaemia
• Diabetic ketoacidosis
• Transfer from animal-source insulin to human insulin
• Transfer to another type or brand of insulin
• Conditions masking early warning symptoms of hypoglycaemia (e.g. long duration of diabetes, intensified insulin therapy, diabetic nerve disease)
• Illness or emotional disturbances
• Increased physical activity or change in usual diet
• Exercise immediately after a meal
• Risk factors for cardiac disease
• Insulin antibodies
• Coadministration of other medication
• May impair ability to drive and operate machinery (as a result of hypoglycaemia)

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

The dosage should be determined according to the individual requirement of the patient

Insulin lispro/ Insulin lispro protamine may be given shortly before meals and, when necessary, soon after meals in the upper arms, thighs, buttocks or abdomen

Insulin lispro/ Insulin lispro protamine should only be given by subcutaneous injection and never intravenously

Not established for use in children below 18 years

Any decision for using insulin lispro and lispro protamine in children must be approved by qualified diabetologist and/or endocrinologist

Pregnancy

• Safe
• Data on a large number of exposed pregnancies do not indicate any adverse effect of insulin lispro on pregnancy or on the health of the foetus/newborn
• It is essential to maintain good control of the insulin-treated (insulin-dependent or gestational diabetes) patient throughout pregnancy.Insulin requirements usually fall during the first trimester and increase during the second and third trimesters
• Patients with diabetes should be advised to inform their doctor if they are pregnant or are contemplating pregnancy. Careful monitoring of glucose control, as well as general health, is essential in pregnant patients with diabetes

Breastfeeding

• Caution
• Human insulin is excreted in human breast milk. For this reason, caution should be exercised when insulin lispro is administered to nursing mothers
• Patients with diabetes who are breastfeeding may require adjustments in diet

Fertility

• Insulin lispro did not induce fertility impairment in animal studies

Renal impairment

• eGFR ≥30-89 ml/min/1.73 m²: No dose adjustment recommended
• eGFR <29 ml/min/1.73 m²: Caution; dose adjustment recommended
  Adjust insulin dose according to blood glucose ranges

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 ranges

Elderly

• Caution; no dose adjustment recommended

Porphyria information

• Not yet classified (NC)

Drugs in Sport

• Prohibited - At all times

Endocrine and Metabolic Disorders

• Hypoglycaemia
  - Listlessness
  - Confusion
  - Palpitations
  - Headache
  - Sweating
  - Vomiting
• Weight gain

Skin and Subcutaneous Tissue Disorders

• Local allergy
  - Redness
  - Swelling
  - Itching at site of injection
• Lipodystrophy

Immune, Blood and Lymphatic System Disorders

• Systemic allergy
  - Rash over the whole body
  - Shortness of breath
  - Wheezing
  - Decreased blood pressure
  - Fast pulse
  - Sweating
• Oedema

Other

• Loss of consciousness

• Agents with hyper- or hypoglycaemic activity
• Oral contraceptives
• Corticosteroids
• Thyroid replacement therapy
• Danazol
• Beta2 stimulants 
• Ritodrine 
• Salbutamol 
• Terbutaline
• Alcohol
• Oral hypoglycaemic agents
• Thiazolidinediones
• Pioglitazone
• Salicylates
• Acetylsalicylic acid
• Sulphate antibiotics
• Antidepressants
• Monoamine oxidase inhibitors
• Selective serotonin reuptake inhibitors
• Angiotensin converting enzyme inhibitors
• Captopril
• Enalapril
• Angiotensin II receptor blockers
• Beta-blockers
• Octreotide

Diabetes mellitus

• Blood glucose
• Electrolytes
• HbA1c 
• Renal function
• Hepatic function
• Weight

Gestational diabetes mellitus

• Blood glucose 4 times daily (1 fasting and 3 postprandial) until well-controlled

Dosing

• A rapid onset and earlier peak of activity is observed with subcutaneous administration insulin lispro/ insulin lispro protamine that allows the preparation to be given within zero to 15 minutes of mealtime, i.e. shortly before or, when necessary, soon after meals. The duration of action of the insulin lispro protamine suspension component of insulin lispro/ insulin lispro protamine is similar to that of a basal insulin
• The time course of action of any insulin may vary considerably in different individuals or at different times in the same individual. As with all insulin preparations, the duration of action of insulin lispro/ insulin lispro protamine is dependent on dose, site of injection, blood supply, temperature and physical activity
• Insulin requirements may be altered during illness or emotional disturbances. Adjustment of dosage may also be necessary if patients undertake increased physical activity or change their usual diet

Method of administration

• Subcutaneous administration should be in the upper arms, thighs, buttocks, or abdomen. Use of injection sites should be rotated so that the same site is not used more than approximately once a month.Patients must be educated to use the proper injection techniques
• When administered subcutaneously, care should be taken when injecting insulin lispro/ insulin lispro protamine to ensure that a blood vessel has not been entered. After injection, the site of injection should not be massaged

Transfer to another type or brand of insulin

• Transferring a patient to another type or brand of insulin should be done under strict medical supervision. Changes in strength, brand (manufacturer), type (regular/soluble, NPH/isophane, etc.), species (animal, human, human insulin analogue), and/or method of manufacture (recombinant DNA versus animal-source insulin) may result in the need for a change in dosage

Avoidance of medication errors

• Patients must be instructed to always check the insulin label before each injection to avoid accidental mix-ups between the two different strengths of insulin products
• Patients must visually verify the dialled units on the dose counter of the pen. Therefore, the requirement for patients to self-inject is that they can read the dose counter on the pen
• Patients who are blind or have poor vision must be instructed to always get help/assistance from another person who has good vision and is trained in using the insulin device

Special precautions for storage and handling

• Before use, store products in a refrigerator (2°C - 8°C). Do not freeze
• Vials in use can be stored at or below 30 °C for 28 days if refrigeration is not possible. Do not expose to excessive heat or sunlight₂
• Cartridges and disposable pens in use should not be refrigerated but should be kept cool (at or below 30 °C) and away from heat and sunlight
• Unrefrigerated cartridges and disposable pens
  containing 3,0 ml cartridges should be discarded
  after 28 days, even if they still contain product. Do
  not use product after the expiry date
• Insulin lispro/ Insulin lispro protamine suspensions should look uniformly cloudy or milky. If the insulin lispro substance (the cloudy material) settles at the bottom of the container, it must be rotated or carefully shaken before injection so that the contents are uniformly mixed
• Do not use premixed suspensions if a deposit of solid particles remains on the bottom or on the wall of the container, giving it a frosted appearance, or if there are clumps floating in the insulin after the container has been rotated or carefully shaken. Also, an insulin lispro suspension should not be used if it is clear and remains clear after the container is rotated or shaken

Incompatibilities

• Mixing insulin lispro/ Insulin lispro protamine with other insulins has not been studied. In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products

Traceability

• In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded

The primary activity of insulin lispro is the regulation of glucose metabolism. In addition, insulins have several anabolic and anti-catabolic actions on a variety of different tissues. Within muscle tissue this includes increasing glycogen, fatty acid, glycerol and protein synthesis and amino acid uptake, while decreasing glycogenolysis, gluconeogenesis, ketogenesis, lipolysis, protein catabolism and amino acid output.

Insulin products are manufactured for pharmacologic use through recombinant DNA technology using either E. coli or Saccharomyces cerevisiae.

Insulin lispro differs from human insulin by containing a lysine and proline at positions B28 and B29, respectively.

COMBINATION PREPARATIONS

25% Insulin Lispro/ 75% Insulin Lispro Protamine

Injection (per ml) 100u

• Humalog Mix 25 (Eli Lilly) originator

50% Insulin Lispro/ 50% Insulin Lispro Protamine

Injection (per ml) 100u 

• Humalog Mix 50 (Eli Lilly) originator