Humalog 100 units/ml Solution for Injection.

HUMALOG is indicated for the treatment of patients with diabetes mellitus who require insulin for the maintenance of normal glucose homeostasis. HUMALOG is also indicated for the initial stabilisation of diabetes mellitus. HUMALOG solutions have a more rapid onset of action and shorter duration of action than human regular insulin. Therefore, in Type 1 diabetes, HUMALOG solutions should be used in regimens that include a longer-acting insulin. However, in patients with Type 2 diabetes, HUMALOG solutions may be used without a longer-acting insulin when used in combination therapy with sulphonylurea agents.

Posology
The dose should be determined by the healthcare professional, according to the requirements of the patient. HUMALOG may be given shortly before meals. When necessary, HUMALOG can be given soon after meals. HUMALOG takes effect rapidly and has a shorter duration of activity (2 to 5 hours) given subcutaneously as compared with soluble insulin. This rapid onset of activity allows a HUMALOG injection (or, in the case of administration by continuous subcutaneous infusion, a HUMALOG bolus) to be given very close to mealtime. The time course of action of any insulin may vary considerably in different individuals or at different times in the same individual. The faster onset of action compared to soluble human insulin is maintained regardless of injection site. As with all insulin preparations, the duration of action of HUMALOG is dependent on dose, site of injection, blood supply, temperature, and physical activity. HUMALOG can be administered in conjunction with a longer-acting insulin or oral sulphonylurea medicines on the advice of a medical practitioner.
Special populations
Renal impairment
Insulin requirements may be reduced in the presence of renal impairment.
Hepatic impairment
Insulin requirements may be reduced in patients with hepatic impairment due to reduced capacity for gluconeogenesis and reduced insulin breakdown; however, in patients with chronic hepatic impairment, an increase in insulin resistance may lead to increased insulin requirements.
Paediatric population
HUMALOG can be used in adolescents and children (see section 5.1).
Method of administration
Subcutaneous use
HUMALOG preparations should be given by subcutaneous injection. The KwikPen is only suitable for subcutaneous injections. HUMALOG in cartridges is only suitable for subcutaneous injections from a Lilly reusable pen or compatible pump systems for continuous subcutaneous infusion (CSII). 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, in order to reduce the risk of lipodystrophy and cutaneous amyloidosis (see section 4.4 and 4.8). When administered subcutaneously care should be taken when injecting HUMALOG to ensure that a blood vessel has not been entered. After injection, the site of injection should not be massaged. Patients must be educated to use proper injection techniques.

Hypersensitivity to insulin lispro or to any of the excipients listed in section 6.1. Hypoglycaemia.

Transferring of a patient to another type or brand
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. For fast-acting insulins, any patient also on basal insulin must optimise dosage of both insulins to obtain glucose control across the whole day, particularly nocturnal/fasting glucose control.
Vial
When mixing HUMALOG with a longer acting insulin, the shorter-acting HUMALOG should be drawn into the syringe first, to prevent contamination of the vial by the longer-acting insulin. Mixing of the insulins ahead of time or just before the injection should be on advice of the medical practitioner. However, a consistent routine must be followed.
Hypoglycaemia and hyperglycaemia
Conditions which may make the early warning symptoms of hypoglycaemia different or less pronounced include long duration of diabetes, intensified insulin therapy, diabetic nerve disease or medications such as beta-blockers. A few patients who have experienced hypoglycaemic reactions after transfer from animal-source insulin to human insulin have reported that the early warning symptoms of hypoglycaemia were less pronounced or different from those experienced with their previous insulin. Uncorrected hypoglycaemic or hyperglycaemic reactions can cause loss of consciousness, coma, or death. The use of dosages which are inadequate or discontinuation of treatment, especially in insulin-dependent diabetics, may lead to hyperglycaemia and diabetic ketoacidosis; conditions which are potentially lethal.
Injection technique
Patients must be instructed to perform continuous rotation of the injection site to reduce the risk of developing lipodystrophy and cutaneous amyloidosis. There is a potential risk of delayed insulin absorption and worsened glycaemic control following insulin injections at sites with these reactions. A sudden change in the injection site to an unaffected area has been reported to result in hypoglycaemia. Blood glucose monitoring is recommended after the change in the injection site, and dose adjustment of antidiabetic medications may be considered.
Insulin requirements and dosage adjustment
Insulin requirements may be increased during illness or emotional disturbances. Adjustment of dosage may also be necessary if patients undertake increased physical activity or change their usual diet. Exercise taken immediately after a meal may increase the risk of hypoglycaemia. A consequence of the pharmacodynamics of rapid-acting insulin analogues is that if hypoglycaemia occurs, it may occur earlier after an injection when compared with soluble human insulin.
Combination of HUMALOG with pioglitazone
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, especially in patients with risk factors for development of cardiac failure. This should be kept in mind, if treatment with the combination of pioglitazone and HUMALOG is considered. If the combination is used, patients should be observed for signs and symptoms of heart failure, weight gain and oedema. Pioglitazone medications should be discontinued if any deterioration in cardiac symptoms occurs.
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 HUMALOG KWIKPEN as well as other 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.
HUMALOG contains sodium
This medicine contains less than 1 mmol sodium (23 mg) per dose, i.e., essentially u201csodium-freeu201d.

Insulin requirements may be increased by medicines with hyperglycaemic activity, such as oral contraceptives, corticosteroids or thyroid replacement therapy, danazol, beta 2 stimulants (such as ritodrine, salbutamol, terbutaline). Insulin requirements may be decreased in the presence of medicines with hypoglycaemic activity, such as oral hypoglycaemics, salicylates (for example, acetylsalicylic acid), sulpha antibiotics, certain anti-depressants (monoamine oxidase inhibitors, selective serotonin reuptake inhibitors), certain angiotensin converting enzyme inhibitors (captopril, enalapril), angiotensin II receptor blockers, beta-blockers, octreotide or alcohol. The healthcare professional should be consulted when using other medicines in addition to HUMALOG (see section 4.4).

Pregnancy
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
Patients with diabetes who are breastfeeding may require adjustments in insulin dose, diet or both.
Fertility
Insulin lispro did not induce fertility impairment in animal studies (see section 5.3).

The patientu2019s ability to concentrate and react may be impaired as a result of hypoglycaemia. This may constitute a risk in situations where these abilities are of special importance (e.g. driving a car or operating machinery). Patients should be advised to take precautions to avoid hypoglycaemia whilst driving, this is particularly important in those who have reduced or absent awareness of the warning signs of hypoglycaemia or have frequent episodes of hypoglycaemia. The advisability of driving should be considered in these circumstances.

Summary of safety profile
Hypoglycaemia is the most frequent undesirable effect of insulin therapy that a patient with diabetes may suffer. Severe hypoglycaemia may lead to loss of consciousness, and in extreme cases, death. No specific frequency for hypoglycaemia is presented, since hypoglycaemia is a result of both the insulin dose and other factors e.g., a patientu2019s level of diet and exercise.
Tabulated list of adverse reactions
The following related adverse reactions from clinical trials are listed below as MedDRA preferred term by system organ class and in order of decreasing incidence (very common: u2265 1/10; common: u2265 1 /100 to < 1/10; uncommon: u2265 1/1 000 to < 1/100; rare: u2265 1/10 000 to < 1/1 000; very rare: < 1/10 000); not known (cannot be estimated form the available data).
MedDRA system organ class
Very common: Immune system disorder - Local allergy
Common: Immune system disorder - Systemic allergy
Uncommon: Skin and subcutaneous tissue disorders - Lipodystrophy
Uncommon: Skin and subcutaneous tissue disorders - Cutaneous amyloidosis
Description of selected adverse reactions
Local allergy
Local allergy in patients is common. Redness, swelling, and itching can occur at the site of insulin injection. This condition usually resolves in a few days to a few weeks. In some instances, this condition may be related to factors other than insulin, such as irritants in the skin cleansing agent or poor injection technique.
Systemic allergy
Systemic allergy, which is rare but potentially more serious, is a generalised allergy to insulin. It may cause a rash over the whole body, shortness of breath, wheezing, reduction in blood pressure, fast pulse, or sweating. Severe cases of generalised allergy may be life-threatening.
Skin and subcutaneous tissue disorders
Lipodystrophy and cutaneous amyloidosis may occur at the injection site and delay local insulin absorption. Continuous rotation of the injection site within the given injection area may help to reduce or prevent these reactions (see section 4.4).
Oedema
Cases of oedema have been reported with insulin therapy, particularly if previous poor metabolic control is improved by intensified insulin therapy.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website. Alternately, report suspected adverse events to the company at [email protected].

Insulins have no specific overdose definitions because serum glucose concentrations are a result of complex interactions between insulin levels, glucose availability and other metabolic processes. Hypoglycaemia may occur as a result of an excess of insulin activity relative to food intake and energy expenditure. Hypoglycaemia may be associated with listlessness, confusion, palpitations, headache, sweating and vomiting. Mild hypoglycaemic episodes will respond to oral administration of glucose or other sugar or saccharated products. Correction of moderately severe hypoglycaemia can be accomplished by intramuscular or subcutaneous administration of glucagon, followed by oral carbohydrate when the patient recovers sufficiently. Patients who fail to respond to glucagon must be given glucose solution intravenously. If the patient is comatose glucagon should be administered intramuscularly or subcutaneously. However, glucose solution must be given intravenously if glucagon is not available or if the patient fails to respond to glucagon. The patient should be given a meal as soon as consciousness is recovered. Sustained carbohydrate intake and observation may be necessary because hypoglycaemia may recur after apparent clinical recovery.