Humalog Mix 100 units Suspension

HUMALOG MIX 25 and HUMALOG MIX 50 are indicated for the treatment of patients with diabetes mellitus who require insulin for the maintenance of normal glucose homeostasis.

The dosage should be determined by the healthcare professional, according to the requirements of the patient. Both HUMALOG MIX 25 and HUMALOG MIX 50 may be given shortly before meals. When necessary, HUMALOG MIX 25 and HUMALOG MIX 50 can be given soon after meals. HUMALOG MIX 25 and HUMALOG MIX 50 should only be given by subcutaneous injection. Under no circumstances should HUMALOG MIX 25 or HUMALOG MIX 50 be given intravenously.

The rapid onset and early peak of activity of Humalog itself is observed following the subcutaneous administration of HUMALOG MIX 25 and HUMALOG MIX 50. This allows HUMALOG MIX 25 and HUMALOG MIX 50 to be given very close to mealtime. The duration of action of the insulin lispro protamine suspension component of HUMALOG MIX 25 and HUMALOG MIX 50 are similar to that of a basal insulin (NPH). 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 HUMALOG MIX 25 and HUMALOG MIX 50 is dependent on dose, site of injection, blood supply, temperature, and physical activity.

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: The safety and effectiveness of HUMALOG MIX 25 and HUMALOG MIX 50 in patients less than 18 years of age have not been established.

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, 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 MIX 25 or HUMALOG MIX 50 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 the proper injection techniques. HUMALOG MIX 25 and HUMALOG MIX 50 KWIKPEN: The KWIKPEN delivers 1 u2013 60 units in steps of 1 unit in a single injection. The needed dose is dialled in units. The number of units is shown in the dose window of the pen. For instructions on the handling and preparation of HUMALOG MIX 25 and HUMALOG MIX 50 refer to section 6.6.

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 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.

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.

Combination of HUMALOG MIX 25 and HUMALOG MIX 50 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 MIX 25 or HUMALOG MIX 50 is considered. If the combination is used, patients should be observed for signs and symptoms of heart failure, weight gain and oedema. Pioglitazone 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 MIX 25 and HUMALOG MIX 50 contain 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), sulphonamide 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. Mixing HUMALOG MIX 25 or HUMALOG MIX 50 with other insulins has not been studied. The healthcare professional should be consulted when using other medication in addition to HUMALOG MIX 25 or HUMALOG MIX 50 (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). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

MedDRA system organ class

• Very common
• Common
• Uncommon
• Rare
• Very rare
• Not known

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 u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications u2013 https://www.sahpra.org.za/Publications/Index/8. Alternatively, 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.