HUMALOG MIX 50,300 IU 3 ml

GENERIC NAME OF THE MEDICINAL PRODUCT
lispro mix

Formulations
Suspension for injection.

Humalog Mix50 is a white, sterile suspension.
Qualitative and quantitative composition:
One ml contains 100U (equivalent to 3,5 mg) insulin lispro (insulin
lispro) (recombinant DNA origin produced in E.coli). Each pack contains 3ml,
equivalent to 300U insulin lispro.

Humalog Mix 50 contains 25% insulin lispro solution and 75% insulin lispro protamine
suspension.

CLINICAL DATA

Witness
Humalog Mix25 is indicated for the treatment of patients with diabetes who require insulin to maintain normal glucose homeostasis.

Dosage and method of administration

The dosage should be determined by the doctor according to the patient's needs.

Humalog Mix 50 can be administered immediately before a meal. When necessary, Humalog Mix 50 can be given soon after meals. Humalog Mix 50 should only be administered by subcutaneous injection. Under no circumstances Humalog Mix 50 should not be administered intravenously.

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 once a month.

Following subcutaneous injection of Humalog Mix 50 should be taken not to penetrate the blood vessel. After injection, the site of injection should not be massaged.
Patients should be educated to use proper injection techniques.

The rapid onset and early peak of activity of Humalog itself is observed following the subcutaneous injection of Humalog Mix 50. This allows Humalog Mix 50 be given immediately before a meal. The duration of action of insulin lispro protamine suspension (BASAL) in Humalog Mix 50 is similar to that of basal insulin (NPH).
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 50 is dependent on dose, site of injection, blood supply, temperature, and physical activity.
Contraindications
Hypersensitivity to insulin lispro or any of the excipients.
Hipoglikemiya.Spetsialni precautions for use

Humalog Mix 50 should under no circumstances be administered intravenously.

Transferring a patient to another type or brand of insulin should be done under strict medical supervision. Changes in the activity, the type (manufacturer), type (regular, NPH, tape, etc.) and source (animal, human, insulin analogue) and / or method of manufacture (recombinant DNA versus animal-source insulin) may require a change in dosage.

Conditions under which the early warning symptoms of hypoglycemia may be different or less pronounced include long duration of diabetes, intensive insulin therapy, nerve disease or diabetes medications such as beta-blockers.

The small number of patients who have experienced hypoglycaemic reactions after transfer from animal insulin to human insulin have reported that 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.

Applying the wrong dose or discontinuation of treatment, especially in insulin-dependent diabetics, may lead to hyperglycaemia and diabetic ketoacidosis, conditions that are potentially lethal.

Insulin requirements may be reduced in renal impairment.
Insulin requirements may be reduced in patients with hepatic impairment due to reduced capacity for gluconeogenesis and reduced insulin degradation, whereas in patients with chronic hepatic impairment, an increase in insulin resistance may lead to increased insulin requirements.

Insulin requirements may be increased during illness or emotional disturbances.

Dose adjustments may be necessary if patients undertake increased physical activity or change
usual diet. Exercise immediately after a meal may increase the risk of hypoglycaemia.

Administration of insulin lispro in children under 12 years of age should be considered only in cases where the expected benefit when compared to regular insulin.
Interactions

Insulin requirements may be increased by substances with hyperglycaemic activity, such as oral contraceptives, corticosteroids or replacement therapy for thyroid disease, danazol, beta 2 stimulants (such as ritodrine, salbutamol, terbutaline).

Insulin requirements may be reduced in the presence of substances with hypoglycaemic activity, such as oral hypoglycemics, salicylates (eg aspirin), antibiotics, sulpha group, certain antidepressants (monoamine oxidase inhibitors 30, selective inhibitors of serotonin reuptake) specific inhibitors of angiotensin converting enzyme inhibitors (captopril, enalapril), angiotensin II blockers receptors, beta-blockers, octreotide or alcohol.

Mixing Humalog Mix 50 with other insulins has not been studied.

When using other medications in addition to Humalog Mix 50 should seek medical attention.
Use during pregnancy and lactation

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 fetus / newborn.

During pregnancy, it is essential to maintain good control of patients who are on insulin therapy (insulin-dependent or gestational diabetes). Insulin requirements usually fall during the first trimester and increase during the second and third trimesters. Patients with diabetes should be advised to notify their physician if they are pregnant or are contemplating pregnancy. It is important for pregnant patients with diabetes is carefully monitoring of glucose control and overall health.

Patients with diabetes who are breastfeeding may require adjustments in insulin dose, diet or both.
Effects on ability to drive and use machines

The patient's 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 (eg driving a car or operating machinery).

Patients should be advised to take precautions to avoid hypoglycaemia while driving, which is especially important in those who have reduced or absent awareness of the warning signs of hypoglycaemia or have frequent episodes of hypoglycaemia. Under these circumstances, it is advisable to avoid driving.

Adverse reactions

Hypoglycemia is the most common adverse effect of insulin therapy, which can be found in patients with diabetes. Severe hypoglycaemia may lead to unconsciousness, and in extreme cases, death. No specific frequency for hypoglycaemia, since hypoglycaemia is a result of insulin dose and other factors such as the patient's diet and exercise.

Local allergic reactions are common. Redness, swelling, and itching can occur at the site of injection of insulin. This condition usually resolves in a few days to a few weeks. In some cases, this condition may be due to factors other than insulin, such as irritants in the skin cleansing agent or poor injection technique. Systemic allergy, which is rare, but potentially more serious, is generalized allergy to insulin. It can cause a rash over the whole body, shortness of breath, wheezing, reduction in blood pressure, rapid pulse, or sweating. Severe cases of generalized allergy may be life threatening.

Lipodystrophy at the injection site is uncommon.
Overdose.

No specific symptoms of an overdose of insulin as serum glucose concentrations are a result of complex interactions between insulin levels, glucose availability and other metabolic processes. Hypoglycemia 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 sweetened 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 do not respond to glucagon must be given glucose solution intravenously.

If the patient is comatose, glucagon should be administered intramuscularly or subcutaneously. If glucagon is not available or the patient does not respond to glucagon must be given glucose solution intravenously. The patient should be given a meal as soon as consciousness is recovered.

Sustained carbohydrate intake and observation since hypoglycemia may recur after apparent clinical recovery.

Pharmacological

Pharmacokinetic properties:

The pharmacokinetics of insulin lispro reflect a compound that is rapidly absorbed and reaches peak blood levels 30 to 70 minutes after subcutaneous injection. The pharmacokinetics of insulin lispro protamine suspension is compatible with that of intermediate acting insulin such as NPH. The pharmacokinetics of Humalog Mix25 are representative of the individual pharmacokinetic properties of the two components. When considering the clinical relevance of these kinetics, it is more appropriate to examine the curves of absorption of glucose.

Insulin lispro maintains more rapid absorption when compared to soluble human insulin in patients with renal impairment. In patients with type 2 diabetes over a wide range of renal function, the pharmacokinetic differences between insulin lispro and soluble human insulin in most cases have been maintained and shown to be independent of renal function. Insulin lispro maintains more rapid absorption and elimination when compared to soluble human insulin in patients with hepatic impairment.

Pharmacodynamic properties:
Pharmacotherapeutic group: Drugs used to treat diabetes. Injectable Insulins and analogues, intermediate combined with fast-acting.

Humalog Mix 50 is a premixed suspension of insulin lispro (fast-acting human insulin analogue) and insulin lispro protamine suspension (human insulin analogue with an average duration of action).

The principal action of insulin lispro is the regulation of glucose metabolism.

In addition, insulins have several anabolic and anti-catabolic actions on different tissues. In muscle tissue increases glycogen, fatty acids, glycerol and protein and amino acid uptake, while decreasing glycogenolysis, gluconeogenesis, ketogenesis, lipolysis, protein catabolism and amino acids.

Insulin lispro has a rapid onset of action (approximately 15 minutes), allowing it to be administered immediately before a meal (within zero to 15 minutes before a meal) than regular insulin (30 to 45 minutes before meals). Rapid onset and early peak of activity of insulin lispro were observed after subcutaneous administration of Humalog Mix25. The profile of activity of Humalog BASAL a period of about 15 hours has characteristics similar to that of basal insulin (NPH).

Glucodynamic response to insulin lispro is not affected by renal or hepatic function. Glucodynamic differences between insulin lispro and soluble human insulin measured during a glucose levels were maintained over a wide range of renal function.

Insulin lispro is equipotent to human insulin on a molar basis, but its effect is more rapid and of shorter duration.

Preclinical safety data

In tests in vitro, including binding of insulin to insulin receptor sites and effects on growing cells, insulin lispro act in a way that is very similar to human insulin. Studies also show that the dissociation of the insulin receptor of insulin lispro e equivalent to human insulin. In toxicological studies, one month and twelve months, no significant toxicity.

In animal studies insulin lispro does not cause impairment of fertility, embryotoxicity or teratogenicity.. PHARMACEUTICAL

PARTICULARS

List of excipients and their amounts

Protamine sulfate
m-cresol {1,76 mg / ml}
Phenol {0,80 mg / ml}
Glycerol
Dibasic sodium phosphate.7H2O
Zinc Oxide
Water for injections
Hydrochloric acid and sodium hydroxide may be used to adjust pH to 7.0 to 7.8.
Incompatibilities

Mixing Humalog Mix25 with other insulins has not been studied. The absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Expiration date

Unopened cartridges 3 years. After inserting the cartridge 28 days.
Special precautions for storage

Unopened cartridges
Store in a refrigerator (2 ° C - 8 ° C). Do not freeze. Do not expose to excessive heat or direct sunlight.

After inserting the cartridge
Do not store above 30 ° C. Do not refrigerate. Pen with a cartridge
should be stored with a needle attached.