Humalog

Humalog

insulin lispro

Manufacturer:

Eli Lilly

Distributor:

Zuellig
Full Prescribing Info
Contents
Insulin lispro (recombinant DNA origin).
Description
One mL contains 100 units (equivalent to 3.5 mg) insulin lispro, Ph. Eur. (recombinant DNA origin produced in E.coli).
Kwikpen: Each container includes 3 mL equivalent to 300 units insulin lispro.
Vial: Each container includes 10 mL equivalent to 1000 units insulin lispro.
Excipients/Inactive Ingredients: m-cresol [3.15 mg/mL] as preservative, Glycerol, Dibasic sodium phosphate. 7H2O, zinc oxide, Water for injection.
Hydrochloric acid and sodium hydroxide may be used to adjust the pH to 7.0-7.8.
Action
Pharmacotherapeutic group: Fast acting human insulin analogue. ATC code: A10A B04.
Pharmacology: Pharmacodynamics: 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 lispro has a rapid onset of action (approximately 15 minutes), thus allowing it to be given closer to a meal (within zero to 15 minutes of the meal) when compared to regular insulin (30 to 45 minutes before). Insulin lispro takes effect rapidly and has a shorter duration of activity (2 to 5 hours) when compared to regular insulin.
Clinical trials in patients with type 1 and type 2 diabetes have demonstrated reduced postprandial hyperglycemia with insulin lispro compared to soluble human insulin.
As with all insulin preparations, the time course of insulin lispro action may vary in different individuals or at different times in the same individual and is dependent on dose, site of injection, blood supply, temperature and physical activity.
The typical activity profile following subcutaneous injection is illustrated as follows. (See figure.)

Click on icon to see table/diagram/image

The previous representation reflects the relative amount of glucose over time required to maintain the subject's whole blood glucose concentrations near fasting levels and is an indicator of the effect of these insulins on glucose metabolism over time.
Clinical trials have been performed in children (61 patients aged 2 to 11) and children and adolescents (481 patients aged 9 to 19 years), comparing insulin lispro to human soluble insulin. The pharmacodynamic profile of insulin lispro in children is similar to that seen in adults.
When used in subcutaneous infusion pumps, treatment with insulin lispro has been shown to result in lower glycosylated hemoglobin levels compared to soluble insulin. In a double-blind, crossover study, the reduction in glycosylated hemoglobin levels after 12 weeks dosing was 0.37 percentage points with insulin lispro, compared to 0.03 percentage points for soluble insulin (p=0.004).
In patients with type 2 diabetes on a maximum doses of sulphonyl urea agents, studies have shown that the addition of insulin lispro significantly reduces HbA1c compared to sulphonyl urea alone. The reduction of HbA1c would also be expected with other insulin products e.g soluble or isophane insulins.
Clinical trials in patients with type 1 and type 2 diabetes have demonstrated a reduced number of episodes of nocturnal hypoglycemia with insulin lispro compared to soluble human insulin. In some studies, reduction of nocturnal hypoglycemia was associated with increased episodes of daytime hypoglycemia.
The glucodynamic response to insulin lispro is not affected by renal or hepatic function impairment. Glucodynamic differences between insulin lispro and soluble human insulin, as measured during a glucose clamp procedure, were maintained over a wide range of renal function.
Insulin lispro has been shown to be equipotent to human insulin on a molar basis but its effect is more rapid and of a shorter duration.
Pharmacokinetics: The pharmacokinetics of insulin lispro reflects a compound that is rapidly absorbed, and achieves peak blood levels 30 to 70 minutes following subcutaneous injection. When considering the clinical relevance of these kinetics, it is more appropriate to examine the glucose utilization curves (as discussed in Pharmacodynamics previously).
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 were generally 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.
Toxicology: Preclinical safety data: In in vitro tests, including binding to insulin receptor sites and effects on growing cells, insulin lispro behaved in a manner that closely resembled human insulin. Studies also demonstrate that the dissociation of binding to the insulin receptor of insulin lispro is equivalent to human insulin. Acute, one month and twelve month toxicology studies produced no significant toxicity findings.
Insulin lispro did not induce fertility impairment, embryotoxicity or teratogenicity in animal studies.
Indications/Uses
For the treatment of adults and children with diabetes mellitus who require insulin for the maintenance of normal glucose homeostasis. Insulin lispro (Humalog) is also indicated for the initial stabilization of diabetes mellitus.
Dosage/Direction for Use
The dosage should be determined by the physician, according to the requirement of the patient.
Insulin lispro (Humalog) may be given shortly before meals. When necessary Insulin lispro (Humalog) can be given soon after meals. Insulin lispro (Humalog) preparations should be given by subcutaneous injection. If necessary, insulin lispro (Humalog) may also be administered intravenously, for example; for the control of blood glucose levels during ketoacidosis, acute illnesses or during intra and postoperative periods.
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.
When administered subcutaneously care should be taken when injecting Insulin lispro (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 the proper injection techniques.
Insulin lispro (Humalog) takes effect rapidly and has a shorter duration of activity (2 to 5 hours) given subcutaneously as compared with regular insulin. This rapid onset of activity allows Insulin lispro (Humalog) injection (or, in the case of administration by continuous subcutaneous infusion, an Insulin lispro [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 Insulin lispro (Humalog) is dependent on dose, site of injection, blood supply, temperature, and physical activity.
Insulin lispro (Humalog) can be used in conjunction with a longer-acting human insulin or oral sulphonylurea agents, on the advice of a physician.
Vial: Use of Humalog in an insulin infusion pump: Only certain CE-marked insulin infusion pumps may be used to infuse insulin lispro. Before infusing insulin lispro, the manufacturers instructions should be studied to ascertain the suitability or otherwise for the particular pump. Read and follow the instructions that accompany the infusion pump. Use the correct reservoir and catheter for the pump. Change the infusion set every 48 hours. Use aseptic technique when inserting the infusion set. In the event of a hypoglycaemic episode, the infusion should be stopped until the episode is resolved. If repeated or severe low blood glucose levels occur, notify your health care professional and consider the need to reduce or stop your insulin infusion. A pump malfunction or obstruction of the infusion set can result in a rapid rise in glucose levels. If an interruption to insulin flow is suspected, follow the instructions in the product literature and if appropriate, notify your health care professional. When used with an insulin infusion pump, Humalog should not be mixed with any other insulin.
Intravenous administration of insulin: Intravenous injection of insulin lispro should be carried out following normal clinical practise for intravenous injections, for example by an intravenous bolus or by an infusion system. Frequent monitoring of the blood glucose levels is required. Infusion systems at concentrations from 0.1U/ml to 1.0U/ml insulin lispro in 0.9% sodium chloride or 5% dextrose are stable at room temperature for 48 hours. It is recommended that the system is primed before starting the infusion to the patient.
Overdosage
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. Hypoglycemia may occur as a result of an excess of insulin activity relative to food intake and energy expenditure.
Hypoglycemia may be associated with listlessness, confusion, palpitations, headache, sweating and vomiting.
Mild hypoglycemic episodes will respond to oral administration of glucose or other sugar or saccharated products.
Correction of moderately severe hypoglycemia 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 hypoglycemia may recur after apparent clinical recovery.
Contraindications
Hypersensitivity to insulin lispro or to any of the excipients.
Hypoglycemia.
Special Precautions
Transferring a patient to another type or brand of insulin should be done under strict medical supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, 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 optimize dosage of both insulins to obtain glucose control across the whole day, particularly nocturnal/fasting glucose control.
Conditions which may make the early warning symptoms of hypoglycemia 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 hypoglycemic reactions after transfer from animal-source insulin to human insulin have reported that the early warning symptoms of hypoglycemia were less pronounced or different from those experienced with their previous insulin. Uncorrected hypoglycemic or hyperglycemic 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 hyperglycemia and diabetic ketoacidosis; conditions which are potentially lethal.
Insulin requirements may be reduced in the presence of renal 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.
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 hypoglycemia. A consequence of the pharmacodynamics of rapid-acting insulin analogues is that if hypoglycemia occurs, it may occur earlier after an injection when compared with soluble human insulin.
Insulin lispro (Humalog) should only be used in children in preference to soluble insulin when a fast action insulin might be beneficial. For example, in the timing of the injections in relation to meals.
Combination of Insulin lispro (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 heart failure. This should be kept in mind, if treatment with the combination of pioglitazone and Insulin lispro (Humalog) 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.
Effects on ability to drive and use machines: The patient's ability to concentrate and react may be impaired as a result of hypoglycemia. 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 hypoglycemia whilst driving, this is particularly important in those who have reduced or absent awareness of the warning signs of hypoglycemia or have frequent episodes of hypoglycemia. The advisability of driving should be considered in these circumstances.
Use In Pregnancy & Lactation
Data on a large number of exposed pregnancies do not indicate any adverse effect of Insulin lispro (Humalog) on pregnancy or on the health of the fetus/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.
Patients with diabetes who are breastfeeding may require adjustments in insulin dose, diet or both.
Adverse Reactions
Hypoglycemia is the most frequent undesirable effect of insulin therapy that a patient with diabetes may suffer. Severe hypoglycemia may lead to loss of consciousness, and in extreme cases, death. No specific frequency for hypoglycemia is presented, since hypoglycemia is a result of both the insulin dose and other factors e.g. a patient's level of diet and exercise.
Local allergy in patients is common (1/100 to <1/10). 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, which is rare (1/10,000 to <1/1,000) but potentially more serious, is a generalized 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 generalized allergy may be life-threatening.
Lipodystrophy at the injection site is uncommon (1/1,000 to <1/100).
Cases of edema 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 authorization of the medical product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.
Drug Interactions
Insulin requirements may be increased by medicinal products with hyperglycemic activity, such as oral contraceptives, corticosteroids, or thyroid replacement therapy, danazol, beta2 stimulants (such as ritodrine, salbutamol, terbutaline).
Insulin requirements may be reduced in the presence of medicinal products with hypoglycemic activity, such as oral hypoglycemics, salicylates (for example, acetylsalicylic acid), sulpha antibiotics, certain antidepressants (monoamine oxidase inhibitors), certain angiotensin converting enzyme inhibitors (captopril, enalapril), angiotensin II receptor blockers, beta-blockers, octreotide or alcohol.
The physician should be consulted when using other medications in addition to Insulin lispro (Humalog) (see Precautions).
Caution For Usage
Incompatibilities: Insulin lispro (Humalog) preparations should not be mixed with insulins produced by other manufacturers or with animal insulin preparations.
Kwikpen: Special Precautions for disposal and other handling: Any unused product or waste material should be disposed of in accordance with local requirements.
Instruction for use and handling: To prevent the possible transmission of disease, each pen must be used by one patient only, even if the needle is changed.
Inspect the Insulin lispro Humalog KwikPen solution. It should be clear and colourless. Do not use Insulin lispro Humalog KwikPen if it appears cloudy, thickened, or slightly coloured or if solid particles are visible.
Handling of the prefilled pen: Before using the KwikPen the user manual included in the package leaflet must be read carefully.
The KwikPen has to be used as recommended in the user manual.
Mixing insulins: Do not mix insulin in vials with insulin in cartridges. See Incompatibilities as follows.
Vial: Any unused product or waste material should be disposed of in accordance with local requirements.
Instructions for use and handling: The vial is to be used in conjunction with an appropriate syringe (100 U markings).
a) Preparing a dose: Inspect the Humalog solution. It should be clear and colourless. Do not use Humalog if it appears cloudy, thickened, or slightly coloured or if solid particles are visible.
i) Humalog: 1. Wash your hands.
2. If using a new vial, flip off the plastic protective cap, but do not remove the stopper.
3. If the therapeutic regimen requires the injection of basal insulin and Humalog at the same time, the two can be mixed in the syringe. If mixing insulins, refer to the instructions for mixing that follow in Section (ii) and Incompatibilities.
4. Draw air into the syringe equal to the prescribed Humalog dose. Wipe the top of the vial with an alcohol swab. Put the needle through the rubber top of the Humalog vial and inject the air into the vial.
5. Turn the vial and syringe upside down. Hold the vial and syringe firmly in one hand.
6. Making sure the tip of the needle is in the Humalog, withdraw the correct dose into the syringe.
7. Before removing the needle from the vial, check the syringe for air bubbles that reduce the amount of Humalog in it. If bubbles are present, hold the syringe straight up and tap its side until the bubbles float to the top. Push them out with the plunger and withdraw the correct dose.
8. Remove the needle from the vial and lay the syringe down so that the needle does not touch anything.
ii) Mixing Humalog with longer-acting Human Insulins (see Incompatibilities): 1. Humalog should be mixed with longer-acting human insulins only on the advice of a doctor.
2. Draw air into the syringe equal to the amount of longer-acting insulin being taken. Insert the needle into the longer-acting insulin vial and inject the air. Withdraw the needle.
3. Now inject air into the Humalog vial in the same manner, but do not withdraw the needle.
4. Turn the vial and syringe upside down.
5. Making sure the tip of the needle is in the Humalog, withdraw the correct dose of Humalog into the syringe.
6. Before removing the needle from the vial, check the syringe for air bubbles that reduce the amount of Humalog in it. If bubbles are present, hold the syringe straight up and tap its side until the bubbles float to the top. Push them out with the plunger and withdraw the correct dose.
7. Remove the needle from the vial of Humalog and insert it into the vial of the longer-acting insulin. Turn the vial and syringe upside down. Hold the vial and syringe firmly in one hand and shake gently. Making sure the tip of the needle is in the insulin, withdraw the dose of longer-acting insulin.
8. Withdraw the needle and lay the syringe down so that the needle does not touch anything.
b) Injecting a dose: 1. Choose a site for injection.
2. Clean the skin as instructed.
3. Stabilise the skin by spreading it or pinching up a large area. Insert the needle and inject as instructed.
4. Pull the needle out and apply gentle pressure over the injection site for several seconds. Do not rub the area.
5. Dispose of the syringe and needle safely.
6. Use of the injection sites should be rotated so that the same is not used more than approximately once a month.
c) Mixing insulins: Do not mix insulin in vials with insulin in cartridges. See Incompatibilities.
Storage
Unused prefilled pens: Store in a refrigerator (2°C-8°C). Do not freeze. Do not expose to excessive heat or direct sunlight.
After first use: Store below 30°C. Do not refrigerate. The prefilled pen should not be stored with the needle attached.
Shelf life: Unused prefilled pens: 3 years.
After first use: 28 days.
ATC Classification
A10AB04 - insulin lispro ; Belongs to the class of fast-acting insulins and analogues. Used in the treatment of diabetes.
Presentation/Packing
Soln for inj (sterile, clear, colorless, aqueous) 100 units/mL (KwikPen/pre-filled pen) 3 mL x 5's, (vial) 10 mL x 1's.
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