Composition, form of production and packaging
The solution for the sc administration is clear, colorless.
insulin detemir 100 ED *
Excipients: glycerol 16 mg, phenol 1.8 mg, metacresol 2.06 mg zinc acetate 65.4 Ојg sodium hydrophosphate dihydrate 0.89 mg sodium chloride 1.17 mg hydrochloric acid or sodium hydroxide qs water d / up to 1 ml.
3 ml (300 units) - glass cartridges (1) - multi-dose disposable syringes for multiple injections (5) - cardboard packs.
* 1 ED contains 142 Ојg of salt-free insulin detemir, which corresponds to 1 unit. human insulin (IU).
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
Mechanism of action
It is produced by the method of biotechnology of recombinant DNA using the strain Saccharomyces cerevisiae. It is a soluble basal analogue of human long-acting insulin with a flat activity profile.
The profile of the action of the Levemir В® FlexPene В® is significantly less variable than that of isophane-insulin and insulin glargine.
The prolonged action of the drug Levemir В® FlexPen В® is due to the expressed self-association of insulin detemir molecules at the injection site and the binding of the drug molecules to albumin by means of a compound with a side fatty acid chain. Insulin detemir is slower than isophane-insulin to peripheral target tissues. These combined delayed distribution mechanisms provide a more reproducible absorption profile and the action of the LevemirВ® FlexPenВ® preparation as compared to isophane-insulin.
For doses of 0.2-0.4 units / kg 50%, the maximum effect of the drug occurs in the interval from 3-4 hours to 14 hours after administration. The duration of action is up to 24 hours, depending on the dose, which allows the administration of 1 time / day or 2 times / day. With a double daily mode of administration, C ss is achieved after the administration of 2-3 doses of the drug.
After sc administration, a pharmacodynamic response was observed, proportional to the dose administered (maximum effect, duration of action, total effect).
In long-term studies, low daily diurnal variations
fasting plasma glucose in the treatment of patients with Leveemir В® FlexPen В® in contrast to isophane-insulin.
In long-term studies in patients with type 2 diabetes mellitus who received basal insulin therapy in combination with oral hypoglycemic drugs, it was demonstrated that glycemic control (in terms of glycosylated hemoglobin - HbA 1c ) against the background of Levemir В® FlexPen В® treatment was comparable to that of patients with type 2 diabetes mellitus in the treatment of isophane-insulin and insulin glargine with low weight gain.
Table 1. Change in body weight with insulin therapy
Duration of the study Insulin Detemir once Insulin Detemir twice Isofan-insulin Insulin glargine
20 weeks + 0.7 kg + 1.6 kg
26 weeks + 1.2 kg + 2.8 kg
52 weeks + 2.3 kg + 3.7 kg + 4 kg
In studies, the combined use of Levemir В® FlexPen В® and oral hypoglycemic medications resulted in a 61-65% decrease in the risk of mild hypoglycemia over night, in contrast to isophane-insulin.
An open randomized clinical trial was conducted with patients with type 2 diabetes mellitus who did not reach the target glycemia against oral hypoglycemic therapy.
The study began with a 12-week preparatory period, during which patients received combined therapy with liraglutide in combination with metformin, and against which 61% of patients achieved HbA 1c <7%. 39% of patients who did not achieve the target glycemic values вЂ‹вЂ‹with combination therapy with liraglutide and metformin were randomized to two treatment groups for further treatment. Patients of one of the therapeutic groups, in addition to the therapy of liraglutide with metformin, were prescribed Levemir В® FlexPen В® in a daily single dose; patients continued to receive liraglutide in combination with metformin for the next 52 weeks. During this period, the therapeutic group, receiving additionally to the therapy of liraglutide with metformin, a daily single injection of Levemir В® FlexPen В® , demonstrated a further decrease in HbA 1c from baseline of 7.6% to a level of 7.1% at the end of the 52-week period, with no episodes of severe hypoglycemia. When adding a dose of Levemir В® FlexPen В® to the therapy with liraglutide, the latter retained its advantage with respect to a statistically significant decrease in body weight in patients (see Table 2).
Table 2. Clinical trial data - therapy with Levemir В® , prescribed in addition to the combined scheme of treatment with liraglutide with metformin
Weeks of treatment Patients randomized to receive Levemir В® FlexPen В® therapy in addition to liraglutide + metformin therapy n = 160 Patients randomized to receive liraglutide + metformin therapy n = 149 P-value change reliability factor
The average change in the value of the indicator HbA 1c in comparison with the initial point of the test (%) 0-26 -0.51 +0.02 <0.0001
0-52 -0.5 0.01 <0.0001
Ratio of patients who have reached the target value of HbA 1c <7% (%) 0-26 43.1 16.8 <0.0001
0-52 51.9 21.5 <0.0001
The change in the body weight of patients compared with the indices at the starting point of the test (kg) 0-26 -0.16 -0.95 0.0283
0-52 -0.05 -1.02 0.0416
Episodes of mild hypoglycemia (by the number of patient-years of exposure of the test drug) 0-26 0.286 0.029 0.0037
0-52 0.228 0.034 0.0011
In long-term studies (в‰Ґ6 months) in patients with type 1 diabetes mellitus, the fasting plasma glucose concentration was better when treated with Levemir В® FlexPenВ® compared to isofan-insulin assigned to the baseline / bolus therapy. Glycemic control (HbA 1c ) against the background of therapy with LevemirВ® FlexPenВ® was comparable to that of isofan-insulin therapy, but with a lower risk of developing nocturnal hypoglycemia and a lack of weight gain when using LevemirВ® FlexPenВ®.
The results of clinical studies on baseline / bolus insulin therapy assessment indicate a comparable incidence of hypoglycemia as a whole against the background of LevemirВ® FlexPenВ® and isophane-insulin therapy. Analysis of the development of nocturnal hypoglycemia in patients with type 1 diabetes mellitus demonstrated a significantly lower incidence of light nocturnal hypoglycemia when using the Levemir В® FlexPen В® drug (when the patient can independently eliminate hypoglycemia and when hypoglycemia is confirmed by measuring the glucose concentration in capillary blood below 2.8 mmol / l or the result of measuring the concentration of glucose in the blood plasma less than 3.1 mmol / l), compared with that when using isophane-insulin; while between the two drugs studied there were no differences in the incidence of episodes of light nocturnal hypoglycemia in patients with type 2 diabetes mellitus.
The profile of nocturnal glycemia is more flat and even in Levemir В® FlexPen В® compared to isophane-insulin, which is reflected in a lower risk of developing nocturnal hypoglycemia.
With the use of the Levemir В® FlexPen В® preparation, antibody production was observed. However, this fact does not affect glycemic control.
A randomized controlled clinical trial of 310 pregnant women with type 1 diabetes mellitus evaluated the efficacy and safety of Levemir В® FlexPen В® in baseline / bolus therapy (152 patients), compared with isophane-insulin (158 patients), in combination with insulin aspart used as prandial insulin.
The results of the study showed that a decrease in HbA 1c at 36 weeks of gestation was seen in patients treated with Levemir В® FlexPen В® as compared to the group receiving isophane-insulin. A group of patients treated with Lewemir В® FlexPen В® and a group receiving isofan-insulin therapy showed similarity throughout the gestation period for the overall profile of HbA 1c .
The target HbA 1c- 6% level at 24 and 36 weeks of gestation was achieved in 41% of patients in the levemir В® FlexPen В® therapy group and in 32% of patients in the isofan-insulin therapy group.
Fasting glucose concentrations at gestational age 24 and 36 weeks were statistically significantly lower in the group of women who took Levemir В® FlexPen В® , compared to the group receiving isofan-insulin therapy.
During the entire period of pregnancy, there were no statistically significant differences between patients who received the Levemir В® FlexPen В® and isofan-insulin, according to the incidence of episodes of hypoglycemia.
Both groups of pregnant women treated with Lewemir В® FlexPen В® and isofan-insulin showed similar results in the incidence of adverse events during their entire pregnancy; However, it was found that the incidence of serious adverse events in women throughout the gestation period in quantitative terms (61 (40%) vs 49 (31%)) in infants during the intrauterine growth period and after birth (36 (24%) vs 32 (20%)) was higher in the Levemir В® FlexPen В® treatment group compared to the isofan-insulin therapy group.
The number of live-born children from mothers who became pregnant after they were randomly assigned to therapeutic groups to receive treatment with one of the tested drugs was 50 (83%) in the LevemirВ® FlexPenВ® treatment group and 55 (89%) in the isophane treatment group -insulin.
The number of children born with congenital malformations was 4 (5%) in the levemir В® FlexPen В® treatment group and 11 (7%) in the isofan-insulin treatment group. Of these, serious congenital malformations were noted in 3 (4%) children in the Levemir В® FlexPen В® treatment group and 3 (2%) in the isofan-insulin treatment group.
Children and teens
The efficacy and safety of Levemir В® FlexPen В® in children has been studied in two controlled clinical trials of 12 months with the participation of adolescents and children over the age of 2 years with type 1 diabetes mellitus (total 694 patients); one of these studies included a total of 82 children with type 1 diabetes in the age group of 2 to 5 years. The results of these studies demonstrated that the glycemic control (HbA 1c ) against the background of therapy with the LevemirВ® FlexPenВ® drug was comparable to that of isofan-insulin therapy, when assigned to baseline / bolus therapy. In addition, there was a lower risk of developing nocturnal hypoglycemia (based on plasma glucose values вЂ‹вЂ‹measured by patients alone) and the absence of weight gain (standard deviation for body weight adjusted according to the sex and age of the patient) against the Levemir В® treatment FlexPen В® , in comparison with isophane-insulin.
One of the clinical trials was extended for a further 12 months (a total of 24 months of clinical data were obtained) in order to obtain a more complete database for evaluating the formation of antibodies in patients with long-term treatment with Lewemer В® FlexPen В® .
The results obtained in the course of the study indicate that during the first year of treatment, when the Levemir В® FlexPen В® drug was taken, an increase in the titer of antibodies to insulin detemir increased; However, by the end of the second year of treatment, the antibody titer to Lewemir В® FlexPen В® was reduced in patients to a level slightly above the baseline at the time of initiation of Levemir В® FlexPen В® . Thus, it has been proved that the formation of antibodies in patients with diabetes mellitus against the background of treatment with Levemir В® FlexPen В® does not adversely affect the level of glycemic control and the dose of insulin detemir.
C max is achieved 6-8 hours after administration. With a double daily mode of administration, C ss is achieved after 2-3 injections. The intra-individual variability of absorption is lower in the Levemir В® FlexPen В® preparation compared to other basal insulin preparations.
The average V d of insulin detemir (approximately 0.1 l / kg) indicates that most of the insulin detemir circulates in the blood.
The results of studies of protein binding in vitro and in vivo indicate the absence of a clinically significant interaction between insulin detemir and fatty acids or other preparations that bind to proteins.
There was no pharmacokinetic or pharmacodynamic interaction between liraglutide and Lewemir В® FlexPen В® , in an equilibrium state, with the simultaneous administration of Type-2 Leuemir В® FlexPen В® in a single dose of 0.5 U / kg and 1.8 mg liraglutide to patients with type 2 diabetes.
Inactivation of insulin detemir is similar to that of human insulin preparations; all formed metabolites are inactive.
Terminal T 1/2 after SC injection is determined by the degree of absorption from the subcutaneous tissue and is 5-7 hours depending on the dose.
Pharmacokinetics in special clinical cases
Clinically significant intervertebral differences in the pharmacokinetics of the Levemir В® FlexPen В® preparation were not revealed.
The pharmacokinetic properties of the Levemir В® FlexPen В® preparation were studied in children (6-12 years) and adolescents (13-17 years old) and compared with pharmacokinetic properties in adult patients with type 1 diabetes mellitus. No differences were found.
Clinically significant differences in the pharmacokinetics of the Levemir В® FlexPen В® drug between elderly and young patients, or between patients with impaired renal and hepatic function and healthy patients, have not been identified.
Pre-clinical safety data
In vitro studies in the human cell line, including studies on binding to insulin receptors and IGF-1 (insulin-like growth factor), have shown that insulin detemir has a low affinity for both receptors and has little effect on cell growth as compared to human insulin.
Preclinical data based on routine studies of pharmacological safety, repeated dose toxicity, genotoxicity, carcinogenic potential, toxic effects on reproductive function, revealed no danger to humans.
- Diabetes mellitus in adults, adolescents and children older than 2 years.
The dose of Levemir В® FlexPen В® should be selected individually in each case, based on the patient's needs.
Based on the results of the studies, the following are recommendations for titration of doses:
Mean plasma glucose values вЂ‹вЂ‹measured independently before breakfast Correction of the dose of Levemir В® FlexPen В® (ED)
> 10 mmol / l (180 mg / dL) +8
9.1-10 mmol / L (163-180 mg / dL) +6
8.1-9 mmol / L (145-162 mg / dL) +4
7.1-8 mmol / L (127-144 mg / dL) +2
6.1-7 mmol / L (109-126 mg / dL) +2
4.1-6.0 mmol / L No change (target value)
If any single value of plasma glucose:
3.1-4 mmol / L (56-72 mg / dl) -2
<3.1 mmol / l (<56 mg / dL) -4
If the Levemir В® FlexPene В® is used as part of the basis / bolus regimen, it should be administered 1 or 2 times / day, based on the patient's need.
Patients who require the use of the drug 2 times / day for optimal control of the level of glycemia, can enter the evening dose either during dinner or at bedtime. Dose adjustment may be necessary with increasing physical activity of the patient, changing his usual diet or with concomitant disease.
The Levemir В® FlexPen В® medicinal preparation can be used both as monotherapy and in combination with bolus insulin. It can also be used in combination with oral hypoglycemic drugs, as well as in addition to existing therapy with liraglutide.
In combination with oral hypoglycemic drugs or in addition to liraglutide, it is recommended to use Levemir В® FlexPen В® once / day, starting at a dose of 10 ED or 0.1-0.2 U / kg. The Levemir В® FlexPen В® medicinal preparation can be administered at any time convenient for the patient during the day, however, after determining the time of daily injection, it is necessary to adhere to the established mode of injection.
Leuemir В® FlexPix В® is intended for use only for administration. Leuemir В® FlexPene В® should not be administered iv. this can lead to severe hypoglycemia. Also, I / m administration of the drug should be avoided. Levemir В® FlexPen В® is not intended for use in insulin pumps.
Levemir В® FlexPen В® is injected into the thigh, anterior abdominal wall, shoulder region, deltoid or gluteal region. Injection sites should be changed regularly even when administered in the same area to reduce the risk of developing lipodystrophy. As with other insulin formulations, duration depends on the dose, site of administration, blood flow rate, temperature and level of physical activity.
Special patient groups
As with other drugs of insulin in elderly patients and patients with renal or hepatic insufficiency should more carefully monitor the concentration of blood glucose and insulin dose detemir adjusted individually.
Children and teens
Efficacy and safety of the drug Levemir В® FleksPen В® in adolescents and children older than 2 years, confirmed in clinical trials lasting up to 12 months.
Translation from other insulins
Translation preparations intermediate-acting insulin and a long-acting insulin preparations for preparation Levemir В® FleksPen В® may require dose adjustments and time of administration.
As with other insulin formulations, it is recommended careful control of the concentration of glucose in the blood during the transfer and during the first weeks of the new drug assignment.
You may need correction concomitant hypoglycemic therapy (dose and time of administration of short insulin preparations or oral hypoglycemic drug dose).
Levemir В® FleksPen В® syringe-pen with a dispenser. The administered dose of insulin in the range from 1 to 60 units can be changed in increments of 1 unit. Needles NovoFayn В® and NovoTvist В® to 8 mm in length designed for use with Levemir В® FleksPen В® . For precautions should always carry a spare insulin delivery device in the case of loss or damage FleksPenВ® .
Before using the drug Levemir В® FleksPen В® , make sure that you select the correct type of insulin.
Preparations for holding the injection: must remove the cap; remove the protective cover from the disposable needle; neatly and tightly screw the needle on LevemirВ® FleksPen В® ; remove large outdoor (not to throw it away) and internal (to throw) caps from the needle. For each injection, you should always use a new needle. Needles do not bend or damage. To avoid accidental punctures, not to wear the inner cap back on the needle.
Preliminary removal of air from the cartridge.In normal use, the pen before each injection in the needle and cartridge can accumulate air. To avoid getting air bubbles and enter the assigned dose please observe the following:
- type 2 ED drug;
- arrange Levemir В® FleksPen В® vertically upward and the needle several times to tap the cartridge fingertip to air bubbles moved to the top of the cartridge;
- holding Levemir В® FleksPen В® needle up, the dose button pressed until it stops; dosage selector back to zero;
- at the end of the needle drop should appear insulin; If it does not, replace the needle and repeat the procedure no more than 6 times. If insulin does not come out of the needle, which indicates that the syringe-pen is defective and not subject to further use.
Setting the dose. Make sure that the dosage selector is set to "0". Dial number of units required for injection. The dosage can be adjusted by rotating the dosage selector in either direction. When rotating the dosage selector should be careful not to accidentally press the start button in order to avoid release of insulin dose. Install a dose greater than the number of units remaining in the cartridge, it is impossible. You can not use the balance scale for measuring the insulin dose.
The introduction of the drug.Insert the needle subcutaneously. To make an injection, press the start button all the way until "0" appears opposite the dosage indicator. With the introduction of the drug should only press the start button. When you turn the dosage selector dose not occur. After injection, the needle should be left under the skin for 6 seconds (this will ensure the full dose of insulin administration). When removing the needle, hold the trigger button is fully pressed, it will provide a full dose of the drug.
Removal of the needle. Close the outer needle cap and unscrew it from the pen. Throw away the needle with caution. After each injection, the needle must be removed. Otherwise, fluid may flow out of the pen, which can lead to improper dosage.
Medical staff, relatives and other caregivers for the sick, should follow the general rules of caution when removing and disposing of needles in order to avoid the risk of accidental needle stick.
Used Levemir В® FleksPen В® should be discarded with the needle detached.
Storage and care. The surface of the pen can be cleaned with a cotton swab dipped in rubbing alcohol. Do not immerse the pen in an alcohol, washed and lubricate it as this may damage the device. Do not re-filling pen.
Adverse events observed in patients treated with Levemir preparation В® , mainly due to developing pharmacological effect of insulin. The proportion of patients treated, who is expected to develop adverse reactions is estimated to be 12%.
The most common adverse reactions that develops during treatment with Levemir В® , is hypoglycemia. From clinical studies it is known that severe hypoglycemia, requiring third party intervention, occurs in approximately 6% of patients treated with Levemir В® .
Injection site reactions may occur more frequently in the treatment of drug Levemir В®Than when administered preparations of human insulin. These reactions include pain, redness, hives, inflammation, bruising, swelling and itching at the injection site. Most injection site reactions are minor and are of a transitory nature, ie usually disappear with continued treatment over a period of several days to several weeks.
At the initial stage insulin may occur violations of refraction and edema. These symptoms are usually transient. Rapid improvement in glycemic control can lead to a state of acute painful neuropathy, which is usually reversible. Intensification of insulin therapy with abrupt improvement in carbohydrate metabolism control can cause a temporary worsening of diabetic retinopathy, while long-term improved glycemic control decreases the risk of progression of diabetic retinopathy.
All adverse reactions presented below, based on data obtained in clinical trials, divided into groups according to the development of a frequency according to MedDRA and organ systems. The frequency of adverse reactions is defined as follows: very common (1/10?), Common (1/100 to <1/10?), Rare (1/1000 to <1/100?), Rarely (1/10 000? to <1/1000), very rare (<1/10 000), not known (can not be estimated from the available data).
By the immune system Infrequent - allergic reactions, potentially allergic reactions, urticaria, rash, rash *; very rare - Anaphylactic reactions *
Metabolism very often - hypoglycaemia
Nervous systemrarely - peripheral neuropathy ( "acute painful neuropathy")
part of the vision infrequently - refractive error, diabetic retinopathy
Skin and subcutaneous tissue disorders uncommon - Lipodystrophy *
Other often - reactions at the injection site; Infrequent - edema
* - see description of certain side reactions..
Description of individual adverse reactions
Allergic reactions, potentially allergic reactions, urticaria, skin rashes, skin rash
In applying the drug Levemir В®a basal-bolus therapy time noted infrequent allergic reactions, potentially allergic reactions, urticaria, skin rashes, and skin rash. However, data from clinical studies showed frequent development of adverse drug reactions when used Levemir В® in combination therapy with other hypoglycemic drugs for oral administration (2.2% of allergic reactions and potentially allergic reactions).
Reactions generalized hypersensitivity (including generalized skin rash, itching, sweating, gastrointestinal upset, angioneurotic edema, shortness of breath, rapid heart rate, decreased blood pressure) is very rare, but potentially life-threatening.
Hypoglycemia is the most common adverse reaction. It can develop if the insulin dose is too high in relation to the insulin requirement. Severe hypoglycemia may lead to unconsciousness and / or convulsions, temporary or permanent impairment of brain function or even death. Symptoms of hypoglycaemia usually develop suddenly and include a "cold" sweat, pale skin, fatigue, nervousness or tremor, anxiety, unusual tiredness or weakness, disorientation, poor concentration, drowsiness, expressed the feeling of hunger, blurred vision, headache, nausea, heart palpitations.
Lipodystrophy (including lipohypertrophy, lipoatrophy) may occur at the injection site. Compliance with the rules of the change of the injection site within a region can help reduce the risk of this adverse reaction.
- increased individual sensitivity to insulin detemir or any of the components.
Do not use the drug Levemir В® FleksPen В® in children under the age of 2 years, as clinical trials in children less than 2 years of age have not been conducted.
PREGNANCY AND LACTATION
In applying the drug Levemir В® FleksPen В® during pregnancy is necessary to consider how the benefits of its use outweigh the risks.
One of randomized controlled clinical trials in pregnant women with type 1 diabetes, in which studied the efficacy and safety of the combined therapy with LevemirВ® FleksPen В® insulin aspart (152 pregnant women), compared with therapy isophane insulin in combination with insulin aspart (158 pregnant women) found no differences in the overall safety profile during pregnancy, pregnancy outcomes or the health of the fetus and newborn.
Additional information on efficacy and safety of treatment with Levemir В® FleksPen В® , obtained from about 300 pregnant women during the post-marketing application, indicate the absence of undesirable side effects of insulin detemir, resulting in occurrence of congenital malformations and malformativnoy or feto / neonatal toxicity.
Reproduction studies in animals did not reveal any toxic effect of the drug on the reproductive system.
In general, the need for careful monitoring of pregnant women with diabetes during the pregnancy, as well as when planning pregnancy. The need for insulin in I trimester usually decreases, then in II and III trimester increases. Soon after delivery, insulin requirements return rapidly to the level it was before pregnancy.
It is unknown whether insulin detemir is excreted in breast milk. It is assumed that insulin detemir not affect the metabolic reactions in the body of the newborn / infant during breastfeeding, because it belongs to a group of peptides that are easily broken down in the digestive tract into amino acids and absorbed by the body.
Breastfeeding women may require adjustment of insulin dose and diet.
APPLICATION FOR FUNCTIONS OF THE LIVER
When renal function should be more carefully control the level of blood glucose and to conduct correction of the dose.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
When hepatic dysfunction should more carefully control the level of blood glucose and to conduct correction of the dose.
APPLICATION FOR CHILDREN
Do not use the drug Levemir В® FleksPen В® in children under the age of 6 years, as clinical studies have not been conducted in this patient population.
APPLICATION IN ELDERLY PATIENTS
In patients of advanced age should be more carefully control the level of glucose in the blood and to carry out a correction dose.
Levemir В® FleksPen В® is soluble basal insulin analog having a prolonged action (up to 24 hours).
Unlike other insulin preparations, drug base / bolus therapy Levemir В® FleksPen В® does not increase body weight.
Treatment with Levemir В® FleksPen В® provides a minimal increase in body weight, compared with isophane insulin and insulin glargine.
The smaller compared to the risk isophane insulin nocturnal hypoglycemia allows to carry out more intense dose titration in order to achieve target blood glucose levels in the base / bolus therapy.
Compared with other insulins, in particular, isophane insulin, a smaller risk of nocturnal hypoglycemia episodes light allows for more intense conduct titration to achieve target blood glucose levels during treatment with Levemir В® FleksPen В® in combination with oral hypoglycemic drugs.
Levemir В® FleksPen В® provides better glycemic control (based on fasting plasma glucose measurement) as compared to using isophane insulin.
Before long journey associated with the change of time zones, the patient should consult with your doctor, as a change of time zone means that the patient should eat or inject insulin at a different time.
Lack of the dose or discontinuation of treatment, especially in type 1 diabetes, may lead to the development of hyperglycemiaor diabetic ketoacidosis. Typically, the first symptoms of hyperglycaemia occur gradually over several hours or days. These symptoms include thirst, frequent urination, nausea, vomiting, drowsiness, redness and dryness of the skin, dry mouth, loss of appetite, the smell of acetone in exhaled air. In type 1 diabetes without treatment hyperglycemia leads to the development of diabetic ketoacidosis and can lead to death.
Hypoglycemia can develop if the insulin dose is too high in relation to the need for insulin, when skipping meals or unplanned intense physical effort.
After compensation of carbohydrate metabolism, for example, intensified insulin therapy, patients may change their typical symptoms of hypoglycemia-harbingers of what patients should be informed. Conventional-harbingers of the symptoms may disappear with prolonged duration of diabetes.
Concomitant diseases, especially infectious and accompanied by fever, usually increase the body's need for insulin.
Correction doses may also be necessary if the patient related renal disease, liver disorders, or adrenal, pituitary, or thyroid.
Translations of the patient with other insulin formulations
Transfer the patient to a new type of insulin or a drug of another manufacturer must be under strict medical supervision. When changing the concentration of the manufacturer, type, species (human, human insulin analog) and / or its method of production may require dosage adjustment. Patients passing on treatment with Levemir В® FleksPen В® with another type of insulin may need changing doses compared with the doses previously used preparations of insulin. Dose adjustment may be performed at the first dose, or t