Saxenda injection solution 6mg/ml Novo Nordisk supports a calorie reduction diet (3 plants)

Pharmacokology

Group of Pharmacological Therapy: drugs used in diabetes, similar to peptide -1 varieties Glucagon (GLP -1).

ATC code: A10BJ02.

Mechanism of action

Liraglutide is a substance similar to Peptide-1 like Glucagon (GLP-1) of a person with acyl mounted with 97% of the amino acid sequence sequence similar to the endogenous GLP-1. Liraglutide attaches and activates receptors GLP-1.

GLP-1 is a physiological regulator that feels delicious and the amount of food is put in, but the exact acting mechanism is not completely clear. Research on animal, peripheral Liraglutide has an impact on specific brain regions associated with regulating cravings, in that place Liraglutide, through GLP-1 receptor activity, increases the feeling of satiety and reduces hunger signals, thus losing body weight.

Pharmacological effects

Liraglutide loses human body weight mainly through reducing fat mass with more visceral fat loss than subcutaneous fat. Liraglutide regulates appetite by increasing the feeling of fullness and anorexia, while reducing the feeling of hunger and digesting food later, thus reducing the amount of food.

Liraglutide does not increase energy consumption compared to placebo.

Liraglutide stimulates insulin secretion and reduces glucagon secretion in a blood glucose -dependent way, thereby reducing glucose both when hungry and after eating. The effect of reducing glucose is more pronounced in patients with predicated diabetes and diabetes than people with normal blood sugar. Clinical trials show that Liraglutide helps to improve and maintain the function of concrete cells, shown via homa-B, and the ratio of insulin compared to insulin.

Clinical efficiency and safety

Liraglutide effectiveness and safety in weight management combined with calories reducing diets and increased physical activity are studied in four random, double -blind, regarded trials of 5,358 patients. Refer to the results of 4 experiments in the drug manual.

Dynamic pharmacokinetics

absorption

After subcutaneous injection, Liraglutide is absorbed slowly, reaching a maximum concentration of about 11 hours after use. The average concentration in the stable state of Liraglutide (area below the AUC curve 24) reaches about 31 nmol/l in obese patients (BMI 30-40 kg/m3) after taking 3 mg Liraglutide.

Liraglutide contact increases to the dose. Liraglutide absolute bioavailability after skin injection is about 55%.

distribution

The average average integral after subcutaneous injection is 20-25 I (for a person weighing about 100 kg).

Liraglutide is strongly connected to plasma proteins (> 98%).

Biological metabolism

During the 24 -hour period after the liraglutide injection, the radioactive mark [H] for healthy people, the main component circulating in plasma is intact Liraglutide. Two small amounts of plasma metabolites are detected (

Elimination

Liraglutide is metabolized in the same way as large molecular proteins without a major elimination agency. After an injection of a dose (H) -Liraglutide, the intact liraglutide is not detected in urine or feces. Only a small part of radioactive activity is excreted in the form of metabolites attached to Liraglutide in urine or feces (6% and 5% respectively). The radioactive activity in urine and feces is mainly eliminated in the first 6-8 days, and corresponds to three small metabolites.

The median of clearance after the injection of Liraglutide under the skin is about 0.9-1.4 liters/hour with a selling time of about 13 hours.

Special patient groups

Elderly: Age does not affect clinical significance to liraglutide pharmacokinetics, based on the results of pharmacokinetic analysis according to the population of overweight and obesity patient data (18-82 years old). There is no need to adjust the dose based on age.

Sex: Based on the results of population pharmacokinetics analysis, women have the level of Liraglutide clearance adjustment according to 24% weight lower than men. Based on the data of contact response, do not need to adjust the dose based on gender.

Race: Racal origin does not affect clinical significance on pharmacokinetics of Liraglutide, based on the results of the pharmacokinetics analysis by population, including overweight patients and white skin, black, Asia and Spanish/air.

Body weight: Liraglutide exposure is reduced along with the body weight gain before treatment. The daily dose of 3.0 mg Liraglutide brings good contact to the whole body within the weight of 60-234 kg that has been assessed in clinical trials. Contact with Liraglutide has not been studied in body weight patients> 234 kg.

Liver: Liraglutide pharmacokinetics with single dose (0.75 mg) is assessed in testing in patients with different levels of liver failure. Liraglutide contacts decreased by 13-23% in mild to moderate liver failure subjects compared to healthy people. Significant exposure (44%) in patients with severe liver failure (Child Pugh> 9).

Renal failure: In a single dose test (0.75 mg), Liraglutide contact in patients with renal impairment is reduced compared to people with normal kidney function. Liraglutide exposure is reduced, equivalent to 33%, 14%, 27%and 26%, in patients with mild renal failure (Creatinine clearance, CRCI 50-80 ml/minute), average (CrCl 30-50 ml/min), and severe (CrCl

Pediatric patients: Saxenda® has not been studied in pediatric patients.

Preceptic safety data

Preceptic data shows that there is no special danger to humans, based on regular studies on pharmacological safety, repetitive dose, or gene toxicity.

There has been a non -fatal C cell tumor in two -year studies on the possibility of cancer in rats and mice. On rats, there is no concentration that does not see the harmful effects (Noael). These tumors are not found in monkeys for 20 months. The findings in rodents are caused by non-gene toxic mechanism, specific through the GLP-1 receptor intermediaries that rodents are particularly sensitive. The relationship with people may be low, but cannot be completely excluded. No other tumors are found related to treatment.

Animal studies do not show direct harm to fertility but early embryo mortality increases slightly with the highest dose. Using Liraglutide in the middle of pregnancy will cause weight loss of the mother animal and reduce the development of the fetus with unclear effects in the ribs and change the skeleton in the rabbit. The growth of newborns in mice was reduced when exposed to Liraglutide, and extended to the post -weaning period in high doses. It is unclear whether this growth is caused by reducing the amount of milk intake due to the direct effect of GLP-1 or reducing milk creation in the mother mouse due to calories reduction.

Patients with type 2 diabetes

Do not use Saxenda® in combination with other GLP-1 bronze drugs.

When starting Saxenda®, it is advisable to consider reducing simultaneous doses of drugs such as insulin or insulin secretion stimulants (such as sulfonylurea) to reduce the risk of hypoglycemia.

Special patient groups

Elderly (65 years)

No dose is based on age. Treatment experience in patients ≥ 75 years old is limited, so the use of drugs for this group of patients is not recommended (see special warning and caution when using and pharmacokinetic properties).

Patients with renal failure

No dose adjustment in patients with mild or medium renal impairment (creatinine clearance ≥30 ml/min). Do not use Saxenda® for patients with severe renal impairment (clearing creatinine

Patients with liver failure

No dose adjustment in patients with mild or medium liver failure. Saxenda® should not be used for patients with severe hepatic failure and should be used carefully for patients with mild or moderate liver failure (see special and cautious warnings when used and pharmacokinetic properties).

Children

Safety and effectiveness of Saxenda® in children and young people under 18 have not been determined.

Note: The above dose is for reference only. Specific dosage depends on the condition and level of progression of the disease. For a suitable dose, you need to consult a doctor or medical specialist.What to do when overdose? The reported events include nausea and vomiting, which are also expected symptoms of Liraglutide overdose. There is no report on heavy hypoglycemia. All patients recover without complications.

When an overdose, suitable supportive treatment should be started depending on the patient's signs and clinical symptoms. Patients should be monitored for clinical signs of dehydration as well as blood glucose.

In an emergency, call the 115 emergency center immediately or go to the nearest local health station.

What to do when forgetting a dose?

It is best to inject as soon as possible. But if the next dose time is less than 12 hours, it is not advisable to compensate for the forgotten dose but should continue the next dose of the regimen once a day.

Do not get an additional dose or increase the dose to compensate for the forgotten injection. For further instructions on how to use, see special caution when canceling and other operations.

Using Liraglutide in these patients is not recommended (see the dosage and usage).

The effect of Liraglutide in weight management has not been surveyed in mild or medium liver failure people, so be careful to use for these patients (see dosage and usage, pharmacokinetic properties).

Experience is limited to patients with bowel inflammation and stomach paralysis associated with diabetes. The use of Liraglutide is not recommended for these patients due to transient side effects, including nausea, vomiting and diarrhea.

pancreatic gland inflammation

Using GLP-1 receptor receptors is associated with the risk of developing acute pancreatitis. There have been a few reports on acute pancreatitis when using Liraglutide. If there is a suspected pancreatitis, Liraglutide should be suspected; If acute pancreatitis is confirmed, do not reuse Liraglutide. Be cautious in patients with a history of pancreatitis.

gallstones and cholecystitis

In clinical trials on weight management, it is commented that the rate of gallstones and cholecystitis in patients with Liraglutide treatment is higher than that of patients using placebo. The fact that losing weight is more likely to increase the risk of gallstones, and so the higher rate of the cholecystitis is explained only in part in part with Liraglutide. Gallstones and cholecystitis may be hospitalized and have gallbladder surgery. Patients should be notified of the typical symptoms of gallstones and cholecystitis.

thyroid disease

In clinical trials on type 2 diabetes, side effects on the thyroid gland, including hyperlcitonin, goiter and thyroid cancer have been reported, especially in patients with previous thyroid disease. In some cases, blood calcitonin is also monitored in weight management tests. Therefore, be careful when using Liraglutide in patients with thyroid disease.

heart rate

The increase in heart rate has been observed when using Liraglutide in clinical trials (see pharmacokinetic characteristics). The clinical significance of an increase in heart rate when treating Liraglutide is unknown, especially in patients with heart disease and cerebrovascular disease, due to limited results in clinical trials. Heart rate should be monitored regularly in accordance with normal clinical practice. Patients need to be notified of symptoms of heart rate increased (brushing chest drums or heartbeat feels fast during rest). For patients with continuous increased heart rate at resting at a clinical significance, Liraglutide should be stopped.

dehydration

Signs and symptoms of dehydration, including renal failure and acute renal failure, have been reported in patients who treat GLP-1 receptor receptors. Patients with Liraglutide treatment should be advised on the risk of dehydration that may be related to the gastrointestinal side effects and take preventive measures to avoid dehydration.

Hypoglycemia in patients with type 2 diabetes

Patients with type 2 diabetes treatment Liraglutide in combination with sulfonylurea may increase the risk of hypoglycemia. The risk of hypoglycemia may be reduced by reducing sulfonylurea dose. The use of Saxenda® for patients undergin treatment has not been evaluated.

Using drugs for women during pregnancy and lactation

The possibility of pregnancy

Not enough data on the use of Liraglutide for pregnant women. Animal studies show that there is a reproductive toxicity (see clinical safety data). The potential risk to humans is unknown.

Liraglutide should not be used during pregnancy. If the patient wants to get pregnant, or detects pregnancy while taking the drug, Liraglutide should be stopped.

breastfeeding

It is unclear whether Liraglutide is excreted in breast milk or not. Animal studies show that the transportation of Liraglutide and the metabolites that are structured closely related to milk is low. Prelopatic research shows that there is a decrease in the growth of newborn mice related to treatment. Due to no experience, 20 does not use Saxenda® during breastfeeding.

fertility

In addition to a slight decrease in the number of fetuses, animal research does not show harmful effects on fertility (see property data clinical).

affects the ability to drive and operate machinery

saxenda® does not have negligible influence or impact on the ability to drive and operate machinery.

Interactive drug

In the laboratory, Liraglutide shows that it is very little likely to have pharmacokinetic interactions with other active ingredients related to Cytochrome P450 (CYP) and plasma protein binding.

Interactive research does not show any clinical absorption delay and therefore no dose adjustment.

Interactive studies are conducted with 1.8 mg liraglutie. The impact on the speed of stomach empty is the same between the liraglutide dose of 1.8 mg and 3.0 mg (area under the paracetamol AUC0-300 minutes). Very few patients treated Liraglutide for at least one severe diarrhea.

diarrhea can affect the absorption of oral medications simultaneously.

warfarin and other Coumarin derivatives

There are no studies on interaction. It does not exclude clinical significance with poor soluble active ingredients or narrow treatment index such as warfarin. At the beginning of Liraglutide treatment for patients who are taking warfarin or other Coumarin derivatives, they should monitor the ratio of international standard Inr standard.

paracetamol (acetaminophen)

Liraglutide does not change the overall contact level of paracetamol after the single dose of 1,000 mg. The highest concentration in plasma (CMAX) of Paracetamol decreased by 31% and the median time reached the highest concentration in plasma (TMAX) up to 15 minutes later. No need to adjust the dose of paracetamol when used simultaneously.

atorvastatin

Liraglutide does not change the total contact level of Atorvastatin after taking the single dose Atorvastatin 40 mg. Therefore, there is no need to adjust the dose when used simultaneously.

griseofulvin

Liraglutide does not change Griseofulvin's entire contact level after taking a single dose of Griseofulvin 500 mg. Griseofulvin's CMAX increased by 37% while TMAX median did not change. No need to adjust the dose of griseofulvin and other old compounds of low solubility and high osmosis.

digoxin

Take a single dose of 1 mg Digoxin with Liraglutide reducing 16% of the area under the curve (AUC) of the digoxin; CMAX decreased by 31%. Digoxin's maximum maximum concentration is delayed from 1 hour to 1.5 hours. Based on this result, no adjustment of Digoxin dose.

lisinopril

Use single dose Lisinopril 20 mg with Liraglutide reduces 15% of the area under the AUC curve of Lisinopril; CMAX decreased by 27%. Lisinopril's TMAX median is slow from 6 to 8 hours when used with Liraglutide. Based on this result, there is no need to adjust the dose of lisinopril.

Oral contraceptives

Liraglutide reduces the cmax of ethinylelestradiol and levonorgestrel, respectively, 12% and 13%, after taking a single dose of oral contraceptives. The maximum concentration time TMAX is 1.5 hours late when using Liraglutide with both compounds. There is no clinical significance for the overall contact of both compounds. Therefore, the effect of contraception is expected not to be affected when used simultaneously Liraglutide.