Victoza, 6 mg/ml 3 ml cartridges in syringe pens 2 pcs

Pharmacotherapeutic group: Hypoglycemic drug – glucagon-like receptor polypeptide agonist.

ATC code – A10BX07.

Indications

Type 2 diabetes

The drug Victoza is indicated in adult patients with type 2 diabetes against a background of diet and exercise to achieve glycemic control as:

• Monotherapy
• Combination therapy with one or more oral hypoglycemic drugs (with metformin, sulfonylurea derivatives, or thiazolidinediones), in patients who have not achieved adequate glycemic control on prior therapy.
• Combination therapy with basal insulin in patients who have not achieved adequate glycemic control on therapy with Victoza® and metformin.
  

Active ingredient

Liraglutide

Composition

1 ml of a solution for subcutaneous injection contains:

the active ingredient:

Liraglutide 6 mg.

auxiliary substances:

Sodium hydrophosphate dihydrate – 1.42 mg;

propylene glycol – 14 mg;

phenol – 5.5 mg;

hydrochloric acid/sodium hydroxide – q.s.;

water for injection – up to 1 ml.

How to take, the dosage

The drug Victoza is used once a day at any time, regardless of meals, it can be administered as a subcutaneous injection in the abdomen, thigh or shoulder. The place and time of injection may be varied without dose adjustment. However, it is preferable to inject at approximately the same time of the day, at a time most convenient for the patient. Further information on the method of administration of Victoza can be found in section “Guidelines for use”. Victoza must not be used intravenously or intramuscularly.

Doses
The starting dose of the drug is 0.6 mg liraglutide per day. After using the drug for at least one week, the dose should be increased to 1.2 mg. There is evidence that in some patients the efficacy of treatment increases when the dose of the drug is increased from 1.2 mg to 1.8 mg. In order to achieve the best glycemic control in the patient and taking into account clinical efficacy, the dose of Victoza may be increased to 1.8 mg after using it in a dose of 1.2 mg for at least one week. Use of the drug at a daily dose higher than 1.8 mg is not recommended.

The use of Victoza is recommended in addition to existing therapy with metformin or combination therapy with metformin and thiazolidinedione. Therapy with metformin and thiazolidinedione can be continued in the same doses.
The drug Victoza is recommended to be added to the ongoing therapy with sulfonylurea derivatives or to combined therapy with metformin and sulfonylurea derivatives. When adding Victozac to therapy with sulfonylurea derivatives, dose reduction of sulfonylurea derivatives should be considered in order to minimize the risk of adverse hypoglycemia.

To adjust the dose of Victoza, self-monitoring of blood glucose is not required. However, at the beginning of therapy with Victoza in combination with sulfonylurea derivatives, such blood glucose self-monitoring may be required to adjust the dose of sulfonylurea derivatives.
Special patient groups
Older age (>65 years): No dose adjustment according to age is required. There is limited experience with the drug in patients aged 75 years and older.

Patients with renal impairment
No dose adjustment is required for patients with mild renal impairment. There is limited experience of using the drug in patients with moderate renal insufficiency. Currently, the use of Victoza in patients with severe renal impairment, including patients with terminal renal failure, is contraindicated
Patients with hepatic impairment
Currently, there is limited experience with the use of Victoza in patients with hepatic impairment, so it is contraindicated in patients with mild, moderate or severe hepatic impairment.

Children and adolescents
No data on the use of Victoza in patients under 18 years of age are available to recommend it for treatment of this group of patients.

Interaction

In vitro evaluation of drug interactions. Liraglutide has shown very low pharmacokinetic interactions with drugs due to metabolism in the cytochrome P450 (CYP) system, as well as binding to plasma proteins.

In vivo evaluation of drug interactions. A slight delay in gastric emptying during liraglutide administration may affect the absorption of concomitant oral medications. Drug interaction studies have not shown any clinically significant delay in absorption of these drugs. Several patients treated with Victoza have had at least one episode of acute diarrhea. Diarrhea may affect absorption of oral medications used concomitantly with Victoza.

Paracetamol. A single use of paracetamol at a dose of 1000 mg against the background use of liraglutide does not cause a change in systemic exposure. The plasma Cmax of paracetamol decreased by 31% and the mean Tmax in plasma increased by 15 min. If liraglutide and paracetamol are taken concomitantly, no dose adjustment of the latter is required.

Atorvastatin. A single use of atorvastatin at a dose of 40 mg with liraglutide does not cause changes in systemic exposure. Thus, no dose adjustment of atorvastatin is required during the use of Victoza. Cmax of atorvastatin in plasma decreased by 38%, and the mean Tmax in plasma against liraglutide increased from 1 to 3 h.

Friseofulvin. A single application of griseofulvin at a dose of 500 mg against the background of liraglutide does not cause a change in systemic exposure. The Cmax of griseofulvin increased by 37%, while the mean plasma Tmax value did not change. No dose adjustment is required for griseofulvin and other drugs with low solubility and high permeability.

Digoxin. Concomitant administration of digoxin at a dose of 1 mg and liraglutide resulted in a 16% decrease in AUC of digoxin; Cmax of digoxin decreased by 31%. The mean plasma Tmax of digoxin increased from 1 to 1.5 h. Based on these results, no dose adjustment of digoxin against liraglutide is required.

Lisinopril. A single use of lisinopril at a dose of 20 mg with liraglutide decreased AUC of lisinopril by 15%; Cmax of lisinopril decreased by 27%. The mean plasma Tmax of lisinopril on liraglutide increased from 6 to 8 h. Based on these results, there is no need to adjust the dose of lisinopril against liraglutide.

Peroral contraceptives. The Cmax of ethinylestradiol and levonorgestrel decreased by 12% and 13%, respectively, after their single use with liraglutide therapy. The use of both drugs together with liraglutide was accompanied by an increase in the Tmax of these drugs by 1.5 h. Liraglutide has no clinically significant effect on the systemic exposure of ethinylestradiol and levonorgestrel in the body. Thus, the expected contraceptive effect of both drugs on liraglutide therapy does not change.

Warfarin and other coumarin derivatives. No interaction studies have been conducted. At the beginning of treatment with Victoza in patients receiving warfarin or other coumarin derivatives, more frequent monitoring of MHO is recommended.

Insulin. No pharmacokinetic or pharmacodynamic interaction between liraglutide and insulin detemir has been observed with a single administration of 0.5 units/kg of insulin detemir with 1.8 mg of liraglutide in patients with type 2 diabetes.

Incompatibilities. Substances added to Victoza may cause degradation of liraglutide. The drug Victoza should not be mixed with other drugs, including infusion solutions.

Directions for use

Patient Instructions

The following instructions should be read carefully before using the Victoza^® syringe pen.

The Victoza syringe pen^® contains 18 mg of liraglutide. The patient can choose any of three possible dosages: 0.6; 1.2 and 1.8 mg. The Victoza^® syringe pen is designed for use with NovoFine^® or NovoTwist^® disposable needles up to 8 mm long and up to 32G (0.25/0.23 mm) thick.

The syringe pen Victorza^®

Needle (example)

Preparing the syringe pen for injection

Check the name and color code on the label of the syringe pen to make sure it contains liraglutide. Using the wrong drug can be harmful to the patient’s health.

A. Remove the cap from the syringe pen.

B. Remove the paper sticker from the disposable needle. Carefully and tightly thread the needle onto the syringe pen.

C. Remove the outer needle cap and set it aside without throwing it away.

D. Remove the inner needle cap and discard it.

Important information. Always use a new needle each time you inject. This measure will prevent contamination, infection, drug leakage from the syringe pen, needle blockage, and guarantee accurate dosing. Follow needle handling precautions to ensure that the needle is not bent or damaged before it is used.

Important information. Never put the inner cap back on the needle. This will prevent the risk of accidental needle sticking.

Care for the syringe pen

Do not attempt to repair or take apart the syringe pen yourself. – Protect the syringe pen from dust, dirt, and all types of liquids.

The syringe pen can be cleaned with a cloth dampened with a mild detergent. Do not immerse the syringe pen in liquids, and do not wash or lubricate it, as this may damage the mechanism.

Important information

The syringe pen is for personal use, do not give it to others. Keep the syringe pen out of the reach of everyone, especially children.

Test a new syringe pen

Important information

Always test the syringe pen as shown below before using a new syringe pen for injections.

If the patient is already using a syringe pen, they need to go to Step H, Dose Setting.

E. Rotate the dose selector until the performance check symbol in the display window aligns with the dose indicator.

F. Holding the syringe pen with the needle up, tap the cartridge several times with your finger to move the air bubbles to the top of the cartridge.

G. Holding the syringe pen with the needle up, press the trigger until 0 mg appears in the indicator window opposite the dose indicator. A drop of medication should appear at the end of the needle. If no drop appears, repeat steps E-G until a drop of liraglutide appears at the end of the needle. If no drop appears at the end of the needle after 4 repetitions, replace the needle with a new one and repeat the E-G operation again. If there is still no drop at the end of the needle, the syringe pen is defective and the patient should use a new syringe pen.

Important information. If the patient has dropped the syringe pen on a hard surface or has any doubt that it is fully functional, a new disposable needle should be attached and the syringe should be tested before starting the medication.

The first step is to make sure that the “0mg” indicator window is facing the dose indicator.

H. Turn the dose selector until the patient’s desired dose (0.6; 1.2 or 1.8 mg) in the indicator window aligns with the dose indicator (mg means mg). You can correct the mistakenly set dose by turning the dose selector forward or backward until the correct dose in the display window aligns with the dose indicator. When you rotate the dose selector backwards, be careful not to accidentally press the start button to prevent the liraglutide dose being ejected. If the dose selector has stopped before the desired patient dose appears in the indicator window opposite the dose indicator, it means that there is not enough liraglutide remaining in the syringe pen to give a full dose. If this is the case, one of the two actions below must be performed.

Inject the correct dose in two doses

Turn the dose selector in either direction until the 0.6 mg or 1.2 mg dose is in line with the dose indicator. Make the injection. Prepare a new syringe pen for the second injection and inject the remaining dose of medication (in milligrams) to complete the full dose. You can only split the dose of medication between the used and new syringe pen if the patient has been trained to do so or if the physician has recommended it. A dose-planning calculator should be used. If the patient does not divide the dose correctly, he or she may inject too little or too much liraglutide.

If the dose selector has stopped before the 0.6 mg appears in the indicator window across from the dose indicator, prepare a new syringe pen for injection and inject the full dose of medication with a new syringe pen.

Important information. Do not attempt to select doses other than 0.6; 1.2 or 1.8 mg. The numbers in the indicator window should be exactly opposite the dose indicator to make sure the patient is getting the correct dose.

The dose selector clicks when you rotate it. Do not use these clicks to measure the dose of liraglutide that the patient needs for injection.

Do not use the cartridge scale to measure the liraglutide dose for injection – it is not accurate enough.

Inject the product

Inject the needle under the skin using the injection technique recommended by your doctor or nurse. Then follow the instructions below:

I. Press the trigger all the way down until “0 mg” appears in the indicator window opposite the dose indicator. Care should be taken not to touch the indicator window with your fingers or press the dose selector, as this can cause the syringe handle mechanism to lock. Hold the trigger fully depressed and the needle under the skin for at least 6 seconds. This will ensure that the full dose of medication is administered.

J. Remove the needle from under the skin. The patient may see a drop of liraglutide on the end of the needle. This is normal and has no effect on the dose of the drug that was just injected.

K. Insert the end of the needle inside the outer cap of the needle without touching the needle or the outer cap.

L. When the needle is in the needle cap, gently push the outer needle cap forward so that the needle fully enters it. Then unscrew the needle. Discard the needle, taking precautions, and cap the syringe pen. If the syringe pen is empty, unscrew the needle and discard the empty syringe pen without the needle. Follow local requirements for disposal of used medical supplies.

Important information. Remove the used needle after each injection and do not store the syringe pen with the needle attached. This will help prevent contamination, infection and leakage of liraglutide from the syringe pen and needle blockage. It will also ensure accurate dispensing.

Important information. Caregivers should handle used needles with extreme care to avoid accidental injections and cross-infection.

Special Instructions

Victoza should not be used in patients with type 1 diabetes mellitus or to treat diabetic ketoacidosis.

Victoza is not a substitute for insulin. The administration of liraglutide to patients already receiving insulin has not been studied.

The experience with Victoza in patients with heart failure of functional classes I-II according to NYHA functional classification of chronic heart failure is limited. There is no experience of Victoza administration in patients with heart failure of functional classes III-IV in accordance with NYHA classification of chronic heart failure.

The experience of using Victoza in patients with inflammatory bowel disease and diabetic paresis of the stomach is limited, so the use of Victoza in these groups of patients is contraindicated. The use of Victoza is associated with the development of transient adverse gastrointestinal reactions, such as nausea, vomiting and diarrhea.

The use of other GFP-1 agonists has been associated with a risk of pancreatitis. Several cases of acute pancreatitis have been reported. Patients should be informed about the characteristic symptoms of developing acute pancreatitis: persistent severe abdominal pain. In case of suspected pancreatitis the therapy with Victoza and other potentially dangerous drugs should be stopped immediately.

In clinical trials of Victoza in selected patients (particularly in patients with pre-existing thyroid disease) adverse thyroid events have been reported, including increased serum calcitonin concentrations, goiter and thyroid neoplasms.

In clinical trials, signs and symptoms of dehydration and renal failure have been reported in patients receiving Victoza. Patients receiving Victoza should be advised of the possible risk of dehydration due to gastrointestinal side effects and the need for precautions to avoid developing hypovolemia.

Patients receiving Victoza in combination with sulfonylurea derivatives have an increased risk of hypoglycemia . The risk of hypoglycemia can be reduced by reducing the dose of sulfonylurea derivatives.

Impact on the ability to drive vehicles and operate machinery. There have been no studies on the effect of the drug Victoza on the ability to drive vehicles and operate mechanisms. It is unlikely that liraglutide may affect the ability to drive vehicles or operate mechanisms. Patients should be advised that they should take precautions to avoid developing hypoglycemia while driving and operating machinery, especially when Victoza is used in combination with sulfonylurea derivatives.

Guidelines for Use

The drug Victoza should not be used if it looks other than a clear and colorless or nearly colorless liquid.

Victose should not be used if it has been frozen.

Victose can be injected with needles up to 8 mm long and up to 32G thick. The syringe pen is intended for use in combination with NovoFine or NovoTwist disposable injection needles.

The injection needles are not included in the package.

The patient must be informed that the used needle must be discarded after each injection and that the syringe pen must not be stored with the needle attached. This measure will prevent contamination, infection, and leakage from the syringe pen and ensure accurate dispensing.

Contraindications

• high sensitivity to the active ingredient or other constituents of the drug
• pregnancy,

pregnancy and breastfeeding;

• diabetes mellitus type 1;
• diabetic ketoacidosis;
• diabetic ketoacidosissevere renal dysfunction;
• disorders of liver function;
• heart failure III-IV functional class (according to NYHA classification);
• inflammatory bowel disease;
• paresis of the stomach;
• under 18 years of age.

With caution: heart failure class I-II (according to NYHA classification); renal function abnormality of moderate severity; age 75 years and older There is limited experience in using the drug in patients in these categories.

Side effects

In clinical trials, the most frequently reported gastrointestinal side effects are: nausea and diarrhea (reported in >10% of patients); vomiting, constipation, abdominal pain and dyspeptic phenomena (reported in ≥1%, but ≤10% of patients).

These gastrointestinal adverse events may occur more frequently at the beginning of therapy with Victoza, but as treatment continues, reactions usually decrease within a few days or weeks. Adverse reactions in the form of headache and upper respiratory tract infections have been observed relatively frequently (1-10% of patients). In addition, the development of hypoglycemic conditions is possible, especially when using Victoza in combination with sulfonylurea derivatives (reported in > 10% of patients). Severe hypoglycemia mainly develops against the background of combined administration of Victoza with sulfonylurea derivatives.

Serious side effects have rarely been reported.

Table 1 summarizes the adverse effects identified in long-term controlled phase III clinical trials of Victoza and in spontaneous (post-marketing) reports. Presented are the adverse reactions identified in long-term phase III clinical trials with an incidence of >5%, provided that their incidence was higher in the group of patients receiving Victoza compared to that in the group of patients receiving the comparison drugs. Also included were adverse reactions with a frequency of development of ≥1%, provided that their frequency was 2 or more times higher than the frequency of adverse reactions in the patient groups receiving the comparison drugs.

The frequency of the remaining spontaneous (post-marketing) reports was calculated based on their occurrence during phase III clinical trials.
All adverse reactions presented below, based on data obtained during clinical trials and in the post-marketing period, are categorized into groups according to the frequency of development according to MedDRA and organ systems. The frequency of development of adverse reactions is defined as: very common (≥ 1/10); common (≥ 1/100 to

Table 1 Adverse reactions identified in long-term placebo-controlled phase III clinical trials and spontaneous (postmarketing) reports

Organs and systems/ adverse reactionsFrequency of development Phase III studiesSpontaneous reportsMetabolic and nutritional disordersHypoglycemiaFrequent AnorexiaFrequent Reduced appetiteFrequent Nervous system disordersHeadacheFrequent GI disturbancesNauseaNauseaVery commonDiarrheaVery common VomitingFrequent DyspepsiaFrequent Upper abdominal painFrequent ConstipationFrequent GastritisFrequent MeteorismFrequent BloatingFrequent Gastroesophageal refluxFrequent BurpingFrequent Immune system disordersAnaphylactic reactions Infection and invasionsInfection of upper respiratory tract infectionsRarely General Renal and urinary tract disordersSomnoxia InfrequentReactions at the injection siteFrequent Renal and urinary tract disordersSerious renal failure* Infrequent Renal dysfunction* Infrequent Metabolic and nutritional disordersElimpathy* Infrequent Skin and subcutaneous tissue disordersSpotting rash InfrequentHealing infrequently/p>

N= 2501 patients receiving Victoza therapy

Hypoglycemia

The majority of episodes of confirmed hypoglycemia reported in clinical trials were mild.
No cases of severe hypoglycemia have been reported during clinical trials when Victoza is used as monotherapy. Severe hypoglycemia may occur infrequently and is mainly observed when Victoza is used in combination with sulfonylurea derivatives (0.02 cases/patient/year). When Victoza in combination with other oral hypoglycemic drugs (not sulfonylurea derivatives) hypoglycemia was very rarely observed (0.001 cases/patient/year).

There have been no cases of severe hypoglycemia during therapy with liraglutide at a dose of 1.8 mg in combination with insulin detemir and metformin. The incidence of mild hypoglycemia was 0.228 cases/patient per year. In the groups of patients treated with liraglutide 1.8 mg and metformin, the incidence of mild hypoglycemia was 0.034 and 0.115 cases/patient per year, respectively.

Gastrointestinal adverse reactions
In most cases, nausea was mild to moderate, transient, and rarely led to discontinuation of therapy.
20.7% of patients receiving Victoza in combination with metformin experienced at least one episode of nausea, and 12.6% had at least one episode of diarrhea. When Victoza was taken in combination with sulfonylurea derivatives, 9.1% of patients experienced at least one episode of nausea and 7.9% had at least one episode of diarrhea.

In long-term controlled clinical trials (26 weeks or more), the rate of patient discontinuation due to the development of adverse events was 7.8% in the group of patients receiving Victoza and 3.4% in the group of patients receiving the comparison drugs. Nausea (2.8% of patients) and vomiting (1.5%) were the most common adverse reactions that led to withdrawal of Victoza.

In patients aged over 70 years, the incidence of gastrointestinal adverse reactions may be higher with Victoza.

In patients with mild renal impairment (creatinine clearance ≤ 60-90 ml/min), the incidence of gastrointestinal adverse reactions may be higher when using Victoza.

Immunogenicity
Given the possibility of immunogenic effects of protein and peptide drugs, the use of Victoza in patients may lead to the formation of antibodies to liraglutide. Antibody formation is noted in an average of 8.6% of patients. The formation of antibodies does not reduce the effectiveness of Victoza.

Injection site reactions
In long-term (26 weeks or more) controlled studies, approximately 2% of patients treated with Victoza experienced injection site reactions. These reactions were usually mild.

Pancreatitis
A few cases of acute pancreatitis have been reported. The overall incidence of adverse thyroid reactions in all interim and long-term clinical trials with liraglutide, placebo, and comparison drugs is 33.5; 30.0; and 21.7 cases per 1,000 patient-years of cumulative exposure, respectively; and the incidence of serious adverse reactions is 5.4; 2.1; and 1.2, respectively.

The most frequent thyroid side effects were thyroid neoplasms, elevated serum calcitonin concentrations, and goiter. The incidence of these events per 1,000 patient-years of exposure was 6.8; 10.9 and 5.4 cases, respectively, in patients receiving liraglutide, compared with 6.4; 10.7 and 2.1 cases in patients receiving placebo and 2.4; 6.0 and 1.8 cases in patients receiving comparison drugs.

Allergic reactions

In the post-registration period, allergic reactions such as urticaria, rash, and pruritus were reported.
Several cases of anaphylactic reactions accompanied by symptoms such as arterial hypotension, palpitations, dyspnea, edema have been described in the post-registration period when using Victoza.

Overdose

Symptoms: during clinical trials and in the post-marketing period, cases of Victoza administration at doses up to 40 times higher than the average recommended dose (72 mg) have been reported, accompanied by severe nausea and vomiting. No cases of severe hypoglycemia were observed. All patients recovered completely without complications.

Treatment: appropriate symptomatic therapy is recommended.

Pregnancy use

There are no adequate data on the use of Victoza in pregnant women. Animal studies have demonstrated reproductive toxicity of the drug. The potential risk to humans is unknown.

The drug Victoza should not be used during pregnancy and insulin treatment is recommended instead. If the patient is preparing for pregnancy or if pregnancy has already occurred, therapy with Victoza should be stopped immediately.

It is not known whether liraglutide is excreted with the breast milk of women. Animal studies have shown that the penetration of liraglutide and closely related structural metabolites into breast milk is low. There is no experience of using Victozau in breastfeeding women. The use of the drug during breastfeeding is contraindicated.