Soliqua SoloStar, 100 units/ml+50 µg/ml 3 ml cartridges in SoloStar syringe pens 3 pcs

In adult patients with type 2 diabetes in combination with metformin as an adjunct to diet therapy and increased physical activity in order to improve glycemic control when metformin monotherapy or a combination of metformin with another oral hypoglycemic drug, or basal insulin monotherapy are not effective.

Active ingredient

Composition

How to take, the dosage

For ease of personalized dosing, SoloStar® is available in two syringe pens that provide a choice of different doses. The difference between the two syringe pens is the dose range of the active ingredients in the syringe pens (see below).

In order to avoid administering the drug by mistake from a different syringe pen (with a different dosage), make sure that the prescription lists the appropriate Soliqua SoloStar® syringe pen for your prescription: the Soliqua SoloStar® Syringe Pen (10-40) or the Soliqua SoloStar® Syringe Pen (30-60).

The maximum daily dose of Soliqua SoloStar® is 60 units (60 units of insulin glargine and 20 µg of lixisenatide).
Soliqua SoloStar® is administered subcutaneously once daily for 1 hour before any meal. Preferably, the prandial (before meal) injection of Soliqua SoloStar® should be given daily before the same meal, chosen as the most appropriate for the patient. If a dose of Soliqua SoloStar® is missed, it should be injected within 1 hour before the next meal.

The dose of Soliqua SoloStar® should be adjusted individually based on clinical response and titrated based on the patient’s insulin needs. The dose of lixisenatide increases or decreases with the dose of insulin glargine and also depends on which of the above syringe pens is used.

Dose adjustments or changes in the timing of administration of Soliqua SoloStar® should only be made under medical supervision with appropriate monitoring of blood glucose concentrations (see section “Special Precautions”).

The initial dose of Soliqua SoloStar®
The starting dose of Soliqua SoloStar®
The starting dose of Soliqua SoloStar® is selected based on previous treatment with hypoglycemic drugs and should not exceed the starting dose of lixisenatide 10 µg.

The starting dose of Soliqua SoloStar®

– For basal insulin administered twice daily or insulin glargine 300 units/ml administered once daily, the initial daily dose of Soliqua SoloStar® must be reduced by 20%.
– For any other basal insulin, the same recommendations as for insulin glargine (100 U/ml) should apply.

Dose titration of Soliqua SoloStar®
Soliqua SoloStar® should be dosed according to the patient’s individual insulin requirements. In order to improve glycemic control, it is recommended to adjust the drug dose based on the determination of plasma glucose concentration on an empty stomach.
During the transition to therapy with Soliqua SoloStar® and in subsequent weeks, it is recommended to monitor blood glucose concentration carefully.

Injection method
Soliqua SoloStar® is injected into the subcutaneous fatty tissue of the front abdominal wall, shoulders or hips.
In order to reduce the risk of lipodystrophy, the injection site should be changed with each new injection within one of the recommended injection sites.

The rate of absorption and thus the onset and duration of action may be affected by physical activity and other changing factors such as stress, intercurrent illness, or changes in concurrent medications or diet.
Soliqua SoloStar® should not be administered intravenously or intramuscularly.

After the first administration of the drug, the syringe pen may be used for 4 weeks, stored at temperatures below 25°C in a light-proof place (do not freeze or refrigerate).

For more information on injecting with the Soliqua SoloStar® 10-40 syringe pen, see “Instructions for Use of the Soliqua SoloStar® 10-40 Syringe Pen (for doses of 10-40 units of drug per day)” below.

For more information about injecting with the Soliqua SoloStar® 30-60 Syringe Pen, see “Instructions for Use of the Soliqua SoloStar® 30-60 Syringe Pen (for doses of 30-60 units per day)” below.

Interaction

Studies on the interaction of the drug Soliqua SoloStar® with other medicinal products have not been conducted.

Insulin glargine
A number of medicinal products affect glucose metabolism, so their concomitant use with insulin may require adjustment of insulin dose and especially close monitoring, including monitoring of blood glucose concentrations.

In addition, signs of adrenergic counterregulation (sympathetic nervous system activation in response to hypoglycemia) may be less pronounced or absent under the influence of sympatholytic drugs such as beta-adrenoblockers, clonidine, guanethidine and reserpine.

Lixisenatide
Lixisenatide is a peptide and is not metabolized by cytochrome P450 isoenzymes. In in vitro studies, lixisenatide did not affect the activity of tested cytochrome P450 system isoenzymes or transporters in humans.

Effect of delayed gastric emptying on absorption of oral medications

Delayed gastric emptying when using lixisenatide may decrease the absorption rate of oral medications. Caution should be exercised when concomitant ingestion of drugs with a narrow therapeutic range or requiring close clinical monitoring. If such drugs should be taken with meals, patients should be advised to take them with the meal when lixisenatide is not administered. Oral medications whose efficacy is particularly dependent on threshold concentrations, such as antibiotics, should be taken at least 1 h before or 4 h after injection of Soliqua SoloStar®.

Gastro-resistant drugs should be taken at least 1 h before- or 4 h after Soliqua SoloStar® injection.

With paracetamol

. There is no need to adjust the dose of paracetamol when used concomitantly with the drug Soliqua SoloStar®, but if rapid onset of action of paracetamol is required, it should be taken 1-4 hours after the injection of Soliqua SoloStar® due to possible increase in tmax of paracetamol in blood plasma.

With oral contraceptive drugs

Patients using oral contraceptive drugs should be advised to take at least 1 h before or 11 h after Soliqua SoloStar® injection.

With atorvastatin

Patients taking atorvastatin should be advised to take it at least 1 h before or 11 h after Soliqua SoloStar® injection.

With warfarin

Warfarin dosage adjustment is not required when combined with Soliqua SoloStar®, but frequent monitoring of the international normalized ratio (INR) at the beginning and after therapy with Soliqua SoloStar® is recommended.

With digoxin
No dose adjustment of digoxin is required when combined with Soliqua SoloStar®.

With ramipril
No dose adjustment is required for ramipril when combined with Soliqua SoloStar®.

Special Instructions

Contraindications

Side effects

The adverse reactions (HP) listed below are presented by organ system (as classified by the Medical Dictionary for Regulatory Affairs (MedDRA)) and the CIOMS (Council for International Organizations of Medical Sciences) HP frequency classification was used: Very common (≥10%); common (≥1%; <10%); infrequent (≥0.1%; rare (≥0.01%; very rare (<0.01%), frequency unknown (the frequency of HP could not be determined from available data).
Brief description of safety profile

The most frequently observed HP during the use of Soliqua SoloStar® was the development of hypoglycemia and HP from the GI tract (see “Description of individual HP” below).

List of HP
Infectious and parasitic diseases
Infrequent: nasopharyngitis, upper respiratory tract infections.

Immune system disorders
Infrequent: urticaria.

Metabolic and nutritional disorders
Very common: hypoglycemia.

Nervous system disorders
Often: dizziness.
Infrequent: headache.

Gastrointestinal disorders
Often: nausea, diarrhea, vomiting.
Infrequent: dyspepsia, abdominal pain.

General disorders and disorders at the site of administration
Infrequent: feeling of fatigue, reactions at the site of administration.
Description of individual HP

Hypoglycemia
Episodes of severe hypoglycemia, especially if they occur repeatedly, may lead to the development of neurological disorders. Cases of prolonged or severe hypoglycemia can be life threatening.

. In many patients, signs and symptoms of neuroglycopenia – lack of glucose in the brain (feeling of fatigue, inadequate fatigue or weakness, decreased ability to concentrate, drowsiness, visual disturbances, headache, nausea, confusion or loss of consciousness, seizures) are preceded by signs of adrenergic counterregulation (activation of the sympathetic nervous system in response to hypoglycemia) hunger, irritability, nervous agitation or tremors, restlessness, pallor, “cold” sweat, tachycardia, palpitations. In general, the more significant and rapid is the decrease in blood glucose concentration, the more pronounced is the adrenergic counterregulation and its manifestations.

Documented hypoglycemic HP occurring with clinical symptoms, or severe hypoglycemic HP

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Patients not treated with insulin Transferring from basal insulin
Soliqua SoloStar® Insulin glargine Lixisenatide Lixisenatide/td> Soliqua SoloStar® Insulin glargine Number of patients 469 467 233 365 Documented hypoglycemia with clinical symptoms * Documented hypoglycemia occurring with clinical symptoms/td> Patients with hypoglycemic episode, number of patients 120 110 15 146 155 (%) (25.6%) (23.6%) (6.4%) (40.0%) (42.5%) Episodes of hypoglycemia per patient-year, number 1.44 1.22 0.34 3.03 4.22 Severe hypoglycemia** Episodes of hypoglycemia per patient-year, number 0 <0.01 0 0.02 <0.01 *Documented, clinically symptomatic hypoglycemia was an episode during which typical symptoms of hypoglycemia were combined with an established plasma blood glucose concentration ≤70 mg/dL (3.9 mmol/L).
** Severe clinically symptomatic hypoglycemia was an episode that required the assistance of others to actively administer carbohydrates, glucagon, or other interventions to maintain basic body vital functions.

Gastrointestinal disorders
Gastrointestinal HP (nausea, vomiting, and diarrhea) were frequently observed HP during treatment. In patients treated with Soliqua SoloStar®, the incidence of treatment-related nausea, diarrhea, and vomiting was 8.4%, 2.2%, and 2.2%, respectively. Gastrointestinal HP were, for the most part, moderately severe and transient. In patients treated with lixisenatide, the incidence of treatment-related nausea, diarrhea, and vomiting was 22.3%, 3%, and 3.9%, respectively.

Lipodystrophy
Subcutaneous administration of injectable drugs containing insulin may lead to the development of lipoatrophy at the injection site (reduction of subcutaneous fatty tissue) or lipohypertrophy (increased tissue density).

Immune system disorders
Allergic reactions (urticaria), possibly associated with the use of Soliqua SoloStar®, have been reported in 0.3% of patients.

During the post-marketing use of insulin glargine and lixisenatide, cases of generalized allergic reactions, including anaphylactic reactions and angioedema have been observed.

Antibody formation
The use of the drug Soliqua SoloStar® may cause the formation of antibodies to insulin glargine and/or lixisenatide (see section “Cautions”).

Reactions at the injection site
Some patients receiving insulin therapy including Soliqua SoloStar® had erythema, local edema and itching at the injection site. These phenomena usually gradually decreased and disappeared without treatment.

Overdose