Suglat - Instructions For Use, Price Of Tablets, Reviews, Analogues

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Suglat

Suglat: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. For violations of liver function
13. 13. Use in the elderly
14. 14. Drug interactions
15. 15. Analogs
16. 16. Terms and conditions of storage
17. 17. Terms of dispensing from pharmacies
18. 18. Reviews
19. 19. Price in pharmacies

Latin name: Suglat

ATX code: A10BK05

Active ingredient: ipragliflozin (Ipragliflozin)

Manufacturer: Astellas Pharma Europe B. V. (Astellas Pharma Europe BV (Netherlands); Astellas Pharma Tech Co., Ltd.) (Japan)

Description and photo update: 2020-15-01

Prices in pharmacies: from 1571 rubles.

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Suglate is a hypoglycemic agent for oral administration.

Release form and composition

The drug is produced in the form of film-coated tablets: biconvex, round, in a light purple film shell (10 pieces in a blister; in a cardboard box with or without first opening control 1, 3, 6 or 10 blisters and instructions for application of Suglate).

1 tablet contains:

• active substance: ipragliflozin - 50 mg (in the form of ipragliflozin L-proline in an amount of 64.3 mg);
• additional components: sodium carboxymethyl starch (type A), microcrystalline cellulose, magnesium stearate, hyprolose;
• film casing: Opadray 03F40025 (macrogol 6000, talc, hypromellose, titanium dioxide, iron dyes red oxide and black oxide).

Pharmacological properties

Pharmacodynamics

Ipragliflozin is an oral selective sodium-dependent glucose transporter type 2 (SGLT2) inhibitor. SGLT2 is one of the main transport proteins involved in the reuptake of glucose in the proximal tubule of the kidney and its active transport from the lumen of the tubule into the blood against the concentration gradient.

The active ingredient of Suglate exhibits 254 times greater selective inhibitory activity with respect to SGLT2 in comparison with SGLT1 - the concentration of half-maximal inhibition (IC50) of ipragliflozin in relation to SGLT2 and SGLT1 is 7.38 and 1880 nmol / L, respectively.

Through a pronounced suppression of SGLT2 expressed in the proximal tubule of the renal nephron, ipragliflozin decreases renal tubular glucose reabsorption and lowers the renal glucose threshold (RGT). Thus, providing an increase in the excretion of glucose in the urine (EGM) and an insulin-independent decrease in its elevated plasma level in the blood. The amount of glucose eliminated by the kidneys depends on its content in the blood and the glomerular filtration rate (GFR).

The enhancement of EGM with suppression of SGLT2 also causes a moderate osmodiuresis and diuretic effect, contributing to a decrease in systolic and diastolic blood pressure (BP). In the course of studies in patients with type 2 diabetes mellitus, it was found that as a result of an increase in EGM, there is a loss of calories and, as a result, a decrease in body weight.

In phase I studies, when establishing EGM, it was demonstrated that in the case of using clinically significant doses of the drug in healthy volunteers, the average increase in EGM over 24 hours was similar and amounted to approximately 39 and 49 thousand mg for a dose of 50 mg, and for a dose of 100 mg - 39-56 thousand mg and 35-48 thousand mg in single and multiple doses, respectively. In persons with type 2 diabetes mellitus, the effect of ipragliflozin on daily EGM was more significant. 14 days after the start of administration in the group receiving the drug, there was a noticeable increase relative to the initial level of the average daily EGM (for a dose of 50 and 100 mg - by 81 and 90 thousand mg, respectively) compared with the placebo group (5 thousand mg) … Due to the increase in EGM, the concentration of glucose in plasma on an empty stomach (FPG) and after a meal decreased,and also fasting serum insulin levels.

In clinical studies, a statistically significant decrease in the content of glycosylated hemoglobin (HbA1c), FPG and body weight was demonstrated when using ipragliflozin in monotherapy. The same results were demonstrated when Suglate was used in combination with pioglitazone, metformin, sulfonylurea derivatives (CM), dipeptidyl peptidase-4 (DPP-4) inhibitors, metformin and sitagliptin, insulin (± DPP-4 inhibitor), nateglinide, α-glucoside inhibitor (α-GI), an analogue of glucagon-like peptide-1 (GLP-1) (± CM).

In the absence of the desired results against the background of treatment with Suglat at a dose of 50 mg, with an increase in the dose to 100 mg, a further decrease in the level of HbA1c, FPG and body weight was recorded.

Pharmacokinetics

After oral administration, ipragliflozin is rapidly absorbed, its plasma level in patients with type 2 diabetes mellitus and in healthy people after single and repeated use increases in a dose-dependent manner. After taking the active substance on an empty stomach, its maximum concentration (C _max) in the blood plasma is observed within 1.1-2.3 hours. With a single dose of 100 mg, the absolute bioavailability is 90.2%.

When using the drug in a dose of 50 mg before meals saturated with fats, an increase in C _{max of} ipragliflozin was observed by 1.23 times and a decrease in the period of its achievement (T _max) by 0.6 hours; The AUC (area under the concentration-time curve) remained unchanged. In the case of using ipragliflozin after a meal rich in fats, its C _max decreased 0.82 times, and T _max increased by 0.9 h; the AUC value did not change. With repeated use of the drug, food did not have a clinically significant effect on its safety and effectiveness, as a result of which Suglate can be used regardless of the regimen and diet.

The average volume of distribution of ipragliflozin (Vd) in an equilibrium state after intravenous (iv) administration at a dose of 25 mg is 127 l, which confirms the extensive distribution of the drug in the tissues. The drug binds to plasma proteins, mainly albumin by 94.6–96.5%. This relationship is comparable in healthy volunteers and patients with type 2 diabetes. In vivo, the fraction of the drug bound to plasma proteins in patients with type 2 diabetes mellitus with functional impairment of the kidneys (with normal renal function or with mild to severe renal dysfunction) was 96.2–97.2% in comparison from 96.7–97.0% in healthy people. The ratio of the content of ipragliflozin in blood / plasma equal to 0,625 for AUCinf (change in AUC over time with extrapolation to infinity) indicated a low degree of distribution of radioactivity in erythrocytes.

Biotransformation of Suglate proceeds mainly in the liver. In blood plasma, feces and urine, 7 metabolites of the active substance were determined: S-oxide, ipraglyflozin sulfate and 5 glucuronides. The metabolism of ipragliflozin is carried out mainly by glucuronidation with the participation of uridine diphosphate glucuronyltransferases (UDP-glucuronyltransferases), mainly UGT2B7, to a lesser extent UGT1A8, UGT1A9 and UGT2B4, with the formation of the main metabolite 2'-O-glylurone.

During in vitro studies, no significant suppression of cytochrome isoenzymes (CYP) and UDP-glucuronosyltransferase (UGT) by ipragliflozin, as well as significant induction of CYP3A4 and CYP1A2 was observed.

The main substance and its metabolites are excreted by the kidneys and through the intestines. The total clearance is 10.9 l / h, while the renal clearance is approximately 0.1 l / h. The average terminal half-life (T _1/2) of ipragliflozin after a single or multiple oral administration at doses of 50 and 100 mg can vary from 11.7 to 19.9 hours. After intravenous administration, only 1.32% of the administered dose of the drug is eliminated in unchanged by the kidneys. According to the results of all studies, the proportion of excretion of unchanged ipragliflozin by the kidneys was insignificant - less than 2%.

After oral administration of 100 mg of the radioactive isotope ¹⁴ C-ipragliflozin, 84.4% of radioactivity was excreted by the kidneys and through the intestine after 48 hours, 67.9% of radioactivity was excreted by the kidneys after 144 hours, and 32.7% through the intestine.

In the dose range from 1 to 600 mg, the AUC value increases in proportion to the dose, while C _max increases to a lesser extent compared to increasing the dose, however, this effect has no clinical significance. Against the background of repeated use of the drug, no signs of autoinhibition or autoinduction were recorded.

In women, the C _{max of} ipragliflozin is higher than in men, but this difference is not significant from a clinical point of view.

In representatives of the Caucasian, Mongoloid, and Negroid races, no clinically significant differences in systemic exposure were found.

Indications for use

Suglate is recommended for use in type 2 diabetes mellitus in order to improve glycemic control:

• monotherapy: in case of ineffectiveness of the treatment with diets and physical activity;
• complex therapy: in combination with other hypoglycemic agents, including CM derivatives, metformin, DPP-4 inhibitors, pioglitazone, insulin (± DPP-4 inhibitor), α-GI inhibitors, metformin with sitagliptin, GLP-1 analogs (including in combination with derivatives of CM), nateglinide, in the absence of adequate glycemic control.

Contraindications

• severe liver failure;
• end stage renal disease, severe renal impairment, or dialysis treatment;
• severe infectious lesions, serious operations and trauma, perioperative period;
• severe ketoacidosis, diabetic coma, or precoma;
• pregnancy and lactation;
• age up to 18 years;
• hypersensitivity to any of the constituents of Suglate.

Suglat, instructions for use: method and dosage

Suglate tablets are taken orally. They should be swallowed whole, without chewing, with water.

The drug is used once a day, regardless of the time of the meal. The initial daily dose of Suglate is 50 mg, if necessary, it can be increased to 100 mg.

With the simultaneous use of Suglate with insulin preparations or drugs that increase the production of the latter (CM derivatives), to reduce the risk of hypoglycemia, it is required to reduce the dose of these drugs.

If 1 dose of ipragliflozin has been missed, you should not use a double dose on the same day.

Side effects

The safety of ipragliflozin was evaluated based on 18 studies of phase IIb, III and IV in patients with type 2 diabetes mellitus, including data from 12 placebo-controlled studies. In 5 studies, ipragliflozin was used as monotherapy, in 12 - as part of a complex treatment with other hypoglycemic agents. One study involved patients with functional impairment of the kidneys.

The most common side effects of Suglate included the following reactions: hypoglycemia, urinary tract infections, genital infections, pollakiuria (or polyuria), rash, eczema, back pain, dizziness, thirst, constipation.

In patients who received Suglate at a dose of 100 mg, the safety profile was similar to that of receiving ipragliflozin at a dose of 50 mg.

Side effects based on a pooled analysis of 12 placebo-controlled studies of 12, 16 or 24 weeks duration, in which 1209 patients received ipragliflozin 50 mg and 796 patients received placebo:

• metabolism: often - thirst, hypoglycemia **; infrequently - feeling of hunger; with an unknown frequency - ketoacidosis ***;
• infections and parasitic infestations: often - infection of the genitals (including genital itching, vulvovaginal candidiasis);
• nervous system: often - dizziness (including postural dizziness);
• immune system: with an unknown frequency - angioedema *;
• organ of vision: infrequently - diabetic retinopathy;
• skin and subcutaneous tissue: often - rash, eczema; infrequently - itching, urticaria;
• digestive system: often - constipation (in most cases, mild); infrequently - vomiting, nausea;
• kidneys and urinary system: often - pollakiuria (or polyuria), urinary tract infection (including pyelonephritis);
• musculoskeletal system: often - back pain; infrequently - myalgia;
• laboratory and instrumental data: often - weight loss;
• general disorders: infrequently - asthenia.

Notes

* - includes swelling of the lips, eyelids and face (recorded only during post-registration observation).

** - especially in the case of a combination with insulin.

*** - presence of ketone bodies in urine (ketoacidosis and ketone bodies in urine were noted only within the framework of post-registration observations).

The incidence of hypoglycemia was related to the type of hypoglycemic therapy. When Suglate was used alone or in combination with other hypoglycemic agents (except insulin), the incidence of this adverse reaction was similar to placebo (2.3 and 1.7%, respectively). Cases of hypoglycemia were predominantly reported in studies of the combination of Suglate with insulin or drugs that activate its secretion (CM derivatives).

The incidence of pollakiuria / polyuria (urinary frequency) was higher in the ipragliflozin group (6%) than in the placebo group (2%).

The incidence of urinary tract infections with Suglate was the same as with placebo. Urinary tract infections and cystitis were mainly noted.

The incidence of adverse effects associated with a decrease in circulating blood volume (BCC), usually in the form of thirst and dizziness, was slightly higher with ipragliflozin (4.9%) than in the placebo group (1.8%).

Most of the cases of the above adverse reactions were mild, rarely of moderate severity, severe cases were not reported. An increase in the Suglate dose and an increase in the duration of therapy did not affect the incidence of these adverse events.

Overdose

In healthy volunteers, studies have demonstrated good tolerance and safety of single doses of ipragliflozin up to 600 mg, as well as its repeated use in doses up to 300 mg once a day.

In case of an overdose of Suglate, symptomatic treatment should be carried out taking into account the clinical condition. It is advisable to prescribe standard supportive measures, including the evacuation of the non-absorbed drug from the gastrointestinal tract, and monitoring the condition.

The excretion of ipragliflozin by dialysis has not been studied.

special instructions

On the background of Suglate therapy, deterioration of renal function may occur, an increase in the level of creatinine and urea in the blood, as well as a decrease in the calculated GFR (eGFR), may occur. Before starting the course of treatment, it is necessary to assess kidney function, as well as periodically monitor it during therapy.

The increase in EGM caused by the action of Suglate can cause a diuretic effect and osmotic diuresis, which in turn can lead to a decrease in BCC and blood pressure. During treatment, adequate hydration and monitoring of the BCC are recommended, including blood pressure measurement, physical examination, laboratory tests, including those reflecting the functional state of the kidneys, and electrolyte analysis.

If symptoms of ketoacidosis develop, such as loss of appetite, increased fatigue, excessive thirst, nausea, vomiting, abdominal pain, respiratory failure, impaired consciousness, laboratory tests, including determination of the concentration of ketone bodies in the blood and urine, are necessary.

If diabetic ketoacidosis is detected, Suglate should be discontinued and appropriate supportive therapy initiated in order to normalize the condition.

During the period of therapy with the drug Suglat, the development of fungal infections of the genital organs is possible, as a result of which it is required to carefully examine the patients for symptoms and signs of these infections, and if they are detected, conduct adequate treatment.

In the implementation of clinical studies of another inhibitor SGLT2, an increase in the incidence of amputation of the lower extremities (mainly toes) was recorded. Whether this effect is specific to the entire pharmacological class has not been established. All diabetic patients should be consulted on routine preventive foot care.

The experience of using Suglate in patients with chronic heart failure (CHF) of I – II functional class according to the classification of the New York Heart Association (NYHA) is limited, with CHF III – IV functional class - absent.

While taking ipragliflozin, as a result of its mechanism of action, positive results of a glucose test in urine will be recorded.

Influence on the ability to drive vehicles and complex mechanisms

There is no information on the negative impact of Suglate on the ability to drive vehicles and control complex mechanisms. However, when using ipragliflozin, patients should take into account the risk of hypoglycemia, especially when it is used in combination with insulin or drugs that stimulate the production of the latter, as well as the possible appearance of side effects due to a decrease in BCC (lowering blood pressure, dizziness).

Application during pregnancy and lactation

Suglate therapy in pregnant women is contraindicated, since its use during pregnancy has not been studied. If pregnancy develops during treatment, the drug must be canceled.

According to the data of preclinical studies, in animals, ipragliflozin penetrated into the fetus, as well as into breast milk, which led to a slowdown in the growth of offspring.

Suglat is contraindicated for use during breastfeeding.

The effect of the drug on fertility in humans has not been studied.

Pediatric use

The pharmacokinetics of ipragliflozin in children and adolescents under the age of 18 have not been studied, therefore, taking Suglat tablets in patients of this age group is contraindicated.

With impaired renal function

After a single use of Suglata in doses of 50 and 100 mg by patients with type 2 diabetes mellitus, the AUC value gradually increased in accordance with the decrease in renal function. In patients with mild renal functional impairment, eGFR was 60 ≤ and <90 ml / min / 1.73 m², the AUC value did not increase or did not increase significantly (1.25 times). In patients with moderate (eGFR - 30 ≤ and <60 ml / min / 1.73 m2) and severe (eGFR - 15 ≤ and <30 ml / min / 1.73 m2) renal impairment, the AUC value increased by 1.21 –1.40 times and 1.46 times, respectively. There was no significant change in C _max. Functional renal disorders did not have a pronounced effect on the binding of ipragliflozin to proteins. The effect of dialysis on the pharmacokinetics of Suglate has not been studied.

In the presence of mild / moderate functional renal impairment, dose adjustment is not required. Suglate is contraindicated in patients with severe renal dysfunction (GFR <30 ml / min / 1.73 m²), end-stage renal failure, or receiving dialysis treatment, due to the possible weakening of the hypoglycemic effect.

For violations of liver function

After a single oral intake of Suglate on an empty stomach at a dose of 100 mg by persons with moderate liver dysfunction (class B, 7-9 points according to the Child-Pugh classification), the AUC and C _max values increased by 1.25 and 1.27 times, respectively, compared to healthy volunteers.

The pharmacokinetics of the drug in patients with severe hepatic impairment has not been studied. Suglat therapy is contraindicated in patients with severe hepatic impairment.

In the presence of mild to moderate liver dysfunctions, dose adjustment is not required.

Use in the elderly

In patients over 65 years of age, no clinically significant increase in ipragliflozin exposure was observed.

Correction of the dose of Suglate is not required for the elderly. However, since the weakening of physiological functions is more often observed in this category of patients, and the risk of dehydration is aggravated, the treatment with Suglatom of gerontological patients over the age of 65 is recommended under close supervision.

Drug interactions

• drugs that lower glucose levels: there was no effect of these drugs in healthy volunteers on the effect of ipraglyflozin on EGM;
• pioglitazone / sitagliptin (single doses): did not affect EGM caused by repeated use of ipragliflozin;
• pioglitazone / glimepiride / sitagliptin (with course administration): did not change the EGM value caused by a single intake of Suglate;
• metformin (with repeated administration): increased EGM while taking ipragliflozin;
• furosemide (loop diuretic): there was a temporary slight effect on the changes in urine volume and electrolyte composition caused by this substance;
• diuretics: ipragliflozin is able to potentiate their effects and aggravate the risk of dehydration and arterial hypotension;
• insulin and drugs that stimulate its secretion: it is possible to increase the threat of hypoglycemia when used together with ipragliflozin, to reduce which it is required to reduce the doses of these drugs and insulin;
• breast cancer resistance protein (BCRP), multiple drug resistance protein 2 (MRP2): in vitro studies have shown that ipragliflozin is not a substrate for these substances;
• UGT inhibitors: an increase in the exposure of Suglate was expected, but its safety remained unchanged, since daily doses of the drug up to 300 mg were well tolerated;
• UGT inducers: a weakening of the Suglate effects was noted; it is required to monitor the effectiveness of the drug and, if necessary, increase its dose from 50 to 100 mg;
• P-glycoprotein (P-gp) inhibitors: interaction studies have not been conducted, but since ipragliflozin is highly bioavailable, no clinically significant effect on its absorption is expected;
• drugs that increase the acidity (pH) of the stomach: there was no change in the bioavailability of ipragliflozin, since pH does not affect its solubility;
• cytochrome P450 (CYP) enzymes 1A2, 2A6, 3A4, 4A1, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1; UGT enzymes including (UGT) 1A1, 1A4, 1A6, 1A9, and 2B7; efflux transporters P-gp, BCRP, MRP2; transport proteins of multiple resistance and elimination of toxins 1 (MATE1) and 2-K (MATE2-K); transporters of substances into the cell (OATP1B1, OATP1B3, OST1, OST2): the inhibitory activity of Suglate in relation to these substances was not detected;
• pioglitazone (CYP2C8 substrate), glimepiride (CYP2C9 substrate), mitiglinide, sitagliptin (in single doses): with repeated use of ipragliflozin, no effect on the pharmacokinetics of these drugs in studies with healthy volunteers has been identified;
• metformin: its effect increased (AUC increased by 1.18 times) while taking ipragliflozin in a daily dose of 300 mg, which was not clinically significant;
• substrates for the above CYP, UGT and transporter enzymes: no drug interactions with these agents are expected.

Analogs

The analogues of Suglate are Jardins, Invokana, Forsiga, Amalvia, Astrozone, Bagomet, Glibenclamide, Gliclazide MV, Diabetalong, Combogliz Prolong, Metformin, Formin Pliva, Yasitara, etc.

Terms and conditions of storage

Keep out of the reach of children at a temperature not exceeding 25 ° C.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Suglate

At the present time, there are no reviews of Suglate left by patients on specialized sites, since the drug was registered in Russia only in May 2019.

Suglat price in pharmacies

The price of Suglate in the form of film-coated tablets (50 mg) can be 2,600-3,000 rubles. per package containing 30 pcs.

Suglat: prices in online pharmacies

Drug name Price Pharmacy

Suglate 50 mg film-coated tablets 30 pcs. 1571 RUB Buy

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!