Onglyza - instructions for use, doses, side effects, contraindications

Active substanceSaxaglyptineSaxaglyptine

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Dosage form: & nbsp

Film-coated tablets

Composition:

One tablet, film-coated, contains: active substances: saxagliptin 2.5 mg or 5.0 mg in the form of saxagliptin hydrochloride; auxiliary substances: lactose monohydrate 99.0 mg *, microcrystalline cellulose 90.0 mg, croscarmellose sodium 10.0 mg, magnesium stearate 1.0 mg **, 1 M hydrochloric acid *** - the necessary amount, Opadrai II white ( % w / w) 26.0 mg [polyvinyl alcohol 40%, titanium dioxide 25%, macrogol (PEG 3350) 20.2%, talc 14.8%], Opadrai II yellow (w / w) 7.0 mg [alcohol polyvinyl 40%, titanium dioxide 24.25%, macrogol (PEG 3350) 20.2%, talc 14.8%, iron oxide yellow oxide (E172) 0.75%] (for a dosage of 2.5 mg), Opadrai II pink (% w / w) 7.0 mg [polyvinyl alcohol 40%, titanium and dioxide 24.25%, macrogol (PEG 3350) 20.2%, talc 14.8%, dye iron oxide red (E172) 0.75%] (for a dosage of 5.0 mg), Opacode blue ink *** * - required amount.

* The amount of lactose can vary depending on the amount of magnesium stearate used.

** The amount of magnesium stearate can vary within the range of 0.5-2 mg. The optimal amount is 1 mg.

*** If necessary, 1 M sodium hydroxide can be used to adjust the pH. **** Composition of Opacod Blue ink (% w / w): shellac 45% in ethanol 55.4%, FD & C Blue # 2 / indigo carmine aluminum pigment (E132) 16%, n-butyl alcohol 15%, propylene glycol 10 , 5%, isopropyl alcohol 3%, 28% ammonium hydroxide 0.1%.Very small amounts of shellac and FD & C Blue # 2 / indigo carmine aluminum pigment remain on the tablets when labeled. Solvents that form part of the ink are removed during the manufacturing process.

Pharmacotherapeutic group:Hypoglycemic agent

ATX: & nbsp

A.10.B.H Inhibitors of dipeptidyl peptidase 4 (DPP-4)

A.10.B.H.03 Saxaglyptine

Pharmacodynamics:

Saksagliptin is a potent selective reversible competitive inhibitor of dipeptidyl peptidase-4 (DPP-4). In patients with type 2 diabetes mellitus (DM2), the administration of saxagliptin leads to suppression of the activity of the DPP-4 enzyme within 24 hours. After ingestion of glucose, inhibition of DPP-4 results in a 2-3 fold increase in the concentration of glucagon-like peptide-1 (GLP-1) and a glucose-dependent insulinotropic polypeptide (GUI), a decrease in glucagon concentration, and an increase in the glucose-dependent response of beta cells, which leads to an increase in the concentration of insulin and the C-peptide. The release of insulin by beta cells of the pancreas and a decrease in glucagon release from pancreatic alpha cells leads to a decrease in fasting glycemia and postprandial glycemia.

Clinical efficacy and safety

In double-blind, randomized, controlled clinical trials, saxagliptin therapy received more than 17,000 patients with CD2.

Glycemic control

The efficacy and safety of the use of saxagliptin in doses of 2.5 mg, 5 mg, and 10 mg once a day were studied in six double-blind placebo-controlled trials involving 4,488 patients with CD2. The reception of the drug was accompanied by a statistically significant improvement in the indices glycosylated hemoglobin (HbAlc), fasting blood plasma glucose (GPN) and postprandial glucose (PPG) of blood plasma compared to the control.

Saxagliptin was administered in the form of monotherapy or combination therapy. Combination therapy with saxagliptin was prescribed additionally to patients uncompensated for monotherapy with metformin, glibenclamide, thiazolidinediones or insulin, or as a starting combination with metformin to patients uncompensated for diet and exercise. When taking saxagliptin at a dose of 5 mg, the decrease in HbAlc was noted after 4 weeks and GPN-after 2 weeks.

In the group of patients who received saxagliptin in combination with metformin, glibenclamide, or thiazolidinediones, a decrease in HbAlc was also noted after 4 weeks and GPN after 2 weeks.

In a study of combination therapy with saxagliptin and insulin (including, in combination with metformin) involving 455 patients with diabetes, a significant reduction in HbAlc and PPG was demonstrated compared with placebo.

In a study of saxagliptin in combination with metformin and sulfonylureas involving 257 patients with diabetes, a significant reduction in HbAlc and PPG was demonstrated compared with placebo in combination with metformin and sulfonyl urea derivatives. The effect of saxagliptin on the lipid profile is similar to that of placebo. Against the background of therapy with saxagliptin, there was no increase in body weight. In a direct comparative study involving 858 patients with CD2, the addition of Onglya® 5 mg to metformin compared with the addition of glipizide to metformin showed a comparable decrease in HbAlc, but was associated with a significantly lower incidence of hypoglycemia - 3% of cases compared with 36.3% with the addition of glipizide, as well as a lack of weight gain in patients receiving saxagliptin therapy (-1.1 kg from baseline in the group of saxagliptin, +1.1 kg in the group of glipizide).At week 104, at least one episode of hypoglycemia occurred in 3.5% of patients in the saxagliptin and metformin group, and 38.4% in the glipizide and metformin group; the change in body weight from the baseline was -1.5 kg and +1.3 kg, respectively.

Cardiovascular outcomes

In the study SAVOR (Evaluation of cardiovascular outcomes in patients with diabetes mellitus, taking saxagliptin) cardiovascular outcomes were studied in 16492 patients with CD2 (12959 patients with confirmed cardiovascular diseases (CVD), 3533 patients with multiple cardiovascular risk factors) and values of 6.5% < HbAlc <12%. Patients were randomized into two groups for therapy with saxagliptin (8280 patients) or placebo (8212 patients), in addition to the standard therapy for each region aimed at controlling glycosylated hemoglobin and cardiovascular risk factors. It was shown that saxagliptin does not increase the risk of cardiovascular complications (such as death from CVD, nonfatal myocardial infarction, nonfatal ischemic stroke) compared with placebo when added to a standard basic (relative risk [RR] 1.00, 95% confidence interval [CI] 0.89, 1.12). It has also been shown that the addition of saxagliptin to basic therapy does not increase the risk of a combined endpoint, including death from CVD, nonfatal myocardial infarction, nonfatal ischemic stroke, hospitalization for chronic heart failure, unstable angina, or coronary artery revascularization compared with placebo RR 1.02, 95% CI 0.94, 1.11).

Overall mortality was comparable in the saxagliptin and placebo groups (RR 1.11, 95% CI 0.96, 1.27).

In the study, there was an increase in the hospitalization rate for chronic heart failure in the saxagliptin group (3.5%, 289 patients) compared to the placebo group (2.8%, 228 patients) with nominal statistical significance (i.e., without correction for multiple end points) (RR 1.27, 95% CI 1.07, 1.51, P = 0.007). In patients with chronic heart failure or renal insufficiency who received saxagliptin, there was no higher incidence of the primary endpoint, secondary endpoint, and overall mortality compared to the placebo group.In the saxagliptin group, the dynamics of the HbAlc value was significantly more pronounced, and the percentage of patients achieving the target HbAlc value was higher than in the placebo group. In this case, the intensification of hypoglycemic therapy or the addition of insulin in the saxagliptin group was required in significantly fewer patients than in the placebo group.

Pharmacokinetics:

In patients with CD2 and healthy volunteers, the pharmacokinetics of saxagliptin and its main metabolite are similar. Saxaglyptine quickly absorbed after ingestion on an empty stomach with the maximum concentration of saxagliptin and the main metabolite in plasma (Cmax) for 2 hours and 4 hours, respectively. With an increase in the dose of saxagliptin a proportional increase in Cmax and an area under the concentration-time curve (AUC) of saxagliptin and its main metabolite was noted. After a single dose of saxagliptin at a dose of 5 mg by healthy volunteers, the mean values of AUC of saxagliptin and its main metabolite were 78 ng / mL and 214 ng / hr, and the C max values in plasma were 24 ng / ml and 47 ng / ml, respectively.

The average duration of the final half-life (t1 / 2) of saxagliptin and its main metabolite was 2.5 h and 3.1 h respectively,and the mean t1 / 2 inhibition of plasma DPP-4 is 27 hours. Inhibition of plasma DPP-4 activity for at least 24 hours after administration of saxagliptin is due to its high affinity for DPP-4 and prolonged binding thereto. A noticeable cumulation of saxagliptin and its main metabolite with long-term administration of the drug 1 time per day was not observed. There was no dependence of the clearance of saxagliptin and its main metabolite on the dose of the drug and the duration of therapy with the administration of saxagliptin once a day at doses from 2.5 mg to 400 mg for 14 days.

Suction

After ingestion, at least 75% of the dose of saxagliptin is absorbed. The intake of food had no significant effect on the pharmacokinetics of saxagliptin in healthy volunteers. Eating high-fat foods had no effect on C max saksaggliptina, while AUC increased by 27% compared with fasting. The time to reach Cmax (Tmax) for saxagliptin increased by approximately 0.5 h when taken together with food as compared with fasting. However, these changes are not clinically relevant.

Distribution

The binding of saxagliptin and its main metabolite to serum proteins is insignificant, so it can be assumed that the distribution of saxagliptin with changes in the protein composition of blood serum, which are noted in hepatic or renal insufficiency, will not undergo significant changes.

Metabolism

Saxagliptin is metabolized mainly with the participation of cytochrome P450 isoenzymes ZA4 / 5 (CYP3A4 / 5) with the formation of an active basic metabolite, the inhibitory effect of which against DPP-4 is 2 times weaker than that of saxagliptin.

Excretion

Saksagliptin is excreted in the urine and with bile. After a single dose administration, 50 mg of labeled 14C-saxagliptin 24% of the dose were excreted by the kidneys in the form of unchanged saksagliptin and 36% - as the main metabolite of saxagliptin. The total radioactivity found in urine corresponded to 75% of the accepted dose of the drug. The mean renal clearance of saxagliptin was about 230 ml / min, the mean glomerular filtration was approximately 120 ml / min. For the main metabolite, the renal clearance was comparable to the mean values of glomerular filtration.About 22% of the total radioactivity was found in feces.

Pharmacokinetics in special clinical situations

Impaired renal function

In patients with mild renal insufficiency, the value of AUC of saxagliptin and its main metabolite were respectively 1.2 and 1.7 times higher than those in persons with normal renal function. This increase in AUC values is not clinically relevant, so dose adjustment is not required.

In patients with moderate and severe renal insufficiency, as well as in patients on hemodialysis, the values of AUC of saxagliptin and its main metabolite were 2.1 and 4.5 times higher, respectively, than those in persons with normal renal function. For patients with moderate and severe renal dysfunction, as well as for patients on hemodialysis, the dose of saxagliptin should be 2.5 mg 1 time per day (see the sections "Dosing and Administration" and "Special instructions").

Impaired liver function

In patients with mild, moderate and severe impairment of liver function, there were no clinically significant changes in the parameters of the pharmacokinetics of saxagliptin, so dose adjustments for such patients are not required.Elderly patients Patients aged 65-80 years did not have clinically significant differences in the parameters of the pharmacokinetics of saxagliptin compared with younger patients (18-40 years), so dose adjustment in elderly patients is not required. However, it should be borne in mind that this category of patients is more likely to have a decrease in renal function (see the section "Dosing and Administration" and "Special instructions").

Indications:

Diabetes mellitus type 2 in addition to diet and exercise to improve glycemic control as: monotherapy; starting combination therapy with metformin; addition to monotherapy with metformin, thiazolidinediones, sulfonylurea derivatives, insulin (including in combination with metformin) in the absence of adequate glycemic control in this therapy; addition to a combination of metformin and sulfonylurea derivatives in the absence of adequate glycemic control in this therapy.

Contraindications:

Increased individual sensitivity to any component of the drug; Serious reactions of hypersensitivity (anaphylaxis or angioedema) to DPP-4 inhibitors; Diabetes mellitus 1type (application not studied); Diabetic ketoacidosis; Congenital intolerance of galactose, lactase deficiency and glucose-galactose malabsorption; Pregnancy, lactation; Age under 18 years (safety and efficacy not studied).

Carefully:With caution: moderate to severe renal failure; elderly patients; joint use with sulfonylureas or insulin derivatives, patients with pancreatitis in the anamnesis (the relationship between taking the drug and an increased risk of pancreatitis is not established).

Dosing and Administration:

Inside, regardless of food intake. Tablets should be swallowed whole, not chewing, not crushing and not breaking.

Monotherapy: The recommended dose of saxagliptin is 5 mg once a day.

Combination therapy: the recommended dose of saxagliptin is 5 mg once a day in combination with metformin, thiazolidinediones, sulfonylureas, insulin (including in combination with metformin); when adding to the combination of metformin and sulfonylureas, the recommended dose of saxagliptin is 5 mg once a day.

With starting combination therapy with metformin The recommended dose of saxagliptin is 5 mg once a day, the initial dose of metformin is 500 mg per day. In case of an inadequate response, the dose of metformin can be increased. If you miss a dose of Onglis®, the missed tablet should be taken as soon as the patient remembers it, but do not take a double dose of the drug for one day.

Use in special patient groups

Patients with impaired renal function

For patients with mild renal insufficiency (CK> 50 ml / min) dose adjustment is not required. For patients with moderate or severe renal failure (QC < 50 ml / min), as well as for patients on hemodialysis, the recommended dose of Onglis® is 2.5 mg once a day. The drug should be taken at the end of the hemodialysis session.

The use of saxagliptin in patients on peritoneal dialysis has not been studied. Before starting therapy with saxagliptin and during treatment, it is recommended that the kidney function be assessed.

Patients with impaired hepatic function

If the liver function is mild, moderate and severe, dose adjustment is not required.

Elderly patients

Dose adjustments in elderly patients are not required. However, when choosing a dose, it should be borne in mind that this category of patients is more likely to have decreased kidney function.

Children

The safety and efficacy of the drug in patients under the age of 18 years has not been studied.

Simultaneous application with powerful inhibitors of CYP3A4 / 5

With simultaneous use with powerful inhibitors of CYP3A4 / 5, such as ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir and telithromycin, the recommended dose of Onglis® is 2.5 mg once daily.

Side effects:

Side effects of the Ongliza ® preparation in studies of glycemic control

The table shows the side effects found in patients with CD2 when taking the drug Onglis® at a dose of 5 mg during clinical trials. The overall incidence of adverse events with the use of the Onglis® 5 mg preparation in monotherapy and in the mode of addition to therapy with metformin, thiazolidinedione or glibenclamide was comparable to that in the placebo group. Scale of adverse reactions frequency: very often (>1/10); often (>1/100, <1/10); infrequently (>1/1000, <1/100); rarely (>1/10000, <1/1000); very rarely (<1/10000).

Table 1. Side effects from data from a pooled analysis of five placebo-controlled clinical trials of Onglis®

Infections and invasions
Upper respiratory tract infections	Often
Infections urinary tract	Often
Gastroenteritis	Often
Sinusitis	Often

From the gastrointestinal side
tract
Vomiting	Often
From the nervous system
Headache	Often

The incidence of hypersensitivity reactions noted by the 24th week of therapy was 1.5% in patients receiving Ongliza® 5 mg and 0.4% in patients receiving placebo. Hypersensitivity reactions that occurred in patients taking the drug Ongliza® did not require hospitalization and were regarded by the treating physicians as not posing a life threat.

Side effects of the drug Ongliza® with combined therapy in studies of glycemic control

In a study on the combined use of saxagliptin and glibenclamide, the incidence of confirmed hypoglycemic episodes was 0.8% in the 5 mg saxagliptin group and 0.7% in the placebo group. The incidence of confirmed episodes of hypoglycemia in patients,who received Onglis® 5 mg in two studies of saxagliptin in the monotherapy regimen, a study on combined therapy with saxagliptin and metformin, and in a study on the combined use of saxagliptin and thiazolidinediones, was comparable to that of placebo.

In a study on the use of a combination of saxagliptin and insulin, the overall incidence of hypoglycaemia was 18.4% in the 5 mg group of saxagliptin and 19.9% in the placebo group, with the incidence of confirmed episodes of hypoglycemia, accompanied by symptoms, were 5.3% and 3.3%, respectively.

In a study on the use of saxagliptin in combination with metformin and sulfonylureas, the overall incidence of hypoglycaemia was 10.1% in patients receiving Onglis® 5 mg and 6.3% in patients receiving placebo, the incidence of confirmed hypoglycemia was 1.6% and 0%, respectively.

In a study on the use of saxagliptin in combination with thiazolidinediones, the incidence of peripheral edema was higher in the 5 mg saxagliptin group than in the placebo group (8.1% and 4.3%, respectively).Peripheral edema was mild or moderate and did not lead to cessation treatment. The incidence of peripheral edema in patients taking Onglys® 5 mg in clinical trials of monotherapy with saxagliptin and combined therapy with metformin or glibenclamide, was comparable to that of placebo (1.7% and 2.4%, respectively).

With starting combination therapy with saxagliptin at a dose of 5 mg and metformin, cases of nasopharyngitis and headache were often noted. The incidence of nasopharyngitis was higher with combined therapy (6.9%) compared with monotherapy with saxagliptin 10 mg (4.2%) and metformin (4.0%). Headache was noted more often in the group of patients on combined therapy with metformin and saxagliptin 5 mg (7.5%) compared with the groups of monotherapy with saxagliptin 10 mg (6.3%) and metformin (5.2%).

Side effects of the drug Onglya® in the SAVOR study

In the SAVOR study, 8240 patients received an Onglya® preparation at a dose of 2.5 mg or 5 mg once daily, and 8173 patients received a placebo. The average duration of therapy with the drug Ongliza®, regardless of interruptions in treatment, was 1.8 years.In 3698 patients (45%), the duration of therapy with the drug Onglysa was 2-3 years.

The overall incidence of adverse events in this study in the group of patients taking Onglis® (72.5%) was comparable to the incidence of adverse events in the placebo group (72.2%). The frequency of withdrawal of therapy due to adverse events was comparable in patients taking Onglis® (4.9%) and placebo (5%).

In the SAVOR study, the effect of the drug Ongliza® on the incidence of cardiovascular complications was evaluated. It has been shown that the addition of Onglys® to therapy does not increase the risk of cardiovascular complications (such as cardiovascular mortality, nonfatal myocardial infarction, nonfatal ischemic stroke) in patients with DM2 compared with placebo (RR 1.00, 95% CI 0.89, 1.12, P <0.001 for

hypothesis comparability of saxagliptin and placebo).

The incidence of pancreatitis confirmed in accordance with the study protocol was 0.3% in the saxagliptin and placebo groups in the population of all randomized patients. The incidence of hypersensitivity reactions was 1.1% in the Onglis® group and placebo.

Hypoglycaemia

The overall incidence of hypoglycemia (noted in patient diaries) in the SAVOR trial was 17.1% in the Onglis ® group and 14.8% in the placebo group. Proportion of patients who experienced severe hypoglycemia against the background of therapy (hypoglycemia, requiring help

third parties) was higher in the saxagliptin group than in the placebo group (2.1% and 1.6%, respectively).

The increased risk of hypoglycemia in general, as well as severe hypoglycemia in the saxagliptin group, was mainly observed in patients receiving sulfonylurea preparations, but not in patients receiving insulin or metformin as a basic therapy. The increased risk of hypoglycemia in general, as well as severe hypoglycemia, is mainly observed in patients with a baseline HbAlc <7%. Postmarketing application

During the post-marketing application of saxagliptin the following side effects are recorded: acute pancreatitis and reactions

hypersensitivity, including anaphylaxis, angioedema, rash and hives. It is impossible to reliably estimate the frequency of development of these phenomena, since messages were received spontaneously from a population of an unidentified size (see Fig.sections "Contraindications" and "Special instructions").

Laboratory research

In clinical studies, the frequency of changes in laboratory parameters when taking saxagliptin at a dose of 5 mg and placebo was comparable. There was a slight decrease in the number of lymphocytes, with the average absolute number of lymphocytes remaining stable and within the normal range with daily intake of saxagliptin for up to 102 weeks. The decrease in the number of lymphocytes was not accompanied by clinically significant undesirable reactions. The clinical importance of reducing the number of lymphocytes on the background of therapy with saxagliptin is not known. In the SAVOR study, a decrease in the number of lymphocytes in the Onglis ® group was noted in 0.5% of patients, in the placebo group in 0.4% of patients.

Interaction:

Analysis of the data from clinical trials suggests that the risk of clinically significant interactions of saxagliptin with other drugs when combined together is small. Metabolism saxagliptin is predominantly mediated by the cytochrome P450 isoenzyme system of Z4 / 5 (CYP3A4 / 5). In in vitro studies, it was shown that saxagliptin and its main metabolite do not inhibit the isoenzymes CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4 and do not induce isoenzymes CYP1A2, 2B6, 2C9, and 3A4. In studies involving healthy volunteers, pharmacokinetic figures saxagliptin and its main metabolite were not significantly changed under the influence of metformin, glibenclamide, pioglitazone, digoxin, simvastatin, diltiazem, ketoconazole, omeprazole, a combination of aluminum hydroxide, magnesium hydroxide and simethicone, and famotidine. Saxaglyptine does not significantly alter the pharmacokinetic indicators of metformin, glibenclamide, pioglitazone, digoxin, simvastatin, diltiazem, ketoconazole or oral combination (estrogen + progestogen) a contraceptive agent. Effect of inductors of isoenzymes CYP3A4 / 5 on the pharmacokinetics of saxagliptin has not been studied. However, the combined use of saxagliptin and inducers of CYP3A4 / 5 isoenzymes, such as carbamazepine, dexamethasone, phenobarbital, phenytoin and rifampicin, can lead to a decrease in the concentration of saxagliptin in plasma and an increase in the concentration of its main metabolite.

Studies of the effects of smoking, dietary intake, intake of herbal preparations and alcohol use on saxagliptin therapy have not been conducted.

Special instructions:

The use of the drug Onglya® in the triple therapy with metformin and thiazolidinediones has not been studied.

Patients with impaired renal function

Recommended dose adjustment for patients with moderate and severe renal insufficiency, as well as for patients on hemodialysis. Before starting therapy and periodically in the process treatment it is recommended to evaluate the kidney function.

Use in combination with drugs that can cause hypoglycemia

Derivatives of sulfonylureas and insulin can cause hypoglycemia, so reducing the dose of sulfonylurea or insulin derivatives may be required to reduce the risk of hypoglycemia when used concomitantly with Onglys®.

Hypersensitivity reactions

During the post-marketing use of saxagliptin, severe hypersensitivity reactions were noted, including anaphylaxis and angioedema. If you develop a serious hypersensitivity reaction, stop using the drug, evaluate other possible causes of the phenomenon and prescribe an alternative therapy for diabetes mellitus (see the sections "Contraindications" and "Side effect").

Pancreatitis

In the post-marketing application of the drug, spontaneous reports of cases of acute pancreatitis were obtained. Patients taking ONLLIZ® should be informed of the characteristic symptoms of acute pancreatitis: prolonged, intense pain in the abdomen. If suspected development of pancreatitis should stop taking Onglisa ® (see sections "With caution" and "Side effect"). The incidence of pancreatitis in the SAVOR study, confirmed in accordance with the study protocol, was 0.3% in the saxagliptin and placebo groups in the population of all randomized patients.

Elderly patients

Of the 16492 patients randomized to the SAVOR study, 8561 patients (51.9%) were 65 years of age or older, and 2330 patients (14.1%) were aged 75 years and older. Of these, 4290 patients age 65 and over and 1169 patients aged 75 years and older received saxagliptin.

According to clinical studies, the efficacy and safety indices in patients aged 65 years and over, 75 years and older did not differ from those in younger patients. Saxaglyptine and its main metabolite is partially excreted by the kidneys, so it should be borne in mind that in elderly patients, kidney function is more likely to decrease.

The drug Ongliza® contains lactose. Patients with congenital intolerance to galactose, lactase deficiency and glucose-galactose malabsorption should not take this drug.

Form release / dosage:Tablets, film-coated 2.5 mg and 5 mg.

Packaging:

10 tablets in a blister of aluminum foil; 3 blisters with instructions for use in a cardboard box with the control of the first opening. The blister is perforated, dividing it into 10 rectangular zones according to the number of tablets.

Storage conditions:At a temperature of no higher than 30 degrees.

Shelf life:3 years

Terms of leave from pharmacies:On prescription

Registration number:LSR-008697/10

Date of registration:25.08.2010

The owner of the registration certificate:AstraZeneca UK LtdAstraZeneca UK Ltd United Kingdom

Manufacturer: & nbsp

BRISTOL-MYERS SQUIBB Company USA

BRISTOL-MYERS SQUIBB, S.r.L. Italy

Representation: & nbspAstraZeneca Pharmaceuticals Ltd.AstraZeneca Pharmaceuticals Ltd.

Information update date: & nbsp12/08/2015

Illustrated instructions

Instructions

Anglis® (Onglyza® )