Zemiglo (Tablets) Instructions for Use

Marketing Authorization Holder

Sanofi (France)

Manufactured By

LG Chem, Ltd. (Republic of Korea)

ATC Code

A10BH06 (Gemigliptin)

Active Substance

Gemigliptin (Rec.INN registered by WHO)

Dosage Form

Zemiglo

Film-coated tablets, 50 mg: 28 or 56 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets orange in color, in the shape of a stylized “lemon”; on one side there is an engraving “LG” and a “~” sign below the inscription, on the other side there is a score mark.

Excipients: microcrystalline cellulose (type 102), microcrystalline cellulose (type 101), croscarmellose sodium, sodium stearyl fumarate.

Coating composition: Opadry II orange*.

*Opadry II orange (85F43172) contains: polyvinyl alcohol, titanium dioxide, macrogol-3350, talc, FD&C Yellow#6/Sunset Yellow FCF Aluminium Lake dye, iron oxide red dye.

14 pcs. – blisters (2) – cardboard packs.
14 pcs. – blisters (4) – cardboard packs.

Clinical-Pharmacological Group

Oral hypoglycemic drug

Pharmacotherapeutic Group

Hypoglycemic agent for oral administration, type 4 dipeptidyl peptidase inhibitor (DPP-4)

Pharmacological Action

An oral hypoglycemic agent, a dipeptidyl peptidase-4 (DPP-4) inhibitor, which increases the level of active incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), thereby reducing blood glucose concentration.

GLP-1 and GIP stimulate the production and release of insulin from pancreatic beta cells. GLP-1 also reduces glucagon secretion from pancreatic alpha cells, leading to decreased glucose production in the liver.

Incretin hormones are rapidly degraded by DPP-4. Gemigliptin selectively inhibits DPP-4 activity, increasing the duration of action of incretin hormones.

Gemigliptin demonstrates 3400 and 9500 times higher selectivity for DPP-4 compared to selectivity for DPP-8 and DPP-9, respectively.

Data obtained from clinical studies have demonstrated good tolerability of gemigliptin.

Pharmacokinetics

After a single oral administration, Gemigliptin is rapidly absorbed from the gastrointestinal tract, with C_max achieved within 1-5 hours.

When taken at the recommended dose of 50 mg, C_max and AUC were 62.7 ng/ml and 743.1 ng×h/ml, respectively.

Systemic exposure increased proportionally with the dose over the range of 25 to 400 mg. Plasma protein binding in vitro is 29% for gemigliptin and 35-48% for its metabolites.

Gemigliptin is metabolized with the involvement of the CYP3A4 isoenzyme.

Gemigliptin and its main metabolite (LC15-0636) account for 65-100% and 0-1.5% of the radioactivity in plasma, respectively.

LC15-0636, a hydroxylated metabolite of gemigliptin, is 2 times more pharmacologically active than Gemigliptin.

After oral administration of [¹⁴C]-labeled gemigliptin to healthy volunteers, 27% of the radioactivity is found in feces and 63% of the radioactivity is found in urine.

The T_1/2 of gemigliptin after oral administration is approximately 17 hours, and the T_1/2 of its metabolite LC15-0636 is 24 hours.

Indications

Type 2 diabetes mellitus in adult patients to improve glycemic control (as an adjunct to diet and exercise).

Can be used as monotherapy or in combination with metformin (in patients with inadequate glycemic control on metformin monotherapy).

ICD codes

Dosage Regimen

Take orally, regardless of meals.

The recommended dose is 50 mg once daily.

Do not exceed the maximum daily dose of 50 mg.

For monotherapy, initiate at 50 mg once daily.

For combination therapy with metformin, use the same 50 mg once daily dose when metformin monotherapy provides inadequate glycemic control.

Administer the tablet whole; do not split or crush.

If a dose is missed, take it as soon as remembered on the same day.

Do not take a double dose to make up for a forgotten one.

For patients with moderate renal impairment (eGFR 30 to less than 60 mL/min/1.73 m²), the recommended dose is 50 mg once daily.

For patients with severe renal impairment (eGFR less than 30 mL/min/1.73 m²) or end-stage renal disease requiring hemodialysis, the recommended dose is 50 mg once daily, administered without regard to the timing of hemodialysis sessions.

No dosage adjustment is required for patients with mild hepatic impairment.

Use with caution in patients with moderate or severe hepatic impairment; no specific dosage recommendation is provided.

No dosage adjustment is required for elderly patients based on age alone.

Adverse Reactions

Infections and parasitic diseases asymptomatic bacteriuria is possible.

Skin and subcutaneous tissue disorders urticaria is possible.

Laboratory and instrumental data increased blood amylase and lipase activity is possible.

Contraindications

Hypersensitivity to gemigliptin; history of severe hypersensitivity reactions (e.g., angioedema, anaphylaxis) associated with the use of other DPP-4 inhibitors; type 1 diabetes mellitus; diabetic ketoacidosis; heart failure NYHA class III-IV; age under 18 years.

With caution

Moderate and severe renal impairment; hepatic impairment; heart failure NYHA class I; history of pancreatitis; elderly age.

Use in Pregnancy and Lactation

Well-controlled studies of gemigliptin in pregnant women have not been conducted, therefore the use of gemigliptin during pregnancy is contraindicated.

It is not known whether Gemigliptin is excreted in human breast milk. Animal studies have shown that Gemigliptin passes into breast milk. The use of gemigliptin is contraindicated during breastfeeding.

Pediatric Use

The drug is contraindicated for use in children and adolescents under 18 years of age.

Special Precautions

No reports of acute pancreatitis associated with gemigliptin use have been received.

However, there are reports of cases of acute pancreatitis in patients taking other DPP-4 inhibitors.

Patients should be informed about the characteristic symptoms of acute pancreatitis, such as persistent severe abdominal pain.

If pancreatitis is suspected, gemigliptin should be discontinued and should not be restarted.

Effect on ability to drive vehicles and machinery

Given the possible development of hypoglycemia with the use of gemigliptin, patients should exercise caution when driving vehicles and operating machinery during its use.

Drug Interactions

Gemigliptin is metabolized with the involvement of the CYP3A4 isoenzyme.

Repeated co-administration of 50 mg gemigliptin and 30 mg pioglitazone resulted in a 15% and 17% decrease in the AUC and C_max of pioglitazone, which is a substrate of the CYP2C8 and CYP3A4 isoenzymes, respectively.

However, these parameters for the active metabolites of pioglitazone did not change.

Rifampicin significantly reduced the exposure of gemigliptin.

Therefore, co-administration with other strong inducers of the CYP3A4 isoenzyme, including rifampicin, dexamethasone, phenytoin, carbamazepine, phenobarbital, and rifabutin, is not recommended.

Repeated co-administration with ketoconazole, a strong inhibitor of the CYP3A4 isoenzyme, resulted in a 1.9-fold increase in the AUC of gemigliptin and its active metabolite.

Repeated co-administration with rifampicin, a strong inducer of the CYP3A4 isoenzyme, resulted in an 80% and 59% decrease in the AUC and C_max of gemigliptin, respectively.

The C_max of the active metabolite of gemigliptin did not change significantly, while the AUC decreased by 41%.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.