Siglivia

SIGLIVIA (50 MG TABLET): Each tablet contains Sitagliptin phosphate monohydrate equivalent to Sitagliptin 50 mg.
A light beige, round and biconvex film-coated tablet engraved with "
Click on icon to see table/diagram/image
" logo on one side and a score with "S" and 50” on the other side.
SIGLIVIA (100 MG TABLET): Each tablet contains Sitagliptin phosphate monohydrate equivalent to Sitagliptin 100 mg.
A dark beige, round and biconvex film-coated tablet engraved with "
Click on icon to see table/diagram/image
" logo on one side and a score with "S" and "100" on the other side.

Pharmacology: Pharmacodynamics: Sitagliptin act as highly selective dipeptidyl peptidase-4 (DPP-4) enzyme inhibitor, resulting in increased and prolonged active incretin levels. Incretin hormones (e.g., glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]) are part of an endogenous system involved in regulation of homeostasis by increasing insulin synthesis and release from pancreatic beta cells and decreasing glucagon secretion from pancreatic alpha cells, leading to reduced hepatic glucose production. Inhibition of DPP-4 results in reduced fasting and postprandial blood glucose concentrations in patients with type 2 diabetes mellitus.
Sitagliptin is a potent and highly selective inhibitor of the enzyme DPP-4 with no effect on DPP-8 or DPP-9 in vitro at concentrations approximating those from therapeutic dosage. Co-administration of Sitagliptin and metformin had an additive effect on active GLP-1 concentrations. Sitagliptin action are glucose dependent, did not lower blood glucose or cause hypoglycemia with healthy subject.
Pharmacokinetics: Absorption: The absolute bioavailability of Sitagliptin is approximately 87%. The drug is rapidly absorbed following oral administration, with a peak plasma concentration occurring about 1 to 4 hours after an oral dose. Following the administration of 50 mg or 100 mg of Sitagliptin, approximately 80% inhibition of DPP-4 activity persists for 12 or 24 hours, respectively. Food does not appear to affect absorption. Administration of Sitagliptin with a high-fat meal had no effect on the pharmacokinetics of the drug.
Distribution: The volume of distribution is 198 L. Sitagliptin is 38% reversible bound to plasma proteins.
Metabolism: Sitagliptin undergoes minimal metabolism, mainly by the cytochrome P450 isoenzyme CYP3A4, and to a lesser extent by CYP2C8. Sitagliptin is a substrate for human organic anion transporter-3 (hOAT-3) and P-glycoprotein.
Excretion: Sitagliptin is eliminated principally by kidneys via active tubular secretion. The drug is excreted in urine 87% (mainly as unchanged drug) and in feces 13%. The terminal half-life is about 12.4 hours. The renal clearance is about 350 mL/min.
Renal impairment: Plasma AUC of Sitagliptin was increased by approximately 1.2-fold and 1.6-fold in patients with mild renal impairment (eGFR ≥60 mL/min/1.73 m² to <90 mL/min/1.73 m²) and patients with moderate renal impairment (eGFR ≥45 mL/min/1.73 m² to <60 mL/min/1.73 m²), respectively. Because increases of magnitude are not clinically relevant, dosage adjustment in these patients is not necessary.
In patients with moderate (eGFR ≥30 mL/min/1.73 m² to <45 mL/min/1.73 m²) to severe (eGFR <30 mL/min/1.73 m², including patients with ESRD on hemodialysis) renal impairment, Sitagliptin plasma AUC increased 2- and 4-fold, respectively. Lower dosages are recommended in patient with eGFR <45 mL/min/1.73 m². See Dosage & Administration.
Type 2 Diabetes: The pharmacokinetics of Sitagliptin in patients with type 2 diabetes are generally similar to those in healthy subjects.
Body mass index, sex and race: Body mass index, sex and race do not have clinically meaningful effect on Sitagliptin pharmacokinetics.
Hepatic impairment: Sitagliptin AUC and C_max increased approximately 21% and 13%, respectively, in subjects with moderate hepatic impairment (Child-Pugh class B). No dosage adjustment is necessary for patients with mild or moderate hepatic impairment. Severe hepatic impairment is not expected to affect the pharmacokinetics of Sitagliptin.
Pediatric: The Pharmacokinetics of Sitagliptin (single dose of 50 mg, 100 mg or 200 mg) were investigated in pediatric patients (10 to 17 years of age) with type 2 diabetes. In this population, the dose-adjusted AUC of Sitagliptin in plasma was approximately 18% lower compared to adult to patients with type 2 diabetes for a 100 mg dose. This is not considered to be a clinically meaningful difference based on the flat PK/PD relationship between the dose of 50 mg and 100 mg in adults.
No studies with Sitagliptin have been performed in pediatric patients <10 years old.
Elderly: Elderly subjects (65 to 80 years) had approximately 19% higher plasma concentrations of Sitagliptin compared to younger subjects. No dosage adjustment is required based on age.

Monotherapy: Sitagliptin is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.
Combination with metformin: Sitagliptin is indicated in patients with type 2 diabetes mellitus to improve glycemic control in combination with metformin as initial therapy when the single agent alone, with diet and exercise, does not provide adequate glycemic control.
Combination with a sulfonylurea: Sitagliptin is indicated in patients with type 2 diabetes mellitus to improve glycemic control in combination with a sulfonylurea when treatment with the single agent alone, with diet and exercise, does not provide adequate glycemic control.
Combination with a PPARγ agonist: Sitagliptin is indicated in patients with type 2 diabetes mellitus to improve glycemic control in combination with a PPARγ agonist (e.g., thiazolidinediones) as initial therapy when the single agent alone, with diet and exercise, does not provide adequate glycemic control.
Combination with metformin and a sulfonylurea: Sitagliptin is indicated in patients with type 2 diabetes mellitus to improve glycemic control in combination with metformin and a sulfonylurea when dual therapy with these agents, with diet and exercise, does not provide adequate glycemic control.
Combination with metformin and a PPARγ agonist: Sitagliptin is indicated in patients with type 2 diabetes mellitus to improve glycemic control in combination with metformin and PPARγ agonist (e.g., thiazolidinediones) when dual therapy with these agents, with diet and exercise, does not provide adequate glycemic control.
Combination with insulin: Sitagliptin is indicated in patients with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycemic control in combination with insulin (with or without metformin).

The recommended dose of Sitagliptin is 100 mg once daily as monotherapy or as combination therapy with metformin, a sulfonylurea, insulin (with or without metformin), PPARγ agonist (e.g., thiazolidinediones), metformin plus a sulfonylurea, or metformin plus a PPARγ agonist. Sitagliptin can be taken with or without food. When Sitagliptin is used in combination with a sulfonylurea or with insulin, a lower dose of sulfonylurea or insulin may be considered to reduce the risk of sulfonylurea- or insulin-induced hypoglycemia.
Patients with renal impairment: Because there is a dosage adjustment based upon renal function, assessment of renal function is recommended prior to initiation of Sitagliptin and periodically thereafter.
For patients with mild renal impairment (estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m² to <90 mL/min/1.73 m²), no dosage adjustment for Sitagliptin is required.
For patients with moderate renal impairment (eGFR ≥45 mL/min/1.73 m² to <60 mL/min/1.73 m²), no dosage adjustment for Sitagliptin is required.
For patients with moderate renal impairment (eGFR ≥30 mL/min/1.73 m² to <45 mL/min/1.73 m²), the dose of Sitagliptin is 50 mg once daily.
For patients with severe renal impairment (eGFR ≥15 mL/min/1.73 m² to <30 mL/min/1.73 m²) or with end-stage renal disease (ESRD) (eGFR <15 mL/min/1.73 m²), including those requiring hemodialysis or peritoneal dialysis, the dose of Sitagliptin is 25 mg once daily. Sitagliptin may be administered without regard to the timing of dialysis.

In the event of an overdose, it is reasonable to employ the usual supportive measure, e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring (including obtaining an electrocardiogram), and institute supportive therapy if required.
Sitagliptin is modestly dialysable, approximately 13.5% of dose was removed over a 3- to 4-hour hemodialysis. Prolonged hemodialysis may be considered if clinically appropriate. It is not known if Sitagliptin is dialysable by peritoneal dialysis.

Sitagliptin is contraindicated in patients with known serious hypersensitivity to Sitagliptin or to any ingredient in the formulation.

Warnings (based on the Ministry of Public Health's Announcement): Do not use in patients with known hypersensitivity to this medicine.
Do not use in type I diabetes treatment, patient with ketoacidosis, severe infection or serious accident.
Pregnant women should avoid using this drug. And breastfeeding women, be careful when using this drug.
Should not use concomitantly with alcohol.
This drug may increase risk of severe joint pain.

Sitagliptin should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.
Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis have been occur in patients taking Sitagliptin. Patients should be informed of the characteristic symptom of acute pancreatitis: persistent, severe abdominal pain. Resolution of pancreatitis has been observed after discontinuation of Sitagliptin, if pancreatitis is suspected, Sitagliptin and other potentially suspect medicinal products should be discontinued.
Sitagliptin is renally excreted. Lower dosage are recommended in patients with eGFR <45 mL/min/1.73 m², as well as in ESRD patients requiring hemodialysis or peritoneal dialysis to achieve plasma concentrations of Sitagliptin similar to those in patients with normal renal function.
Hypoglycemia has been observed when Sitagliptin was used in combination with insulin or a sulfonylurea. Therefore, to reduce the risk of sulfonylurea- or insulin induced hypoglycemia, a lower dose of sulfonylurea or insulin may be considered.
Serious hypersensitivity reactions have been occurred in patients treated with Sitagliptin including anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. Onset of these reactions occurred within the first 3 months after initiation of treatment with Sitagliptin, but such reactions may occur after the first dose. If a hypersensitivity reaction is suspected, discontinue Sitagliptin, assess for other potential causes for the event, and institute alternative treatment for diabetes.
Bullous pemphigoid requiring hospitalization have been occurred with DPP-4 inhibitor use. Patients in such cases usually recovered after discontinuation of the DPP-4 inhibitor and treatment with topical or systemic immunosuppressive therapy. Patients should be advised to report the development of blisters or erosions while receiving Sitagliptin. If bullous pemphigoid is suspected, Sitagliptin should be discontinued and referral to a dermatologist should be considered for diagnosis and appropriate treatment.
Effects on ability to drive and use machines: Sitagliptin has no or negligible influence on the ability to drive and use machines. However, when driving or using machines, it should be taken into account that dizziness has been occurred. In addition, patients should be alerted to the risk of hypoglycemia when Sitagliptin is used in combination with a sulfonylurea or with insulin.

Pregnancy: There are no adequate and well-controlled studies in pregnant women. Therefore, the safety of Sitagliptin in pregnant women is not known. Sitagliptin is not recommended for use in pregnancy.
Breast-feeding: Sitagliptin is distributed into milk in rats; data are lacking regarding the presence of the drug in human milk. Therefore, Sitagliptin should not be used by a woman who is nursing.

Blood and lymphatic system disorders: Rare: Thrombocytopenia.
Immune system disorders: Frequency not known: Hypersensitivity reaction including anaphylaxis.
Metabolism and nutrition disorders: Common: Hypoglycemia.
Nervous system disorders: Common: Headache.
Uncommon: Dizziness.
Respiratory, thoracic and mediastinal disorders: Common: Upper respiratory tract infection, nasopharyngitis.
Frequency not known: Interstitial lung disease.
Gastrointestinal disorders: Uncommon: Constipation, vomiting, diarrhea.
Frequency not known: Acute pancreatitis, fatal and non-fatal hemorrhagic and necrotizing pancreatitis.
Skin and subcutaneous tissue disorders: Uncommon: Pruritus.
Frequency not known: Angioedema, rash, urticaria, cutaneous vasculitis, exfoliative skin conditions including Stevens-Johnson syndrome, bullous pemphigoid.
Musculoskeletal and connective tissue disorders: Frequency not known: Arthralgia, myalgia, back pain, arthropathy.
Renal and urinary disorders: Frequency not known: Impaired renal function, acute renal failure.
General disorders: Common: Peripheral edema.

Sitagliptin does not inhibit CYP isozymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4 or induce CYP3A4. Pharmacokinetic interactions with drugs metabolized by these isoenzymes (including metformin, thiazolidinediones (e.g., rosiglitazone), sulfonylureas (e.g., glyburide), simvastatin, warfarin, or oral contraceptives) did not have clinically meaningful. Co-administration of multiple twice-daily doses of metformin with Sitagliptin did not meaningfully after the pharmacokinetics of Sitagliptin in patients with type 2 diabetes.
Concomitant administration of Sitagliptin with digoxin resulted in a slightly increase in peak plasma concentrations and area under the concentration-time curve (AUC) of digoxin (18% and 11%, respectively). While these increases are not considered clinically important, patients receiving digoxin should be monitored appropriately; however, no digoxin or Sitagliptin dosage adjustment is needed.
Concomitant administration of cyclosporin (a potent probe inhibitor of p-glycoprotein) and Sitagliptin may increase absorption and plasma concentrations of Sitagliptin. However, this interaction is not considered clinically important and no dosage adjustment for Sitagliptin is recommended when co-administered with cyclosporin or other p-glycoprotein inhibitors (e.g., ketoconazole).
Population pharmacokinetic analyses have been conducted in patients with type 2 diabetes. Concomitant medications did not have a clinically meaningful effect on the pharmacokinetics of Sitagliptin. Medication assessed were those that are commonly administered to patients with type 2 diabetes including cholesterol-lowering agents (e.g., statins, fibrates, ezetimibe), anti-platelet agents (e.g., clopidogrel), antihypertensives (e.g., ACE inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, hydrochlorothiazide), analgesics and non-steroidal anti-inflammatory agents (e.g., naproxen, diclofenac, celecoxib), anti-depressants (e.g., bupropion, fluoxetine, sertraline), antihistamines (e.g., cetirizine), proton-pump inhibitors (e.g., omeprazole, lansoprazole), and medications for erectile dysfunction (e.g., sildenafil).

Store below 30°C, protect from light.

Antidiabetic Agents

A10BH01 - sitagliptin ; Belongs to the class of dipeptidyl peptidase 4 (DPP-4) inhibitors. Used in the treatment of diabetes.

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