Reditn

REDITN 50: Yellow coloured, biconvex, round shaped, film-coated tablets debossed with "5" on one side and plain on other side.
Each film-coated tablet contains Sitagliptin phosphate (Anhydrous) 62.030 mg equivalent to Sitagliptin 50.00 mg.
REDITN 100: Brown coloured, biconvex, round shaped, film-coated tablets debossed with "10" on one side and plain on other side.
Each film-coated tablet contains Sitagliptin phosphate (Anhydrous) 124.060 mg equivalent to Sitagliptin 100.00 mg.

Pharmacology: Pharmacodynamics: Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor, which exerts its actions in patients with type 2 diabetes by slowing the inactivation of incretin hormones. Concentrations of the active, intact hormones are increased by sitagliptin, thereby increasing and prolonging the action of these hormones. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are released by the intestine throughout the day, and levels are increased in response to a meal. These hormones are rapidly inactivated by the enzyme, DPP-4. The incretins are part of an endogenous system involved in the physiologic regulation of glucose homeostasis. When blood glucose concentrations are normal or elevated, GLP-1 and GIP increase insulin synthesis and release from pancreatic beta cells by intracellular signaling pathways involving cyclic AMP. GLP-1 also lowers glucagon secretion from pancreatic alpha cells leading to reduced hepatic glucose production, and GLP-1 slows gastric emptying time. Sitagliptin increases insulin release and decreases glucagon levels in the circulation in a glucose-dependent manner; GLP-1 does not increase insulin secretion when the glucose concentration is less than 90 mg/dL. The contributions of GIP, which increases insulin secretion and regulates fat metabolism, overall effects of sitagliptin are unclear at this time. Sitagliptin is of benefit in patients with type 2 diabetes mellitus as their GLP-1 concentrations are decreased in response to a meal. Sitagliptin demonstrates selectivity for DPP-4 and does not inhibit DPP-8 or DPP-9 activity in vitro at concentrations approximating those from therapeutic doses. The long-term safety of DPP-4 inhibitors are currently under investigation as DPP-4 is not an enzyme specific for the breakdown of incretin hormones. In fact, DPP-4 is responsible for the metabolism of many peptides including peptide YY, neuropeptide Y, and growth hormone-releasing hormone. DPP-4 is involved with T-cell activation and is expressed on lymphocytes as CD26. Whether there are long-term neurological or immunological consequences of inhibiting DPP-4 is unclear at this time.
Pharmacokinetics: Absorption: Bioavailability: Absolute bioavailability of sitagliptin is 87%.
Rapidly absorbed following oral administration; at steady state (within 3 days of therapy initiation), peak plasma concentrations generally attained ≤3 hours following administration of recommended doses.
Onset: Reduction in postprandial plasma glucose excursion: Approximately 60 minutes.
Duration: Approximately 80% inhibition of DPP-4 activity persists for 12 or 24 hours following administration of ≥50 or ≥100 mg, respectively, of sitagliptin.
Food: Food does not appear to affect absorption.
Special Populations: Renal impairment results in increased plasma AUC. Removed modestly by hemodialysis; time to peak plasma drug concentration increased in a limited number of patients with end-stage renal disease requiring hemodialysis.
Moderate hepatic impairment results in increased peak plasma concentrations and AUC not considered clinically important.
In geriatric patients, modest increases in plasma concentrations compared with younger adults.
Distribution: Extent: Distributed into milk in rats not known whether distributed into human milk.
Plasma Protein Binding: 38%.
Metabolism: Metabolized to a limited extent by CYP isoenzymes 3A4 and 2C8 to inactive metabolites.
Elimination Route: Eliminated principally by kidneys via active tubular secretion. Excreted in urine (87%) mainly as unchanged drug and in feces (13%).
Half-life: 12.4 hours.
Special Populations: Renal impairment results in increased terminal elimination half-life.

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 or 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 (i.e., thiazolidinediones) as initial therapy or 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 a PPARγ agonist (i.e., 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).

Recommended Dose: 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), a 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. (See Use with Medications Known To Cause Hypoglycemia under Precautions).
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 [consider the other alternate brands available in Thailand]. Sitagliptin may be administered without regard to the timing of dialysis.
Hepatic impairment: No dose adjustment is necessary for patients with mild to moderate hepatic impairment. Sitagliptin has not been studied in patients with severe hepatic impairment and care should be exercised. However, because sitagliptin is primarily renally eliminated, severe hepatic impairment is not expected to affect the pharmacokinetics of sitagliptin.
Elderly: No dose adjustment is necessary based on age.
Paediatric population: Sitagliptin should not be used in children and adolescents 10 to 17 years of age because of insufficient efficacy.
Mode of administration: For oral use.
Sitagliptin can be taken with or without food.

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

Known serious hypersensitivity (e.g., anaphylaxis, angioedema) to sitagliptin or any ingredient in formulation.

Pancreatitis: There have been postmarketing reports of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, in patients taking sitagliptin. After initiation of sitagliptin, patients should be observed carefully for signs and symptoms of pancreatitis. If pancreatitis is suspected, sitagliptin should promptly be discontinued and appropriate management should be initiated. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using sitagliptin.
Heart Failure: An association between dipeptidyl peptidase-4 (DPP-4) inhibitor treatment and heart failure has been observed in cardiovascular outcomes trials for two other members of the DPP-4 inhibitor class. These trials evaluated patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease.
Consider the risks and benefits of sitagliptin prior to initiating treatment in patients at risk for heart failure, such as those with a prior history of heart failure and a history of renal impairment, and observe these patients for signs and symptoms of heart failure during therapy. Advise patients of the characteristic symptoms of heart failure and to immediately report such symptoms. If heart failure develops, evaluate and manage according to current standards of care and consider discontinuation of sitagliptin.
Assessment of Renal Function: Assessment of renal function is recommended prior to initiating sitagliptin and periodically thereafter. A dosage adjustment is recommended in patients with moderate or severe renal impairment and in patients with ESRD requiring hemodialysis or peritoneal dialysis. Caution should be used to ensure that the correct dose of Sitagliptin is prescribed for patients with moderate (eGFR ≥30 mL/min/1.73 m² to <45 mL/min/1.73 m²) or severe (eGFR ≥15 mL/min/1.73 m² to <30 mL/min/1.73 m²) renal impairment.
There have been postmarketing reports of worsening renal function, including acute renal failure, sometimes requiring dialysis. A subset of these reports involved patients with renal impairment, some of whom were prescribed inappropriate doses of sitagliptin. A return to baseline levels of renal impairment has been observed with supportive treatment and discontinuation of potentially causative agents. Consideration can be given to cautiously reinitiating Sitagliptin if another etiology is deemed likely to have precipitated the acute worsening of renal function.
Sitagliptin has not been found to be nephrotoxic in preclinical studies at clinically relevant doses, or in clinical trials.
Use with Medications Known To Cause Hypoglycemia: When sitagliptin was used in combination with a sulfonylurea or with insulin, medications known to cause hypoglycemia, the incidence of hypoglycemia was increased over that of placebo used in combination with a sulfonylurea or with insulin. Therefore, a lower dose of sulfonylurea or insulin may be required to reduce the risk of hypoglycemia.
Hypersensitivity Reactions: There have been postmarketing reports of serious hypersensitivity reactions in patients treated with sitagliptin. These reactions include 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, with some reports occurring 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.
Angioedema has also been reported with other DPP-4 inhibitors. Use caution in a patient with a history of angioedema with another DPP-4 inhibitor because it is unknown whether such patients will be predisposed to angioedema with sitagliptin.
Severe and Disabling Arthralgia: There have been postmarketing reports of severe and disabling arthralgia in patients taking DPP-4 inhibitors. The time to onset of symptoms following initiation of drug therapy varied from one day to years. Patients experienced relief of symptoms upon discontinuation of the medication. A subset of patients experienced a recurrence of symptoms when restarting the same drug or a different DPP-4 inhibitor. Consider DPP-4 inhibitors as a possible cause for severe joint pain and discontinue drug if appropriate.
Concomitant Therapy with Hypoglycemic Agents: Greater incidence of hypoglycemia when sitagliptin used in combination with a sulfonylurea or insulin. May require lower dosage of concomitant insulin secretagogue (e.g., sulfonylurea) or insulin to reduce risk of hypoglycemia.
Loss of Glycemic Control: Possible loss of glycemic control during periods of stress (e.g., fever, trauma, infection, surgery). Temporary discontinuance of sitagliptin and administration of insulin may be required. May reinstitute sitagliptin therapy after acute episode of hyperglycemia has resolved.
Bullous Pemphigoid: Postmarketing cases of bullous pemphigoid requiring hospitalization have been reported with DPP-4 inhibitor use. In reported cases, patients typically recovered with topical or systemic immunosuppressive treatment and discontinuation of the DPP-4 inhibitor. Tell patients to report 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.
Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with sitagliptin.
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 and somnolence have been reported.
In addition, patients should be alerted to the risk of hypoglycaemia when sitagliptin is used in combination with a sulphonylurea or with insulin.

Pregnancy: Data lacking on use of sitagliptin in pregnant women. In animal studies, no adverse developmental effects observed when sitagliptin was administered to pregnant rats and rabbits during organogenesis at doses ≤30 times the human 100-mg dose (based on AUC).
Lactation: Sitagliptin distributed into milk in rats; not known whether distributed into human milk. Use caution.
Fertility: Animal data do not suggest an effect of treatment with sitagliptin on male and female fertility. Human data are lacking.

Sitagliptin monotherapy or add-on therapy with metformin and/or a thiazolidinedione or glimepiride: Nasopharyngitis, upper respiratory tract infection, peripheral edema, headache.
Sitagliptin in combination with ertugliflozin: Adverse effects similar to those reported with ertugliflozin alone.
Sitagliptin in combination with metformin: Diarrhea, upper respiratory infection, headache.
Sitagliptin in combination with metformin and glimepiride: Hypoglycemia, headache.
Sitagliptin in combination with insulin: Hypoglycemia.

Metabolized to a limited extent by CYP isoenzymes 3A4 and 2C8 to inactive metabolites.
Drugs Metabolized by Hepatic Microsomal Enzymes: Does not inhibit CYP isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4 in vitro or induce CYP3A4. Pharmacokinetic interactions with drugs metabolized by these isoenzymes unlikely.
Drugs Affecting or Affected by P-glycoprotein (P-gp) Transport System: Substrate of P-gp transport system. Potential pharmacokinetic interaction (increased absorption and renal clearance of sitagliptin) with P-gp inhibitors.
Clinically important pharmacokinetic interactions with P-gp inhibitors unlikely. Does not appear to inhibit P-gp transport system. Pharmacokinetic interactions with substrates of P-gp unlikely.
Drugs Secreted by Renal Tubular Cationic Transport: Substrate of organic anion transport system; pharmacokinetic interaction unlikely with substrates of organic cationic transport system.
Protein-bound Drugs: Pharmacokinetic interaction unlikely.
Specific Drugs: See table.

Click on icon to see table/diagram/image

Storage Condition: Store below 30°C.

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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