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Sitagliptin Hydrochloride Oral

FDA Drug Information • Also known as: Brynovin

Brand Names
Brynovin
Drug Class
Dipeptidyl Peptidase 4 Inhibitor [EPC]
Route
ORAL
Dosage Form
SOLUTION
Product Type
HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION BRYNOVIN (sitagliptin) oral solution contains sitagliptin hydrochloride (HCl), an orally-active inhibitor of the DPP-4 enzyme. Sitagliptin HCl is described chemically as ((3R)-3-Amino-1-(3-(trifluoromethy1)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-y1)-4-(2,4,5-trifluorophenyl)butan-l-one HCl monohydrate. The empirical formula is C 16 H 15 F 6 N 5 O

  • HCl.H 2 O and the molecular weight is 461.79. The structural formula is: Sitagliptin HCl is a white to off-white, crystalline, non-hygroscopic powder. It is soluble in water; very slightly soluble in ethanol; and practically insoluble in n-Heptane. BRYNOVIN oral solution is a clear, colorless to nearly colorless oral solution. Each mL contains 27.24 mg of sitagliptin HCl, equivalent to 25 mg of sitagliptin. BRYNOVIN contains the following inactive ingredients: butylated hydroxyanisole, citric acid anhydrous, edetate disodium, hydroxyethyl cellulose, methylparaben sodium, polysorbate 80, purified water, sodium citrate dihydrate, and sweetener/flavoring agent. Structure

    • What Is Sitagliptin Hydrochloride Oral Used For?

    1 INDICATIONS & USAGE BRYNOVIN is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use BRYNOVIN is not recommended in patients with type 1 diabetes. BRYNOVIN has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using BRYNOVIN. [see Warnings and Precautions ( 5.1 )] . BRYNOVIN is a dipeptidyl peptidase-4 (DPP-4) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. ( 1 ) Limitations of Use:

  • BRYNOVIN is not recommended in patients with type 1 diabetes. ( 1 )
  • BRYNOVIN has not been studied in patients with a history of pancreatitis. ( 1 )

    • Dosage and Administration

    2 DOSAGE & ADMINISTRATION The recommended dose of BRYNOVIN is 100 mg orally once daily (4 mL). BRYNOVIN can be taken with or without food. ( 2.1 ) Dosage adjustment is recommended for patients with eGFR less than 45 mL/min/1.73 m 2 . ( 2.2 ) Dosage Adjustment in Patients with Renal Impairment ( 2.2 ) eGFR greater than or equal to 30 mL/min/1.73 m 2 to less than 45 mL/min/1.73 m 2 eGFR less than 30 mL/min/1.73 m 2 (including patients with end stage renal disease [ESRD] on dialysis) 50 mg once daily (2 mL) 25 mg once daily (1 mL) 2.1 Recommended Dosage and Administration Measure the BRYNOVIN dose using a calibrated oral syringe or oral dosing cup scored using metric units of measurements (i.e., mL). The recommended dosage of BRYNOVIN is 100 mg (4 mL) taken orally once daily. BRYNOVIN can be taken with or without food [see Clinical Pharmacology ( 12.3 )] . 2.2 Recommendations for Use in Renal Impairment Assess renal function prior to initiation of BRYNOVIN and periodically thereafter [see Use in Specific Populations ( 8.6 )] . For patients with an estimated glomerular filtration rate (eGFR) greater than or equal to 45 mL/min/1.73 m 2 to less than 90 mL/min/1.73 m 2 , no dosage adjustment for BRYNOVIN is required. For patients with moderate renal impairment (eGFR greater than or equal to 30 mL/min/1.73 m 2 to less than 45 mL/min/1.73 m 2 ), the dosage of BRYNOVIN is 50 mg (2 mL) once daily. For patients with severe renal impairment (eGFR less than 30 mL/min/1.73 m 2 ) or with end-stage renal disease (ESRD) requiring hemodialysis or peritoneal dialysis, the dosage of BRYNOVIN is 25 mg (1 mL) once daily. BRYNOVIN may be administered without regard to the timing of dialysis.

    Side Effects (Adverse Reactions)

    6 ADVERSE REACTIONS The following adverse reactions are also discussed elsewhere in the labeling:

  • Pancreatitis [ see Warnings and Precautions ( 5.1 ) ]
  • Heart Failure [ see Warnings and Precautions ( 5.2 ) ]
  • Acute Renal Failure [ see Warnings and Precautions ( 5.3 ) ]
  • Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues [ see Warnings and Precautions ( 5.4 ) ]
  • Hypersensitivity Reactions [ see Warnings and Precautions ( 5.5 ) ]
  • Severe and Disabling Arthralgia [ see Warnings and Precautions ( 5.6 ) ]
  • Bullous Pemphigoid [ see Warnings and Precautions ( 5.7 ) ] Most common adverse reactions (incidence ≥5%) are: upper respiratory tract infection, nasopharyngitis and headache. In the add-on to sulfonylurea and add-on to insulin trials, hypoglycemia was also more commonly reported in patients treated with sitagliptin compared to placebo. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Azurity Pharmaceuticals, Inc., at 1-800-461-7449 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of BRYNOVIN has been established for glycemic control in patients with type 2 diabetes mellitus based in adequate and well-controlled trials of sitagliptin tablets, referenced below as “sitagliptin” [see Clinical Studies ( 14 )] . Common Adverse Reactions In controlled clinical trials as both monotherapy and combination therapy with metformin, pioglitazone, or rosiglitazone and metformin, the overall incidence of adverse reactions, hypoglycemia, and discontinuation of therapy due to clinical adverse reactions with sitagliptin were similar to placebo. In combination with glimepiride, with or without metformin, the overall incidence of clinical adverse reactions with sitagliptin was higher than with placebo, in part related to a higher incidence of hypoglycemia (see Table 3); the incidence of discontinuation due to clinical adverse reactions was similar to placebo. Two placebo-controlled monotherapy trials, one of 18- and one of 24-week duration, included patients treated with sitagliptin 100 mg daily, sitagliptin 200 mg daily, and placebo. Five placebo-controlled add-on combination therapy trials were also conducted: one with metformin; one with pioglitazone; one with metformin and rosiglitazone; one with glimepiride (with or without metformin); and one with insulin (with or without metformin). In these trials, patients with inadequate glycemic control on a stable dosage of the background therapy were randomized to add-on therapy with sitagliptin 100 mg daily or placebo. The adverse reactions, excluding hypoglycemia, in ≥5% of patients treated with sitagliptin 100 mg daily and more commonly than in patients treated with placebo, are shown in Table 1 for the clinical trials of at least 18 weeks duration. Incidences of hypoglycemia are shown in Table 3. Table 1:Placebo-Controlled Clinical Trials of Sitagliptin Monotherapy or Add-on Combination Therapy with Pioglitazone, Metformin + Rosiglitazone, or Glimepiride +/- Metformin: Adverse Reactions (Excluding Hypoglycemia) Reported in ≥5% of Patients and More Commonly than in Patients Given Placebo* Number of Patients (%) Monotherapy (18 or 24 weeks) Sitagliptin 100 mg Placebo N = 443 N = 363 Nasopharyngitis 23 (5.2) 12 (3.3) Combination with Pioglitazone (24 weeks) Sitagliptin 100 mg + Pioglitazone Placebo + Pioglitazone N = 175 N = 178 Upper Respiratory Tract Infection 11 (6.3) 6 (3.4) Headache 9 (5.1) 7 (3.9) Combination with Metformin + Rosiglitazone (18 weeks) Sitagliptin 100 mg + Metformin + Rosiglitazone Placebo + Metformin + Rosiglitazone N = 181 N = 97 Upper Respiratory Tract Infection 10 (5.5) 5 (5.2) Nasopharyngitis 11 (6.1) 4 (4.1) Combination with Glimepiride...

    • Drug Interactions

    7 DRUG INTERACTIONS 7.1 Concomitant Use with Insulin or Insulin Secretagogues BRYNOVIN lowers blood glucose in patients with type 2 diabetes mellitus. Coadministration of BRYNOVIN with insulin or an insulin secretagogue (e.g., sulfonylurea) or insulin may require lower dosages of the insulin secretagogue or insulin to reduce the risk of hypoglycemia. [See Warnings and Precautions ( 5.4 )].

    Contraindications

    4 CONTRAINDICATIONS BRYNOVIN is contraindicated in patients with a history of a serious hypersensitivity reaction to sitagliptin or any of the excipients in BRYNOVIN. Serious hypersensitivity reactions, including anaphylaxis and angioedema have been reported [see Warnings and Precautions ( 5.5 ) and Adverse Reactions ( 6.2 )]. History of a serious hypersensitivity reaction to sitagliptin or any of the excipients in BRYNOVIN, such as anaphylaxis or angioedema. ( 4 )

    Pregnancy and Breastfeeding

    8.1 Pregnancy Risk Summary The limited available data with sitagliptin in pregnant women are not sufficient to inform a drug- associated risk for major birth defects and miscarriage. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see Clinical Considerations] . No adverse developmental effects were observed when sitagliptin was administered to pregnant rats and rabbits during organogenesis at oral doses up to 30-times and 20-times, respectively, the 100 mg clinical dose, based on AUC [see Data]. The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with a hemoglobin A1C >7% and has been reported to be as high as 20-25% in women with a hemoglobin A1C >10%. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre- eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, still birth, and macrosomia related morbidity. Data Animal Data In embryo-fetal development trials, sitagliptin administered to pregnant rats and rabbits during organogenesis (gestation day 6 to 20) did not adversely affect developmental outcomes at oral doses up to 250 mg/kg (30-times the 100 mg clinical dose) and 125 mg/kg (20-times the 100 mg clinical dose), respectively, based on AUC. Higher doses in rats associated with maternal toxicity increased the incidence of rib malformations in offspring at 1,000 mg/kg, or approximately 100-times the clinical dose, based on AUC. Placental transfer of sitagliptin was observed in pregnant rats and rabbits. Sitagliptin administered to female rats from gestation day 6 to...

    Overdosage

    10 OVERDOSAGE In the event of an overdose with BRYNOVIN, consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. Employ the usual supportive measures dictated by the patient’s clinical status. Sitagliptin is modestly dialyzable. In clinical trials, 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.

    How Supplied

    16 HOW SUPPLIED/STORAGE AND HANDLING BRYNOVIN (sitagliptin) oral solution 25 mg/mL is supplied as a clear colorless, to nearly colorless aqueous solution in an amber glass bottle with a child resistant closure. Each bottle contains 120 mL oral solution, NDC 24338-017-01 Storage Store refrigerated at 2°C to 8°C (36°F to 46°F) [see USP]; Protect from light. Avoid excessive heat and freezing. Discard unused portion 90 days after first opening.

    About This Information

    This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

    What are side effects?

    Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

    What are drug interactions?

    Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.