Boxed Warning (Black Box)
BOXED WARNING WARNING: LACTIC ACIDOSIS Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic ac...
ZITUVIMET XR
SITAGLIPTIN AND METFORMIN HYDROCHLORIDE
Manufacturer: Zydus Pharmaceuticals USA Inc.
Clinical information
Indications & Usage
1 INDICATIONS AND USAGE ZITUVIMET XR is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use ZITUVIMET XR is not recommended in patients with type 1 diabetes mellitus. ZITUVIMET XR 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 ZITUVIMET XR [see Warnings and Precautions ( 5.2 )]. ZITUVIMET XR is a combination of sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and metformin hydrochloride (HCl), a biguanide indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. ( 1 ) Limitations of Use: Not for the treatment of type 1 diabetes mellitus. ( 1 ) Has not been studied in patients with a history of pancreatitis. ( 1 )
Dosage & Administration
2 DOSAGE AND ADMINISTRATION Take ZITUVIMET XR orally once daily with a meal. Patients taking two ZITUVIMET XR tablets should take the tablets together. ( 2.1 ) Individualize the dosage of ZITUVIMET XR on the basis of the patient's current regimen, effectiveness, and tolerability. ( 2.1 ) The maximum recommended daily dose is 100 mg of sitagliptin and 2,000 mg of metformin HCl extended-release. ( 2.1 ) The recommended starting dose in patients not currently treated with metformin is 100 mg sitagliptin and 1,000 mg metformin HCl once daily, with gradual dose escalation recommended to reduce gastrointestinal side effects associated with metformin. ( 2.1 ) The starting dose in patients already treated with metformin should provide sitagliptin dosed as 100 mg and the dose of metformin already being taken once daily. For patients taking metformin HCl 850 mg twice daily or 1,000 mg twice daily, the recommended starting dose of ZITUVIMET XR is two 50 mg sitagliptin and 1,000 mg metformin HCl extended-release tablets once daily. ( 2.1 ) Maintain the same total daily dose of sitagliptin and metformin when changing between sitagliptin and metformin immediate-release or sitagliptin and metformin extended-release and ZITUVIMET XR. ( 2.1 ) Prior to initiation, assess renal function with estimated glomerular filtration rate (eGFR) ( 2.2 ) Do not use in patients with eGFR below 30 mL/min/1.73 m 2 . ZITUVIMET XR is not recommended in patients with eGFR between 30 to 45 mL/min/1.73 m 2 . Limit dose of sitagliptin to 50 mg once daily if eGFR falls below 45 mL/min/1.73 m 2 . ZITUVIMET XR may need to be discontinued at time of, or prior to, iodinated contrast imaging procedures. ( 2.3 ) 2.1 Recommended Dosage and Administration Take ZITUVIMET XR orally once daily with a meal. Patients taking two ZITUVIMET XR tablets should take the two tablets together once daily. Individualize the dosage of ZITUVIMET XR on the basis of the patient's current regimen, effectiveness, and tolerability. The maximum recommended daily dose is 100 mg of sitagliptin and 2,000 mg of metformin hydrochloride (HCl) extended-release. The recommended starting dose in patients not currently treated with metformin is 100 mg sitagliptin and 1,000 mg metformin HCl extended-release once daily, with gradual dose escalation recommended to reduce gastrointestinal side effects associated with metformin. The starting dose in patients already treated with metformin should provide 100 mg sitagliptin and the previously prescribed dose of metformin. For patients taking metformin HCl immediate-release 850 mg twice daily or 1,000 mg twice daily, the recommended starting dose of ZITUVIMET XR is two 50 mg sitagliptin and 1,000 mg metformin HCl extended-release tablets taken together once daily. Maintain the same total daily dose of sitagliptin and metformin when changing between sitagliptin and metformin HCl immediate-release or sitagliptin and metformin extended-release and ZITUVIMET XR. Do not split, crush or chew ZITUVIMET XR tablets. 2.2 Recommendations for Use in Renal Impairment Assess renal function prior to initiation of ZITUVIMET XR and periodically thereafter. ZITUVIMET XR is contraindicated in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m 2 [see Contraindications ( 4 ) and Warnings and Precautions ( 5.1 )] . Initiation of ZITUVIMET XR in patients with an eGFR between 30 and 45 mL/min/1.73 m 2 is not recommended. In patients taking ZITUVIMET XR whose eGFR later falls below 45 mL/min/1.73 m 2 , assess the benefit risk of continuing therapy and limit dose of the sitagliptin component to 50 mg once daily. 2.3 Discontinuation for Iodinated Contrast Imaging Procedures Discontinue ZITUVIMET XR at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/min/1.73 m 2 ; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure; restart ZITUVIMET XR if renal function is stable [see Warnings and Precautions ( 5.1 )] .
Contraindications
4 CONTRAINDICATIONS ZITUVIMET XR is contraindicated in patients with: Severe renal impairment (eGFR below 30 mL/min/1.73 m 2 ) [see Warnings and Precautions ( 5.1 )] . Acute or chronic metabolic acidosis, including diabetic ketoacidosis. A history of a serious hypersensitivity reaction to sitagliptin , metformin, or any of the excipients in ZITUVIMET XR. Serious hypersensitivity reactions including anaphylaxis or angioedema have been reported [see Warnings and Precautions ( 5.7 ) and Adverse Reactions ( 6.2 )]. Severe renal impairment: eGFR below 30 mL/min/1.73 m 2 . ( 4 ) Metabolic acidosis, including diabetic ketoacidosis. ( 4 ) History of a serious hypersensitivity reaction to ZITUVIMET XR, sitagliptin, or metformin, such as. anaphylaxis or angioedema) ( 4 )
Safety
Adverse Reactions
6 ADVERSE REACTIONS The following adverse reactions are also discussed elsewhere in the prescribing information: Lactic Acidosis [see Warnings and Precautions ( 5.1 )] Pancreatitis [see Warnings and Precautions ( 5.2 )] Heart Failure [see Warnings and Precautions ( 5.3 )] Acute Renal Failure [see Warnings and Precautions ( 5.4 )] Vitamin B 12 Deficiency [see Warnings and Precautions ( 5.5 )] Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues [see Warnings and Precautions ( 5.6 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.7 )] Severe and Disabling Arthralgia [see Warnings and Precautions ( 5.8 )] Bullous Pemphigoid [see Warnings and Precautions ( 5.9 )] Most common adverse reactions (incidence ≥5%) of patients simultaneously started on sitagliptin and metformin and more commonly than in patients treated with placebo were diarrhea, upper respiratory tract infection, and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 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. Common Adverse Reactions Sitagliptin and Metformin Immediate-Release Coadministration in Patients with Type 2 Diabetes Mellitus Inadequately Controlled on Diet and Exercise Table 1 summarizes the most common (≥5% of patients) adverse reactions reported in a 24-week placebo-controlled factorial trial in which sitagliptin and metformin immediate-release were coadministered to patients with type 2 diabetes mellitus inadequately controlled on diet and exercise. Table 1: Sitagliptin and Metformin Immediate-Release Coadministered to Patients with Type 2 Diabetes Mellitus Inadequately Controlled on Diet and Exercise: Adverse Reactions Reported in ≥5% of Patients Receiving Combination Therapy (and Greater than in Patients Receiving Placebo) Intent-to-treat population. Number of Patients (%) Placebo Sitagliptin 100 mg once daily Metformin HCl Immediate-Release 500 mg or 1,000 mg twice daily Data pooled for the patients given the lower and higher doses of metformin. Sitagliptin 50 mg twice daily + Metformin HCl Immediate-Release 500 mg or 1,000 mg twice daily N = 176 N = 179 N = 364 N = 372 Diarrhea 7 (4) 5 (2.8) 28 (7.7) 28 (7.5) Upper Respiratory Tract Infection 9 (5.1) 8 (4.5) 19 (5.2) 23 (6.2) Headache 5 (2.8) 2 (1.1) 14 (3.8) 22 (5.9) Sitagliptin Add-on Therapy in Patients with Type 2 Diabetes Mellitus Inadequately Controlled on Metformin Immediate-Release Alone In a 24-week placebo-controlled trial of sitagliptin 100 mg administered once daily added to a twice daily metformin immediate-release regimen, there were no adverse reactions reported in ≥5% of patients and more commonly than in patients given placebo. Discontinuation of therapy due to clinical adverse reactions was similar to the placebo treatment group (sitagliptin and metformin immediate-release, 1.9%; placebo and metformin immediate-release, 2.5%). Gastrointestinal Adverse Reactions The incidences of pre-selected gastrointestinal adverse experiences in patients treated with sitagliptin and metformin immediate-release were similar to those reported for patients treated with metformin immediate-release alone. See Table 2. Table 2: Pre-selected Gastrointestinal Adverse Reactions Reported in Patients with Type 2 Diabetes Mellitus Receiving Sitagliptin and Metformin Immediate-Release Number of Patients (%) Trial of Sitagliptin and Metformin Immediate-Release in Patients Inadequately Controlled on Diet and Exercise Trial of Sitagliptin Add-on in Patients Inadequately Controlled on Metformin Immediate-Release Alone Placebo Sitagliptin 100 mg once daily Metformin HCl Immediate-Release 500 mg or 1,000 mg twice daily Data pooled for the patients given the lower and higher doses of metformin. Sitagliptin 50 mg twice daily + Metformin HCl Immediate-Release 500 mg or 1,000 mg twice daily Placebo and Metformin HCL Immediate- Release ≥1,500 mg daily Sitagliptin 100 mg once daily and Metformin HCl Immediate- Release ≥1,500 mg daily N = 176 N = 179 N = 364 N = 372 N = 237 N = 464 Diarrhea 7 (4) 5 (2.8) 28 (7.7) 28 (7.5) 6 (2.5) 11 (2.4) Nausea 2 (1.1) 2 (1.1) 20 (5.5) 18 (4.8) 2 (0.8) 6 (1.3) Vomiting 1 (0.6) 0 (0) 2 (0.5) 8 (2.2) 2 (0.8) 5 (1.1) Abdominal Pain Abdominal discomfort was included in the analysis of abdominal pain in the trial of initial therapy. 4 (2.3) 6 (3.4) 14 (3.8) 11 (3) 9 (3.8) 10 (2.2) Sitagliptin in Combination with Metformin Immediate-Release and Glimepiride In a 24-week placebo-controlled trial of sitagliptin 100 mg as add-on therapy in patients with type 2 diabetes mellitus inadequately controlled on metformin immediate-release and glimepiride (sitagliptin, N=116; placebo, N=113), the adverse reactions reported in ≥ 5% of patients treated with sitagliptin and more commonly than in patients treated with placebo were: hypoglycemia (Table 3) and headache (6.9%, 2.7%). Sitagliptin in Combination with Metformin Immediate-Release and Rosiglitazone In a placebo-controlled trial of sitagliptin 100 mg as add-on therapy in patients with type 2 diabetes mellitus inadequately controlled on metformin immediate-release and rosiglitazone (sitagliptin, N=181; placebo, N=97), the adverse reactions reported through Week 18 in ≥ 5% of patients treated with sitagliptin and more commonly than in patients treated with placebo were: upper respiratory tract infection (sitagliptin, 5.5%; placebo, 5.2%) and nasopharyngitis (6.1%, 4.1%). Through Week 54, the adverse reactions reported in ≥ 5% of patients treated with sitagliptin and more commonly than in patients treated with placebo were: upper respiratory tract infection (sitagliptin, 15.5%; placebo, 6.2%), nasopharyngitis (11%, 9.3%), peripheral edema (8.3%, 5.2%), and headache (5.5%, 4.1%). Sitagliptin in Combination with Metformin Immediate-Release and Insulin In a 24-week placebo-controlled trial of sitagliptin 100 mg as add-on therapy in patients with type 2 diabetes mellitus inadequately controlled on metformin immediate-release and insulin (sitagliptin, N=229; placebo, N=233), the only adverse reaction reported regardless of investigator assessment of causality in ≥ 5% of patients treated with sitagliptin and more commonly than in patients treated with placebo was hypoglycemia (Table 3). Hypoglycemia In the above trials (N=5), adverse reactions of hypoglycemia were based on all reports of symptomatic hypoglycemia; a concurrent glucose measurement was not required although most (77%) reports of hypoglycemia were accompanied by a blood glucose measurement ≤70 mg/dL. When the combination of sitagliptin and metformin immediate-release was coadministered with a sulfonylurea or with insulin, the percentage of patients reporting at least one adverse reaction of hypoglycemia was higher than that observed with placebo and metformin immediate-release coadministered with a sulfonylurea or with insulin (Table 3). Table 3: Incidence and Rate of Hypoglycemia Adverse reactions of hypoglycemia were based on all reports of symptomatic hypoglycemia; a concurrent glucose measurement was not required: Intent-to-treat population. in Placebo-Controlled Clinical Trials of Sitagliptin in Combination with Metformin Immediate-Release Coadministered with Glimepiride or Insulin Add-On to Glimepiride + Metformin Immediate-Release (24 weeks) Sitagliptin 100 mg + Metformin Immediate-Release + Glimepiride Placebo + Metformin Immediate-Release + Glimepiride N = 116 N = 113 Overall (%) 19 (16.4) 1 (0.9) Rate (episodes/patient-year) Based on total number of events (i.e., a single patient may have had multiple events). 0.82 0.02 Severe (%) Severe events of hypoglycemia were defined as those events requiring medical assistance or exhibiting depressed level/loss of consciousness or seizure. 0 (0) 0 (0) Add-On to Insulin + Metformin Immediate-Release (24 weeks) Sitagliptin 100 mg + Metformin Immediate-Release + Insulin Placebo + Metformin Immediate-Release + Insulin N = 229 N = 233 Overall (%) 35 (15.3) 19 (8.2) Rate (episodes/patient-year) 0.98 0.61 Severe (%) 1 (0.4) 1 (0.4) The overall incidence of reported adverse reactions of hypoglycemia in patients with type 2 diabetes mellitus inadequately controlled on diet and exercise was 0.6% in patients given placebo, 0.6% in patients given sitagliptin alone, 0.8% in patients given metformin immediate-release alone, and 1.6% in patients given sitagliptin in combination with metformin immediate-release. In patients with type 2 diabetes mellitus inadequately controlled on metformin immediate-release alone, the overall incidence of adverse reactions of hypoglycemia was 1.3% in patients given add-on sitagliptin and 2.1% in patients given add-on placebo. In the trial of sitagliptin and add-on combination therapy with metformin immediate-release and rosiglitazone, the overall incidence of hypoglycemia was 2.2% in patients given add-on sitagliptin and 0% in patients given add-on placebo through Week 18. Through Week 54, the overall incidence of hypoglycemia was 3.9% in patients given add-on sitagliptin and 1% in patients given add-on placebo. In an additional 30-week placebo-controlled trial of patients with type 2 diabetes mellitus inadequately controlled with metformin comparing the maintenance of sitagliptin 100 mg versus withdrawal of sitagliptin when initiating basal insulin therapy, the event rate and incidence of documented symptomatic hypoglycemia (blood glucose measurement ≤70 mg/dL) did not differ between the sitagliptin and placebo groups. Vital Signs and Electrocardiograms With the combination of sitagliptin and metformin immediate-release, no clinically meaningful changes in vital signs or in electrocardiogram parameters (ECG) (including the QTc interval) were observed. Pancreatitis In a pooled analysis of 19 double-blind clinical trials that included data from 10,246 patients randomized to receive sitagliptin 100 mg/day (N=5,429) or corresponding (active or placebo) control (N=4,817), the incidence of acute pancreatitis was 0.1 per 100 patient-years in each group (4 patients with an event in 4,708 patient-years for sitagliptin and 4 patients with an event in 3,942 patient-years for control). Sitagliptin The most common adverse experience in sitagliptin monotherapy reported in ≥5% of patients and more commonly than in patients given placebo was nasopharyngitis. Metformin Extended-Release In a 24-week clinical trial in which extended-release metformin or placebo was added to glyburide therapy, the most common (>5% and greater than placebo) adverse reactions in the combined treatment group were hypoglycemia (13.7% vs. 4.9%), diarrhea (12.5% vs. 5.6%), and nausea (6.7% vs. 4.2%). Laboratory Tests Sitagliptin The incidence of laboratory adverse reactions was similar in patients treated with sitagliptin and metformin immediate-release (7.6%) compared to patients treated with placebo and metformin (8.7%). In most but not all trials, a small increase in white blood cell count (approximately 200 cells/microL difference in WBC vs. placebo; mean baseline WBC approximately 6,600 cells/microL) was observed due to a small increase in neutrophils. This change in laboratory parameters is not considered to be clinically relevant. Metformin In controlled clinical trials of metformin of 29-week duration, a decrease to subnormal levels of previously normal serum vitamin B 12 levels, without clinical manifestations, was observed in approximately 7% of patients. 6.2 Postmarketing Experience Additional adverse reactions have been identified during postapproval use of sitagliptin with metformin, sitagliptin, or metformin. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Skin and subcutaneous tissue disorders: hypersensitivity reactions including anaphylaxis, angioedema, rash, urticaria, cutaneous vasculitis, bullous pemphigoid, and exfoliative skin conditions including Stevens-Johnson syndrome Respiratory, thoracic and mediastinal disorders: upper respiratory tract infection Hepatobiliary disorders: hepatic enzyme elevations; cholestatic, hepatocellular, and mixed hepatocellular liver injury Gastrointestinal disorders: acute pancreatitis, including fatal and non-fatal hemorrhagic and necrotizing pancreatitis, constipation, vomiting, mouth ulceration, stomatitis Renal and urinary disorders : worsening renal function, including acute renal failure (sometimes requiring dialysis) and tubulointerstitial nephritis Musculoskeletal and connective tissue disorders: severe and disabling arthralgia, myalgia, pain in extremity, back pain, pruritus, rhabdomyolysis Nervous system disorders: headache.
Drug Interactions
7 DRUG INTERACTIONS Table 4 presents clinically significant drug interactions with ZITUVIMET XR: Table 4: Clinically Significant Drug Interactions with ZITUVIMET XR Carbonic Anhydrase Inhibitors Clinical Impact: Carbonic anhydrase inhibitors frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs with ZITUVIMET XR may increase the risk for lactic acidosis. Intervention: Consider more frequent monitoring of these patients. Examples: Topiramate, zonisamide, acetazolamide or dichlorphenamide. Drugs that Reduce Metformin Clearance Clinical Impact: Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transporter-2 [OCT 2 ] / multidrug and toxin extrusion [MATE] inhibitors) could increase systemic exposure to metformin and may increase the risk for lactic acidosis [see Clinical Pharmacology ( 12.3 )] . Intervention: Consider the benefits and risks of concomitant use with ZITUVIMET XR. Examples: Ranolazine, vandetanib, dolutegravir, and cimetidine. Alcohol Clinical Impact: Alcohol is known to potentiate the effect of metformin on lactate metabolism. Intervention: Warn patients against alcohol intake while receiving ZITUVIMET XR. Insulin Secretagogues or Insulin Clinical Impact: Coadministration of ZITUVIMET XR with an insulin secretagogue (e.g., sulfonylurea) or insulin may increase the risk of hypoglycemia. Intervention: Patients receiving an insulin secretagogue or insulin may require lower doses of the insulin secretagogue or insulin. Drugs Affecting Glycemic Control Clinical Impact: Certain drugs tend to produce hyperglycemia and may lead to loss of glycemic control. Intervention: When such drugs are administered to a patient receiving ZITUVIMET XR, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving ZITUVIMET XR, observe the patient closely for hypoglycemia. Examples: Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. Carbonic anhydrase inhibitors may increase risk of lactic acidosis. Consider more frequent monitoring. ( 7 ) Drugs that reduce metformin clearance (such as ranolazine, vandetanib, dolutegravir, and cimetidine) may increase the accumulation of metformin. Consider the benefits and risks of concomitant use. ( 7 ) Alcohol can potentiate the effect of metformin on lactate metabolism. Warn patients against excessive alcohol intake. ( 7 )
Additional information
Description
11 DESCRIPTION ZITUVIMET XR tablets for oral use contain two antihyperglycemic medications: sitagliptin and metformin hydrochloride. Sitagliptin Sitagliptin is an orally-active inhibitor of the DPP-4 enzyme. Sitagliptin free base drug substance is used to manufacture ZITUVIMET XR. Sitagliptin free base is described chemically as 7-[(3R)-3-amino-1-oxo-4-(2,4,5-trifluorophenyl)butyl]-5,6,7,8-tetrahydro-3-(trifluoromethyl)-1,2,4-triazolo[4,3-α]pyrazine with an empirical formula of C 16 H 15 F 6 N 5 O and a molecular weight of 407.31. The structural formula is: Sitagliptin free base is a white to off-white, non-hygroscopic powder. It is soluble in methanol and slightly soluble in water. Metformin HCl Metformin HCl ( N , N -dimethylimidodicarbonimidic diamide HCl) is a white crystalline powder with a molecular formula of C 4 H 11 N 5 •HCl and a molecular weight of 165.62. Metformin HCl is freely soluble in water, slightly soluble in ethanol (95%), practically insoluble in acetone and in methylene chloride. The pK a of metformin HCl is 12.4. The pH of a 1% aqueous solution of metformin HCl is 6.68. The structural formula is as shown: ZITUVIMET XR ZITUVIMET XR is available as film-coated tablets containing: 50 mg sitagliptin and 389.93 mg of metformin equivalent to 500 mg metformin HCl (ZITUVIMET XR 50/500). 50 mg sitagliptin and 779.86 mg of metformin equivalent to 1,000 mg metformin HCl (ZITUVIMET XR 50/1,000). 100 mg sitagliptin and 779.86 mg of metformin equivalent to 1,000 mg metformin HCl (ZITUVIMET XR 100/1,000). All doses of ZITUVIMET XR contain the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, dibasic calcium phosphate anhydrous, ferric oxide yellow, hypromellose, magnesium stearate, malic acid, microcrystalline cellulose, povidone, pregelatinized starch (maize) and sodium stearyl fumarate. In addition, the film-coating for all doses contains the following inactive ingredients: polyethylene glycol, polyvinyl alcohol-partially hydrolyzed, iron oxide yellow, talc and titanium dioxide. Additionally, ZITUVIMET XR 50 mg/500 mg and 100 mg/1,000 mg tablets film-coating contain the inactive ingredient red iron oxide and 50 mg/1,000 mg and 100 mg/1,000 mg tablets film-coating contain the FD&C yellow#6 Aluminum Lake. Image Image
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Tablets supplied as follows: Contents Description How Supplied NDC 50 mg sitagliptin and 500 mg metformin HCl extended-release tablets Light orange to beige colored, oval shaped, film-coated tablets debossed with "1804" on one side and plain on the other side. Bottles of 60 tablets with child-resistant closure NDC 70710-1804-6 50 mg sitagliptin and 1,000 mg metformin HCl extended-release tablets Yellow to beige colored, oval shaped, film-coated tablets debossed with "1805" on one side and plain on the other side. Bottles of 60 tablets with child-resistant closure NDC 70710-1805-6 100 mg sitagliptin and 1,000 mg metformin HCl extended-release tablets Reddish brown to brown colored, oval shaped, film-coated tablets debossed with "1806" on one side and plain on the other side. Bottles of 30 tablets with child-resistant closure NDC 70710-1806-3 Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Store in a dry place with cap tightly closed. Keep ZITUVIMET XR in the original container to protect it from moisture. Use ZITUVIMET XR within 1 month of opening the bottle.
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