Sitagliptin and Metformin Hydrochloride 50 mg; 1000 mg Tablet, Film Coated, 60-count — NDC 60505-3659-06 package photo

Sitagliptin and Metformin Hydrochloride 50 mg; 1000 mg Tablet, Film Coated, 60-count

by Apotex Corp. · 60 TABLET, FILM COATED in 1 BOTTLE (60505-3659-6)
NDC 60505-3659-06
🏷️ FDA NDC (as labeled) 60505-3659-6 billing pads the package segment with a zero
This package
Contains60-count Cost per ea$1.76 NADAC Per package$105.59 / 60 tablets Pack sizes2 compare ↓
Also comes in: 180 tablets 60505-3659-07
Rx only Generic On market Non-controlled
🗂️ Data synced Aug 27, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

🆔 Identity & classification

FDA NDC (as labeled) 60505-3659-6
Product NDC 60505-3659
11-digit billing NDC 60505365906
NCPDP billing unit EA — each (per item)
RxCUI 2709488, 2709491
UNII 786Z46389E, TS63EW8X6F
UPC 0360505365869, 0360505365968
Application # ANDA202426
SPL Set ID 950613e2-e959-6b57-e172-251ddc53c64c
Established class (EPC) Biguanide; Dipeptidyl Peptidase 4 Inhibitor
Mechanism of action Dipeptidyl Peptidase 4 Inhibitors
Chemical class Biguanides
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2026-05-28
Route ORAL
Dosage form TABLET, FILM COATED
Substance SITAGLIPTIN PHOSPHATE; METFORMIN HYDROCHLORIDE
GPI-14 27992502700340
GCN Seq No 062532
GCN 98307
HICL code 034665
Ingredient (HICL) Sitagliptin Phos/Metformin Hcl
HIC1 code C
Therapeutic class — broad (HIC1) Electrolyte Balance/Metabolism/Nutrition
HIC2 code C4
Therapeutic class — intermediate (HIC2) Antihyperglycemics
HIC3 code C4F
Therapeutic class — specific (HIC3) Antihyperglycemic,Dpp-4 Inhibitor-Biguanide Combs.
AHFS code 68:20.04.00
AHFS class Biguanides
FDB label name SITAGLIPTIN PHOS-METF 50-1,000
FDB brand name Sitagliptin Phos-Metformin
Legend status F — Federal legend — prescription drug or device
TE code (Orange Book) AB · RLD · RS
Why two NDCs? The FDA registers this code as 60505-3659-6 — a 5-4-1 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the package segment → 60505-3659-06. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

🏷️ RxNorm drug class

This medicine belongs to the Dipeptidyl Peptidase 4 Inhibitor class.

Pharmacologic class Dipeptidyl Peptidase 4 Inhibitor
Drug family (ATC) Dipeptidyl peptidase 4 (DPP-4) inhibitors
How it works Dipeptidyl Peptidase 4 Inhibitors
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

🏭 Manufacturer & labeler

LabelerApotex Corp.
Application holderAPOTEX INC
FDA applicationANDA202426 (ANDA)
Labeler code60505
First marketedMay 2026
Product typeHuman Prescription Drug
Portfolio306 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

Label name SITAGLIPTIN PHOS-METF 50-1,000 Ingredient Sitagliptin Phos/Metformin Hcl
📖 What it is MedlinePlus · NLM

Metformin is used alone or with other medications, including insulin, to treat type 2 diabetes (condition in which the body does not use insulin normally and, therefore, cannot control the amount of sugar in the blood). Metformin is in a class of drugs called biguanides. Metformin helps to control the amount of glucose (sugar) in your blood. It decreases the amount of glucose you absorb from your food and the amount of glucose made by your liver. Metformin also increases your body's response to insulin, a natural substance that controls the amount of glucose in the blood. Metformin is not used...

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • It's a two-in-one pill that tackles high blood sugar in two different ways. The sitagliptin part helps your body hold onto natural gut hormones that tell your pancreas to release m...
  • What exactly is this medication doing to help my blood sugar?
  • Diarrhea, nausea, and stomach discomfort are the most common complaints, especially in the first few weeks. Taking it with meals — not on an empty stomach — is the single most impo...
  • What stomach side effects should I expect when I start this medication?
📖 Read our full Metformin / Sitagliptin guide →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

💊 What it looks like

Color Pink / Red
ShapeOval
Imprint5;1
Size19 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

🧪 Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII M28OL1HH48
    Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
  • UNII 1K09F3G675
    Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
  • UNII RFW2ET671P
    Hydroxypropyl cellulose is a plant-derived thickening agent made from cellulose. It acts as a binder to hold tablet ingredients together and as a film-former to coat tablets or control how fast the medicine releases.
  • UNII R75537T0T4
    Hypromellose 2910 is a plant-derived thickening agent made from cellulose. It serves as a binder that holds tablet ingredients together, a film-coating for pills, and a viscosity controller in liquids.
  • UNII 70097M6I30
    Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
  • UNII PNR0YF693Y
    A plant-based powder made from purified wood cellulose. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in the stomach.
  • UNII Q662QK8M3B
    Polyethylene glycol 8000 is a synthetic polymer made from ethylene oxide. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and add bulk to the medicine.
  • UNII FZ989GH94E
    Povidone is a synthetic polymer made from a plastic-like material. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in your stomach so the medicine can be absorbed.
  • UNII 8D4SNN7V92
    Propyl gallate is a synthetic antioxidant derived from gallic acid. It prevents oils and fats in the medicine from oxidizing and spoiling, helping the product stay stable and effective during storage.
  • UNII 15FIX9V2JP
    Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.

10 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMedingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

💲 Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eaPer package
Retail pharmacies payNADAC · weekly $1.760 $105.59 / 60 tablets
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
NADAC price history (per ea) — tap or hover for the price & month
Aug 2026 $1.760 $1.760
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Sitagliptin and Metformin Hydrochloride 50 mg/1; 1000 mg 00781-5802-60 Sandoz 60 tablets $1.760 AB Availability likely
Sitagliptin and Metformin Hydrochloride 50 mg/1; 1000 mgthis 60505-3659-06 Apotex 60 tablets $1.760 AB Availability likely
Janumet 50 mg/1; 1000 mg 00006-0577-03 Merck 14 tablets AB FDA listed
Janumet 50 mg/1; 1000 mg 50090-5502-00 A-S 60 tablets AB FDA listed
Sitagliptin and Metformin Hydrochloride 50 mg/1; 1000 mg 84677-0053-18 Golden 180 tablets AB FDA listed
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2026
On the market since
May 2026
📍
2026
Currently FDA-listed
listed with the FDA
🔓
·
Generic on the market
this product is a generic
This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

🔬 Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Sitagliptin and Metformin Hydrochloride — the ingredient across all brands.

Top reported reactions

Blood Glucose Increased1,507
Diarrhoea1,385
Nausea1,101
Fatigue897
Acute Kidney Injury822
Vomiting771
Weight Decreased712

Age at onset

Neonate1
Infant1
Child2
Adolescent2
Adult1,177
Elderly1,293

Reporter sex

0 reports
Male · 50%
Female · 49%
Unknown · 1%

Serious outcomes

Hospitalization6,973
Death2,107
Life-threatening1,280
Disabling637
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 1,645 0
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDCDescription Per unit Per pack Marketing startStatus
60505-3659-06 You're viewing this 60 TABLET, FILM COATED in 1 BOTTLE (60505-3659-6) $1.76 / ea $105.59 2026-05-28 Active
60505-3659-07 180 TABLET, FILM COATED in 1 BOTTLE (60505-3659-7) $1.76 / ea $316.77 2026-05-28 Active

You're viewing the smallest of 2 pack sizes for this product.

This pack has the lowest per-ea cost of the 2 priced pack sizes ($1.76 NADAC).

Pack size FAQ

What quantity is in NDC 60505-3659-06?
NDC 60505-3659-06 is a 60-count package — 60 tablet, film coated in 1 bottle.
What is the difference between NDC 60505-3659-06 and NDC 60505-3659-07?
Both are Sitagliptin and Metformin Hydrochloride 50 mg; 1000 mg Tablet, Film Coated — the drug itself is identical. NDC 60505-3659-06 is the 60-count package, while NDC 60505-3659-07 is the 180 tablets package.
What NDC number is used to bill for this package of Sitagliptin and Metformin Hydrochloride 50 mg; 1000 mg Tablet, Film Coated?
Bill NDC 60505-3659-06 — the 11-digit billing format is 60505365906. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning ~2 min read

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 acidosis was characterized by elevated blood lactate levels (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio, and metformin plasma levels generally >5 mcg/mL [see Warnings and Precautions ( 5.1 )].

Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and hepatic impairment. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the full prescribing information [see Dosage and Administration ( 2.2 ), Contraindications (4), Warnings and Precautions (5.1), Drug Interactions (7), and Use in Specific Populations (8.6, 8.7)].

If metformin-associated lactic acidosis is suspected, immediately discontinue sitagliptin and metformin hydrochloride tablets and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended [see Warnings and Precautions ( 5.1 )]. WARNING: LACTIC ACIDOSIS See full prescribing information for complete boxed warning.

Postmarketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Symptoms included malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Laboratory abnormalities included elevated blood lactate levels, anion gap acidosis, increased lactate/pyruvate ratio, and metformin plasma levels generally >5 mcg/mL.

( 5.1 ) Risk factors include renal impairment, concomitant use of certain drugs, age ≥65 years old, radiological studies with contrast, surgery and other procedures, hypoxic states, excessive alcohol intake, and hepatic impairment. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high-risk groups are provided in the Full Prescribing Information. (5.1 ) If lactic acidosis is suspected, discontinue sitagliptin and metformin hydrochloride tablets and institute general supportive measures in a hospital setting.

Prompt hemodialysis is recommended. ( 5.1 )

🎯 Indications and Usage 179 words

1 INDICATIONS AND USAGE Sitagliptin and metformin hydrochloride tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use Sitagliptin and metformin hydrochloride tablets should not be used in patients with type 1 diabetes mellitus. Sitagliptin and metformin hydrochloride tablets have 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 sitagliptin and metformin hydrochloride tablets [see Warnings and Precautions (5.2)]. Sitagliptin and metformin hydrochloride tablets 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: Sitagliptin and metformin hydrochloride tablets should not be used in patients with type 1 diabetes.

( 1 ) Sitagliptin and metformin hydrochloride has not been studied in patients with a history of pancreatitis. ( 1 , 5.2 )

⏱️ Dosage and Administration ~3 min read

2 DOSAGE AND ADMINISTRATION Take sitagliptin and metformin hydrochloride tablets orally twice daily with meals. ( 2.1 ) Individualize the dosage of sitagliptin and metformin hydrochloride tablets 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.

( 2.1 ) The recommended starting dose in patients not currently treated with metformin is 50 mg sitagliptin and 500 mg metformin HCl twice 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 50 mg twice daily (100 mg total daily dose) and the dose of metformin already being taken. For patients taking metformin HCl 850 mg twice daily, the recommended starting dose of sitagliptin and metformin hydrochloride tablets is 50 mg sitagliptin and 1,000 mg metformin HCl twice daily.

( 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 . Sitagliptin and metformin hydrochloride tablets are not recommended in patients with eGFR between 30 and less than 45 mL/min/1.73 m 2 . Sitagliptin and metformin hydrochloride tablets may need to be discontinued at time of, or prior to, iodinated contrast imaging procedures.

( 2.3 )

2.1Recommended Dosing Take sitagliptin and metformin hydrochloride tablets orally twice daily with meals. Individualize the dosage of sitagliptin and metformin hydrochloride tablets 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).

Do not split or divide sitagliptin and metformin hydrochloride tablets. The recommended starting dose in patients not currently treated with metformin is 50 mg sitagliptin and 500 mg metformin HCl twice 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 sitagliptin dosed as 50 mg twice daily (100 mg total daily dose) and the dose of metformin already being taken.

For patients taking metformin HCl 850 mg twice daily, the recommended starting dose of sitagliptin and metformin hydrochloride tablets is 50 mg sitagliptin and 1,000 mg metformin HCl twice daily.

2.2Recommendations for Use in Renal Impairment Assess renal function prior to initiation of sitagliptin and metformin hydrochloride tablets and periodically thereafter. Sitagliptin and metformin hydrochloride tablets are 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 )]. Sitagliptin and metformin hydrochloride tablets are not recommended in patients with an eGFR between 30 and less than 45 mL/min/1.73 m 2 because these patients require a lower dosage of sitagliptin than what is available in the fixed combination sitagliptin and metformin hydrochloride tablets product.

2.3Discontinuation for Iodinated Contrast Imaging Procedures Discontinue sitagliptin and metformin hydrochloride tablets 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 sitagliptin and metformin hydrochloride tablets if renal function is stable [see Warnings and Precautions ( 5.1 )].

💊 Dosage Forms and Strengths 81 words

3 DOSAGE FORMS AND STRENGTHS Tablets: Sitagliptin 50 mg and metformin HCl 500 mg tablets are light pink, oval shaped, biconvex film-coated tablet. Engraved “5-5” on one side, plain on the other side. Sitagliptin 50 mg and metformin HCl 1,000 mg tablets are red, oval shaped, biconvex film-coated tablet.

Engraved “5-1” on one side, plain on the other side. Tablets: sitagliptin 50 mg and metformin HCL 500 mg tablets sitagliptin 50 mg and metformin HCL 1,000 mg tablets ( 3 )

Contraindications 109 words

4 CONTRAINDICATIONS Sitagliptin and metformin hydrochloride tablets are contraindicated in patients with: Severe renal impairment (eGFR below 30 mL/min/1.73m 2 [see Warnings and Precautions ( 5.1 )]. Acute or chronic metabolic acidosis, including diabetic ketoacidosis. History of a serious hypersensitivity reaction to sitagliptin and metformin hydrochloride tablets, sitagliptin, or metformin, such as anaphylaxis or angioedema [see Warnings and Precautions (5.7) ; Adverse Reactions (6.2].

Severe renal impairment: (eGFR below 30 mL/min/1.73m 2 ) ( 4 ) Metabolic acidosis, including diabetic ketoacidosis. ( 4 ) History of a serious hypersensitivity reaction to sitagliptin and metformin hydrochloride tablets, sitagliptin, or metformin such as anaphylaxis or angioedema. ( 5.7 , 6.2 )

⚠️ Warnings and Cautions ~2 min read

5 WARNINGS AND PRECAUTIONS Lactic Acidosis: See Boxed warning. ( 5.1 ) Pancreatitis: There have been postmarketing reports of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. If pancreatitis is suspected, promptly discontinue sitagliptin and metformin hydrochloride tablets.

( 5.2 ) Heart Failure: Has been observed with two other members of the DPP-4 inhibitor class. Consider risks and benefits of sitagliptin and metformin hydrochloride tablets in patients who have known risk factors for heart failure. Monitor patients for signs and symptoms.

( 5.3 ) Acute Renal Failure: Has been reported postmarketing, sometimes requiring dialysis. Before initiating sitagliptin and metformin hydrochloride tablets and at least annually thereafter, assess renal function. ( 5.4 ) Vitamin B 12 Deficiency : Metformin may lower vitamin B 12 levels.

Measure hematologic parameters annually and vitamin B 12 at 2 to 3 year intervals and manage any abnormalities. ( 5.5 ) Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues: Increased risk of hypoglycemia when used in combination with insulin and/or an insulin secretagogue. A lower dose of insulin or insulin secretagogue may be required.

( 5.6 ) Hypersensitivity Reactions: There have been postmarketing reports of serious allergic and hypersensitivity reactions in patients treated with sitagliptin such as anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. Promptly stop sitagliptin and metformin hydrochloride tablets, assess for other potential causes, institute appropriate monitoring and treatment. ( 5.7 ) Severe and Disabling Arthralgia: Has been reported in patients taking DPP-4 inhibitors.

Consider as a possible cause for severe joint pain and discontinue drug if appropriate. ( 5.8 ) Bullous Pemphigoid: There have been postmarketing reports requiring hospitalization in patients taking DPP-4 inhibitors. Tell patients to report development of blisters or erosions.

If bullous pemphigoid is suspected, discontinue sitagliptin and metformin hydrochloride tablets. ( 5.9 )

5.1Lactic Acidosis There have been postmarketing cases of metformin-associated lactic acidosis, including fatal cases. These cases had a subtle onset and were accompanied by nonspecific symptoms such as malaise, myalgias, abdominal pain, respiratory distress, or increased somnolence; however, hypothermia, hypotension and resistant bradyarrhythmias have occurred with severe acidosis. Metformin-associated lactic acidosis was characterized by elevated blood lactate concentrations (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate/pyruvate ratio; metformin plasma levels were generally >5 mcg/mL.

Metformin decreases liver uptake of lactate increasing lactate blood levels which may increase the risk of lactic acidosis, especially in patients at risk. If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, along with immediate discontinuation of sitagliptin and metformin hydrochloride tablets. In sitagliptin and metformin hydrochloride-treated patients with a diagnosis or strong suspicion of lactic acidosis, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin (metformin HCl is dialyzable, with a clearance of up to 170 mL/min under good hemodynamic conditions).

Hemodialysis has often resulted in reversal of symptoms and recovery. Educate patients and their families about the symptoms of lactic acidosis and if these symptoms occur instruct them to discontinue sitagliptin and metformin hydrochloride tablets and report these symptoms to their health care provider. For each of the known and possible risk factors for metformin-associated lactic acidosis, recommendations to reduce the risk of and manage metformin-associated lactic acidosis are provided below: Renal Impairment The po…

🤒 Adverse Reactions ~3 min read

6 ADVERSE REACTIONS The following adverse reactions are also discussed elsewhere in the labeling: 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 )] The most common adverse reactions reported in ≥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 Apotex Corp. at 1-800-706-5575 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical 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. Sitagliptin and Metformin Coadministration in Patients with Type 2 Diabetes Inadequately Controlled on Diet and Exercise Table 1 summarizes the most common (≥5% of patients) adverse reactions reported (regardless of investigator assessment of causality) in a 24-week placebo-controlled factorial study in which sitagliptin and metformin were coadministered to patients with type 2 diabetes inadequately controlled on diet and exercise.

Table 1: Sitagliptin and Metformin Coadministered to Patients with Type 2 Diabetes Inadequately Controlled on Diet and Exercise: Adverse Reactions Reported (Regardless of Investigator Assessment of Causality) in ≥5% of Patients Receiving Combination Therapy (and Greater than in Patients Receiving Placebo) * Number of Patients (%) Placebo Sitagliptin 100 mg once daily Metformin HCl 500 mg/ Metformin HCl 1,000 mg twice daily † Sitagliptin 50 mg twice daily + Metformin HCl 500 mg/ Metformin HCl 1,000 mg twice daily † N = 176 N = 179 N = 364 † N = 372 † * Intent-to-treat population. † Data pooled for the patients given the lower and higher doses of metformin.

Diarrhea 7 (4.0) 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 Inadequately Controlled on Metformin Alone In a 24-week placebo-controlled trial of sitagliptin 100 mg administered once daily added to a twice daily metformin regimen, there were no adverse reactions reported regardless of investigator assessment of causality 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, 1.9%; placebo and metformin, 2.5%). Gastrointestinal Adverse Reactions The incidences of pre-selected gastrointestinal adverse experiences in patients treated with sitagliptin and metformin were similar to those reported for patients treated with metformin alone. See Table 2.

Table 2: Pre-selected Gastrointestinal Adverse Reactions (Regardless of Investigator Assessment of Causality) Reported in Patients with Type 2 Diabetes Receiving Sitagliptin and Metformin Number of Patients (%) Study of Sitagliptin and Metformin in Patients Inadequately Controlled on Diet and Exercise Study of Sitagliptin Add-on in Patients Inadequately Controlled on Metformin Alone Placebo Sitagliptin 100 mg once daily Metformin HCl 500 mg/ Metformin HCl 1,000 mg twice daily * Sitagliptin 50 mg twice daily + Metformin HCl 500 mg/ Metformin HCl 1,000 mg twice daily * Placebo and Metformin…

🔄 Drug Interactions ~2 min read

7 DRUG INTERACTIONS Table 4 presents clinically significant drug interactions with sitagliptin and metformin hydrochloride tablets: Table 4: Clinically Significant Drug Interactions with Sitagliptin and Metformin Hydrochloride Tablets 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 sitagliptin and metformin hydrochloride tablets 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 sitagliptin and metformin hydrochloride tablets. 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 sitagliptin and metformin hydrochloride tablets. Insulin Secretagogues or Insulin Clinical Impact : Coadministration of sitagliptin and metformin hydrochloride tablets 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 sitagliptin and metformin hydrochloride tablets, observe the patient closely for loss of blood glucose control. When such drugs are withdrawn from a patient receiving sitagliptin and metformin hydrochloride tablets, 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 )

👥 Use in Specific Populations ~3 min read

8 USE IN SPECIFIC POPULATIONS Females and Males of Reproductive Potential: Advise premenopausal females of the potential for an unintended pregnancy. ( 8.3 ) Geriatric Use: Assess renal function more frequently. ( 8.5 ) Hepatic Impairment: Avoid use in patients with hepatic impairment. ( 8.7 )

8.1Pregnancy Risk Summary The limited available data with sitagliptin and metformin hydrochloride tablets in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage. Published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk [see Data]. 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. No adverse developmental effects were observed when metformin was administered to pregnant Sprague Dawley rats and rabbits during organogenesis at doses up to 2-and 6-times, respectively, a 2,000 mg clinical dose, based on body surface area [see Data]. The estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes with a Hemoglobin A1c >7% and has been reported to be as high as 20 to 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 Human Data Published data from post-marketing studies do not report a clear association with metformin and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin is used during pregnancy. However, these studies cannot definitely establish the absence of any risk because of methodological limitations, including small sample size and inconsistent comparator groups. Animal Data Sitagliptin and Metformin No animal reproduction studies were conducted with the coadministration of sitagliptin and metformin.

Sitagliptin In embryo-fetal development studies, 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 lactation day 21 caused no functional or behavioral toxicity in offspring of rats at doses up to 1,000 mg/kg. Metformin Metformin did not cause adverse developmental effects when administered to pregnant Sprague Dawley rats and rabbits up to 600 mg/kg/day during the period of organogenesis.

This represents an exposure of about 2-and 6-times a 2,000 mg clinical dose based on body surface area (mg/m 2 ) for rats and rabbits, respectively.

8.2Lactation Risk Summary There is no information regarding the presence of sitagliptin and metformin hydrochloride in human milk, the effects on the breastfed infant, or the effects on milk production. Limited published studies report that metformin is present in human milk [see Data].…

🤰 Pregnancy ~2 min read

8.1Pregnancy Risk Summary The limited available data with sitagliptin and metformin hydrochloride tablets in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage. Published studies with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk [see Data]. 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. No adverse developmental effects were observed when metformin was administered to pregnant Sprague Dawley rats and rabbits during organogenesis at doses up to 2-and 6-times, respectively, a 2,000 mg clinical dose, based on body surface area [see Data]. The estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes with a Hemoglobin A1c >7% and has been reported to be as high as 20 to 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 Human Data Published data from post-marketing studies do not report a clear association with metformin and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin is used during pregnancy. However, these studies cannot definitely establish the absence of any risk because of methodological limitations, including small sample size and inconsistent comparator groups. Animal Data Sitagliptin and Metformin No animal reproduction studies were conducted with the coadministration of sitagliptin and metformin.

Sitagliptin In embryo-fetal development studies, 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 lactation day 21 caused no functional or behavioral toxicity in offspring of rats at doses up to 1,000 mg/kg. Metformin Metformin did not cause adverse developmental effects when administered to pregnant Sprague Dawley rats and rabbits up to 600 mg/kg/day during the period of organogenesis.

This represents an exposure of about 2-and 6-times a 2,000 mg clinical dose based on body surface area (mg/m 2 ) for rats and rabbits, respectively.

🧒 Pediatric Use ~1 min read

8.4Pediatric Use The safety and effectiveness of sitagliptin and metformin hydrochloride tablets have not been established in pediatric patients. Three 20-week double-blind, placebo-controlled studies each with 34-week extensions were conducted to evaluate the efficacy and safety of sitagliptin in 410 pediatric patients aged 10 to 17 years with inadequately controlled type 2 diabetes, with or without insulin therapy (HbA1c 6.5 to 10% for patients not on insulin, HbA1c 7 to 10% for patients on insulin). At study entry, patients in study 1 were not treated with oral antihyperglycemic agents; patients in studies 2 and 3 were on maximally tolerated metformin therapy.

The primary efficacy endpoint was the change from baseline in HbA1c after 20 weeks of therapy. The pre-specified primary efficacy analyses included data from study 1 and pooled data from studies 2 and 3, regardless of glycemic rescue or treatment discontinuation. In both efficacy analyses, the effect of treatment with sitagliptin was not significantly different from placebo.

In study 1, the mean baseline HbA1c was 7.5%, and 12% of patients were on insulin therapy. At week 20, the change from baseline in HbA1c in patients treated with sitagliptin (N=95) was 0.06% compared to 0.23% in patients treated with placebo (N=95), a difference of -0.17% (95% CI: -0.62, 0.28). In studies 2 and 3, the mean baseline HbA1c was 8.0%, 15% of patients were on insulin and 72% were on metformin HCl doses of greater than 1,500 mg daily.

At week 20, the change from baseline in HbA1c in patients treated with sitagliptin (N=107) was -0.23% compared to 0.09% in patients treated with placebo (N=113), a difference of -0.33% (95% CI: -0.70, 0.05).

🧓 Geriatric Use 193 words

8.5Geriatric Use Sitagliptin and Metformin Hydrochloride In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of lactic acidosis. Renal function should be assessed more frequently in elderly patients [See Contraindications ( 4 ); Warnings and Precautions (5.1, 5.4); Clinical Pharmacology (12.3)] .

Sitagliptin Of the total number of subjects (N=3,884) in clinical studies of sitagliptin, 725 patients were 65 years and over, while 61 patients were 75 years and over. No overall differences in safety or effectiveness were observed between subjects 65 years and over and younger subjects. While this and other reported clinical experience have not identified differences in responses between the elderly and younger patients, greater sensitivity of some older individuals cannot be ruled out.

Metformin Controlled clinical studies of metformin did not include sufficient numbers of elderly patients to determine whether they respond differently from younger patients, although other reported clinical experience has not identified differences in responses between the elderly and young patients.

🆘 Overdosage 179 words

10 OVERDOSAGE In the event of overdose with sitagliptin and metformin hydrochloride tablets, contact the Poison Control Center. 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 indicated 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.

Overdose of metformin has occurred, including ingestion of amounts greater than 50 grams. Hypoglycemia was reported in approximately 10% of cases, but no causal association with metformin has been established. Lactic acidosis has been reported in approximately 32% of metformin overdose cases [see Warnings and Precautions ( 5.1 )].

Metformin is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom metformin overdosage is suspected.

🧬 Clinical Pharmacology ~3 min read

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Sitagliptin and Metformin hydrochloride Sitagliptin and metformin hydrochloride tablets combines two antihyperglycemic agents with complementary mechanisms of action to improve glycemic control in patients with type 2 diabetes mellitus: sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and metformin HCl, a member of the biguanide class. Sitagliptin Sitagliptin is a DPP-4 inhibitor, which is believed to exert 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.

By increasing and prolonging active incretin levels, sitagliptin increases insulin release and decreases glucagon levels in the circulation in a glucose-dependent manner. 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. Metformin Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes mellitus, lowering both basal and postprandial plasma glucose.

Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may decrease.

12.2Pharmacodynamics Sitagliptin In patients with type 2 diabetes mellitus, administration of sitagliptin led to inhibition of DPP-4 enzyme activity for a 24-hour period. After an oral glucose load or a meal, this DPP-4 inhibition resulted in a 2- to 3-fold increase in circulating levels of active GLP-1 and GIP, decreased glucagon concentrations, and increased responsiveness of insulin release to glucose, resulting in higher C-peptide and insulin concentrations. The rise in insulin with the decrease in glucagon was associated with lower fasting glucose concentrations and reduced glucose excursion following an oral glucose load or a meal.

In studies with healthy subjects, sitagliptin did not lower blood glucose or cause hypoglycemia. Sitagliptin and Metformin Coadministration In a two-day study in healthy subjects, sitagliptin alone increased active GLP-1 concentrations, whereas metformin alone increased active and total GLP-1 concentrations to similar extents. Coadministration of sitagliptin and metformin had an additive effect on active GLP-1 concentrations.

Sitagliptin, but not metformin, increased active GIP concentrations. It is unclear what these findings mean for changes in glycemic control in patients with type 2 diabetes mellitus. Cardiac Electrophysiology In a randomized, placebo-controlled crossover study, 79 healthy subjects were administered a single oral dose of sitagliptin 100 mg, sitagliptin 800-mg (8 times the recommended dose), and placebo.

At the recommended dose of 100 mg, there was no effect on the QTc interval obtained at the peak plasma concentration, or at any other time during the study. Following the 800 mg dose, the maximum increase in the placebo-corrected mean change in QTc from baseline at 3 hours postdose wa…

🧬 Mechanism of Action ~1 min read

12.1Mechanism of Action Sitagliptin and Metformin hydrochloride Sitagliptin and metformin hydrochloride tablets combines two antihyperglycemic agents with complementary mechanisms of action to improve glycemic control in patients with type 2 diabetes mellitus: sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and metformin HCl, a member of the biguanide class. Sitagliptin Sitagliptin is a DPP-4 inhibitor, which is believed to exert 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.

By increasing and prolonging active incretin levels, sitagliptin increases insulin release and decreases glucagon levels in the circulation in a glucose-dependent manner. 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. Metformin Metformin is an antihyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes mellitus, lowering both basal and postprandial plasma glucose.

Metformin decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may decrease.

📦 How Supplied / Storage and Handling 115 words

16 HOW SUPPLIED/STORAGE AND HANDLING Sitagliptin and Metformin Hydrochloride 50 mg/500 mg tablets are light pink, oval shaped, biconvex film-coated tablet. Engraved “5-5” on one side, plain on the other side. They are supplied as follows: Bottles of 60s (NDC 60505-3658-6) Bottles of 180s (NDC 60505-3658-7) Sitagliptin and Metformin Hydrochloride 50 mg/1,000 mg tablets are red, oval shaped, biconvex film-coated tablet.

Engraved “5-1” on one side, plain on the other side. They are supplied as follows: Bottles of 60s (NDC 60505-3659-6) Bottles of 180s (NDC 60505-3659-7) Store at 20° to 25°C (68° to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F), [see USP Controlled Room Temperature]. Dispense in a tight container [see USP].

📋 Description ~1 min read

11 DESCRIPTION Sitagliptin and metformin hydrochloride tablets for oral use contain two antihyperglycemic drugs: sitagliptin and metformin HCl. Sitagliptin Sitagliptin is an orally-active inhibitor of the dipeptidyl peptidase-4 (DPP-4) enzyme. Sitagliptin is present in sitagliptin and metformin hydrochloride tablets in the form of sitagliptin phosphate monohydrate.

Sitagliptin phosphate monohydrate is described chemically as 7-[( R )-3-Amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,2,4-triazolo[4,3- a ]pyrazine monophosphate monohydrate with a molecular formula of C 16 H 15 F 6 N 5 O•H 3 PO 4 •H 2 O and a molecular weight of 523.32. The structural formula is: Sitagliptin phosphate monohydrate is a white or almost white, crystalline, non-hygroscopic powder. It is soluble in water, very slightly soluble in anhydrous ethanol and practically insoluble in heptane.

Metformin HCl Metformin HCl (N,N-dimethylimidodicarbonimidic diamide hydrochloride) is not chemically or pharmacologically related to any other classes of oral antihyperglycemic agents. Metformin HCl is a white or almost white 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 alcohol, and is practically insoluble in acetone and methylene chloride.

The pK a of metformin is 12.4. The pH of a 1% aqueous solution of metformin HCl is 6.68. The structural formula is as shown: Sitagliptin and Metformin Hydrochloride Tablets Sitagliptin and metformin hydrochloride tablets are available as film-coated tablets containing: 64.25 mg sitagliptin monohydrate equivalent to 50 mg of sitagliptin and 500 mg metformin HCl (Sitagliptin and metformin hydrochloride tablets 50/500).

64.25mg sitagliptin monohydrate equivalent to 50 mg of sitagliptin and 1,000 mg metformin HCl (Sitagliptin and metformin hydrochloride tablets 50/1,000). Each film-coated tablet of sitagliptin and metformin hydrochloride tablets contains the following inactive ingredients: croscarmellose sodium, ferric oxide red, hydroxypropyl cellulose, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone, propyl gallate, and titanium dioxide.

💬 Information for Patients ~3 min read

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Lactic Acidosis Explain the risks of lactic acidosis, its symptoms, and conditions that predispose to its development. Advise patients to discontinue sitagliptin and metformin hydrochloride tablets immediately and to promptly notify their healthcare provider if unexplained hyperventilation, myalgias, malaise, unusual somnolence or other nonspecific symptoms occur.

Counsel patients against excessive alcohol intake and inform patients about the importance of regular testing of renal function while receiving sitagliptin and metformin hydrochloride tablets. Instruct patients to inform their doctor that they are taking sitagliptin and metformin hydrochloride tablets prior to any surgical or radiological procedure, as temporary discontinuation may be required [see Warnings and Precautions (5.1)]. Pancreatitis Inform patients that acute pancreatitis has been reported during postmarketing use of sitagliptin and metformin hydrochloride tablets.

Inform patients that persistent severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting, is the hallmark symptom of acute pancreatitis. Instruct patients to promptly discontinue sitagliptin and metformin hydrochloride tablets and contact their physician if persistent severe abdominal pain occurs [see Warnings and Precautions (5.2)]. Heart Failure Inform patients of the signs and symptoms of heart failure.

Before initiating sitagliptin and metformin hydrochloride tablets, ask patients about a history of heart failure or other risk factors for heart failure including moderate to severe renal impairment. Instruct patients to contact their health care provider as soon as possible if they experience symptoms of heart failure, including increasing shortness of breath, rapid increase in weight or swelling of the feet [see Warnings and Precautions (5.3)]. Vitamin B 12 Deficiency Inform patients about the importance of regular monitoring of hematological parameters while receiving sitagliptin and metformin hydrochloride tablets [see Warnings and Precautions (5.5)].

Hypoglycemia Inform patients that the incidence of hypoglycemia is increased when sitagliptin and metformin hydrochloride tablets are added to an insulin secretagogue (e.g., sulfonylurea) or insulin therapy. Explain to patients receiving sitagliptin and metformin hydrochloride tablets in combination with these medications the risks of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development [see Warnings and Precautions (5.6)]. Hypersensitivity Reactions Inform patients that allergic reactions have been reported during postmarketing use of sitagliptin, one of the components of sitagliptin and metformin hydrochloride tablets.

If symptoms of allergic reactions (including rash, hives, and swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or swallowing) occur, patients must stop taking sitagliptin and metformin hydrochloride tablets and seek medical advice promptly. Severe and Disabling Arthralgia Inform patients that severe and disabling joint pain may occur with this class of drugs. The time to onset of symptoms can range from one day to years.

Instruct patients to seek medical advice if severe joint pain occurs [see Warnings and Precautions (5.8)]. Bullous Pemphigoid Inform patients that bullous pemphigoid may occur with this class of drugs. Instruct patients to seek medical advice if blisters or erosions occur [see Warnings and Precautions (5.9)].

Females of Reproductive Age: Inform females that treatment with sitagliptin and metformin hydrochloride tablets may result in ovulation in some premenopausal anovulatory women which may lead to unintended pregnancy [see Use in Specific Populations (8.3)]. Administration Instructions Inform patients that the tablets must never be split or divided before swallowing. All re…

💬 Medication Guide ~3 min read

Medication Guide Sitagliptin and Metformin Hydrochloride (sit-a-glip-tin and met-for-min hye-droe-klor-ide) Tablets, for oral use Read this Medication Guide carefully before you start taking sitagliptin and metformin hydrochloride tablets and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment.

If you have any questions about sitagliptin and metformin hydrochloride tablets, ask your doctor or pharmacist. What is the most important information I should know about sitagliptin and metformin hydrochloride tablets? Sitagliptin and metformin hydrochloride tablets can cause serious side effects, including: 1.

Lactic Acidosis. Metformin, one of the medicines in sitagliptin and metformin hydrochloride tablets, can cause a rare but serious condition called lactic acidosis (a buildup of an acid in the blood) that can cause death. Lactic acidosis is a medical emergency and must be treated in the hospital.

Stop taking sitagliptin and metformin hydrochloride tablets and call your doctor right away if you have any of the following symptoms, which could be signs of lactic acidosis: you feel cold in your hands or feet you feel dizzy or lightheaded you have a slow or irregular heartbeat you feel very weak or tired you have unusual (not normal) muscle pain you have trouble breathing you feel sleepy or drowsy you have stomach pains, nausea or vomiting Most people who have had lactic acidosis with metformin have other things that, combined with the metformin, led to the lactic acidosis.

Tell your doctor if you have any of the following, because you have a higher chance for getting lactic acidosis with sitagliptin and metformin hydrochloride tablets if you: have severe kidney problems or your kidneys are affected by certain x-ray tests that use injectable dye have liver problems drink alcohol very often, or drink a lot of alcohol in short-term "binge" drinking get dehydrated (lose a large amount of body fluids). This can happen if you are sick with a fever, vomiting, or diarrhea. Dehydration can also happen when you sweat a lot with activity or exercise and do not drink enough fluids. have surgery have a heart attack, severe infection, or stroke are 65 years of age or older The best way to keep from having a problem with lactic acidosis from metformin is to tell your doctor if you have any of the problems in the list above.

Your doctor may decide to stop your sitagliptin and metformin hydrochloride tablets for a while if you have any of these things. Sitagliptin and metformin hydrochloride tablets can have other serious side effects. See “ What are the possible side effects of sitagliptin and metformin hydrochloride tablets? ” 2.

Pancreatitis (inflammation of the pancreas) which may be severe and lead to death. Certain medical problems make you more likely to get pancreatitis. Before you start taking sitagliptin and metformin hydrochloride tablets, tell your doctor if you have ever had: pancreatitis stones in your gallbladder (gallstones) a history of alcoholism high blood triglyceride levels Stop taking sitagliptin and metformin hydrochloride tablets and call your doctor right away if you have pain in your stomach area (abdomen) that is severe and will not go away.

The pain may be felt going from your abdomen through to your back. The pain may happen with or without vomiting. These may be symptoms of pancreatitis.

3 . Heart failure . Heart failure means that your heart does not pump blood well enough.

Before you start taking sitagliptin and metformin hydrochloride tablets, tell your doctor if you have ever had heart failure or have problems with your kidneys. Contact your doctor right away if you have any of the following symptoms: increasing shortness of breath or trouble breathing, especially when you lie down swelling or fluid retention, especially in the feet, ankles or legs an unusually fast increase in weight unusual tire…

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
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