Home › NDC Lookup › Ingredients › Alogliptin And Metformin Hydrochloride › 50090-5993-00
alogliptin and metformin hydrochloride 12.5 mg; 1000 mg Tablet, Film Coated, 90-count — NDC 50090-5993-00 package photo

alogliptin and metformin hydrochloride 12.5 mg; 1000 mg Tablet, Film Coated, 90-count

by A-S Medication Solutions · 90 TABLET, FILM COATED in 1 BOTTLE (50090-5993-0)
NDC 50090-5993-00
🏷️ FDA NDC (as labeled) 50090-5993-0 billing pads the package segment with a zero
Rx only Brand On market Non-controlled
🗂️ Data synced Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

🆔 Identity & classification

FDA NDC (as labeled) 50090-5993-0
Product NDC 50090-5993
11-digit billing NDC 50090599300
NCPDP billing unit EA — each (per item)
RxCUI 1368385
UNII EEN99869SC, 786Z46389E
Application # NDA203414
SPL Set ID 9112d6b9-4771-4194-886d-7db887470bcc
Established class (EPC) Biguanide; Dipeptidyl Peptidase 4 Inhibitor
Mechanism of action Dipeptidyl Peptidase 4 Inhibitors
Chemical class Biguanides
DEA schedule Non-controlled
Marketing category NDA AUTHORIZED GENERIC
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2016-04-08
Route ORAL
Dosage form TABLET, FILM COATED
Substance ALOGLIPTIN BENZOATE; METFORMIN HYDROCHLORIDE
GPI-14 27992502100330
GPI class Alogliptin-metFORMIN HCl
GCN Seq No 070527
GCN 34088
HICL code 039970
Ingredient (HICL) Alogliptin Benz/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 ALOGLIPTIN-METFORMIN 12.5-1000
FDB brand name Alogliptin-Metformin
Legend status F — Federal legend — prescription drug or device
Why two NDCs? The FDA registers this code as 50090-5993-0 — 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 → 50090-5993-00. 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

LabelerA-S Medication Solutions
Application holderTAKEDA PHARMACEUTICALS USA INC
FDA applicationNDA203414 (NDA AUTHORIZED GENERIC)
Labeler code50090
First marketedApr 2016
Product typeHuman Prescription Drug
Portfolio2,781 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 ALOGLIPTIN-METFORMIN 12.5-1000 Ingredient Alogliptin Benz/Metformin Hcl

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
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 Yellow
ShapeOval
Imprint12;5;1000;322M
Size22 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 68401960MK
    Crospovidone is a synthetic polymer made from polyvinylpyrrolidone. It acts as a disintegrant, helping tablets break apart quickly in the stomach so the medicine dissolves and absorbs into the body.
  • UNII EX438O2MRT
    Ferric oxide yellow is a naturally occurring iron compound used as a colorant in medications. It gives tablets, capsules, and other forms a yellow or golden hue for identification and appearance.
  • UNII 0WZ8WG20P6
    Hypromellose 2910 is a plant-based cellulose derivative that acts as a thickener, binder, and film-coating agent. It helps control how quickly the medicine dissolves and protects the tablet or capsule from moisture and light.
  • 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 3OWL53L36A
    A natural sugar alcohol derived from seaweed or synthesized in the lab. It's used as a filler to add bulk, a sweetener in sugar-free formulas, and a disintegrant to help tablets break apart in the stomach.
  • UNII OP1R32D61U
    Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
  • 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 7SEV7J4R1U
    A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
  • 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.

9 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 DailyMed — ingredient 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 eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
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 · Q2 2026 $2.95 $265.63 / 90 tablets
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
alogliptin and metformin hydrochloride 12.5 mg/1; 1000 mg 45802-0211-72 Padagis 60 tablets $2.494 — Availability likely —
alogliptin and metformin hydrochloride 12.5 mg/1; 1000 mgthis 50090-5993-00 A-S 90 tablets — — FDA listed —
Kazano 12.5 mg/1; 1000 mg 64764-0337-01 Takeda 14 tablets — — FDA listed —
About this product: this is an authorized generic — the brand-name product marketed without its brand name. 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

🏛️
2013
First FDA approval
Jan 2013
📍
2026
Currently FDA-listed
13 years listed
🛡️
2029
Latest patent/protection listed
not a guaranteed launch date
🔒No FDA-approved generic found

We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through May 2029. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Jan 25, 2013 RLD RS ⏳ ~2.7 yr to latest listed protection

Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.

Patents & exclusivity — FDA Orange Book
US 7807689 — drug substance (U-1337)
US 7807689 — drug substance (U-1337)
US 8900638 — drug product
US 8900638 — drug product
Exclusivity M-300
Exclusivity M-300
2013 2015 2017 2019 2021 2023 2025 2027 2029
Today
LOE
Substance patent Formulation patent Method-of-use patent Exclusivity Pediatric +6mo
🏛️FDA exclusivity
FDA-granted marketing protection. It’s separate from patents and may be shorter than patent protection.
🧪Product / substance patents
Patents covering the active ingredient, product, formulation, or related drug features.
🎯Method-of-use patents
Patents covering specific approved uses. These can sometimes be carved out with a “skinny label,” but not always.
🛈 What do these terms mean?
Patent
Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
Substance patent
Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
Formulation (product) patent
Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
Method-of-use patent
A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
Skinny label
A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
Exclusivity
FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
Paragraph IV
A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
RLD / RS
Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
TE / AB rating
FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
LOE (loss of exclusivity)
The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.

Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.

Listed patents (4)
PatentTypeUse codeExpires
US 7807689 ↗ Drug substance U-1337 Jun 27, 2028
US 7807689 ↗ Drug substance U-1337 Jun 27, 2028
US 8900638 ↗ Drug product — May 24, 2029
US 8900638 ↗ Drug product — May 24, 2029
FDA exclusivity
CodeWhat it grantsExpires
M-300New indication / labeling change (3-year)Jul 27, 2026
M-300New indication / labeling change (3-year)Jul 27, 2026
Common questions
Is there a generic version of ALOGLIPTIN-METFORMIN 12.5-1000?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for ALOGLIPTIN-METFORMIN 12.5-1000. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until May 2029 — an estimate, not a guaranteed launch date.
The FDA approved a generic — why can’t I get it at my pharmacy yet?
FDA approval and pharmacy availability are two different things. The FDA can approve a generic years before it actually reaches pharmacies, because the brand company may still hold patents or have a settlement that delays the launch. A manufacturer also has to choose to make and sell it, and have supply ready. So a drug can be “FDA-approved generic exists” and still be brand-only at the counter today.
Why do different websites show different generic release dates?
Generic availability is not based on one single date. Some sources use the first exclusivity expiration, some use the last product patent, and others use the latest method-of-use patent. Patent challenges, settlements, licenses, and label carve-outs can also change the real-world launch date. This page shows the underlying Orange Book dates so you can see why estimates may differ.
What does “FDA listed” mean?
It means the product appears in the FDA’s official NDC directory. That’s a good sign a product exists and is intended for the U.S. market, but on its own it does not confirm a pharmacy can fill it today. Where we have recent retail pricing data (NADAC) for a product, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Orange Book for a patent or exclusivity on the brand product. It can affect when a full generic version becomes widely available — but it is not a guaranteed generic launch date. Generics sometimes arrive earlier (through a settlement or patent challenge) or later (a manufacturer still has to make and sell one).
What does “current Orange Book estimate” mean?
It means we are using the latest patent and exclusivity dates currently listed in the FDA Orange Book. It is not a guaranteed launch date.
Can a generic come out before the last patent expires?
Sometimes. A generic company may challenge a patent, settle with the brand manufacturer, receive a license, or obtain approval with a narrower label that avoids a patented use. In other cases, the last listed protection may delay full-label generic competition.
Can a generic come out after the listed dates?
Yes. Even after patents or exclusivity expire, a generic still needs FDA approval and a manufacturer must choose to market it. Supply, litigation, business decisions, or regulatory issues can delay actual availability.
What is the difference between patents and exclusivity?
Patents are legal protections usually issued by the U.S. Patent and Trademark Office. FDA exclusivity is marketing protection granted by the FDA. They are separate, and either one can affect generic timing.
Why are there multiple patent dates?
One drug can have several patents covering different things: the active ingredient, a formulation, a manufacturing process, or a specific approved use. That is why a page may show several expiration dates instead of one simple generic date.
Built from FDA Orange Book patent and exclusivity data. Dates are refreshed from public FDA data when available; the marker is max(latest patent expiry, latest exclusivity expiry). Paragraph-IV settlements and first-filer 180-day exclusivity can shift the real date; a method-of-use patent may allow an earlier skinny-label generic for non-protected indications. Generic launch timing is an estimate, not a guarantee.
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 Alogliptin and metformin hydrochloride — the ingredient across all brands.

Top reported reactions

Arteriosclerosis2
Diarrhoea2
Nausea2
Rash2
Atrial Fibrillation1
Back Pain1
Blood Testosterone Abnormal1

Age at onset

Adult1
Elderly5

Reporter sex

13 reports
Male · 54%
Female · 46%

Serious outcomes

Hospitalization3
Life-threatening1
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 4 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 Marketing startStatus
50090-5993-00 You're viewing this 90 TABLET, FILM COATED in 1 BOTTLE (50090-5993-0) 2022-06-10 Active

🧭 About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The FDA registers it as 50090-5993-0, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 50090-5993-00, written without dashes as 50090599300. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 50090-5993-00, the first segment (50090) is the labeler code FDA assigned to A-S Medication Solutions; the middle segment (5993) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (00) identifies this exact package size and type. Together they name one specific package of one specific product.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by A-S Medication Solutions. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
A-S Medication Solutions is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.

📄 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 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide
🚨 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 (greater than 5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally greater than 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 alogliptin and metformin HCl 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 greater than 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 alogliptin and metformin HCl tablets and institute general supportive measures in a hospital setting.

Prompt hemodialysis is recommended. ( 5.1 )

🎯 Indications and Usage 105 words ▾

1 INDICATIONS AND USAGE Alogliptin and metformin HCl tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Alogliptin and metformin HCl tablets are a combination of alogliptin, a dipeptidyl-peptidase-4 (DPP-4) inhibitor and metformin, 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: Should not be used in patients with type 1 diabetes mellitus.

( 1 ) Limitations of Use Alogliptin and metformin HCl tablets should not be used in patients with type 1 diabetes mellitus.

⏱️ Dosage and Administration ~2 min read ▾

2 DOSAGE AND ADMINISTRATION Individualize the starting dose based on the patient's current regimen. ( 2.1 ) Give twice daily with food. ( 2.1 ) Adjust the dosing based on effectiveness and tolerability while not exceeding the maximum recommended daily dose of 25 mg alogliptin and 2000 mg metformin HCl.

( 2.1 ) Prior to initiation, assess renal function with estimated glomerular filtration rate (eGFR). ( 2.2 ) Do not use in patients with eGFR below 60 mL/min/1.73 m 2 . Alogliptin and metformin HCl tablets may need to be discontinued at time of, or prior to, iodinated contrast imaging procedures.

( 2.3 )

2.1Recommendations for All Patients Healthcare providers should individualize the starting dose of alogliptin and metformin HCl tablets based on the patient's current regimen. Alogliptin and metformin HCl tablets should be taken twice daily with food with gradual dose escalation to reduce the gastrointestinal (GI) side effects due to metformin. Do not split tablets.

Dosing may be adjusted based on effectiveness and tolerability while not exceeding the maximum recommended daily dose of 25 mg alogliptin and 2000 mg metformin hydrochloride (HCl). The following doses are available: 12.5 mg alogliptin and 500 mg metformin HCl 12.5 mg alogliptin and 1000 mg metformin HCl

2.2Recommendations for Use in Renal Impairment Assess renal function prior to initiation of alogliptin and metformin HCl tablets and periodically thereafter. Alogliptin and metformin HCl tablets 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) ] . Alogliptin and metformin HCl tablets are not recommended in patients with an eGFR between 30 and 59 mL/min/1.73 m 2 because these patients require a lower daily dosage of alogliptin than what is available in the fixed combination alogliptin and metformin HCl tablets product.

Alogliptin and metformin HCl tablets require no dose adjustment in patients with an eGFR of 60 mL/min/1.73 m 2 or greater.

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

💊 Dosage Forms and Strengths 71 words ▾

3 DOSAGE FORMS AND STRENGTHS 12.5 mg/500 mg tablets are pale yellow, oblong, film-coated tablets with "12.5/500" debossed on one side and "322M" debossed on the other side 12.5 mg/1000 mg tablets are pale yellow, oblong, film-coated tablets with "12.5/1000" debossed on one side and "322M" debossed on the other side Tablets: 12.5 mg alogliptin and 500 mg metformin HCl, 12.5 mg alogliptin and 1000 mg metformin HCl. ( 3 )

⛔ Contraindications 111 words ▾

4 CONTRAINDICATIONS Alogliptin and metformin HCl tablets are 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 with or without coma. Serious hypersensitivity reaction to alogliptin or metformin or any of the exciptients, such as anaphylaxis, angioedema and severe cutaneous adverse reactions [see Warnings and Precautions (5.4) , 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 alogliptin or metformin or any of the excipients.

( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Lactic acidosis: See boxed warning. ( 5.1 ) Pancreatitis: There have been postmarketing reports of acute pancreatitis. If pancreatitis is suspected, promptly discontinue alogliptin and metformin HCl tablets.

( 5.2 ) Heart failure: Consider the risks and benefits of alogliptin and metformin HCl tablets prior to initiating treatment in patients at risk for heart failure. If heart failure develops, evaluate and manage according to current standards of care and consider discontinuation of alogliptin and metformin HCl tablets. ( 5.3 ) Hypersensitivity: There have been postmarketing reports of serious hypersensitivity reactions in patients treated with alogliptin such as anaphylaxis, angioedema and severe cutaneous adverse reactions, including Stevens-Johnson syndrome.

In such cases, promptly discontinue alogliptin and metformin HCl tablets, assess for other potential causes, institute appropriate monitoring and treatment and initiate alternative treatment for diabetes. ( 5.4 ) Hepatic effects: Postmarketing reports of hepatic failure, sometimes fatal. Causality cannot be excluded.

If liver injury is detected, promptly interrupt alogliptin and metformin HCl tablets and assess patient for probable cause, then treat cause if possible, to resolution or stabilization. Do not restart alogliptin and metformin HCl tablets if liver injury is confirmed and no alternative etiology can be found. ( 5.5 ) Vitamin B 12 deficiency: Metformin may lower vitamin B 12 levels.

Measure hematologic parameters annually and B 12 at 2 to 3 year intervals and manage any abnormalties. ( 5.6 ) Hypoglycemia with Concomitant Use with Insulin or Insulin Secretaqoques: When used with an insulin secretagogue (e.g., sulfonylurea) or with insulin, a lower dose of the insulin secretagogue or insulin may be required to reduce the risk of hypoglycemia. ( 5.7 ) Arthralgia: 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 of bullous pemphigoid requiring hospitalization in patients taking DPP-4 inhibitors. Tell patients to report development of blisters or erosions.

If bullous pemphigoid is suspected, discontinue alogliptin and metformin HCl tablets. ( 5.9 )

5.1Lactic Acidosis Lactic 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 (greater than 5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate:pyruvate ratio; metformin plasma levels generally greater than 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 alogliptin and metformin HCl tablets. In alogliptin and metformin HCl tablets-treated patients with a diagnosis or strong suspicion of lactic acidosis, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin (metformin hydrochloride 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 alogliptin and metformin HCl tablets and report these s…

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following serious adverse reactions are described below or elsewhere in the prescribing information: Pancreatitis [see Warnings and Precautions (5.2) ] Heart Failure [see Warnings and Precautions (5.3) ] Hypersensitivity Reactions [see Warnings and Precautions (5.4) ] Hepatic Effects [see Warnings and Precautions (5.5) ] Severe and Disabling Arthralgia [see Warnings and Precautions (5.8) ] Bullous Pemphigoid [see Warnings and Precautions (5.9) ] The most common adverse reactions (4% or greater incidence) are upper respiratory tract infection, nasopharyngitis, diarrhea, hypertension, headache, back pain and urinary tract infection.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-877-TAKEDA-7 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. Alogliptin and Metformin Hydrochloride Over 2700 patients with type 2 diabetes have received alogliptin coadministered with metformin in four large, randomized, double-blind controlled clinical trials. The mean exposure to alogliptin and metformin HCl tablets was 58 weeks, with more than 1400 subjects treated for more than one year.

These included two 26 week placebo-controlled studies, one 52 week active control study and an interim analysis of a 104 week active-controlled study. In the alogliptin and metformin HCl tablets arm, the mean duration of diabetes was approximately six years, the mean body mass index (BMI) was 31 kg/m 2 (56% of patients had a BMI ≥30 kg/m 2 ) and the mean age was 55 years (18% of patients ≥65 years of age). In a pooled analysis of these four controlled clinical studies, the overall incidence of adverse reactions was 74% in patients treated with alogliptin and metformin HCl tablets compared to 75% treated with placebo.

Overall discontinuation of therapy due to adverse reactions was 6.2% with alogliptin and metformin HCl tablets compared to 1.9% in placebo, 6.4% in metformin and 5.0% in alogliptin. Adverse reactions reported in ≥4% of patients treated with alogliptin and metformin HCl tablets and more frequently than in patients who received alogliptin, metformin or placebo are summarized in Table 1. Table 1.

Adverse Reactions Reported in ≥4% of Patients Treated with Alogliptin and Metformin HCl Tablets and More Frequently Than in Patients Receiving Either Alogliptin, Metformin or Placebo Number of Patients (%) Alogliptin and Metformin HCl Tablets Alogliptin and metformin HCl tablets – includes data pooled for patients receiving alogliptin 25 and 12.5 mg combined with various dose of metformin Alogliptin Alogliptin – includes data pooled for patients receiving alogliptin 25 and 12.5 mg Metformin Metformin – includes data pooled for patients receiving various doses of metformin Placebo N=2794 N=222 N=1592 N=106 Upper respiratory tract infection 224 (8.0) 6 (2.7) 105 (6.6) 3 (2.8) Nasopharyngitis 191 (6.8) 7 (3.2) 93 (5.8) 2 (1.9) Diarrhea 155 (5.5) 4 (1.8) 105 (6.6) 3 (2.8) Hypertension 154 (5.5) 5 (2.3) 96 (6.0) 6 (5.7) Headache 149 (5.3) 11 (5.0) 74 (4.6) 3 (2.8) Back pain 119 (4.3) 1 (0.5) 72 (4.5) 1 (0.9) Urinary tract infection 116 (4.2) 4 (1.8) 59 (3.7) 2 (1.9) Hypoglycemia In a 26 week, double-blind, placebo-controlled study of alogliptin in combination with metformin, the number of patients reporting hypoglycemia was 1.9% in the alogliptin 12.5 mg with metformin HCl 500 mg, 5.3% in the alogliptin 12.5 mg with metformin HCl 1000 mg, 1.8% in the metformin HCl 500 mg and 6.3% in the metformin HCl 1000 mg treatment groups.

In a 26 week placebo-controlled study of alogliptin 25 mg administered once daily as add-on to metformin regimen, the number of patients reporting hypoglycemic events was 0% in the alogliptin with…

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Carbionic 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 ) Metformin Hydrochloride 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 ALOGLIPTIN WITH METFORMIN HYDROCHLORIDE TABLETS may increase the risk of 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 [OCT2]/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.

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 excessive alcohol intake while receiving ALOGLIPTIN WITH METFORMIN HYDROCHLORIDE TABLETS. Insulin Secretagogues and Insulin Clinical Impact: Coadministration of ALOGLIPTIN WITH METFORMIN HYDROCHLORIDE TABLETS with an insulin secretagogue (e.g., sulfonylurea) or with insulin may increase the risk of hypoglycemia.

Intervention: Patients may require a lower dose 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 ALOGLIPTIN WITH METFORMIN HYDROCHLORIDE TABLETS, the patient should be closely observed for loss of blood glucose control.

When such drugs are withdrawn from a patient receiving ALOGLIPTIN WITH METFORMIN HYDROCHLORIDE TABLETS, the patient should be observed closely for hypoglycemia. Examples: Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs and isoniazid Alogliptin Cytochrome (CYP) P450, CYP-Substrates or Inhibitors Clinical Impact: Alogliptin is primarily renally excreted. Cytochrome (CYP) P450-related metabolism is negligible.

No significant drug-drug interactions were observed with the CYP-substrates or inhibitors tested or with renally excreted drugs [see Clinical Pharmacology (12.3) ] .

👥 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 ) Pediatrics: Safety and effectiveness of alogliptin and metformin HCl tablets in patients below the age of 18 have not been established. ( 8.4 ) Geriatric Use: Assess renal function more frequently. ( 8.5 ) Hepatic Impairment: Avoid use in patients with hepatic impairment. ( 8.7 )

8.1Pregnancy Risk Summary Limited available data with alogliptin and metformin HCl tablets or alogliptin 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 ].

Concomitant administration of alogliptin and metformin in pregnant rats during the period of organogenesis did not cause adverse developmental effects in offspring at maternal exposures up to 28 times and two times the 25 mg and 2000 mg clinical doses, respectively [see Data ]. The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with a HbA1c > 7 and has been reported to be as high as 20-25% in women with HbA1c > 10. The estimated background risk of miscarriage for the indicated population is unknown.

In the U.S. general population, the estimated background risk of major defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, 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 malformations, 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 metformin-associated risk because of methodological limitations, including small sample size and inconsistent comparator groups. Animal Data Alogliptin and Metformin Concomitant administration of alogliptin and metformin in pregnant rats during the period of organogenesis did not cause adverse developmental effects in offspring at a dose of 100 mg/kg alogliptin and 150 mg/kg metformin, or approximately 28 and two times the clinical dose of alogliptin (25 mg) and metformin (2000 mg), respectively based on plasma drug exposure (AUC).

Alogliptin Alogliptin administered to pregnant rabbits and rats during the period of organogenesis did not cause adverse developmental effects at doses of up to 200 mg/kg and 500 mg/kg, or 149 times and 180 times the 25 mg clinical dose, respectively, based on plasma drug exposure (AUC). Placental transfer of alogliptin into the fetus was observed following oral dosing to pregnant rats. No adverse developmental outcomes were observed in offspring when alogliptin was administered to pregnant rats during gestation and lactation at doses up to 250 mg/kg (approximately 95 times the 25 mg clinical dose, based on AUC).

Metformin Hydrochloride Metformin hydrochloride 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 two to six times a clinical dose of 2000 mg 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 alogliptin and metformin or alogliptin in human milk, the…

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Risk Summary Limited available data with alogliptin and metformin HCl tablets or alogliptin 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 ].

Concomitant administration of alogliptin and metformin in pregnant rats during the period of organogenesis did not cause adverse developmental effects in offspring at maternal exposures up to 28 times and two times the 25 mg and 2000 mg clinical doses, respectively [see Data ]. The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with a HbA1c > 7 and has been reported to be as high as 20-25% in women with HbA1c > 10. The estimated background risk of miscarriage for the indicated population is unknown.

In the U.S. general population, the estimated background risk of major defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, 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 malformations, 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 metformin-associated risk because of methodological limitations, including small sample size and inconsistent comparator groups. Animal Data Alogliptin and Metformin Concomitant administration of alogliptin and metformin in pregnant rats during the period of organogenesis did not cause adverse developmental effects in offspring at a dose of 100 mg/kg alogliptin and 150 mg/kg metformin, or approximately 28 and two times the clinical dose of alogliptin (25 mg) and metformin (2000 mg), respectively based on plasma drug exposure (AUC).

Alogliptin Alogliptin administered to pregnant rabbits and rats during the period of organogenesis did not cause adverse developmental effects at doses of up to 200 mg/kg and 500 mg/kg, or 149 times and 180 times the 25 mg clinical dose, respectively, based on plasma drug exposure (AUC). Placental transfer of alogliptin into the fetus was observed following oral dosing to pregnant rats. No adverse developmental outcomes were observed in offspring when alogliptin was administered to pregnant rats during gestation and lactation at doses up to 250 mg/kg (approximately 95 times the 25 mg clinical dose, based on AUC).

Metformin Hydrochloride Metformin hydrochloride 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 two to six times a clinical dose of 2000 mg based on body surface area (mg/m 2 ) for rats and rabbits, respectively.

🧒 Pediatric Use 19 words ▾

8.4Pediatric Use Safety and effectiveness of alogliptin and metformin HCl tablets in pediatric patients have not been established.

🧓 Geriatric Use ~1 min read ▾

8.5Geriatric Use Alogliptin and Metformin Hydrochloride Elderly patients are more likely to have decreased renal function. Monitor renal function in the elderly more frequently [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3) ] . Of the total number of patients (N = 2095) in clinical safety and efficacy studies, 343 (16.4%) patients were 65 years and older and 37 (1.8%) patients were 75 years and older.

No overall differences in safety or effectiveness were observed between these patients and younger patients. While this and other reported clinical experiences have not identified differences in responses between the elderly and younger patients, greater sensitivity of some older individuals cannot be excluded. Alogliptin Of the total number of patients (N=9052) in clinical safety and efficacy studies treated with alogliptin, 2257 (24.9%) patients were 65 years and older and 386 (4.3%) patients were 75 years and older.

No overall differences in safety or effectiveness were observed between patients 65 years and over and younger patients. Metformin Hydrochloride Controlled studies of metformin did not include sufficient numbers of subjects age 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

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 and cardiac function, and of concomitant disease or other drug therapy and the higher risk of lactic acidosis. Assess renal function more frequently in elderly patients [see Contraindications (4) , Warnings and Precautions (5.1) and Clinical Pharmacology (12.3) ].

🆘 Overdosage 174 words ▾

10 OVERDOSAGE Alogliptin 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) ] .

In the event of an overdose, it is reasonable to institute the necessary clinical monitoring and supportive therapy as dictated by the patient's clinical status. Per clinical judgment, it may be reasonable to initiate removal of unabsorbed material from the gastrointestinal tract. Alogliptin is minimally dialyzable; over a three-hour hemodialysis session, approximately 7% of the drug was removed.

Therefore, hemodialysis is unlikely to be beneficial in an overdose situation. It is not known if alogliptin is dialyzable by peritoneal dialysis. Metformin Hydrochloride Metformin is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions.

Hemodialysis may be useful for removal of accumulated drug from patients in whom metformin overdosage is suspected. To contact the poison control center, call 1-800-222-1222.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Alogliptin and Metformin Hydrochloride Alogliptin and metformin HCl tablets combine two antihyperglycemic agents with complementary and distinct mechanisms of action to improve glycemic control in patients with type 2 diabetes: alogliptin, a selective inhibitor of DPP-4, and metformin HCl, a member of the biguanide class. Alogliptin Increased concentrations of the incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released into the bloodstream from the small intestine in response to meals.

These hormones cause insulin release from the pancreatic beta cells in a glucose-dependent manner but are inactivated by the dipeptidyl peptidase-4 (DPP-4) enzyme within minutes. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, reducing hepatic glucose production. In patients with type 2 diabetes, concentrations of GLP-1 are reduced but the insulin response to GLP-1 is preserved.

Alogliptin is a DPP-4 inhibitor that slows the inactivation of the incretin hormones, thereby increasing their bloodstream concentrations and reducing fasting and postprandial glucose concentrations in a glucose-dependent manner in patients with type 2 diabetes mellitus. Alogliptin selectively binds to and inhibits DPP-4 but not DPP-8 or DPP-9 activity in vitro at concentrations approximating therapeutic exposures. Metformin Hydrochloride Metformin is a biguanide that improves glucose tolerance in patients with type 2 diabetes, 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 daylong plasma insulin response may actually decrease.

12.2Pharmacodynamics Alogliptin Single-dose administration of alogliptin to healthy subjects resulted in a peak inhibition of DPP-4 within two to three hours after dosing. The peak inhibition of DPP-4 exceeded 93% across doses of 12.5 mg to 800 mg. Inhibition of DPP-4 remained above 80% at 24 hours for doses greater than or equal to 25 mg.

Peak and total exposure over 24 hours to active GLP-1 were three- to four-fold greater with alogliptin (at doses of 25 to 200 mg) than placebo. In a 16 week, double-blind, placebo-controlled study, alogliptin 25 mg demonstrated decreases in postprandial glucagon while increasing postprandial active GLP-1 levels compared to placebo over an eight hour period following a standardized meal. It is unclear how these findings relate to changes in overall glycemic control in patients with type 2 diabetes mellitus.

In this study, alogliptin 25 mg demonstrated decreases in two hour postprandial glucose compared to placebo (-30 mg/dL versus 17 mg/dL, respectively). Multiple-dose administration of alogliptin to patients with type 2 diabetes also resulted in a peak inhibition of DPP-4 within one to two hours and exceeded 93% across all doses (25 mg, 100 mg and 400 mg) after a single dose and after 14 days of once daily dosing. At these doses of alogliptin, inhibition of DPP-4 remained above 81% at 24 hours after 14 days of dosing.

12.3Pharmacokinetics Absorption and Bioavailability Alogliptin and Metformin Hydrochloride In bioequivalence studies of alogliptin and metformin HCl tablets, the area under the plasma concentration curve (AUC) and maximum concentration (C max ) of both the alogliptin and the metformin component following a single dose of the combination tablet were bioequivalent to the alogliptin 12.5 mg concomitantly administered with metformin HCl 500 or 1000 mg tablets under fasted conditions in healthy subjects. Administration of alogliptin and metformin HCl tablets with food resulted in no change in total exposure (AUC) of alogliptin and metformin.

Mean peak plasma concentrations of alogliptin and…

🧬 Mechanism of Action ~1 min read ▾

12.1Mechanism of Action Alogliptin and Metformin Hydrochloride Alogliptin and metformin HCl tablets combine two antihyperglycemic agents with complementary and distinct mechanisms of action to improve glycemic control in patients with type 2 diabetes: alogliptin, a selective inhibitor of DPP-4, and metformin HCl, a member of the biguanide class. Alogliptin Increased concentrations of the incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released into the bloodstream from the small intestine in response to meals.

These hormones cause insulin release from the pancreatic beta cells in a glucose-dependent manner but are inactivated by the dipeptidyl peptidase-4 (DPP-4) enzyme within minutes. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, reducing hepatic glucose production. In patients with type 2 diabetes, concentrations of GLP-1 are reduced but the insulin response to GLP-1 is preserved.

Alogliptin is a DPP-4 inhibitor that slows the inactivation of the incretin hormones, thereby increasing their bloodstream concentrations and reducing fasting and postprandial glucose concentrations in a glucose-dependent manner in patients with type 2 diabetes mellitus. Alogliptin selectively binds to and inhibits DPP-4 but not DPP-8 or DPP-9 activity in vitro at concentrations approximating therapeutic exposures. Metformin Hydrochloride Metformin is a biguanide that improves glucose tolerance in patients with type 2 diabetes, 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 daylong plasma insulin response may actually decrease.

📦 How Supplied / Storage and Handling 16 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Product: 50090-5993 NDC: 50090-5993-0 90 TABLET, FILM COATED in a BOTTLE

📋 Description ~1 min read ▾

11 DESCRIPTION Alogliptin and metformin HCl tablets contain two oral antihyperglycemic drugs used in the management of type 2 diabetes: alogliptin and metformin hydrochloride. Alogliptin Alogliptin is a selective, orally bioavailable inhibitor of the enzymatic activity of dipeptidyl peptidase-4 (DPP-4). Chemically, alogliptin is prepared as a benzoate salt, which is identified as 2-({6-[(3 R )-3-aminopiperidin-1-yl]-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2 H )-yl}methyl)benzonitrile monobenzoate.

It has a molecular formula of C 18 H 21 N 5 O 2 ∙C 7 H 6 O 2 and a molecular weight of 461.51 daltons; the structural formula is: Alogliptin benzoate is a white to off-white crystalline powder containing one asymmetric carbon in the aminopiperidine moiety. It is soluble in dimethylsulfoxide, sparingly soluble in water and methanol, slightly soluble in ethanol and very slightly soluble in octanol and isopropyl acetate. Chemical Structure Metformin Hydrochloride Metformin hydrochloride ( N,N -dimethylimidodicarbonimidic diamide hydrochloride) is not chemically or pharmacologically related to any other classes of oral antihyperglycemic agents.

Metformin hydrochloride is a white to off-white crystalline compound with a molecular formula of C 4 H 11 N 5 ∙HCl and a molecular weight of 165.63. Metformin hydrochloride is freely soluble in water and is practically insoluble in acetone, ether and chloroform. The pKa of metformin is 12.4.

The pH of a 1% aqueous solution of metformin hydrochloride is 6.68. The structural formula is as shown: Alogliptin and metformin HCl tablets are available as a tablet for oral administration containing 17 mg alogliptin benzoate equivalent to 12.5 mg alogliptin and: 500 mg metformin hydrochloride which is equivalent to 389.93 mg metformin base (12.5 mg/500 mg) or 1000 mg metformin hydrochloride which is equivalent to 779.86 mg metformin base (12.5 mg/1000 mg). Alogliptin and metformin HCl tablets contain the following inactive ingredients: mannitol, microcrystalline cellulose, povidone, crospovidone, and magnesium stearate; the tablets are film-coated with hypromellose 2910, talc, titanium dioxide and ferric oxide yellow.

Chemical Structure

💬 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 alogliptin and metformin HCl 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 importance of regular testing of renal function while receiving alogliptin with metformin tablets.

Instruct patients to inform their doctor that they are taking alogliptin with metformin 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 use of alogliptin. should be Educate 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 alogliptin and metformin HCl 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 alogliptin and metformin HCl tablets, patients should be asked about a history of heart failure or other risk factors for heart failure including moderate to severe renal impairment.

Instruct patients to contact their healthcare providers 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) ]. Hypersensitivity Reactions Inform patients that allergic reactions have been reported during use of alogliptin and metformin. Insturct patients if symptoms of allergic reactions (including skin rash, hives and swelling of the face, lips, tongue and throat that may cause difficulty in breathing or swallowing) occur, patients should instructed discontinue alogliptin and metformin HCl tablets and seek medical advice promptly. [see Warnings and Precautions (5.4) ].

Hepatic Effects Inform patients that postmarketing reports of liver injury, sometimes fatal, have been reported during use of alogliptin. Instruct patients that if signs or symptoms of liver injury occur, patients should be instructed to discontinue alogliptin and metformin HCl tablets and seek medical advice promptly. [see Warnings and Precautions (5.5) ]. Vitamin B12 Levels Inform patients about the importance of regular hematological parameters while receiving treatment with metformin. [see Warnings and Precautions (5.6) ] Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues Inform patients that hypoglycemia can occur, particularly when an insulin secretagogue or insulin is used in combination with alogliptin with metformin HCl tablets.

Educate patients about the risks, symptoms and appropriate management of hypoglycemia. [see Warnings and Precautions (5.7) ]. 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) ].

Dosage Instruct patients to take alogliptin with metformin hydrochloride tablets only as prescribed twice daily and that it should be taken with food. Instruct patients if a dose is missed, not to double their next dose. Instruct patients that the tablets…

💬 Medication Guide ~3 min read ▾

MEDICATION GUIDE alogliptin and metformin hydrochloride tablets Read this Medication Guide carefully before you start taking alogliptin with 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 treatment.

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

Lactic Acidosis. Metformin, one of the medicines in alogliptin with 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.

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 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 alogliptin with 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 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 listed above. You doctor may decide to stop alogliptin with metformin hydrochloride tablets for a while if you have any of these things.

Alogliptin with metformin hydrochloride tablets can have other serious side effects. See " What are the possible side effects of alogliptin with metformin hydrochloride tablets? " 2. Inflammation of the pancreas (pancreatitis).

Alogliptin, one of the medicines in alogliptin with metformin hydrochloride tablets, may cause pancreatitis, which may be severe. Certain medical conditions make you more likely to get pancreatitis. Before you start taking alogliptin with metformin hydrochloride tablets: Tell your doctor if you have ever had: pancreatitis high blood triglyceride levels kidney problems stones in your gallbladder (gall stones) liver problems history of alcoholism Stop taking alogliptin with 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 your heart does not pump blood well enough. Before you start taking alogliptin with metformin hydrochloride tablets: Tell your healthcare provider if you have ever had heart failure or have problems with your kidneys.

Contact your healthcare provider right away if you have any of the following symptoms: increasing shortness of breath or trouble breathing especially when lying down an unusually fast increase in weight unusual tiredness swelling of feet, ankles, or legs These may be symptoms of heart failure. What is alogliptin with metf…

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
← 50090-5992-00 · A-S 50090-5996-00 · A-S →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.