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Carbidopa, Levodopa and Entacapone 25 mg; 100 mg; 200 mg Tablet, Film Coated — NDC 33342-0493-12 package photo

Carbidopa, Levodopa and Entacapone 25 mg; 100 mg; 200 mg Tablet, Film Coated

by Macleods Pharmaceuticals Limited · 10 BLISTER PACK in 1 CARTON (33342-493-12) / 10 TABLET, FILM COATED in 1 BLISTER PACK
NDC 33342-0493-12
🏷️ FDA NDC (as labeled) 33342-493-12 billing pads the product segment with a zero
This package
Contains10 tablet, film coated in 1 blister pack Pack sizes2 compare ↓
Also priced by: Part D plans $1.30/unit — full pricing hub ↓
Also comes in: 100 tablets 33342-0493-11
Rx only Generic On market Non-controlled
🗂️ Data synced Sep 17, 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

⚠️
Other active recalls for Carbidopa, Levodopa And Entacapone (different manufacturers) — 1 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class II · Oct 7, 2025 — Product mix up: complaint received that sealed medication bottle contained Carbidopa, Levodopa, and Entacapone film-coated tablets (37.5 mg/150 mg/200 mg) instead of labelled lower strength Carbidopa, Levodopa, and Entacapone film-coated tablets (25 mg/100 mg/200 mg). (Rising Pharma Holding, Inc.) · FDA recall D-0029-2026
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗

🆔 Identity & classification

FDA NDC (as labeled) 33342-493-12
Product NDC 33342-493
11-digit billing NDC 33342049312
RxCUI 403850, 403851, 403852, 730988, 810083, 810090
UNII MNX7R8C5VO, 4975G9NM6T, 46627O600J
UPC 0333342491121, 0333342496119, 0333342492128, 0333342496126 +8 more
Application # ANDA214495
SPL Set ID f0d9d7a8-1d06-4119-b2bc-42b3ec08d45b
Established class (EPC) Aromatic Amino Acid Decarboxylation Inhibitor; Catechol-O-Methyltransferase Inhibitor; Aromatic Amino Acid
Mechanism of action DOPA Decarboxylase Inhibitors; Catechol O-Methyltransferase Inhibitors
Chemical class Amino Acids, Aromatic
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2025-04-15
Route ORAL
Dosage form TABLET, FILM COATED
Substance CARBIDOPA; LEVODOPA; ENTACAPONE
TE code (Orange Book) AB · RLD · RS
Why two NDCs? The FDA registers this code as 33342-493-12 — a 5-3-2 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 product segment → 33342-0493-12. 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 Aromatic Amino Acid Decarboxylation Inhibitor class.

Pharmacologic class Aromatic Amino Acid Decarboxylation Inhibitor
How it works DOPA Decarboxylase 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

LabelerMacleods Pharmaceuticals Limited
Application holderMACLEODS PHARMACEUTICALS LTD
FDA applicationANDA214495 (ANDA)
Labeler code33342
First marketedApr 2025
Product typeHuman Prescription Drug
Portfolio385 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

📖 What it is MedlinePlus · NLM

Entacapone is an inhibitor of catechol-O-methyltransferase (COMT). It is used in combination with levodopa and carbidopa (Sinemet) to treat the end-of-dose 'wearing-off' symptoms of Parkinson's disease. Entacapone helps the levodopa and carbidopa work better by allowing more of it to reach the brain, where it has its effects. This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • Each ingredient does a different job, and together they work better than any one alone. Levodopa is the main ingredient that your brain converts into dopamine — the chemical that's...
  • Why does my prescription have three ingredients? Wouldn't one drug be simpler?
  • This is a known and harmless effect of entacapone. It can cause your urine to look darker than usual, sometimes with a reddish or brownish tint. It's not a sign that something is w...
  • My urine looks dark or reddish — should I be worried?
📖 Read our full Carbidopa / Entacapone / Levodopa guide →

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 Brown
ShapeOval
ImprintM;70
Size17 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 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 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 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 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 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 3NXW29V3WO
    Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for 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 7CVR7L4A2D
    A starch-derived carbohydrate produced by breaking down corn, potato, or tapioca starch. It functions as a filler and binder to give the medicine bulk and texture, and sometimes as a mild sweetener or texture enhancer in powders and tablets.
  • UNII 6OZP39ZG8H
    Polysorbate 80 is a synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together in medications and improves how the product disperses in the body.
  • UNII U725QWY32X
    Povidone K30 is a synthetic polymer made from petroleum. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in the stomach so the medicine can be absorbed.
  • UNII ETJ7Z6XBU4
    Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and 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.

12 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 $1.30 $130.36 / 100 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
Carbidopa, Levodopa, and Entacapone 25 mg/1; 100 mg/1; 200 mg 00781-5637-01 Sandoz 100 tablets $0.683 AB Availability likely —
Carbidopa, Levodopa And Entacapone 25 mg/1; 100 mg/1; 200 mg 16571-0691-01 Rising 100 tablets $0.683 AB Availability likely —
carbidopa, levodopa and entacapone 25 mg/1; 100 mg/1; 200 mg 62332-0797-31 Alembic 100 tablets $0.683 AB Availability likely —
Carbidopa, Levodopa and Entacapone 25 mg/1; 100 mg/1; 200 mgthis 33342-0493-12 Macleods 10 tablets — AB FDA listed —
carbidopa, levodopa and entacapone 25 mg/1; 100 mg/1; 200 mg 46708-0797-31 Alembic 100 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

🏛️
2025
On the market since
Apr 2025
📍
2026
Currently FDA-listed
1 year listed
🔓
·
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 Carbidopa, levodopa and entacapone — the ingredient across all brands.

Top reported reactions

Fall69
Death54
Hallucination52
Parkinson^s Disease41
Dyskinesia28
Urinary Tract Infection27
Confusional State24

Reporter sex

0 reports

Serious outcomes

Death88
Disabling6
Life-threatening4
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 64 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
33342-0493-11 100 TABLET, FILM COATED in 1 BOTTLE (33342-493-11) 2025-04-15 Active
33342-0493-12 You're viewing this 10 BLISTER PACK in 1 CARTON (33342-493-12) / 10 TABLET, FILM COATED in 1 BLISTER PACK 2025-04-15 Active

Pack size FAQ

What quantity is in NDC 33342-0493-12?
NDC 33342-0493-12 is listed by the FDA — 10 blister pack in 1 carton / 10 tablet, film coated in 1 blister pack.
What NDC number is used to bill for this package of Carbidopa, Levodopa and Entacapone 25 mg; 100 mg; 200 mg Tablet, Film Coated?
Bill NDC 33342-0493-12 — the 11-digit billing format is 33342049312. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

🧭 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 33342-493-12, 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: 33342-0493-12, written without dashes as 33342049312. 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 33342-0493-12, the first segment (33342) is the labeler code FDA assigned to Macleods Pharmaceuticals Limited; the middle segment (0493) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (12) 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 Macleods Pharmaceuticals Limited. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 1 other package presentation of this same product, including 100 tablets (33342-0493-11). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Macleods Pharmaceuticals Limited 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.
🎯 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
🎯 Indications and Usage 192 words ▾

1 INDICATIONS & USAGE Carbidopa, levodopa and entacapone tablets, is indicated for the treatment of Parkinson’s disease. Carbidopa, levodopa and entacapone tablets can be used: To substitute (with equivalent strengths of each of the three components) carbidopa/levodopa and entacapone previously administered as individual products. To replace carbidopa/levodopa therapy (without entacapone) when patients experience the signs and symptoms of end-of-dose “wearing-off” and when they have been taking a total daily dose of levodopa of 600 mg or less and have not been experiencing dyskinesias.

Carbidopa, levodopa and entacapone tablets, a combination drug consisting of levodopa (aromatic amino acid), carbidopa (aromatic amino acid decarboxylation inhibitor), and entacapone (catechol-O-methyltransferase (COMT) inhibitor) is indicated for the treatment of Parkinson’s disease. Carbidopa, levodopa and entacapone tablets is to be used: • To substitute (with equivalent strengths of each of the three components) for carbidopa/levodopa and entacapone previously administered as individual products ( 1 ) • To replace carbidopa/levodopa therapy (without entacapone) when patients experience the signs and symptoms of end-of-dose “wearingoff” and when they have been taking a total daily dose of levodopa of 600 mg or less and have not been experiencing dyskinesias ( 1 )

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Carbidopa, levodopa and entacapone tablets should be used as a substitute for patients already stabilized on equivalent doses of carbidopa/levodopa and entacapone. However, some patients who have been stabilized on a given dose of carbidopa/levodopa may be treated with Carbidopa, levodopa and entacapone tablets if a decision has been made to add entacapone (see below). Therapy should be individualized and adjusted according to the desired therapeutic response.

Evaluate vitamin B6 levels prior to starting treatment with carbidopa/levodopa therapies. ( 2.1 ) The optimum daily dosage of Carbidopa, levodopa and entacapone tablets must be determined by careful titration in each patient ( 2.2 ) Individual tablets should not be split or fractionated. Administer only one tablet at each dosing interval ( 2.6 ) 2.1.

Management of Vitamin B6 Levels Evaluatevitamin B6 levels prior to initiating carbidopa/levodopa therapies, including carbidopa, levodopa and entacapone tablets, periodically during treatment, and as clinically indicated [see Warnings and Precautions (5.10)] . If vitamin B6 levels are low, supplement to sufficient levels per standard of care. Patients may initiate and continue treatment with carbidopa, levodopa and entacapone tablets while supplementing vitamin B6.

2.2Dosing Information The optimum daily dosage of Carbidopa, levodopa and entacapone tablets must be determined by careful titration in each patient. Clinical experience with daily doses above 1,600 mg of entacapone is limited. The maximum recommended daily dose of Carbidopa, levodopa and entacapone tablets depends on the strength used.

The maximum number of tablets to be used in a 24-hour period is less with the highest strength (Carbidopa, levodopa and entacapone tablets 200) than with lower strengths (see Table 1). Studies show that peripheral dopa decarboxylase is saturated by carbidopa at approximately 70 mg per day to 100 mg per day. Patients receiving less than this amount of carbidopa are more likely to experience nausea and vomiting.

Table 1: Maximum Recommended Dose of Carbidopa, levodopa and entacapone tablets in a 24-hour Period Carbidopa, levodopa and entacapone tablets Dosage Strength Maximum Number of Tablets in a 24-hour Period 12.5 mg /50 mg /200 mg18.75 mg /75 mg /200 mg 25 mg /100 mg /200 mg31.25mg /125mg /200 mg37.5 mg /150 mg /200 mg 8 50 mg/200 mg/200 mg 6

2.3Converting Patients from Carbidopa, Levodopa, and Entacapone to Carbidopa, levodopa and entacapone tablets Patients currently treated with entacapone 200 mg with each dose of non-extended release carbidopa/levodopa tablet, can switch to the corresponding strength of carbidopa, levodopa and entacapone tablets containing the same amounts of levodopa and carbidopa. For example, patients receiving one tablet of carbidopa/levodopa 25 mg/100 mg and one tablet of entacapone 200 mg at each administration can switch to a single carbidopa, levodopa and entacapone 25 mg/100 mg/200 mg tablet (containing 25 mg of carbidopa, 100 mg of levodopa and 200 mg of entacapone).

2.4Converting Patients from Carbidopa and Levodopa Products to Carbidopa, levodopa and entacapone tablets There is no experience in transferring patients currently treated with extended release formulations of carbidopa/levodopa, or carbidopa/levodopa products that are not combined in a 1:4 ratio of carbidopa to levodopa. Patients with a history of moderate or severe dyskinesias or taking more than 600 mg of the levodopa component per day are likely to require a reduction in their daily levodopa dose when entacapone is added.

Because dose adjustment of the individual carbidopa or levodopa component is not possible with fixed-dose products, initially titrate patients to a dose that is tolerated and that meets their individual therapeutic need using a separate carbidopa/levodopa tablet (1:4 ratio) plus an entacapone tablet. Once the patient’s individual dose of carbidopa/levodopa plus entacapone dose has be…

💊 Dosage Forms and Strengths ~2 min read ▾

3 DOSAGE FORMS & STRENGTHS Each Carbidopa, levodopa and entacapone film coated tablet, provided in 6 single-dose strengths, contains carbidopa, USP and levodopa, USP in a 1:4 ratio and a 200 mg dose of entacapone, USP. Carbidopa, levodopa and entacapone tablets is supplied as film-coated tablets for oral administration in the following 6 strengths: Carbidopa, levodopa and entacapone film coated tablets 12.5 mg/50 mg/200 mg containing 12.5 mg of carbidopa, 50 mg of levodopa, and 200 mg of entacapone. Brown coloured, round shaped, biconvex, film coated tablets debossed with "M 71" on one side and plain surface on the other side.

Carbidopa, levodopa and entacapone film coated tablets 18.75 mg/75 mg/200 mg containing 18.75 mg of carbidopa, 75 mg of levodopa, and 200 mg of entacapone. Brown coloured, oval shaped, biconvex, film coated tablets debossed with “M 72” on one side and plain surface on the other side. Carbidopa, levodopa and entacapone film coated tablets 25 mg/100 mg/200 mg containing 25 mg of carbidopa, 100 mg of levodopa, and 200 mg of entacapone.

Brown coloured, oval shaped, biconvex, film coated tablets debossed with “M 73” on one side and plain surface on the other side. Carbidopa, levodopa and entacapone film coated tablets 31.25 mg/125 mg/200 mg containing 31.25 mg of carbidopa, 125 mg of levodopa, and 200 mg of entacapone. Brown coloured, oval shaped, biconvex, film coated tablets debossed with “M 74” on one side and plain surface on the other side.

Carbidopa, levodopa and entacapone film coated tablets 37.5 mg/150 mg/200 mg containing 37.5 mg of carbidopa, 150 mg of levodopa, and 200 mg of entacapone. Brown coloured, oval shaped, biconvex, film coated tablets debossed with "M 75" on one side and plain surface on the other side. Carbidopa, levodopa and entacapone film coated tablets 50 mg/200 mg/200 mg containing 50 mg of carbidopa, 200 mg of levodopa, and 200 mg of entacapone.

Brown coloured, oval shaped, biconvex, film coated tablets debossed with "M 70" on one side and plain surface on the other side. Each Carbidopa, levodopa and entacapone tablet contains a 1:4 ratio of carbidopa to levodopa and 200 mg of entacapone (mg of carbidopa per mg of levodopa per mg of entacapone) • Carbidopa, levodopa and entacapone tablets 12.5 mg/50 mg/200 mg (12.5 mg per 50 mg per 200 mg) • Carbidopa, levodopa and entacapone tablets 18.75 mg/75 mg/200 mg (18.75 mg per 75 mg per 200 mg) • Carbidopa, levodopa and entacapone tablets 25 mg/100 mg/200 mg (25 mg per 100 mg per 200 mg) • Carbidopa, levodopa and entacapone tablets 31.25 mg/125 mg/200 mg (31.25 mg per 125 mg per 200 mg) • Carbidopa, levodopa and entacapone tablets 37.5 mg/150 mg/200 mg (37.5 mg per 150 mg per 200 mg) • Carbidopa, levodopa and entacapone tablets 50 mg/200 mg/200 mg (50 mg per 200 mg per 200 mg)

⛔ Contraindications 63 words ▾

4 CONTRAINDICATIONS Carbidopa, levodopa and entacapone tablets is contraindicated in patients: Taking nonselective monoamine oxidase (MAO) inhibitors (e.g., phenelzine and tranylcypromine). These nonselective MAO inhibitors must be discontinued at least two weeks prior to initiating therapy with Carbidopa, levodopa and entacapone tablets. With narrow-angle glaucoma. • Concomitant use of nonselective monoamine oxidase (MAO) inhibitors ( 4 ) • Narrow-angle glaucoma ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS The following adverse reactions described in this section are related to at least one of the components of Carbidopa, levodopa and entacapone tablets (i.e., levodopa, carbidopa, and/or entacapone) based upon the safety experience in clinical trials (especially pivotal trials) or in postmarketing reports. • May cause falling asleep during activities of daily living without apparent warning, and daytime drowsiness and somnolence ( 5.1 ) • May cause syncope and hypotension/orthostatic hypotension ( 5.2 ) • May cause or exacerbate dyskinesia ( 5.3 ) • May cause depression and suicidality ( 5.4 ) • May cause hallucinations and/or other psychotic-like behavior ( 5.5 ) • May cause problems with impulse control and compulsive behaviors ( 5.6 ) • Abrupt discontinuation may cause hyperpyrexia and confusion ( 5.7 ) • May cause diarrhea and/or drug-induced colitis ( 5.8 ) • May cause rhabdomyolysis ( 5.9 )

5.1Falling Asleep During Activities of Daily Living and Somnolence Patients with Parkinson’s disease treated with Carbidopa, levodopa and entacapone tablets or other carbidopa/levodopa products have reported suddenly falling asleep without prior warning of sleepiness while engaged in activities of daily living (including the operation of motor vehicles). Some of these episodes resulted in accidents. Although many of these patients reported somnolence while taking entacapone, some did not perceive warning signs, such as excessive drowsiness, and believed that they were alert immediately prior to the event.

Some of these events have been reported to occur up to one year after initiation of treatment. Somnolence was reported in 2% of patients taking entacapone and 0% in placebo in controlled trials. It is reported that falling asleep while engaged in activities of daily living always occurs in a setting of pre-existing somnolence, although patients may not give such a history.

For this reason, prescribers should reassess patients for drowsiness or sleepiness especially since some of the events occur well after the start of treatment. Prescribers should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities. Patients who have already experienced somnolence and/or an episode of sudden sleep onset should not participate in these activities during treatment with Carbidopa, levodopa and entacapone tablets.

Before initiating treatment with Carbidopa, levodopa and entacapone tablets, advise patients of the potential to develop drowsiness and specifically ask about factors that may increase this risk such as use of concomitant sedating medications and the presence of sleep disorders. If a patient develops daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.), Carbidopa, levodopa and entacapone tablets should ordinarily be discontinued [see Dosage and Administration ( 2.6 ) and Warnings and Precautions ( 5.7 )].

If the decision is made to continue Carbidopa, levodopa and entacapone tablets, patients should be advised not to drive and to avoid other potentially dangerous activities. There is insufficient information to establish whether dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living.

5.2Hypotension, Orthostatic Hypotension and Syncope Reports of syncope were generally more frequent in patients in both treatment groups who had had a prior episode of documented hypotension (although the episodes of syncope, obtained by history, were themselves not documented with vital sign measurement). Hypotension, orthostatic hypotension, and syncope are observed in patients treated with drugs that increase central dopaminergic tone including Carbidopa, levodopa and entacapone tablets.

5.3Dyskinesia Dyskinesia (involuntary movements) may occur or be exacerbated at lower dosages and sooner with Carbido…

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in the Warnings and Precautions sections of labeling: Falling Asleep During Activities of Daily Living and Somnolence [see Warnings and Precautions ( 5.1 )] Hypotension/Orthostatic Hypotension and Syncope [see Warnings and Precautions ( 5.2 )] Dyskinesia [see Warnings and Precautions ( 5.3 )] Depression and suicidality [see Warnings and Precautions ( 5.4 )] Hallucinations/Psychotic-Like Behavior [see Warnings and Precautions ( 5.5 )] Impulse Control and/or Compulsive Behaviors [see Warnings and Precautions ( 5.6 )] Withdrawal-Emergent Hyperpyrexia and Confusion [see Warnings and Precautions ( 5.7 )] Diarrhea and Colitis [see Warnings and Precautions ( 5.8 )] Rhabdomyolysis [see Warnings and Precautions ( 5.9) ] Vitamin B6 Deficiency and Seizures [see Warnings and Precautions ( 5.10 )] Peptic Ulcer Disease [see Warnings and Precautions ( 5.13 )] The most common adverse reactions (incidence 3% higher than placebo incidence) are dyskinesias, hyperkinesia, diarrhea, nausea, abdominal pain, vomiting, dry mouth and urine discoloration ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Macleods Pharma USA, Inc. at 1-888-943-3210 or 1-855-926-3384 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, the incidence of adverse reactions (number of unique patients experiencing an adverse reaction associated with treatment/total number of patients treated) observed in the clinical trials of a drug cannot be directly compared to the incidence of adverse reactions in the clinical trials of another drug and may not reflect the incidence of adverse reactions observed in clinical practice. Entacapone The most commonly observed adverse reactions (incidence at least 3% greater than placebo incidence) in the double-blind, carbidopa-levodopa-placebo-controlled trials of entacapone (N=1,003 patients) associated with the use of carbidopa-levodopa-entacapone alone and not seen at an equivalent frequency among the placebo-treated patients were: dyskinesia, diarrhea, nausea, hyperkinesia, abdominal pain, vomiting, dry mouth, and urine discoloration.

The treatment difference incidence for premature study discontinuation for entacapone with levodopa and dopa decarboxylase inhibitor in the double-blind, placebo-controlled trials was 5%. The treatment difference incidence for the most frequent causes of study discontinuation was 2% for diarrhea, and 1% for other specific adverse reactions including psychiatric reasons, dyskinesia/ hyperkinesia, nausea, or abdominal pain. Adverse Reaction Incidence in Controlled Clinical Studies of Entacapone Table 2 lists treatment emergent adverse reactions that occurred in at least 1% of patients treated with carbidopa/levodopa and 200 mg of entacapone who participated in the double-blind, placebo-controlled studies, and that were numerically more common in this group than in the carbidopa/levodopa plus placebo group.

In these studies, either entacapone or placebo was added to carbidopa/levodopa (or benserazide/levodopa). Table 2: Summary of Patients With Adverse Reactions After Start of Trial Drug Administration At Least 1% in Entacapone Group and Greater Than Placebo SYSTEM ORGAN CLASS Adverse Reaction Carbidopa/levodopa plus Entacapone (n=603) % of patients Carbidopa/levodopa plus Placebo (n=400) % of patients SKIN AND APPENDAGES DISORDERS Sweating Increased 2 1 MUSCULOSKELETAL SYSTEM DISORDERS Back Pain 5 3 CENTRAL AND PERIPHERAL NERVOUS SYSTEM DISORDERS Dyskinesia 25 15 Hyperkinesia 10 5 Hypokinesia 9 8 Dizziness 8 6 SPECIAL SENSES, OTHER DISORDERS Taste Perversion 1 0 PSYCHIATRIC DISORDERS Anxiety 2 1 Somnolence 2 0 Agitation 1 0 GASTROINTESTINAL SYSTEM DISORDERS Nausea 14 8 Diarrhea 10 4 Abdominal Pain 8 4 Constipation 6 4 Vomiting 4 1 Mouth Dry 3 0 Dyspepsia 2 1 Flatulence 2 0 Gastritis 1 0 Gastrointestinal Disorders NOS 1 0 RESPIRA…

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS • Drugs metabolized by COMT: use with caution ( 5.11 , 7.2 ) • Anti-hypertensive agents: dose adjustment may be required ( 7.3 ) • Tricyclic antidepressants: risk of hypertension and dyskinesia reported during concomitant use with carbidopa/levodopa ( 7.4 ) • Dopamine D2 receptor antagonists, isoniazid, phenytoin, papaverine and iron salts: may reduce efficacy of Carbidopa, levodopa and entacapone tablets ( 7.5 , 7.6 , 7.7 , 7.8 , 7.9 ) • Drugs that interfere with biliary excretion, glucuronidation and intestinal beta-glucuronidase: dose adjustment of Carbidopa, levodopa and entacapone tablets may be required ( 7.10 ) • Drugs metabolized by CYP2C9 (e.g., coumadin): dose adjustment of Carbidopa, levodopa and entacapone tablets may be required; monitor INR when initiating Carbidopa, levodopa and entacapone tablets in patients on coumadin ( 7.11 )

7.1MAO Inhibitors Patients receiving nonselective MAO inhibitors and carbidopa, levodopa and entacapone may be at risk of increased adrenergic tone. Therefore, the use of Carbidopa, levodopa and entacapone tablets is contraindicated in patients receiving nonselective MAO inhibitors [see Contraindications ( 4 )].

7.2Drugs Metabolized by Catechol-O-Methyltransferase (COMT) Drugs known to be metabolized by COMT, such as isoproterenol, epinephrine, norepinephrine, dopamine, dobutamine, alpha-methyldopa, apomorphine, isoetherine, and bitolterol should be administered with caution in patients receiving entacapone regardless of the route of administration (including inhalation), as their interaction may result in increased heart rates, possibly arrhythmias, and excessive changes in blood pressure [see Warnings and Precautions ( 5.11 )].

7.3Antihypertensive Agents Symptomatic postural hypotension has occurred when carbidopa/levodopa was added to the treatment of patients receiving antihypertensive drugs. When starting therapy with Carbidopa, levodopa and entacapone tablets, dosage adjustment of antihypertensive drug may be required.

7.4Tricyclic Antidepressants There have been reports of adverse reactions, including hypertension and dyskinesia, resulting from the concomitant use of tricyclic antidepressants and carbidopa/levodopa.

7.5Dopamine D2 Receptor Antagonists Dopamine D2 receptor antagonists (e.g., metoclopramide, phenothiazines, butyrophenones, risperidone) may reduce the therapeutic effects of levodopa.

7.6Isoniazid Isoniazid may reduce the therapeutic effects of levodopa, a dose increase may be necessary.

7.7Phenytoin The beneficial effects of levodopa in Parkinson’s disease have been reported to be reversed by phenytoin. Patients taking phenytoin with carbidopa/levodopa should be carefully observed for loss of therapeutic response. Carbidopa, levodopa and entacapone tablets dosage should be increased as clinically needed in patients receiving phenytoin.

7.8Papaverine The beneficial effects of levodopa in Parkinson’s disease have been reported to be reversed by papaverine. Patients taking papaverine with carbidopa/levodopa should be carefully observed for loss of therapeutic response. Carbidopa, levodopa and entacapone tablets dosage should be increased as clinically needed in patients receiving papaverine.

7.9Iron Salts Iron salts or multi vitamins containing iron salts should be coadministered with caution. Iron salts can form chelates with levodopa, carbidopa and entacapone and consequently reduce bioavailability of levodopa, carbidopa and entacapone.

7.10Drugs Known to Interfere with Biliary Excretion, Glucuronidation, and Intestinal Beta-glucuronidase As most entacapone excretion is via the bile, caution should be exercised when drugs known to interfere with biliary excretion, glucuronidation, and intestinal beta-glucuronidase are given concurrently with entacapone. These include probenecid, cholestyramine, and some antibiotics (e.g., erythromycin, rifampicin, ampicillin and chloramphenicol).

7.11Drugs Metabolized via CYP2C9 (e.g.,coumadin) The dosa…

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS • Pregnancy: based on animal data, may cause fetal harm ( 8.1 )

8.1Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of Carbidopa, levodopa and entacapone tablets in pregnant women. In animals, administration of carbidopa-levodopa or entacapone during pregnancy was associated with developmental toxicity, including increased incidences of fetal malformations (see Data). The estimated background risk of major birth defects and miscarriage in the indicated population is unknown.

In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively. Data Animal data In nonclinical studies in which carbidopa-levodopa was administered to pregnant animals, increased incidences of visceral and skeletal malformations were observed in rabbits at all doses and ratios of carbidopa-levodopa tested, which ranged from 10 times (carbidopa)-5 times (levodopa) to 20 times (carbidopa)-10 times (levodopa) the maximum recommended human dose (MRHD) of 1,600 mg/day.

In rats, there was a decrease in the number of live pups delivered by dams receiving approximately two times (carbidopa)-five times (levodopa) the MRHD throughout organogenesis. No effects on malformation frequencies were observed in mice receiving up to 20 times the MRHD of carbidopa-levodopa. In embryo-fetal development studies of entacapone, pregnant animals received doses of up to 1,000 mg/kg/day (rats) or 300 mg/kg/day (rabbits) throughout organogenesis.

Increased incidences of fetal variations were evident in litters from rats treated with the highest dose, in the absence of overt signs of maternal toxicity. The maternal plasma entacapone exposure (AUC) associated with this dose was approximately 34 times that in humans at the MRHD. Increased frequencies of abortions and late/total resorptions and decreased fetal weights were observed in the litters of rabbits treated with maternally toxic doses of 100 mg/kg/day (plasma AUCs less than that in humans at the MRHD) or greater.

There were no increases in malformation rates in these studies. When entacapone was administered to female rats prior to mating and during early gestation, an increased incidence of fetal eye anomalies (macrophthalmia, microphthalmia, anophthalmia) was observed in the litters of dams treated with doses of 160 mg/kg/day (plasma AUCs seven times that in humans at the MRHD) or greater, in the absence of maternal toxicity. Administration of up to 700 mg/kg/day (plasma AUCs 28 times that in humans at the MRHD) to rats during the latter part of gestation and throughout lactation produced no evidence of developmental impairment in the offspring.

8.2Lactation Risk Summary Levodopa has been detected in human milk after administration of carbidopa-levodopa. There are no data on the presence of entacapone or carbidopa in human milk, the effects of levodopa, carbidopa, or entacapone on the breastfed infant, or the effects on milk production. However, inhibition of lactation may occur because levodopa decreases secretion of prolactin [see Clinical Pharmacology ( 12.6 )].

Carbidopa and entacapone are excreted in rat milk. In lactating rat, oral administration of radiolabeled entacapone resulted in levels of entacapone and/or metabolites in milk up to 2 to 3 times that in plasma. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Carbidopa, levodopa and entacapone tablets and any potential adverse effects on the breastfed infant from Carbidopa, levodopa and entacapone tablets or from the underlying maternal condition.

8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.

8.5Geriatric Use Of the total number of subjects in clinical studies of Carbidopa, levodopa and entacapone tablets, 43.8% were 65 years old and over, while 7.2% were 7…

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of Carbidopa, levodopa and entacapone tablets in pregnant women. In animals, administration of carbidopa-levodopa or entacapone during pregnancy was associated with developmental toxicity, including increased incidences of fetal malformations (see Data). The estimated background risk of major birth defects and miscarriage in the indicated population is unknown.

In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively. Data Animal data In nonclinical studies in which carbidopa-levodopa was administered to pregnant animals, increased incidences of visceral and skeletal malformations were observed in rabbits at all doses and ratios of carbidopa-levodopa tested, which ranged from 10 times (carbidopa)-5 times (levodopa) to 20 times (carbidopa)-10 times (levodopa) the maximum recommended human dose (MRHD) of 1,600 mg/day.

In rats, there was a decrease in the number of live pups delivered by dams receiving approximately two times (carbidopa)-five times (levodopa) the MRHD throughout organogenesis. No effects on malformation frequencies were observed in mice receiving up to 20 times the MRHD of carbidopa-levodopa. In embryo-fetal development studies of entacapone, pregnant animals received doses of up to 1,000 mg/kg/day (rats) or 300 mg/kg/day (rabbits) throughout organogenesis.

Increased incidences of fetal variations were evident in litters from rats treated with the highest dose, in the absence of overt signs of maternal toxicity. The maternal plasma entacapone exposure (AUC) associated with this dose was approximately 34 times that in humans at the MRHD. Increased frequencies of abortions and late/total resorptions and decreased fetal weights were observed in the litters of rabbits treated with maternally toxic doses of 100 mg/kg/day (plasma AUCs less than that in humans at the MRHD) or greater.

There were no increases in malformation rates in these studies. When entacapone was administered to female rats prior to mating and during early gestation, an increased incidence of fetal eye anomalies (macrophthalmia, microphthalmia, anophthalmia) was observed in the litters of dams treated with doses of 160 mg/kg/day (plasma AUCs seven times that in humans at the MRHD) or greater, in the absence of maternal toxicity. Administration of up to 700 mg/kg/day (plasma AUCs 28 times that in humans at the MRHD) to rats during the latter part of gestation and throughout lactation produced no evidence of developmental impairment in the offspring.

🧒 Pediatric Use 13 words ▾

8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.

🧓 Geriatric Use 102 words ▾

8.5Geriatric Use Of the total number of subjects in clinical studies of Carbidopa, levodopa and entacapone tablets, 43.8% were 65 years old and over, while 7.2% were 75 years old and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients; however, greater sensitivity of some older individuals cannot be excluded. Carbidopa, levodopa and entacapone tablets have not been studied in Parkinson’s disease patients or in healthy volunteers older than 75 years [see Clinical Pharmacology ( 12.3 )].

🆘 Overdosage ~2 min read ▾

10 OVERDOSAGE

10.1Signs and Symptoms of Overdosage There are very few cases of overdose with levodopa reported in the published literature. Based on the available information, the acute symptoms of levodopa and dopa decarboxylase inhibitor overdose can be expected to arise from dopaminergic overstimulation. Doses of a few grams may result in CNS disturbances, with an increasing likelihood of cardiovascular disturbance (e.g., hypotension, tachycardia) and more severe psychiatric problems at higher doses.

An isolated report of rhabdomyolysis and another of transient renal insufficiency suggest that levodopa overdose may give rise to systemic complications, secondary to dopaminergic overstimulation. COMT inhibition by entacapone treatment is dose-dependent. A massive overdose of entacapone may theoretically produce a 100% inhibition of the COMT enzyme in people, thereby preventing the O-methylation of endogenous and exogenous catechols.

In clinical trials, the highest single dose of entacapone administered to humans was 800 mg, resulting in a plasma concentration of 14.1 mcg per mL. The highest daily dose given to humans was 2,400 mg, administered in one study as 400 mg six times daily with carbidopa/levodopa for 14 days in 15 Parkinson’s disease patients, and in another study as 800 mg three times daily for 7 days in 8 healthy volunteers. At this daily dose, the peak plasma concentrations of entacapone averaged 2.0 mcg per mL (at 45 min, compared to 1.0 mcg per mL and 1.2 mcg per mL with 200 mg entacapone at 45 min.).

Abdominal pain and loose stools were the most commonly observed adverse events during this study. Daily doses as high as 2,000 mg entacapone have been administered as 200 mg 10 times daily with carbidopa/levodopa or benserazide/levodopa for at least 1 year in 10 patients, for at least 2 years in 8 patients and for at least 3 years in 7 patients. Overall, however, clinical experience with daily doses above 1,600 mg is limited.

10.2Management of Overdosage Hospitalization is advised, and general supportive measures should be employed, along with immediate gastric lavage and repeated doses of charcoal over time. This may hasten the elimination of entacapone in particular, by decreasing its absorption and reabsorption from the GI tract. Intravenous fluids should be administered judiciously and an adequate airway maintained.

Respiratory, circulatory and renal function should be monitored and appropriate supportive measures employed. Electrocardiographic monitoring should be instituted and the patient carefully observed for the development of arrhythmias; if required, appropriate antiarrhythmic therapy should be given. The possibility that the patient may have taken other drugs, increasing the risk of drug interactions (especially catechol-structured drugs) should be taken into consideration.

To date, no experience has been reported with dialysis; hence, its value in overdosage is not known. Hemodialysis or hemoperfusion is unlikely to reduce entacapone levels due to its high binding to plasma proteins. Pyridoxine is not effective in reversing the actions of Carbidopa, levodopa and entacapone tablets.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Levodopa Current evidence indicates that symptoms of Parkinson’s disease are related to depletion of dopamine in the corpus striatum. Administration of dopamine is ineffective in the treatment of Parkinson’s disease because it does not cross the blood-brain barrier. However, levodopa the metabolic precursor of dopamine, does cross the blood-brain barrier, and is presumably converted to dopamine in the brain.

This is thought to be the mechanism whereby levodopa relieves the symptoms of Parkinson’s disease. Carbidopa When levodopa is administered orally, it is rapidly decarboxylated to dopamine in extracerebral tissues so that only a small portion of a given dose is transported unchanged to the central nervous system. Carbidopa inhibits the decarboxylation of peripheral levodopa, making more levodopa available for delivery to the brain.

Entacapone Entacapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT). COMT catalyzes the transfer of the methyl group of S-adenosyl-L-methionine to the phenolic group of substrates that contain a catechol structure. Physiological substrates of COMT include DOPA, catecholamines (dopamine, norepinephrine, and epinephrine) and their hydroxylated metabolites.

When decarboxylation of levodopa is prevented by carbidopa, COMT becomes the major metabolizing enzyme for levodopa, catalyzing its metabolism to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD).

12.3Pharmacokinetics The pharmacokinetics of Carbidopa, levodopa and entacapone tablets has been studied in healthy subjects (age 45 years to 75 years). Overall, following administration of corresponding doses of levodopa, carbidopa and entacapone as Carbidopa, levodopa and entacapone tablets or as carbidopa and levodopa product plus Comtan (entacapone) tablets, the mean plasma concentrations of levodopa, carbidopa, and entacapone are comparable. Absorption and Distribution Both levodopa and entacapone are rapidly absorbed and eliminated, and their distribution volume is moderately small.

Carbidopa is absorbed and eliminated slightly more slowly compared with levodopa and entacapone. There are substantial inter-and intra-individual variations in the absorption of levodopa, carbidopa and entacapone, particularly concerning its C max . The food-effect on the Carbidopa, levodopa and entacapone tablet has not been evaluated.

Because levodopa competes with certain amino acids for transport across the gut wall, the absorption of levodopa may be impaired in some patients after eating a high protein meal. Meals rich in large neutral amino acids may delay and reduce the absorption of levodopa [see Patient Counseling Information ( 17 )]. Levodopa The pharmacokinetic properties of levodopa following the administration of single-dose carbidopa, levodopa and entacapone tablets are summarized in Table 3.

Table 3: Pharmacokinetic Characteristics of Levodopa with Different Tablet Strengths of Carbidopa, levodopa and entacapone tablets (mean ± SD) Tablet Strength AUC 0-∞ (nanogram h per mL) C max (nanogram per mL) T max (h) 12.5 mg per 50 mg per 200 mg 1,040 ± 314 470 ± 154 1.1 ± 0.5 25 mg per 100 mg per 200 mg 2,910 ± 715 975 ± 247 1.4 ± 0.6 37.5 mg per 150 mg per 200 mg 3,770 ± 1,120 1,270 ± 329 1.5 ± 0.9 50 mg per 200 mg per 200 mg 6,115 ± 1,536 1,859 ± 455 1.76 ±

0.7Levodopa is bound to plasma protein only to a minor extent (about 10% to 30%). Carbidopa Following administration of Carbidopa, levodopa and entacapone tablets as a single dose to healthy male and female subjects, the peak concentration of carbidopa was reached within 2.5 hours to 3.4 hours on average. The mean C max ranged from about 40 nanogram per mL to 225 nanogram per mL and the mean AUC from 170 nanogram•h per mL to 1,200 nanogram•h per mL, with different Carbidopa, levodopa and entacapone tablets strengths providing 12.5 mg, 25 mg, 37.5 mg, or 50 mg of carbidopa.

Carbidopa is approximately 36% bound to plasma protein. E…

🧬 Mechanism of Action 196 words ▾

12.1Mechanism of Action Levodopa Current evidence indicates that symptoms of Parkinson’s disease are related to depletion of dopamine in the corpus striatum. Administration of dopamine is ineffective in the treatment of Parkinson’s disease because it does not cross the blood-brain barrier. However, levodopa the metabolic precursor of dopamine, does cross the blood-brain barrier, and is presumably converted to dopamine in the brain.

This is thought to be the mechanism whereby levodopa relieves the symptoms of Parkinson’s disease. Carbidopa When levodopa is administered orally, it is rapidly decarboxylated to dopamine in extracerebral tissues so that only a small portion of a given dose is transported unchanged to the central nervous system. Carbidopa inhibits the decarboxylation of peripheral levodopa, making more levodopa available for delivery to the brain.

Entacapone Entacapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT). COMT catalyzes the transfer of the methyl group of S-adenosyl-L-methionine to the phenolic group of substrates that contain a catechol structure. Physiological substrates of COMT include DOPA, catecholamines (dopamine, norepinephrine, and epinephrine) and their hydroxylated metabolites.

When decarboxylation of levodopa is prevented by carbidopa, COMT becomes the major metabolizing enzyme for levodopa, catalyzing its metabolism to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD).

📦 How Supplied / Storage and Handling ~2 min read ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Carbidopa, levodopa and entacapone is supplied as film-coated tablets for oral administration in the following six strengths: Carbidopa, levodopa and entacapone film coated tablets 12.5 mg/50 mg/200 mg containing 12.5 mg of carbidopa, 50 mg of levodopa, and 200 mg of entacapone. Brown coloured, round shaped, biconvex, film coated tablets debossed with "M 71" on one side and plain surface on the other side. HDPE bottle of 100 tablets NDC 33342-491-11 100 Tablets (10 x 10 Unit-dose) NDC 33342-491-12 Carbidopa, levodopa and entacapone film coated tablets 18.75 mg/75 mg/200 mg containing 18.75 mg of carbidopa, 75 mg of levodopa, and 200 mg of entacapone.

Brown coloured, oval shaped, biconvex, film coated tablets debossed with "M 72" on one side and plain surface on the other side. HDPE bottle of 100 tablets NDC 33342-492-11 100 Tablets (10 x 10 Unit-dose) NDC 33342-492-12 Carbidopa, levodopa and entacapone film coated tablets 25 mg/100 mg/200 mg containing 25 mg of carbidopa, 100 mg of levodopa, and 200 mg of entacapone. Brown coloured, oval shaped, biconvex, film coated tablets debossed with "M 73" on one side and plain surface on the other side.

HDPE bottle of 100 tablets NDC 33342-493-11 100 Tablets (10 x 10 Unit-dose) NDC 33342-493-12 Carbidopa, levodopa and entacapone film coated tablets 31.25 mg/125 mg/200 mg containing 31.25 mg of carbidopa, 125 mg of levodopa, and 200 mg of entacapone. Brown coloured, oval shaped, biconvex, film coated tablets debossed with "M 74" on one side and plain surface on the other side. HDPE bottle of 100 tablets NDC 33342-494-11 100 Tablets (10 x 10 Unit-dose) NDC 33342-494-12 Carbidopa, levodopa and entacapone film coated tablets 37.5 mg/150 mg/200 mg containing 37.5 mg of carbidopa, 150 mg of levodopa, and 200 mg of entacapone.

Brown coloured, oval shaped, biconvex, film coated tablets debossed with "M 75" on one side and plain surface on the other side. HDPE bottle of 100 tablets NDC 33342-495-11 100 Tablets (10 x 10 Unit-dose) NDC 33342-495-12 Carbidopa, levodopa and entacapone film coated tablets 50 mg/200 mg/200 mg containing 50 mg of carbidopa, 200 mg of levodopa, and 200 mg of entacapone. Brown coloured, oval shaped, biconvex, film coated tablets debossed with "M 70" on one side and plain surface on the other side.

HDPE bottle of 100 tablets NDC 33342-496-11 100 Tablets (10 x 10 Unit-dose) NDC 33342-496-12 Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature.] Dispense in tight container (USP).

📋 Description ~1 min read ▾

11 DESCRIPTION Carbidopa, levodopa and entacapone tablets is a combination of carbidopa, levodopa, and entacapone for the treatment of Parkinson’s disease. Carbidopa, an inhibitor of aromatic amino acid decarboxylation, is a white, crystalline compound, slightly soluble in water, with a molecular weight of 244.3. It is designated chemically as (-)-L-(α-hydrazino-(α-methyl-β-(3,4-dihydroxybenzene) propanoic acid monohydrate.

Its empirical formula is C 10 H 14 N 2 O 4 •H 2 O, and its structural formula is: Tablet content is expressed in terms of anhydrous carbidopa, which has a molecular weight of 226.3. Levodopa, an aromatic amino acid, is a white, crystalline compound, slightly soluble in water, with a molecular weight of 197.2. It is designated chemically as (-)-L-α-amino-β-(3,4-dihydroxybenzene) propanoic acid.

Its empirical formula is C 9 H 11 NO 4 , and its structural formula is: Entacapone, a COMT inhibitor, is a nitro-catechol-structured compound with a molecular weight of 305.3. The chemical name of entacapone is (E)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethyl-2-propenamide. Its empirical formula is C 14 H 15 N 3 O 5 and its structural formula is: Carbidopa, levodopa and entacapone film coated tablets is supplied as tablets in 6 strengths: 12.5 mg of carbidopa, USP; 50 mg of levodopa, USP and 200 mg of entacapone USP 18.75 mg of carbidopa, USP; 75 mg of levodopa, USP and 200 mg of entacapone USP 25 mg of carbidopa, USP; 100 mg of levodopa, USP and 200 mg of entacapone USP 31.25 mg of carbidopa, USP; 125 mg of levodopa, USP and 200 mg of entacapone USP 37.5 mg of carbidopa, USP; 150 mg of levodopa, USP and 200 mg of entacapone USP 50 mg of carbidopa, USP; 200 mg of levodopa, USP and 200 mg of entacapone USP Inactive Ingredients: Colloidal silicon dioxide, Croscarmellose sodium, Crospovidone, Magnesium stearate, Maltodextrin, Microcrystalline cellulose, Povidone.

The coating material Instacoat Brown HIS consists of Hypromellose, Polysorbate 80, Red Iron Oxide, Titanium Dioxide, Yellow Iron Oxide cle-str-carb.jpg cle-str-levo.jpg cle-str-enta.jpg

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Falling Asleep During Activities of Daily Living and Somnolence Advise patients about the potential for sedating effects associated with Carbidopa, levodopa and entacapone tablets including somnolence and the possibility of falling asleep while engaged in activities of daily living. Because somnolence can be a frequent adverse reaction with potentially serious consequences, patients should not drive a motor vehicle, operate heavy machinery or engage in other potentially dangerous activities until they have gained sufficient experience with Carbidopa, levodopa and entacapone tablets to determine whether or not it affects their mental and/or motor performance adversely [see Warnings and Precautions ( 5.1 )].

Advise patients that if increased somnolence or episodes of falling asleep during activities of daily living (e.g., conversations, eating, driving a motor vehicle, etc.) are experienced at any time during treatment, they should not drive or participate in potentially dangerous activities until they have contacted their physician. Advise patients to speak with their health care prescriber before taking alcohol, sedating medications, or other CNS depressants (e.g., benzodiazepines, antipsychotics, antidepressants, etc.) because of the possible additive effects in combination with Carbidopa, levodopa and entacapone tablets.

Hypotension, Orthostatic Hypotension and Syncope Advise patients that they may develop symptomatic (or asymptomatic) postural (orthostatic) hypotension or nonorthostatic hypotension while taking Carbidopa, levodopa and entacapone tablets. Hypotension/orthostatic hypotension may occur more frequently during initial therapy. Patients should not rise rapidly after sitting or lying down, especially if they have been doing so for prolonged periods and especially at the initiation of treatment with Carbidopa, levodopa and entacapone tablets.

Advise patients about the potential for syncope in patients using dopamine agonists. For this reason, inform patients about the possibility of syncope while taking Carbidopa, levodopa and entacapone tablets [see Warnings and Precautions ( 5.2 )]. Dyskinesias Inform patients that Carbidopa, levodopa and entacapone tablets may cause and/or exacerbate pre-existing dyskinesias [see Warnings and Precautions ( 5.3 )].

Hallucinations and/or Psychotic-Like Behavior Inform patients that hallucinations and other psychotic-like behavior can occur while taking Carbidopa, levodopa and entacapone tablets [see Warnings and Precautions ( 5.5 )]. Impulse Control and/or Compulsive Behaviors Advise patients that they may experience impulse control and/or compulsive behaviors while taking one or more of the medications used for the treatment of Parkinson’s disease, including Carbidopa, levodopa and entacapone tablets. Ask patients about the development of new or increased gambling urges, sexual urges, urges for uncontrolled spending, or other intense urges while being treated with Carbidopa, levodopa and entacapone tablets.

Advise patients to inform their physician or health care provider if they experience new or increased gambling urges, increased sexual urges or other intense urges while taking Carbidopa, levodopa and entacapone tablets. Physicians should consider dose reduction or stopping the medication if a patient develops such urges while taking Carbidopa, levodopa and entacapone tablets [see Warnings and Precautions ( 5.6 )]. Withdrawal-Emergent Hyperpyrexia and Confusion Advise patients that they may develop fever and confusion as part of a syndrome resembling NMS and possibly with other clinical features (e.g., muscle rigidity, autonomic dysfunction, hyper-or hypotension, etc.).

This fever and confusion syndrome may particularly occur with dose reductions or withdrawal of Carbidopa, levodopa and entacapone tablets but may also develop after initiation of treatment. Advise patients to contact their healthcare provider if they wish to discontinue or decr…

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