Home › NDC Lookup › Ingredients › Sodium Phenylbutyrate › 72542-0400-18
OLPRUVA sodium phenylbutyrate Kit — NDC 72542-0400-18 package photo

OLPRUVA sodium phenylbutyrate Kit

by Acer Therapeutics Inc. · 90 BOX in 1 CARTON (72542-400-18) / 1 KIT in 1 BOX (72542-400-02) * 1 FOR SUSPENSION in 1 PACKET (72542-002-01) * 1 FOR SUSPENSION in 1 PACKET (72542-000-01)
NDC 72542-0400-18
🏷️ FDA NDC (as labeled) 72542-400-18 billing pads the product segment with a zero
Rx only Brand 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

🆔 Identity & classification

FDA NDC (as labeled) 72542-400-18
Product NDC 72542-400
11-digit billing NDC 72542040018
NCPDP billing unit EA — each (per item)
Application # NDA214860
SPL Set ID 89abc31c-43e8-4809-9eb7-172cb31a86f1
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2022-12-22
Route ORAL
Dosage form KIT
GPI-14 3090806000B140
GCN Seq No 084238
GCN 53447
HICL code 011317
Ingredient (HICL) Sodium Phenylbutyrate
HIC1 code D
Therapeutic class — broad (HIC1) Biliary System/Gastro-Intestinal System
HIC2 code D9
Therapeutic class — intermediate (HIC2) Ammonia Inhibitors
HIC3 code D9A
Therapeutic class — specific (HIC3) Ammonia Inhibitors
AHFS code 40:10.00.00
AHFS class Ammonia Detoxicants
FDB label name OLPRUVA 4 GRAM DOSE KIT
FDB brand name Olpruva
Legend status F — Federal legend — prescription drug or device
Why two NDCs? The FDA registers this code as 72542-400-18 — 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 → 72542-0400-18. 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.

🏭 Manufacturer & labeler

LabelerAcer Therapeutics Inc.
Application holderACER THERAPEUTICS INC
FDA applicationNDA214860 (NDA)
Labeler code72542
First marketedDec 2022
Product typeHuman Prescription Drug
Portfolio10 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 OLPRUVA 4 GRAM DOSE KIT Ingredient Sodium Phenylbutyrate
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.

🧪 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.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

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 $131.83 —
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
Olpruva 72542-0300-09 Acer 1 kit — — FDA listed —
Olpruva 72542-0600-18 Acer 1 kit — — FDA listed —
Pheburane 483 mg/g 71770-0210-10 Medunik 174 g — — FDA listed —
Olpruvathis 72542-0400-18 Acer 1 kit — — FDA listed —
Olpruva 72542-0500-18 Acer 1 kit — — FDA listed —
Olpruva 72542-0200-09 Acer 1 kit — — FDA listed —
Olpruva 72542-0667-18 Acer 1 kit — — FDA listed —
About this product: this is the brand-name version. We did not find an FDA-approved generic match for this exact strength, form and route.
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

🏛️
2022
First FDA approval
Dec 2022
📍
2026
Currently FDA-listed
4 years listed
🛡️
2036
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 Oct 2036. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Dec 22, 2022 RLD RS ⏳ ~10.1 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 11202767 — method of use (U-3502)
US 11202767 — method of use (U-3502)
US 11202767 — method of use (U-3502)
US 11202767 — method of use (U-3502)
US 11202767 — method of use (U-3502)
US 11202767 — method of use (U-3502)
US 11202767 — method of use (U-3502)
US 11202767 — method of use (U-3502)
US 11433041 — drug product
US 11433041 — drug product
US 11154521 — drug product
US 11433041 — drug product
US 11154521 — drug product
US 11433041 — drug product
US 11433041 — drug product
US 11433041 — drug product
US 11154521 — drug product
US 11154521 — drug product
US 11154521 — drug product
US 11154521 — drug product
US 11433041 — drug product
US 11433041 — drug product
US 11154521 — drug product
US 11154521 — drug product
2022 2024 2026 2028 2030 2032 2034 2036
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 (24)
PatentTypeUse codeExpires
US 11202767 ↗ Method of use U-3502 Oct 17, 2036
US 11202767 ↗ Method of use U-3502 Oct 17, 2036
US 11202767 ↗ Method of use U-3502 Oct 17, 2036
US 11202767 ↗ Method of use U-3502 Oct 17, 2036
US 11202767 ↗ Method of use U-3502 Oct 17, 2036
US 11202767 ↗ Method of use U-3502 Oct 17, 2036
US 11202767 ↗ Method of use U-3502 Oct 17, 2036
US 11202767 ↗ Method of use U-3502 Oct 17, 2036
US 11433041 ↗ Drug product — Oct 17, 2036
US 11433041 ↗ Drug product — Oct 17, 2036
US 11154521 ↗ Drug product — Oct 17, 2036
US 11433041 ↗ Drug product — Oct 17, 2036
US 11154521 ↗ Drug product — Oct 17, 2036
US 11433041 ↗ Drug product — Oct 17, 2036
US 11433041 ↗ Drug product — Oct 17, 2036
US 11433041 ↗ Drug product — Oct 17, 2036
US 11154521 ↗ Drug product — Oct 17, 2036
US 11154521 ↗ Drug product — Oct 17, 2036
US 11154521 ↗ Drug product — Oct 17, 2036
US 11154521 ↗ Drug product — Oct 17, 2036
US 11433041 ↗ Drug product — Oct 17, 2036
US 11433041 ↗ Drug product — Oct 17, 2036
US 11154521 ↗ Drug product — Oct 17, 2036
US 11154521 ↗ Drug product — Oct 17, 2036
Common questions
Is there a generic version of OLPRUVA 4 GRAM DOSE KIT?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for OLPRUVA 4 GRAM DOSE KIT. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until Oct 2036 — 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.

📊 Medicare Part D spend CMS · PART D · 2025 (Q1-Q4)

Medicare Part D (outpatient prescription) spending for Olpruva — the program that covers self-administered drugs. 1 manufacturer.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Olpruva. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Total Part D spend
$573.8K
Claims incl. refills
13
Beneficiaries
—
Spend / beneficiary
—
Spend / claim
$44,138.80
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

🔬 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 Sodium phenylbutyrate — the ingredient across all brands.

Top reported reactions

Hyperammonaemia56
Vomiting42
Death35
Ammonia Increased32
Nausea28
Diarrhoea27
Decreased Appetite25

Reporter sex

420 reports
Male · 43%
Female · 56%
Unknown · 1%

Serious outcomes

Hospitalization164
Death84
Life-threatening13
Disabling7
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 22 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
72542-0400-18 You're viewing this 90 BOX in 1 CARTON (72542-400-18) / 1 KIT in 1 BOX (72542-400-02) * 1 FOR SUSPENSION in 1 PACKET (72542-002-01) * 1 FOR SUSPENSION in 1 PACKET (72542-000-01) 2022-12-22 Active

🧭 About this NDC listing & data coverage

Finished prescription product Kit / multi-component package

Kit / multi-component package

This NDC identifies a kit — a package containing more than one component. Structured data (pricing, ingredients, equivalents) is often reported per component rather than for the kit NDC itself, which can make this page look thinner than the components' own pages.

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) — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is 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 72542-400-18, 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: 72542-0400-18, written without dashes as 72542040018. 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 72542-0400-18, the first segment (72542) is the labeler code FDA assigned to Acer Therapeutics Inc.; the middle segment (0400) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (18) 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 Acer Therapeutics Inc.. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Acer Therapeutics Inc. 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 187 words ▾

1 INDICATIONS AND USAGE OLPRUVA is indicated as adjunctive therapy to standard of care, which includes dietary management, for the chronic management of adult and pediatric patients weighing 20 kg or greater and with a body surface area (BSA) of 1.2 m 2 or greater, with urea cycle disorders (UCDs) involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS). OLPRUVA is a nitrogen-binding agent indicated as adjunctive therapy to standard of care, which includes dietary management, for the chronic management of adult and pediatric patients weighing 20 kg or greater and with a body surface area (BSA) of 1.2 m 2 or greater, with urea cycle disorders (UCDs) involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS).

( 1 ) Limitations of Use: OLPRUVA is not indicated for the treatment of acute hyperammonemia. ( 1 ) Limitations of Use Episodes of acute hyperammonemia may occur in patients while on OLPRUVA. OLPRUVA is not indicated for the treatment of acute hyperammonemia, which can be a life-threatening medical emergency that requires rapid acting interventions to reduce plasma ammonia levels.

⏱️ Dosage and Administration ~2 min read ▾

2 DOSAGE AND ADMINISTRATION OLPRUVA treatment should be supervised by a healthcare provider experienced in the treatment of UCDs. For preparation and administration, see full prescribing information. ( 2.1 , 2.4 ) The recommended dosage is 9.9 -13 g/m 2 /day.

( 2.1 ) Monitor plasma ammonia levels to determine the need for dosage adjustment. ( 2.2 ) Monitor patients for potential neurotoxicity. ( 2.2 ) For patients with hepatic impairment, start at the lower end of the recommended dosing range.

( 2.3 )

2.1Recommended Dosage OLPRUVA treatment should be supervised by a healthcare provider experienced in the treatment of urea cycle disorders. The recommended dosage of OLPRUVA for patients with urea cycle disorders is 9.9 –13 g/m 2 /day orally. Divide the calculated total daily dose into three to six doses.

Administer as three to six divided doses and take with food. Round each individual dose of OLPRUVA to the nearest available dosage strength. The maximum dosage is 20 grams per day.

Combine OLPRUVA with dietary protein restriction and, in some cases, amino acid supplementation (e.g., essential amino acids, arginine, citrulline, and protein-free calorie supplements). If a dose is missed, take the missed dose as soon as possible on the same day.

2.2Dosage Administration and Monitoring Monitor plasma ammonia levels to determine the need for dosage adjustment. Adjust the OLPRUVA dosage to maintain the plasma ammonia level within the normal range for the patient's age, taking into consideration their clinical condition (e.g., nutritional requirements, protein intake, growth parameters, etc.). Monitor patients for potential neurotoxicity and obtain measurements of plasma phenylacetate and phenylacetylglutamine levels [ see Warnings and Precautions ( 5.1 ), Adverse Reactions ( 6 ) ].

If neurologic symptoms (e.g., vomiting, nausea, headache, somnolence, or confusion) are present in the absence of high ammonia levels or other incurrent illnesses, consider reducing the dose of OLPRUVA.

2.3Dosage Adjustment in Patients with Hepatic Impairment For patients with hepatic impairment, start at the lower end of the recommended dosing range and maintain patients on the lowest dose necessary to control plasma ammonia levels [ see Use in Specific Populations ( 8.7 ) ].

2.4Preparation and Administration Instructions For oral administration only. Do not administer via gastrostomy or nasogastric tubes. Pour the entire contents of the Mix-Aid packet into approximately 4 ounces of water in a cup and stir, forming a suspension.

Pour the entire contents of the OLPRUVA packet(s) into the suspension and stir. Drink the entire suspension within 5 minutes after stirring to minimize dissolution of coating. After 30 minutes, the suspension should be discarded.

Pour another 4 ounces of water into the cup and drink to make sure that any OLPRUVA remaining in the cup is consumed.

💊 Dosage Forms and Strengths 61 words ▾

3 DOSAGE FORMS AND STRENGTHS For oral suspension: 2 g, 3 g, 4 g, 5 g, 6 g, and 6.67 g of sodium phenylbutyrate as white to off-white pellets in packet(s) for reconstitution. For oral suspension: 2 g, 3 g, 4 g, 5 g, 6 g, and 6.67 g of sodium phenylbutyrate as pellets in packets for reconstitution. ( 3 )

⛔ Contraindications 7 words ▾

4 CONTRAINDICATIONS None. None. ( 4 )

⚠️ Warnings and Cautions ~2 min read ▾

5 WARNINGS AND PRECAUTIONS Neurotoxicity of Phenylacetate : Increased exposure to phenylacetate, the major metabolite of OLPRUVA, may be associated with neurotoxicity in patients with UCDs. Consider reducing the dose if neurotoxicity symptoms are present. ( 5.1 ) Hypokalemia : Renal excretion of phenylacetylglutamine may induce urinary loss of potassium.

Monitor serum potassium during therapy and initiate appropriate treatment when necessary. ( 5.2 ) Conditions Associated with Edema : Calculate the total amount of sodium patients will be exposed to based on their body surface area. If a patient develops new-onset edema or worsening edema while on treatment, discontinue administration of OLPRUVA and initiate appropriate therapy.

( 5.3 )

5.1Neurotoxicity of Phenylacetate Increased exposure to phenylacetate, the major metabolite of OLPRUVA, may be associated with neurotoxicity in patients with UCDs. In a study of adult cancer patients receiving intravenous phenylacetate, 250-300 mg/kg/day for 14 days, repeated at 4-week intervals, signs and symptoms of neurotoxicity, which were reversible upon discontinuation, were seen at plasma concentrations ≥ 3.5 mmol/L, and included somnolence, fatigue, and light headedness [ see Adverse Reactions ( 6 ) ]. OLPRUVA is not approved for intravenous use or for treatment of patients with cancer.

If symptoms of vomiting, nausea, headache, somnolence, or confusion are present in the absence of high ammonia levels or other intercurrent illnesses, consider reducing the dose of OLPRUVA [ see Dosage and Administration ( 2.2 ) ]. Phenylacetate caused neurotoxicity when given subcutaneously in rat pups [ see Use in Specific Populations ( 8.4 ) ].

5.2Hypokalemia Renal excretion of phenylacetylglutamine may induce urinary loss of potassium. Monitor serum potassium during therapy and initiate appropriate treatment when necessary.

5.3Conditions Associated with Edema OLPRUVA contains 124 mg (5.4 mmol) of sodium per gram of sodium phenylbutyrate (12.4% w/w) and the Mix-Aid contains 5 mg of sodium per packet, corresponding to 2.5 g (108 mmol) of sodium in the maximum daily dose of 20 g of OLPRUVA. In order to decide if administration of OLPRUVA is appropriate in patients with diseases that involve edema, such as heart failure, cirrhosis, or nephrosis, calculate the total amount of sodium patients will be exposed to based on their BSAs [ see Dosage and Administration ( 2.1 ) ].

If a patient develops new-onset edema or worsening edema while on treatment, discontinue administration of OLPRUVA and initiate appropriate therapy.

🤒 Adverse Reactions ~1 min read ▾

6 ADVERSE REACTIONS The following adverse reactions associated with the use of sodium phenylbutyrate were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Most common adverse reactions (incidence ≥ 3%) are amenorrhea or menstrual dysfunction (irregular menstrual cycles), decreased appetite, body odor and bad taste or taste aversion.

Less Common Clinical Adverse Reactions Blood and lymphatic system disorders: aplastic anemia, ecchymoses Cardiac disorders: arrhythmia Gastrointestinal disorders: abdominal pain, gastritis, nausea and vomiting, constipation, rectal bleeding, peptic ulcer disease, pancreatitis Metabolism and nutrition disorders: increased weight, edema Nervous system disorders: syncope, headache Psychiatric disorders: depression Renal and urinary disorders: renal tubular acidosis Skin and subcutaneous tissue disorders: rash Laboratory Adverse Reactions Blood and lymphatic system disorders: anemia, leukopenia and leukocytosis, thrombocytopenia, thrombocytosis Hepatobiliary disorders: hyperbilirubinemia, increased blood alkaline phosphatase, increased transaminases Metabolism and nutrition disorders: acidosis, alkalosis, hyperchloremia, hypophosphatemia, hyperuricemia, hyperphosphatemia, hypernatremia, hypokalemia, hypoalbuminemia, decreased total protein Clinical Adverse Reactions with Use of Phenylacetate Nervous system disorders: Neurotoxicity was reported in cancer patients receiving intravenous phenylacetate, the major metabolite of OLPRUVA (OLPRUVA is not approved for intravenous use or for treatment of patients with cancer).

Signs and symptoms were predominately somnolence, fatigue, and dizziness (lightheadedness); less frequently reported were headache, dysgeusia, hypoacusis, disorientation, memory impairment, and exacerbation of a pre-existing neuropathy. Most common adverse reactions (incidence ≥ 3%) are menstrual dysfunction, decreased appetite, body odor and bad taste or taste aversion. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Acer Therapeutics Inc. at 1-844-600-2237 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

🔄 Drug Interactions 147 words ▾

7 DRUG INTERACTIONS Valproic Acid, Haloperidol, or Corticosteroids : May increase plasma ammonia levels; monitor ammonia levels closely. ( 7.1 ) Probenecid : May inhibit renal excretion of metabolites of OLPRUVA including phenylacetate and phenylacetylglutamine; monitor for potential neurotoxicity. ( 7.2 )

7.1Potential for Other Drugs to Affect Ammonia Corticosteroids Use of corticosteroids may cause the breakdown of body protein and increase plasma ammonia levels. Valproic Acid and Haloperidol Hyperammonemia may be induced by haloperidol and by valproic acid. Monitor plasma ammonia levels closely when corticosteroids, valproic acid, or haloperidol is used concomitantly with OLPRUVA.

7.2Potential for Other Drugs to Affect OLPRUVA Probenecid Probenecid may inhibit renal excretion of the metabolites of OLPRUVA including phenylacetate and phenylacetylglutamine. Monitor patients for potential neurotoxicity and measure plasma phenylacetate and phenylacetylglutamine levels when probenecid is used concomitantly with OLPRUVA [ see Dosage and Administration ( 2.2 ) ].

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy Risk Summary Available data with sodium phenylbutyrate use in pregnant women are insufficient to identify a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with sodium phenylbutyrate. Based on published animal data, phenylacetate may be neurotoxic to the developing brain ( see Data ).

There are serious risks to the mother and fetus associated with untreated urea cycle disorders during pregnancy which can result in serious morbidity and mortality to the mother and fetus ( see Clinical Considerations ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Pregnancy is a time of increased metabolic demand which increases the risk for hyperammonemic episodes when metabolic demands are not met. Hyperammonemic episodes in pregnancy are associated with impaired cognition in the mother and an increased risk of maternal and fetal death.

Data Animal Data In rats, intrauterine exposure to phenylacetate produced lesions in the neonatal brain in layer 5 of the cortical pyramidal cells; dendritic spines were longer and thinner than normal and reduced in number.

8.2Lactation Risk Summary There are no data on the presence of sodium phenylbutyrate and its metabolite in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for OLPRUVA and any potential adverse effects on the breastfed infant from OLPRUVA or from the underlying maternal condition.

8.4Pediatric Use The safety and effectiveness of OLPRUVA have been established as adjunctive therapy to the standard of care, which includes dietary management, in the chronic management of pediatric patients weighing 20 kg or greater and with a body surface area 1.2 m 2 or greater, with urea cycle disorders (UCDs) involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS). OLPRUVA is not indicated for the treatment of acute hyperammonemia which can be a life-threatening medical emergency that requires rapid acting interventions to reduce plasma ammonia levels.

The sodium content of OLPRUVA has the potential to cause new-onset edema or worsening edema from salt and water retention, particularly in patients with underlying predisposing conditions [ see Warnings and Precautions ( 5.3 ) ]. OLPRUVA is not approved in pediatric patients weighing less than 20 kg or in pediatric patients weighing 20 kg or greater with a BSA of less than 1.2 m 2 . Neurotoxicity has been observed in juvenile animals with phenylacetate exposure [ see Warnings and Precautions ( 5.1 ) ].

Juvenile Animal Toxicity Data When given subcutaneously to neonatal rats, 190-474 mg/kg phenylacetate caused decreased proliferation and increased loss of neurons, and it reduced CNS myelin. Cerebral synapse maturation was retarded, and the number of functioning nerve terminals in the cerebrum was reduced, which resulted in impaired brain growth.

8.5Geriatric Use Clinical studies of OLPRUVA did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. 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…

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy Risk Summary Available data with sodium phenylbutyrate use in pregnant women are insufficient to identify a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with sodium phenylbutyrate. Based on published animal data, phenylacetate may be neurotoxic to the developing brain ( see Data ).

There are serious risks to the mother and fetus associated with untreated urea cycle disorders during pregnancy which can result in serious morbidity and mortality to the mother and fetus ( see Clinical Considerations ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Pregnancy is a time of increased metabolic demand which increases the risk for hyperammonemic episodes when metabolic demands are not met. Hyperammonemic episodes in pregnancy are associated with impaired cognition in the mother and an increased risk of maternal and fetal death.

Data Animal Data In rats, intrauterine exposure to phenylacetate produced lesions in the neonatal brain in layer 5 of the cortical pyramidal cells; dendritic spines were longer and thinner than normal and reduced in number.

🧒 Pediatric Use ~1 min read ▾

8.4Pediatric Use The safety and effectiveness of OLPRUVA have been established as adjunctive therapy to the standard of care, which includes dietary management, in the chronic management of pediatric patients weighing 20 kg or greater and with a body surface area 1.2 m 2 or greater, with urea cycle disorders (UCDs) involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS). OLPRUVA is not indicated for the treatment of acute hyperammonemia which can be a life-threatening medical emergency that requires rapid acting interventions to reduce plasma ammonia levels.

The sodium content of OLPRUVA has the potential to cause new-onset edema or worsening edema from salt and water retention, particularly in patients with underlying predisposing conditions [ see Warnings and Precautions ( 5.3 ) ]. OLPRUVA is not approved in pediatric patients weighing less than 20 kg or in pediatric patients weighing 20 kg or greater with a BSA of less than 1.2 m 2 . Neurotoxicity has been observed in juvenile animals with phenylacetate exposure [ see Warnings and Precautions ( 5.1 ) ].

Juvenile Animal Toxicity Data When given subcutaneously to neonatal rats, 190-474 mg/kg phenylacetate caused decreased proliferation and increased loss of neurons, and it reduced CNS myelin. Cerebral synapse maturation was retarded, and the number of functioning nerve terminals in the cerebrum was reduced, which resulted in impaired brain growth.

🧓 Geriatric Use 83 words ▾

8.5Geriatric Use Clinical studies of OLPRUVA did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. 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, or cardiac function and of concomitant disease or other drug therapy.

🆘 Overdosage 66 words ▾

10 OVERDOSAGE Overdoses of OLPRUVA exceeding ten-fold the maximum recommended dosage may produce emesis, CNS depression, metabolic acidosis with or without respiratory alkalosis, hypernatremia, hypokalemia, and hypophosphatemia. Symptoms of overdose overlap with those of acute hyperammonemia. If overdose occurs, discontinue OLPRUVA, monitor plasma phenylacetate and ammonia levels closely, and institute appropriate emergency management, which may include hemodialysis, continuous veno-venous hemofiltration (CVVH) or extracorporeal membrane oxygenation (ECMO).

🧬 Clinical Pharmacology ~2 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Sodium phenylbutyrate is a pro-drug and is metabolized to phenylacetate. Phenylacetate is a metabolically active compound that conjugates with glutamine via acetylation to form phenylacetylglutamine. Phenylacetylglutamine is excreted by the kidneys, hence providing an alternate vehicle for waste nitrogen excretion.

12.2Pharmacodynamics In patients with urea cycle disorders, sodium phenylbutyrate decreased elevated plasma ammonia and glutamine levels.

12.3Pharmacokinetics The pharmacokinetics of phenylbutyrate and its metabolite phenylacetate were characterized in healthy adult subjects following a single oral administration of OLPRUVA (5 g of sodium phenylbutyrate) with suspension agent under fasted and fed conditions. Absorption The pharmacokinetic parameters for the maximum plasma concentration (C max ) and area under the plasma concentration-time curve (AUC) of phenylbutyrate and phenylacetate under fasted conditions are summarized in Table 1. Table 1 C max and AUC of Phenylbutyrate and Phenylacetate Following a Single Oral Dose Administration of OLPRUVA (5 g) in Healthy Subjects Under Fasted Conditions PK Parameters Phenylbutyrate Results (Mean ± SD) Phenylacetate Results (Mean ± SD) C max (μg/mL) 229 ± 48 39 ± 14 AUC inf (hr•μg/mL) 510 ± 129 183 ± 76 Effect of Food Compared to those under fasted conditions, phenylbutyrate C max was decreased by 50% and AUC inf decreased by 39% when OLPRUVA was administered with a high-fat meal (total 980 calories with 55% fat).

For the metabolite phenylacetate, C max decreased by 32% and AUC inf decreased by 29% with a high-fat meal compared to fasted conditions. Distribution The apparent volume of distribution of phenylbutyrate was

7.2L under fasted conditions. Elimination The mean half-life of phenylbutyrate was 0.5 hours under fasted conditions. The mean half-life of phenylacetate was 1.2 hours under fasted conditions.

Metabolism Following oral administration, sodium phenylbutyrate is metabolized by β-oxidation into phenylacetate which is converted to its coenzyme A ester, phenylacetyl-coenzyme A and further conjugated with glutamine to form phenylacetylglutamine. Phenylacetylglutamine is excreted by the kidneys. The major sites for metabolism of sodium phenylbutyrate are the liver and kidneys.

Phenylacetate is also hydrolyzed by esterases in liver and blood. Excretion Approximately 80-100% of sodium phenylbutyrate is excreted by the kidneys within 24 hours as phenylacetylglutamine. For each gram of sodium phenylbutyrate administered, it is estimated that between 0.12-0.15 grams of phenylacetylglutamine nitrogen are produced.

Specific Populations Patients with Renal Impairment or Hepatic Impairment OLPRUVA has not been studied in patients with renal impairment or in patients with hepatic impairment. Drug Interaction Studies In vitro or clinical studies with OLPRUVA for determination of potential drug-drug interaction have not been conducted.

🧬 Mechanism of Action 44 words ▾

12.1Mechanism of Action Sodium phenylbutyrate is a pro-drug and is metabolized to phenylacetate. Phenylacetate is a metabolically active compound that conjugates with glutamine via acetylation to form phenylacetylglutamine. Phenylacetylglutamine is excreted by the kidneys, hence providing an alternate vehicle for waste nitrogen excretion.

📦 How Supplied / Storage and Handling 183 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING OLPRUVA (sodium phenylbutyrate) for oral suspension is available in dosage strengths of 2 g, 3 g, 4 g, 5 g, 6 g, and 6.67 g of sodium phenylbutyrate as white to off-white pellets. Each dose is packaged in a dosage envelope containing one or two packets of sodium phenylbutyrate for oral suspension and a suspending agent packet (labeled as Mix-Aid). A 30-day supply of OLPRUVA is provided in a kit containing 90 dosage envelopes.

Table 2 OLPRUVA Available Dosage Strengths Dosage Strength OLPRUVA packet(s) in each envelope Envelope NDC Kit NDC 2 g one 2 g packet (NDC 72542-002-01) 72542-200-02 72542-200-09 3 g one 3 g packet (NDC 72542-003-01) 72542-300-02 72542-300-09 4 g two 2 g packets 72542-400-02 72542-400-18 5 g one 2 g packet and one 3 g packet 72542-500-02 72542-500-18 6 g two 3 g packets 72542-600-02 72542-600-18 6.67 g one 3 g packet and one 3.67 g packet (NDC 72542-367-01) 72542-667-02 72542-667-18 Store OLPRUVA at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].

📋 Description 148 words ▾

11 DESCRIPTION OLPRUVA (sodium phenylbutyrate) for oral suspension is a nitrogen binding agent. Sodium phenylbutyrate is a white to yellowish-white powder. It is freely soluble in water and in methanol, and practically insoluble in acetone and diethyl ether.

It is known chemically as sodium 4-phenylbutyrate with a molecular weight of 186.19 and molecular formula C 10 H 11 NaO 2 . Structural Formula: OLPRUVA is supplied in dosage envelopes containing 2 g (equivalent to 1.75 g phenylbutyrate), 3 g (equivalent to 2.63 g phenylbutyrate), 4 g (equivalent to 3.51 g phenylbutyrate), 5 g (equivalent to 4.38 g phenylbutyrate), 6 g (equivalent to 5.26 g phenylbutyrate), and 6.67 g (equivalent to 5.85 g phenylbutyrate) of sodium phenylbutyrate in one or two packets. OLPRUVA is a polymer coated formulation which contains the following inactive ingredients: amino methacrylate copolymer, hypromellose, microcrystalline cellulose, polyethylene glycol 6000, silicon dioxide, and talc.

Structural Formula

💬 Information for Patients 185 words ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Patient Information and Instructions for Use ). Neurotoxicity Advise the patient or caregiver that neurotoxicity may occur during OLPRUVA treatment. Inform the patient or caregiver of the signs and symptoms of this risk and to contact the healthcare provider immediately if signs and symptoms occur [ see Warnings and Precautions ( 5.1 ) ].

Preparation and Administration Inform the patient or caregiver that the OLPRUVA packet(s) must be mixed with the prepared Mix-Aid suspension and to drink the entire suspension within 5 minutes after stirring to minimize dissolution of coating. After 30 minutes, the suspension should be discarded [ see Dosage and Administration ( 2.3 ) ]. Inform the patient or caregiver that if a dose is missed, take the missed dose as soon as possible on the same day [ see Dosage and Administration ( 2.1 ) ].

Manufactured for: Acer Therapeutics Inc. 300 Washington St. Newton, MA 02458 For more information call Acer Therapeutics Inc. at 1-844-600-2237. © 2022 Acer Therapeutics Inc.

All rights reserved. 65003012 Acer Therapeutics Logo

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
← 72542-0300-09 · Acer 72542-0500-18 · Acer →
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.