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Hydrocodone Bitartrate 80 mg Tablet, Extended Release, 60-count — NDC 47781-0396-60 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Hydrocodone Bitartrate 80 mg Tablet, Extended Release, 60-count — NDC 47781-396-60 (Billing 47781-0396-60)

by Alvogen Inc. · 60 TABLET, EXTENDED RELEASE in 1 BOTTLE

This is a package of 60 tablets of Hydrocodone Bitartrate 80 mg Tablet, Extended Release from Alvogen Inc., marketed since Mar 2021 and currently FDA-listed. It is this product's only package size.

NDC 47781-0396-60
🏷️ FDA NDC (as labeled) 47781-396-60 billing pads the product segment with a zero
Rx only Generic On market CII 🛡 REMS ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

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

NDC database record

One package, one record: these facts belong to NDC 47781-396-60 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
47781 labeler · 396 product · 60 package
Package marketed since
Mar 3, 2021
Sample package
No — commercial package
Listing certified through
Dec 31, 2027
Billing quantity
60 EA per package
Barcode (UPC)
0347781394608, 0347781397609, 0347781395605, 0347781398606 +3 more
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 47781-396-60
Product NDC 47781-396
11-digit billing NDC 47781039660
NCPDP billing unit EA — each (per item)
RxCUI 1595730, 1595740, 1595746, 1595752, 1595758, 1595764, 1595770
UNII NO70W886KK
UPC 0347781394608, 0347781397609, 0347781395605, 0347781398606 +3 more
Application # ANDA208269
SPL Set ID f7b55d14-0980-b680-8ceb-7489ff65455e
Established class (EPC) Opioid Agonist
Mechanism of action Opioid Agonists
DEA schedule CII
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2021-03-03
Route ORAL
Dosage form TABLET, EXTENDED RELEASE
Substance HYDROCODONE BITARTRATE
TE code (Orange Book) AB · RLD · RS

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 6510003010A850
GPI class HYDROcodone Bitartrate ER
GCN Seq No 073181
GCN 37545
HICL code 001731
Ingredient (HICL) Hydrocodone Bitartrate
HIC1 code H
Therapeutic class — broad (HIC1) Nervous System (Except Autonomic)
HIC2 code H3
Therapeutic class — intermediate (HIC2) Analgesics
HIC3 code H3A
Therapeutic class — specific (HIC3) Opioid Analgesics
AHFS code 28:08.08.00
AHFS class Opioid Agonists (28:08)
FDB label name HYDROCODONE ER 80 MG TABLET
FDB brand name Hydrocodone Bitartrate Er
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 073181
  • GCN: 37545
  • GPI-14 (Medi-Span): 6510003010A850
  • HICL (First Databank): 001731
  • AHFS class code: 28:08.08.00
  • RxCUI (RxNorm): 1595730
Why two NDCs? The FDA registers this code as 47781-396-60 — 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 → 47781-0396-60. 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 Opioid Agonist class.

Pharmacologic class Opioid Agonist
Drug family (ATC) Opium alkaloids and derivatives
How it works Opioid Agonists
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.

Clinical

Label name HYDROCODONE ER 80 MG TABLET Ingredient Hydrocodone Bitartrate
📗 Our plain-language guide HelloPharmacist
  • Hydrocodone extended-release is for severe, persistent pain that needs an around-the-clock opioid when other treatments haven't worked or aren't enough. It isn't meant for as-neede...
  • Swallow it whole, by mouth. Never crush, chew, cut or dissolve it, since that can release a dangerous dose at once. The capsules are taken about every 12 hours and the tablets once...
  • No. Alcohol can raise hydrocodone levels and cause a potentially fatal overdose. Avoid alcohol-containing products too, and check with me before combining it with sleep aids, anxie...
  • Nausea, constipation, vomiting, dizziness, headache, sleepiness and fatigue are the most common. Call for help right away if breathing slows, you can't stay awake, or you faint.
📖 Read our full Hydrocodone guide →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

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 $28.06 $1,683.40 / 60 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.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
47781-0396-60 You're viewing this Main listing 60 TABLET, EXTENDED RELEASE in 1 BOTTLE 2021-03-03 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Hysingla ER 80 mg 59011-0275-60 Knoa 60 tablets $48.655 AB Availability likely —
Hydrocodone Bitartrate 80 mgthis 47781-0396-60 Alvogen 60 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

🏛️
2021
On the market since
Mar 2021
📍
2026
Currently FDA-listed
5 years 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.

What it looks like

Color White / Brown / Pink / Blue / Purple / Green / Yellow
ShapeRound
ImprintA398
Size12 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.

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.

Manufacturer & labeler

LabelerAlvogen Inc.
Application holderALVOGEN INC
FDA applicationANDA208269 (ANDA)
Labeler code47781
First marketedMar 2021
DEA scheduleCII
Product typeHuman Prescription Drug
Portfolio51 products on file

More NDCs from Alvogen Inc. labeler code 47781

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.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide 🍼 Nursing Mothers 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🔒 Drug Abuse and Dependence 🔒 Controlled Substance 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🚨 Boxed Warning ~3 min read ▾

WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF HYDROCODONE BITARTRATE EXTENDED-RELEASE TABLETS Addiction, Abuse, and Misuse Because the use of hydrocodone bitartrate extended-release tablets exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death, assess each patient’s risk prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions [see Warnings and Precautions ( 5.1 )] . Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of hydrocodone bitartrate extended-release tablets, especially during initiation or following a dosage increase.

To reduce the risk of respiratory depression, proper dosing and titration of hydrocodone bitartrate extended-release tablets are essential. Instruct patients to swallow hydrocodone bitartrate extended-release tablets whole; crushing, chewing, or dissolving hydrocodone bitartrate extended-release tablets can cause rapid release and absorption of a potentially fatal dose of hydrocodone [see Warnings and Precautions ( 5.2 )] . Accidental Ingestion Accidental ingestion of even one dose of hydrocodone bitartrate extended-release tablets, especially by children, can result in a fatal overdose of hydrocodone [see Warnings and Precautions ( 5.2 )] .

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of hydrocodone bitartrate extended-release tablets and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see Warnings and Precautions ( 5.3 ), Drug Interactions ( 7 )].

Neonatal Opioid Withdrawal Syndrome (NOWS) Advise pregnant women using opioids for an extended period of time of the risk of Neonatal Opioid Withdrawal Syndrome, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery [see Warnings and Precautions ( 5.4 )] . Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) Healthcare providers are strongly encouraged to complete a REMS-compliant education program and to counsel patients and caregivers on serious risks, safe use, and the importance of reading the Medication Guide with each prescription [see Warnings and Precautions ( 5.5 )] .

Cytochrome P450 3A4 Interaction The concomitant use of hydrocodone bitartrate extended-release tablets with all cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in hydrocodone plasma concentration. Regularly evaluate patients receiving hydrocodone bitartrate extended-release tablets and any CYP3A4 inhibitor or inducer [ see Warnings and Precautions ( 5.6 ), Drug Interactions ( 7 ), and Clinical Pharmacology ( 12.3 )].

WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF HYDROCODONE BITARTRATE EXTENDED-RELEASE TABLETS See full prescribing information for complete boxed warning. Hydrocodone bitartrate extended-release tablets expose users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess patient’s risk before prescribing, and reassess regularly for these behaviors and conditions.

( 5.1 ) Serious, life-threatening, or fatal respiratory depression may occur, especially upon initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of hydrocodone bitartrate extended-release tablets are essential. Instruct patients to swallow hydrocodone… [Excerpted — this section continues on DailyMed.]

🎯 Indications and Usage ~1 min read ▾

1 INDICATIONS AND USAGE Hydrocodone bitartrate extended-release tablets are indicated for the management of severe and persistent pain that requires an opioid analgesic and that cannot be adequately treated with alternative options, including immediate-release opioids. Limitations of Use Because of the risks of addiction, abuse, misuse, overdose and death, which can occur at any dosage or duration and persist over the course of therapy [see Warnings and Precautions ( 5.1 )] , reserve opioid analgesics, including hydrocodone bitartrate extended-release tablets, for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.

Hydrocodone bitartrate extended-release tablets are not indicated as an as-needed (prn) analgesic. Hydrocodone bitartrate extended-release tablets are an opioid agonist indicated for the management of severe and persistent pain that requires an opioid analgesic and that cannot be adequately treated with alternative options, including immediate-release opioids. ( 1 ) Limitations of Use Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy, reserve opioid analgesics, including hydrocodone bitartrate extended-release tablets for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.

( 1 , 5.1 ) Hydrocodone bitartrate extended-release tablets are not indicated as an as-needed (prn) analgesic. ( 1 )

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Hydrocodone bitartrate extended-release tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of extended-release/long-acting opioids and how to mitigate the associated risks. ( 2.1 ) Daily doses of hydrocodone bitartrate extended-release tablets greater than or equal to 80 mg are only for use in patients in whom tolerance to an opioid of comparable potency has been established. ( 2.1 ) Patients considered opioid-tolerant are those taking, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid.

( 2.1 ) Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. ( 2.1 ) Reserve titration to higher doses of hydrocodone bitartrate extended-release tablets for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. ( 2.1 , 5.1 ) Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse.

( 2.1 , 5.1 ) Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with hydrocodone bitartrate extended-release tablets. Consider this risk when selecting an initial dose and when making dose adjustments. ( 2.1 , 5.2 ) Hydrocodone bitartrate extended-release tablets are administered orally once daily (every 24 hours).

( 2.1 ) Instruct patients to swallow hydrocodone bitartrate extended-release tablets intact, and not to crush, chew, or dissolve the tablets (risk of potentially fatal overdose). ( 2.1 , 5.1 ) Instruct patients to take tablets one at a time, with enough water to ensure complete swallowing immediately after placing in the mouth. ( 2.1 , 5.13 ) For patients who are not opioid tolerant, initiate with 20 mg tablets orally every 24 hours.

( 2.3 ) Discuss opioid overdose reversal agents and options for acquiring them with the patient and/or caregiver, both when initiating and renewing treatment with hydrocodone bitartrate extended-release tablets, especially if the patient has additional risk factors for overdose, or close contacts at risk for exposure and overdose. ( 2.2 , 5.1 , 5.2 , 5.3 ) To convert to hydrocodone bitartrate extended-release tablets from another opioid, follow the conversion instructions to obtain an estimated dose. ( 2.3 ) Dose titration of hydrocodone bitartrate extended-release tablets may occur every 3 to 5 days.

( 2.4 ) Periodically reassess patients receiving hydrocodone bitartrate extended-release tablets to evaluate the continued need for opioid analgesics to maintain pain control, for the signs or symptoms of adverse reactions, and for the development of addiction, abuse, or misuse. ( 2.4 ) Patients with Severe Hepatic Impairment : Initiate dosing with one half of the recommended starting dosage and titrate carefully. Regularly evaluate for respiratory depression, sedation, and hypotension.

( 2.5 ) Patients with Moderate to Severe Renal Impairment and End-Stage Renal Disease : Initiate dosing at one half the recommended starting dosage and titrate carefully. Regularly evaluate for signs of respiratory depression, sedation, and hypotension. ( 2.6 ) Do not rapidly reduce or abruptly discontinue hydrocodone bitartrate extended-release tablets in a physically-dependent patient because rapid reduction or abrupt discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide.

( 2.7 , 5.16 )

2.1Important Dosage and Administration Instructions Hydrocodone bitartrate extended-release tablets should be pre… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 179 words ▾

3 DOSAGE FORMS AND STRENGTHS 20 mg film-coated extended-release tablets (white, round, film-coated tablet, “A392” printed in black ink on one side, blank on the other side) 30 mg film-coated extended-release tablets (beige, round, film-coated tablet, “A393” printed in black ink on one side, blank on the other side) 40 mg film-coated extended-release tablets (pink, round, film-coated tablet, “A394” printed in black ink on one side, blank on the other side) 60 mg film-coated extended-release tablets (blue, round, film-coated tablet, “A395” printed in black ink on one side, blank on the other side) 80 mg film-coated extended-release tablets (violet, round, film-coated tablet, “A396” printed in black ink on one side, blank on the other side) 100 mg film-coated extended-release tablets (green, round, film-coated tablet, “A397” printed in black ink on one side, blank on the other side) 120 mg film-coated extended-release tablets (yellow, round, film-coated tablet, “A398” printed in black ink on one side, blank on the other side) Extended-release tablets: 20 mg, 30 mg, 40 mg, 60 mg, 80 mg, 100 mg, and 120 mg ( 3 )

⛔ Contraindications 124 words ▾

4 CONTRAINDICATIONS Hydrocodone bitartrate extended-release tablets are contraindicated in patients with: Significant respiratory depression [see Warnings and Precautions ( 5.2 )] Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions ( 5.8 )] Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions ( 5.13 , 5.14 )] Hypersensitivity to hydrocodone or any component of hydrocodone bitartrate extended-release tablets.

Significant respiratory depression ( 4 ) Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment ( 4 ) Known or suspected gastrointestinal obstruction, including paralytic ileus ( 4 ) Hypersensitivity to hydrocodone or to any other components of hydrocodone bitartrate extended-release tablets ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Opioid-Induced Hyperalgesia and Allodynia : Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. If OIH is suspected, carefully consider appropriately decreasing the dose of the current opioid analgesic, or opioid rotation. ( 5.7 ) Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients : Regularly evaluate, particularly during initiation and titration.

( 5.8 ) Adrenal Insufficiency : If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. ( 5.9 ) Severe Hypotension : Regularly evaluate during dosage initiation and titration. Avoid use of hydrocodone bitartrate extended-release tablets in patients with circulatory shock.

( 5.10 ) QTc Prolongation : Avoid use in patients with congenital long QTc syndrome. In patients who develop QTc prolongation, consider reducing the dose. ( 5.11 , 12.2 ) Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness : Monitor for sedation and respiratory depression.

Avoid use of hydrocodone bitartrate extended-release tablets in patients with circulatory shock. ( 5.12 ) Risk of Obstruction in Patients who have Difficulty Swallowing or have Underlying GI Disorders that may Predispose them to Obstruction : Consider use of an alternative analgesic. ( 5.14 )

5.1Addiction, Abuse, and Misuse Hydrocodone bitartrate extended-release tablets contain hydrocodone, a Schedule II controlled substance. As an opioid, hydrocodone bitartrate extended-release tablets expose users to the risks of addiction, abuse, and misuse. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed hydrocodone bitartrate extended-release tablets.

Addiction can occur at recommended doses and if the drug is misused or abused. The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy. In postmarketing studies, addiction, abuse, misuse, and fatal and non-fatal opioid overdose were observed in patients with long-term opioid use [see Adverse Reactions ( 6.2 )] .

Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing hydrocodone bitartrate extended-release tablets, and reassess all patients receiving hydrocodone bitartrate extended-release tablets for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the prescribing of hydrocodone bitartrate extended-release tablets for the proper management of pain in any given patient.

Patients at increased risk may be prescribed opioids such as hydrocodone bitartrate extended-release tablets, but use in such patients necessitates intensive counseling about the risks and proper use of hydrocodone bitartrate extended-release tablets along with frequent reevaluation for signs of addiction, abuse, and misuse. Consider recommending or prescribing an opioid overdose reversal agent [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.2 )]. Abuse or misuse of hydrocodone bitartrate extended-release tablets by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of the hydrocodone and can result in overdose and death [see Drug Abuse and Dependence ( 9.2 ), Overdosage ( 10 )] .

Opioids are sought for nonmedical use and are subject to diversion from legitimate prescribed use. Consider these risks when prescribing or dispensing hydrocodone bitartrate extended-release tablets. Strategies to reduce these risks include prescribing the drug in t… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Addiction, Abuse, and Misuse [see Warnings and Precautions ( 5.1 )] Life-Threatening Respiratory Depression [see Warnings and Precautions ( 5.2 )] Interactions with Benzodiazepine or Other CNS Depressants [see Warnings and Precautions ( 5.3 )] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions ( 5.4 )] Opioid-Induced Hyperalgesia and Allodynia [see Warnings and Precautions ( 5.7 )] Adrenal Insufficiency [see Warnings and Precautions ( 5.9 )] Severe Hypotension [see Warnings and Precautions ( 5.10 )] Gastrointestinal Adverse Reactions [see Warnings and Precautions ( 5.13 , 5.14 )] Seizures [see Warnings and Precautions ( 5.15 )] Withdrawal [see Warnings and Precautions ( 5.16 )] Most common treatment-emergent adverse events (incidence ≥ 5%) are constipation, nausea, vomiting, fatigue, upper respiratory tract infection, dizziness, headache, and somnolence.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Alvogen, Inc. at 1-866-770-3024 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. A total of 1,827 patients were treated with hydrocodone bitartrate extended-release tablets in controlled and open-label chronic pain clinical trials. Five hundred patients were treated for 6 months and 364 patients were treated for 12 months.

The clinical trial population consisted of patients who were not opioid tolerant and opioid-experienced patients with persistent moderate to severe chronic pain. The common adverse reactions (≥2%) reported by patients in clinical trials comparing hydrocodone bitartrate extended-release tablets (20 mg/day to 120 mg/day) with placebo are shown in Table 2 below: Table 2: Adverse Reactions Reported in ≥2% of Patients during the Open-Label Titration Period and Double-Blind Treatment Period: Patients Who Were Not Opioid Tolerant and Opioid-Experienced Patients Open-label Titration Period Double-blind Treatment Period MedDRA Preferred Term (N=905) (%) Placebo (N=292) (%) Hydrocodone Bitartrate Extended-Release Tablets (N=296) (%) Nausea 16 5 8 Constipation 9 2 3 Vomiting 7 3 6 Dizziness 7 2 3 Headache 7 2 2 Somnolence 5 1 1 Fatigue 4 1 1 Pruritus 3 <1 0 Tinnitus 2 1 2 Insomnia 2 2 3 Decreased appetite 1 1 2 Influenza 1 1 3 The adverse reactions seen in controlled and open-label chronic pain studies are presented below in the following manner: most common (≥5%), common (≥1% to <5%), and less common (<1%).

The most common adverse reactions (≥5%) reported by patients treated with hydrocodone bitartrate extended-release tablets in the chronic pain clinical trials were constipation, nausea, vomiting, fatigue, upper respiratory tract infection, dizziness, headache, somnolence. The common (≥1% to <5%) adverse events reported by patients treated with hydrocodone bitartrate extended-release tablets in the chronic pain clinical trials organized by MedDRA (Medical Dictionary for Regulatory Activities) System Organ Class were: Ear and labyrinth disorders tinnitus Gastrointestinal disorders abdominal pain, abdominal pain upper, diarrhea, dry mouth, dyspepsia, gastroesophageal reflux disease General disorders and administration site conditions chest pain, chills, edema peripheral, pain, pyrexia Infections and infestations bronchitis, gastroenteritis, gastroenteritis viral, influenza, nasopharyngitis, sinusitis, urinary tract infection Injury, poisoning and procedural complications fall, muscle strain Metabolism and nutrition disorders decreased appetite Musculoskeletal and connective tissue disorders arthralgia, back pain, muscle spasms, musculoskeletal pain, myalgia, pain in extremity Nervous system disorders lethargy, m… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Table 3 includes clinically significant drug interactions with hydrocodone bitartrate extended-release tablets. Table 3: Clinically Significant Drug Interactions with Hydrocodone Bitartrate Extended-Release Tablets Inhibitors of CYP3A4 Clinical Impact: The concomitant use of hydrocodone bitartrate extended-release tablets and CYP3A4 inhibitors can increase the plasma concentration of hydrocodone, resulting in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of hydrocodone bitartrate extended-release tablets and CYP3A4 inhibitors, particularly when an inhibitor is added after a stable dose of hydrocodone bitartrate extended-release tablets is achieved [see Warnings and Precautions ( 5.6 )] .

After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the hydrocodone plasma concentration will decrease [see Clinical Pharmacology ( 12.3 )] , resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to hydrocodone. Intervention: If concomitant use is necessary, consider dosage reduction of hydrocodone bitartrate extended-release tablets until stable drug effects are achieved. Evaluate patients at frequent intervals for respiratory depression and sedation.

If a CYP3A4 inhibitor is discontinued, consider increasing the hydrocodone bitartrate extended-release tablets dosage until stable drug effects are achieved. Assess for signs of opioid withdrawal. Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir).

CYP3A4 Inducers Clinical Impact: The concomitant use of hydrocodone bitartrate extended-release tablets and CYP3A4 inducers can decrease the plasma concentration of hydrocodone [see Clinical Pharmacology ( 12.3 )] , resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to hydrocodone [see Warnings and Precautions ( 5.6 )] . After stopping a CYP3A4 inducer, as the effects of the inducer decline, the hydrocodone plasma concentration will increase [see Clinical Pharmacology ( 12.3 )] , which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression.

Intervention: If concomitant use is necessary, consider increasing the hydrocodone bitartrate extended-release tablet dosage until stable drug effects are achieved. Evaluate for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider hydrocodone bitartrate extended-release tablet dosage reduction and evaluate patients at frequent intervals for signs of respiratory depression and sedation.

Examples: Rifampin, carbamazepine, phenytoin Benzodiazepines and Other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death [see Warnings and Precautions ( 5.3 )] . Intervention: Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

Limit dosages and durations to the minimum required. Inform patients and caregivers of this potential interaction and educate them on the signs and symptoms of respiratory depression (including sedation). If concomitant use is warranted, consider recommending or prescribing an opioid overdose reversal agent [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.1 , 5.2 , 5.3 )] .

Examples: Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids (gabapentin or pregabalin), other opioids, alcohol. Serotonergic Drugs Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter sys… [Excerpted — this section continues on DailyMed.]

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Pregnancy : May cause fetal harm. ( 8.1 ) Lactation : Not recommended. ( 8.2 )

8.1Pregnancy Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions ( 5.4 )] . Available data with hydrocodone bitartrate extended-release tablets in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies with hydrocodone in rats and rabbits no embryotoxicity or teratogenicity was observed.

However, reduced pup survival rates, reduced fetal/pup body weights, and delayed ossification were observed at doses causing maternal toxicity. In all of the studies conducted, the exposures in animals were less than the human exposure [see Data] . The 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 Fetal/neonatal adverse reactions Use of opioid analgesics for extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth.

Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions ( 5.4 )] .

Labor and Delivery Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid overdose reversal agent, such as naloxone or nalmefene, must be available for reversal of opioid-induced respiratory depression in the neonate. Hydrocodone bitartrate extended-release tablets are not recommended for use in pregnant women during or immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate.

Opioid analgesics, including hydrocodone bitartrate extended-release tablets, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression.

Data Animal Data No evidence of embryotoxicity or teratogenicity was observed after oral administration of hydrocodone throughout the period of organogenesis in rats and rabbits at doses up to 30 mg/kg/day (approximately 0.1 and 0.3 times, respectively, the human hydrocodone dose of 120 mg/day based on AUC exposure comparisons). However, in these studies, reduced fetal body weights and delayed ossification were observed in rat at 30 mg/kg/day and reduced fetal body weights were observed in rabbits at 30 mg/kg/day (approximately 0.1 and 0.3 times, respectively, the human hydrocodone dose of 120 mg/day based on AUC exposure comparisons).

In a pre- and post-natal development study pregnant rats were administered oral hydrocodone throughout the period of gestation and lactation. At a dose of 30 mg/kg/day decreased pup viability, pup survival indices, litter size and pup body weight were observed. This dose is approximately 0.1 times the human hydrocodone dose of 120 mg/day based on AUC exposure comparisons.

8.2Lactation Ri… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions ( 5.4 )] . Available data with hydrocodone bitartrate extended-release tablets in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies with hydrocodone in rats and rabbits no embryotoxicity or teratogenicity was observed.

However, reduced pup survival rates, reduced fetal/pup body weights, and delayed ossification were observed at doses causing maternal toxicity. In all of the studies conducted, the exposures in animals were less than the human exposure [see Data] . The 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 Fetal/neonatal adverse reactions Use of opioid analgesics for extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth.

Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions ( 5.4 )] .

Labor and Delivery Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid overdose reversal agent, such as naloxone or nalmefene, must be available for reversal of opioid-induced respiratory depression in the neonate. Hydrocodone bitartrate extended-release tablets are not recommended for use in pregnant women during or immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate.

Opioid analgesics, including hydrocodone bitartrate extended-release tablets, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression.

Data Animal Data No evidence of embryotoxicity or teratogenicity was observed after oral administration of hydrocodone throughout the period of organogenesis in rats and rabbits at doses up to 30 mg/kg/day (approximately 0.1 and 0.3 times, respectively, the human hydrocodone dose of 120 mg/day based on AUC exposure comparisons). However, in these studies, reduced fetal body weights and delayed ossification were observed in rat at 30 mg/kg/day and reduced fetal body weights were observed in rabbits at 30 mg/kg/day (approximately 0.1 and 0.3 times, respectively, the human hydrocodone dose of 120 mg/day based on AUC exposure comparisons).

In a pre- and post-natal development study pregnant rats were administered oral hydrocodone throughout the period of gestation and lactation. At a dose of 30 mg/kg/day decreased pup viability, pup survival indices, litter size and pup body weight were observed. This dose is approximately 0.1 times the human hydrocodone dose of 120 mg/day based on AUC exposure comparisons.

🧒 Pediatric Use 73 words ▾

8.4Pediatric Use The safety and effectiveness of hydrocodone bitartrate extended-release tablets in pediatric patients have not been established. Hydrocodone bitartrate extended-release tablets gradually forms a viscous hydrogel (i.e., a gelatinous mass) when exposed to water or other fluids. Pediatric patients may be at increased risk of esophageal obstruction, dysphagia, and choking because of a smaller gastrointestinal lumen if they ingest hydrocodone bitartrate extended-release tablets [see Warnings and Precautions ( 5.13 )] .

🧓 Geriatric Use ~1 min read ▾

8.5Geriatric Use In a controlled pharmacokinetic study, elderly subjects (greater than 65 years) compared to young adults had similar plasma concentrations of hydrocodone [see Clinical Pharmacology ( 12.3 )] . Of the 1827 subjects exposed to hydrocodone bitartrate extended-release tablets in the pooled chronic pain studies, 241 (13%) were age 65 and older (including those age 75 and older), while 42 (2%) were age 75 and older. In clinical trials with appropriate initiation of therapy and dose titration, no untoward or unexpected adverse reactions were seen in the elderly patients who received hydrocodone bitartrate extended-release tablets.

In general, use caution when selecting a dosage for an elderly patient, 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. Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration.

Titrate the dosage of hydrocodone bitartrate extended-release tablets slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see Warnings and Precautions ( 5.8 )] . Hydrocodone is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to regularly evaluate renal function.

🆘 Overdosage ~2 min read ▾

10 OVERDOSAGE Clinical Presentation Acute overdosage with hydrocodone can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, hypoglycemia, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see Clinical Pharmacology ( 12.2 )] . Toxic leukoencephalopathy has been reported after opioid overdose and can present hours, days, or weeks after apparent recovery from the initial intoxication.

Treatment of Overdose In case of overdose, priorities are the re-establishment of a patent airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema accompanying overdose as indicated. Cardiac arrest or arrhythmias will require advanced life support measures.

For clinically significant respiratory or circulatory depression secondary to hydrocodone overdose, administer an opioid overdose reversal agent such as naloxone or nalmefene. Because the duration of opioid reversal is expected to be less than the duration of action of hydrocodone in hydrocodone bitartrate extended-release tablets, carefully monitor the patient until spontaneous respiration is reliably re-established. Hydrocodone bitartrate extended-release tablets will continue to release hydrocodone and add to the hydrocodone load for 24 to 48 hours or longer following ingestion, necessitating prolonged monitoring.

If the response to an opioid overdose reversal agent is suboptimal or only brief in nature, administer additional reversal agent as directed by the product’s prescribing information. In an individual physically dependent on opioids, administration of the recommended dose of the opioid overdose reversal agent will precipitate an acute withdrawal syndrome. The severity of the withdrawal syndrome produced will depend on the degree of physical dependence and the dose of the reversal agent administered.

If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the reversal agent should be initiated with care and by titration with smaller than usual doses of the reversal agent.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Hydrocodone is a full opioid agonist with relative selectivity for the mu-opioid receptor, although it can interact with other opioid receptors at higher doses. The principal therapeutic action of hydrocodone is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia with hydrocodone.

Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory and CNS depression. The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug.

12.2Pharmacodynamics Cardiac Electrophysiology QTc interval prolongation was studied in a double-blind, placebo- and positive-controlled 3-treatment parallel-group, dose-escalating study of hydrocodone bitartrate extended-release tablets in 196 healthy subjects. QTc interval prolongation was observed following hydrocodone bitartrate extended-release tablets 160 mg per day. The maximum mean (90% upper confidence bound) difference in the QTc interval between hydrocodone bitartrate extended-release tablets and placebo (after baseline-correction) at steady state was 6 (9) milliseconds, 7 (10) milliseconds, and 10 (13) milliseconds at hydrocodone bitartrate extended-release tablet doses of 80 mg, 120 mg and 160 mg respectively.

For clinical implications of the prolonged QTc interval, [see Warnings and Precautions ( 5.11 )] . Effects on the Central Nervous System Hydrocodone produces respiratory depression by direct action on brainstem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and electrical stimulation.

Hydrocodone causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origin may produce similar findings). Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see Overdosage ( 10 )] .

Effects on the Gastrointestinal Tract and Other Smooth Muscle Hydrocodone causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone is increased to the point of spasm, resulting in constipation.

Other opioid-induced effects may include a reduction in biliary and pancreatic secretions, spasm of sphincter of Oddi, transient elevations in serum amylase, and opioid-induced esophageal dysfunction (OIED). Effects on the Cardiovascular System Hydrocodone produces peripheral vasodilation, which may result in orthostatic hypotension or syncope Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes, sweating, and/or orthostatic hypotension. Effects on the Endocrine System Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans [see Adverse Reactions ( 6.2 )] .

They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon. Use of opioids for an extended period of time may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility. The causal role of opioids in the clinical syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date [see Adverse Reactions ( 6.2) ] .

Effec… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 113 words ▾

12.1Mechanism of Action Hydrocodone is a full opioid agonist with relative selectivity for the mu-opioid receptor, although it can interact with other opioid receptors at higher doses. The principal therapeutic action of hydrocodone is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia with hydrocodone.

Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory and CNS depression. The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug.

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

16 HOW SUPPLIED/STORAGE AND HANDLING Hydrocodone Bitartrate Extended-Release Tablets 20 mg are white, round, film-coated tablets, with “A392” printed in black ink on one side, and blank on the other side. They are supplied in opaque plastic bottles with a child-resistant closure. (NDC 47781-392-60, Bottle of 60 tablets).

Hydrocodone Bitartrate Extended-Release Tablets 30 mg are beige, round, film-coated tablets, with “A393” printed in black ink on one side, and blank on the other side. They are supplied in opaque plastic bottles with a child-resistant closure. (NDC 47781-393-60, Bottle of 60 tablets).

Hydrocodone Bitartrate Extended-Release Tablets 40 mg are pink, round, film-coated tablets, with “A394” printed in black ink on one side, and blank on the other side. They are supplied in opaque plastic bottles with a child-resistant closure. (NDC 47781-394-60, Bottle of 60 tablets).

Hydrocodone Bitartrate Extended-Release Tablets 60 mg are blue, round, film-coated tablets, with “A395” printed in black ink on one side, and blank on the other side. They are supplied in opaque plastic bottles with a child-resistant closure. (NDC 47781-395-60, Bottle of 60 tablets).

Hydrocodone Bitartrate Extended-Release Tablets 80 mg are violet, round, film-coated tablets, with “A396” printed in black ink on one side, and blank on the other side. They are supplied in opaque plastic bottles with a child-resistant closure. (NDC 47781-396-60, Bottle of 60 tablets).

Hydrocodone Bitartrate Extended-Release Tablets 100 mg are green, round, film-coated tablets, with “A397” printed in black ink on one side, and blank on the other side. They are supplied in opaque plastic bottles with a child-resistant closure. (NDC 47781-397-60, Bottle of 60 tablets).

Hydrocodone Bitartrate Extended-Release Tablets 120 mg are yellow, round, film-coated tablets, with “A398” printed in black ink on one side, and blank on the other side. They are supplied in opaque plastic bottles with a child-resistant closure. (NDC 47781-398-60, Bottle of 60 tablets).

Store at 25°C (77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant container, as defined by the USP. Store Hydrocodone Bitartrate Extended-Release Tablets securely and dispose of properly.

📋 Description ~1 min read ▾

11 DESCRIPTION Hydrocodone bitartrate extended-release tablets are supplied in 20 mg, 30 mg, 40 mg, 60 mg, 80 mg, 100 mg and 120 mg film-coated tablets for oral administration. The tablet strengths describe the amount of hydrocodone per tablet as the bitartrate salt. Hydrocodone bitartrate is an opioid agonist.

Its chemical name is 4,5α-epoxy-3-methoxy-17-methylmorphinan-6-one tartrate (1:1) hydrate (2:5). Its structural formula is: Empirical formula: C 18 H 21 NO 3 • C 4 H 6 O 6 • 2½H 2 O; Molecular weight: 494.49. Hydrocodone bitartrate exists as fine white crystals or a crystalline powder.

It is affected by light. It is soluble in water, slightly soluble in alcohol, and insoluble in ether and chloroform. The 20 mg, 30 mg, 40 mg, 60 mg, 80 mg, 100 mg and 120 mg tablets contain the following inactive ingredients: hydroxypropyl cellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol (PEG), polyethylene oxide, polysorbate 80, polyvinyl alcohol, talc, and titanium dioxide.

The 30 mg tablets also contain iron oxide red and iron oxide yellow. The 40 mg tablets also contain iron oxide red. The 60 mg tablets also contain FD&C Blue #2.

The 80 mg tablets also contain D&C Red #27 and FD&C Blue #1. The 100 mg tablets also contain FD&C Blue #2 and iron oxide yellow. The 120 mg tablets also contain iron oxide yellow.

The tablet imprinting ink contains ammonium hydroxide, butyl alcohol, iron oxide black, isopropyl alcohol, propylene glycol, and shellac.

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Storage and Disposal Because of the risks associated with accidental ingestion, misuse, and abuse, advise patients to store hydrocodone bitartrate extended-release tablets securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home. Inform patients that leaving hydrocodone bitartrate extended-release tablets unsecured can pose a deadly risk to others in the home [see Warnings and Precautions ( 5.1 , 5.2 ), Drug Abuse and Dependence ( 9.2 )] .

Advise patients and caregivers that when medicines are no longer needed, they should be disposed of promptly. Expired, unwanted, or unused hydrocodone bitartrate extended-release tablets should be disposed of by flushing the unused medication down the toilet if a drug take-back option is not readily available. Inform patients that they can visit www.fda.gov/drugdisposal for a complete list of medicines recommended for disposal by flushing, as well as additional information on disposal of unused medicines.

Addiction, Abuse, and Misuse Inform patients that the use of hydrocodone bitartrate extended-release tablets, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose or death [see Warnings and Precautions ( 5.1 )] . Instruct patients not to share hydrocodone bitartrate extended-release tablets with others and to take steps to protect hydrocodone bitartrate extended-release tablets from theft or misuse. Life-Threatening Respiratory Depression Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting hydrocodone bitartrate extended-release tablets or when the dosage is increased, and that it can occur even at recommended dosages.

Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [see Warnings and Precautions ( 5.2 ), Overdosage ( 10 )] . Accidental Ingestion Inform patients that accidental ingestion, especially by children, may result in respiratory depression or death [see Warnings and Precautions ( 5.2 )] . Interaction with Benzodiazepines and other CNS Depressants Inform patients and caregivers that potentially fatal additive effects may occur if hydrocodone bitartrate extended-release tablets are used with benzodiazepines or other CNS depressants, including alcohol (e.g., non-­benzodiazepine sedative/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids [gabapentin or pregabalin], and other opioids), and not to use these concomitantly unless supervised by a health care provider [see Warnings and Precautions ( 5.3 ), Drug Interactions ( 7 )] .

Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene). Discuss the importance of having access to an opioid overdose reversal agent, especially if the patient has risk factors for overdose (e.g., concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose) or if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose.

Discuss with the patient the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program) [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.3 )] . Educate patients and caregivers on how to recognize the signs and symptoms of an overdose. Explain to patients and caregivers that effects of opioid overdose reversal agents like naloxone and nalmefene are temporary, and that they must call 911 or get… [Excerpted — this section continues on DailyMed.]

💬 Medication Guide ~3 min read ▾

Medication Guide Hydrocodone Bitartrate (hye'' droe koe' done bye tar' trate) Extended-Release Tablets, CII Hydrocodone bitartrate extended-release tablets are: A strong prescription pain medicine that contains an opioid (narcotic) that is used to manage severe and persistent pain that requires an extended treatment period with a daily opioid pain medicine, when other non-opioid pain medicines do not treat your pain well enough or you cannot tolerate them. A long-acting (extended-release) opioid pain medicine that can put you at risk for overdose and death.

Even if you take your dose correctly as prescribed you are at risk for opioid addiction, abuse, and misuse that can lead to death. Not to be taken on an “as needed” basis. Important information about hydrocodone bitartrate extended-release tablets: Get emergency help or call 911 right away if you take too many hydrocodone bitartrate extended-release tablets (overdose) .

When you first start taking hydrocodone bitartrate extended-release tablets, when your dose is changed, or if you take too much (overdose), serious or life-threatening breathing problems that can lead to death may occur. Ask your healthcare provider about medicines like naloxone or nalmefene that can be used in an emergency to reverse an opioid overdose. Taking hydrocodone bitartrate extended-release tablets with other opioid medicines, benzodiazepines,gabapentinoids (gabapentin or pregabalin), alcohol, or other central nervous system depressants (including street drugs) can cause severe drowsiness, decreased awareness, breathing problems, coma, and death.

Never give anyone else your hydrocodone bitartrate extended-release tablets. They could die from taking it. Selling or giving away hydrocodone bitartrate extended-release tablets is against the law.

Store hydrocodone bitartrate extended-release tablets securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home. Do not take hydrocodone bitartrate extended-release tablets if you have: severe asthma, trouble breathing, or other lung problems. a bowel blockage or have narrowing of the stomach or intestines. Before taking hydrocodone bitartrate extended-release tablets, tell your healthcare provider if you have a history of: head injury, seizures liver, kidney, thyroid problems problems urinating pancreas or gallbladder problems heart rhythm problems (long QT syndrome) abuse of street or prescription drugs, alcohol addiction, opioid overdose, or mental health problems Tell your healthcare provider if you are: noticing your pain getting worse.

If your pain gets worse after you take hydrocodone bitartrate extended-release tablets, do not take more of hydrocodone bitartrate extended-release tablets without first talking to your healthcare provider. Talk to your healthcare provider if the pain that you have increases, if you feel more sensitive to pain, or if you have new pain after taking hydrocodone bitartrate extended-release tablets. pregnant or planning to become pregnant . Use of hydrocodone bitartrate extended-release tablets for an extended period of time during pregnancy can cause withdrawal symptoms in your newborn baby that could be life-threatening if not recognized and treated. breastfeeding .

Not recommended during treatment with hydrocodone bitartrate extended-release tablets. It may harm your baby. living in a household where there are small children or someone who has abused street or prescription drugs. taking prescription or over-the-counter medicines, vitamins, or herbal supplements. Taking hydrocodone bitartrate extended-release tablets with certain other medicines can cause serious side effects and could lead to death.

When taking hydrocodone bitartrate extended-release tablets: Do not change your dose. Take hydrocodone bitartrate extended-release tablets exactly as prescribed by your healthcare provider. Use the lowest dose possible for the shortest time needed.

Take your prescribe… [Excerpted — this section continues on DailyMed.]

🍼 Nursing Mothers 56 words ▾

8.3Females and Males of Reproductive Potential Infertility Use of opioids for an extended period of time may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible [see Adverse Reactions ( 6.2 ), Clinical Pharmacology ( 12.2 ), Nonclinical Toxicology ( 13.1 )] .

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Absorption Hydrocodone bitartrate extended-release tablets are a single-entity extended-release formulation of hydrocodone that yields a gradual increase in plasma hydrocodone concentrations with a median T max of 14 to 16 hours noted for different dose strengths. Peak plasma levels may occur in the range of 6 to 30 hours after single-dose hydrocodone bitartrate extended-release tablets administration. Systemic exposure (AUC and C max ) increased linearly with doses from 20 to 120 mg.

Both C max and AUC increased slightly more than dose proportionally (Table 6). The mean terminal half-life (t 1/2 ) was similar for all hydrocodone bitartrate extended-release tablets dose strengths ranging from 7 to 9 hours. Table 6.

Mean (SD) Single-Dose Pharmacokinetic Parameters of Hydrocodone Bitartrate Extended-Release Tablets Dose Strength (mg) AUCinf (ng•h/mL) C max (ng/mL) T max * (h) 20 284 (128) 14.6 (5.5) 16 (6, 24) 40 622 (252) 33.9 (11.8) 16 (6, 24) 60 1009 (294) 53.6 (15.4) 14 (10, 30) 80 1304 (375) 69.1 (17.2) 16 (10, 24) 120 1787 (679) 110 (44.1) 14 (6, 30) * median (minimum, maximum) As compared to an immediate-release hydrocodone combination product, hydrocodone bitartrate extended-release tablets at the same daily dose results in similar bioavailability but with lower maximum concentrations at steady state (Figure 3).

Figure 3: Mean Steady-State Plasma Hydrocodone Concentration Profile Steady-state plasma hydrocodone concentrations were confirmed on day 3 of once-daily dosing of hydrocodone bitartrate extended-release tablets. The extent of accumulation of systemic exposure was 1.3 and 1.1 fold with respect to AUC and C max at steady-state. The mean terminal half-life (t 1/2 ) at steady state was 7 hours.

Median T max values were 14 hours (range: 12 to 24 hours) on both Day 1 and Day 5 following once daily administration of hydrocodone bitartrate extended-release tablets for five days. Daily fluctuation in peak to trough plasma levels of hydrocodone were higher at 80 mg and 120 mg doses of hydrocodone bitartrate extended-release tablets compared to 30 mg dose (Table 7). Table 7.

Mean (SD) Steady-State Hydrocodone Pharmacokinetic Parameters Regimen AUC24,ss (ng•h/mL) C max ,ss (ng/mL) C min ,ss (ng/mL) % Fluctuation* Hydrocodone Bitartrate Extended-Release Tablets 30 mg q24h 443 (128) 26.4 (7.4) 16.7 (5.2) 61 (6.4, 113) 80 mg q24h 1252 (352) 82.6 (25.7) 28.2 (12) 105 (36, 214) 120 mg q24h 1938 (729) 135 (50) 63.6 (29) 97.9 (32, 250) * Mean (minimum, maximum); Percentage fluctuation in plasma concentration is derived as (C max ,ss – C min ,ss)*100/Cavg,ss. Food Effects C max and AUC of hydrocodone bitartrate extended-release 120 mg tablets were similar under low fat conditions relative to fasting conditions (17% and 9% higher, respectively).

C max was higher (54%) under high fat conditions relative to fasting conditions; however, AUC of hydrocodone bitartrate extended-release 120 mg tablets was only 20% higher when co-administered with a high fat meal. Hydrocodone bitartrate extended-release tablets may be administered without regard to meals. Distribution Following administration of hydrocodone bitartrate extended-release tablets, the typical (70 kg adult) value of apparent volume of distribution (V/F) is 402 L, suggesting extensive tissue distribution.

The extent of in vivo binding of hydrocodone to human plasma proteins was minimal with a mean % bound at 36%. Elimination Metabolism Hydrocodone exhibits a complex pattern of metabolism, including N -demethylation, O -demethylation, and 6-keto reduction to the corresponding 6-α-and 6-β-hydroxy metabolites. CYP3A4 mediated N -demethylation to inactive norhydrocodone is the primary metabolic pathway of hydrocodone with a lower contribution from CYP2B6 and CYP2C19.

The minor metabolite hydromorphone (<3% of the circulating parent hydrocodone) was mainly formed by CYP2D6 mediated O -demethylation with a smaller contribution by CYP2B6 and CYP2C19. Hydromorphone… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics ~3 min read ▾

12.2Pharmacodynamics Cardiac Electrophysiology QTc interval prolongation was studied in a double-blind, placebo- and positive-controlled 3-treatment parallel-group, dose-escalating study of hydrocodone bitartrate extended-release tablets in 196 healthy subjects. QTc interval prolongation was observed following hydrocodone bitartrate extended-release tablets 160 mg per day. The maximum mean (90% upper confidence bound) difference in the QTc interval between hydrocodone bitartrate extended-release tablets and placebo (after baseline-correction) at steady state was 6 (9) milliseconds, 7 (10) milliseconds, and 10 (13) milliseconds at hydrocodone bitartrate extended-release tablet doses of 80 mg, 120 mg and 160 mg respectively.

For clinical implications of the prolonged QTc interval, [see Warnings and Precautions ( 5.11 )] . Effects on the Central Nervous System Hydrocodone produces respiratory depression by direct action on brainstem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and electrical stimulation.

Hydrocodone causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origin may produce similar findings). Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see Overdosage ( 10 )] .

Effects on the Gastrointestinal Tract and Other Smooth Muscle Hydrocodone causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone is increased to the point of spasm, resulting in constipation.

Other opioid-induced effects may include a reduction in biliary and pancreatic secretions, spasm of sphincter of Oddi, transient elevations in serum amylase, and opioid-induced esophageal dysfunction (OIED). Effects on the Cardiovascular System Hydrocodone produces peripheral vasodilation, which may result in orthostatic hypotension or syncope Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes, sweating, and/or orthostatic hypotension. Effects on the Endocrine System Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans [see Adverse Reactions ( 6.2 )] .

They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon. Use of opioids for an extended period of time may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility. The causal role of opioids in the clinical syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date [see Adverse Reactions ( 6.2) ] .

Effects on the Immune System Opioids have been shown to have a variety of effects on components of the immune system in in vitro and animal models. The clinical significance of these findings is unknown. Overall, the effects of opioids appear to be modestly immunosuppressive.

Concentration—Efficacy Relationships The minimum effective analgesic concentration will vary widely among patients especially among patients who have been previously treated with opioid agonists. The minimum effective analgesic concentration of hydrocodone for any individual patient may increase over time due to an increase in pain, the development of a new pain syndrome, and/or the development of analgesic tolerance [see Dosage and Administration ( 2.1 , 2.4 )] . Concentration—Adverse Experience Relations… [Excerpted — this section continues on DailyMed.]

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Moderate to Severe Chronic Lower Back Pain Study The efficacy and safety of hydrocodone bitartrate extended-release tablets was evaluated in a randomized double-blind, placebo-controlled, multi-center, 12-week clinical trial in both opioid-experienced patients and patients who were not opioid tolerant with moderate to severe chronic low back pain. A total of 905 chronic low back pain patients (opioid naive and opioid-experienced) who were not responsive to their prior analgesic therapy entered an open-label conversion and dose- titration period for up to 45 days with hydrocodone bitartrate extended-release tablets.

Patients were dosed once daily with hydrocodone bitartrate extended-release tablets (20 mg to 120 mg). Patients stopped their prior opioid analgesics and/or nonopioid analgesics prior to starting hydrocodone bitartrate extended-release tablet treatment. Optional use of rescue medication (immediate-release oxycodone 5 mg) up to 2 doses (2 tablets) was permitted during the dose titration period.

For inadequately controlled pain, hydrocodone bitartrate extended-release tablets dose was allowed to be increased once every 3 to 5 days until a stabilized and tolerable dose was identified. During the dose-titration period, 65% of the patients achieved a stable hydrocodone bitartrate extended-release tablets dose and entered the double-blind treatment period. The remaining subjects discontinued from the dose-titration period for the following reasons: adverse events (10%); lack of therapeutic effect (5%); confirmed or suspected diversion (3%); subject’s choice (5%); lost to follow-up (2%); administrative reasons (2%); and failure to achieve protocol-defined reduction in pain score (7%).

Following the dose titration period, 588 patients (65%) were randomized at a ratio of 1:1 into a 12-week double-blind treatment period with their fixed stabilized dose of hydrocodone bitartrate extended-release tablets (or matching placebo). These patients met the study randomization criteria of adequate analgesia (pain reduction of at least 2 points to a score of 4 or less on a 0 to 10 numerical rating scale) and acceptable tolerability of hydrocodone bitartrate extended-release tablets. Patients randomized to placebo were given a blinded taper of hydrocodone bitartrate extended-release tablets according to a pre-specified tapering schedule, 3 days on each step-down dose (reduced by 25% to 50% from the previous dose).

Patients were allowed to use rescue medication (immediate-release oxycodone 5 mg) up to 6 doses (6 tablets) per day depending on their randomized hydrocodone bitartrate extended-release tablets dose. During the double-blind period, 229 treated patients (77%) completed the 12-week treatment with hydrocodone bitartrate extended-release tablets and 210 patients (72%) completed on placebo. Overall, 10% of patients discontinued due to lack of therapeutic effect (5% in hydrocodone bitartrate extended-release patients and 15% in placebo patients); 5% of patients discontinued due to adverse events (6% in hydrocodone bitartrate extended-release tablet-treated patients and 3% in placebo patients).

Hydrocodone bitartrate extended-release tablets provided greater analgesia compared with placebo. There was a statistically significant difference in the weekly average pain scores at Week 12 between the two groups. The percentage of patients (responders) in each group who demonstrated improvement in their weekly average pain scores at Week 12, as compared with screening is shown in Figure 4.

The figure is cumulative, so that patients whose change from screening is, for example, 30%, are also included at every level of improvement below 30%. Patients who did not complete the study were classified as non-responders. Treatment with hydrocodone bitartrate extended-release tablets resulted in a higher proportion of responders, defined as patients with at least a 30% and 50% improvement, as compared with placebo.

Figure 4. P… [Excerpted — this section continues on DailyMed.]

🔒 Drug Abuse and Dependence ~3 min read ▾

9 DRUG ABUSE AND DEPENDENCE

9.1Controlled Substance Hydrocodone bitartrate extended-release tablets contain hydrocodone bitartrate, a Schedule II controlled substance.

9.2Abuse Hydrocodone bitartrate extended-release tablets contain hydrocodone, a substance with high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see Warnings and Precautions ( 5.1 )] . Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects.

Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. Misuse and abuse of hydrocodone bitartrate extended-release tablets increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death.

The risk is increased with concurrent abuse of hydrocodone bitartrate extended-release tablets with alcohol and other CNS depressants. Abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. In addition, abuse of opioids can occur in the absence of addiction.

All patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Patients at high risk of hydrocodone bitartrate extended-release tablets abuse include those with a history of prolonged use of any opioid, including products containing hydrocodone, those with a history of drug or alcohol abuse, or those who use hydrocodone bitartrate extended-release tablets in combination with other abused drugs. "Drug-seeking" behavior is very common in persons with substance use disorders.

Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control.

Hydrocodone bitartrate extended-release tablets, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised. Proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Risks Specific to Abuse of Hydrocodone Bitartrate Extended-Release Tablets Abuse of hydrocodone bitartrate extended-release tablets poses a risk of overdose and death. This risk is increased with concurrent use of hydrocodone bitartrate extended-release tablets with alcohol and/or other CNS depressants [see Warnings and Precautions ( 5.1 , 5.3 ), Drug Interactions ( 7 )] . Abuse may occur by taking intact tablets in quantities greater than prescribed or without legitimate purpose, by crushing and chewing or snorting the crushed formulation, or by injecting a solution made from the crushed formulation.

Taking cut, br… [Excerpted — this section continues on DailyMed.]

🔒 Controlled Substance 15 words ▾

9.1Controlled Substance Hydrocodone bitartrate extended-release tablets contain hydrocodone bitartrate, a Schedule II controlled substance.

🧪 Nonclinical Toxicology ~1 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Hydrocodone was evaluated for carcinogenic potential in rats and mice. In a two-year bioassay in rats, doses up to 25 mg/kg in males and females were administered orally and no treatment-related neoplasms were observed (exposure is equivalent to 0.2 times the human hydrocodone dose of 120 mg/day based on AUC exposure comparisons). In a two-year bioassay in mice, doses up to 200 mg/kg in males and 100 mg/kg in females were administered orally and no treatment-related neoplasms were observed (exposure is equivalent to 3.5 times and 3.0 times, respectively, the human hydrocodone dose of 120 mg/day based on AUC exposure comparisons).

Mutagenesis Hydrocodone was genotoxic in the mouse lymphoma assay in the presence of rat S9 metabolic activation but not in the absence of rat metabolic activation. However, hydrocodone was not genotoxic in the mouse lymphoma assay with or without human S9 metabolic activation. There was no evidence of genotoxic potential with hydrocodone in an in vitro bacterial reverse mutation assay with Salmonella typhimurium and Escherichia coli with or without metabolic activation or in an in vivo mouse bone marrow micronucleus test with or without metabolic activation.

Impairment of Fertility No effect on fertility or general reproductive performance was seen with oral administration of hydrocodone to male and female rats at doses up to 25 mg/kg/day (approximately 0.06 times and 0.08 times, respectively, the human hydrocodone dose of 120 mg/day based on AUC exposure comparisons).

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~1 min read ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Hydrocodone was evaluated for carcinogenic potential in rats and mice. In a two-year bioassay in rats, doses up to 25 mg/kg in males and females were administered orally and no treatment-related neoplasms were observed (exposure is equivalent to 0.2 times the human hydrocodone dose of 120 mg/day based on AUC exposure comparisons). In a two-year bioassay in mice, doses up to 200 mg/kg in males and 100 mg/kg in females were administered orally and no treatment-related neoplasms were observed (exposure is equivalent to 3.5 times and 3.0 times, respectively, the human hydrocodone dose of 120 mg/day based on AUC exposure comparisons).

Mutagenesis Hydrocodone was genotoxic in the mouse lymphoma assay in the presence of rat S9 metabolic activation but not in the absence of rat metabolic activation. However, hydrocodone was not genotoxic in the mouse lymphoma assay with or without human S9 metabolic activation. There was no evidence of genotoxic potential with hydrocodone in an in vitro bacterial reverse mutation assay with Salmonella typhimurium and Escherichia coli with or without metabolic activation or in an in vivo mouse bone marrow micronucleus test with or without metabolic activation.

Impairment of Fertility No effect on fertility or general reproductive performance was seen with oral administration of hydrocodone to male and female rats at doses up to 25 mg/kg/day (approximately 0.06 times and 0.08 times, respectively, the human hydrocodone dose of 120 mg/day based on AUC exposure comparisons).

📄 Recent Major Changes 28 words ▾

RECENT MAJOR CHANGES SECTION Boxed Warning 12/2025 Indications and Usage (1) 12/2025 Dosage and Administration (2.2, 2.3, 2.7) 12/2025 Warnings and Precautions (5.1, 5.2, 5.3, 5.14, 5.16) 12/2025

📄 Package Label / Principal Display Panel ~1 min read ▾

NDC 47781- 392 -60 Hydrocodone Bitartrate Extended-Release Tablets CII 20 mg Attention Dispenser: Accompanying Medication Guide must be provided to the patient upon dispensing. Swallow tablets whole. Do not cut, break, chew, crush, or dissolve. 60 Tablets Rx only

NDC 47781- 393 -60 Hydrocodone Bitartrate Extended-Release Tablets CII 30 mg Attention Dispenser: Accompanying Medication Guide must be provided to the patient upon dispensing. Swallow tablets whole. Do not cut, break, chew, crush, or dissolve. 60 Tablets Rx only

NDC 47781- 394 -60 Hydrocodone Bitartrate Extended-Release Tablets CII 40 mg Attention Dispenser: Accompanying Medication Guide must be provided to the patient upon dispensing. Swallow tablets whole. Do not cut, break, chew, crush, or dissolve. 60 Tablets Rx only

NDC 47781- 395 -60 Hydrocodone Bitartrate Extended-Release Tablets CII 60 mg Attention Dispenser: Accompanying Medication Guide must be provided to the patient upon dispensing. Swallow tablets whole. Do not cut, break, chew, crush, or dissolve. 60 Tablets Rx only

NDC 47781- 396 -60 Hydrocodone Bitartrate Extended-Release Tablets CII 80 mg Attention Dispenser: Accompanying Medication Guide must be provided to the patient upon dispensing. Swallow tablets whole. Do not cut, break, chew, crush, or dissolve. 60 Tablets Rx only

NDC 47781- 397 -60 Hydrocodone Bitartrate Extended-Release Tablets CII 100 mg Attention Dispenser: Accompanying Medication Guide must be provided to the patient upon dispensing. Swallow tablets whole. Do not cut, break, chew, crush, or dissolve. 60 Tablets Rx only

NDC 47781- 398 -60 Hydrocodone Bitartrate Extended-Release Tablets CII 120 mg Attention Dispenser: Accompanying Medication Guide must be provided to the patient upon dispensing. Swallow tablets whole. Do not cut, break, chew, crush, or dissolve. 60 Tablets Rx only

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

Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Hysingla ER (matched by generic name) — 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 Hysingla ER. CMS lists 2 products for this generic; we show the highest-spend one. 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.
Period
Total Part D spend
$3.12M
Claims incl. refills
4.5K
Beneficiaries
1.8K
Spend / beneficiary
$1,778.43
Spend / claim
$700.68
Trend by period
💵 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.
🛡
This drug has a REMS. A Risk Evaluation & Mitigation Strategy is an FDA-required safety program. It may require enrollment, counseling, or monitoring to manage a serious risk. See the boxed warning & full label below, and REMS@FDA ↗.

About this NDC listing & data coverage

Finished prescription product
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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.
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“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 form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
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 Alvogen Inc.. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Alvogen 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.
← 47781-0395-60 · Alvogen 47781-0397-60 · Alvogen →
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.