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Methadone Hydrochloride 5 mg/5mL Solution, 500 mL — NDC 0054-3555-63 (Billing 00054-3555-63)

by Hikma Pharmaceuticals USA Inc. · 500 mL in 1 BOTTLE

This is a package of 500 mL of Methadone Hydrochloride 5 mg/5mL Solution from Hikma Pharmaceuticals USA Inc., marketed since May 1981 and currently FDA-listed; retail pharmacies pay about $0.0566 per mL (NADAC). It is this product's only package size.

NDC 00054-3555-63
🏷️ FDA NDC (as labeled) 0054-3555-63 billing pads the labeler 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

⚠️
Other active recalls for Methadone Hydrochloride (different manufacturers) — 1 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class III · Dec 19, 2024 — Failed Tablet/Capsule Specifications: Illegible product identification for the unit dose configuration only. (West-Ward Columbus Inc) · FDA recall D-0183-2025
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 0054-3555-63
Product NDC 0054-3555
11-digit billing NDC 00054355563
NCPDP billing unit ML — per mL (volume)
RxCUI 864761, 864769
UNII 229809935B
UPC 0300543555631, 0300543556638
Application # ANDA087393
SPL Set ID 8c363f90-c378-48ae-abbc-aeb25c9bf5cb
Established class (EPC) Opioid Agonist
Mechanism of action Full Opioid Agonists
DEA schedule CII
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 1981-05-22
Route ORAL
Dosage form SOLUTION
Substance METHADONE HYDROCHLORIDE
TE code (Orange Book) AA · RLD · RS

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

GPI-14 65100050102010
GPI class Methadone HCl
GCN Seq No 004238
GCN 16400
HICL code 001745
Ingredient (HICL) Methadone Hcl
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 METHADONE 5 MG/5 ML SOLUTION
FDB brand name Methadone Hcl
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 004238
  • GCN: 16400
  • GPI-14 (Medi-Span): 65100050102010
  • HICL (First Databank): 001745
  • AHFS class code: 28:08.08.00
  • RxCUI (RxNorm): 864761
Why two NDCs? The FDA registers this code as 0054-3555-63 — a 4-4-2 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 labeler segment → 00054-3555-63. 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) Drugs used in opioid dependence
How it works Full 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 METHADONE 5 MG/5 ML SOLUTION Ingredient Methadone Hcl
📗 Our plain-language guide HelloPharmacist
  • Depending on the product, it treats severe, long-term pain or opioid addiction, as detox or maintenance. Injection is for pain or short-term use when you can't take pills. It isn't...
  • Always use a graduated measuring device, never a kitchen spoon. Double-check the dose in mg versus mL and the strength on your bottle. If you're unsure, ask me before you take it.
  • Dizziness, lightheadedness, sleepiness, nausea, vomiting, sweating and constipation are most common. Call for help if breathing slows, you faint, or your heartbeat feels irregular.
  • Don't mix them unless your prescriber says so. Alcohol, benzodiazepines and similar drugs can cause deep sedation, slow breathing, coma and death.
📖 Read our full Methadone guide →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

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 mLPer package
Retail pharmacies payNADAC · weekly $0.057 $28.30 / 500 ml
Medicaid paysCMS SDUD · 12 mo $0.3397 $169.85 / 500 ml
Medicare drug plans payPart D · Q2 2026 $0.0648 $32.40 / 500 ml
NADAC price history (per mL) — tap or hover for the price & month
Feb 2025 $0.057 $0.057
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
00054-3555-63 You're viewing this Main listing 500 mL in 1 BOTTLE 1981-05-22 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Methadone Hydrochloride 5 mg/5mLthis 00054-3555-63 Hikma 500 ml $0.057 AA FDA listed —
Methadone Hydrochloride 5 mg/5mL 00406-6225-05 SpecGx 500 ml $0.057 AA FDA listed —
Methadone Hydrochloride 5 mg/5mL 60687-0818-86 American 10 cups — AA FDA listed —
Methadone Hydrochloride 5 mg/5mL 66689-0711-16 VistaPharm, 500 ml — AA FDA listed —
Methadone Hydrochloride 5 mg/5mL 68094-0031-62 Precision 10 cups — AA FDA listed —
Methadone Hydrochloride 5 mg/5mL 68094-0331-58 Precision 1 syringe — AA 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

🏛️
1981
On the market since
May 1981
📍
2026
Currently FDA-listed
45 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.

Inactive Ingredients / Excipients

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

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

  • UNII 3K9958V90M
    A liquid solvent derived from fermentation or chemical synthesis. In medicines, alcohol dissolves active ingredients, helps preserve the product, and improves how the body absorbs certain drugs.
  • UNII XF417D3PSL
    Anhydrous citric acid is a sour, crystalline powder derived from citric acid with water removed. In medicines, it acts as a buffer to control pH, adds tartness to improve taste, and helps tablets disintegrate.
  • UNII 8SKN0B0MIM
    Benzoic acid is a naturally occurring organic acid used as a preservative in medicines and foods. It helps prevent bacterial and fungal growth to extend shelf life and maintain product stability.
  • UNII WZB9127XOA
    A synthetic red dye used to color medications and make them easier to identify. It serves as a colorant in tablets, capsules, and liquid formulations.
  • UNII H77VEI93A8
    A synthetic yellow dye used to color medications. It helps identify the drug and make it visually distinctive, with no effect on how the medicine works.
  • UNII PDC6A3C0OX
    Glycerin is a clear, thick liquid derived from plant oils or fats. It acts as a humectant to retain moisture, a sweetener, and a solvent in medications.
  • UNII 506T60A25R
    Sorbitol is a natural sugar alcohol derived from glucose. It serves as a sweetener, humectant, and bulking agent in medications to improve taste and help maintain moisture in the product.
  • UNII 059QF0KO0R
    Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.

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

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

Inactive ingredient FAQ

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

Manufacturer & labeler

LabelerHikma Pharmaceuticals USA Inc.
Application holderHIKMA PHARMACEUTICALS USA INC
FDA applicationANDA087393 (ANDA)
Labeler code00054
First marketedMay 1981
DEA scheduleCII
Product typeHuman Prescription Drug
Portfolio726 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

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 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔒 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 METHADONE HYDROCHLORIDE ORAL SOLUTION Risk of Medication Errors Dosing errors can result in accidental overdose and death. Avoid dosing errors that may result from confusion between mg and mL and confusion with methadone solutions of different concentrations, when prescribing, dispensing, and administering Methadone Hydrochloride Oral Solution, 5 mg per 5 mL or 10 mg per 5 mL. Ensure that the dose is communicated clearly and dispensed accurately.

Instruct patients and caregivers on how to measure and take or administer the correct dose of Methadone Hydrochloride Oral Solution and to use extreme caution when measuring the dose. Strongly advise patients to obtain and always use a graduated device that can measure and deliver the prescribed dose accurately, and to never use household teaspoons or tablespoons to measure a dose because these are not accurate measuring devices [see Dosage and Administration ( 2.1 ), Warnings and Precautions ( 5.1 )] . Addiction, Abuse, and Misuse Because the use of Methadone Hydrochloride Oral Solution 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 ( 5.2 )] .

Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of Methadone Hydrochloride Oral Solution, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of Methadone Hydrochloride Oral Solution are essential [see Warnings and Precautions ( 5.3 )] . Accidental Ingestion Accidental ingestion of even one dose of Methadone Hydrochloride Oral Solution, especially by children, can result in a fatal overdose of methadone [see Warnings and Precautions ( 5.3 )] .

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 Methadone Hydrochloride Oral Solution and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see Warnings and Precautions ( 5.4 ), Drug Interactions ( 7 )] .

Neonatal Opioid Withdrawal Syndrome (NOWS) Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of use of Methadone Hydrochloride Oral Solution during pregnancy. NOWS may be life-threatening if not recognized and treated in the neonate. The balance between the risks of NOWS and the benefits of maternal Methadone Hydrochloride Oral Solution use may differ based on the risks associated with the mother’s underlying condition, pain, or addiction.

Advise the patient of the risk of NOWS so that appropriate planning for management of the neonate can occur [see Warnings and Precautions ( 5.6 )]. 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 ( 5.7 )] . Life-threatening QT Prolongation QT interval prolongation and serious arrhythmia (torsades de pointes) have occurred during treatment with methadone.

Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. Closely monitor patients with risk factors for development of prolonged QT interval, a history of cardiac conduction abnormalities, and tho… [Excerpted — this section continues on DailyMed.]

🎯 Indications and Usage ~2 min read ▾

1 INDICATIONS AND USAGE Methadone Hydrochloride Oral Solution is 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 ( 5.2 )] , reserve opioid analgesics, including Methadone Hydrochloride Oral Solution, for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. • Methadone Hydrochloride Oral Solution is not indicated as an as-needed (prn) analgesic. • Detoxification treatment of opioid addiction (heroin or other morphine-like drugs). • Maintenance treatment of opioid addiction (heroin or other morphine-like drugs), in conjunction with appropriate social and medical services.

Limitations of Use: • Methadone products used for the treatment of opioid addiction in detoxification or maintenance programs are subject to the conditions for distribution and use required under 42 CFR 8.12 [see Dosage and Administration ( 2.1 )] . • Methadone Hydrochloride Oral Solution is 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, reserve opioid analgesics, including Methadone Hydrochloride Oral Solution, 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 , 5.2 ) • Methadone Hydrochloride Oral Solution is not indicated as an as-needed (prn) analgesic. ( 1 ) • Detoxification treatment of opioid addiction (heroin or other morphine-like drugs). • Maintenance treatment of opioid addiction (heroin or other morphine-like drugs), in conjunction with appropriate social and medical services. ( 1 ) Limitations of Use: • Methadone products used for the treatment of opioid addiction in detoxification or maintenance programs are subject to the conditions for distribution and use required under 42 CFR 8.12.

( 2.1 )

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION • Consider recommending or prescribing an opioid overdose reversal agent (e.g., naloxone, nalmefene) based on the patient’s risk factors for overdose ( 2.3 , 5.2 , 5.4 , 5.8 ). Management of Pain: • Methadone Hydrochloride Oral Solution 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 ) • Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals.

Reserve titration to higher doses of Methadone Hydrochloride Oral Solution 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 ) • 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 ( 5.2 ) • Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with Methadone Hydrochloride Oral Solution.

Consider this risk when selecting an initial dose and making dose adjustments ( 2.1 , 5.4 ) • To convert to methadone hydrochloride from another opioid, use available conversion factors to obtain estimated dose. ( 2.4 ) • Titrate slowly with dose increases no more frequent than every 3 to 5 days. ( 2.5 ) • Periodically reassess patients receiving methadone hydrochloride 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.

( 2.5 ) • Do not rapidly reduce or abruptly discontinue methadone in a physically dependent patient because rapid reduction or abrupt discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. ( 2.6 , 5.17 ) Initiation of Detoxification and Maintenance Treatment: • A single dose of 20 to 30 mg may be sufficient to suppress withdrawal syndrome. ( 2.7 )

2.1Conditions for Distribution and Use of Methadone Products for the Treatment of Opioid Addiction Code of Federal Regulations, Title 42, Sec 8: Methadone products when used for the treatment of opioid addiction in detoxification or maintenance programs, shall be dispensed only by opioid treatment programs (and agencies, practitioners or institutions by formal agreement with the program sponsor) certified by the Substance Abuse and Mental Health Services Administration and approved by the designated state authority.

Certified treatment programs shall dispense and use methadone in oral form only and according to the treatment requirements stipulated in the Federal Opioid Treatment Standards (42 CFR 8.12). See below for important regulatory exceptions to the general requirement for certification to provide opioid agonist treatment. Failure to abide by the requirements in these regulations may result in criminal prosecution, seizure of the drug supply, revocation of the program approval, and injunction precluding operation of the program.

Regulatory Exceptions to the General Requirement for Certification to Provide Opioid Agonist Treatment: • During inpatient care, when the patient was admitted for any condition other than concurrent opioid addiction (pursuant to 21CFR 1306.07(c)), to facilitate the treatment of the primary admitting diagnosis). • During an emergency period of no longer than 3 days while definitive care for the addiction is being sought in an appropriately licensed facility (pursuant to 21CFR 1306.07(b)).

2.2Important General Information • Ensure accuracy when prescribing, dispensing, and administering Methadone Hydrochloride Oral Solution to avoid dosing errors due to confusion between mg and mL, and with other methadone hydrochloride oral solutions of different con… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 75 words ▾

3 DOSAGE FORMS AND STRENGTHS Each 5 mL of clear or nearly clear orange colored Methadone Hydrochloride Oral Solution USP contains methadone hydrochloride USP 5 mg or 10 mg. The concentration of the 5 mg per 5 mL solution is 1 mg/mL and the concentration of the 10 mg per 5 mL solution is 2 mg/mL. Oral Solution: Each 5 mL contains 5 mg or 10 mg of Methadone Hydrochloride Oral Solution. ( 3 )

⛔ Contraindications 120 words ▾

4 CONTRAINDICATIONS Methadone Hydrochloride Oral Solution is contraindicated in patients with: • Significant respiratory depression [see Warnings and Precautions ( 5.4 )] • Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions ( 5.9 )] • Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions ( 5.14 )] • Hypersensitivity (e.g., anaphylaxis) to methadone [see Adverse Reactions ( 6 )] • 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 methadone ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS • Opioid Induced Hyperalgesia (OIH) 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. ( 5.9 ) • Serotonin Syndrome: Potentially life-threatening condition could result from concomitant serotonergic drug administration.

Discontinue Methadone Hydrochloride Oral Solution if serotonin syndrome is suspected. ( 5.10 ) • Risk of Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, Debilitated Patients: Regularly evaluate, particularly during initiation and titration. ( 5.11 ) • Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid.

( 5.12 ) • Severe Hypotension: Regularly evaluate during dose initiation and titration. Avoid use in patients with circulatory shock. ( 5.13 ) • Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness: Regularly evaluate for sedation and respiratory depression.

Avoid use of methadone in patients with impaired consciousness or coma. ( 5.14 )

5.1Risk of Accidental Overdose and Death due to Medication Errors Dosing errors can result in accidental overdose and death. Avoid dosing errors that may result from confusion between mg and mL and confusion with methadone solutions of different concentrations, when prescribing, dispensing, and administering Methadone Hydrochloride Oral Solution. Ensure that the dose is communicated clearly and dispensed accurately.

Instruct patients and caregivers on how to measure and take or administer the correct dose of Methadone Hydrochloride Oral Solution and to use extreme caution when measuring the dose. Strongly advise patients to obtain and always use a graduated device that can measure and deliver the prescribed dose accurately, and to never use household teaspoons or tablespoons to measure a dose because these are not accurate measuring devices.

5.2Addiction, Abuse and Misuse Methadone Hydrochloride Oral Solution contains methadone, a Schedule II controlled substance. As an opioid, Methadone Hydrochloride Oral Solution exposes users to the risks of addiction, abuse, and misuse . As long-acting opioids such as Methadone Hydrochloride Oral Solution have pharmacological effects over an extended period of time, there is a greater risk for overdose and death [see Drug Abuse and Dependence ( 9 )] .

Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed Methadone Hydrochloride Oral Solution and in those who obtain the drug illicitly. 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 )] . Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing Methadone Hydrochloride Oral Solution, and reassess all patients receiving Methadone Hydrochloride Oral Solution for the development of these behaviors or 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 proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as Methadone Hydrochloride Oral Solution, but use in such patients necessitates intensive counseling about the risks and proper use of Methadone Hydrochloride O… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~2 min read ▾

6 ADVERSE REACTIONS The following serious adverse reactions are described, or described in greater detail, in other sections: • Addiction, Abuse, and Misuse [see Warnings and Precautions ( 5.2 )] • Life Threatening Respiratory Depression [see Warnings and Precautions ( 5.4 )] • QT Prolongation [see Warnings and Precautions ( 5.5 )] • Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions ( 5.6 )] • Interactions with Benzodiazepines and Other CNS Depressants [see Warnings and Precautions ( 5.8 )] • Opioid-Induced Hyperalgesia and Allodynia [see Warnings and Precautions ( 5.9 )] • Serotonin Syndrome [see Warnings and Precautions ( 5.10 )] • Adrenal Insufficiency [see Warnings and Precautions ( 5.11 )] • Severe Hypotension [see Warnings and Precautions ( 5.12 )] • Gastrointestinal Adverse Reactions [see Warnings and Precautions ( 5.14 )] • Seizures [see Warnings and Precautions ( 5.15 )] • Withdrawal [see Warnings and Precautions ( 5.16 )] The following adverse reactions associated with the use of methadone were identified in clinical studies or postmarketing reports.

Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The major hazards of methadone are respiratory depression and, to a lesser degree, systemic hypotension. Respiratory arrest, shock, cardiac arrest, and death have occurred.

The most frequently observed adverse reactions include lightheadedness, dizziness, sedation, nausea, vomiting and sweating. These effects seem to be more prominent in ambulatory patients and in those who are not suffering severe pain. In such individuals, lower doses are advisable.

Other adverse reactions include the following: Body as a Whole: asthenia (weakness), edema, headache Cardiovascular: arrhythmias, bigeminal rhythms, bradycardia, cardiomyopathy, ECG abnormalities, extrasystoles, flushing, heart failure, hypotension, palpitations, phlebitis, QT interval prolongation, syncope, T-wave inversion, tachycardia, torsades de pointes , ventricular fibrillation, ventricular tachycardia Central Nervous System: agitation, confusion, disorientation, dysphoria, euphoria, insomnia, hallucinations, seizures, visual disturbances, congenital oculomotor disorders (nystagmus, strabismus) Endocrine: hypogonadism, decreased testosterone Gastrointestinal: abdominal pain, anorexia, biliary tract spasm, constipation, dry mouth, glossitis Hematologic: reversible thrombocytopenia has been described in opioid addicts with chronic hepatitis Metabolic: hypokalemia, hypomagnesemia, weight gain Renal: antidiuretic effect, urinary retention or hesitancy Reproductive: amenorrhea, reduced libido and/or potency, reduced ejaculate volume, reduced seminal vesicle and prostate secretions, decreased sperm motility, abnormalities in sperm morphology Respiratory: pulmonary edema, respiratory depression Skin and Subcutaneous Tissue: pruritus, urticaria, other skin rashes, and rarely, hemorrhagic urticaria Hypersensitivity: Anaphylaxis has been reported with ingredients contained in Methadone Hydrochloride Oral Solution.

Serotonin Syndrome : Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. Adrenal Insufficiency : Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Androgen Deficiency : Cases of androgen deficiency have occurred with use of opioids for an extended period of time [see Clinical Pharmacology ( 12.2 )].

Hyperalgesia and Allodynia: Cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration [see Warnings and Precautions ( 5.9 )] . Hypoglycemia: Cases of hypoglycemia have been reported in patients taking methadone [see Warnings and Precautions ( 5.19 )] . Opioid-induced esophageal dysfunction (OIED) Cases o… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~3 min read ▾

7 DRUG INTERACTIONS Inhibitors of CYP3A4, CYP2B6, CYP2C19, CYP2C9, or CYP2D6 Clinical Impact: Methadone undergoes hepatic N-demethylation by several cytochrome P450 (CYP) isoforms, including CYP3A4, CYP2B6, CYP2C19, CYP2C9, and CYP2D6. The concomitant use of Methadone Hydrochloride Oral Solution and CYP3A4, CYP2B6, CYP2C19, CYP2C9, or CYP2D6 inhibitors can increase the plasma concentration of methadone, resulting in increased or prolonged opioid effects, and may result in a fatal overdose, particularly when an inhibitor is added after a stable dose of Methadone Hydrochloride Oral Solution is achieved.

These effects may be more pronounced with concomitant use of drugs that inhibit more than one of the CYP enzymes listed above. After stopping a CYP3A4, CYP2B6, CYP2C19, CYP2C9, or CYP2D6 inhibitor, as the effects of the inhibitor decline, the methadone plasma concentration can decrease [see Clinical Pharmacology ( 12.3 )] , resulting in decreased opioid efficacy or withdrawal symptoms in patients physically dependent on methadone. Intervention: If concomitant use is necessary, consider dosage reduction of Methadone Hydrochloride Oral Solution until stable drug effects are achieved.

Evaluate patients at frequent intervals for respiratory depression and sedation. If a CYP3A4, CYP2B6, CYP2C19, CYP2C9, or CYP2D6 inhibitor is discontinued, consider increasing the Methadone Hydrochloride Oral Solution dosage until stable drug effects are achieved. Evaluate for signs of opioid withdrawal.

Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir), fluconazole, fluvoxamine, some selective serotonin reuptake inhibitors (SSRIs) (e.g., sertraline, fluvoxamine) Inducers of CYP3A4, CYP2B6, CYP2C19, or CYP2C9 Clinical Impact: The concomitant use of Methadone Hydrochloride Oral Solution and CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducers can decrease the plasma concentration of methadone [see Clinical Pharmacology ( 12.3 )] , resulting in decreased efficacy or onset of withdrawal symptoms in patients physically dependent on methadone.

These effects could be more pronounced with concomitant use of drugs that can induce multiple CYP enzymes. After stopping a CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducer, as the effects of the inducer decline, the methadone plasma concentration can increase [see Clinical Pharmacology ( 12.3 )] , which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression, sedation, or death. Intervention: If concomitant use is necessary, consider increasing the Methadone Hydrochloride Oral Solution dosage until stable drug effects are achieved.

Evaluate for signs of opioid withdrawal. If a CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducer is discontinued, consider Methadone Hydrochloride Oral Solution dose reduction and evaluate patients at frequent intervals for signs of respiratory depression and sedation. Examples: Rifampin, carbamazepine, phenytoin, St.

John’s Wort, phenobarbital 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. Intervention: For Patients Being Treated for Pain 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, 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 ( 2.3 ) and Warnings and Precautions ( 5.2 , 5.3 , 5.4 )] . For Patients Being Treated for Opioid Addiction Cessation of b… [Excerpted — this section continues on DailyMed.]

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS • Lactation : Monitor breastfed infants for increased drowsiness and breathing difficulties. ( 8.2 )

8.1Pregnancy Risk Summary The majority of available data from clinical trials, observational studies, case series, and case reports on methadone use in pregnancy do not indicate an increased risk of major malformations specifically due to methadone. Pregnant women involved in methadone maintenance programs have been reported to have improved prenatal care leading to reduced incidence of obstetric and fetal complications and neonatal morbidity and mortality when compared to women using illicit drugs. Several factors, including maternal use of illicit drugs, nutrition, infection and psychosocial circumstances, complicate the interpretation of investigations of the children of women who take methadone during pregnancy.

Information is limited regarding dose and duration of methadone use during pregnancy, and most maternal exposure in these studies appears to occur after the first trimester of pregnancy ( see Data ). Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of use of opioids for an extended period of time during pregnancy [see Warnings and Precautions ( 5.6 )] . In published animal reproduction studies, methadone administered subcutaneously during the early gestational period produced neural tube defects (i.e., exencephaly and cranioschisis) in the hamster at doses 2 times the human daily oral dose of 120 mg/day on a mg/m2 basis (HDD) and in mice at doses equivalent to the HDD.

Administration of methadone to pregnant animals during organogenesis and through lactation resulted decreased litter size, increased pup mortality, decreased pup body weights, developmental delays, and long-term neurochemical changes in the brain of offspring which correlate with altered behavioral responses that persist through adulthood at exposures comparable to and less than the HDD. Administration of methadone to male rodents prior to mating with untreated females resulted in increased neonatal mortality and significant differences in behavioral tests in the offspring at exposures comparable to and less than the HDD ( see Data ).

Based on animal data, advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated Maternal and Embryo-fetal Risk: Untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes such as low birth weight, preterm birth, and fetal death. In addition, untreated opioid addiction often results in continued or relapsing illicit opioid use.

Dosage Adjustment During Pregnancy: Dosage adjustment using higher doses or administering the daily dose in divided doses may be necessary in pregnant women treated with methadone. Pregnant women appear to have significantly lower trough plasma methadone concentrations, increased plasma methadone clearance, and shorter methadone half-life than after delivery [see Dosage and Administration ( 2.9 ) and Clinical Pharmacology ( 12.3 )] . Withdrawal signs and symptoms should be closely monitored and the dose adjusted as necessary.

Fetal/Neonatal Adverse Reactions: Neonatal opioid withdrawal syndrome may occur in newborn infants of mothers who are receiving treatment with methadone. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and/or failure to gain weight. Signs of neonatal withdrawal usually occur in the first days after birth.

The duration and severity of neonatal opioid withdrawal syndrome may va… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Risk Summary The majority of available data from clinical trials, observational studies, case series, and case reports on methadone use in pregnancy do not indicate an increased risk of major malformations specifically due to methadone. Pregnant women involved in methadone maintenance programs have been reported to have improved prenatal care leading to reduced incidence of obstetric and fetal complications and neonatal morbidity and mortality when compared to women using illicit drugs. Several factors, including maternal use of illicit drugs, nutrition, infection and psychosocial circumstances, complicate the interpretation of investigations of the children of women who take methadone during pregnancy.

Information is limited regarding dose and duration of methadone use during pregnancy, and most maternal exposure in these studies appears to occur after the first trimester of pregnancy ( see Data ). Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of use of opioids for an extended period of time during pregnancy [see Warnings and Precautions ( 5.6 )] . In published animal reproduction studies, methadone administered subcutaneously during the early gestational period produced neural tube defects (i.e., exencephaly and cranioschisis) in the hamster at doses 2 times the human daily oral dose of 120 mg/day on a mg/m2 basis (HDD) and in mice at doses equivalent to the HDD.

Administration of methadone to pregnant animals during organogenesis and through lactation resulted decreased litter size, increased pup mortality, decreased pup body weights, developmental delays, and long-term neurochemical changes in the brain of offspring which correlate with altered behavioral responses that persist through adulthood at exposures comparable to and less than the HDD. Administration of methadone to male rodents prior to mating with untreated females resulted in increased neonatal mortality and significant differences in behavioral tests in the offspring at exposures comparable to and less than the HDD ( see Data ).

Based on animal data, advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated Maternal and Embryo-fetal Risk: Untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes such as low birth weight, preterm birth, and fetal death. In addition, untreated opioid addiction often results in continued or relapsing illicit opioid use.

Dosage Adjustment During Pregnancy: Dosage adjustment using higher doses or administering the daily dose in divided doses may be necessary in pregnant women treated with methadone. Pregnant women appear to have significantly lower trough plasma methadone concentrations, increased plasma methadone clearance, and shorter methadone half-life than after delivery [see Dosage and Administration ( 2.9 ) and Clinical Pharmacology ( 12.3 )] . Withdrawal signs and symptoms should be closely monitored and the dose adjusted as necessary.

Fetal/Neonatal Adverse Reactions: Neonatal opioid withdrawal syndrome may occur in newborn infants of mothers who are receiving treatment with methadone. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and/or failure to gain weight. Signs of neonatal withdrawal usually occur in the first days after birth.

The duration and severity of neonatal opioid withdrawal syndrome may vary. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions ( 5.6 )]… [Excerpted — this section continues on DailyMed.]

🧒 Pediatric Use 23 words ▾

8.4Pediatric Use The safety, effectiveness, and pharmacokinetics of methadone in pediatric patients below the age of 18 years have not been established.

🧓 Geriatric Use ~1 min read ▾

8.5Geriatric Use Clinical studies of methadone did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently compared to younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. Elderly patients (aged 65 years or older) may have increased sensitivity to methadone.

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 Methadone Hydrochloride Oral Solution slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see Warnings and Precautions ( 5.3 )] . Methadone 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 of methadone 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 )] . In severe overdosage, particularly by the intravenous route, apnea, circulatory collapse, cardiac arrest, and death may occur.

Methadone overdosage is associated with rhabdomyolysis. Seek medical attention, especially if abuse/misuse results in prolonged immobilization. Toxic leukoencephalopathy has been reported after opioid overdose, and can present hours, days, or weeks after apparent recovery from the initial intoxication.

Hearing loss has been reported after methadone overdose, in some cases permanent. Treatment of Overdose In case of overdose, priorities are the reestablishment of a patent and protected 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 as indicated.

Cardiac arrest or arrhythmias will require advanced life-support measures. For clinically significant respiratory or circulatory depression secondary to opioid 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 methadone in Methadone Hydrochloride Oral Solution, carefully monitor the patient until spontaneous respiration is reliably re-established.

If the response to an opioid overdose reversal agent is suboptimal or only brief in nature, administer additional reversal agent as directed in the product’s prescribing information. In an individual physically dependent on opioids, administration of the recommended dosage of opioid overdose reversal agent will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced 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 begin 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 Methadone hydrochloride is a mu-agonist; a synthetic opioid analgesic with multiple actions qualitatively similar to those of morphine, the most prominent of which involves the central nervous system and organs composed of smooth muscle. The principal therapeutic uses for methadone are for analgesia and for detoxification or maintenance in opioid addiction. The methadone withdrawal syndrome, although qualitatively similar to that of morphine, differs in that the onset is slower, the course is more prolonged, and the symptoms are less severe.

Some data also indicate that methadone acts as an antagonist at the N-methyl-D-aspartate (NMDA) receptor. The contribution of NMDA receptor antagonism to methadone’s efficacy is unknown.

12.2Pharmacodynamics Effects on the Central Nervous System Methadone produces respiratory depression by direct action on brain stem 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. Methadone 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 origins may produce similar findings). Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations. Some NMDA receptor antagonists have been shown to produce neurotoxic effects in animals.

Effects on the Gastrointestinal Tract and Other Smooth Muscle Methadone 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 Methadone 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 )] . 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 )] . 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 methadone 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 ( 2.2 , 2.5 )] .

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

🧬 Mechanism of Action 110 words ▾

12.1Mechanism of Action Methadone hydrochloride is a mu-agonist; a synthetic opioid analgesic with multiple actions qualitatively similar to those of morphine, the most prominent of which involves the central nervous system and organs composed of smooth muscle. The principal therapeutic uses for methadone are for analgesia and for detoxification or maintenance in opioid addiction. The methadone withdrawal syndrome, although qualitatively similar to that of morphine, differs in that the onset is slower, the course is more prolonged, and the symptoms are less severe.

Some data also indicate that methadone acts as an antagonist at the N-methyl-D-aspartate (NMDA) receptor. The contribution of NMDA receptor antagonism to methadone’s efficacy is unknown.

📦 How Supplied / Storage and Handling 155 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Methadone is a controlled substance. Like fentanyl, morphine, oxycodone, hydromorphone, and oxymorphone, methadone is controlled under Schedule II of the Federal Controlled Substances Act. Methadone may be targeted for theft and diversion by criminals [see Warnings and Precautions ( 5.2 )].

Dispense in a tight, light-resistant container as defined in the USP/NF. Store at 20° to 25ºC (68º to 77°F), with excursions permitted between 15° to 30°C (59° to 86° F). [See USP Controlled Room Temperature.] Store Methadone Hydrochloride Oral Solution securely and dispose of properly [see Patient Counseling Information ( 17 )]. Methadone Hydrochloride Oral Solution USP 5 mg per 5 mL (1 mg/mL) is supplied as a clear or nearly clear, orange-colored, citrus-flavored solution.

NDC 0054-3555-63: Bottle of 500 mL 10 mg per 5 mL (2 mg/mL) is supplied as a clear or nearly clear, orange-colored, citrus-flavored solution. NDC 0054-3556-63: Bottle of 500 mL DEA order form required.

📋 Description 124 words ▾

11 DESCRIPTION Methadone hydrochloride is chemically described as 6-(dimethylamino)-4,4-diphenyl-3-hepatanone hydrochloride. Methadone hydrochloride USP is a white powder that is water-soluble. Its molecular formula is C 21 H 27 NO• HCl and it has a molecular weight of 345.91.

Methadone hydrochloride has a melting point of 235°C, and a pKa of 8.25 in water at 20°C. Its octanol/water partition coefficient at pH 7.4 is 117. A solution (1:100) in water has a pH between 4.5 and 6.5.

It has the following structural formula: Each 5 mL of Methadone Hydrochloride Oral Solution contains 5 mg or 10 mg of methadone hydrochloride USP and the following inactive ingredients: alcohol (8%), benzoic acid, citric acid, FD&C Red #40, FD&C Yellow #6, flavoring (lemon), glycerin, sorbitol, and water. methadone-hcl-chem-structure.jpg

💬 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 Methadone Hydrochloride Oral Solution 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 Methadone Hydrochloride Oral Solution unsecured can pose a deadly risk to others in the home [see Warnings and Precautions ( 5.2 , 5.3 ), 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 Methadone Hydrochloride Oral Solution 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.

Medication Errors Strongly advise patients and caregivers to always use a graduated oral syringe or measuring cup, with metric units of measurements (i.e., mL), to correctly measure the prescribed amount of medication. Inform patients and caregivers that oral dosing devices may be obtained from their pharmacy and to never use household teaspoons or tablespoons to measure Methadone Hydrochloride Oral Solution [see Warnings and Precautions ( 5.1 )] . Advise patients and caregivers that Methadone Hydrochloride Oral Solution, is available in two concentrations: 5 mg per 5 mL and 10 mg per 5 mL.

Inform patients and caregivers about which concentration they have been prescribed and provide detailed instruction on how to measure and take or administer the correct dose of Methadone Hydrochloride Oral Solution, and to always use a graduated oral syringe or measuring cup when administering Methadone Hydrochloride Oral Solution, to ensure that the dose is measured and administered accurately. If the prescribed concentration is changed, instruct patients and caregivers on how to correctly measure the new dose to avoid errors which could result in accidental overdose and death.

Addiction, Abuse, and Misuse Inform patients that the use of Methadone Hydrochloride Oral Solution, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose or death [see Warnings and Precautions ( 5.2 )] . Instruct patients not to share Methadone Hydrochloride Oral Solution with others and to take steps to protect Methadone Hydrochloride Oral Solution 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 Methadone Hydrochloride Oral Solution 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 ( 5.4 )] . 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) and discuss the importance of having access to an opioid overdose reversal agent, both when initiating and renewing treatment with Methadone Hydrochloride Oral Solution.

Because patients being treated for opioid use disorder are at risk for relapse, discuss the importance of having access to an opioid overdose reversal agent. Also discuss the importance of having access to an opioid overdose reversal agent if the patient has household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose. D… [Excerpted — this section continues on DailyMed.]

💬 Medication Guide ~3 min read ▾

MEDICATION GUIDE Methadone Hydrochloride (meth’ a done hye” droe klor’ ide) Oral Solution USP, CII Rx only Methadone Hydrochloride Oral Solution is: • 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 pain treatments such as non-opioid pain medicines or immediate-release opioid medicines do not treat your pain well enough or you cannot tolerate them. • A long-acting 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 than can lead to death. • Not to be taken on an “as needed” basis. • Also used to manage drug addiction. Important information about Methadone Hydrochloride Oral Solution: • Get emergency help or call 911 right away if you take too much Methadone Hydrochloride Oral Solution (overdose). When you first start taking Methadone Hydrochloride Oral Solution, 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 Methadone Hydrochloride Oral Solution 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 Methadone Hydrochloride Oral Solution. They could die from taking it.

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

If your pain gets worse after you take Methadone Hydrochloride Oral Solution, do not take more of Methadone Hydrochloride Oral Solution 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 Methadone Hydrochloride Oral Solution. • pregnant or planning to become pregnant. Use of Methadone Hydrochloride Oral Solution 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.

Talk to your doctor if you are pregnant or plan to be pregnant. • breastfeeding. Methadone Hydrochloride Oral Solution passes into breast milk and may harm your baby. Carefully observe infants for increased sleepiness (more than usual), breathing difficulties, or limpness.

Seek immediate medical care if you notice these signs. • 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 Methadone Hydrochloride Oral Solution with certain other medicines may cause serious side effects. When taking Methadone Hydrochloride Oral Solution: • Do not change your dose.

Take Methadone Hydrochloride Oral Solution ex… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Absorption Following oral administration the bioavailability of methadone ranges between 36% to 100% and peak plasma concentrations are achieved between 1 to 7.5 hours. Dose proportionality of methadone pharmacokinetics is not known. However, after administration of daily oral doses ranging from 10 to 225 mg, the steady-state plasma concentrations ranged between 65 to 630 ng/mL and the peak concentrations ranged between 124 to 1,255 ng/mL.

Effect of food on the bioavailability of methadone has not been evaluated. Distribution Methadone is a lipophilic drug and the steady-state volume of distribution ranges between 1.0 to

8.0L/kg. In plasma, methadone is predominantly bound to α1-acid glycoprotein (85% to 90%). Methadone is secreted in saliva, breast milk, amniotic fluid and umbilical cord plasma.

Elimination Metabolism: Methadone is primarily metabolized by N-demethylation to an inactive metabolite, 2-ethylidene-1,5dimethyl-3,3-diphenylpyrrolidene (EDDP). Cytochrome P450 enzymes, primarily CYP3A4, CYP2B6, CYP2C19, CYP2C9, and CYP2D6, are responsible for conversion of methadone to EDDP and other inactive metabolites, which are excreted mainly in the urine. Methadone appears to be a substrate for P-glycoprotein but its pharmacokinetics do not appear to be significantly altered in case of P-glycoprotein polymorphism or inhibition.

Excretion: The elimination of methadone is mediated by extensive biotransformation, followed by renal and fecal excretion. Published reports indicate that after multiple dose administration the apparent plasma clearance of methadone ranged between 1.4 and 126 L/h, and the terminal half-life (T 1/2 ) was highly variable and ranged between 8 to 59 hours in different studies. Methadone is a basic (pKa=9.2) compound and the pH of the urinary tract can alter its disposition in plasma.

Also, since methadone is lipophilic, it has been known to persist in the liver and other tissues. The slow release from the liver and other tissues may prolong the duration of methadone action despite low plasma concentrations. Drug Interaction Studies Cytochrome P450 Interactions: Methadone undergoes hepatic N-demethylation by cytochrome P450 (CYP) isoforms, principally CYP3A4, CYP2B6, CYP2C19, and to a lesser extent by CYP2C9 and CYP2D6.

Co-administration of methadone with CYP inducers may result in more rapid metabolism and potential for decreased effects of methadone, whereas administration with CYP inhibitors may reduce metabolism and potentiate methadone’s effects. Although antiretroviral drugs such as efavirenz, nelfinavir, nevirapine, ritonavir, lopinavir+ritonavir combination are known to inhibit some CYPs, they are shown to reduce the plasma levels of methadone, possibly due to CYP induction activity [see Drug Interactions ( 7 )]. Cytochrome P450 Inducers: The following drug interactions were reported following co-administration of methadone with known inducers of cytochrome P450 enzymes: Rifampin: In patients well-stabilized on methadone, concomitant administration of rifampin resulted in a marked reduction in serum methadone levels and a concurrent appearance of withdrawal symptoms.

Phenytoin: In a pharmacokinetic study with patients on methadone maintenance therapy, phenytoin administration (250 mg twice daily initially for 1 day followed by 300 mg daily for 3 to 4 days) resulted in an approximately 50% reduction in methadone exposure and withdrawal symptoms occurred concurrently. Upon discontinuation of phenytoin, the incidence of withdrawal symptoms decreased and methadone exposure increased to a level comparable to that prior to phenytoin administration. St.

John’s Wort, Phenobarbital, Carbamazepine: Administration of methadone with other CYP3A4 inducers may result in withdrawal symptoms. Cytochrome P450 Inhibitors: Voriconazole: Voriconazole can inhibit the activity of CYP3A4, CYP2C9, and CYP2C19. Repeat dose administration of oral voriconazole (400 mg every 12 hours for 1 day, then 200 m… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics ~2 min read ▾

12.2Pharmacodynamics Effects on the Central Nervous System Methadone produces respiratory depression by direct action on brain stem 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. Methadone 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 origins may produce similar findings). Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations. Some NMDA receptor antagonists have been shown to produce neurotoxic effects in animals.

Effects on the Gastrointestinal Tract and Other Smooth Muscle Methadone 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 Methadone 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 )] . 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 )] . 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 methadone 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 ( 2.2 , 2.5 )] .

Concentration - Adverse Reaction Relationships There is a relationship between increasing methadone plasma concentration and increasing frequency of dose-related opioid adverse reactions such as nausea, vomiting, CNS effects, and respiratory depression. In opioid-tolerant patients, the situation may be altered by the development of tolerance to opioid-related adverse reactions [see Dosage and Administration ( 2.2 , 2.4 , 2.5 )] .

🔒 Drug Abuse and Dependence ~3 min read ▾

9 DRUG ABUSE AND DEPENDENCE

9.1Controlled Substance Methadone Hydrochloride Oral Solution contains methadone, a Schedule II controlled substance.

9.2Abuse Methadone Hydrochloride Oral Solution contains methadone, 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 ( 5.2 )] . 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 Methadone Hydrochloride Oral Solution 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 Methadone Hydrochloride Oral Solution 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 Methadone Hydrochloride Oral Solution abuse include those with a history of prolonged use of any opioid, including products containing methadone, those with a history of drug or alcohol abuse, or those who use Methadone Hydrochloride Oral Solution 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.

Methadone Hydrochloride Oral Solution, 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 Methadone Hydrochloride Oral Solution Abuse of Methadone Hydrochloride Oral Solution poses a risk of overdose and death. The risk is increased with concurrent use of Methadone Hydrochloride Oral Solution with alcohol and/or other CNS depressants. Methadone Hydrochloride Oral Solution is approved for oral use only.

Inappropriate intravenous, intramuscular, or subcutaneous use of Methadone Hydrochloride Oral Solution can result in death, local tissue necrosis, infection, pulmonary granulomas, increased risk of endocarditis, and valvular heart injury, and embolism. Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.… [Excerpted — this section continues on DailyMed.]

🔒 Controlled Substance 14 words ▾

9.1Controlled Substance Methadone Hydrochloride Oral Solution contains methadone, a Schedule II controlled substance.

🧪 Nonclinical Toxicology ~2 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis The results of carcinogenicity assessment in B6C2F1 mice and Fischer 344 rats following dietary administration of two doses of methadone HCl have been published. Mice consumed 15 mg/kg/day or 60 mg/kg/day methadone for two years. These doses were approximately 0.6 and 2.5 times a human daily oral dose of 120 mg/day on a body surface area basis (HDD).

There was a significant increase in pituitary adenomas in female mice treated with 15 mg/kg/day but not with 60 mg/kg/day. Under the conditions of the assay, there was no clear evidence for a treatment-related increase in the incidence of neoplasms in male rats. Due to decreased food consumption in males at the high dose, male rats consumed 16 mg/kg/day and 28 mg/kg/day of methadone for two years.

These doses were approximately 1.3 and 2.3 times the HDD. In contrast, female rats consumed 46 mg/kg/day or 88 mg/kg/day for two years. These doses were approximately 3.7 and 7.1 times the HDD.

Under the conditions of the assay, there was no clear evidence for a treatment-related increase in the incidence of neoplasms in either male or female rats. Mutagenesis There are several published reports on the potential genetic toxicity of methadone. Methadone tested positive in the in vivo mouse dominant lethal assay and the in vivo mammalian spermatogonial chromosome aberration test.

Additionally, methadone tested positive in the E. coli DNA repair system and Neurospora crassa and mouse lymphoma forward mutation assays. In contrast, methadone tested negative in tests for chromosome breakage and disjunction and sex-linked recessive lethal gene mutations in germ cells of Drosophila using feeding and injection procedures. Impairment of Fertility Published animal studies show that methadone treatment of males can alter reproductive function.

Methadone produces decreased sexual activity (mating) of male rats at 10 mg/kg/day (corresponding to 0.3 times the human daily oral dose of 120 mg/day based on body surface area). Methadone also produces a significant regression of sex accessory organs and testes of male mice and rats at 0.2 and 0.8 times the HDD, respectively. Methadone treatment of pregnant rats from Gestation Day 14 to 19 reduced fetal blood testosterone and androstenedione in males.

Decreased serum levels of testosterone were observed in male rats that were treated with methadone (1.3 to 3.3 mg/kg/day for 14 days, corresponding to 0.1 to 0.3 times the HDD) or 10 to 15 mg/kg/day for 10 days (0.8 to 1.2 times the HDD).

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~2 min read ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis The results of carcinogenicity assessment in B6C2F1 mice and Fischer 344 rats following dietary administration of two doses of methadone HCl have been published. Mice consumed 15 mg/kg/day or 60 mg/kg/day methadone for two years. These doses were approximately 0.6 and 2.5 times a human daily oral dose of 120 mg/day on a body surface area basis (HDD).

There was a significant increase in pituitary adenomas in female mice treated with 15 mg/kg/day but not with 60 mg/kg/day. Under the conditions of the assay, there was no clear evidence for a treatment-related increase in the incidence of neoplasms in male rats. Due to decreased food consumption in males at the high dose, male rats consumed 16 mg/kg/day and 28 mg/kg/day of methadone for two years.

These doses were approximately 1.3 and 2.3 times the HDD. In contrast, female rats consumed 46 mg/kg/day or 88 mg/kg/day for two years. These doses were approximately 3.7 and 7.1 times the HDD.

Under the conditions of the assay, there was no clear evidence for a treatment-related increase in the incidence of neoplasms in either male or female rats. Mutagenesis There are several published reports on the potential genetic toxicity of methadone. Methadone tested positive in the in vivo mouse dominant lethal assay and the in vivo mammalian spermatogonial chromosome aberration test.

Additionally, methadone tested positive in the E. coli DNA repair system and Neurospora crassa and mouse lymphoma forward mutation assays. In contrast, methadone tested negative in tests for chromosome breakage and disjunction and sex-linked recessive lethal gene mutations in germ cells of Drosophila using feeding and injection procedures. Impairment of Fertility Published animal studies show that methadone treatment of males can alter reproductive function.

Methadone produces decreased sexual activity (mating) of male rats at 10 mg/kg/day (corresponding to 0.3 times the human daily oral dose of 120 mg/day based on body surface area). Methadone also produces a significant regression of sex accessory organs and testes of male mice and rats at 0.2 and 0.8 times the HDD, respectively. Methadone treatment of pregnant rats from Gestation Day 14 to 19 reduced fetal blood testosterone and androstenedione in males.

Decreased serum levels of testosterone were observed in male rats that were treated with methadone (1.3 to 3.3 mg/kg/day for 14 days, corresponding to 0.1 to 0.3 times the HDD) or 10 to 15 mg/kg/day for 10 days (0.8 to 1.2 times the HDD).

📄 Recent Major Changes 29 words ▾

Boxed Warning ………………………………………………………..10/2025 Indications and Usage ( 1 )……………………………………………..10/2025 Dosage and Administration ( 2.3 , 2.6 )…………………………………10/2025 Warnings and Precautions ( 5.2 , 5.3 , 5.4 , 5.15 )………………………..10/2025

📄 Package Label / Principal Display Panel 62 words ▾

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL NDC 0054- 3555 -63 500 mL Methadone Hydrochloride Oral Solution USP CII 5 mg per 5mL Rx only 5 mg per 5 mL bottle label

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL NDC 0054- 3556 -63 500 mL Methadone Hydrochloride Oral Solution USP CII 10 mg per 5mL (2 mg/mL) Rx only 10 mg per 5 mL (2 mg/mL) bottle label

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

Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for this package alone, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q1 2026 · 5 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
22.3K
Units reimbursed last 4 qtrs
5.3M
Gross reimbursed last 4 qtrs
$1.8M
Avg / prescription
$80.45
Avg / unit
$0.3397
Latest quarter Q1 2026
15.5KRx
Medicaid pays / mL
$0.3397
gross reimbursed
vs
NADAC / mL
$0.0566
acquisition cost
=
Spread
+$0.2831
+500% vs cost
What Medicaid paid per mL (before rebates; includes the pharmacy’s dispensing fee) compared with NADAC — the average price pharmacies pay to buy the drug. A positive spread means Medicaid reimbursed more than the purchase price, before manufacturer rebates.
Fee-for-service vs managed care ⓘ
13% FFS 87% MCO
Fee-for-service · 2,955 Rx Managed care · 19,367 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: 5,964 units · 104 per 100k residents MN Wisconsin: no data reported WI Michigan: no data reported MI New York: 15,735 units · 80.4 per 100k residents NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: 5,184,696 units · 122,483 per 100k residents OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: no data reported IL Indiana: 1,129 units · 16.5 per 100k residents IN Ohio: 2,760 units · 23.4 per 100k residents OH Pennsylvania: 18,128 units · 140 per 100k residents PA New Jersey: no data reported NJ Massachusetts: 7,932 units · 113 per 100k residents MA California: 23,738 units · 60.9 per 100k residents CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported NE Missouri: no data reported MO Kentucky: no data reported KY West Virginia: no data reported WV Virginia: no data reported VA Maryland: no data reported MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: no data reported AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: 14,369 units · 133 per 100k residents NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: no data reported LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: 12,879 units · 42.2 per 100k residents TX Florida: no data reported FL
Units reimbursed · per 100k residents
16.5122,483
gray = no data reported ⓘ
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 Oregon 122,483 /100k
2 Pennsylvania 140 /100k
3 North Carolina 133 /100k
4 Massachusetts 113 /100k
5 Minnesota 104 /100k
6 New York 80.4 /100k
7 California 60.9 /100k
8 Texas 42.2 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.
🛡
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 ↗.
← 00054-3553-44 · Hikma 00054-3556-63 · Hikma →
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.