HomeNDC LookupIngredientsMethadone Hydrochloride › 66689-0820-10
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Methadone Hydrochloride 10 mg Tablet, 100-count

by VistaPharm, LLC · 100 TABLET in 1 BOTTLE (66689-820-10)
NDC 66689-0820-10
🏷️ FDA NDC (as labeled) 66689-820-10 billing pads the product segment with a zero
Rx only Generic On market CII 🛡 REMS
🗂️ Data synced Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →
⚠️
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

FDA NDC (as labeled) 66689-820-10
Product NDC 66689-820
11-digit billing NDC 66689082010
NCPDP billing unit EA — each (per item)
RxCUI 864706
UNII 229809935B
Application # ANDA040241
SPL Set ID 4c8b541c-33e8-4969-b258-af150808d46e
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 2018-11-22
Marketing end 2027-02-28
Route ORAL
Dosage form TABLET
Substance METHADONE HYDROCHLORIDE
GCN Seq No 004240
GCN 16420
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 HCL 10 MG TABLET
FDB brand name Methadone Hcl
Legend status F — Federal legend — prescription drug or device
Why two NDCs? The FDA registers this code as 66689-820-10 — 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 → 66689-0820-10. 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.

🏭 Manufacturer & labeler

LabelerVistaPharm, LLC
Application holderVISTAPHARM LLC
FDA applicationANDA040241 (ANDA)
Labeler code66689
First marketedNov 2018
DEA scheduleCII
Product typeHuman Prescription Drug
Portfolio19 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

Label name METHADONE HCL 10 MG TABLET Ingredient Methadone Hcl
📗 Our plain-language guide HelloPharmacist
  • Methadone is reserved for severe, persistent pain that needs around-the-clock treatment and hasn't responded well to other options. It's a long-acting opioid, which means it works...
  • Why is my doctor prescribing methadone instead of a regular painkiller?
  • When methadone is used for opioid addiction — not pain — federal law requires it to be dispensed only through certified opioid treatment programs. These clinics follow strict safet...
  • Why does methadone need to be dispensed at a special clinic for opioid treatment?
📖 Read our full Methadone 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.

🧪 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 3SY5LH9PMK
    Anhydrous lactose is a milk sugar with no water content. It acts as a filler and binder in tablets and capsules, adding bulk and helping ingredients stick together.
  • UNII 70097M6I30
    Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
  • UNII OP1R32D61U
    Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
  • UNII O8232NY3SJ
    A plant-based carbohydrate derived from corn kernels. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in your stomach for absorption.
  • UNII C151H8M554
    A natural sugar derived from sugar cane or sugar beets. It's used as a sweetener, filler, and binder to improve taste, add bulk, and help hold tablet or capsule ingredients together.
  • UNII 7SEV7J4R1U
    A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.

6 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 DailyMedingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

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

💲 Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eaPer package
Retail pharmacies payNADAC · weekly $0.175 $17.52 / 100 tablets
Medicaid paysCMS SDUD · 12 mo $0.2342 $23.42 / 100 tablets
Medicare drug plans payPart D · Q2 2026 $0.2238 $22.38 / 100 tablets
NADAC price history (per ea) — tap or hover for the price & month
Dec 2023 Dec 2025 Apr 2026 Aug 2026 $0.193 $0.148
▲ Up 18% over the last 12 months.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Methadone Hydrochloride 10 mg 42806-0318-01 Epic 100 tablets $0.098 AA FDA listed save 44%
Methadone Hydrochloride 10 mg 13107-0089-01 Aurolife 100 tablets $0.158 AA FDA listed save 10%
Methadone Hydrochloride 10 mg 00054-0710-20 Hikma 100 tablets $0.175 AA Discontinued
Methadone Hydrochloride 10 mg 00406-5771-01 SpecGx 100 tablets $0.175 AA Availability likely
Methadone Hydrochloride 10 mg 00904-7417-61 Major 100 tablets $0.175 AA Availability likely
Methadone Hydrochloride 10 mg 31722-0947-01 Camber 100 tablets $0.175 AA Availability likely
Methadone Hydrochloride 10 mg 64850-0604-01 Elite 100 tablets $0.175 AA Availability likely
Methadone Hydrochloride 10 mgthis 66689-0820-10 VistaPharm, 100 tablets $0.175 Availability likely
Methadone Hydrochloride 10 mg 66689-0836-99 VistaPharm, 100 tablets $0.175 AA Availability likely
Methadone Hydrochloride 10 mg 67877-0660-01 Ascend 100 tablets $0.175 AA Discontinued
Methadone Hydrochloride 10 mg 71335-1360-00 Bryant 168 tablets AA FDA listed
Methadone Hydrochloride 10 mg 72865-0121-01 XLCare 100 tablets AA FDA listed
Methadone Hydrochloride 10 mg 60687-0910-01 American 100 tablets 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

🏛️
2018
On the market since
Nov 2018
📍
2026
Currently FDA-listed
8 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.

🗺️ 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 66689-0820-10, 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 – Q4 2025 · 4 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
27
Units reimbursed last 4 qtrs
2.7K
Gross reimbursed last 4 qtrs
$627.29
Avg / prescription
$23.23
Avg / unit
$0.2342
Latest quarter Q4 2025
0Rx
Medicaid pays / ea
$0.2342
gross reimbursed
vs
NADAC / ea
$0.1752
acquisition cost
=
Spread
+$0.0590
+34% vs cost
What Medicaid paid per ea (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
48% FFS 52% MCO
Fee-for-service · 13 Rx Managed care · 14 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: no data reported MN Wisconsin: no data reported WI Michigan: 1,564 units · 15.6 per 100k residents MI New York: no data reported NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: no data reported 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: no data reported IN Ohio: no data reported OH Pennsylvania: no data reported PA New Jersey: no data reported NJ Massachusetts: no data reported MA California: 1,115 units · 2.9 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: no data reported 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: no data reported TX Florida: no data reported FL
Units reimbursed · per 100k residents
2.915.6
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 Michigan 15.6 /100k
2 California 2.9 /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 ↗.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
66689-0820-10 You're viewing this 100 TABLET in 1 BOTTLE (66689-820-10) 2018-11-22 Active

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning ~3 min read

WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF METHADONE HYDROCHLORIDE TABLETS A ddiction, Abuse, and Misuse Because the use of methadone hydrochloride 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 methadone hydrochloride tablets, especially during initiation or following a dosage increase.

To reduce the risk of respiratory depression, proper dosing and titration of methadone hydrochloride tablets are essential [see Warnings and Precautions ( 5.2 )] . Accidental Ingestion Accidental ingestion of even one dose of methadone hydrochloride tablets, especially by children, can result in a fatal overdose of methadone [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 methadone hydrochloride 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) Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of use of methadone hydrochloride tablets 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 material methadone hydrochloride tablets 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 ( 5.5 )]. 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 ( 5.6 )] .

Li f e - T hreatening QT Prolongation Q T 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 those taking medications affecting cardiac conduction for changes in cardiac rhythm during initiation and titration of methadone hydrochloride tablets [see Warnings and Precautions ( 5.4 )] .

C ytochrome P450 Interaction T he concomitant use of methadone hydrochloride tablets with all cytochrome P450 3A4, 2B6, 2C19, 2C9 or 2D6 inhibitors may result in an increase in methadone plasma concentrations, which could cause potentially fatal respiratory depression. In addition, discontinuation of concomitantly used cytochrome P450 3A4, 2B6, 2C19, or 2C9 inducers may also result in an increase in methadone plasma concentration. Follow patients closely for respiratory depression and sedation, and consider dosage reduction with any changes of concomitant medications that can result in an increase in methadone levels [ see Warnings and Precautions ( 5.7 ), Drug Interactions ( 7 )].

C onditions For Distribution And Use Of Methadone Products For The Treatment Of Opio…

🎯 Indications and Usage ~2 min read

1 INDICATIONS AND USAGE Methadone hydrochloride tablets are indicated for the: 1. Management of severe and persistent pain that requires an extended treatment with a daily opioid analgesic that cannot be adequately treated with alternative options, including immediate-release opioids Limitations of Use Because of the risks of addiction, abuse, and 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 methadone hydrochloride tablets for use in patients for whom alternative analgesic treatment options (e.g., non-opioid analgesics or opioid combination products) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.

Methadone hydrochloride tablets are not indicated as an as-needed (prn) analgesic. ( 1 ) 2. Detoxification treatment of opioid addiction (heroin or other morphine-like drugs).

3. 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 tablet is indicated for the management of severe and persistent pain that requires opioid analgesic and that cannot be adequately treated with alternative options, including immediate-release opioids. L i mitations 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 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 ) Methadone hydrochloride tablets are 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 reversal agent (e.g., naloxone, nalmefene) based on the patient’s risk factors for overdose ( 2.3 , 5.1 , 5.2 , 5.3 ) Management of Pain Methadone hydrochloride 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 ) 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 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 ) 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 ( 5.1 ) Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with methadone hydrochloride tablets.

Consider this risk when selecting an initial dose and when making dose adjustments ( 2.1 , 5.2 ) To convert to methadone hydrochloride tablets 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 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.

( 2.5 ) Do not rapidly reduce or abruptly discontinue methadone hydrochloride 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. ( 2.6 , 5.16 ) Initi a ti o n 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 The peak respiratory depressant effect of methadone occurs later and persists longer than its peak therapeutic effect. A high degree of opioid tolerance does not eliminate the possibility of methadone overdose, iatrogenic or otherwise. Deat…

💊 Dosage Forms and Strengths 32 words

3 DOSAGE FORMS AND STRENGTHS 10 mg, white, round, biconvex, tablet, debossed “ E ” over “131” on one side and bisected on the other side. Tablets: 10 mg. ( 3 )

Contraindications 115 words

4 CONTRAINDICATIONS Methadone hydrochloride 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 ( 5.10 )] . 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 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. ( 5.8 ) S e ro t o ni n Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration.

Discontinue methadone hydrochloride tablets if serotonin syndrome is suspected. ( 5.9 ) Risk of Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients : Regularly evaluate closely, particularly during initiation and titration. ( 5.10 ) A d r e na l Insufficiency : If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid.

( 5.11 ) S e v e r e Hypotension : Regularly evaluate during dose initiation and titration. Avoid use in patients with circulatory shock. ( 5.12 ) Ri s k s of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness : Monitor for sedation and respiratory depression.

Avoid use of methadone hydrochloride tablets in patients with impaired consciousness or coma. ( 5.13 )

5.1Addiction, Abuse and Misuse Methadone hydrochloride tablets contain methadone, a Schedule II controlled substance. As an opioid, methadone hydrochloride tablets expose users to the risks of addiction, abuse, and misuse. As long-acting opioids such as methadone hydrochloride tablets 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 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 )] . Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing methadone hydrochloride tablets, and reassess all patients receiving methadone hydrochloride 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 proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as methadone hydrochloride tablets, but use in such patients necessitates intensive counseling about the risks and proper use of methadone hydrochloride tablets along with the frequent reevaluation for signs of addiction, abuse, and misuse. Consider recommending or prescribing an opioid reversal agent [see Dosage and Administration ( 2.3 ), Warnings and Precautions ( 5.2 )] .

Abuse or misuse of methadone hydrochloride tablets by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of the methadone and can result in overdose and death [see Overdosage ( 10 )] . Opioids are sought for nonmedical use and are subject to diversion from legitimate prescribed use. Consider these risks when prescribing or dispensing methadone hydrochloride tablets.

Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on careful storage of the drug during the course of treatment and proper disposal of unused drug. Contact local state professional licensing board o…

🤒 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 ( 5.1 )] Life Threatening Respiratory Depression [see Warnings and Precautions ( 5. 2 )] QT Prolongation [see Warnings and Precautions ( 5. 4 )] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions ( 5.5 )] Interactions with Benzodiazepines and other CNS Depressants [see Warnings and Precautions ( 5.3 )] Opioid-Induced Hyperalgesia and Allodynia [see Warnings and Precautions ( 5.8 )] Serotonin Syndrome [see Warnings and Precautions ( 5.9 )] 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: hypoglycemia, 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 tablets.

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 chronic 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 ( 5.8 )] . Hypoglycemia: Cases of hypoglycemia have been reported in patients taking methadone [see Warnings and Precautions ( 5.18 )]. Opioid-induced esophageal dysfunction (OIED): Cases of O…

🔄 Drug Interactions ~3 min read

7 DRUG INTERACTIONS A nti - R e t rov i r a l Agents : May result in decreased efficacy or, in certain cases, increased toxicity. ( 7 ) Po t e ntia ll y Arrhythmogenic Agents : Pharmacodynamic interactions may occur. Monitor patients closely for cardiac conduction changes.

( 7 ) Mi x e d Agonist/Antagonist and Partial Agonist Opioid Analgesics : Avoid use with methadone hydrochloride tablets because they may reduce analgesic effect of methadone hydrochloride tablets or precipitate withdrawal symptoms. ( 5.16 , 7 ) M o n o a m in e Oxidase Inhibitors (MAOIs) : Can potentiate the effects of methadone. Avoid concomitant use in patients receiving MAOIs or within 14 days of stopping treatment with an MAOI.

( 7 ) 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 tablets 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 tablets 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 tablets 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 tablets 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 tablets 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 tablets 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 tablets dosage 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…

👥 Use in Specific Populations ~3 min read

8 USE IN SPECIFIC POPULATIONS L actati o n : 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/m 2 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. C li n i cal Considerations D i sease-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.

D osage 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 hydrochloride tablets. 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 hydrochloride tablets. 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 sev…

🤰 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/m 2 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. C li n i cal Considerations D i sease-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.

D osage 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 hydrochloride tablets. 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 hydrochloride tablets. 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…

🧒 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 tablets slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression [see Warnings and Precautions ( 5.10 )] . 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 with 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 reversal would be expected to be less than the duration of action of methadone in methadone hydrochloride tablets, carefully monitor the patient until spontaneous respiration is reliably reestablished.

If the response to opioid overdose reversal agent is suboptimal or not sustained, administer additional reversal agent as directed in the product’s prescribing information. In an individual physically dependent on opioids, administration of the recommended usual dosage of the 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 be begun 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 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, and 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. C oncentration–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 )] .

C oncentration–Ad…

🧬 Mechanism of Action 109 words

12.1Mechanism of Action Methadone hydrochloride is a mu-agonist; a synthetic opioid 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 97 words

16 HOW SUPPLIED/STORAGE AND HANDLING Methadone Hydrochloride Tablets, USP 10 mg , white, round, biconvex, tablet, de-bossed “E” over “131” on one side and bisected on the other side and available as: NDC 66689-820-10: Bottles of 100 Dispense contents with a child-resistant closure (as required) and in a tight, light-resistant container as defined in the USP/NF. Store at 20° to 25°C (68° to 77°F), with excursions permitted between 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature.] Store methadone hydrochloride tablets securely and dispose of properly [ see Patient Counseling Information ( 17 ) ].

📋 Description 108 words

11 DESCRIPTION Methadone hydrochloride is chemically described as 6-(dimethylamino)-4,4-diphenyl-3-hepatanone hydrochloride. Methadone hydrochloride USP is a white powder. 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 methadone hydrochloride tablet, USP contains 10 mg methadone hydrochloride USP and the following inactive ingredients: anhydrous lactose, compressible sugar, corn starch, magnesium stearate, microcrystalline cellulose, and talc. Chemical Structure

💬 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 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 methadone hydrochloride 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 methadone hydrochloride 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 methadone hydrochloride 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 methadone hydrochloride tablets with others and to take steps to protect methadone hydrochloride 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 methadone hydrochloride 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 )] . Accidental Ingestion Inform patients that accidental ingestion, especially by children, may result in respiratory depression or death [see Warnings and Precautions ( 5.2 )] . Symptoms of Arrhythmia Instruct patients to seek medical attention immediately if they experience symptoms suggestive of an arrhythmia (such as palpitations, near syncope, or syncope) when taking methadone [see Warnings and Precautions ( 5.4 )] .

Interactions with Benzodiazepines and Other CNS Depressants Inform patients and caregivers that potentially fatal additive effects may occur if methadone hydrochloride tablets are used with benzodiazepines or other CNS depressants (e.g., alcohol, 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) and discuss the importance of having access to an opioid overdose reversal agent, both when initiating and renewing treatment with methadone hydrochloride tablets. 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.

Discuss with the patient the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter (some products), or as part of a community-based program) [ see Dosage and Administration ( 2.3 ), Warnings and Pr…

💬 Medication Guide ~3 min read

Medication Guide Methadone Hydrochloride Tablets, USP (METH-ah-done), CII Rx Only Methadone Hydrochloride Tablet 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 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 that can lead to death.

Not to be taken on an “as needed” basis. Also used to manage drug addiction. Important information about Methadone Hydrochloride Tablets: Get emergency help or call 911 right away if you take too much Methadone Hydrochloride Tablets (overdose) .

When you first start taking methadone hydrochloride 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 methadone hydrochloride 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 methadone hydrochloride tablets. They could die from taking it. Selling or giving away methadone hydrochloride tablets is against the law.

Store methadone hydrochloride 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 Methadone Hydrochloride 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 Methadone Hydrochloride Tablets, tell your healthcare provider if you have a history of: head injury, seizures liver, kidney, thyroid problems problems urinating heart rhythm problems (Long QT syndrome) pancreas or gallbladder problems 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 methadone hydrochloride tablets, do not take more of methadone hydrochloride 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 methadone hydrochloride tablets. Pregnant or plan to become pregnant. If you take methadone hydrochloride tablets while pregnant, your baby may have symptoms of opioid withdrawal or respiratory depression at birth.

Talk to your doctor if you are pregnant or plan to become pregnant. Breastfeeding. Methadone 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 tablets with certain other medicines may cause serious side effects. When taking Methadone Hydrochloride Tablets: Do not change your dose.

Take methadone hydrochloride tablets exactly as prescribed by your healthcare provider. Use the lowest dose possible for the shortest time needed. Do not take more than your prescribed dose in 24 hours.

If you take methadone hydrochloride tablets for pain and miss a dose, take methadone hydrochloride tablets as soon as possible and then take your next dose 8 or 12…

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