Methadone API Manufacturers & Suppliers
0 verified results
Get full market intelligence report
All Methadone data. Full access. Full negotiation power
€399,-
This product is listed at the international narcotic list. The purchase and handling are strictly ruled
by national and international laws. Pharmaoffer will validate buyers and suppliers before an order
can be settled.
Commercial-scale Suppliers
To view suppliers for this material, you need to be logged in first.
This is because of international laws regarding narcotic materials. Furthermore, the contents of this page are only accessible if you are professionaly active in the pharmaceutical industry. In case you are, it is possible to register on our platform, and after your account is approved by our team you will be able to view suppliers and send your request.
When insight is your advantage
Full data, full access, full negotiation power
Total market transparency
|
Supplier trade data access
|
Buyer / supplier flow comparison
Trusted by 30,000+ registered pharma professionals:
Reach multinationals, SMEs, compounding pharmacies & more!
Methadone | CAS No: 76-99-3 | GMP-certified suppliers
A medication that supports management of severe pain when alternatives are insufficient and enables detoxification and maintenance treatment for opioid dependence within structured care programs.
Therapeutic categories
AnalgesicsAnticholinergic AgentsAntidepressive AgentsAntitussive AgentsCentral Nervous System AgentsCentral Nervous System Depressants
Generic name
Methadone
Molecule type
small molecule
CAS number
76-99-3
DrugBank ID
DB00333
Approval status
Approved drug
ATC code
N07BC02
Primary indications
- Methadone is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatment options are inadequate
- It's recommended that use is reserved for use in patients for whom alternative treatment options (eg, nonopioid analgesics, opioid combination products) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain
- Methadone is also indicated for detoxification treatment of opioid addiction (heroin or other morphine-like drugs), and for maintenance substitution treatment for opioid dependence in adults in conjunction with appropriate social and medical services
Product Snapshot
- Methadone is an oral and parenteral small-molecule opioid available in solutions, tablets, syrups, concentrates, and injectable formulations
- It is used for severe pain management and for detoxification or maintenance substitution treatment in opioid dependence programs
- It is approved and marketed in the US and Canada
Clinical Overview
Methadone, CAS 76-99-3, is a synthetic diphenylmethane derivative indicated for severe pain requiring an opioid analgesic and for detoxification and maintenance treatment of opioid dependence. It is used in opioid agonist treatment programs to suppress withdrawal symptoms and support stabilization when combined with appropriate medical and social care.
Its pharmacology is defined by full agonist activity at the µ‑opioid receptor, with additional agonism at κ‑ and σ‑opioid receptors. Methadone also antagonizes NMDA receptors and inhibits serotonin and norepinephrine reuptake, contributing to its utility in neuropathic and cancer pain. It is administered as a racemate, with R‑methadone providing most analgesic activity. These combined mechanisms result in analgesia, respiratory depression, miosis, reduced gastrointestinal motility, and suppression of withdrawal symptoms.
Methadone exhibits high oral bioavailability and a prolonged, variable half‑life that can exceed its analgesic duration. It is metabolized primarily by CYP2B6 and CYP3A pathways and acts as both a substrate and inhibitor of several CYP enzymes. Renal clearance of unchanged drug is limited, and accumulation is minimal in renal impairment.
Safety considerations include dose‑dependent respiratory depression, with peak depressant effects occurring later and lasting longer than peak analgesia. Methadone can prolong the QT interval via potassium channel inhibition, with rare cases of torsades de pointes reported, particularly at higher doses or in the presence of electrolyte disturbances or interacting drugs. Additional risks include hypotension, constipation, endocrine effects, and incomplete cross‑tolerance when converting from other opioids. Dependence and withdrawal can occur with abrupt discontinuation.
Methadone is used globally in both pain management and opioid dependence programs, with various oral solution and tablet formulations available.
For API procurement, sourcing should focus on suppliers with demonstrated control of stereochemical composition, validated impurity profiles, and compliance with pharmacopoeial monographs and controlled substance regulations.
Its pharmacology is defined by full agonist activity at the µ‑opioid receptor, with additional agonism at κ‑ and σ‑opioid receptors. Methadone also antagonizes NMDA receptors and inhibits serotonin and norepinephrine reuptake, contributing to its utility in neuropathic and cancer pain. It is administered as a racemate, with R‑methadone providing most analgesic activity. These combined mechanisms result in analgesia, respiratory depression, miosis, reduced gastrointestinal motility, and suppression of withdrawal symptoms.
Methadone exhibits high oral bioavailability and a prolonged, variable half‑life that can exceed its analgesic duration. It is metabolized primarily by CYP2B6 and CYP3A pathways and acts as both a substrate and inhibitor of several CYP enzymes. Renal clearance of unchanged drug is limited, and accumulation is minimal in renal impairment.
Safety considerations include dose‑dependent respiratory depression, with peak depressant effects occurring later and lasting longer than peak analgesia. Methadone can prolong the QT interval via potassium channel inhibition, with rare cases of torsades de pointes reported, particularly at higher doses or in the presence of electrolyte disturbances or interacting drugs. Additional risks include hypotension, constipation, endocrine effects, and incomplete cross‑tolerance when converting from other opioids. Dependence and withdrawal can occur with abrupt discontinuation.
Methadone is used globally in both pain management and opioid dependence programs, with various oral solution and tablet formulations available.
For API procurement, sourcing should focus on suppliers with demonstrated control of stereochemical composition, validated impurity profiles, and compliance with pharmacopoeial monographs and controlled substance regulations.
Identification & chemistry
| Generic name | Methadone |
|---|---|
| Molecule type | Small molecule |
| CAS | 76-99-3 |
| UNII | UC6VBE7V1Z |
| DrugBank ID | DB00333 |
Pharmacology
| Summary | Methadone is a synthetic opioid that primarily acts as a full agonist at the µ‑opioid receptor, with additional activity at κ‑ and σ‑opioid receptors that supports its analgesic and withdrawal‑suppressing effects. It also antagonizes NMDA receptors and inhibits serotonin and norepinephrine reuptake, contributing to its antinociceptive profile and distinguishing it from other opioids. The racemic formulation contains (R)-methadone as the main mediator of opioid receptor activity, while the (S)-isomer contributes non‑opioid pharmacologic effects. |
|---|---|
| Mechanism of action | Methadone is a synthetic opioid analgesic with full agonist activity at the µ-opioid receptor. While agonism of the µ-opioid receptor is the primary mechanism of action for the treatment of pain, methadone also acts as an agonist of κ- and σ-opioid receptors within the central and peripheral nervous systems. Interestingly, methadone differs from [morphine] (which is considered the gold standard reference opioid) in its antagonism of the N-methyl-D-aspartate (NMDA) receptor and its strong inhibition of serotonin and norepinephrine uptake, which likely also contributes to its antinociceptive activity. Methadone is administered as a 50:50 racemic mixture of (R)- and (S)-stereoisomers, with (R)-methadone demonstrating ~10-fold higher affinity and potency for the µ-opioid receptor than the (S) stereoisomer.The analgesic activity of the racemate is almost entirely due to the (R)-isomer, while the (S)-isomer lacks significant respiratory depressant activity but does have antitussive effects. While methadone shares similar effects and risks of other opioids such as [morphine], [hydromorphone], [oxycodone], and [fentanyl] it has a number of unique pharmacokinetic and pharmacodynamic properties that distinguish it from them and make it a useful agent for the treatment of opioid addiction. For example, methadone abstinence 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. |
| Pharmacodynamics | Overall, methadone's pharmacological actions result in analgesia, suppression of opioid withdrawal symptoms, sedation, miosis (through binding to receptors in the pupillary muscles), sweating, hypotension, bradycardia, nausea and vomiting (via binding within the chemoreceptor trigger zone), and constipation. Like many basic drugs, methadone also enters mast cells and releases histamine by a non-immunological mechanism leading to flushing, pruritus, and urticaria, which can commonly be misattributed to an allergic reaction. Compared to other opioids, methadone has fewer active metabolites and therefore a lower risk of neuropsychiatric toxicity. This means that higher doses needed to manage severe pain or addiction are less likely to result in delirium, hyperalgesia, or seizures. Similar to morphine, both methadone isomers are 5-HT(3) receptor antagonists, although l-methadone produces greater inhibition than d-methadone. Methadone's effects are reversible by naloxone with a pA2 value similar to its antagonism of morphine. **Dependence and Tolerance** As with other opioids, tolerance and physical dependence may develop upon repeated administration of methadone and there is a potential for development of psychological dependence. Physical dependence and tolerance reflect the neuroadaptation of the opioid receptors to chronic exposure to an opioid and are separate and distinct from abuse and addiction. Tolerance, as well as physical dependence, may develop upon repeated administration of opioids, and are not by themselves evidence of an addictive disorder or abuse. Patients on prolonged therapy should be tapered gradually from the drug if it is no longer required for pain control. Withdrawal symptoms may occur following abrupt discontinuation of therapy or upon administration of an opioid antagonist. Some of the symptoms that may be associated with abrupt withdrawal of an opioid analgesic include body aches, diarrhea, gooseflesh, loss of appetite, nausea, nervousness or restlessness, anxiety, runny nose, sneezing, tremors or shivering, stomach cramps, tachycardia, trouble with sleeping, unusual increase in sweating, palpitations, unexplained fever, weakness and yawning. **Cardiac Conduction Effects** Laboratory studies, both in vivo and in vitro, have demonstrated that methadone inhibits cardiac potassium channels and prolongs the QT interval. Cases of QT interval prolongation and serious arrhythmia (torsades de pointes) have been observed during treatment with methadone. These cases appear to be more commonly associated with, but not limited to, higher dose treatment (> 200 mg/day). Methadone should be administered with particular caution to patients already at risk for development of prolonged QT interval (e.g., cardiac hypertrophy, concomitant diuretic use, hypokalemia, hypomagnesemia). Careful monitoring is recommended when using methadone in patients with a history of cardiac conduction disease, those taking medications affecting cardiac conduction, and in other cases where history or physical exam suggest an increased risk of dysrhythmia. **Respiratory Depression and Overdose** Serious, life-threatening, or fatal respiratory depression may occur with use of methadone. Patients should be monitored for respiratory depression, especially during initiation of methadone or following a dose increase. Respiratory depression is of particular concern in elderly or debilitated patients as well as in those suffering from conditions accompanied by hypoxia or hypercapnia when even moderate therapeutic doses may dangerously decrease pulmonary ventilation. Methadone should be administered with extreme caution to patients with conditions accompanied by hypoxia, hypercapnia, or decreased respiratory reserve such as: asthma, chronic obstructive pulmonary disease or cor pulmonale, severe obesity, sleep apnea syndrome, myxedema, kyphoscoliosis, and CNS depression or coma. In these patients, even usual therapeutic doses of methadone may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea. Alternative, non-opioid analgesics should be considered, and methadone should be employed only under careful medical supervision at the lowest effective dose. Infants exposed in-utero or through breast milk are at risk of life-threatening respiratory depression upon delivery or when nursed. Methadone's peak respiratory depressant effects typically occur later, and persist longer than its peak analgesic effects, in the short-term use setting. These characteristics can contribute to cases of iatrogenic overdose, particularly during treatment initiation and dose titration. **Head Injury and Increased Intracranial Pressure** The respiratory depressant effects of opioids and their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions or a pre-existing increase in intracranial pressure. Furthermore, opioids produce effects which may obscure the clinical course of patients with head injuries. In such patients, methadone must be used with caution, and only if it is deemed essential. **Incomplete Cross-tolerance between Methadone and other Opioids** Patients tolerant to other opioids may be incompletely tolerant to methadone. Incomplete cross-tolerance is of particular concern for patients tolerant to other µ-opioid agonists who are being converted to methadone, thus making the determination of dosing during opioid conversion complex. Deaths have been reported during conversion from chronic, high-dose treatment with other opioid agonists. A high degree of “opioid tolerance” does not eliminate the possibility of methadone overdose, iatrogenic or otherwise. Crosstolerance between morphine and methadone has been demonstrated, as steady-state plasma methadone concentrations required for effectiveness (C50%) were higher in abstinent rats previously dosed with morphine, as compared to controls. **Misuse, Abuse, and Diversion of Opioids** Methadone is a mu-agonist opioid with an abuse liability similar to morphine. Methadone, like morphine and other opioids used for analgesia, has the potential for being abused and is subject to criminal diversion. Methadone can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when dispensing Methadone in situations where the clinician is concerned about an increased risk of misuse, abuse, or diversion. **Hypotensive Effect** The administration of methadone may result in severe hypotension in patients whose ability to maintain normal blood pressure is compromised (e.g., severe volume depletion). **Gastrointestinal Effects** Methadone and other morphine-like opioids have been shown to decrease bowel motility and cause constipation. This primarily occurs through agonism of opioid receptors in the gut wall. Methadone may obscure the diagnosis or clinical course of patients with acute abdominal conditions. **Sexual Function/Reproduction** Reproductive function in human males may be decreased by methadone treatment. Reductions in ejaculate volume and seminal vesicle and prostate secretions have been reported in methadone-treated individuals. In addition, reductions in serum testosterone levels and sperm motility, and abnormalities in sperm morphology have been reported. Long-term use of opioids may be associated with decreased sex hormone levels and symptoms such as low libido, erectile dysfunction, or infertility. |
Targets
| Target | Organism | Actions |
|---|---|---|
| Mu-type opioid receptor | Humans | agonist |
| NMDA receptor | Humans | antagonist |
| Delta-type opioid receptor | Humans | agonist |
ADME / PK
| Absorption | Methadone is one of the more lipid-soluble opioids and is well absorbed from the gastrointestinal tract. Following oral administration of methadone, bioavailability ranges from 36-100%, with a marked interindividual variation. It can be detected in blood as soon as 15-45 minutes following administration with peak plasma concentrations achieved between 1 to 7.5 hours. A second peak is observed ~4 hours after administration and is likely due to enterohepatic circulation. Dose proportionality of methadone pharmacokinetics is not known. Following 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 1255 ng/mL. Effect of food on the bioavailability of methadone has not been evaluated. Slower absorption is observed in opioid users compared to healthy subjects, which may reflect the pharmacological effect of opioids in slowing gastric emptying and mobility. Due to the large inter-individual variation in methadone pharmacokinetics and pharmacodynamics, treatment should be individualized to each patient. There was an up to 17-fold interindividual variation found in methadone blood concentrations for a given dosage, likely due in part to individual variability in CYP enzyme function.There is also a large variability in pharmacokinetics between methadone's enantiomers, which further complicates pharmacokinetic interpretation and study. |
|---|---|
| Half-life | Due to interindividual differences in pharmacokinetics, estimates of methadone's half-life have ranged from 15–207 hourswith official monographs listing it between 7-59 hours. |
| Protein binding | Methadone is highly bound to plasma proteins. While it primarily binds to α1-acid glycoprotein (85-90%), it also binds to albumin and other tissue and plasma proteins including lipoproteins. Methadone is unusual in the opioid class, in that there is extensive binding to tissue proteins and fairly slow transfer between some parts of this tissue reservoir and the plasma. |
| Metabolism | Methadone undergoes fairly extensive first-pass metabolism. Cytochrome P450 enzymes, primarily CYP3A4, CYP2B6, and CYP2C19 and to a lesser extent CYP2C9, CYP2C8, and CYP2D6, are responsible for conversion of methadone to EDDP (2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine) and other inactive metabolites, which are excreted mainly in the urine. Methadone first undergoes N-demethylation to form a highly unstable compound that spontaneously converts to EDDP through cyclization and dehydration. EDDP is then converted to 2-ethyl5-methyl-3,3-diphenyl-1-pyrroline (EDMP). Both EDDP and EDMP are inactive. The CYP isozymes also demonstrate different affinities for metabolizing the different methadone enantiomers: CYP2C19, CYP3A7, and CYP2C8 preferentially metabolize (R)-methadone while CYP2B6, CYP2D6, and CYP2C18 preferentially metabolize (S)-methadone. CYP3A4 does not have an enantiomer preference. Single nucleotide polymorphisms (SNPs) within the cytochrome P450 enzymes can impact methadone pharmacokinetics and contribute to the interindividual variation in response to methadone therapy. In particular, CYP2B6 polymorphisms have been shown to impact individual response to methadone as it is the predominant determinant involved in the N-demethylation of methadone, clearance, and the metabolic ratios of [methadone\]/[EDDP].The SNPs CYP2B6\*6, \*9, \*11, CYP2C19\*2, \*3, CYP3A4\*1B, and CYP3A5\*3 result in increased methadone plasma concentrations, decreased N-demethylation, and decreased methadone clearance, while homozygous carriers of CYP2B6\*6/\*6 demonstrate diminished metabolism and clearance of methadone.See the pharmacogenomics section for further information. Pharmacogenomic effects on the CYP enzymes can be significant as the long half-life of methadone can result in some individuals having higher than normal therapeutic levels which puts them at risk of dose-related side effects. For example, elevated (R)-methadone levels can increase the risk of respiratory depression, while elevated (S)-methadone levels can increase the risk of severe cardiac arrhythmias due to prolonged QTc interval. |
| Route of elimination | The elimination of methadone is mediated by extensive biotransformation, followed by renal and fecal excretion. Unmetabolized methadone and its metabolites are excreted in urine to a variable degree. |
| Volume of distribution | Due to interindividual differences in pharmacokinetics, estimates of methadone's volume of distribution have ranged from 189-470 Lwith monographs listing it between 1.0-8.0L/kg.As this is higher than physiological volumes of total body water, methadone is highly distributed in the body including brain, gut, kidney, liver, muscle, and lung. A population pharmacokinetic study found that subject gender and weight explained ~33% of the variance in the apparent volume of distribution of methadone. Methadone is found to be secreted in saliva, sweat, breast milk, amniotic fluid and umbilical cord plasma. The concentration in cord blood is about half the maternal levels. |
| Clearance | Due to interindividual differences in pharmacokinetics, estimates of methadone's clearance have ranged from 5.9–13 L/h hourswith approved monographs listing it between 1.4 to 126 L/h. |
Formulation & handling
- Low aqueous solubility and high lipophilicity favor use of acidic salts or co‑solvent systems for oral solutions and parenteral concentrates.
- Solid oral forms require solubilizing excipients or granulation approaches to ensure consistent dissolution of the hydrophobic API.
- For injectable use, maintain controlled pH and appropriate solvent systems to keep the API in solution and ensure stability during storage and handling.
Regulatory status
| Lifecycle | Patent‑expiry timing will largely determine competitive dynamics, with both the US and Canada typically seeing rapid generic entry once protections lapse. In these markets, the API generally progresses quickly into a mature, multi‑supplier phase following loss of exclusivity. |
|---|
| Markets | Canada, US |
|---|
Supply Chain
| Supply chain summary | Methadone is supplied by multiple established manufacturers and repackagers, with no single originator dominating current production, reflecting its long-established status in therapy. Branded products such as Diskets and regional brands like Apo‑methadone indicate presence mainly in the US and Canada. Patent expiry occurred long ago, so the market is fully open to generic competition with mature multi‑supplier availability. |
|---|
Safety
| Toxicity | In severe overdosage, particularly by the intravenous route, apnea, circulatory collapse, cardiac arrest, and death may occur. |
|---|
High Level Warnings:
- Severe overexposure, especially via intravenous routes, can precipitate respiratory arrest, acute circulatory collapse, and cardiac arrest
- Processes should incorporate controls that prevent accidental high-dose exposure
- Handling and transfer operations should minimize aerosolization or leakage due to risk of rapid-onset central respiratory depression
Methadone is a type of Opioid analgesics
Opioid analgesics are a subcategory of pharmaceutical Active Pharmaceutical Ingredients (APIs) that are commonly used for pain management. These potent substances interact with specific receptors in the central nervous system, producing analgesic effects and reducing the perception of pain. Opioid analgesics are derived from opium alkaloids or synthetic compounds that mimic their effects. They are classified based on their strength, with some being classified as strong opioids (e.g., morphine, fentanyl) and others as weak opioids (e.g., codeine, tramadol). These APIs work by binding to opioid receptors, primarily located in the brain, spinal cord, and gastrointestinal tract. By activating these receptors, opioid analgesics modulate pain signals, resulting in pain relief. Additionally, they can induce feelings of euphoria, sedation, and respiratory depression, which can be both beneficial and potentially harmful.
Due to their potency and potential for abuse, opioid analgesics are tightly regulated substances. They are primarily prescribed for acute and chronic pain management, such as post-surgical pain, cancer pain, and severe injuries. However, their misuse and addiction potential have led to a public health crisis in many countries.
In conclusion, opioid analgesics are a subcategory of pharmaceutical APIs that play a crucial role in pain management. While they provide effective pain relief, their use requires careful monitoring and adherence to prescribing guidelines to mitigate the risks associated with their potential for abuse and addiction.
Methadone (Opioid analgesics), classified under Analgesics
Analgesics are a category of pharmaceutical Active Pharmaceutical Ingredients (APIs) that are commonly used to relieve pain. They are designed to alleviate discomfort by targeting the body's pain receptors or by reducing inflammation. Analgesics are widely utilized in the medical field to manage various types of pain, ranging from mild to severe.
One of the primary classes of analgesics is nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs work by inhibiting the production of prostaglandins, substances that contribute to pain and inflammation. This class includes well-known drugs like ibuprofen and naproxen. Another class of analgesics is opioids, which are derived from opium or synthetic compounds that mimic the effects of opium. Opioids act on the central nervous system to reduce pain perception and provide potent pain relief. Examples of opioids include morphine, codeine, and oxycodone.
Analgesics are available in various forms, such as tablets, capsules, creams, and injections, allowing for different routes of administration based on the patient's needs. They are commonly used to manage pain associated with conditions like arthritis, headaches, dental procedures, and post-operative recovery.
It is important to note that analgesics should be used under medical supervision, as improper use or overuse can lead to adverse effects, including gastrointestinal complications, addiction, and respiratory depression in the case of opioids. Therefore, it is crucial for healthcare professionals to assess each patient's individual needs and prescribe the appropriate analgesic and dosage.
In summary, analgesics are a vital category of pharmaceutical APIs used to alleviate pain by targeting pain receptors or reducing inflammation. With various classes and forms available, they provide valuable options for pain management when used responsibly and under medical guidance.
Frequently asked questions about Methadone API
Sourcing
What matters most when sourcing GMP-grade Methadone?
When sourcing GMP-grade Methadone, the key considerations are compliance with U.S. and Canadian regulatory requirements and documented GMP manufacturing and repackaging practices. Reliable suppliers should provide full traceability and quality documentation suitable for controlled substances. Given the mature, multi‑supplier market, verification of consistent specifications and secure supply chain controls is essential.
Which documents are typically required when sourcing Methadone API?
Request the core API documentation set: CoA (11 companies), GMP (8 companies), CEP (6 companies), USDMF (6 companies), MSDS (4 companies). Confirm versions and validity dates match the destination market to avoid delays in qualification.
Which manufacturers are known to produce Methadone API?
Known or reported manufacturers for Methadone: Duchefa Farma B.V., Saneca Pharma, Hänseler AG, Vonage Pharma (Former Pluvia Endo), Temad Co.. Evaluate their GMP history, scale, and regional coverage before requesting dossiers or allocating demand.
How can I request quotes for Methadone API from GMP suppliers?
Submit quote requests through the supplier listings with your specs and required documents (specifications, target volume, delivery timeline, and destination). Providing consistent details upfront speeds comparable offers and clarifies technical feasibility.
Is a GMP audit report available for Methadone manufacturers?
Audit reports may be requested for Methadone: 3 GMP audit reports available. Confirm the scope and recency of any audit before relying on it for qualification decisions.
How many suppliers offer Methadone API on Pharmaoffer?
Reported supplier count for Methadone: 11 verified suppliers. Filter listings by certifications, regions, and delivery options to match your qualification plan.
Which countries are known to manufacture Methadone API?
Production countries reported for Methadone: India (3 producers), Slovakia (2 producers), Switzerland (1 producer). Knowing the manufacturing geography helps anticipate logistics lead times and import compliance needs.
Which certifications do suppliers of Methadone usually hold?
Common certifications for Methadone suppliers: CoA (11 companies), GMP (8 companies), CEP (6 companies), USDMF (6 companies), MSDS (4 companies). Always verify issuing authorities and expiry dates when reviewing audit packages.
Technical
What is Methadone (CAS 76-99-3) used for?
Methadone is used to manage severe pain requiring an opioid analgesic and to support detoxification or long‑term maintenance therapy in opioid dependence. In opioid agonist treatment programs, it suppresses withdrawal symptoms and helps stabilize patients when combined with appropriate clinical care.
Which therapeutic class does Methadone fall into?
Methadone belongs to the following therapeutic categories: Analgesics, Anticholinergic Agents, Antidepressive Agents, Antitussive Agents, Central Nervous System Agents. This positioning helps teams compare alternative APIs, anticipate pharmacology expectations, and align early research priorities.
What conditions is Methadone mainly prescribed for?
The primary indications for Methadone: Methadone is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatment options are inadequate, It's recommended that use is reserved for use in patients for whom alternative treatment options (eg, nonopioid analgesics, opioid combination products) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain, Methadone is also indicated for detoxification treatment of opioid addiction (heroin or other morphine-like drugs), and for maintenance substitution treatment for opioid dependence in adults in conjunction with appropriate social and medical services. These use cases frame the target patient populations and help prioritize formulation and safety evaluations.
How does Methadone work?
Methadone is a synthetic opioid analgesic with full agonist activity at the µ-opioid receptor. While agonism of the µ-opioid receptor is the primary mechanism of action for the treatment of pain, Methadone also acts as an agonist of κ- and σ-opioid receptors within the central and peripheral nervous systems. Interestingly, Methadone differs from [morphine] (which is considered the gold standard reference opioid) in its antagonism of the N-methyl-D-aspartate (NMDA) receptor and its strong inhibition of serotonin and norepinephrine uptake, which likely also contributes to its antinociceptive activity.
Methadone is administered as a 50:50 racemic mixture of (R)- and (S)-stereoisomers, with (R)-Methadone demonstrating ~10-fold higher affinity and potency for the µ-opioid receptor than the (S) stereoisomer.The analgesic activity of the racemate is almost entirely due to the (R)-isomer, while the (S)-isomer lacks significant respiratory depressant activity but does have antitussive effects.
While Methadone shares similar effects and risks of other opioids such as [morphine], [hydromorphone], [oxycodone], and [fentanyl] it has a number of unique pharmacokinetic and pharmacodynamic properties that distinguish it from them and make it a useful agent for the treatment of opioid addiction. For example, Methadone abstinence 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.
What should someone know about the safety or toxicity profile of Methadone?
Methadone has a dose‑dependent risk of respiratory depression, which may appear later and last longer than its analgesic effect, and severe overexposure can lead to respiratory arrest, circulatory collapse, or cardiac arrest. It can prolong the QT interval and has been associated with rare cases of torsades de pointes, particularly at higher doses or with interacting drugs or electrolyte abnormalities. Additional concerns include hypotension, constipation, endocrine effects, and dependence with the potential for withdrawal if stopped abruptly. Handling of the API requires controls to prevent accidental high‑dose exposure and minimize aerosolization or leakage due to the risk of rapid‑onset respiratory depression.
What are important formulation and handling considerations for Methadone as an API?
Methadone’s low aqueous solubility and high lipophilicity require use of acidic salts or co‑solvent systems to maintain solubility in oral solutions and parenteral concentrates. Solid oral formulations benefit from solubilizing excipients or granulation methods to support consistent dissolution. Injectable products need controlled pH and suitable solvent systems to keep the API in solution and preserve stability during storage and handling.
Is Methadone a small molecule?
Methadone is classified as a small molecule. That classification shapes process design, impurity profiling, and analytical control strategies.
Are there special stability concerns for oral Methadone?
Oral Methadone has stability concerns related to its low aqueous solubility and high lipophilicity, which favor use of acidic salts or co‑solvent systems to keep it in solution. Solid oral forms may require solubilizing excipients or specific granulation approaches to ensure consistent dissolution. Maintaining appropriate pH in solution formulations is important to preserve solubility and stability during storage.
Regulatory
Where is Methadone approved or in use globally?
Methadone is reported as approved in the following major regions: Canada, US. Understanding geographic coverage informs regulatory filings, supply planning, and risk assessments before escalating procurement.
Pharmaoffer
How does Pharmaoffer’s Smart Sourcing Service help with Methadone procurement?
Pharmaoffer's Smart Sourcing Service coordinates compliant suppliers, documentation, and competitive quotes for Methadone. It centralizes outreach, follow-ups, and document validation to shorten procurement timelines.
Is Methadone included in the PRO Data Insights coverage?
PRO Data Insights coverage for Methadone: 2588 verified transactions across 512 suppliers and 36 buyers worldwide. Use the dataset to benchmark suppliers and monitor regulatory activity where available.
Where can I access the API market report for Methadone?
Market report availability for Methadone: Report Available. The report highlights demand trends, pricing drivers, and supplier landscape insights for procurement planning.
