Methadone Hydrochloride Concentrate
Loading...Methadone Hydrochloride Concentrate Recall
Get an alert when a recall is issued.
Questions & Answers
Side Effects & Adverse Reactions
Methadone Hydrochloride Oral Concentrate, USP is for oral administration only. The preparation must not be injected. Methadone Hydrochloride Oral Concentrate, USP, if dispensed, should be packaged in child-resistant containers and kept out of reach of children to prevent accidental ingestion.
Respiratory depression is the chief hazard associated with methadone hydrochloride administration. Methadone's peak respiratory depressant effects typically occur later, and persist longer than its peak analgesic effects, in the short-tem use setting. These characteristics can contribute to cases of iatrogenic overdose, particularly during treatment and dose titration.
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 central nervous system (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. Methadone should be used at the lowest effective dose and only under careful medical supervision.
This information is intended to alert the prescribing to comprehensively evaluate the risks and benefits of methadone treatment. The intent is not to deter the appropriate use of methadone in patients with a history of cardiac disease.
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). Although most cases involve patients being treated for pain with large, multiple daily doses of methadone, cases have been reported in patients receiving doses commonly used in maintenance treatment of opioid addiction. In most of the cases seen at typical maintenance doses, concomitant medications and/or clinical conditions such as hypokalemia are noted as contributing factors. However, the evidence strongly suggests that methadone possesses the potential for adverse cardiac conduction effects in some patients.
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 abnormalities, those taking medications affecting cardiac conduction, and in other cases where history or physical exam suggest an increased risk of dysrhythmia. QT prolongation has also been reported in patients with no prior cardiac history who have received high doses of methadone. Patients developing QT prolongation while on methadone treatment should be evaluated for the presence of modifiable risk factors, such as concomitant medications with cardiac effects, drugs which might cause electrolyte abnormalities and drugs which might act as inhibitors of methadone metabolism.
The potential risks of methadone, including the risk of life-threatening arrhythmias, should be weighed against the risks of discontinuing methadone treatment. In the patient being treated for opiate dependence with methadone maintenance therapy, these risks include a very high likelihood of relapse to illicit drug use following methadone discontinuation.
The use of methadone in patients already known to have a prolonged QT interval has not been systematically studied. The potential risks of methadone should be weighed against the substantial morbidity and mortality associated with untreated opioid addiction.
When treating patients with methadone, an individualized benefit to risk assessment should be carried out and should include evaluation of patient presentation and complete medical history. For patients judged to be at risk, careful monitoring of cardiovascular status, including evaluation of QT prolongation and dysrhythmias should be performed.
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 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.
Methadone is a µ-agonist opioid with an abuse liability similar to that of morphine and other opiod agonists and is a Schedule II controlled substance. 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 Hydrochloride Oral Concentrate, USP in situations where the clinician is concerned about an increased risk of misuse, abuse, or diversion. Abuse of Methadone poses a risk of overdose and death. This risk is increased with concurrent abuse of methadone with alcohol and other substances. In addition, parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.
Healthcare professionals should contact their State Professional Licensing Board or State Controlled Substances Authority for information on how to prevent and detect abuse or diversion of this product.
Patients receiving other opioid analgesics, general anesthetics, phenothiazines or other tranquilizers, sedatives, hypnotics, or other CNS depressants (including alcohol) concomitantly with methadone may experience respiratory depression, hypotension, profound sedation, or coma (see PRECAUTIONS).
Methadone may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression. Deaths associated with illicit use of methadone frequently have involved concomitant benzodiazepine abuse.
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.
The administration of opioids may obscure the diagnosis or clinical course of patients with acute abdominal conditions.
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).
Legal Issues
There is currently no legal information available for this drug.
FDA Safety Alerts
There are currently no FDA safety alerts available for this drug.
Manufacturer Warnings
There is currently no manufacturer warning information available for this drug.
FDA Labeling Changes
There are currently no FDA labeling changes available for this drug.
Uses
- For detoxification treatment of opioid addiction (heroin or other morphine-like drugs).
- For maintenance treatment of opioid addiction (heroin or other morphine-like drugs), in conjunction with appropriate social and medical services.
Outpatient maintenance and outpatient detoxification treatment may be provided only by Opioid Treatment Programs (OTPs) certified by the Federal Substance Abuse and Mental Health Services Administration (SAMHSA) and registered by the Drug Enforcement Administration (DEA). This does not preclude the maintenance treatment of a patient with concurrent opioid addiction who is hospitalized for conditions other than opioid addiction and who requires temporary maintenance during the critical period of his/her stay, or of a patient whose enrollment has been verified in a program which has been certified for maintenance treatment with methadone.
History
There is currently no drug history available for this drug.
Other Information
Methadone Hydrochloride Oral Concentrate, USP, is supplied in two formulations. The first is supplied as a cherry flavored liquid concentrate. The second is a dye-free, sugar-free, unflavored liquid concentrate. Each liquid concentrate contains 10 mg of methadone hydrochloride per mL.
Methadone hydrochloride is chemically described as 3-heptanone, 6-(dimethylamino)-4, 4-diphenyl-, hydrochloride. Methadone hydrochloride is a white, essentially odorless, bitter-tasting crystalline powder. It is very soluble in water, soluble in isopropranolol and in chloroform, and practically insoluble in ether and in glycerine. It is present in Methadone Hydrochloride Oral Concentrate, USP, as the racemic mixture. Methadone hydrochloride has a melting point of 235°C, a pKa of 8.25 in water at 20°C, a solution (1 part per 100) pH between 4.5 and 6.5, a partition coefficient of 117 at pH 7.4 in octanol/water. Its structural formula is:
| C21H27NO•HCl MW= 345.91 |
Other ingredients of Methadone Hydrochloride Oral Concentrate, USP: Artificial Cherry Flavor; Sorbic Acid, NF; Potassium Sorbate, NF; FD&C Red No. 40; D&C Red No. 33; Poloxamer 188, NF; Propylene Glycol, USP; Glycerin, USP; Sucrose, NF, and Purified Water, USP.
Other ingredients of Methadone Hydrochloride Oral Concentrate, USP (Dye-Free, Sugar-Free, Unflavored): Citric Acid Anhydrous, USP; Purified Water, USP, and Sodium Benzoate, NF.
Sources
Methadone Hydrochloride Concentrate Manufacturers
-
Vistapharm Inc
![Methadone Hydrochloride Concentrate [Vistapharm Inc]](/wp-content/themes/bootstrap/assets/img/loading2.gif)
Methadone Hydrochloride Concentrate | Vistapharm Inc
Methadone differs from many other opioid agonists in several important ways. Methadone's pharmacokinetic properties, coupled with high interpatient variability in its absorption, metabolism, and relative analgesic potency, necessitate a cautious and highly individualized approach to prescribing. Particular vigilance is necessary during treatment initiation, during conversion from one opioid to another, and during dose titration.
While methadone's duration of analgesic action (typically 4 to 8 hours) in the setting of single-dose studies approximates that of morphine, methadone's plasma elimination half-life is substantially longer than that of morphine (typically 8 to 59 hours vs. 1 to 5 hours). Methadone's peak respiratory depressant effects typically occur later, and persist longer than its peak analgesic effects. Also, with repeated dosing, methadone may be retained in the liver and then slowly released, prolonging the duration of action despite low plasma concentrations. For these reasons, steady-state plasma concentrations, and full analgesic effects, are usually not attained until 3 to 5 days of dosing. Additionally, incomplete cross-tolerance between µ-opioid agonists makes determination of dosing during opioid conversion complex.
The complexities associated with methadone dosing can contribute to cases of iatrogenic overdose, particularly during treatment initiation and dose titration. A high degree of "opioid tolerance" does not eliminate the possibility of methadone overdose, iatrogenic or otherwise. Deaths have been reported during conversion to methadone from chronic, high-dose treatment with other opioid agonists and during initiation of methadone treatment of addiction in subjects previously abusing high doses of other agonists.
Detoxification and Maintenance Treatment of Opiate DependenceFor detoxification and maintenance of opiate dependence methadone should be administered in accordance with the treatment standards cited in 42 CFR Section 8.12, including limitations on unsupervised administration.
Induction/Initial DosingThe initial methadone dose should be administered, under supervision, when there are no signs of sedation or intoxication, and the patient shows symptoms of withdrawal. Initially, a single dose of 20 to 30 mg of methadone will often be sufficient to suppress withdrawal symptoms. The initial dose should not exceed 30 mg. If same-day dosing adjustments are to be made, the patient should be asked to wait 2 to 4 hours for further evaluation, when peak levels have been reached. An additional 5 to 10 mg of methadone may be provided if withdrawal symptoms have not been suppressed or if symptoms reappear. The total daily dose of methadone on the first day of treatment should not ordinarily exceed 40 mg. Dose adjustments should be made over the first week of treatment based on control of withdrawal symptoms at the time of expected peak activity (e.g., 2 to 4 hours after dosing). Dose adjustment should be cautious; deaths have occurred in early treatment due to the cumulative effects of the first several days' dosing. Patients should be reminded that the dose will "hold" for a longer period of time as tissue stores of methadone accumulate.
Initial doses should be lower for patients whose tolerance is expected to be low at treatment entry. Loss of tolerance should be considered in any patient who has not taken opioids for more than 5 days. Initial doses should not be determined by previous treatment episodes or dollars spent per day on illicit drug use.
For Short-term DetoxificationFor patients preferring a brief course of stabilization followed by a period of medically supervised withdrawal, it is generally recommended that the patient be titrated to a total daily dose of about 40 mg in divided doses to achieve an adequate stabilizing level. Stabilization can be continued for 2 to 3 days, after which the dose of methadone should be gradually decreased. The rate at which methadone is decreased should be determined separately for each patient. The dose of methadone can be decreased on a daily basis or at 2-day intervals, but the amount of intake should remain sufficient to keep withdrawal symptoms at a tolerable level. In hospitalized patients, a daily reduction of 20% of the total daily dose may be tolerated. In ambulatory patients, a somewhat slower schedule may be needed.
For Maintenance TreatmentPatients in maintenance treatment should be titrated to a dose at which opioid symptoms are prevented for 24 hours, drug hunger or craving is reduced, the euphoric effects of self-administered opioids are blocked or attenuated, and the patient is tolerant to the sedative effects of methadone. Most commonly, clinical stability is achieved at doses between 80 to 120 mg/day.
For Medically Supervised Withdrawal After a Period of Maintenance TreatmentThere is considerable variability in the appropriate rate of methadone taper in patients choosing medically supervised withdrawal from methadone treatment. It is generally suggested that dose reductions should be less than 10% of the established tolerance or maintenance dose, and that 10 to 14-day intervals should elapse between dose reductions. Patients should be apprised of the high risk of relapse to illicit drug use associated with discontinuation of methadone maintenance treatment.
-
Roxane Laboratories, Inc
Methadone Hydrochloride Concentrate | Roxane Laboratories, Inc
Methadone differs from many other opioid agonists in several important ways. Methadone's pharmacokinetic properties, coupled with high interpatient variability in its absorption, metabolism, and relative analgesic potency, necessitate a cautious and highly individualized approach to prescribing. Particular vigilance is necessary during treatment initiation, during conversion from one opioid to another, and during dose titration.
While methadone’s duration of analgesic action (typically 4 to 8 hours) in the setting of single-dose studies approximates that of morphine, methadone’s plasma elimination half-life is substantially longer than that of morphine (typically 8 to 59 hours vs. 1 to 5 hours). Methadone's peak respiratory depressant effects typically occur later, and persist longer than its peak analgesic effects. Also, with repeated dosing, methadone may be retained in the liver and then slowly released, prolonging the duration of action despite low plasma concentrations. For these reasons, steady-state plasma concentrations, and full analgesic effects, are usually not attained until 3 to 5 days of dosing. Additionally, incomplete cross-tolerance between mu-opioid agonists makes determination of dosing during opioid conversion complex.
The complexities associated with methadone dosing can contribute to cases of iatrogenic overdose, particularly during treatment initiation and dose titration. A high degree of "opioid tolerance" does not eliminate the possibility of methadone overdose, iatrogenic or otherwise. Deaths have been reported during conversion to methadone from chronic, high-dose treatment with other opioid agonists and during initiation of methadone treatment of addiction in subjects previously abusing high doses of other agonists.
Detoxification and Maintenance Treatment of Opiate DependenceFor detoxification and maintenance of opiate dependence methadone should be administered in accordance with the treatment standards cited in 42 CFR Section 8.12, including limitations on unsupervised administration.
Induction/Initial DosingThe initial methadone dose should be administered, under supervision, when there are no signs of sedation or intoxication, and the patient shows symptoms of withdrawal. Initially, a single dose of 20 to 30 mg of methadone will often be sufficient to suppress withdrawal symptoms. The initial dose should not exceed 30 mg. If same-day dosing adjustments are to be made, the patient should be asked to wait 2 to 4 hours for further evaluation, when peak levels have been reached. An additional 5 to 10 mg of methadone may be provided if withdrawal symptoms have not been suppressed or if symptoms reappear. The total daily dose of methadone on the first day of treatment should not ordinarily exceed 40 mg. Dose adjustments should be made over the first week of treatment based on control of withdrawal symptoms at the time of expected peak activity (e.g., 2 to 4 hours after dosing). Dose adjustment should be cautious; deaths have occurred in early treatment due to the cumulative effects of the first several days’ dosing. Patients should be reminded that the dose will “hold” for a longer period of time as tissue stores of methadone accumulate.
Initial doses should be lower for patients whose tolerance is expected to be low at treatment entry. Loss of tolerance should be considered in any patient who has not taken opioids for more than 5 days. Initial doses should not be determined by previous treatment episodes or dollars spent per day on illicit drug use.
For Short-Term DetoxificationFor patients preferring a brief course of stabilization followed by a period of medically supervised withdrawal, it is generally recommended that the patient be titrated to a total daily dose of about 40 mg in divided doses to achieve an adequate stabilizing level. Stabilization can be continued for 2 to 3 days, after which the dose of methadone should be gradually decreased. The rate at which methadone is decreased should be determined separately for each patient. The dose of methadone can be decreased on a daily basis or at 2-day intervals, but the amount of intake should remain sufficient to keep withdrawal symptoms at a tolerable level. In hospitalized patients, a daily reduction of 20% of the total daily dose may be tolerated. In ambulatory patients, a somewhat slower schedule may be needed.
For Maintenance TreatmentPatients in maintenance treatment should be titrated to a dose at which opioid symptoms are prevented for 24 hours, drug hunger or craving is reduced, the euphoric effects of self-administered opioids are blocked or attenuated, and the patient is tolerant to the sedative effects of methadone. Most commonly, clinical stability is achieved at doses between 80 to 120 mg/day.
For Medically Supervised Withdrawal After a Period of Maintenance TreatmentThere is considerable variability in the appropriate rate of methadone taper in patients choosing medically supervised withdrawal from methadone treatment. It is generally suggested that dose reductions should be less than 10% of the established tolerance or maintenance dose, and that 10 to 14-day intervals should elapse between dose reductions. Patients should be apprised of the high risk of relapse to illicit drug use associated with discontinuation of methadone maintenance treatment.
-
Roxane Laboratories, Inc
Methadone Hydrochloride Concentrate | International Medication Systems, Limited
For Relief of Pain and as Pre-anesthetic: The usual adult dose is 10 mg every 4 hours, depending on the severity of the condition and the patient’s response. The usual individual dose range is 5 to 15 mg. The usual daily dose range is 12 to 120 mg.
Usual Pediatric Subcutaneous: 100 to 200 μg (0.1 to 0.2 mg) per kg body weight, not to exceed 15 mg per dose.
For Open Heart Surgery: Large doses (0.5 to 3 mg/kg) of morphine are administered intravenously as the sole anesthetic or with a suitable anesthetic agent. The patients are given oxygen and cardiovascular function is not depressed by morphine, as long as adequate ventilation is maintained.
For Severe Chronic Pain Associated with Terminal Cancer: Continuous Intravenous Infusion - Prior to the initiation of the morphine infusion (in concentrations between 0.2 to 1 mg/mL), a loading dose of 15 mg or higher of morphine sulfate may be administeredby I.V. push to alleviate pain.
The infusion dosage range is 0.8 mg/hr to 80 mg/hr, though doses of up to 144 mg/hr have been used. Thus, for the 1 mg/mL solution, the infusion may be run from 0.8 mL/hr to 80 mL/hr, and for the 0.5 mg/mL solution, the infusion may be run from 1.6 mL/hr to 160 mL/hr.
A constant infusion rate must be maintained with an infusion pump in order to assure proper dosage control. Care must be taken to avoid overdosage (respiratory depression) or abrupt cessation of therapy, which may give rise to withdrawal symptoms.NOTE: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
![Methadone Hydrochloride Concentrate [Roxane Laboratories, Inc]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=e72841bf-364b-49b1-8e69-7e26ddcd2657&name=be690f1f-2534-4c85-b62b-a9f3e7fea972-02.jpg)
![Methadone Hydrochloride Concentrate [Roxane Laboratories, Inc]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=e360d6b6-d9ef-487d-bf14-fcbbee8beb29&name=Carton.jpg)
Login To Your Free Account