METHADONE HYDROCHLORIDE ORAL SOLUTION USP5 mg per 5 mL, 10 mg per 5 mL

methadone hydrochloride (Methadone hydrochloridesolution 
[Roxane Laboratories, Inc.]

CONDITIONS FOR DISTRIBUTION AND USE OF METHADONE PRODUCTS:

Code of Federal Regulations, Title 21, Sec. 291.505

METHADONE PRODUCTS, WHEN USED FOR TREATMENT OF NARCOTIC ADDICTION IN DETOXIFICATION OR MAINTENANCE PROGRAMS, SHALL BE DISPENSED ONLY BY APPROVED HOSPITAL PHARMACIES, APPROVED COMMUNITY PHARMACIES, AND MAINTENANCE PROGRAMS APPROVED BY THE FOOD AND DRUG ADMINISTRATION AND THE DESIGNATED STATE AUTHORITY.

APPROVED MAINTENANCE PROGRAMS SHALL DISPENSE AND USE METHADONE IN ORAL FORM ONLY AND ACCORDING TO THE TREATMENT REQUIREMENTS STIPULATED IN THE FEDERAL METHADONE REGULATIONS (21 CFR 291.505).

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.

A METHADONE PRODUCT, WHEN USED AS AN ANALGESIC, MAY BE DISPENSED IN ANY LICENSED PHARMACY.

Rx only.

DESCRIPTION

Each 5 mL of solution for oral administration contains:

Methadone Hydrochloride.............. 5 mg or 10 mg

Alcohol 8%

Inactive Ingredients:

The oral solution contains alcohol, FD&C Red #40, FD&C Yellow #6, flavoring, glycerin, sorbitol, water, and other ingredients.

Chemically, methadone hydrochloride is 3-Heptanone, 6-(dimethylamino)-4,4-diphenyl-, hydrochloride, which can be represented by the following structural formula:

Image from Drug Label Content

Methadone hydrochloride acts as a narcotic analgesic.

CLINICAL PHARMACOLOGY

Methadone hydrochloride is a synthetic narcotic analgesic with multiple actions quantitatively similar to those of morphine, the most prominent of which involve the central nervous system and organs composed of smooth muscle. The principal actions of therapeutic value are analgesia and sedation and detoxification or temporary maintenance in narcotic addiction. The 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.

When administered orally, methadone is approximately one-half as potent as when given parenterally. Oral administration results in a delay of the onset, a lowering of the peak, and an increase in the duration of analgesic effect.

INDICATIONS AND USAGE

Methadone hydrochloride is indicated for relief of severe pain, for detoxification treatment of narcotic addiction, and for temporary maintenance treatment of narcotic addiction.

NOTE

If methadone is administered for treatment of heroin dependence for more than three weeks, the procedure passes from treatment of the acute withdrawal syndrome (detoxification) to maintenance therapy. Maintenance treatment is permitted to be undertaken only by approved methadone programs. This does not preclude the maintenance treatment of an addict who is hospitalized for medical conditions other than addiction and who requires temporary maintenance during this critical period of his stay or whose enrollment has been verified in a program which has approval for maintenance treatment with methadone.

CONTRAINDICATIONS

Hypersensitivity to methadone.

WARNINGS

Methadone hydrochloride, a narcotic, is a Schedule II controlled substance under the Federal Controlled Substances Act.

DRUG DEPENDENCE - METHADONE CAN PRODUCE DRUG DEPENDENCE OF THE MORPHINE TYPE AND, THEREFORE, HAS THE POTENTIAL FOR BEING ABUSED. PSYCHIC DEPENDENCE, PHYSICAL DEPENDENCE, AND TOLERANCE MAY DEVELOP UPON REPEATED ADMINISTRATION OF METHADONE, AND IT SHOULD BE PRESCRIBED AND ADMINISTERED WITH THE SAME DEGREE OF CAUTION APPROPRIATE TO THE USE OF MORPHINE.

Interaction with Other Central-Nervous-System Depressants

Methadone should be used with caution and in reduced dosage in patients who are concurrently receiving other narcotic analgesics, general anesthetics, phenothiazines, other tranquilizers, sedative-hypnotics, tricyclic antidepressants, and other CNS depressants (including alcohol). Respiratory depression, hypotension, and profound sedation or coma may result.

Anxiety

Since methadone, as used by tolerant subjects at a constant maintenance dosage, is not a tranquilizer, patients who are maintained on this drug will react to life problems and stresses with the same symptoms of anxiety as do other individuals. The physician should not confuse such symptoms with those of narcotic abstinence and should not attempt to treat anxiety by increasing the dosage of methadone. The action of methadone in maintenance treatment is limited to the control of narcotic symptoms and is ineffective for relief of general anxiety.

Head Injury and Increased Intracranial Pressure

The respiratory depressant effects of methadone and its capacity to elevate cerebrospinal-fluid pressure may be markedly exaggerated in the presence of increased intracranial pressure. Furthermore, narcotics produce side effects that 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.

Asthma and Other Respiratory Conditions

Methadone should be used with caution in patients having an acute asthmatic attack, in those with chronic obstructive pulmonary disease or cor pulmonale, and in individuals with a substantially decreased respiratory reserve, preexisting respiratory depression, hypoxia, or hypercapnia. In such patients, even usual therapeutic doses of narcotics may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea.

Hypotensive Effect

The administration of methadone may result in severe hypotension in an individual whose ability to maintain his blood pressure has already been compromised by a depleted blood volume or concurrent administration of such drugs as the phenothiazines or certain anesthetics.

Use in Ambulatory Patients

Methadone may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a car or operating machinery. The patient should be cautioned accordingly.

Methadone, like other narcotics, may produce orthostatic hypotension in ambulatory patients.

Use in Pregnancy

Safe use in pregnancy has not been established in relation to possible adverse effects on fetal development. Therefore, methadone should not be used in pregnant women unless, in the judgment of the physician, the potential benefits outweigh the possible hazards.

Methadone is not recommended for obstetric analgesia because its long duration of action increases the probability of respiratory depression in the newborn.

Use in Children

Methadone is not recommended for use as an analgesic in children, since documented clinical expereince has been insufficient to establish a suitable dosage regimen for the pediatric age group.

PRECAUTIONS

Interaction with Pentazocine

Patients who are addicted to heroin or who are on the methadone maintenance program may experience withdrawal symptoms when given pentazocine.

Interaction with Rifampin

The concurrent administration of rifampin may possibly reduce the blood concentration of methadone. The mechanism by which rifampin may decrease blood concentrations of methadone is not fully understood although enhanced microsomal drug-metabolized enzymes may influence drug disposition.

Acute Abdominal Conditions

The administration of methadone or other narcotics may obscure the diagnosis or clinical course in patients with acute abdominal conditions.

Interaction with Monoamine Oxidase (MAO) Inhibitors

Therapeutic doses of meperidine have precipitated severe reactions in patients concurrently receiving monoamine oxidase inhibitors or those who have received such agents within 14 days. Similar reactions thus far have not been reported with methadone; but if the use of methadone is necessary in such patients, a sensitivity test should be performed in which repeated small incremental doses are administered over the course of several hours while the patient’s condition and vital signs are under careful observation.

Special-Risk Patients

Methadone should be given with caution and the initial dose should be reduced in certain patients, such as the elderly or debilitated and those with severe impairment of hepatic or renal function, hypothyroidism, Addison’s disease, prostatic hypertrophy, or urethral stricture.

ADVERSE REACTIONS

THE MAJOR HAZARDS OF METHADONE, AS OF OTHER NARCOTIC ANALGESICS, ARE RESPIRATORY DEPRESSION AND, TO A LESSER DEGREE, CIRCULATORY DEPRESSION. RESPIRATORY ARREST, SHOCK, AND CARDIAC ARREST 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 chronic pain. In such individuals, lower doses are advisable. Some adverse reactions may be alleviated in the ambulatory patient if he lies down.

Other adverse reactions include the following:

Central Nervous System - Euphoria, dysphoria, weakness, headache, insomnia, agitation, disorientation, and visual disturbances.

Gastrointestinal - Dry mouth, anorexia, constipation and biliary tract spasm.

Cardiovascular - Flushing of the face, bradycardia, palpitation, faintness, and syncope.

Genitourinary - Urinary retention or hesitancy, antidiuretic effect, and reduced libido and/or potency.

Allergic - Pruritus, urticaria, other skin rashes, edema, and, rarely, hemorrhagic urticaria.

Hematologic - Reversible thrombocytopenia has been described in a narcotics addict with chronic hepatitis.

DOSAGE AND ADMINISTRATION

For Relief of Severe Pain

Dosage should be adjusted according to the severity of the pain and the response of the patient. Occasionally it may be necessary to exceed the usual dosage recommended in cases of exceptionally severe pain or in those patients who have become tolerant to the analgesic effects of narcotics.

The usual adult dosage is 2.5 mg to 10 mg every three or four hours as necessary.

For Detoxification Treatment

THE DRUG SHALL BE ADMINISTERED DAILY UNDER CLOSE SUPERVISION AS FOLLOWS:

A detoxification treatment course shall not exceed 21 days and may not be repeated earlier than four weeks after completion of the preceding course.

The oral form of administration is preferred. However, if the patient is unable to ingest oral medication, he may be started on the parenteral form initially.

In detoxification, the patient may receive methadone when there are significant symptoms of withdrawal. The dosage schedules indicated below are recommended but could be varied in accordance with clinical judgment. Initially, a single oral dose of 15 to 20 mg of methadone will often be sufficient to suppress withdrawal symptoms. Additional methadone may be provided if withdrawal symptoms are not suppressed or if symptoms reappear. When patients are physically dependent on high doses, it may be necessary to exceed these levels. Forty mg per day in single or divided doses will usually constitute an adequate stabilizing dosage level. Stabilization can be continued for two to three days, and then the amount of methadone normally will be gradually decreased. The rate at which methadone is decreased will be determined separately with each patient. The dose of methadone can be decreased on a daily basis or at two-day intervals, but the amount of intake shall always be sufficient to keep withdrawal symptoms at a tolerable level. In hospitalized patients, a daily reduction of 20 percent of the total daily dose may be tolerated and may cause little discomfort. In ambulatory patients, a somewhat slower schedule may be needed. If methadone is administered for more than three weeks, the procedure is considered to have progressed from detoxification or treatment of the acute withdrawal syndrome to maintenance treatment, even though the goal and intent may be eventual total withdrawal.

OVERDOSAGE

Symptoms

Serious overdosage of methadone is characterized by respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, maximally constricted pupils, skeletal-muscle flaccidity, cold and clammy skin, and sometimes, bradycardia and hypotension. In severe overdosage, particularly by the intravenous route, apnea, circulatory collapse, cardiac arrest, and death may occur.

Treatment

Primary attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled ventilation. If a nontolerant person, especially a child, takes a large dose of methadone, effective narcotic antagonists are available to counteract the potentially lethal respiratory depression. The physician must remember, however, that methadone is a long-acting depressant (36 to 48 hours), whereas the antagonists act for much shorter periods (one to three hours). The patient must, therefore, be monitored continuously for recurrence of respiratory depression and treated repeatedly with the narcotic antagonist as needed. If the diagnosis is correct and respiratory depression is due only to overdosage of methadone, the use of other respiratory stimulants is not indicated.

An antagonist should not be administered in the absence of clinically significant respiratory or cardiovascular depression. Intravenously administered naloxone is the drug of choice to reverse signs of intoxication. Because of the relatively short half-life of naloxone as compared with methadone, repeated injections may be required until the status of the patient remains satisfactory. Naloxone may also be administered by continuous intravenous infusion.

Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated.

NOTE

IN AN INDIVIDUAL PHYSICALLY DEPENDENT ON NARCOTICS, THE ADMINISTRATION OF THE USUAL DOSE OF A NARCOTIC ANTAGONIST WILL PRECIPITATE AN ACUTE WITHDRAWAL SYNDROME. THE SEVERITY OF THIS SYNDROME WILL DEPEND ON THE DEGREE OF PHYSICAL DEPENDENCE AND THE DOSE OF THE ANTAGONIST ADMINISTERED. THE USE OF A NARCOTIC ANTAGONIST IN SUCH A PERSON SHOULD BE AVOIDED IF POSSIBLE. IF IT MUST BE USED TO TREAT SERIOUS RESPIRATORY DEPRESSION IN THE PHYSICALLY DEPENDENT PATIENT, THE ANTAGONIST SHOULD BE ADMINISTERED WITH EXTREME CARE AND BY TITRATION WITH SMALLER THAN USUAL DOSES OF THE ANTAGONIST.

HOW SUPPLIED

Methadone Hydrochloride Oral Solution USP

5 mg per 5 mL clear, orange-colored, citrus-flavored solution

NDC 0054-3555-63: Bottles of 500 mL.

10 mg per 5 mL clear, orange-colored, citrus-flavored solution

NDC 0054-3556-63: Bottles of 500 mL.

Store at Controlled Room

Temperature 15°-30°C (59°-86°F).

4056301/01 100

© RLI, 2000

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Methadone hydrochloride (Methadone hydrochloride)
PRODUCT INFO
Product Code 0054-3555 Dosage Form SOLUTION
Route Of Administration ORAL DEA Schedule CII
INGREDIENTS
Name (Active Moiety) Type Strength
methadone hydrochloride (methadone) Active 5 MILLIGRAM  In 5 MILLILITER
alcohol Inactive  
FD&C Red #40 Inactive  
FD&C Yellow #6 Inactive  
flavoring Inactive  
glycerin Inactive  
other ingredients Inactive  
sorbitol Inactive  
water Inactive  
IMPRINT INFORMATION
Characteristic Appearance Characteristic Appearance
Color Score
Shape Symbol
Imprint Code Coating
Size
PACKAGING
# NDC Package Description Multilevel Packaging
1 0054-3555-63 500 MILLILITER In 1 BOTTLE, PLASTIC None

Methadone hydrochloride (Methadone hydrochloride)
PRODUCT INFO
Product Code 0054-3556 Dosage Form SOLUTION
Route Of Administration ORAL DEA Schedule CII
INGREDIENTS
Name (Active Moiety) Type Strength
methadone hydrochloride (methadone) Active 10 MILLIGRAM  In 5 MILLILITER
alcohol Inactive  
FD&C Red #40 Inactive  
FD&C Yellow #6 Inactive  
flavoring Inactive  
glycerin Inactive  
other ingredients Inactive  
sorbitol Inactive  
water Inactive  
IMPRINT INFORMATION
Characteristic Appearance Characteristic Appearance
Color Score
Shape Symbol
Imprint Code Coating
Size
PACKAGING
# NDC Package Description Multilevel Packaging
1 0054-3556-63 500 MILLILITER In 1 BOTTLE, PLASTIC None

Revised: 07/2006Roxane Laboratories, Inc.