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Generic Name: Levomethadyl


Levomethadyl acetate—Levacetylmethadol {02} .

Primary: CN101

Note: Controlled substance classification—

U.S.—II. {01}
Commonly used brand name(s): Orlaam.

Other commonly used names are
LAAM, LAM, levacetylmethadol, levo-alpha-acetylmethadol, levomethadyl acetate, and MK790 {02} {03} {04} {05}.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

Not commercially available in Canada.


Opioid (narcotic) abuse therapy adjunct—
Note: Levomethadyl is an opioid (narcotic) analgesic, but is not used for relief of pain.


General considerations
In the U.S., levomethadyl is permitted to be dispensed only through opioid addiction treatment programs approved by the Food and Drug Administration (FDA), Drug Enforcement Administration (DEA), and designated state authorities. Use of levomethadyl in such programs is subject to treatment requirements stipulated in Federal regulations. {01} {05}


Opioid (narcotic) drug use, illicit (treatment adjunct)—Levomethadyl is indicated as an adjunct to other measures, which may include psychological and social counseling and medical and rehabilitative services, in the treatment of opioid dependence {01} {05}. It may be used in detoxification programs (to assist withdrawal from illicit opioids) and in maintenance programs (to discourage illicit use of other opioids) {01} {05} {07}. Appropriate evaluation, planning, counseling, and follow-up are essential components of successful treatment {01}. There is no evidence that administration of an opioid alone is effective treatment for opioid addiction {01}.

Note: In the U.S., Federal regulations permit specific opioids (levomethadyl and methadone) to be used in approved detoxification and interim or comprehensive maintenance treatment programs {05}. Levomethadyl is administered only 3 times a week and may be particularly useful for patients who do not require daily visits to the clinic, whereas methadone must be administered every day and may be more useful for patients who benefit from the support of daily clinic visits {01}. Also, because some patients experience effects perceived as aversive during treatment with one opioid or the other, the selection of a particular opioid may depend on patient acceptance {07} {15} {16}.
Short-term (up to 30 days) or long-term (up to 180 days) detoxification programs use an opioid to alleviate adverse physiological or psychological consequences of withdrawal from illicit opioids, with dosage gradually being decreased until a drug-free state is achieved. After 180 days, patients who have not achieved a drug-free state are considered to be receiving maintenance treatment. Patients may also be enrolled directly into a maintenance program without first attempting detoxification. In maintenance treatment programs, relatively stable doses of opioid are given on a continuing basis as a substitute for illicit opioids. {05}
Detoxification and comprehensive maintenance programs must include a full range of medical and rehabilitative services in addition to opioid administration. However, patients who are awaiting admission to a comprehensive maintenance program may receive up to 120 days of interim maintenance treatment, which consists only of opioid administration and needed medical services. {05}


Physicochemical characteristics:

Chemical group—
    Opioid analgesic; chemically related to both oxymorphone and naloxone {08}.
Molecular weight—
    Levomethadyl acetate hydrochloride: 389.97 {02}

Octanol:water partition coefficient
    405:1 {01}.

Mechanism of action/Effect:

Levomethadyl is a mu-receptor opioid agonist. It substitutes for opioids of the morphine type, thereby suppressing withdrawal symptoms in individuals who are addicted to such agents. With chronic use, levomethadyl produces cross-tolerance to the effects of other mu-receptor agonists, including the subjective ``high'' they produce, and decreases the addict's desire for such drugs. {01}

Other actions/effects:

Levomethadyl produces effects characteristic of mu-receptor opioid analgesics, including analgesia, respiratory depression, sedation, pupillary constriction, and physical dependence. {01}


Rapid {01}.


Extensive. The volume of distribution is about 20 L per kg of body weight (L/kg) {01}.

Protein binding:

High (approximately 80%); primarily to an alpha globulin {09}. Studies in heroin addicts {10} have demonstrated that levomethadyl, levomethadyl's active metabolites, and methadone bind to, compete for, and displace each other from the same protein-binding sites {09} {10}.


Levomethadyl undergoes extensive {11}first-pass metabolism {01} {11}to the active demethylated metabolite nor-levomethadyl (nor-LAAM), which is further demethylated to a second active metabolite, dinor-levomethadyl (dinor-LAAM). Smaller quantities of levomethadyl are also deacetylated to methadol, nor-methadol, and dinor-methadol. The rate of biotransformation is subject to interindividual variability. Although biotransformation to nor-LAAM generally occurs more slowly in males than in females, the differences are not as great as the interindividual differences. {01}



Levomethadyl: Approximately 6 hours {10}.


Levomethadyl: Approximately 2.6 days {01} {10}.

nor-LAAM: Approximately 2 days {01}.

dinor-LAAM: Approximately 4 days {01}.

Onset of action:

Although some opioid analgesic effects are apparent 2 to 4 hours after an oral dose, suppression of opioid withdrawal symptoms occurs after a delay of at least several days {01}, during which levomethadyl's active metabolites are forming and accumulating {01} {07}.

Time to peak concentration:

Levomethadyl—Usually 1.5 to 2 hours, {01} but up to 4 hours in some studies {10} {12}.

nor-LAAM—Usually 4 to 7 hours, but up to 10 hours in some individuals {11}.

dinor-LAAM—Usually 5 to 7 hours, but 24 to 48 hours in some individuals {11}.

Peak serum concentration

One study in 12 patients reported substantial interindividual variability in the peak concentrations of levomethadyl and its active metabolites after single and multiple doses. Plasma concentrations of levomethadyl, nor-LAAM, and dinor-LAAM were higher after multiple doses than after single doses, but the concentrations of the metabolites, especially dinor-LAAM, were increased to a greater extent than those of levomethadyl {11}.

Studies of peak and trough steady-state concentrations showed that there is great interindividual variability in levomethadyl concentrations over a 72-hour dosing interval. Also, although the concentration of levomethadyl itself decreased considerably during the 72-hour interval, the concentrations of the active metabolites, especially dinor-LAAM, decreased to a much lesser extent. {01}

Time to steady state

Three-times-per-week dosing schedule—1 to 2 weeks {01} (approximately 9, 8, and 12.5 days for levomethadyl, nor-LAAM, and dinor-LAAM, respectively). {11}

Time to peak effect

Suppression of opioid withdrawal symptoms—Approximately 7 to 10 days after initiation of treatment {01}.

Duration of action:

Suppression of opioid withdrawal symptoms:

Single 30- to 60-mg dose: 24 to 48 hours {01}.

Single 80-mg or higher dose: 48 to 72 hours {01}.

    Approximately 27% of a dose is eliminated in the urine as levomethadyl and various metabolites (nor-LAAM, dinor-LAAM, methadol, nor-methadol, and dinor-methadol) {11}. The disposition of the remainder of the dose has not been determined in humans, but extensive biliary elimination has been demonstrated in animal studies {10}.

Precautions to Consider


Levomethadyl was not carcinogenic in 2-year studies in rats given 13 mg per kg of body weight (mg/kg) (77 mg per square meter of body surface area [mg/m 2]) or in mice given 30 mg/kg (90 mg/m 2) {01}.


Levomethadyl was not mutagenic in the Ames test, the unscheduled DNA synthesis and repair test, in vitro mouse lymphoma cell studies, or in vivo rat chromosomal aberration tests {01}. However, levomethadyl exhibited mutagenic activity in the ad-3 forward mutation assay in N. crassa in concentrations of 150 mcg per mL (mcg/mL) in vitro and in the heritable translocation assay in mice receiving 21 mg/kg (63 mg/m 2) {01} {08}. The significance of these findings to clinical use in humans is not known {01}.


Methadone is the agent of choice for pregnant women in comprehensive maintenance treatment programs {05}. There are no clinical data on the safety of levomethadyl during pregnancy {01}. Levomethadyl administration should not be started or continued during pregnancy {01} {05} except by the written order of a physician who determines levomethadyl to be the best choice of therapy for an individual patient {05}. In the U.S., Federal regulations require that women of childbearing potential receive a pregnancy test prior to initiation of, and monthly during, levomethadyl maintenance treatment {01} {05}.

Animal reproduction studies have not been completed {01}. However, in one study administration of 0.2 or 2 mg/kg per day to rats prior to and throughout gestation caused opioid dependence in both the dams and pups. The larger dose also produced high incidences of premature delivery, stillbirths, and decreased pup weights. However, there were no differences in the rates of implantation, resorption, or morphological abnormalities between treated and control groups. {13}

FDA Pregnancy Category C {01}.

Labor and delivery—

The effects of levomethadyl on labor and delivery are not known {01}.

Postpartum —
Use of levomethadyl during pregnancy may result in respiratory depression and/or physical dependence with delayed emergence of withdrawal symptoms in the neonate {01}.


It is not known whether levomethadyl is distributed into breast milk in quantities sufficient to affect the nursing infant {01}.


In the U.S., Federal regulations prohibit use of levomethadyl in addicts younger than 18 years of age {01} {05}.


No information is available on the relationship of age to the effects of levomethadyl in geriatric patients.


Opioid analgesics may decrease or inhibit salivary flow, thus contributing to the development of caries, periodontal disease, oral candidiasis, and discomfort.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Alcohol or
» CNS depression–producing medications, other (See Appendix II )    (concurrent use may increase the CNS depressant, respiratory depressant, and hypotensive effects of these medications and/or levomethadyl; a reduction in dosage of levomethadyl and/or other prescribed CNS depressants may be required if concurrent use is necessary; also, opioid addicts should be warned of the risk of additive effects and potential for serious toxicity if they abuse alcohol or other CNS depressants while receiving levomethadyl {01})

» Enzyme inducers, hepatic, cytochrome P450 (see Appendix II )    (induction of the hepatic cytochrome P450 enzyme system may increase the rate of levomethadyl metabolism to its active metabolites and enhance its peak effectiveness, but may also shorten its duration of action {01})

» Enzyme inhibitors, hepatic (see Appendix II )    (inhibition of hepatic enzymes may slow the onset, lower the peak activity, and/or increase the duration of action of levomethadyl; adjustment of levomethadyl dosage and/or the interval between doses may be required {01})

» Opioid analgesics, mixed agonist/antagonist, such as:
» Opioid analgesics, partial mu-receptor agonist, such as:
Dezocine or
» Opioid antagonists, such as:
Naltrexone    (these medications may precipitate withdrawal symptoms if administered to a patient receiving levomethadyl therapy; the severity of withdrawal symptoms will depend on the potency and dose of the antagonist or partial agonist and on the degree to which physical dependence is present {01})

    (opioid analgesics such as levomethadyl will be ineffective if treatment is initiated in a patient receiving naltrexone, which blocks the therapeutic effects of opioids {21})

» Opioid analgesics, mu-receptor agonist, other, such as:
Sufentanil    (chronic use of levomethadyl produces cross-tolerance to the therapeutic effects, but not necessarily to the toxic effects, of other mu-receptor opioid agonists, leading to a considerably higher-than-normal dosage requirement for other mu-receptor agonists and a substantial risk of additive toxicity; deaths have occurred early in levomethadyl treatment in opioid addicts who continued to use illicit opioids during the 1- to 2-week delay in levomethadyl's onset of action. Administration of a mu-receptor opioid analgesic to levomethadyl-treated patients, if necessary for therapeutic purposes, requires extreme caution and careful monitoring. Opioid agonists that are N-demethylated to long-acting, excitatory metabolites [e.g., meperidine, propoxyphene] should not be used because the high dosage requirement also leads to an unacceptably high risk of metabolite-induced toxicity {01})

Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

Note: The following laboratory value alterations have not been documented with levomethadyl. However, they are commonly produced by other mu-receptor opioid agonists and should be considered potential effects of levomethadyl also.
Because of the long half-life of levomethadyl and its active metabolites, effects on laboratory values may persist for several days after treatment has been discontinued.

With diagnostic test results
Gastric emptying studies    (opioid analgesics may delay gastric emptying, thereby invalidating test results {14})

Hepatobiliary imaging using technetium Tc 99m disofenin    (delivery of technetium Tc 99m disofenin to the small bowel may be prevented because of opioid analgesic–induced constriction of the sphincter of Oddi and increased biliary tract pressure; these actions result in delayed visualization and thus resemble obstruction of the common bile duct {14})

With physiology/laboratory test values
Amylase, plasma and
Lipase, plasma    (values may be increased because opioid analgesics can cause contractions of the sphincter of Oddi and increased biliary tract pressure {14})

Cerebrospinal fluid (CSF) pressure    (may be increased; effect is secondary to respiratory depression–induced carbon dioxide retention {14})

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).

Risk-benefit should be considered when the following medical problems exist
Abdominal conditions, acute    (diagnosis or clinical course may be obscured {01} )

» Asthma, acute attack or
» Respiratory depression, acute or
» Respiratory impairment or disease, chronic    (risk of apnea because opioids decrease respiratory drive and increase airway resistance {01})

» Cardiac dysrhythmias    (cases of QT interval prolongation and severe arrhythmias, including torsade de pointes, have been reported in patients using levomethadyl; levomethadyl may increase the risk of serious and possibly life threatening pro-arrhythmic effects, administer with extreme caution to patients who may be at risk for development of prolonged QT syndrome including congestive heart failure, bradycardia, use of a diuretic, cardiac hypertrophy, hypokalemia, or hypomagnesia; careful monitoring is recommended during therapy{24})

Dependence on or abuse of nonopioid medications, history of, including alcoholism or
Emotional instability or
Suicidal ideation or attempts    (addicts often attempt suicide using combinations of opioids and other drugs of abuse. Patients who continue to use illicit opioids or other CNS-active medications despite adequate levomethadyl therapy require individualized evaluation and treatment planning; hospitalization may be necessary {01} )

Diagnostic, surgical, or other procedure requiring general anesthesia or sedation    (levomethadyl-induced alterations in patient response to medications that may be used in conjunction with general anesthesia or sedation [e.g., tolerance to the therapeutic effects of mu-receptor opioid agonists; increased risk of severe CNS and/or respiratory depression with anesthetics, sedatives, and opioid analgesics] and the risk of precipitating withdrawal via use of opioid antagonists, mixed agonists/antagonists, or partial mu-receptor agonists must be taken into consideration when selecting medications and dosages to be administered {01} )

Diarrhea associated with pseudomembranous colitis caused by antibiotics or
Diarrhea caused by poisoning    (opioids may slow the elimination of toxic material, and it is generally recommended that they not be administered until after toxins have been cleared from the gastrointestinal tract; {14} however, levomethadyl administration should not be interrupted if these conditions occur during treatment {22})

Gallbladder disease or gallstones    (opioids may cause biliary colic {14})

Gastrointestinal tract surgery, recent    (opioids may alter gastrointestinal motility {14} )

Head injury or
Increased intracranial pressure, pre-existing or
Intracranial lesions    (increased risk of respiratory depression and further elevation of cerebrospinal fluid pressure; also, opioids may cause sedation and pupillary changes that may obscure the clinical course of head injury {01})

Hepatic function impairment or
Renal function impairment    (although studies have not been done in patients with clinically significant hepatic or renal function impairment, the possibility must be considered that formation of levomethadyl's active metabolites and/or elimination of levomethadyl and its active metabolites may be substantially altered; because of its less complex metabolic profile, methadone may be preferable for such patients {01})

Hypothyroidism {01}    (risk of respiratory depression and prolonged CNS depression is greatly increased)

» Inflammatory bowel disease, severe    (risk of toxic megacolon may be increased {14})

Prostatic hypertrophy or obstruction or {01}
Urethral stricture or {01}
Urinary tract surgery, recent {14}    (increased risk of urinary retention, which may be induced by these conditions as well as by opioids)

Sensitivity to levomethadyl, history of {01}

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Drug screen    (in the U.S., Federal regulations mandate screening for drugs of abuse [amphetamines, barbiturates, cocaine, other opioids, and any other agents known to be abused in the program's locality] at the time a prospective patient first appears at the treatment center. Further testing is not required for patients undergoing detoxification from opioid drugs. Patients receiving interim maintenance treatment must be tested at least twice during a 120-day interim program, and patients receiving comprehensive maintenance treatment must be tested at least 8 times at random intervals during the first year of treatment and at least quarterly thereafter {05})

» Electrocardiogram (ECG)    (all patients should undergo an initial ECG prior to administration of levomethadyl to determine if a prolonged QT interval is present (QT c greater than 430 [male] ms or 450 [female] ms). If there is a prolonged interval, levomethadyl should not be administered. For patients who would benefit from levomethadyl therapy, an ECG should be performed prior to treatment, 12 to 14 days after initiating treatment, and periodically thereafter.{24})

» Pregnancy test    (in the U.S., Federal regulations require that women of childbearing potential receive a pregnancy test prior to initiation of, and monthly during, levomethadyl maintenance therapy {01} {05}because levomethadyl administration should not be started or continued during pregnancy {01} {05} except by the written order of a physician who determines levomethadyl to be the best choice of therapy for an individual patient {05})

Side/Adverse Effects

Note: Many symptoms typical of opioid withdrawal (listed below) occur during levomethadyl treatment. Early in treatment, while levomethadyl's active metabolites are forming and accumulating, such symptoms probably indicate withdrawal from illicit opioid analgesics. {01} {07} However, they may continue to occur many weeks after treatment has begun, especially on the days between doses. {01} Adjustment of levomethadyl dosage, {01} supplemental low doses of methadone, {01} {07} and/or a suppressant such as clonidine or guanabenz {07} may be needed.
In addition to the side/adverse effects listed below, the following have been reported in patients receiving levomethadyl (although a causal relationship has not been established): Amenorrhea; electrocardiographic irregularities, including prolongation of the QT interval and nonspecific ST-T wave changes; hepatitis; liver function test abnormalities; and pyuria.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent (1 to 3%) {23}
Edema (swelling of face, fingers, feet, and/or lower legs; weight gain)
mental depression
skin rash

Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent (3% or higher) {23}
Abdominal pain
general feeling of discomfort or illness
joint pain
sexual problems in males
trouble in sleeping

Incidence less frequent (1 to 3%) {23}
Back pain
blurred vision
CNS symptoms (anxiety; decreased sensitivity to stimulation; drowsiness; false sense of well-being; headache; unusual dreams)
decreased desire for sex
dry mouth
flu-like syndrome
hot flashes
nausea and vomiting
runny nose
Note: In some clinical trials, a significant number of patients experienced symptoms of stimulation, {15} {16} such as anxiety and nervousness, {15} on the day of administration. {15} {16} Some patients continued to experience these symptoms on the days between doses, {15} whereas others experienced symptoms such as lack of energy, dysphoria, and depression. {16}
Patients should be advised to report severe drowsiness or stimulation (e.g., feeling ``wired'') at the next visit to the clinic, because dosage adjustment may be needed. {23}

Incidence less than 1% {23}
Hypotension, postural (dizziness, lightheadedness, or feeling faint when rising from a lying or sitting position)
muscle pain
watery eyes

Those indicating possible withdrawal and/or the need for dosage adjustment or other treatment if they occur during therapy or after medication is discontinued
Body aches
fast heartbeat
increased sweating
loss of appetite
nausea or vomiting
nervousness, restlessness, or irritability
runny nose
shivering or trembling
stomach cramps
trouble in sleeping
unexplained fever
unusually large pupils of eyes

For specific information on the agents used in the management of levomethadyl overdose, see:

   • Naloxone (Systemic) monograph; and/or
   • Charcoal, Activated (Oral-Local) monograph.
For more information on the management of overdose, contact a Poison Control Center (see Poison Control Center Listing ).

Levomethadyl toxicity is more likely to develop when therapy is started in patients who have not developed tolerance to the effects of opioids. {01} In nontolerant patients, initial doses of 20 to 40 mg may cause somnolence, and larger initial doses may cause serious toxicity. Opioid-tolerant individuals may also experience symptoms, but at higher initial doses. {01}

Although overdose with levomethadyl alone has been reported rarely, as a result of too-frequent (daily) administration, most overdoses have involved ingestion of other opioids in addition to levomethadyl. {01} Deaths have occurred when patients continued to use illicit opioids after initiation of levomethadyl treatment. {07}

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Cold, clammy skin


low blood pressure

pinpoint pupils of eyes

respiratory depression (blue lips, fingernails, or skin; slow or troubled breathing)

severe dizziness, drowsiness, muscle weakness, nervousness, or restlessness

slow heartbeat

Note: In severe overdosage, extreme CNS and respiratory depression may result in apnea, shock, pulmonary edema, cardiac arrest, and death {01}.

Treatment of overdose
Primary importance should be given to maintaining adequate ventilation. Assessing the patient's respiratory status and, if necessary, administering oxygen or otherwise assisting respiration are essential. Provision of an artificial airway may be necessary. {01} {14}

To decrease absorption—Emptying the stomach by inducing emesis and/or administering activated charcoal {01}. The initial dose of charcoal should be followed by a cathartic, such as magnesium citrate, if the charcoal is not pre-mixed with sorbitol {17}. Gastric lavage may also be performed {14} {17}. During these procedures, care should be taken to protect the airway of any patient who is not fully alert {01}. However, treatment of respiratory depression or other life-threatening complications must take precedence {14}.

To enhance elimination—Forced diuresis, peritoneal dialysis, hemoperfusion, and hemodialysis are not likely to be effective for removal of levomethadyl because of its lipophilicity and large volume of distribution {01}.

Specific treatment—Administering naloxone, keeping in mind that rapid reversal of opioid effects may precipitate severe withdrawal symptoms, which may rarely lead to cardiac instability, in this patient population. Administration of several doses of naloxone, starting with considerably lower-than-usual quantities that may be increased gradually, if necessary, until the desired effect has been achieved is preferable to administration of large, single doses. Prolonged naloxone treatment, via repeated injections or continuous intravenous infusion, is likely to be necessary because of levomethadyl's long duration of action. Oral administration of the long-acting opioid antagonist naltrexone may precipitate prolonged withdrawal symptoms and is not recommended. {01} See the package insert or Naloxone (Systemic) for specific dosing guidelines for use of this product.


Respiration, oxygenation, patient alertness, and vital signs should be monitored {01}. Because of levomethadyl's long duration of action, prolonged observation will be needed. {01}.

A screen for other medications, especially other drugs of abuse, should be performed {01} and additional treatment instituted as required.

Supportive care—

Supportive measures include establishing intravenous lines, hydration, and administering vasopressors if necessary. {14}

Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Levomethadyl (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to levomethadyl

Pregnancy—Not starting levomethadyl during pregnancy; methadone is preferred medication for treating pregnant opioid addicts

Use in children—Use in patients up to 18 years of age not permitted by U.S. Federal regulations

Other medications, especially alcohol or other CNS depressants, hepatic enzyme inducers or inhibitors, other opioid analgesics, and opioid antagonists
Other medical problems, especially cardiac arrhythmia, diarrhea caused by antibiotics or by poisoning, asthma or other respiratory problems, and severe inflammatory bowel disease

Proper use of this medication
» Medication usually taken at clinic 3 times per week; at home doses permitted if patient is deemed responsible

» Proper dosing

Precautions while using this medication
» Importance of compliance with other measures necessary for rehabilitation, e.g., counseling, attending support group meetings, making lifestyle changes

» Avoiding use of alcoholic beverages and illicit opioids or other CNS depressants during therapy, even if experiencing withdrawal symptoms and cravings, because of the risk of potentially fatal additive toxicity or overdose

» Caution if severe drowsiness occurs, especially when treatment initiated or dosage adjusted

» Getting up slowly from a lying or sitting position; lying down for a while may relieve symptoms associated with postural hypotension, such as dizziness, light-headedness, or feeling faint

» Need to inform physicians and dentists of levomethadyl use, particularly if any kind of surgery (including dental surgery) or emergency treatment is required

Possible need for regimen to prevent severe constipation

Possible dryness of mouth; using sugarless gum or candy, ice, or saliva substitute for relief; checking with dentist if dry mouth continues for more than 2 weeks

» Female patients only: Not becoming pregnant during treatment; discussing planned pregnancy with counselor ahead of time; informing counselor if pregnancy suspected

» If transferring to methadone: Not taking first dose of methadone for at least 48 hours after last dose of levomethadyl

» Suspected overdose: Getting emergency help at once; need to inform emergency practitioners that the patient is physically dependent on a long-acting opioid, naloxone is likely to precipitate withdrawal, and prolonged observation and monitoring are needed

Side/adverse effects
Getting emergency help immediately if respiratory depression or other symptoms of overdose occur

Signs and symptoms of other potential side effects, especially edema, mental depression, and skin rash

Informing counselor at clinic if severe drowsiness, severe stimulation, or withdrawal symptoms occurred after previous dose

General Dosing Information
In the U.S., levomethadyl is available only through treatment programs that have been approved by the Food and Drug Administration, Drug Enforcement Agency, and designated state authorities {01} {05}.

Levomethadyl is given only by the oral route. The commercially available oral solution must be diluted before being administered to the patient. Treatment centers that dispense both levomethadyl and methadone (which must also be dispensed as a dilute liquid) should use liquids of different colors for preparing each medication, so that they can be distinguished from each other readily. {01} {05}

Levomethadyl is to be ingested by the patient at the treatment center. If it is determined that the patient is responsible in handling opioid drugs then levomethadyl take-home doses are permitted.{24}{01}{05}.

Levomethadyl treatment should be initiated using a dose that suppresses withdrawal symptoms and decreases craving for illicit opioids without inducing excessive opioid effects {01}. Interpatient variability in levomethadyl kinetics and each patient's level of tolerance to opioids must be taken into account when selecting initial dosage {01}. However, because of levomethadyl's slow onset of action and the risk of toxicity if dosage is increased too rapidly, elimination of withdrawal symptoms and craving may not be possible during the first 1 or 2 weeks of therapy {01}. Patients may need extra counseling and support {01} and/or administration of a withdrawal suppressant, preferably a non-opiod such as clonidine or guanabenz, {07} during this time. Alternatively, treatment may be initiated with methadone (especially if the patient's degree of tolerance to opioids is not known), since effective dosage can be achieved more rapidly, and the patient transferred to levomethadyl after a few weeks {01}. The changeover from methadone to levomethadyl may be accomplished in a single dose {01}.

Levomethadyl is usually administered 3 times a week (on Monday, Wednesday, and Friday or on Tuesday, Thursday, and Saturday), {01} but some patients experience withdrawal symptoms during the 72-hour Friday-to-Monday or Saturday-to-Tuesday interval {01} {07}. Administration of a higher dose on Friday or Saturday prevents or minimizes this problem in most patients {01} {07}. However, in a clinical trial patients receiving such a regimen reported feeling overmedicated on the day that the higher dose was given and undermedicated after the next (lower) dose {18}. For some patients, use of a withdrawal suppressant such as clonidine or guanabenz {07}; provision of a low take-home dose of methadone (if the patient meets the criteria specified in U.S. Federal regulations for take-home methadone) {01} {07}; arranging the patient's schedule so that the 72-hour interval occurs during the week, so that a small dose of methadone can be administered to the patient at the clinic if necessary {01}; or administration of levomethadyl on an every-other-day basis {01} may be necessary. Levomethadyl should not be administered daily because rapid accumulation of the medication and its active metabolites may lead to an overdose {01}.

Patients receiving levomethadyl may be transferred directly to methadone {01} {19}, although some patients may experience mild withdrawal symptoms during the first 1 or 2 weeks {19}. The initial dose of methadone, which should be taken at least 48 hours after the last dose of levomethadyl, should be 80% of the patient's lower levomethadyl dose. For example, a patient receiving three-times-a week treatment with 80, 80, and 100 mg of levomethadyl would be given 64 mg of methadone per day, initially. The daily dose of methadone may be increased or decreased by 5 or 10 mg if symptoms of withdrawal or opioid excess occur. {01} This regimen may also be used, provided that the regulations and requirements for take-home methadone are met, when a levomethadyl-treated patient who is unable to attend the clinic regularly for a period of time (for example, because of illness or travel) requires a temporary transfer to take-home methadone. {01} {05} The risk of the methadone's being diverted to illicit use must be considered. The number of take-home methadone doses should be 2 fewer than the number of days of expected absence, but must not exceed the maximum number of take-home doses specified in U.S. Federal regulations. When the patient returns to the clinic levomethadyl may be resumed, following the same dosage regimen as before the temporary change in treatment. However, if the last methadone dose was taken more than 48 hours previously, levomethadyl should be reintroduced at a dose based on clinical and/or toxicological evaluation of the patient. {01}

Discontinuation of levomethadyl maintenance therapy may be considered after the patient has achieved behavioral objectives outlined in the patient's comprehensive treatment plan, i.e., stopped using illicit drugs, reached social and occupational goals, and changed his or her lifestyle to decrease the risk of relapse. Treatment should not be stopped prematurely, and appropriate nonpharmacological support should be provided to reduce further the risk of relapse. Stable long-term treatment is preferable to cycles of discontinuation of therapy followed by recidivism. {01} Treatment has been successfully discontinued by abrupt withdrawal or by reducing dosage gradually (by 5 to 10% per week). {01} One study comparing both methods of detoxification found that withdrawal symptoms were not more severe, and a significantly higher number of patients were successfully withdrawn from maintenance treatment without returning to illicit opioid use, when levomethadyl was stopped abruptly. {20}

Safety considerations for handling this medication
Because of the risk of diversion of this potent opioid, security measures stipulated in the U.S. Federal Code of Regulations should be taken to safeguard supplies of the medication {01} {03}.

There are no known hazards associated with dermal or aerosol exposure to levomethadyl. However, if the medication is spilled onto an individual, contaminated clothing should be removed and the exposed skin rinsed with cool water {01}.

Oral Dosage Forms


Usual adult dose
Opioid (narcotic) abuse therapy adjunct

Patients not receiving prior methadone maintenance treatment—Oral, 20 to 40 mg for the first dose. Subsequent doses, given at forty-eight- or seventy-two-hour intervals, may be increased by 5 to 10 mg until the desired effects (absence of withdrawal symptoms and decreased craving for illicit opioids) have been achieved or decreased by the same amount if undue sedation or other symptoms of opioid excess occur. {01}

Patients transferred from methadone maintenance treatment—Oral, a quantity of levomethadyl equivalent to 1.2 to 1.3 times the patient's daily methadone dose, up to a maximum of 120 mg, for the first dose. Subsequent doses, administered at forty-eight- or seventy-two-hour intervals, should be adjusted according to the response of the individual patient, using caution not to increase the dose too rapidly because of the risk of toxicity. Dosage is generally increased by 5 to 10 mg every second or third dose. {01}

Dosage must be individualized according to the patient's tolerance and response. Most patients can be stabilized on 60 to 80 mg, administered three times a week at forty-eight- or seventy-two-hour intervals. However, maintenance doses as low as 10 mg and as high as 140 mg, administered three times a week, have been used in clinical trials. If necessary to prevent withdrawal over a seventy-two-hour interdose interval, the dose prior to this interval may be increased, in 6- to 10-mg increments, to up to forty percent higher than the doses given prior to a forty-eight-hour interval. At least two weeks are required to achieve a new clinical plateau after each adjustment of levomethadyl dosage.{01}

Following an unplanned lapse of one dose:

   —If the patient comes to the clinic to be dosed on the day following a missed scheduled dose (misses Monday, arrives Tuesday) the regular Monday dose should be administered on Tuesday, with the scheduled Wednesday dose administered on Thursday and the Friday dose given on Saturday. The patient's regular schedule may be resumed the following Monday (missed Wednesday, receives the regular dose on Thursday and Saturday, and returns to the regular Monday/Wednesday/Friday dosing schedule the next week).{24}
   —If a patient misses one dose and comes to the clinic on the day of the next scheduled dose (misses Monday, arrives Wednesday), the usual dose will be well tolerated in most instances, although a reduced dose may be appropriate in selected cases.{24}Following an unplanned lapse of more than one dose:

   —Patients should be reintroduced at an initial dose of 1/2 or 3/4 their previous levomethadyl dose, followed by increases of 5 to 10 mg every dosing day (48 or 72 hour intervals) until their previous maintained dose is achieved. Patients who have been off of treatment for more than one week should be reinducted.{24}

Note: U.S. Federal regulations require that single doses of 140 mg or more be justified in the patient's record {05}.

Usual adult prescribing limits
Initial induction dose—40 mg (if the patient's level of opioid tolerance is unknown) or 120 mg (if the patient's level of tolerance, based on methadone dosage requirements, is known). {01}

Maintenance—Dosage should not exceed 140 mg three times a week or every other day, or two 130-mg doses and one 180-mg dose per week. {01}

Usual pediatric dose
U.S. Federal regulations prohibit use of levomethadyl in patients younger than 18 years of age {01} {05}.

Usual geriatric dose
See Usual adult dose.

Strength(s) usually available

10 mg per mL (Rx) [Orlaam{01} (methylparaben 1.8 mg ) (and propylparaben 0.2 mg per mL)]

Not commercially available.

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), protected from freezing, unless otherwise specified by manufacturer.

Preparation of dosage form:
U.S. Federal regulations stipulate that the oral solution must be diluted before being administered to the patient. The liquid used for dilution should be colored differently than a liquid used to prepare methadone solutions in the same clinic {01} {09}.

Developed: 08/11/1995
Revised: 08/05/2001

  1. Orlaam package insert (Bio-Development—US), Rec. 9/93.Undated
  1. Fleeger C, editor. USP dictionary of USAN and international drug names. 1995. Rockville, MD: The United States Pharmacopeial Convention, Inc., 1994: 382.
  1. Human drugs: Drugs for narcotic addiction treatment—Levo-alpha-acetyl-methadol, 38704. Department of Health and Human Services, Food and Drug Administration. Fed Regist 58 (137) 1993 Tuesday, July 20.
  1. Schedules of controlled substances: Levo-alphacetylmethadol, 43795. Department of Justice, Drug Enforcement Administration. Fed Regist 58 (158) 1993 Wednesday, August 18.
  1. 291.505. Conditions for the use of narcotic drugs; appropriate methods of professional practice for medical treatment of the narcotic addiction of various classes of narcotic addicts under section 4 of the Comprehensive Drug Abuse Prevention and Control Act of 1970. Code of Federal Regulations. 21: Food and Drugs. Washington, Office of the Federal Register, National Archives and Records Service, General Services Administration; for sale by the Supt of Docs, U.S. Govt Print Off. 1994; 124-45.
  1. Drugs Directorate Guidelines. The use of opioids in the management of opioid dependence. Ottawa, Ont: Health Protection Branch, Health and Welfare Canada, 1992 August.
  1. Tennant FS, Rawson RA, Pumphrey E, et al. Clinical experiences with 959 opioid-dependent patients treated with levo-alpha-acetylmethadol (LAAM). J Subst Abuse Treat 1986; 3: 195-202.
  1. Brusick D, Matheson D, Jagannath D, et al. Genetic screening of compounds used in drug abuse treatment. III. LAAM. Drug Chem Toxicol 1981; 4: 19-35.
  1. Toro-Goyco E, Martin BR, Harris LS. Binding of l-alpha-acetylmethadol and its metabolites to blood constituents. Biochem Pharmacol 1980; 29: 1897-902.
  1. Henderson GL, Wilson BK, Lau DHM. Plasma l-alpha-acetylmethadol (LAAM) after acute and chronic administration. Clin Pharmacol Ther 1977; 21: 16-25.
  1. Finkle BS, Jennison RA, Chinn DM, et al. Plasma and urine disposition of l-alpha-acetylmethadol and its principal metabolites in man. J Anal Toxicol 1982; 6: 100-5.
  1. Kaiko RF, Inturrisi CE. Disposition of acetylmethadol in relation to pharmacologic action. Clin Pharmacol Ther 1975; 18: 96-103.
  1. Lichtblau L, Sparber SB. Outcome of pregnancy in rats chronically exposed to l-alpha-acetylmethadol (LAAM). J Pharmacol Exp Ther 1981; 218: 303-8.
  1. Opioid (Narcotic) Analgesics (Systemic) monograph draft for USP DI 1986.
  1. Zangwell BC, McGahan P, Dorozynsky L, et al. How effective is LAAM treatment? Clinical comparison with methadone. NIDA Res Monogr 1986; 67: 249-55.
  1. Marcovici M, O"Brien CP, McLellan AT, et al. A clinical, controlled study of l-alpha-acetylmethadol in the treatment of narcotic addiction. Am J Psychiatry 1981; 138: 234-6.
  1. Clinical Toxicology/Substance Abuse panel meeting 4/19/94.
  1. Hough G, Washton AM, Resnick RB. Addressing the diversion of take-home methadone: LAAM as the sole treatment choice for patients seeking maintenance therapy. NIDA Res Monogr 1983; 43: 302-9.
  1. Ling W, Blakis M, Holmes ED, et al. Restabilization with methadone after methadyl acetate maintenance. Arch Gen Psychiatry 1980; 37: 194-6.
  1. Judson BA, Goldstein A, Inturrisi CE. Methadyl acetate (LAAM) in the treatment of heroin addicts. II. Double-blind comparison of graduated and abrupt detoxification. Arch Gen Psychiatry 1983; 40: 834-40.
  1. ReVia (naltrexone) package insert (DuPont Pharma—US), Rev 1/95, Rec 2/95.
  1. Panel comments, monograph draft 5/95.
  1. Orlaam package insert (Roxane—US), Rec. 7/95.Undated
  1. Product Information: Orlaam®, levomethadyl. Roxane Laboratories, Columbus, Ohio. (PI revised 5/2001) PI reviewed 7/2001

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.