"The US Food and Drug Administration (FDA) is investigating the "rare but serious" risk for slowed or difficult breathing in children 17 and younger treated with the opioid analgesic tramadol.
"This risk may be increased in children tr"...
(Generic versions may still be available.)
Physicians should be alert to palpitations, syncope, or other symptoms suggestive of episodes of irregular cardiac rhythm in patients taking ORLAAM and promptly evaluate such cases (see WARNINGS , Effects on Cardiac Conduction ).
Patients presenting for ORLAAM (levomethadyl acetate) treatment are frequently in withdrawal from heroin or other opiates. They may display typical withdrawal symptoms which should be differentiated from ORLAAM (levomethadyl acetate) 's side effects. Patients may exhibit some or all of the following signs and symptoms associated with withdrawal from opiates: lacrimation, rhinorrhea, sneezing, yawning, perspiration, gooseflesh, fever, chilliness alternating with flushing, restlessness, irritability, insomnia, weakness, anxiety, depression, dilated pupils, tremors, tachycardia, abdominal cramps, body aches, anorexia, nausea, vomiting, diarrhea, and weight loss. Control of such symptoms is a primary goal of therapy. However, because of the slow onset and long half-lives of ORLAAM (levomethadyl acetate) , nor-LAAM and dinor-LAAM, overly aggressive increases in dosage to control these withdrawal symptoms with ORLAAM (levomethadyl acetate) may result in overdose (see INDIVIDUALIZATION OF DOSAGE ).
Signs and Symptoms of ORLAAM (levomethadyl acetate) Excess
The interaction between the development and maintenance of opioid tolerance and ORLAAM (levomethadyl acetate) dose can be complex. Dose reduction is recommended in cases where patients develop signs and symptoms of excessive ORLAAM (levomethadyl acetate) effect, characterized by complaints of "feeling wired", poor concentration, drowsiness, and possibly dizziness on standing.
ORLAAM (levomethadyl acetate) Withdrawal
Patients may experience withdrawal symptoms (nasal congestion, abdominal symptoms, diarrhea, muscle aches, anxiety) over the 72-hour dosing interval if the dose of ORLAAM (levomethadyl acetate) is too low. This may be managed as described under INDIVIDUALIZATION OF DOSAGE , but physicians should be alert to the possible need for dose or dose schedule adjustments if patients complain of weekend withdrawal symptoms in the last day of the 72-hour dosing interval.
Adverse Reactions on Stable Therapy
The following adverse events were observed in the 25-site, 623-patient usage study in male and female opiate addicts (see CLINICAL TRIALS ). These signs and symptoms were reported during the second and third months of treatment with ORLAAM (levomethadyl acetate) , and were considered severe enough to require medical evaluation. In this study, both questionnaires and spontaneous reports were used to gather information. Questionnaire-elicited symptom frequencies were about five times as frequent as the spontaneous reporting frequencies given below.
Incidence greater than 1%, Probably Causally Related
*Reactions in 3-9% of patients; reactions in 1-3% are unmarked.
Musculoskeletal Arthralgia *
Special Senses Blurred vision.
Incidence less than 1%, Probably Causally Related
Special Senses Tearing.
Causal Relationship Unknown
These reactions were reported with low frequency in controlled and uncontrolled studies of LAAM, are not known to be causally related to the administration of the drug, and are provided as alerting information for physicians.
The following adverse reactions have been reported in the post-marketing setting (all reactions in less than 1% of patients).
Urogenital Breast enlargement.
ORLAAM (levomethadyl acetate) is a Schedule II controlled substance under the Federal Controlled Substances Act. ORLAAM (levomethadyl acetate) produces dependence of the morphine-type and has potential for abuse. Tolerance and physical dependence will develop upon repeated administration. As with methadone and any other narcotic administered to narcotic addicts, ORLAAM (levomethadyl acetate) is at risk for diversion and illicit use, and should be handled accordingly (see WARNINGS ).
Read the Orlaam (levomethadyl acetate) Side Effects Center for a complete guide to possible side effects
No interaction studies have been performed in humans. ORLAAM (levomethadyl acetate) is metabolized by the cytochrome P450 isoform, CYP3A4. The addition of drugs that induce this enzyme could increase the levels of active metabolites in a patient that was previously at steady-state.
Potentially Arrhythmogenic Agents Any drug known to have the potential to prolong the QT interval should not be used together with ORLAAM (levomethadyl acetate) . Possible pharmacodynamic interactions can occur between ORLAAM (levomethadyl acetate) and potentially arrhythmogenic agents such as class I or III antiarrhythmics, antihistamines that prolong the QT interval, antimalarials, calcium channel blockers, neuroleptics that prolong the QT interval, and antidepressants
Caution should be used when prescribing concomitant drugs known to induce hypokalemia or hypomagnesemia as they may precipitate QT prolongation and interact with ORLAAM (levomethadyl acetate) . These would include diuretics, laxatives and supraphysiological use of steroid hormones with mineralocorticoid potential.
Polydrug and Alcohol Abusers Patients who are known to abuse sedatives, tranquilizers, propoxyphene, antidepres-sants, benzodiazepines, and alcohol should be warned of the risk of serious overdose if these substances are taken while on ORLAAM (levomethadyl acetate) maintenance.
Interaction with Narcotic Antagonists, Mixed Agonists/Antago-nists, Partial Agonists, and Pure Agonists As with other mu agonists, patients maintained on ORLAAM (levomethadyl acetate) may experience withdrawal symptoms when administered pure narcotic antagonists, such as naloxone, naltrexone, and nalmefene, or when administered mixed agonists/antagonists or partial agonists such as pentazocine, nalbuphine, butorphanol, and buprenorphine.
In addition, agonists such as meperidine and propoxyphene, which are N-demethylated to long-acting, excitatory metabolites, should not be used by patients taking ORLAAM (levomethadyl acetate) because they would be ineffective unless given in such high doses that the risk of toxic effects of the metabolites becomes unacceptable.
Anesthesia and Analgesia Patients receiving ORLAAM (levomethadyl acetate) will develop a similar level of tolerance for opioids as patients receiving methadone. Anesthetists and other practitioners should be prepared to adjust their management of these patients accordingly.
Other Drug Interactions The anti-tuberculosis drug rifampin has been found to produce a marked (50%) reduction in serum methadone levels, leading to the appearance of symptoms of withdrawal in well-stabilized methadone maintenance patients. Similar effects on serum methadone levels have been observed for carbamazepine, phenobarbital, and phenytoin. The presumed mechanism for this effect is the induction of methadone metabolizing enzymes. Since ORLAAM (levomethadyl acetate) is metabolized into a more active metabolite, nor-LAAM, administration of these drugs may increase ORLAAM (levomethadyl acetate) 's peak activity and/or shorten its duration of action.
Conversely, drugs like erythromycin, cimetidine, and anti-fungal drugs like ketoconazole that inhibit hepatic metabolism, may slow the onset, lower the activity, and/or increase the duration of action of ORLAAM (levomethadyl acetate) . Caution and close observation of patients receiving these drugs are advised to allow early detection of any need to adjust the dose or dosing interval.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 12/8/2004
Additional Orlaam Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.