SIDE EFFECTS

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 ).

Heroin or Methadone Withdrawal Reactions

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

Body as a Whole Asthenia * , back pain, chills, edema, hot flashes (males 2:1), flu syndrome and malaise (11%).

Gastrointestinal Abdominal pain * , constipation * , diarrhea, dry mouth, nausea and vomiting.

Musculoskeletal Arthralgia *

Nervous System Abnormal dreams, anxiety, decreased sex drive, depression, euphoria, headache, hypesthesia, insomnia (9.1%), nervousness * , somnolence.

Respiratory Cough, rhinitis, and yawning.

Skin/appendages Rash, sweating * .

Special Senses Blurred vision.

Urogenital Difficult ejaculation * , impotence * .

Incidence less than 1%, Probably Causally Related

Cardiovascular Postural hypotension.

Musculoskeletal Myalgia.

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.

Cardiovascular Hypertension

Hepatic Hepatitis and abnormal liver function tests.

Urogenital Amenorrhea, pyuria.

The following adverse reactions have been reported in the post-marketing setting (all reactions in less than 1% of patients).

Body as a Whole Altered hormone level, chest pain.

Cardiovascular QT interval prolongation, torsade de pointes, cardiac arrest, ST segment elevation, ventricular tachycardia, myocardial infarction, angina pectoris, syncope, migraine.

Nervous System Convulsions, confusion, hallucination, incoordination, amnesia.

Respiratory Apnea, dyspnea.

Urogenital Breast enlargement.

DRUG DEPENDENCE

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 entire FDA prescribing information for Orlaam (Levomethadyl Acetate) »