FDA BLACK-BOX WARNING
WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; ULTRA-RAPID METABOLISM OF CODEINE AND OTHER RISK FACTORS FOR LIFETHREATENING RESPIRATORY DEPRESSION IN CHILDREN; NEONATAL OPIOID WITHDRAWL SYNDROME; and INTERACTIONS WITH DRUGS AFFECTING CYTOCHROME P450 ISOENZYMES
Addiction, Abuse, and Misuse
FIORINAL with CODEINE exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing FIORINAL with CODEINE, and monitor all patients regularly for the development of these behaviors and conditions.
Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression may occur with use of FIORINAL with CODEINE. Monitor for respiratory depression, especially during initiation of FIORINAL with CODEINE or following a dose increase.
Accidental ingestion of even one dose of FIORINAL with CODEINE, especially by children, can result in a fatal overdose of FIORINAL with CODEINE.
Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants
Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.
Reserve concomitant prescribing of FIORINAL with CODEINE and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
Limit dosages and durations to the minimum required.
Follow patients for signs and symptoms of respiratory depression and sedation.
Ultra-Rapid Metabolism of Codeine and Other Risk Factors for Life-Threatening Respiratory Depression in Children
Life-threatening respiratory depression and death have occurred in children who received codeine. Most of the reported cases occurred following tonsillectomy and/or adenoidectomy, and many of the children had evidence of being an ultrarapid metabolizer of codeine due to a CYP2D6 polymorphism. FIORINAL with CODEINE is contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see Contraindications (4)]. Avoid the use of FIORINAL with CODEINE in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of codeine.
Neonatal Opioid Withdrawal Syndrome
Prolonged use of FIORINAL with CODEINE during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
Death Related to Ultra-Rapid Metabolism of Codeine to Morphine
Respiratory depression and death have occurred in children who received codeine following tonsillectomy and/or adenoidectomy and had evidence of being ultra-rapid metabolizers of codeine due to a CYP2D6 polymorphism.
Interactions with Drugs Affecting Cytochrome P450 Isoenzymes
The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex. Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with FIORINAL with CODEINE requires careful consideration of the effects on codeine, and the active metabolite, morphine.
One hazard of taking these drugs continuously for longer than several weeks is drug-induced dependence. Do not stop taking your drug suddenly. With the help of your doctor, work out a schedule for slowly lowering the amount of the drug you take by about 5 to 10 percent each day. Keep a written record of the dosage reduction schedule with you. These steps will make it much easier to become drug free without developing distressing symptoms of drug withdrawal.
Fiorinal with Codeine can increase the risk of hip fracture.
There have been a number of case reports of liver damage involving a possible drug interaction between isoniazid, a medication used to prevent and treat tuberculosis (TB), and acetaminophen, an over-the-counter painkiller and the active ingredient in Tylenol. Isoniazid alone, especially as people get older, has been documented to cause liver damage. Acetaminophen, alone in large doses or probably in combination with alcohol, also increases the risk of liver damage. The combination of acetaminophen with isoniazid, according to the authors of these case reports, may also be dangerous.
If you are taking isoniazid for tuberculosis or have a positive TB skin test and are using the drug, consult your physician before using acetaminophen or any combination product containing acetaminophen. Discuss alternatives to acetaminophen with your physician.
Aspirin/Reye's Syndrome Alert
Do not use the aspirin-containing products for treating chicken pox, flu, or flulike illness. They will increase the risk of contracting Reye’s syndrome, a rare but often fatal disease.