FDA advisory committees support changing codeine contraindications for children

SILVER SPRING, MD. – A joint meeting of the Food and Drug Administration’s Pulmonary-Allergy Drugs Advisory Committee (PADAC) and the Drug Safety and Risk Management Advisory Committee (DSaRM) on Dec. 10 voted overwhelmingly to support expanding the current contraindication for codeine to preclude its use for any pain management in all children under age 18 years.

Twenty members of the joint advisory panel voted for the aforementioned contraindication, while six members elected to contraindicate for any pain management in children younger than 12 years old, and another two members voted only to contraindicate for children younger than age 6 years. Only one member – Dr. Maureen Finnegan of the DSaRM – voted not to make any changes to the current contraindications for codeine.

The joint advisory panel also voted to contraindicate the use of codeine for the treatment of cough in all children younger than age 18 years by a similarly robust margin: 20 members voted for contraindicating in all pediatric patients, five voted to contraindicate only in patients younger than age 12 years, one voted to contraindicate in children younger than age 6 years, and three members voted not to make any changes at all.

The final voting question, asking whether to remove codeine from the FDA monograph for over-the-counter use in treating cough in children, was almost unanimously supported by the voting members of both committees. Only one member – Dr. Lorraine J. Gudas, a temporary voting member – supported removing codeine from the monograph only for children under age 2 years. Dr. Finnegan abstained from voting on this charge, telling the committee that “this is totally out of my wheelhouse.”

The decision to vote on approving amendments to the contraindications for codeine use – which would affect not just the monogram, but labeling as well – comes on the heels of the FDA announcing this summer that they would be investigating the safety of codeine-containing drugs in children, asking health care providers and patients to report any adverse events associated with the drug.

The joint advisory panel cited reports of respiratory depression and death in pediatric patients, variability of codeine metabolism based upon CYP2D6 activity, and the fact that “some regulatory agencies have restricted use of codeine for both cough and analgesia in pediatric patients” as their key reasons for considering the changes to current contraindications, according to Dr. Sally Seymour, the FDA’s Deputy Director for Safety.

In a presentation on codeine use for pediatric analgesia, FDA Medical Officer Dr. Timothy Jiang cited several studies detailing adverse events in children taking codeine-containing drugs. One 2007 study by Voronov et al involved a 29-month-old boy of North African heritage who took codeine/acetaminophen following adenotonsillectomy for “recurrent tonsillitis and mild-moderate sleep apnea;” the boy was found unresponsive the day after the operation, but was later resuscitated.

In another study – a 2009 study in the New England Journal of Medicine by Catherine Ciszkowski and her associates – cites a similar situation of a 2-year-old boy receiving codeine after adenotonsillectomy, only to be found unresponsive; in this case, however, the boy died 2 days after the operation. Additionally, Dr. Jiang cited a 2012 search of the Adverse Event Reporting System, looking at data from 1969 through May 1, 2012, which found that six additional cases of death, as well as seven literature cases that mentioned patients’ CYPD26 status as possibly contributing.

The FDA is not required to follow the advice of its advisory panels, but often does. No members of the panel reported any relevant financial conflicts of interest.

[email protected]

SILVER SPRING, MD. – A joint meeting of the Food and Drug Administration’s Pulmonary-Allergy Drugs Advisory Committee (PADAC) and the Drug Safety and Risk Management Advisory Committee (DSaRM) on Dec. 10 voted overwhelmingly to support expanding the current contraindication for codeine to preclude its use for any pain management in all children under age 18 years.

Twenty members of the joint advisory panel voted for the aforementioned contraindication, while six members elected to contraindicate for any pain management in children younger than 12 years old, and another two members voted only to contraindicate for children younger than age 6 years. Only one member – Dr. Maureen Finnegan of the DSaRM – voted not to make any changes to the current contraindications for codeine.

The joint advisory panel also voted to contraindicate the use of codeine for the treatment of cough in all children younger than age 18 years by a similarly robust margin: 20 members voted for contraindicating in all pediatric patients, five voted to contraindicate only in patients younger than age 12 years, one voted to contraindicate in children younger than age 6 years, and three members voted not to make any changes at all.

The final voting question, asking whether to remove codeine from the FDA monograph for over-the-counter use in treating cough in children, was almost unanimously supported by the voting members of both committees. Only one member – Dr. Lorraine J. Gudas, a temporary voting member – supported removing codeine from the monograph only for children under age 2 years. Dr. Finnegan abstained from voting on this charge, telling the committee that “this is totally out of my wheelhouse.”

The decision to vote on approving amendments to the contraindications for codeine use – which would affect not just the monogram, but labeling as well – comes on the heels of the FDA announcing this summer that they would be investigating the safety of codeine-containing drugs in children, asking health care providers and patients to report any adverse events associated with the drug.

The joint advisory panel cited reports of respiratory depression and death in pediatric patients, variability of codeine metabolism based upon CYP2D6 activity, and the fact that “some regulatory agencies have restricted use of codeine for both cough and analgesia in pediatric patients” as their key reasons for considering the changes to current contraindications, according to Dr. Sally Seymour, the FDA’s Deputy Director for Safety.

In a presentation on codeine use for pediatric analgesia, FDA Medical Officer Dr. Timothy Jiang cited several studies detailing adverse events in children taking codeine-containing drugs. One 2007 study by Voronov et al involved a 29-month-old boy of North African heritage who took codeine/acetaminophen following adenotonsillectomy for “recurrent tonsillitis and mild-moderate sleep apnea;” the boy was found unresponsive the day after the operation, but was later resuscitated.

In another study – a 2009 study in the New England Journal of Medicine by Catherine Ciszkowski and her associates – cites a similar situation of a 2-year-old boy receiving codeine after adenotonsillectomy, only to be found unresponsive; in this case, however, the boy died 2 days after the operation. Additionally, Dr. Jiang cited a 2012 search of the Adverse Event Reporting System, looking at data from 1969 through May 1, 2012, which found that six additional cases of death, as well as seven literature cases that mentioned patients’ CYPD26 status as possibly contributing.

The FDA is not required to follow the advice of its advisory panels, but often does. No members of the panel reported any relevant financial conflicts of interest.

[email protected]

SILVER SPRING, MD. – A joint meeting of the Food and Drug Administration’s Pulmonary-Allergy Drugs Advisory Committee (PADAC) and the Drug Safety and Risk Management Advisory Committee (DSaRM) on Dec. 10 voted overwhelmingly to support expanding the current contraindication for codeine to preclude its use for any pain management in all children under age 18 years.

Twenty members of the joint advisory panel voted for the aforementioned contraindication, while six members elected to contraindicate for any pain management in children younger than 12 years old, and another two members voted only to contraindicate for children younger than age 6 years. Only one member – Dr. Maureen Finnegan of the DSaRM – voted not to make any changes to the current contraindications for codeine.

The joint advisory panel also voted to contraindicate the use of codeine for the treatment of cough in all children younger than age 18 years by a similarly robust margin: 20 members voted for contraindicating in all pediatric patients, five voted to contraindicate only in patients younger than age 12 years, one voted to contraindicate in children younger than age 6 years, and three members voted not to make any changes at all.

The final voting question, asking whether to remove codeine from the FDA monograph for over-the-counter use in treating cough in children, was almost unanimously supported by the voting members of both committees. Only one member – Dr. Lorraine J. Gudas, a temporary voting member – supported removing codeine from the monograph only for children under age 2 years. Dr. Finnegan abstained from voting on this charge, telling the committee that “this is totally out of my wheelhouse.”

The decision to vote on approving amendments to the contraindications for codeine use – which would affect not just the monogram, but labeling as well – comes on the heels of the FDA announcing this summer that they would be investigating the safety of codeine-containing drugs in children, asking health care providers and patients to report any adverse events associated with the drug.

The joint advisory panel cited reports of respiratory depression and death in pediatric patients, variability of codeine metabolism based upon CYP2D6 activity, and the fact that “some regulatory agencies have restricted use of codeine for both cough and analgesia in pediatric patients” as their key reasons for considering the changes to current contraindications, according to Dr. Sally Seymour, the FDA’s Deputy Director for Safety.

In a presentation on codeine use for pediatric analgesia, FDA Medical Officer Dr. Timothy Jiang cited several studies detailing adverse events in children taking codeine-containing drugs. One 2007 study by Voronov et al involved a 29-month-old boy of North African heritage who took codeine/acetaminophen following adenotonsillectomy for “recurrent tonsillitis and mild-moderate sleep apnea;” the boy was found unresponsive the day after the operation, but was later resuscitated.

In another study – a 2009 study in the New England Journal of Medicine by Catherine Ciszkowski and her associates – cites a similar situation of a 2-year-old boy receiving codeine after adenotonsillectomy, only to be found unresponsive; in this case, however, the boy died 2 days after the operation. Additionally, Dr. Jiang cited a 2012 search of the Adverse Event Reporting System, looking at data from 1969 through May 1, 2012, which found that six additional cases of death, as well as seven literature cases that mentioned patients’ CYPD26 status as possibly contributing.

The FDA is not required to follow the advice of its advisory panels, but often does. No members of the panel reported any relevant financial conflicts of interest.

[email protected]