Applies to codeine: oral solution, oral tablets.
Warning
Special Alerts:
- FDA drug safety communication (4/13/2023):500 As part of its ongoing efforts to address the nation’s opioid crisis, FDA is requiring several updates to the prescribing information of opioid pain medicines. The changes are being made to provide additional guidance for safe use of these drugs while also recognizing the important benefits when used appropriately. The changes apply to both immediate-release (IR) and extended-release/long-acting preparations (ER/LA).
- Updates to the IR opioids state that these drugs should not be used for an extended period unless the pain remains severe enough to require an opioid pain medicine and alternative treatment options are insufficient, and that many acute pain conditions treated in the outpatient setting require no more than a few days of an opioid pain medicine.
- Updates to the ER/LA opioids recommend that these drugs be reserved for severe and persistent pain requiring an extended period of treatment with a daily opioid pain medicine and for which alternative treatment options are inadequate.
- A new warning is being added about opioid-induced hyperalgesia (OIH) for both IR and ER/LA opioid pain medicines. This includes information describing the symptoms that differentiate OIH from opioid tolerance and withdrawal.
- Information in the boxed warning for all IR and ER/LA opioid pain medicines will be updated and reordered to elevate the importance of warnings concerning life-threatening respiratory depression, and risks associated with using opioid pain medicines in conjunction with benzodiazepines or other medicines that depress the central nervous system (CNS).
- Other changes will also be required in various other sections of the prescribing information to educate clinicians, patients, and caregivers about the risks of these drugs.
REMS:
FDA approved a REMS for codeine to ensure that the benefits outweigh the risk. The REMS may apply to one or more preparations of codeine and consists of the following: medication guide and elements to assure safe use. See the FDA REMS page ([Web]).
Side effects include:
When used for pain relief (particularly in ambulatory patients not experiencing severe pain): lightheadedness, dizziness, sedation, nausea, vomiting, sweating.
When used at antitussive doses: nausea, vomiting, constipation (with repeated doses), dizziness, sedation, palpitation, pruritus.
For Healthcare Professionals
Applies to codeine: compounding powder, injectable solution, oral solution, oral tablet.
General
The most frequently observed adverse reactions include drowsiness lightheadedness, dizziness, sedation, shortness of breath, nausea, vomiting, sweating, and constipation.[Ref]
Respiratory
Respiratory depression resulting in death has been reported in children who received codeine postoperatively following tonsillectomy and/or adenoidectomy. These children had evidence of being ultra-rapid metabolizers of codeine. Death has also been reported in nursing infants exposed to high levels of morphine in breast milk due to their breastfeeding mother being an ultra-rapid metabolizer of codeine.[Ref]
Uncommon (0.1% to 1%): Bronchospasm, laryngospasm, respiratory depression
Frequency not reported: Respiratory arrest, dyspnea
Postmarketing reports: Deaths due to respiratory depression[Ref]
Cardiovascular
Uncommon (0.1% to 1%): Heartbeat irregularities, blood pressure changes, syncope
Frequency not reported: Flushing, hypotension, palpitations, circulatory depression, shock, cardiac arrest, circulatory depression, bradycardia, tachycardia, edema[Ref]
Nervous system
Common (1% to 10%): Drowsiness, dizziness
Uncommon (0.1% to 1%): Headache, lightheadedness, feeling faint, paradoxical CNS stimulation (especially in children), disorientation, restlessness, shakiness, somnolence, weakness
Frequency not reported: Seizures[Ref]
Other
Frequency not reported: Fatigue, vertigo, malaise, hypothermia, fever, addiction, tolerance, dependence, withdrawal reactions upon discontinuation of chronically administered drug included diarrhea, sweating, vomiting, insomnia, agitation, tremor, body aches, gooseflesh, loss of appetite, nervousness or restlessness, runny nose, sneezing, shivering, stomach cramps, nausea, sleep disturbances, yawning, weakness, tachycardia, fever, irritability, mydriasis[Ref]
Hypersensitivity
Uncommon (0.1% to 1%): Itching, facial swelling, pruritus, urticaria, histamine release (hypotension, sweating, flushing of the face, tachycardia, breathlessness)
Frequency not reported: Allergic reactions including maculopapular rash[Ref]
Gastrointestinal
Common (1% to 10%): Constipation
Uncommon (0.1% to 1%): Dry mouth, loss of appetite, nausea, vomiting, paralytic ileus, toxic megacolon, anorexia, stomach cramps
Frequency not reported: Gastrointestinal distress, anorexia, diarrhea, pancreatitis[Ref]
Hepatic
Frequency not reported: Biliary spasm[Ref]
Genitourinary
Uncommon (0.1% to 1%): Urinary retention or hesitance, ureteric spasm, reduced libido and/or potency[Ref]
Dermatologic
Uncommon (0.1% to 1%): Rash
Frequency not reported: Sweating, urticaria, pruritus[Ref]
Ocular
Uncommon (0.1% to 1%): Miosis, blurred or double vision
Frequency not reported: Visual disturbances[Ref]
Endocrine
Uncommon (0.1% to 1%): Antidiuretic effect
Frequency not reported: Decreased libido or potency, erectile dysfunction, sexual dysfunction[Ref]
Psychiatric
Uncommon (0.1% to 1%): Euphoria, dysphoria, unusual dreams, hallucinations, insomnia, anxiety
Frequency not reported: Mood changes, restlessness, confusion, mental depression[Ref]
Metabolic
Frequency not reported: Hyperglycemia, anorexia[Ref]
