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Codeine Sulfate Generic Name & Formulations
Legal Class
General Description
Pharmacological Class
How Supplied
Contact supplier
Manufacturer
Mechanism of Action
Codeine sulfate is an opioid agonist relatively selective for the mu-opioid receptor, but with a much weaker affinity than morphine. The analgesic properties of codeine have been speculated to come from its conversion to morphine, although the exact mechanism of analgesic action remains unknown.
Codeine Sulfate Indications
Indications
Management of mild to moderate pain, where treatment with an opioid is appropriate and for which alternative treatments are inadequate.
Limitations of Use
Due to risks of addiction, abuse, and misuse with opioids (can occur at any dosage or duration), reserve for use in patients for whom alternative treatment options (eg, non-opioid analgesics, opioid combination products) are not tolerated or inadequate to provide analgesia. Should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate.
Codeine Sulfate Dosage and Administration
Adult
Use lowest effective dose for shortest duration. Swallow whole. Individualize. Initially 15–60mg every 4hrs as needed (max 60mg per dose or 360mg per day). Withdraw gradually (esp. if opioid-dependent), taper by ≤10–25% every 2–4 weeks.
Children
Not established.
Codeine Sulfate Contraindications
Contraindications
Children <12yrs. Post-op management in children <18yrs following tonsillectomy and/or adenoidectomy. Significant respiratory depression. Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment. Known or suspected GI obstruction, including paralytic ileus. During or within 14 days of MAOIs.
Codeine Sulfate Boxed Warnings
Boxed Warning
Serious and life-threatening risks from use of Codeine Sulfate tablets: Addiction, abuse, and misuse; Life-threatening respiratory depression; Accidental ingestion; Risks from concomitant use with benzodiazepines or other CNS depressants; Neonatal opioid withdrawal syndrome; Opioid analgesic risk evaluation and mitigation strategy (REMS); Ultra-rapid metabolism of codeine and other risk factors for life-threatening respiratory depression in children; Interactions with drugs affecting cytochrome P450 isoenzymes.
Codeine Sulfate Warnings/Precautions
Warnings/Precautions
Assess the potential need for access to naloxone when initiating and renewing therapy. Consider prescribing naloxone based on risk factors for overdose (eg, history of opioid use disorder, prior opioid overdose, household members or other close contacts at risk for accidental ingestion or overdose). Abuse potential (monitor). Life-threatening respiratory depression esp. during initiation or following dose increases. Accidental exposure may cause fatal overdose (esp. in children). Sleep-related breathing disorders (including central sleep apnea [CSA], sleep-related hypoxemia); consider dose reduction if CSA develops. Avoid in adolescents 12–18yrs with conditions associated with hypoventilation (eg, post-op status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, concomitant drugs that cause respiratory depression). Opioid-induced hyperalgesia (OIH) and allodynia; consider reducing current opioid analgesic dose or rotating opioid if OIH is suspected. COPD, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression; monitor and consider non-opioid analgesics. Adrenal insufficiency. Monitor for signs of hypotension when initiating or titrating dose. Head injury. Increased intracranial pressure, brain tumors; monitor. Seizure disorders. CNS depression. Impaired consciousness, coma, shock; avoid. Biliary tract disease. Acute pancreatitis. Ultra-rapid metabolizers (due to CYP2D6 polymorphism): avoid. Reevaluate periodically. Avoid abrupt cessation. Hepatic or renal impairment: reduce dose. Drug abusers. Elderly. Cachectic. Debilitated. Pregnancy; potential neonatal opioid withdrawal syndrome during prolonged use. Labor & delivery, nursing mothers: not recommended.
Codeine Sulfate Pharmacokinetics
Absorption
Absorbed from the gastrointestinal tract with maximum plasma concentration occurring 60 minutes post administration.
Distribution
Volume of distribution: ~3–6 L/kg. Plasma protein bound: ~7–25%.
Elimination
Renal (90%). Half-life: ~3 hours.
Codeine Sulfate Interactions
Interactions
See Contraindications. Increased risk of hypotension, respiratory depression, sedation with benzodiazepines or other CNS depressants (eg, non-benzodiazepine sedatives/hypnotics, anxiolytics, general anesthetics, tranquilizers, muscle relaxants, antipsychotics, alcohol, other opioids); reserve concomitant use in those for whom alternative options are inadequate; limit dosages/durations to minimum required; monitor closely; consider prescribing naloxone if concomitant use is warranted. Risk of serotonin syndrome with serotonergic drugs (eg, SSRIs, SNRIs, TCAs, triptans, 5-HT3 antagonists, mirtazapine, trazodone, tramadol, cyclobenzaprine, metaxalone, MAOIs, linezolid, IV methylene blue); monitor and discontinue if suspected. Avoid concomitant mixed agonist/antagonist opioids (eg, butorphanol, nalbuphine, pentazocine) or partial agonist (eg, buprenorphine); may reduce effects and/or precipitate withdrawal symptoms. Potentiated by CYP3A4 inhibitors (eg, macrolides, azole antifungals, protease inhibitors). Antagonized by CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin). May be affected by CYP2D6 inhibitors (eg, amiodarone, paroxetine, fluoxetine, bupropion, quinidine). May antagonize diuretics; monitor. Paralytic ileus may occur with anticholinergics. May increase serum amylase.
Codeine Sulfate Adverse Reactions
Adverse Reactions
Drowsiness, lightheadedness, dizziness, sedation, shortness of breath, nausea, vomiting, sweating; respiratory depression, orthostatic hypotension, syncope, OIH and allodynia.
Codeine Sulfate Clinical Trials
See Literature
Codeine Sulfate Note
Not Applicable
Codeine Sulfate Patient Counseling
See Literature
