Codeine

DEA Class; Rx

Common Brand Names; 

Oral opioid agonist
Used for the treatment of mild to moderate pain, where treatment with an opioid is appropriate and for which alternative treatments are inadequate
Metabolism is highly variable and unpredictable; use in patients younger than 12 years is contraindicated

Hypersensitivity to codeine

Significant respiratory depression

Children younger than 12 years

Postoperative pain management in children (<18 years) who have undergone tonsillectomy and/or adenoidectomy

Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment

Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within last 14 days

Known or suspected gastrointestinal obstruction, including paralytic ileus

• Constipation
• Drowsiness
• Hypotension
• Tachycardia or bradycardia
• Confusion
• Dizziness
• False feeling of well-being
• Headache
• Lightheadedness
• Malaise
• Paradoxical CNS stimulation
• Restlessness
• Rash, urticaria
• Anorexia
• Nausea, vomiting
• Xerostomia
• Ureteral spasm, urination decreased
• LFTs increased
• Burning at injection site
• Weakness
• Blurred vision
• Dyspnea
• Histamine release
• Hypotension, with IV use
• Anaphylactoid reaction (rare)
• Seizure, with excessive doses
• Respiratory depression
• Severe hypotension
• Life-threatening respiratory depression
• Neonatal opioid withdrawal syndrome
• Death related to ultra-rapid metabolizers of codeine
• Adrenal insufficiency
• Gastrointestinal adverse reactions
• Seizures
• Euphoria
• Dysphoria
• Abdominal pain
• Pruritus
• Sweating
• Serotonin syndrome
• Anaphylaxis
• Androgen deficiency

Codeine sulfate tablets contain codeine, a schedule II controlled substance; as an opioid, codeine sulfate tablets exposes users to risks of addiction, abuse, and misuse; addiction can occur at recommended dosages and if drug is misused or abused; assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing codeine sulfate tablets, and monitor; risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression); potential for these risks should not prevent proper management of pain in any given patient; patients at increased risk may be prescribed opioids such as codeine sulfate tablets, but use in such patients necessitates intensive counseling about risks and proper use of codeine sulfate along with intensive monitoring for signs of addiction, abuse, and misuse; prescribe the drug in smallest appropriate quantity and advise patient on proper disposal of unused drug

Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia; opioid use increases risk of CSA in a dose-dependent fashion; in patients who present with CSA, consider decreasing opioid dosage using best practices for opioid taper

Therapy may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients; there is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics); monitor patients for signs of hypotension after initiating or titrating dosage; in patients with circulatory shock, therapy may cause vasodilation that can further reduce cardiac output and blood pressure; avoid therapy in patients with circulatory shock

In patients who may be susceptible to intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), therapy may reduce respiratory drive, and resultant CO2 retention can further increase intracranial pressure; monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy; opioids may obscure clinical course in a patient with a head injury; avoid the use in patients with impaired consciousness or coma

Contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus; may cause spasm of sphincter of Oddi; opioids may cause increases in serum amylase; monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms

Pregnancy: Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth; observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly; opioids cross placenta and may produce respiratory depression and psycho-physiologic effects in neonates; an opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate; codeine sulfate is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate; opioid analgesics can prolong labor through actions which temporarily reduce strength, duration, and frequency of uterine contractions

Lactation: Codeine is secreted into human milk; in women with normal codeine metabolism (normal CYP2D6 activity), amount of codeine secreted into human milk is low and dose-dependent; some women are ultra-rapid metabolizers of codeine; these women achieve higher-than-expected serum levels of codeine’s active metabolite, morphine, leading to higher-than-expected levels of morphine in breast milk and potentially dangerously high serum morphine levels in their breastfed infants that can potentially lead to serious adverse reactions, including death, in nursing infants; there is no information on effects of codeine on milk production