Drug information of codeine

Mechanism of effect

Binds to opioid receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; causes cough suppression by direct central action in the medulla; produces generalized CNS depression

Pharmacodynamic

Codeine, an opiate agonist in the CNS, is similar to other phenanthrene derivatives such as morphine. It is selective for the mu receptor, but with a much weaker affinity than morphine. The analgesic properties of codeine have been speculated to come from its conversion to morphine. The principle therapeutic action is analgesia.

Codeine concentrations do not correlate with brain concentration or relief of pain. The minimum effective concentration is highly variable is influenced by numerous factors, including age, previous opioid use, age, and general medical condition. However, the effective dose for patients that have developed tolerance is significantly higher than the opioid-naive patients.

Pharmacokinetics

Absorption

Onset: 30-60 min (PO); 10-30 min (IM)

Duration: 4-6 hr

Peak plasma time: 0.5-1 hr

Distribution

Protein bound: 25%

Vd: 3.5 L/kg (PO); 2.6 L/kg (IM)

Metabolism

Prodrug metabolized to morphine by CYP2D6; demethylated/conjugated in liver

Elimination

Half-life: 3-4 hr

Excretion: Urine, feces

Drug indications

Restless Legs Syndrome

Dosage

Pain

15-60 mg PO q4-6hr PRN; not to exceed 360 mg/day in naive patients

Cough

7.5-30 mg PO q4-6hr PRN

Drug contraindications

Breast feeding , gastrointestinal tract Obstruction , Hypersensitivity to this drug or components

Side effects

Headache , nausea , dizziness , vomiting , Blurred vision , rash , vertigo , asthenia , urticaria , anorexia , dry skin , oliguria , difficulty urinating , Restlessness , lightheadedness

Interactions

Sodium Oxybate , Tapentadol , rasagiline , Aripiprazole , Alprazolam , Amitriptyline , Iopamidol , Olanzapine , Buspirone , Pentazocine , Hydrocodone , Zaleplon , Meprobamate , Loxapine , Butalbital and Acetaminophen , fentanyl , Quetiapine , methylene blue , propoxyphene , morphine , iohexol (Omnipaque) , Zolpidem , Phenobarbital , Lorazepam , Clobazam , Clozapine , Clonazepam , perphenazine , Primidone , Pimozide , Tramadol , Diazepam , Risperidone , Pindolol , Promazine , Peginterferon alfa-2b , Chloral hydrate , Molindone , Asenapine , Alvimopan , Paraldehyde , Butorphanol , Bendroflumethiazide , Acetaminophen and benzhydrocodone , Difenoxin , pexidartinib , Estazolam , Oxymorphone , Methscopolamine , Ethchlorvynol , Naltrexone and Bupropion , Pasireotide , Gefitinib , nalbuphine , Florbetapir F18

Alerts

• Concerns related to adverse effects:

CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

Constipation: May cause or aggravate constipation; chronic use may result in obstructive bowel disease, particularly in those with underlying intestinal motility disorders. May also be problematic in patients with unstable angina and patients post-myocardial infarction. Consider preventative measures (eg, stool softener, increased fiber) to reduce the potential for constipation.

Hypotension: May cause severe hypotension (including orthostatic hypotension and syncope); use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs that may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Monitor for symptoms of hypotension following initiation or dose titration.

Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone).

Respiratory depression: Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely for respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

• Disease-related concerns:

Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions.

Adrenocortical insufficiency: Use with caution in patients with adrenal insufficiency, including Addison disease. Long-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction, infertility, mood disorders, and osteoporosis.

Biliary tract impairment: Use with caution in patients with biliary tract dysfunction, including acute pancreatitis; may cause constriction of sphincter of Oddi.

CNS depression/coma: Avoid use in patients with impaired consciousness or coma, as these patients are susceptible to effects of CO₂ retention.

Delirium tremens: Use with caution in patients with delirium tremens.

Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure.

Hepatic impairment: Use with caution in patients with severe hepatic impairment.

Mental health conditions: Use opioids with caution for chronic pain in patients with mental health conditions (eg, depression, anxiety disorders, post-traumatic stress disorder) due to increased risk for opioid use disorder and overdose; more frequent monitoring is recommended.

Obesity: Use with caution in patients who are morbidly obese.

Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture.

Renal impairment: Use with caution in patients with renal failure.

Respiratory disease: Use with caution and monitor for respiratory depression in patients with significant COPD and those having a substantially decreased respiratory reserve, or preexisting respiratory depression. Critical respiratory depression may occur, even at therapeutic dosages. Consider the use of alternative nonopioid analgesics in these patients.

Sleep-disordered breathing: Use opioids with caution for chronic pain and titrate dosage cautiously in patients with risk factors for sleep-disordered breathing, including HF and obesity. Avoid opioids in patients with moderate to severe sleep-disordered breathing.

Seizure disorders: Use with caution in patients with a history of seizure disorders; may cause or exacerbate seizures.

Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.

• Concurrent drug therapy issues:

Benzodiazepines or other CNS depressants: Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Limit dosage and durations to the minimum required.

Special populations:

Elderly: Use with caution in the elderly; may be more sensitive to adverse effects. Use opioids for chronic pain with caution in this age group; monitor closely. Clearance may also be reduced in older adults (with or without renal impairment).

Neonates: Neonatal withdrawal syndrome: Prolonged use during pregnancy can cause neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated according to protocols developed by neonatology experts. Signs and symptoms include irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, and failure to gain weight.

Pediatric: Life-threatening respiratory depression and death have occurred in children who received codeine. Most of the reported cases occurred following tonsillectomy and/or adenoidectomy. Avoid the use of codeine in pediatric patients 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of codeine. Risk factors include conditions associated with hypoventilation, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression.

Points of recommendation

Patient should not use codeine if have severe breathing problems, a blockage in their stomach or intestines, or frequent asthma attacks.

Codeine can slow or stop breathing. MISUSE OF THIS MEDICINE CAN CAUSE ADDICTION, OVERDOSE, OR DEATH, especially in a child or other person using the medicine without a prescription.

This medicine is not for use in children younger than 12 years old, and is not for use in anyone under 18 who recently had surgery to remove their tonsils or adenoids.

Taking this medicine during pregnancy may cause life-threatening withdrawal symptoms in the newborn.

Pregnancy level

C

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 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.

Breast feeding warning

 Codeine is secreted into human milk; there is no information on effects of codeine on milk production.

Related drugs

Dextromethorphan , fentanyl , Buprenorphine , Tapentadol , Tramadol , Levorphanol , morphine , Hydrocodone , hydromorphone , Pentazocine , Butorphanol , nalbuphine