Codeine Sulfate (codeine sulfate)

Dosage of codeine sulfate and codeine phosphate is expressed in terms of the salt.

Codeine-containing preparations are administered orally.

Codeine sulfate is commercially available as a single-entity tablet preparation. Codeine phosphate is commercially available in the following fixed-combination preparations for oral use: codeine/acetaminophen, promethazine/codeine, promethazine/phenylephrine/codeine, butalbital/acetaminophen/caffeine/codeine, and butalbital/aspirin/caffeine/codeine. See the full prescribing information for additional information on these combination preparations. Codeine also may be commercially available in over-the-counter (OTC) preparations in combination with antihistamines, expectorants, or decongestants. See the FDA Orange Book and the manufacturer's Drug Facts for additional information.

Codeine sulfate tablets should be stored at 20-25degreesC (excursions permitted between 15-30degreesC) in a secure location; protect from moisture.

No dosing information is available for this tab.

No dosing information is available for this tab.

Codeine is metabolized by cytochrome P-450 (CYP) 2D6 to its active metabolite, morphine. Codeine is also metabolized by CYP3A4 to an inactive metabolite.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Children younger than 12 years of age.

*Postoperative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy.

*Significant respiratory depression.

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

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

*Known or suspected GI obstruction, including paralytic ileus.

*Hypersensitivity to codeine or any components of the formulation.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

The most common adverse reactions reported with codeine sulfate tablets include drowsiness, lightheadedness, dizziness, sedation, shortness of breath, nausea, vomiting, and sweating.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

Safety and effectiveness of codeine have not been established in pediatric patients. Pediatric patients receiving codeine for the management of pain, especially those who are obese, have obstructive sleep apnea or severe lung disease, or have evidence of ultrarapid metabolism of CYP2D6 substrates, are at increased risk of respiratory depression. Serious adverse events, including deaths, have been reported during postmarketing experience in pediatric patients receiving codeine. Between January 1969 and May 2015, the FDA Adverse Event Reporting System (FAERS) received 64 reports of respiratory depression, including 24 reports of death, worldwide that were associated with codeine use in pediatric patients younger than 18 years of age. Ten of the 64 reports provided information about CYP2D6 metabolizer status. Seven of these patients were ultrarapid or extensive metabolizers of CYP2D6 substrates; 5 of which reported death. Most of the cases of respiratory depression, including most of the deaths, occurred in children younger than 12 years of age. Respiratory depression may occur despite therapeutic serum concentrations of codeine or morphine; 1 patient who had concentrations within the therapeutic range died following use of codeine for management of pain after tonsillectomy and adenoidectomy.

Codeine-containing preparations are contraindicated in children younger than 12 years of age and contraindicated for postoperative pain management following tonsillectomy and/or adenoidectomy in pediatric patients younger than 18 years of age. Avoid the use of codeine in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of the drug unless the benefits outweigh the risks. Risk factors include conditions associated with hypoventilation, such as postoperative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression.

Available data with codeine are insufficient to inform a drug-associated risk of major birth defects and miscarriage. In animal studies, embryolethal and fetotoxic effects were observed in animals administered codeine during the period of organogenesis.

Opioids cross the 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 is not recommended for use in women during and immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate. Opioid analgesics, including codeine, can prolong labor through actions that temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilatation, which may shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excessive sedation and respiratory depression.

Use of opioid analgesics for an extended period during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly.

Breastfeeding is not recommended during treatment with codeine, especially in patients who have evidence of ultrarapid metabolism of CYP2D6 substrates. Serious adverse events (e.g., excessive sedation, difficulty nursing, respiratory depression), including death, have been reported in nursing infants exposed to codeine. At least one case of opioid toxicity resulting in neonatal death has been reported in the nursing infant of a woman receiving codeine; genetic testing of the woman indicated that she was an ultrarapid metabolizer of codeine. Higher than expected concentrations of morphine were found in breast milk and in the blood of the infant. Somnolence has been reported more frequently in nursing infants whose mothers received codeine in combination with acetaminophen compared with those whose mothers received acetaminophen alone; evidence of ultrarapid metabolism of CYP2D6 substrates was identified in some of these women. Concentrations of morphine in breast milk are low and dose-dependent in women who are normal metabolizers of codeine. FDA-approved tests (e.g., AmpliChip(R) CYP450 Test) are available to identify an individual's CYP2D6 genotype. Infants exposed to codeine through breast milk should be monitored closely for clinical manifestations of opioid toxicity (e.g., sedation, difficulty breastfeeding or breathing, hypotonia). Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic or breastfeeding is stopped.

In general, select dosage with caution in geriatric patients, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. Titrate dosage of codeine slowly in geriatric patients and frequently re-evaluate the patient for CNS and respiratory depression.

Geriatric patients may have increased sensitivity to codeine. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. Respiratory depression is the main risk for geriatric patients treated with opioids and has occurred after large initial doses in patients who were not opioid-tolerant or when opioids were co-administered with other drugs that depress respiration. Titrate the dosage of codeine slowly in geriatric patients and frequently re-evaluate for signs of CNS and respiratory depression.

Codeine is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Elderly patients are more likely to have decreased renal function; dosing should be selected with care and renal function should be regularly evaluated.