Do not abruptly discontinue codeine sulfate tablets in a physically dependent patient because rapid discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. Tablets: 15 mg, 30 mg, and 60 mg 3. Significant respiratory depression. Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment.
Known or suspected gastrointestinal obstruction, including paralytic ileus. Hypersensitivity to codeine. Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. Severe Hypotension : Monitor during dosage initiation and titration. Avoid use of codeine sulfate tablets in patients with circulatory shock. Avoid use of codeine sulfate tablets in patients with impaired consciousness or coma.
The most common adverse reactions include: drowsiness, lightheadedness, dizziness, sedation, shortness of breath, nausea, vomiting, and sweating. Pregnancy: May cause fetal harm. Lactation: Breastfeeding not recommended. Addiction, Abuse, and Misuse Codeine sulfate tablets expose patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers.
Healthcare providers are strongly encouraged to:. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of codeine sulfate tablets. Monitor for respiratory depression, especially during initiation of codeine sulfate tablets or following a dose increase [see Warnings and Precautions 5.
Accidental Ingestion Accidental ingestion of even one dose of codeine sulfate tablets, especially by children, can result in a fatal overdose of codeine [see Warnings and Precautions 5. Avoid the use of codeine sulfate tablets in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of codeine.
Neonatal Opioid Withdrawal Syndrome Prolonged use of codeine sulfate tablets during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [ see Warnings and Precautions 5.
Interactions with Drugs Affecting Cytochrome P Isoenzymes The effects of concomitant use or discontinuation of cytochrome P 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex. Use of cytochrome P 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine sulfate tablets requires careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine. Reserve concomitant prescribing of codeine sulfate tablets and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
Follow patients for signs and symptoms of respiratory depression and sedation. Codeine sulfate tablets are indicated for the management of mild to moderate pain, where treatment with an opioid is appropriate and for which alternative treatments are inadequate. Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses [ s ee Warnings and Precautions 5.
Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions 5 ]. Initiate the dosing regimen for each patient individually, taking into account the patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions 5.
Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and following dosage increases with codeine sulfate tablets and adjust the dosage accordingly [ see Warnings and Precautions 5. Initiate treatment with codeine sulfate tablets in a dosing range of 15 to 60 mg every 4 hours as needed for pain. Adult doses of codeine sulfate tablets higher than 60 mg provide no further efficacy but are associated with greater adverse reactions.
The maximum 24 hour dose is mg. There is inter-patient variability in the potency of opioid drugs and opioid formulations. Therefore, a conservative approach is advised when determining the total daily dosage of codeine sulfate tablets.
Individually titrate codeine sulfate tablets to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving codeine sulfate to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse [see Warnings and Precautions 5. If the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing the codeine sulfate tablets dosage.
If unacceptable opioid-related adverse reactions are observed, consider reducing the dosage. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions. Do not abruptly discontinue codeine sulfate tablets in patients who may be physically dependent on opioids. Rapid discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide.
Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. Patients may also attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances. When a decision has been made to decrease the dose or discontinue therapy in an opioid-dependent patient taking codeine sulfate tablets, there are a variety of factors that should be considered, including the dose of codeine sulfate tablets the patient has been taking, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient.
It is important to ensure ongoing care of the patient and to agree on an appropriate tapering schedule and follow-up plan so that patient and provider goals and expectations are clear and realistic. When opioid analgesics are being discontinued due to a suspected substance use disorder, evaluate and treat the patient, or refer for evaluation and treatment of the substance use disorder.
Treatment should include evidence-based approaches, such as medication assisted treatment of opioid use disorder. Complex patients with co-morbid pain and substance use disorders may benefit from referral to a specialist. There are no standard opioid tapering schedules that are suitable for all patients. Good clinical practice dictates a patient-specific plan to taper the dose of the opioid gradually.
For patients on codeine sulfate tablets who are physically opioid dependent, initiate the taper by a small enough increment e. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper. It may be necessary to provide the patient with lower dosage strengths to accomplish a successful taper. Reassess the patient frequently to manage pain and withdrawal symptoms, should they emerge.
Common withdrawal symptoms include restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate.
If withdrawal symptoms arise, it may be necessary to pause the taper for a period of time or raise the dose of the opioid analgesic to the previous dose, and then proceed with a slower taper.
In addition, monitor patients for any changes in mood, emergence of suicidal thoughts, or use of other substances. A multimodal approach to pain management may optimize the treatment of chronic pain, as well as assist with the successful tapering of the opioid analgesic [see Warnings and Precautions 5.
Codeine sulfate tablets contain codeine, a Schedule II controlled substance. As an opioid, codeine sulfate tablets exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence 9 ]. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed codeine sulfate tablets. Addiction can occur at recommended dosages and if the drug is misused or abused.
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. The potential for these risks should not, however, prevent the 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 the risks and proper use of codeine sulfate tablets along with intensive monitoring for signs of addiction, abuse, and misuse.
Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing codeine sulfate tablets. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug [ s ee Patient Counseling Information 17 ]. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.
Healthcare providers are strongly encouraged to do all of the following:. The FDA Blueprint can be found at www. Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended.
Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Carbon dioxide CO 2 retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of codeine sulfate tablets, the risk is greatest during the initiation of therapy or following a dosage increase.
Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with and following dosage increases of codeine sulfate tablets.
To reduce the risk of respiratory depression, proper dosing and titration of codeine sulfate tablets are essential [see Dosage and Administration 2. Overestimating the codeine sulfate tablets dosage when converting patients from another opioid product can result in a fatal overdose with the first dose.
Accidental ingestion of even one dose of codeine sulfate tablets, especially by children, can result in respiratory depression and death due to an overdose of codeine. Opioids can cause sleep-related breathing disorders including central sleep apnea CSA and sleep-related hypoxemia.
Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper [see Dosage and Administration 2. Life-threatening respiratory depression and death have occurred in children who received codeine. Codeine is subject to variability in metabolism based upon CYP2D6 genotype described below , which can lead to an increased exposure to the active metabolite morphine.
Based upon post-marketing reports, children younger than 12 years old appear to be more susceptible to the respiratory depressant effects of codeine, particularly if there are risk factors for respiratory depression. Because of the risk of life-threatening respiratory depression and death:. At least one death was reported in a nursing infant who was exposed to high levels of morphine in breast milk because the mother was an ultra-rapid metabolizer of codeine.
Breastfeeding is not recommended during treatment with codeine sulfate tablets [see Use in Specific Populations 8. Some individuals may be ultra-rapid metabolizers because of a specific CYP2D6 genotype e. These individuals convert codeine into its active metabolite, morphine, more rapidly and completely than other people. This rapid conversion results in higher than expected serum morphine levels.
Even at labeled dosage regimens, individuals who are ultra-rapid metabolizers may have life-threatening or fatal respiratory depression or experience signs of overdose such as extreme sleepiness, confusion, or shallow breathing [see Overdosage 10 ].
Therefore, individuals who are ultra-rapid metabolizers should not use codeine sulfate tablets. Prolonged use of codeine sulfate tablets during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly.
Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Use in Specific Populations 8.
The effects of concomitant use or discontinuation of cytochrome P 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex. The concomitant use of codeine sulfate tablets with all cytochrome P 3A4 inhibitors, such as macrolide antibiotics e. The concomitant use of codeine sulfate tablets with all cytochrome P 3A4 inducers or discontinuation of a cytochrome P 3A4 inhibitor may result in lower codeine levels, greater norcodeine levels, and less metabolism via 2D6 with resultant lower morphine levels.
This may be associated with a decrease in efficacy, and in some patients, may result in signs and symptoms of opioid withdrawal. Follow patients receiving codeine sulfate tablets and any CYP3A4 inhibitor or inducer for signs and symptoms that may reflect opioid toxicity and opioid withdrawal when codeine sulfate tablets are used in conjunction with inhibitors and inducers of CYP3A4.
If concomitant use of a CYP3A4 inhibitor is necessary or if a CYP3A4 inducer is discontinued, consider dosage reduction of codeine sulfate tablets until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. If concomitant use of a CYP3A4 inducer is necessary or if a CYP3A4 inhibitor is discontinued, consider increasing the codeine sulfate tablets dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal [ Dr ug Interactions 7 ].
Discontinuation of a concomitantly used cytochrome P 2D6 inhibitor may result in a decrease in codeine plasma concentration and an increase in active metabolite morphine plasma concentration which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression.
Follow patients receiving codeine sulfate tablets and any CYP2D6 inhibitor for signs and symptoms that may reflect opioid toxicity and opioid withdrawal when codeine sulfate tablets are used in conjunction with inhibitors of CYP2D6.
If concomitant use with a CYP2D6 inhibitor is necessary, follow the patient for signs of reduced efficacy or opioid withdrawal and consider increasing the codeine sulfate tablets dosage. After stopping use of a CYP2D6 inhibitor, consider reducing the codeine sulfate tablets dosage and follow the patient for signs and symptoms of respiratory depression or sedation [see Drug Interactions 7 ].
Profound sedation, respiratory depression, coma, and death may result from the concomitant use of codeine sulfate tablets with benzodiazepines or other CNS depressants e. Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics [ s ee Drug Interactions 7 ]. If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use.
In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response.
Follow patients closely for signs and symptoms of respiratory depression and sedation. Advise both patients and caregivers about the risks of respiratory depression and sedation when codeine sulfate tablets are used with benzodiazepines or other CNS depressants including alcohol and illicit drugs. Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined.
Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs [see Drug Interactions 7 , Patient Counseling Information 17 ]. The use of codeine sulfate tablets in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.
P atients with Chronic Pulmonary Disease. Codeine sulfate tablets-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of codeine sulfate tablets [see Warnings and Precautions 5.
E l derly, Cachectic, or Debilitated Patients. Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients [ s ee Warnings and Precautions 5.
Monitor such patients closely, particularly when initiating and titrating codeine sulfate tablets and when codeine sulfate tablets are given concomitantly with other drugs that depress respiration [see Warnings and Precautions 5. Alternatively, consider the use of non-opioid analgesics in these patients. Codeine sulfate tablets should not be used in patients taking MAOIs or within 14 days of stopping such treatment [see Drug Interactions 7 ]. Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.
Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers.
Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency. Codeine sulfate tablets 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.
Monitor these patients for signs of hypotension after initiating or titrating the dosage of codeine sulfate tablets. In patients with circulatory shock, codeine sulfate tablets may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of codeine sulfate tablets in patients with circulatory shock.
In patients who may be susceptible to the intracranial effects of CO 2 retention e. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with codeine sulfate tablets.
Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of codeine sulfate tablets in patients with impaired consciousness or coma. Codeine sulfate tablets are contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.
The codeine in codeine sulfate tablets may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms. The codeine in codeine sulfate tablets may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures.
Monitor patients with a history of seizure disorders for worsened seizure control during codeine sulfate tablets therapy. Do not abruptly discontinue codeine sulfate tablets in a patient physically dependent on opioids. When discontinuing codeine sulfate tablets in a physically-dependent patient, gradually taper the dosage. Rapid tapering of codeine in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain [see Dosage and Administration 2.
Codeine sulfate tablets may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of codeine sulfate tablets and know how they will react to the medication [see Patient Counseling Information 17 ]. The following serious adverse reactions are described, or described in greater detail, in other sections:.
The following adverse reactions associated with the use of codeine were identified in clinical studies or postmarketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Serious adverse reactions associated with codeine were respiratory depression and, to a lesser degree, circulatory depression, respiratory arrest, shock, and cardiac arrest.
The most frequently observed adverse reactions with codeine administration included drowsiness, lightheadedness, dizziness, sedation, shortness of breath, nausea, vomiting, sweating, and constipation. Other adverse reactions included allergic reactions, euphoria, dysphoria, abdominal pain, and pruritis. Other less frequently observed adverse reactions expected from opioid analgesics, including codeine sulfate tablets, include:.
C ardiovascular System : faintness, flushing, hypotension, palpitations, syncope. D i gestive System : abdominal cramps, anorexia, diarrhea, dry mouth, gastrointestinal distress, pancreatitis.
N ervous System : anxiety, drowsiness, fatigue, headache, insomnia, nervousness, shakiness, somnolence, vertigo, visual disturbances, weakness.
Serotonin Syndrome : Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. A drenal Insufficiency : Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.
A naphylaxis : Anaphylaxis has been reported with ingredients contained in codeine sulfate tablets. A ndrogen Deficiency : Cases of androgen deficiency have occurred with chronic use of opioids [see Clinical Pharmacology Table 1 includes clinically significant drug interactions with codeine sulfate tablets. C li n i cal Impact:. The concomitant use of codeine sulfate tablets with CYP3A4 inhibitors, may result in an increase in codeine plasma concentrations with subsequently greater metabolism by cytochrome CYP2D6, resulting in greater morphine levels, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression, particularly when an inhibitor is added after a stable dose of codeine sulfate tablets is achieved [see Warnings and Precautions 5.
After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, it may result in lower codeine levels, greater norcodeine levels, and less metabolism via CYP2D6 with resultant lower morphine levels [see Clinical Pharmacology If concomitant use of CYP3A4 inhibitor is necessary, consider dosage reduction of codeine sulfate tablets until stable drug effects are achieved. If a CYP3A4 inhibitor is discontinued, consider increasing the codeine sulfate tablets dosage until stable drug effects are achieved.
Monitor for signs of opioid withdrawal. Macrolide antibiotics e. CY P 3A4 Inducers. The concomitant use of codeine sulfate tablets and CYP3A4 inducers can result in lower codeine levels, greater norcodeine levels, and less metabolism via 2D6 with resultant lower morphine levels [see Clinical Pharmacology After stopping a CYP3A4 inducer, as the effects of the inducer decline, codeine plasma concentrations may increase with subsequently greater metabolism by cytochrome CYP2D6, resulting in greater morphine levels [see Clinical Pharmacology If concomitant use of a CYP3A4 inducer is necessary, follow the patient for reduced efficacy and signs of opioid withdrawal and consider increasing the codeine sulfate tablets dosage as needed.
If a CYP3A4 inducer is discontinued, consider codeine sulfate tablets dosage reduction and monitor for signs of respiratory depression and sedation at frequent intervals. Codeine is metabolized by CYP2D6 to form morphine.
The concomitant use of codeine sulfate tablets and CYP2D6 inhibitors can increase the plasma concentration of codeine, but can decrease the plasma concentration of active metabolite morphine, which could result in reduced analgesic efficacy or symptoms of opioid withdrawal, particularly when an inhibitor is added after a stable dose of codeine sulfate tablets is achieved [see Clinical Pharmacology After stopping a CYP2D6 inhibitor, as the effects of the inhibitor decline, the codeine plasma concentration will decrease but the active metabolite morphine plasma concentration will increase, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression [see Clinical Pharmacology If concomitant use with a CYP2D6 inhibitor is necessary, or if a CYP2D6 inhibitor is discontinued after concomitant use, consider dosage adjustment of codeine sulfate tablets and monitor patients closely at frequent intervals.
If concomitant use with CYP2D6 inhibitors is necessary, follow the patient for reduced efficacy or signs and symptoms of opioid withdrawal and consider increasing the codeine sulfate tablets as needed.
After stopping use of a CYP2D6 inhibitor, consider reducing the codeine sulfate tablets and monitor the patient for signs and symptoms of respiratory depression or sedation. Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation [see Warnings and Precautions 5. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue codeine sulfate tablets if serotonin syndrome is suspected.
MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity e. Do not use codeine sulfate tablets in patients taking MAOIs or within 14 days of stopping such treatment.
If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of other opioids such as oxycodone, hydrocodone, oxymorphone, or buprenorphine to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. Codeine may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.
D i u retics. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. A n ticholinergic Drugs. Monitor patients for signs of urinary retention or reduced gastric motility when codeine sulfate tablets are used concomitantly with anticholinergic drugs. R i sk Summary. Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions 5.
Available data with codeine sulfate tablets are insufficient to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, codeine administration during organogenesis has been shown to produce delayed ossification in the offspring of mice at 1. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U. C li n i cal Considerations. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn.
Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [ see Warnings and Precautions 5. Labor or Delivery: 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 sulfate tablets are not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate.
Opioid analgesics, including codeine sulfate tablets, can prolong labor through actions which 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 dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. Animal Data: Studies on the reproductive and developmental effects of codeine have been reported in the published literature in hamsters, rats, mice and rabbits.
This dose is 0. Codeine and its active metabolite, morphine, are present in human milk. There are published studies and cases that have reported excessive sedation, respiratory depression, and death in infants exposed to codeine via breast milk.
Women who are ultra-rapid metabolizers of codeine achieve higher than expected serum levels of morphine, potentially leading to higher levels of morphine in breast milk that can be dangerous in their breastfed infants.
In women with normal codeine metabolism normal CYP2D6 activity , the amount of codeine secreted into human milk is low and dose-dependent. There is no information on the effects of codeine on milk production. Because of the potential for serious adverse reactions, including excess sedation, respiratory depression, and death in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with codeine sulfate tablets [see Warnings and Precautions 5.
If infants are exposed to codeine sulfate tablets through breast milk, they should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breastfeeding is stopped. Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible [ s ee Adverse Reactions 6 ].
The safety and effectiveness of codeine sulfate tablets in pediatric patients have not been established. Life-threatening respiratory depression and death have occurred in children who received codeine [see Warnings and Precautions 5. Children with sleep apnea may be particularly sensitive to the respiratory depressant effects of codeine. Codeine sulfate tablets are contraindicated for all children younger than 12 years of age [see Contraindications 4 ]. Avoid the use of codeine sulfate tablets in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of codeine 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 [see Warnings and Precautions 5. Elderly patients aged 65 years or older 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 chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration.
Titrate the dosage of codeine sulfate tablets slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression [see Warnings and Precautions 5. 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. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
No formal studies have been conducted in patients with hepatic impairment so the pharmacokinetics of codeine in this patient population are unknown. Start these patients with a lower than normal dosage of codeine sulfate tablets or with longer dosing intervals and titrate slowly while monitoring for signs of respiratory depression, sedation, and hypotension.
Codeine pharmacokinetics may be altered in patients with renal failure. Clearance may be decreased and the metabolites may accumulate to much higher plasma levels in patients with renal failure as compared to patients with normal renal function. Codeine sulfate tablets contains codeine, a substance with a high potential for abuse similar to other opioids including fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, oxymorphone, and tapentadol.
Codeine sulfate tablets can be abused and is subject to misuse, addiction, and criminal diversion [see Warnings and Precautions 5. All patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carry the risk of addiction even under appropriate medical use. Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal.
Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control. Abuse and addiction are separate and distinct from physical dependence and tolerance. Healthcare providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts.
In addition, abuse of opioids can occur in the absence of true addiction. Codeine sulfate tablets, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised.
Skip any missed dose if it is almost time for your next dose. Do not use two doses at one time. Seek emergency medical attention or call the Poison Help line at A codeine overdose can be fatal, especially in a child or other person using the medicine without a prescription. Overdose can cause severe muscle weakness, cold and clammy skin, pinpoint pupils, very slow breathing, extreme drowsiness, or coma. Avoid driving or hazardous activity until you know how this medicine will affect you.
Dizziness or drowsiness can cause falls, accidents, or severe injuries. Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat. Opioid medicine can slow or stop your breathing, and death may occur. A person caring for you should seek emergency medical attention if you have slow breathing with long pauses, blue colored lips, or if you are hard to wake up.
Seek medical attention right away if you have symptoms of serotonin syndrome, such as: agitation, hallucinations, fever, sweating, shivering, fast heart rate, muscle stiffness, twitching, loss of coordination, nausea, vomiting, or diarrhea.
Serious side effects may be more likely in older adults and those who are overweight, malnourished, or debilitated. Long-term use of opioid medication may affect fertility ability to have children in men or women. It is not known whether opioid effects on fertility are permanent. This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may have breathing problems or withdrawal symptoms if you start or stop taking certain other medicines.
Tell your doctor if you also use an antibiotic, antifungal medication, heart or blood pressure medication, seizure medication, or medicine to treat HIV or hepatitis C. Opioid medication can interact with many other drugs and cause dangerous side effects or death. Be sure your doctor knows if you also use:. This list is not complete. Other drugs may affect codeine, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed here.
Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed. Every effort has been made to ensure that the information provided by Cerner Multum, Inc. Drug information contained herein may be time sensitive.
Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient.
Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects.
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