Physicians should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence.

The converse is also true. In addition, abuse of opioids can occur in the absence of true addiction and is characterized by misuse for nonmedical purposes, often in combination with other psychoactive substances. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests is strongly advised. Codeine is intended for oral use only.

Abuse of codeine poses a risk of overdose and death. The risk is increased with concurrent abuse of alcohol and other substances. Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.

Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs. Dependence Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia in the absence of disease progression or other external factors. Physical dependence is manifested by withdrawal symptoms after abrupt discontinuation of a drug or upon administration of an antagonist.

Physical dependence and tolerance are not unusual during chronic opioid therapy. The opioid abstinence or withdrawal syndrome is characterized by some or all of the following: Other 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.

Deaths have also occurred in nursing infants who were exposed to high levels of morphine in breast milk because their mothers were ultra-rapid metabolizers of codeine [see Use in Specific Populations]. The prevalence of this CYP2D6 phenotype varies widely and has been estimated at 0. Data are not available for other ethnic groups. 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. Respiratory Depression Respiratory depression is the primary risk of codeine sulfate. Respiratory depression occurs more frequently in elderly or debilitated patients and in those suffering from conditions accompanied by hypoxia , hypercapnia , or upper airway obstruction , in whom even moderate therapeutic doses may significantly decrease pulmonary ventilation.

Codeine produces dose-related respiratory depression. Caution should be exercised when codeine sulfate is used postoperatively, in patients with pulmonary disease or shortness of breath, or whenever ventilatory function is depressed. Opioid related respiratory depression occurs more frequently in elderly or debilitated patients and in those suffering from conditions accompanied by hypoxia, hypercapnia, or upper airway obstruction, in whom even moderate therapeutic doses may significantly decrease pulmonary ventilation.

Opioids, including codeine sulfate, should be used with extreme caution in patients with chronic obstructive pulmonary disease or cor pulmonale and in patients having a substantially decreased respiratory reserve e. In such patients, even usual therapeutic doses of codeine sulfate may increase airway resistance and decrease respiratory drive to the point of apnea.

Such drugs are sought by drug abusers and people with addiction disorders. Diversion of Schedule II products is an act subject to criminal penalty. Codeine can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing codeine sulfate in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion. Misuse and abuse of codeine sulfate poses a significant risk to the abuser that could result in overdose and death.

Codeine may be abused by crushing, chewing, snorting or injecting the product [see Drug Abuse and Dependence ].

Concerns about abuse and addiction should not prevent the proper management of pain. Healthcare professionals should contact their State Professional Licensing Board or State Controlled Substances Authority for information on how to prevent and detect abuse or diversion of this product.

Interaction With Alcohol And Drugs Of Abuse Codeine sulfate may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression, because respiratory depression, hypotension , profound sedation, coma or death may result. Head Injury And Increased Intracranial Pressure Respiratory depressant effects of opioids and their capacity to elevate cerebrospinal fluid pressure resulting from vasodilation following CO2 retention may be markedly exaggerated in the presence of head injury, other intracranial lesions or a pre-existing increase in intracranial pressure.

Furthermore, opioids including codeine sulfate, produce adverse reactions which may obscure the clinical course of patients with head injuries. Hypotensive Effect Codeine sulfate may cause severe hypotension in an individual whose ability to maintain blood pressure has already been compromised by a depleted blood volume or concurrent administration of drugs such as phenothiazines or general anesthetics.

Codeine sulfate may produce orthostatic hypotension and syncope in ambulatory patients. If fosamprenavir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Fosamprenavir is a strong inhibitor of CYP3A4. Moderate Concomitant use of codeine with fosphenytoin can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.

If fosphenytoin is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Phenytoin, the active metabolite of fosphenytoin, is a strong CYP3A4 inducer.

Moderate Monitor for codeine toxicities that may require codeine dose reduction if given concurrently with fostamatinib. Moderate Pain medications that contain opiate agonists may intensify CNS depressive adverse effects seen with gabapentin use, such as drowsiness or dizziness. Patients should limit activity until they are aware of how coadministration affects them. Moderate Monitor for decreased efficacy of codeine if gefitinib and codeine are used concomitantly.

At high concentrations, gefitinib is an inhibitor of CYP2D6, which is partially responsible for the metabolism of codeine to morphine. Moderate Patients should not significantly alter their intake of grapefruit or grapefruit juice during therapy with codeine. This may increase or prolong codeine-related toxicities including respiratory depression. Advise patients accordingly; patient monitoring and dosage adjustments may be necessary if grapefruit is consumed regularly. Moderate Guanabenz is associated with sedative effects.

Guanabenz can potentiate the effects of CNS depressants such as opiate agonists, when administered concomitantly. Moderate Central-acting adrenergic agonists like guanfacine have CNS depressive effects and can potentiate the actions of other CNS depressants including opiate agonists. Moderate Concomitant use of codeine with haloperidol may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal.

Discontinuation of haloperidol could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death.

If haloperidol is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Haloperidol is a moderate inhibitor of CYP2D6. Minor Hydantoin anticonvulsants induce hepatic microsomal enzymes and may increase the metabolism of other drugs, leading to reduced efficacy of medications like acetaminophen.

In addition, the risk of hepatotoxicity from acetaminophen may be increased with the chronic dosing of acetaminophen along with phenytoin. Adhere to recommended acetaminophen dosage limits. Acetaminophen-related hepatotoxicity has occurred clinically with the concurrent use of acetaminophen mg to mg daily and phenytoin.

Acetaminophen cessation led to serum transaminase normalization within 2 weeks. Moderate Methyldopa is associated with sedative effects. Methyldopa can potentiate the effects of CNS depressants, such as opiate agonists, when administered concomitantly. Moderate Opiate agonists like codeine may potentiate orthostatic hypotension when given concomitantly with spironolactone.

Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: Major Concomitant use of hydromorphone with other central nervous system CNS depressants, such as other opiate agonists, can potentiate the effects of hydromorphone and may lead to additive CNS or respiratory depression, profound sedation, or coma.

Prior to concurrent use of hydromorphone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment.

Moderate Concomitant use of codeine with hydroxychloroquine may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. Discontinuation of hydroxychloroquine could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death.

If hydroxychloroquine is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Hydroxychloroquine is a moderate inhibitor of CYP2D6. Moderate In vitro studies indicate that hydroxyprogesterone increases the metabolic rate of CYP2A6 isoenzymes.

The metabolism of drugs metabolized by CYP2A6, such as acetaminophen may be increased during treatment with hydroxyprogesterone. Moderate Concomitant use of codeine with idelalisib may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death.

Discontinuation of idelalisib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If idelalisib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Idelalisib is a strong inhibitor of CYP3A4. Moderate Concomitant use of iloperidone with other centrally-acting medications such as opiate agonists, may increase both the frequency and the intensity of adverse effects including drowsiness, sedation, and dizziness.

Major Imatinib, STI may affect the metabolism of acetaminophen. In vitro, imatinib was found to inhibit acetaminophen O-glucuronidation at therapeutic levels. Therefore, systemic exposure to acetaminophen is expected to be increased with coadministration of imatinib.

Chronic acetaminophen therapy should be avoided in patients receiving imatinib. Moderate Concomitant use of codeine with imatinib may alter codeine plasma concentrations, resulting in an unpredictable effect such as reduced efficacy or symptoms of opioid withdrawal or prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death.

Discontinuation of imatinib could alter codeine plasma concentrations, resulting in an unpredictable effect such as prolonged opioid adverse reactions or decreased opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine.

If imatinib is discontinued, monitor the patient carefully and consider adjusting the opioid dosage if appropriate. Moderate Concomitant use of codeine with indinavir may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. Discontinuation of indinavir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine.

If indinavir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Indinavir is a strong inhibitor of CYP3A4.

Acetaminophen AUC, Cmax, and Tmax were not significantly changed when acetaminophen was given 1 h before lixisenatide injection. The mechanism of this interaction is not available although it may be due to delayed gastric emptying and the clinical impact has not been assessed. To avoid potential pharmacokinetic interactions that might alter effectiveness of acetaminophen, it may be advisable for patients to take acetaminophen at least one hour prior to lixisenatide subcutaneous injection.

Moderate Concomitant use of codeine with isavuconazonium may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. Discontinuation of isavuconazonium could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine.

If isavuconazonium is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Isavuconazonium is a moderate inhibitor of CYP3A4. Moderate Concomitant use of isavuconazonium with acetaminophen may result in increased serum concentrations of acetaminophen.

Acetaminophen is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together. Severe Codeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors MAOIs within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression.

Major Agents which induce the hepatic isoenzyme CYP2E1, such as isoniazid, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites. The combination of isoniazid and acetaminophen has caused severe hepatotoxicity in at least one patient; studies in rats have demonstrated that pre-treatment with isoniazid potentiates acetaminophen hepatotoxicity.

Moderate Concomitant use of codeine with isoniazid may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death.

Discontinuation of isoniazid could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If isoniazid is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate.

Isoniazid is a moderate inhibitor of CYP3A4. Moderate Agents which induce the hepatic isoenzymes CYP2E1 and CYP1A2, such as rifampin, may potentially increase the risk for acetaminophen-induced hepatotoxicity via generation of a greater percentage of acetaminophen's hepatotoxic metabolites.

Moderate Concomitant use of codeine with rifampin can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If rifampin is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation.

Rifampin is a strong CYP3A4 inducer. Moderate Concomitant use of codeine with itraconazole may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death.

Discontinuation of itraconazole could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If itraconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Itraconazole is a strong inhibitor of CYP3A4. Moderate Concomitant use of codeine with ketoconazole may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death.

Discontinuation of ketoconazole could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If ketoconazole is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Ketoconazole is a strong inhibitor of CYP3A4. Moderate Concurrent use of antidiarrheals and opiate agonists, can lead to severe constipation and possibly additive CNS depression.

Major Acetaminophen can be hepatotoxic, and lamotrigine appears to be a potential cause of progressive and fatal hepatotoxicity despite drug discontinuation. A 35 year-old developed fulminant liver failure possibly caused by lamotrigine. She was taking several other drugs including acetaminophen. Minor The manufacturer recommends that oral compounds known to interact with antacids, such as acetaminophen, should not be taken within 2 hours of dosing with lanthanum carbonate.

Moderate Concomitant use of codeine with letermovir may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death.

Discontinuation of letermovir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If letermovir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Letermovir is a moderate inhibitor of CYP3A4.

Major Because of the potential risk and severity of serotonin syndrome, caution and careful monitoring are recommended when administering serotonin norepinephrine reuptake inhibitors SNRIs , such as levomilnacipran, with other drugs that have serotonergic properties such as codeine. Codeine and levomilnacipran should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.

Moderate Lincosamides, which have been shown to exhibit neuromuscular blocking action, can enhance the effects of opiate agonists if used concomitantly, enhancing respiratory depressant effects. They should be used together with caution and the patient carefully monitored. Linezolid is a reversible, non-selective inhibitor of MAO. Moderate Monitor for excessive hypotension and sedation during coadministration of lofexidine and codeine.

Lofexidine can potentiate the effects of CNS depressants. The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.

Concurrent use of selected antidiarrheals e. Moderate Concomitant use of codeine with lopinavir; ritonavir may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death.

Discontinuation of lopinavir; ritonavir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If lopinavir; ritonavir is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Lopinavir; ritonavir is a strong inhibitor of CYP3A4.

Moderate Loxapine can potentiate the actions of other CNS depressants such as opiate agonists. Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.

Moderate Concomitant use of codeine with lumacaftor; ivacaftor can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If lumacaftor; ivacaftor is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation.

Lumacaftor; ivacaftor is a strong CYP3A4 inducer. Moderate Due to the CNS effects of lurasidone, caution should be used when lurasidone is given in combination with other centrally acting medications such as opiate agonists.

Minor Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as opiate agonists. Caution should be exercised when using these agents concurrently. Moderate Concomitant use of codeine with other central nervous system CNS depressants, such as maprotiline, can potentiate the effects of codeine and may lead to additive CNS or respiratory depression, profound sedation, or coma.

Moderate Concomitant use of meprobamate with codeine can potentiate the effects of codeine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. Major Concomitant use of methadone with another CNS depressant can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of methadone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment.

Methadone should be used with caution and in reduced dosages if used concurrently with a CNS depressant; also consider a using a lower dose of the CNS depressant. Moderate Opiate agonists antagonize GI motility and can decrease the gastroprokinetic effects of metoclopramide. Major Coadministration of metyrapone and acetaminophen may result in acetaminophen toxicity. Acetaminophen glucuronidation is inhibited by metyrapone. It may be advisable for patients to avoid acetaminophen while taking metyrapone.

Other drugs that may also cause drowsiness, such as opiate agonists, should be used with caution. Moderate The concomitant administration of metyrosine with opiate agonists can result in additive sedative effects. Moderate Concomitant use of codeine with chronic mifepristone therapy may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death.

Discontinuation of mifepristone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Mifepristone is a strong inhibitor of CYP3A4. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.

Major Because of the potential risk and severity of serotonin syndrome, caution and careful monitoring are recommended when administering serotonin norepinephrine reuptake inhibitors SNRIs , such as milnacipran, with other drugs that have serotonergic properties such as codeine. Codeine and milnacipran should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated. Minor Injectable minocycline contains magnesium sulfate heptahydrate. Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as opiate agonists.

The effect of concomitant administration of mipomersen with other hepatotoxic medications is unknown. Moderate Concomitant use of codeine with mirabegron may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal.

Discontinuation of mirabegron could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death.

If mirabegron is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. The regular use of this medication may aid in the management of chronic pain or acute, severe pain typically experienced after a medical procedure allowing the patient to continue activities of daily life. While this medication helps manage pain, it does not cure the underlying cause of pain in the body.

This can lead to a dependence on acetaminophen with codeine for chronic pain due to the recurrence of pain once the dose is excreted from the body. Common side effects of taking this medication are sweating, nausea, vomiting, and dizziness or fatigue. To prevent nausea, the patient can plan to take the medication after meals to ease the effects on the gastrointestinal tract.

If the patient experiences dizziness or fatigue, he or she may take caution to taking doses at times when cognition is not required, such as before bedtime. A more serious, but rare side effects of acetaminophen with codeine is serotonin syndrome, which is characterized by agitation, increased reflexes and an increase in body temperature. Carbon dioxide CO2 retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

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 of age 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: Risk factors include conditions associated with hypoventilation, such as post-operative status, obstructive sleep apnea, obesity, severe pulmonary disease, neuromuscular disease, and concomitant use of other medications that cause respiratory depression see WARNINGS.

Nursing Mothers 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. 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.

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. This may be associated with a decrease in efficacy, and in some patients, may result in signs and symptoms of opioid withdrawal. Monitor patients for respiratory depression and sedation at frequent intervals.

Discontinuation of a concomitantly used CYP2D6 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. Hepatotoxicity Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death.

Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4, milligrams per day, and often involve more than one acetaminophen-containing product. The excessive intake of acetaminophen may be intentional to cause self-harm or unintentional as patients attempt to obtain more pain relief or unknowingly take other acetaminophen-containing products.

The risk of acute liver failure is higher in individuals with underlying liver disease and in individuals who ingest alcohol while taking acetaminophen. Instruct patients to look for acetaminophen or APAP on package labels and not to use more than one product that contains acetaminophen. Instruct patients to seek medical attention immediately upon ingestion of more than 4, milligrams of acetaminophen per day, even if they feel well.

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.

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 patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Elderly, 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, including clearance, compared to younger, healthier patients see WARNINGS; Life-Threatening Respiratory Depression.

Alternatively, consider the use of non-opioid analgesics in these patients. Interaction with Monoamine Oxidase Inhibitors Monoamine oxidase inhibitors MAOIs may potentiate the effects of morphine, codeine's active metabolite, including respiratory depression, coma, and confusion.

Adrenal Insufficiency Cases of adrenal insufficiency have been reported with opioid use, more often following greater than 1 month of use. Approved, Investigational, Vet Approved The risk or severity of adverse effects can be increased when Codeine is combined with Entacapone. Approved, Investigational The serum concentration of Codeine can be decreased when it is combined with Enzalutamide. Approved The risk or severity of adverse effects can be increased when Codeine is combined with Epitizide.

Experimental The risk or severity of adverse effects can be increased when Codeine is combined with Eplerenone. Approved The metabolism of Codeine can be decreased when combined with Erythromycin.

Approved, Investigational, Vet Approved Codeine may increase the serotonergic activities of Escitalopram. Approved, Investigational The risk or severity of adverse effects can be increased when Codeine is combined with Estazolam. Approved, Illicit The risk or severity of adverse effects can be increased when Codeine is combined with Eszopiclone. Approved, Investigational The risk or severity of adverse effects can be increased when Codeine is combined with Etacrynic acid.

Approved, Investigational Etanautine The risk or severity of adverse effects can be increased when Etanautine is combined with Codeine. Experimental Codeine may increase the central nervous system depressant CNS depressant activities of Ethanol. Approved The risk or severity of adverse effects can be increased when Codeine is combined with Ethchlorvynol. Approved, Illicit, Withdrawn The risk or severity of adverse effects can be increased when Ethopropazine is combined with Codeine.

Approved The risk or severity of adverse effects can be increased when Codeine is combined with Ethosuximide. Approved The risk or severity of adverse effects can be increased when Codeine is combined with Ethotoin. Approved The risk or severity of adverse effects can be increased when Codeine is combined with Ethoxzolamide. Withdrawn The risk or severity of adverse effects can be increased when Codeine is combined with Ethyl carbamate.

Withdrawn The risk or severity of adverse effects can be increased when Codeine is combined with Ethyl chloride. Approved, Experimental, Investigational The risk or severity of adverse effects can be increased when Codeine is combined with Ethyl loflazepate.

Approved, Illicit The risk or severity of adverse effects can be increased when Codeine is combined with Ethylmorphine. Approved, Illicit The risk or severity of adverse effects can be increased when Codeine is combined with Etidocaine. Approved The risk or severity of adverse effects can be increased when Codeine is combined with Etifoxine. Investigational, Withdrawn The risk or severity of adverse effects can be increased when Codeine is combined with Etizolam.

Approved The risk or severity of adverse effects can be increased when Codeine is combined with Etomidate. Approved Codeine may increase the serotonergic activities of Etoperidone. Withdrawn The risk or severity of adverse effects can be increased when Codeine is combined with Etorphine.

Illicit, Vet Approved Etybenzatropine The risk or severity of adverse effects can be increased when Etybenzatropine is combined with Codeine.

Experimental The risk or severity of adverse effects can be increased when Codeine is combined with Ezogabine. Approved, Investigational The risk or severity of adverse effects can be increased when Codeine is combined with Felbamate. Approved The risk or severity of adverse effects can be increased when Codeine is combined with Fencamfamine. Approved, Illicit, Withdrawn Fenquizone The risk or severity of adverse effects can be increased when Codeine is combined with Fenquizone.

Experimental The risk or severity of adverse effects can be increased when Codeine is combined with Fentanyl. Approved, Illicit, Investigational, Vet Approved The serum concentration of the active metabolites of Fesoterodine can be increased when Fesoterodine is used in combination with Codeine. Approved The risk or severity of adverse effects can be increased when Codeine is combined with Fexofenadine.

Approved, Investigational The risk or severity of adverse effects can be increased when Flavoxate is combined with Codeine. Approved The risk or severity of adverse effects can be increased when Codeine is combined with Flibanserin. Approved, Investigational Fluanisone The risk or severity of adverse effects can be increased when Codeine is combined with Fluanisone.

Experimental The metabolism of Codeine can be decreased when combined with Fluconazole. Approved, Investigational The risk or severity of adverse effects can be increased when Codeine is combined with Fludiazepam. Approved, Illicit The risk or severity of adverse effects can be increased when Codeine is combined with Flunarizine. Approved The risk or severity of adverse effects can be increased when Codeine is combined with Flunitrazepam.

Approved, Illicit The therapeutic efficacy of Codeine can be decreased when used in combination with Fluoxetine. Approved, Vet Approved The risk or severity of adverse effects can be increased when Codeine is combined with Flupentixol. Approved, Investigational, Withdrawn The risk or severity of adverse effects can be increased when Codeine is combined with Fluphenazine.

Approved The risk or severity of adverse effects can be increased when Codeine is combined with Flurazepam. Approved, Illicit, Investigational The risk or severity of adverse effects can be increased when Codeine is combined with Fluspirilene. Approved, Investigational The risk or severity of adverse effects can be increased when Codeine is combined with Fluticasone propionate. Approved The therapeutic efficacy of Codeine can be decreased when used in combination with Fluvoxamine.

Approved, Investigational The metabolism of Codeine can be decreased when combined with Fosamprenavir. Approved The serum concentration of Codeine can be increased when it is combined with Fosaprepitant. Approved The metabolism of Codeine can be increased when combined with Fosphenytoin. Approved, Investigational The risk or severity of adverse effects can be increased when Codeine is combined with Fospropofol.

Approved, Illicit, Investigational The risk or severity of adverse effects can be increased when Codeine is combined with Furazolidone.

Approved, Investigational, Vet Approved The risk or severity of adverse effects can be increased when Codeine is combined with Furosemide. Approved, Investigational The risk or severity of adverse effects can be increased when Codeine is combined with Gabapentin. Approved, Investigational The risk or severity of adverse effects can be increased when Codeine is combined with Gabapentin Enacarbil.

Approved, Investigational Gallamine The risk or severity of adverse effects can be increased when Gallamine is combined with Codeine. Experimental The risk or severity of adverse effects can be increased when Gallamine Triethiodide is combined with Codeine. Approved The risk or severity of adverse effects can be increased when Codeine is combined with Gamma Hydroxybutyric Acid. Approved, Illicit, Investigational Gepefrine may increase the analgesic activities of Codeine.

Experimental The risk or severity of adverse effects can be increased when Codeine is combined with Gepirone. Investigational The risk or severity of adverse effects can be increased when Codeine is combined with Glutethimide.

Approved, Illicit The risk or severity of adverse effects can be increased when Glycopyrronium is combined with Codeine. Approved, Investigational, Vet Approved The risk or severity of adverse effects can be increased when Codeine is combined with Guanfacine.

Approved, Investigational The risk or severity of adverse effects can be increased when Codeine is combined with Halazepam. Approved, Illicit, Withdrawn The therapeutic efficacy of Codeine can be decreased when used in combination with Haloperidol.

Approved The risk or severity of adverse effects can be increased when Codeine is combined with Halothane. Approved, Vet Approved The risk or severity of adverse effects can be increased when Codeine is combined with Harmaline.

Experimental The risk or severity of adverse effects can be increased when Codeine is combined with Heroin. Approved, Illicit, Investigational The risk or severity of adverse effects can be increased when Codeine is combined with Hexobarbital. Approved The risk or severity of adverse effects can be increased when Homatropine is combined with Codeine. Approved The risk or severity of adverse effects can be increased when Codeine is combined with Hydracarbazine.

Experimental The risk or severity of adverse effects can be increased when Codeine is combined with Hydrochlorothiazide. Approved, Illicit The risk or severity of adverse effects can be increased when Codeine is combined with Hydroflumethiazide.

Approved, Investigational The risk or severity of adverse effects can be increased when Codeine is combined with Hydromorphone. Approved, Illicit Hydroxyamphetamine may increase the analgesic activities of Codeine. Approved Hydroxyzine may increase the central nervous system depressant CNS depressant activities of Codeine. Approved The risk or severity of adverse effects can be increased when Hyoscyamine is combined with Codeine.

Approved Ibopamine The risk or severity of adverse effects can be increased when Codeine is combined with Ibopamine. Experimental The metabolism of Codeine can be decreased when combined with Idelalisib. Approved The risk or severity of adverse effects can be increased when Codeine is combined with Iloperidone. Approved The metabolism of Codeine can be decreased when combined with Imatinib.

Approved The therapeutic efficacy of Codeine can be decreased when used in combination with Imipramine. Approved Codeine may increase the serotonergic activities of Indalpine.

Investigational, Withdrawn The risk or severity of adverse effects can be increased when Codeine is combined with Indapamide. Approved The therapeutic efficacy of Codeine can be decreased when used in combination with Indinavir. Approved The risk or severity of adverse effects can be increased when Codeine is combined with Indiplon. Investigational Iofetamine I may increase the analgesic activities of Codeine. Approved The risk or severity of adverse effects can be increased when Ipratropium bromide is combined with Codeine.

Approved The risk or severity of adverse effects can be increased when Codeine is combined with Iproclozide. Withdrawn The risk or severity of adverse effects can be increased when Codeine is combined with Iproniazid. Withdrawn The serum concentration of Codeine can be increased when it is combined with Isavuconazole. Approved, Investigational The metabolism of Codeine can be decreased when combined with Isavuconazonium.

Approved, Investigational The risk or severity of adverse effects can be increased when Codeine is combined with Isocarboxazid. Approved The risk or severity of adverse effects can be increased when Codeine is combined with Isoflurane.

Approved, Vet Approved The therapeutic efficacy of Codeine can be decreased when used in combination with Isoniazid. Approved, Investigational The risk or severity of adverse effects can be increased when Codeine is combined with Isosorbide. Approved, Investigational The metabolism of Codeine can be decreased when combined with Isradipine. Approved, Investigational The metabolism of Codeine can be decreased when combined with Itraconazole.

Approved, Investigational The serum concentration of Codeine can be increased when it is combined with Ivacaftor. Approved The risk or severity of adverse effects can be increased when Codeine is combined with Ketamine. Approved, Vet Approved The risk or severity of adverse effects can be increased when Codeine is combined with Ketazolam.

Approved The risk or severity of adverse effects can be increased when Codeine is combined with Ketobemidone. Approved, Investigational The therapeutic efficacy of Codeine can be decreased when used in combination with Ketoconazole. Approved, Investigational The risk or severity of adverse effects can be increased when Codeine is combined with Lamotrigine.

Approved, Investigational The metabolism of Codeine can be decreased when combined with Lanreotide. Approved The risk or severity of adverse effects can be increased when Codeine is combined with Levetiracetam. Approved, Investigational The risk or severity of adverse effects can be increased when Codeine is combined with Levobupivacaine. Approved, Investigational The risk or severity of adverse effects can be increased when Codeine is combined with Levocabastine. Approved, Investigational The risk or severity of adverse effects can be increased when Codeine is combined with Levocetirizine.

Approved The risk or severity of adverse effects can be increased when Codeine is combined with Levodopa. Approved The risk or severity of adverse effects can be increased when Codeine is combined with Levomethadyl Acetate. Approved, Investigational Codeine may increase the serotonergic activities of Levomilnacipran.

Approved, Investigational The risk or severity of adverse effects can be increased when Codeine is combined with Levorphanol. Approved The risk or severity of adverse effects can be increased when Codeine is combined with Lidocaine.

Approved, Vet Approved Lisdexamfetamine may increase the analgesic activities of Codeine. Approved, Investigational The risk or severity of adverse effects can be increased when Codeine is combined with Lithium.

Experimental The risk or severity of adverse effects can be increased when Codeine is combined with Lofentanil. Illicit The therapeutic efficacy of Codeine can be increased when used in combination with Lofexidine. Approved, Investigational The therapeutic efficacy of Codeine can be decreased when used in combination with Lopinavir.

Approved The risk or severity of adverse effects can be increased when Codeine is combined with Loprazolam.

Experimental The risk or severity of adverse effects can be increased when Codeine is combined with Loratadine. Approved, Investigational The risk or severity of adverse effects can be increased when Lorazepam is combined with Codeine. Approved The therapeutic efficacy of Codeine can be decreased when used in combination with Lorcaserin. Approved The risk or severity of adverse effects can be increased when Codeine is combined with Lormetazepam.

Approved The serum concentration of Codeine can be increased when it is combined with Lorpiprazole.

Tylenol-Codeine NO.3

Experimental, Illicit The risk or card of adverse effects can be increased when Codeine is combined with Ecopipam. Concomitant use may result in an increase in codeine plasma concentrations, resulting in greater metabolism by CYP2D6 and increased morphine concentrations. If rifampin is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation, drug card for codeine. Moderate Concomitant use of codeine with carbamazepine can decrease codeine levels, resulting in less metabolism by CYP2D6 and decreased morphine concentrations; this for result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If modafinil is discontinued, consider a dose reduction of codeine and frequently monitor for signs or respiratory depression and sedation. Experimental The risk or severity of adverse effects can be increased when Cyclopentolate is combined with Codeine. Discontinuation of darunavir could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. Experimental The risk or severity of adverse effects can be increased when Codeine is combined with Mersalyl. Approved, Investigational The risk or severity of adverse effects can be increased when Rufinamide is combined drug Codeine. Approved, Illicit, Withdrawn The risk or severity of adverse effects can be increased when Ethopropazine is combined with Codeine. Drink spiked with rohypnol Codeine may increase the serotonergic activities of Etoperidone. These higher-than-normal codeines of morphine in the blood may lead to life-threatening or fatal respiratory depression or signs of overdose such as extreme sleepiness, confusion, or shallow breathing. Minor Although an interaction is possible, these drugs may be used together.

Tylenol with Codeine

Investigational The risk or severity of adverse effects can be increased codeine Codeine is combined with Glutethimide. Use codeine sulfate with caution and in reduced dosages in patients taking these agents. Elagolix is a weak to moderate For inducer. Approved The risk or severity of adverse effects can be increased when Codeine is combined with Lidocaine. Adverse Reactions The following serious adverse reactions are described, or described in greater detail, in levlen with antibiotics sections: Induction of emesis is not recommended because of the drug for CNS depression and seizures. Discontinuation of ribociclib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine, drug card for codeine. Moderate Concomitant use of codeine card chloramphenicol may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, drug card for codeine, increased morphine concentrations, and prolonged opioid adverse for, including codeine, respiratory depression, profound sedation, coma, and death. Renal Impairment Codeine pharmacokinetics may be altered in codeines with renal failure, drug card for codeine. The closer to drug and the larger the dose used, the greater the possibility of respiratory depression in the newborn. These higher-than-normal levels of morphine in the blood may lead to life-threatening or fatal respiratory for or signs of overdose such as extreme sleepiness, confusion, or shallow breathing. Approved, Investigational Gallamine The card or severity of adverse effects can be increased card Gallamine is combined with Codeine.

Drinking Lean: The Codeine Based Drink Associated With Hip Hop Culture

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© Copyright 2017 Drug card for codeine :: Discount Card for Patients; monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved..