Prescription Drug Information: Acetaminophen and Codeine Phosphate (Page 3 of 6)

PRECAUTIONS


Risks of Driving and Operating Machinery

Acetaminophen and codeine phosphate 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 acetaminophen and codeine phosphate tablets and know how they will react to the medication (see PRECAUTIONS; Information for Patients/Caregivers).

Information for Patients/Caregivers

Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Storage and Disposal
Because of the risks associated with accidental ingestion, misuse, and abuse, advise patients to store acetaminophen and codeine phosphate tablets securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home (see WARNINGS and DRUG ABUSE AND DEPENDENCE). Inform patients that leaving acetaminophen and codeine phosphate tablets unsecured can pose a deadly risk to others in the home.
Advise patients and caregivers that when medicines are no longer needed, they should be disposed of promptly. Inform patients that medicine take-back options are the preferred way to safely dispose of most types of unneeded medicines. If no take back programs or DEA-registered collectors are available, instruct patients to dispose of acetaminophen and codeine phosphate tablets by following these four steps:

  • Mix acetaminophen codeine phosphate tablets (do not crush) with an unpalatable substance such as dirt, cat litter, or coffee grounds;
  • Place the mixture in a container such as a sealed plastic bag;
  • Throw the container in the household trash;
  • Delete all personal information on the prescription label of the empty bottle.

Inform patients that they can visit www.fda.gov/drugdisposal for all additional information on disposal of unused medicines.

Addiction, Abuse and Misuse

Inform patients that the use of acetaminophen and codeine phosphate tablets, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death (see WARNINGS). Instruct patients not to share acetaminophen and codeine phosphate tablets with others and to take steps to protect acetaminophen and codeine phosphate tablets from theft or misuse.

Life-Threatening Respiratory Depression

Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting acetaminophen and codeine phosphate tablets or when the dosage is increased, and that it can occur even at recommended dosages.
Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose (see WARNINGS, Life-Threatening Respiratory Depression).
Accidental Ingestion
Inform patients that accidental ingestion, especially by children, may result in respiratory depression or death (see WARNINGS).
Interactions with Benzodiazepines and Other CNS Depressants
Inform patients and caregivers that potentially fatal additive effects may occur if acetaminophen and codeine phosphate tabletsis used with benzodiazepines or other CNS depressants, including alcohol, and not to use these drugs concomitantly unless supervised by a healthcare provider (see WARNINGS, PRECAUTIONS, Drug Interactions).

Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose
Discuss with the patient and caregiver the availability of naloxone for the emergency treatment of opioid overdose, both when initiating and renewing treatment with acetaminophen and codeine phosphate tablets. Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist or as part of a community program) (see WARNINGS, Life-Threatening Respiratory Depression; DOSAGE AND ADMINISTRATION).
Educate patients and caregivers on how to recognize the signs and symptoms of an overdose.
Explain to patients and caregivers that naloxone’s effects are temporary, and that they must call 911 or get emergency medical help right away in all cases of known or suspected opioid overdose, even if naloxone is administered (see OVERDOSAGE).
If naloxone is prescribed, also advise patients and caregivers:

  • How to treat with naloxone in the event of an opioid overdose,
  • To tell family and friends about their naloxone and to keep it in place where family and friends can access it an emergency,
  • To read the Patient Information (or other educational material) that will come with their naloxone. Emphasize the importance of doing this before an opioid emergency happens, so the patient and caregiver will know what to do.

Ultra-Rapid Metabolism of Codeine and Other Risk Factors for Life-Threatening Respiratory Depression in Children

Advise caregivers that acetaminophen and codeine phosphate tablets are contraindicated in all children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy. Advise caregivers of children 12 to 18 years of age receiving acetaminophen and codeine phosphate tablets to monitor for signs of respiratory depression (see WARNINGS).

Inform patients and caregivers that potentially fatal additive effects may occur if acetaminophen and codeine phosphate tablets are used with benzodiazepines or other CNS depressants, including alcohol, and not to use these drugs concomitantly unless supervised by a healthcare provider (see WARNINGS,PRECAUTIONS; Drug Interactions).

Hyperalgesia and Allodynia

Inform patients and caregivers not to increase opioid dosage without first consulting a clinician. Advise patients to seek medical attention if they experience symptoms of hyperalgesia, including worsening pain, increased sensitivity to pain, or new pain (see WARNINGS; Adverse Reactions).

Serotonin Syndrome

Inform patients that opioids could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms and signs of serotonin syndrome and to seek medical attention right away if symptoms develop.

Instruct patients to inform their healthcare provider if they are taking, or plan to take serotonergic medications (see PRECAUTIONS;Drug Interactions).

MAOI Interaction

Inform patients not to take acetaminophen and codeine phosphate tablets while using any drugs that inhibit monoamine oxidase. Patients should not start MAOIs while taking acetaminophen and codeine phosphate tablets (see PRECAUTIONS; Drug Interactions).

Important Administration Instructions

Instruct patients how to properly take acetaminophen and codeine phosphate tablets (see DOSAGE AND ADMINISTRATION).

  • Advise patients not to adjust the dose of acetaminophen and codeine phosphate tablets without consulting a physician or other healthcare professional.

Important Discontinuation Instructions

  • In order to avoid development withdrawal symptoms, instruct patient not to discontinue acetaminophen and codeine phosphate tablets without first discussing a tapering plan with the prescriber (see DOSAGE AND ADMINISTRATION).

Maximum Daily Dose of Acetaminophen

Inform patients not to take more than 4,000 milligrams of acetaminophen per day. Advise patients to call their healthcare provider if they have taken more than the recommended dose.

Driving or Operating Heavy Machinery

Inform patients that acetaminophen and codeine phosphate tablets may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery and to avoid such tasks while taking this product, until they know how they will react to the medication.

Constipation

Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention (see ADVERSE REACTIONS, and CLINICAL PHARMACOLOGY).

Adrenal Insufficiency

Inform patients that opioids could cause adrenal insufficiency, a potentially life-threatening condition. Adrenal insufficiency may present with non-specific symptoms and signs such as nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. Advise patients to seek medical attention if they experience a constellation of these symptoms (see WARNINGS).

Hypotension

Inform patients that acetaminophen and codeine phosphate tablets may cause orthostatic hypotension and syncope. Instruct patients how to recognize symptoms of low blood pressure and how to reduce the risk of serious consequences should hypotension occur (e.g., sit or lie down, carefully rise from a sitting or lying position) (see WARNINGS; Hypotension).

Anaphylaxis

Inform patients that anaphylaxis has been reported with ingredients contained in acetaminophen and codeine phosphate tablets. Advise patients how to recognize such a reaction, and if they develop signs of allergy such as a rash or difficulty breathing to stop taking acetaminophen and codeine phosphate tablets and seek medical attention (see CONTRAINDICATIONS, and ADVERSE REACTIONS).

Pregnancy

Neonatal Opioid Withdrawal Syndrome

Inform female patients of reproductive potential that use of acetaminophen and codeine phosphate tablets for an extended period of time during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated (see WARNINGS; PRECAUTIONS,Pregnancy).

Embryo-Fetal Toxicity

Inform female patients of reproductive potential that acetaminophen and codeine phosphate tablets can cause fetal harm and to inform the prescriber of a known or suspected pregnancy (see PRECAUTIONS; Pregnancy).

Lactation

Advise women that breastfeeding is not recommended during treatment with acetaminophen and codeine phosphate tablets (see PRECAUTIONS;Nursing Mothers).

Infertility

Inform patients that use of opioids for an extended period of time may cause reduced fertility. It is not known whether these effects on fertility are reversible (see ADVERSE REACTIONS).

Drug Interactions

CYP2D6 Inhibitors

Codeine is metabolized by CYP2D6 to form morphine. The concomitant use of acetaminophen and codeine phosphate tablets and CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, bupropion, quinidine) 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 acetaminophen and codeine phosphate tablets are 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 acetaminophen and codeine phosphate tablets and evaluate patients closely at frequent intervals.

If concomitant use with CYP2D6 inhibitors is necessary, assess the patient for reduced efficacy or signs and symptoms of opioid withdrawal and consider increasing the acetaminophen and codeine phosphate tablets as needed.

After stopping use of a CYP2D6 inhibitor, consider reducing the acetaminophen and codeine phosphate tablets and evaluate the patient for signs and symptoms of respiratory depression or sedation.

CYP3A4 Inhibitors

The concomitant use of Acetaminophen and Codeine Phosphate tablets and CYP3A4 inhibitors, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), and protease inhibitors (e.g., ritonavir), 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 Acetaminophen and Codeine Phosphate tablets is achieved (see WARNINGS).

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), resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to codeine.

If concomitant use of CYP3A4 inhibitor is necessary, consider dosage reduction of acetaminophen and codeine tablets until stable drug effects are achieved. Evaluate patients at frequent intervals for respiratory depression and sedation.

If a CYP3A4 inhibitor is discontinued, consider increasing the acetaminophen and codeine phosphate tablets dosage until stable drug effects are achieved. Assess for signs of opioid withdrawal.

CYP3A4 Inducers

The concomitant use of acetaminophen and codeine phosphate tablets and CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin) can result in lower codeine levels, greater norcodeine levels, and less metabolism via 2D6 with resultant lower morphine levels (see CLINICAL PHARMACOLOGY), resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence (see WARNINGS).

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), which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression.

If concomitant use of a CYP3A4 inducer is necessary, follow the patient for reduced efficacy and signs of opioid withdrawal and consider increasing the acetaminophen and codeine phosphate tablets dosage as needed. Assess for respiratory depression and sedation.

If a CYP3A4 inducer is discontinued, consider acetaminophen and codeine phosphate tablets dose reduction and evaluate patients at frequency intervals for signs of respiratory depression and sedation.

Benzodiazepines and Other Central Nervous System (CNS) Depressants

Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics and other opioids, 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. Inform patients and caregivers of this potential interaction, educate them on the signs and symptoms of respiratory depression (including sedation). If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid (see WARNINGS).

Serotonergic Drugs

The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Examples of these drugs include, selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that effect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), and monoamine oxidase (MAO) inhibitors (used to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue) (see PRECAUTIONS; Information for Patients/Caregivers).

If concomitant use is warranted, frequently evaluate the patient, particularly during treatment initiation and dose adjustment. Discontinue acetaminophen and codeine phosphate tablets immediately if serotonin syndrome is suspected.

Monoamine Oxidase Inhibitors (MAOIs)

The concomitant use of opioids and MAOIs, such as phenelzine, tranylcypromine, linezolid, may manifest as serotonin syndrome or opioid toxicity.

Advise patients taking acetaminophen and codeine phosphate tablets not to use 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, hydrocodone, or buprenorphine) to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.

Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics

The concomitant use of opioids with other opioid analgesics, such as butorphanol, nalbuphine, pentazocine, may reduce the analgesic effect of acetaminophen and codeine phosphate tablets and/or precipitate withdrawal symptoms.

Advise patient to avoid concomitant use of these drugs.

Muscle Relaxants

Acetaminophen and codeine may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.

If concomitant use is warranted, because respiratory depression may be greater than otherwise expected, decrease the dosage of acetaminophen and codeine phosphate tablets and/or the muscle relaxant as necessary. Due to the risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider prescribing naloxone for the emergency treatment of opioid overdose (see WARNINGS).

Diuretics

Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.

If concomitant use is warranted, evaluate patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed.

Anticholinergic Drugs

The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.

If concomitant use is warranted, evaluate patients for signs of urinary retention or reduced gastric motility when acetaminophen and codeine phosphate tablets are used concomitantly with anticholinergic drugs.

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