Get your patient on Acetaminophen And Codeine Phosphate - Acetaminophen And Codeine Phosphate solution (Acetaminophen And Codeine Phosphate)

Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy [see WARNINGS ] , reserve opioid analgesics, including acetaminophen and codeine phosphate oral solution, for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.

Ensure accuracy when prescribing, dispensing, and administering acetaminophen and codeine phosphate oral solution to avoid dosing errors due to confusion between mg and mL, and with other acetaminophen and codeine phosphate solutions of different concentrations, which could result in accidental overdose and death. Ensure the proper dose is communicated and dispensed. When writing prescriptions, include both the total dose in mg and the total dose in volume.

Instruct patients and caregivers on how to accurately measure and take or administer the correct dose of acetaminophen and codeine phosphate oral solution.

Strongly advise patients and caregivers to always use a graduated oral syringe or measuring cup, with metric units of measurements (i.e., mL), to correctly measure the prescribed amount of medication.

Inform patients and caregivers that oral dosing devices may be obtained from their pharmacy and to never use household teaspoons or tablespoons to measure acetaminophen and codeine phosphate oral solution.

Acetaminophen and codeine phosphate oral solution should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks.

Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals [see WARNINGS ]. Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of acetaminophen and codeine phosphate oral solution for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks.

Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available.

There is variability in the opioid analgesic dose and duration needed to adequately manage pain due both to the cause of pain and to individual patient factors. Initiate the dosing regimen for each patient individually, taking into account the patient's underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse [see WARNINGS ].

Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with acetaminophen and codeine phosphate oral solution. Consider this risk when selecting an initial dose and when making dose adjustments [see WARNINGS ].

Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene). Discuss the importance of having access to an opioid overdose reversal agent, especially if the patient has risk factors for overdose (e.g., concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose) or if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose. The presence of risk factors for overdose should not prevent the management of pain in any patient [see WARNINGS; Addiction, Abuse, and Misuse ; Life-Threatening Respiratory Depression ; Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants ].

Discuss the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program).

There are important differences among the opioid overdose reversal agents, such as route of administration, product strength, approved patient age range, and pharmacokinetics. Be familiar with these differences, as outlined in the approved labeling for those products, prior to recommending or prescribing such an agent.

15 mL (1 tablespoonful) every 4 hours as needed.

Individually titrate acetaminophen and codeine phosphate oral solution to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving acetaminophen and codeine phosphate oral solution to assess the maintenance of pain control, signs and symptoms of opioid withdrawal, and other adverse reactions, as well as reassess for the development of addiction, abuse, or misuse [see WARNINGS ]. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration.

If the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing the acetaminophen and codeine phosphate oral solution dosage. If after increasing the dosage, unacceptable opioid-related adverse reactions are observed (including an increase in pain after dosage increase), consider reducing the dosage [see WARNINGS ]. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

Do not rapidly reduce or abruptly discontinue acetaminophen and codeine phosphate oral solution in patients who may be physically dependent on opioids. Rapid reduction or abrupt discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid reduction or abrupt 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 acetaminophen and codeine phosphate oral solution, there are a variety of factors that should be considered, including the total daily dose of opioid (including acetaminophen and codeine phosphate oral solution) 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 acetaminophen and codeine phosphate oral solution who are physically opioid-dependent, initiate the taper by a small enough increment (e.g., no greater than 10% to 25% of the total daily dose) to avoid withdrawal symptoms, and proceed with dose-lowering at an interval of every 2 to 4 weeks. 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, evaluate patients for any changes in mood, emergence of suicidal thoughts, or use of other substances.

When managing patients taking opioid analgesics, particularly those who have been treated for an extended period of time and/or with high doses for chronic pain, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper. 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/Withdrawal , DRUG ABUSE AND DEPENDENCE ].

When a patient who has been taking acetaminophen and codeine phosphate oral solution regularly and may be physically dependent no longer requires therapy with acetaminophen and codeine phosphate oral solution, taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal. If the patient develops these signs or symptoms, raise the dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both. Do not abruptly discontinue acetaminophen and codeine phosphate oral solution in a physically-dependent patient [see WARNINGS , DRUG ABUSE AND DEPENDENCE ].

A prospective, observational cohort study estimated the risks of addiction, abuse, and misuse in patients initiating long-term use of Schedule II opioid analgesics between 2017 and 2021. Study participants included in one or more analyses had been enrolled in selected insurance plans or health systems for at least one year, were free of at least one outcome at baseline, completed a minimum number of follow-up assessments, and either: 1) filled multiple extended-release/long-acting opioid analgesic prescriptions during a 90 day period (n=978); or 2) filled any Schedule II opioid analgesic prescriptions covering at least 70 of 90 days (n=1,244). Those included also had no dispensing of the qualifying opioids in the previous 6 months.

Over 12 months:

• approximately 1% to 6% of participants across the two cohorts newly met criteria for addiction, as assessed with two validated interview-based measures of moderate-to-severe opioid use disorder based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, and
• approximately 9% and 22% of participants across the two cohorts newly met criteria for prescription opioid abuse and misuse [defined in DRUG ABUSE AND DEPENDENCE ], respectively, as measured with a validated self-reported instrument.

A retrospective, observational cohort study estimated the risk of opioid-involved overdose or opioid overdose-related death in patients with new long-term use of Schedule II opioid analgesics from 2006 through 2016 (n=220,249). Included patients had been enrolled in either one of two commercial insurance programs, one managed care program, or one Medicaid program for at least 9 months. New long-term use was defined as having Schedule II opioid analgesic prescriptions covering at least 70 days' supply over the 3 months prior to study entry and none during the preceding 6 months. Patients were excluded if they had an opioid-involved overdose in the 9 months prior to study entry. Overdose was measured using a validated medical code-based algorithm with linkage to the National Death Index database. The 5-year cumulative incidence estimates for opioid-involved overdose or opioid overdose-related death ranged from approximately 1.5% to 4% across study sites, counting only the first event during follow-up. Approximately 17% of first opioid overdoses observed over the entire study period (5-11 years, depending on the study site) were fatal. Higher baseline opioid dose was the strongest and most consistent predictor of opioid-involved overdose or opioid overdose-related death. Study exclusion criteria may have selected patients at lower risk of overdose, and substantial loss to follow-up (approximately 80%) also may have biased estimates.

The risk estimates from the studies described above may not be generalizable to all patients receiving opioid analgesics, such as those with exposures shorter or longer than the duration evaluated in the studies.

To report SUSPECTED ADVERSE REACTIONS, contact Allucent at 1-866-511-6754 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

Codeine is metabolized by CYP2D6 to form morphine. The concomitant use of acetaminophen and codeine phosphate oral solution 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 oral solution 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 acetaminophen and codeine phosphate oral solution 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 oral solution as needed.

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

The concomitant use of acetaminophen and codeine phosphate oral solution 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 oral solution 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 phosphate oral solution 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 oral solution dosage until stable drug effects are achieved. Assess for signs of opioid withdrawal.

The concomitant use of acetaminophen and codeine phosphate oral solution 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, evaluate the patient for reduced efficacy and signs of opioid withdrawal and consider increasing the acetaminophen and codeine phosphate oral solution dosage as needed. Assess for respiratory depression and sedation.

If a CYP3A4 inducer is discontinued, consider an acetaminophen and codeine phosphate oral solution dose reduction and evaluate patients at frequent intervals for signs of respiratory depression and 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. Inform patients and caregivers of this potential interaction and educate them on the signs and symptoms of respiratory depression (including sedation). If concomitant use is warranted, consider recommending or prescribing an opioid overdose reversal agent [see WARNINGS , DOSAGE and ADMINISTRATION ].

Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids (gabapentin or pregabalin), other opioids, alcohol.

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), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), 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 ].

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

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 oral solution 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.

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

Advise patient to avoid concomitant use of these drugs.

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 oral solution and/or the muscle relaxant as necessary. Due to the risk of respiratory depression with concomitant use of skeletal muscle relaxants, (i.e., cyclobenzaprine, metaxalone) and opioids, consider recommending or prescribing an opioid overdose reversal agent [see WARNINGS , DOSAGE AND ADMINSTRATION ].

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.

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 oral solution is used concomitantly with anticholinergic drugs.

Codeine is an opioid agonist relatively selective for the mu-opioid receptor, but with a much weaker affinity than morphine. The analgesic properties of codeine have been speculated to come from its conversion to morphine, although the exact mechanism of analgesic action remains unknown.

The precise mechanism of the analgesic properties of acetaminophen is not established but is thought to involve central actions.

The behavior of the individual components is described below.

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

Dispense in a tight, light-resistant container with a child-resistant closure.

Store acetaminophen and codeine phosphate oral solution securely and dispose of properly [see PRECAUTIONS/Information for Patients ].