Pharmacokinetics

The behavior of the individual components is described below.

Risk of Accidental Overdose and Death due to Medication Errors

Dosing errors can result in accidental overdose and death. Avoid dosing errors that may result from confusion between mg and mL and confusion with acetaminophen and codeine phosphate solutions of different concentrations, when prescribing, dispensing, and administering CAPITAL® AND CODEINE ORAL SUSPENSION. Ensure that the dose is communicated clearly and dispensed accurately.

Addiction, Abuse, and Misuse

CAPITAL® AND CODEINE ORAL SUSPENSION contains codeine phosphate and is a Schedule V controlled substance. As an opioid, codeine phosphate exposes users to the risks of addiction, abuse, and misuse [see DRUG ABUSE AND DEPENDENCE].

Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed CAPITAL® AND CODEINE ORAL SUSPENSION. Addiction can occur at recommended dosages and if the drug is misused or abused.

Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing CAPITAL® AND CODEINE ORAL SUSPENSION, and monitor all patients receiving CAPITAL® AND CODEINE ORAL SUSPENSION for the development of these behaviors or conditions. 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.g., major depression). 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 CAPITAL® AND CODEINE ORAL SUSPENSION, but use in such patients necessitates intensive counseling about the risks and proper use of CAPITAL® AND CODEINE ORAL SUSPENSION 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 CAPITAL® AND CODEINE ORAL SUSPENSION. 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 [see PRECAUTIONS; Information for Patients]. 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.

Life-Threatening Respiratory Depression

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. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status [see OVERDOSAGE]. Carbon dioxide (CO2) 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 CAPITAL® AND CODEINE ORAL SUSPENSION, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with and following dosage increases of CAPITAL® AND CODEINE ORAL SUSPENSION.

To reduce the risk of respiratory depression, proper dosing and titration of CAPITAL® AND CODEINE ORAL SUSPENSION are essential [see DOSAGE AND ADMINISTRATION]. Overestimating the CAPITAL® AND CODEINE ORAL SUSPENSION 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 CAPITAL® AND CODEINE ORAL SUSPENSION, especially by children, can result in respiratory depression and death due to an overdose of codeine.

Neonatal Opioid Withdrawal Syndrome

Prolonged use of CAPITAL® AND CODEINE ORAL SUSPENSION 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. 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 PRECAUTIONS; Information for Patients, Pregnancy].

Risks of Concomitant Use or Discontinuation of Cytochrome P450 3A4 Inhibitors and Inducers

Concomitant use of CAPITAL® AND CODEINE ORAL SUSPENSION with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of codeine and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression [see WARNINGS], particularly when an inhibitor is added after a stable dose of CAPITAL® AND CODEINE ORAL SUSPENSION is achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in CAPITAL® AND CODEINE ORAL SUSPENSION-treated patients may increase codeine plasma concentrations and prolong opioid adverse reactions. When using CAPITAL® AND CODEINE ORAL SUSPENSION with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in CAPITAL® AND CODEINE ORAL SUSPENSION-treated patients, monitor patients closely at frequent intervals and consider dosage reduction of CAPITAL® AND CODEINE ORAL SUSPENSION until stable drug effects are achieved [see PRECAUTIONS; Drug Interactions].

Concomitant use of CAPITAL® AND CODEINE ORAL SUSPENSION with CYP3A4 inducers or discontinuation of an CYP3A4 inhibitor could decrease codeine plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to CAPITAL® AND CODEINE ORAL SUSPENSION. When using CAPITAL® AND CODEINE ORAL SUSPENSION with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, monitor patients closely at frequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur [see PRECAUTIONS; Drug Interactions].

Risks due to Interactions with Central Nervous System Depressants

Hypotension, profound sedation, respiratory depression, coma, and death may result if CAPITAL® AND CODEINE ORAL SUSPENSION is used concomitantly with alcohol or other central nervous system (CNS) depressants (e.g., benzodiazepines and other sedatives/hypnotics, anxiolytics, and tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids).

When considering the use of CAPITAL® AND CODEINE ORAL SUSPENSION in a patient taking a CNS depressant, assess the duration of use of the CNS depressant and the patient’s response, including the degree of tolerance that has developed to CNS depression. Additionally, evaluate the patient’s use of alcohol or illicit drugs that can cause CNS depression. If the decision to begin CAPITAL® AND CODEINE ORAL SUSPENSION is made, start with a lower dosage of CAPITAL® AND CODEINE ORAL SUSPENSION, monitor patients for signs of respiratory depression, sedation, and hypotension, and consider using a lower dose of the concomitant CNS depressant [see PRECAUTIONS; Drug Interactions].

Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients

The use of CAPITAL® AND CODEINE ORAL SUSPENSION in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.

Patients with Chronic Pulmonary Disease: CAPITAL® AND CODEINE ORAL SUSPENSION-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 CAPITAL® AND CODEINE ORAL SUSPENSION [see WARNINGS].

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 or altered clearance compared to younger, healthier patients [see WARNINGS].

Monitor such patients closely, particularly when initiating and titrating CAPITAL® AND CODEINE ORAL SUSPENSION and when CAPITAL® AND CODEINE ORAL SUSPENSION is given concomitantly with other drugs that depress respiration [see WARNINGS]. Alternatively, consider the use of non-opioid analgesics in these patients.

Adrenal Insufficiency

Cases of adrenal insufficiency have been reported with opioid use, more often following greater than 1 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.

Head Injury and Increased Cranial Pressure

In the presence of head injury or other intracranial lesions, the respiratory depressant effects of codeine and other narcotics may be markedly enhanced, as well as their capacity for elevating cerebrospinal fluid pressure. Narcotics also produce other CNS depressant effects, such as drowsiness, that may further obscure the clinical course of the patients with head injuries.

Abdominal Conditions

Codeine or other narcotics may obscure signs on which to judge the diagnosis or clinical course of patients with acute abdominal conditions.

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 4000 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 4000 milligrams of acetaminophen per day, even if they feel well.

Serious Skin Reactions

Rarely, acetaminophen may cause serious skin reactions such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Patients should be informed about the signs of serious skin reactions and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.

Death Related to Ultra-Rapid Metabolism of Codeine to Morphine

Respiratory depression and death have occurred in children who received codeine in the post-operative period following tonsillectomy and/or adenoidectomy and had evidence of being ultra-rapid metabolizers of codeine (i.e., multiple copies of the gene for cytochrome P450 isoenzyme 2D6 or high morphine concentrations). Deaths have also occurred in nursing infants who are exposed to high levels of morphine in breast milk because their mothers were ultra-rapid metabolizers of codeine [see PRECAUTIONS; Nursing Mothers].

Some individuals may be ultra-rapid metabolizers because of a specific CYP2D6 genotype (gene duplications denoted as *1/*1xN or *1/*2xN). The prevalence of this CYP2D6 phenotype varies widely and has been estimated at 0.5 to 1% in Chinese and Japanese, 0.5 to 1% in Hispanics, 1 to 10% in Caucasians, 3% in African Americans, and 16 to 28% in North Africans, Ethiopians, and Arabs. 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. 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].

Children with obstructive sleep apnea who are treated with codeine for post-tonsillectomy and/or adenoidectomy pain may be particularly sensitive to the respiratory depressant effects of codeine that has been rapidly metabolized to morphine. Codeine-containing products are contraindicated for post-operative pain management in all pediatric patients undergoing tonsillectomy and/or adenoidectomy [see CONTRAINDICATIONS].

When prescribing codeine-containing products, healthcare providers should choose the lowest effective dose for the shortest period of time and inform patients and caregivers about these risks and the signs of morphine overdose [see OVERDOSAGE].

Hypersensitivity/anaphylaxis

There have been post-marketing reports of hypersensitivity and anaphylaxis associated with use of acetaminophen. Clinical signs included swelling of the face, mouth, and throat, respiratory distress, urticaria, rash, pruritus, and vomiting. There were infrequent reports of life-threatening anaphylaxis requiring emergency medical attention. Instruct patients to discontinue CAPITAL® AND CODEINE ORAL SUSPENSION immediately and seek medical care if they experience these symptoms. Do not prescribe CAPITAL® AND CODEINE ORAL SUSPENSION for patients with acetaminophen allergy.

General

CAPITAL® AND CODEINE ORAL SUSPENSION should be prescribed with caution in certain special-risk patients, such as the elderly or debilitated, and those with severe impairment of renal or hepatic function, head injuries, elevated intracranial pressure, acute abdominal conditions, hypothyroidism, urethral stricture, Addison's disease, or prostatic hypertrophy.

Information for Patients

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Do not take CAPITAL® AND CODEINE ORAL SUSPENSION if you are allergic to any of its ingredients.

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If you develop signs of allergy such as a rash or difficulty breathing stop taking CAPITAL® AND CODEINE ORAL SUSPENSION and contact your healthcare provider immediately.

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Do not take more than 4000 milligrams of acetaminophen per day. Call your doctor if you took more than the recommended dose.

Laboratory Tests

In patients with severe hepatic or renal disease, effects of therapy should be monitored with serial liver and/or renal function tests.

Drug Interactions

Drug/Laboratory Test Interactions

Codeine may increase serum amylase levels.

Acetaminophen may produce false-positive test results for urinary 5-hydroxyindoleacetic acid.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No adequate studies have been conducted in animals to determine whether acetaminophen and codeine have a potential for carcinogenesis or mutagenesis.

Acetaminophen and codeine have been found to have no mutagenic potential using the Ames Salmonella-Microsomal Activation test, the Basc test on Drosophila germ cells, and the Micronucleus test on mouse bone marrow.

Pregnancy

Labor or Delivery

Nursing Mothers

Acetaminophen is excreted in breast milk in small amounts, but the significance of its effects on nursing infants is not known. Because of the potential for serious adverse reactions in nursing infants from acetaminophen, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Codeine is secreted into human milk. In women with normal codeine metabolism (normal CYP2D6 activity), the amount of codeine secreted into human milk is low and dose-dependent. Despite the common use of codeine products to manage postpartum pain, reports of adverse events in infants are rare. However, some women are ultra-rapid metabolizers of codeine. These women achieve higher-than-expected serum levels of codeine's active metabolite, morphine, leading to higher-than-expected levels of morphine in breast milk and potentially dangerously high serum morphine levels in their breastfed infants. Therefore, maternal use of codeine can potentially lead to serious adverse reactions, including death, in nursing infants [see WARNINGS; Death Related to Ultra-Rapid Metabolism of Codeine to Morphine].

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for CAPITAL® AND CODEINE ORAL SUSPENSION and any potential adverse effects on the breastfed infant from CAPITAL® AND CODEINE ORAL SUSPENSION or from the underlying maternal condition.

Infants exposed to CAPITAL® AND CODEINE ORAL SUSPENSION through breast milk 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 breast-feeding is stopped.

Pediatric Use

Safe dosage of acetaminophen and codeine phosphate oral suspension has not been established in pediatric patients below the age of 3 years.

Geriatric Use

Elderly patients (aged 65 years or older) may have increased sensitivity to CAPITAL® AND CODEINE ORAL SUSPENSION. 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 CAPITAL® AND CODEINE ORAL SUSPENSION slowly in geriatric patients [see WARNINGS].

Controlled Substance

CAPITAL® AND CODEINE ORAL SUSPENSION contains codeine phosphate, and is a Schedule V controlled substance.

Abuse

CAPITAL® AND CODEINE ORAL SUSPENSION contains codeine phosphate, a substance with a high potential for abuse similar to other opioids including hydrocodone, oxycodone, and morphine. CAPITAL® AND CODEINE ORAL SUSPENSION can be abused and is subject to misuse, addiction, and criminal diversion [see WARNINGS].

All patients treated with opioids require careful monitoring for signs of abuse and addiction, since use of opioid analgesic products carries 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.

“Drug-seeking” behavior is very common in persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating health care provider(s). “Doctor shopping” (visiting multiple prescribers) to obtain additional prescriptions is common among drug abusers and people suffering from untreated addiction. 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. Health care 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.

CAPITAL® AND CODEINE ORAL SUSPENSION, 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.

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

Both tolerance and physical dependence can develop during chronic opioid therapy. 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). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.

Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (pentazocine, butorphanol, nalbuphine), or partial agonists (buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage.

CAPITAL® AND CODEINE ORAL SUSPENSION should not be abruptly discontinued [see DOSAGE AND ADMINISTRATION]. If CAPITAL® AND CODEINE ORAL SUSPENSION is abruptly discontinued in a physically-dependent patient, a withdrawal syndrome may occur. Some or all of the following can characterize this syndrome: 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.

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see PRECAUTIONS; Pregnancy].

Clinical Presentation

Acute overdose with codeine can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations. In acetaminophen overdosage: dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necrosis, hypoglycemic coma and coagulation defects may also occur.

Early symptoms following a potentially hepatotoxic overdose may include: nausea, vomiting, diaphoresis and general malaise. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours post-ingestion.

Treatment of Overdose

A single or multiple drug overdose with acetaminophen and codeine is a potentially lethal polydrug overdose, and consultation with a regional poison control center is recommended. Immediate treatment includes support of cardiorespiratory function and measures to reduce drug absorption.

In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support techniques.

The opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression resulting from opioid overdose. For clinically significant respiratory or circulatory depression secondary to codeine overdose, administer an opioid antagonist. Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to codeine overdose.

Because the duration of opioid reversal is expected to be less than the duration of action of codeine in CAPITAL® AND CODEINE ORAL SUSPENSION, carefully monitor the patient until spontaneous respiration is reliably re-established. If the response to an opioid antagonist is suboptimal or only brief in nature, administer additional antagonist as directed by the product’s prescribing information.

In an individual physically dependent on opioids, administration of the recommended usual dosage of the antagonist will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the antagonist should be begun with care and by titration with smaller than usual doses of the antagonist. Gastric decontamination with activated charcoal should be administered just prior to N-acetylcysteine (NAC) to decrease systemic absorption if acetaminophen ingestion is known or suspected to have occurred within a few hours of presentation. Serum acetaminophen levels should be obtained immediately if the patient presents 4 hours or more after ingestion to assess potential risk of hepatotoxicity; acetaminophen levels drawn less than 4 hours post-ingestion may be misleading. To obtain the best possible outcome, NAC should be administered as soon as possible where impending or evolving liver injury is suspected. Intravenous NAC may be administered when circumstances preclude oral administration.

Vigorous supportive therapy is required in severe intoxication. Procedures to limit the continuing absorption of the drug must be readily performed since the hepatic injury is dose dependent and occurs early in the course of intoxication.

Important Dosage and Administration Instructions

Ensure accuracy when prescribing, dispensing, and administering CAPITAL® AND CODEINE ORAL SUSPENSION to avoid dosing errors due to confusion between mg and mL, and with other acetaminophen/codeine 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.

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].

Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy and following dosage increases with CAPITAL® AND CODEINE ORAL SUSPENSION and adjust the dosage accordingly [see WARNINGS].

Initial Dosage

CAPITAL® AND CODEINE ORAL SUSPENSION (Acetaminophen and codeine phosphate oral suspension) contains 120 mg of acetaminophen and 12 mg of codeine phosphate per 5 mL (teaspoonful) and is given orally.

The recommended dose of codeine phosphate in children is 0.5 mg/kg body weight.

The usual doses are:

Children: (7 to 12 years): 10 mL (2 teaspoonfuls) 3 or 4 times daily.

(3 to 6 years): 5 mL (1 teaspoonful) 3 or 4 times daily.

(under 3 years): safe dosage has not been established.

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

Titration and Maintenance of Therapy

Individually titrate CAPITAL® AND CODEINE ORAL SUSPENSION to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving CAPITAL® AND CODEINE ORAL SUSPENSION 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]. 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 CAPITAL® AND CODEINE ORAL SUSPENSION 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.

Discontinuation of CAPITAL® AND CODEINE ORAL SUSPENSION

When a patient who has been taking CAPITAL® AND CODEINE ORAL SUSPENSION regularly and may be physically dependent no longer requires therapy with CAPITAL® AND CODEINE ORAL SUSPENSION, use a gradual downward titration of the dosage to prevent signs and symptoms of withdrawal. Do not stop CAPITAL® AND CODEINE ORAL SUSPENSION abruptly [see WARNINGS, DRUG ABUSE AND DEPENDENCE].

STORAGE

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