Acetaminophen and Codeine Oral Solution

Name: Acetaminophen and Codeine Oral Solution

Description

Acetaminophen and Codeine Phosphate Oral Solution is pharmacologically classified as an analgesic.

Acetaminophen, 4’-hydroxyacetanilide, a slightly bitter, white, odorless, crystalline powder, is a non-opioid, non-salicylate analgesic and antipyretic. It has the following structural formula:

Codeine phosphate, 7,8-didehydro-4,5α-epoxy-3-methoxy-17-methylmorphinan-6α-ol phosphate (1:1) (salt) hemihydrate, a white crystalline powder, is an opioid agonist. It has the following structural formula:

Each Acetaminophen and Codeine Phosphate Oral Solution, USP 120 mg/12 mg per 5 mL, for oral administration, contains:

Acetaminophen.........................120 mg

Codeine Phosp ...........................12 mg

(Warning: May be habit-forming)

Alcohol............................................7%

INACTIVE INGREDIENTS

Artificial cherry flavor, citric acid, FD&C Yellow No. 6, propylene glycol, purified water, saccharin sodium, sodium benzoate, and sucrose.

Adverse Reactions

To report SUSPECTED ADVERSE REACTIONS, contact Hi-Tech Pharmacal Co., Inc. at 1-800-262-9010 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

The following adverse reactions have been identified during post approval use of acetaminophen and codeine phosphate oral solution. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Addiction, Abuse, and Misuse [see WARNINGS] • Life-Threatening Respiratory Depression [see WARNINGS] • Neonatal Opioid Withdrawal Syndrome [see WARNINGS] • Ultra-rapid Metabolizers of Codeine [see WARNINGS] • Interactions with CNS Depressants [see WARNINGS] • Severe Hypotension [see WARNINGS] • Gastrointestinal Adverse Reactions [see WARNINGS] • Seizures [see WARNINGS] • Withdrawal [see WARNINGS]

Serious adverse reactions associated with codeine are respiratory depression and, to a lesser degree, circulatory depression, respiratory arrest, shock, and cardiac arrest.

The most frequently observed adverse reactions with codeine administration include drowsiness, lightheadedness, dizziness, sedation, shortness of breath, nausea, vomiting, sweating, and constipation.

Other adverse reactions include allergic reactions, euphoria, dysphoria, abdominal pain, pruritis, rash, thrombocytopenia, and agranulocytosis.

Other less frequently observed adverse reactions expected from opioid analgesics, including acetaminophen and codeine phosphate oral solution:

Cardiovascular System: faintness, flushing, hypotension, palpitations, syncope

Digestive System: abdominal cramps, anorexia, diarrhea, dry mouth, gastrointestinal distress, pancreatitis

Nervous System: anxiety, drowsiness, fatigue, headache, insomnia, nervousness, shakiness, somnolence, vertigo, visual disturbances, weakness

Skin and Appendages: rash, sweating, urticarial

• Serotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. • Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. • Anaphylaxis: Anaphylaxis has been reported with ingredients contained in acetaminophen and codeine phosphate oral solution.

Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids [see CLINICAL PHARMACOLOGY].

Overdosage

Following an acute overdosage, toxicity may result from codeine or acetaminophen.

Clinical Presentation

Codeine

Acute overdosage 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.

Acetaminophen

Dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect of acetaminophen. Renal tubular necrosis, hypoglycemic coma, and coagulation defects may also occur.

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

Treatment of Overdose

Codeine

In case of codeine 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 serious arrhythmias will require advanced life-support measures.

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 acetaminophen and codeine phosphate oral solution overdose, administer an opioid antagonist. Only administer opioid antagonists in the presence of clinically significant respiratory, circulatory and/or central nervous system depression secondary to codeine overdose. In patients who are physically dependent on any opioid agonist including acetaminophen and codeine phosphate oral solution, an abrupt or complete reversal of opioid effects may precipitate an acute withdrawal syndrome. The severity of the withdrawal syndrome produced will depend on the degree of physical dependence and the dose of the antagonist administered. Please see the prescribing information for the specific opioid antagonist for details of their proper use.

Because the duration of opioid reversal is expected to be less than the duration of action of acetaminophen and codeine phosphate oral solution, carefully monitor the patient until spontaneous respiration is reliably reestablished. 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.

Acetaminophen

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.

Dosage and administration

Important Dosage and Administration Instructions

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 oral 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.

Ensure that the dose is communicated clearly and dispensed accurately. A household teaspoon or tablespoon is not an adequate measuring device. Given the inexactitude of the household spoon measure and the risk of using a tablespoon instead of a teaspoon, which could lead to overdosage, it is strongly recommended that caregivers obtain and use a calibrated measuring device. Health care providers should recommend a calibrated device that can measure and deliver the prescribed dose accurately, and instruct caregivers to use extreme caution in measuring the dosage [see WARNINGS].

Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see WARNINGS].

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 to 72 hours of initiating therapy and following dosage increases with acetaminophen and codeine phosphate oral solution and adjust the dosage accordingly [see WARNINGS].

Initial Dosage

Initiating Treatment with Acetaminophen and Codeine Phosphate Oral Solution

Dosage should be adjusted according to severity of pain and response of the patient. However, it should be kept in mind that tolerance to codeine can develop with continued use and that the incidence of untoward effects is dose related. Adult doses of codeine higher than 60 mg are associated with an increased incidence of adverse reactions and are not associated with greater efficacy.

Acetaminophen and codeine phosphate oral solution 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 for children is 0.5 mg/kg body weight.

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.

Conversion from Other Opioids to Acetaminophen and Codeine Phosphate Oral Solution

There is inter-patient variability in the potency of opioid drugs and opioid formulations. Therefore, a conservative approach is advised when determining the total daily dosage of acetaminophen and codeine phosphate oral solution. It is safer to underestimate a patient’s 24-hour acetaminophen and codeine phosphate oral solution dosage than to overestimate the 24-hour acetaminophen and codeine phosphate oral solution dosage and manage an adverse reaction due to overdose.

Titration and Maintenance of Therapy

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 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 acetaminophen and codeine phosphate oral solution 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 Acetaminophen and Codeine Phosphate Oral Solution

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].

How supplied

Acetaminophen and Codeine Phosphate Oral Solution, USP is supplied in in 16 fl oz bottles, and 5 mL unit dose, 10 mL unit dose, 12.5 mL unit dose and 15 mL unit dose in tray of ten cups.

Storage

Store at 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].

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

Manufactured by:

Hi-Tech Pharmacal Co., Inc.

Amityville, NY 11701

Rev.079:13 04/17

(web3)