Indications and Usage
Pentazocine Hydrochloride and Acetaminophen Tablets are indicated for the relief of mild to moderate pain.
Dosage and Administration
Adult
The usual adult dose is 1 caplet every 4 hours as needed for pain relief, up to a maximum of 6 caplets per day.
Discontinuation
Due to the potential for withdrawal symptoms associated with abrupt discontinuation, consideration should be given to tapering patients off pentazocine hydrochloride and acetaminophen tablets after prolonged periods of treatment with pentazocine hydrochloride and acetaminophen tablets (See PRECAUTIONS, Drug Abuse and Dependence).
Contraindications
Pentazocine hydrochloride and acetaminophen tablets are contraindicated in patients who are hypersensitive to either pentazocine or acetaminophen.
Adverse Reactions
Clinical experience with pentazocine hydrochloride and acetaminophen tablets have been insufficient to define all possible adverse reactions with this combination. However, reactions reported after oral administration of pentazocine hydrochloride in 50 mg dosage include the following:
Cardiovascular: hypertension, hypotension, circulatory depression, tachycardia.
Respiratory: rarely respiratory depression,
Acute CNS Manifestations: Hallucinations (usually visual), disorientation, and confusion
Other CNS effects: grand mal convulsions, increase in intracranial pressure, dizziness, lightheadedness, hallucinations, sedation, euphoria, headache, confusion, disorientation; infrequently weakness, disturbed dreams, insomnia, syncope, and depression; and rarely tremor, irritability, excitement, tinnitus.
Autonomic: sweating; infrequently flushing; and rarely chills.
Gastrointestinal: nausea, vomiting, constipation; diarrhea, anorexia, dry mouth, Biliary tract spasm, and rarely abdominal distress.
Allergic: edema of the face, anaphylactic shock, dermatitis including pruritus, flushed skin including plethora, infrequently rash; and rarely urticaria.
Ophthalmic: visual blurring and focusing difficulty, miosis.
Hematologic: depression of white blood cells (especially granulocytes) with rare cases of agranulocytosis, which is usually reversible, moderate transient eosinophilia.
Dependence and Withdrawal Symptoms: (See WARNINGS, PRECAUTIONS, and DRUG ABUSE AND DEPENDENCE Sections).
Other: urinary retention, paresthesia, serious skin reactions, including erythema multiforme, Stevens-Johnson Syndrome, toxic epidermal necrolysis, and alterations in rate or strength of uterine contractions during labor.
A few cases of hypersensitivity to acetaminophen have been reported, as manifested by anaphylaxis, angioneurotic edema, thrombocytopenic purpura, skin rashes, and rarely hemolytic anemia and agranulocytosis. Occasionally individuals respond to ordinary doses with nausea and vomiting and diarrhea.
Drug Interactions
CNS Depressants
Other central nervous system (CNS) depressants including sedatives, hypnotics, general anesthetics, antiemetics, phenothiazines, or other tranquilizers or alcohol increases the risk of respiratory depression, hypotension, profound sedation, or coma. Use morphine sulfate with caution and in reduced dosages in patients taking these agents.
Opioid Agonist Analgesics
Pentazocine hydrochloride and acetaminophen tablets can antagonize the effects of a pure opioid agonist analgesic and/or may precipitate withdrawal symptoms.
Monoamine Oxidase Inhibitors (MAOIs)
Concomitant use of monoamine oxidase inhibitors (MAOIs) with pentazocine hydrochloride and acetaminophen tablets may cause CNS excitation and hypertension through their respective effects on catecholamines. Caution should therefore be observed in administering pentazocine hydrochloride and acetaminophen tablets to patients who are currently receiving MAOIs or who have received them within the preceding 14 days.
Anticholinergics
Anticholinergics or other medications with anticholinergic activity when used concurrently with opioid analgesics may result in increased risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Tobacco
Smoking tobacco could enhance the metabolic clearance rate of pentazocine reducing the clinical effectiveness of a standard dose of pentazocine.
Overdosage
Signs and Symptoms
For pentazocine alone in single doses above 60 mg there have been reports of the occurrence of nalorphine-like psychotomimetic effects such as anxiety, nightmares, strange thoughts, and hallucinations. Somnolence, marked respiratory depression associated with increased blood pressure and tachycardia have also resulted as have seizures, hypotension, dizziness, nausea, vomiting, lethargy, and paresthesias. The respiratory depression is antagonized by naloxone (see Treatment ). Circulatory failure and deepening coma may occur in more severe cases, particularly in patients who have also ingested other CNS depressants such as alcohol, sedative/hypnotics, or antihistamines.
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 48-72 hours post-ingestion.
Treatment
Adequate measures to maintain ventilation and general circulatory support should be employed. Assisted or controlled ventilation, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated. Consideration should be given to gastric lavage and gastric aspiration to reduce drug absorption.
Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated. Assisted or controlled ventilation should also be considered. For respiratory depression due to overdosage or unusual sensitivity to pentazocine hydrochloride and acetaminophen tablets, parenteral naloxone is a specific and effective 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 then 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.
Description
Pentazocine Hydrochloride and Acetaminophen Tablets are a combination of pentazocine hydrochloride, USP, equivalent to 25 mg base and acetaminophen, USP, 650 mg.
Pentazocine is a member of the benzazocine series (also known as the benzomorphan series). Chemically, pentazocine is (2R*,6R*,11R*)1,2,3,4,5,6-hexahydro-6,11-dimethyl-3-(3-methyl-2-butenyl)-2,6-methano-3-benzazocin-8-ol, a white, crystalline substance soluble in acidic aqueous solutions, and has the following structural formula:
C19H27NO HCl M.W. 321.88
Chemically, acetaminophen is Acetamide, N-(4-hydroxyphenyl)-, and has the following structural formula:
C8H9NO2 M.W. 151.16
Pentazocine is an analgesic and acetaminophen is an analgesic and antipyretic.
Inactive ingredients: colloidal silicon dioxide, FD&C Blue # 1 aluminum lake, microcrystalline cellulose, sodium lauryl sulfate, sodium starch glycolate, and stearic acid.
Clinical Pharmacology
Pentazocine is a Schedule IV opioid analgesic with agonist/antagonist action which when administered orally is approximately equivalent on a mg for mg basis in analgesic effect to codeine.
Acetaminophen is an analgesic and antipyretic.
Pentazocine weakly antagonizes the analgesic effects of morphine, meperidine, and phenazocine; in addition, it produces incomplete reversal of cardiovascular, respiratory, and behavioral depression induced by morphine and meperidine. Pentazocine has about 1/50 the antagonistic activity of nalorphine. It also has sedative activity.
Onset of significant analgesia with pentazocine usually occurs between 15 and 30 minutes after oral administration, and duration of action is usually three hours or longer.
Pentazocine is well absorbed from the gastrointestinal tract. Plasma levels closely correspond to the onset, duration, and intensity of analgesia. The time to mean peak concentration in 24 normal volunteers was 1.7 hours (range 0.5 to 4 hours) after oral administration and the mean plasma elimination half-life was 3.6 hours (range 1.5 to 10 hours).
The action of pentazocine is terminated for the most part by biotransformation in the liver with some free pentazocine excreted in the urine. The products of the oxidation of the terminal methyl groups and glucuronide conjugates are excreted by the kidney. Elimination of approximately 60% of the total dose occurs within 24 hours. Pentazocine passes into fetal circulation.
Onset of significant analgesic and antipyretic activity of acetaminophen when administered orally occurs within 30 minutes and is maximal at approximately 2 1/2 hours. The pharmacological mode of action of acetaminophen is unknown at this time.
Acetaminophen is rapidly and almost completely absorbed from the gastrointestinal tract. In 24 normal volunteers the time to mean peak plasma concentration was 1 hour (range 0.25 to 3 hours) after oral administration and the mean plasma elimination half-life was 2.8 hours (range 2 to 4 hours).
The effect of pentazocine on acetaminophen plasma protein binding or vice versa has not been established. For acetaminophen there is little or no plasma protein binding at normal therapeutic doses. When toxic doses of acetaminophen are ingested and drug plasma levels exceed 90 mcg/mL, plasma binding may vary from 8% to 43%.
Acetaminophen is conjugated in the liver with glucuronic acid and to a lesser extent with sulfuric acid. Approximately 80% of acetaminophen is excreted in the urine after conjugation and about 3% is excreted unchanged. The drug is also conjugated to a lesser extent with cysteine and additionally metabolized by hydroxylation.
If pentazocine hydrochloride and acetaminophen tablets are taken every 4 hours over an extended period of time, accumulation of pentazocine and to a lesser extent, acetaminophen, may occur.
How Supplied / Storage and Handling
Pentazocine Hydrochloride and Acetaminophen Tablets are light blue capsule shaped, tablets debossed “NL” on left side and “670” on right side of bisect and plain on the other side.
Bottles of 100 (NDC 43386-670-01).
Bottles of 100 (NDC 43386-670-05)
Store at 25°C (77°F); excursions permitted between 15°-30°C (59°-86°F). [See USP.]
Dispense in a tight, light-resistant container as defined in the USP.
DEA Order Form Required.
Manufactured by:
Novel Laboratories, Inc.
Somerset, NJ 08873
Distributed by:
GAVIS Pharmaceuticals, LLC
Somerset, NJ 08873
GIN-670-02
Rev: 06/2011
Patient Counseling Information
Patients receiving pentazocine hydrochloride and acetaminophen tablets should be given the following instructions by the physician:
- Do not take pentazocine hydrochloride and acetaminophen tablets if you are allergic to any of its ingredients.
- If you develop signs/symptoms of allergy such as a rash, hives, itching, vomiting, swelling of the face or mouth, or difficulty breathing, stop taking pentazocine hydrochloride and acetaminophen tablets and contact your healthcare provider immediately.
- Do not take more than 4000 milligrams of acetaminophen (alone or in combination with other products containing acetaminophen). Seek medical attention immediately upon ingestion of more than 4000 milligrams of acetaminophen per day, even if you feel well. Look for acetaminophen or APAP on package labels. Do not use more than one product that contains acetaminophen.
- Contact your healthcare provider if you took more than the recommended dose.
- Patients should be advised that pentazocine hydrochloride and acetaminophen tablet is a narcotic pain reliever, and should be taken only as directed.
- The dose of pentazocine hydrochloride and acetaminophen tablets should not be adjusted without consulting with a physician or other healthcare professional.
- Patients should be advised that pentazocine hydrochloride and acetaminophen tablets may cause drowsiness, dizziness, or lightheadedness and may impair mental and/or physical ability required for the performance of potentially hazardous tasks (e.g., driving, operating machinery). Patients started on pentazocine hydrochloride and acetaminophen tablets or patients whose dose has been adjusted should refrain from any potentially dangerous activity until it is established that they are not adversely affected.
- Pentazocine hydrochloride and acetaminophen tablets will add to the effect of alcohol and other CNS depressants (such as antihistamines, sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and monoamine oxidase [MAO]inhibitors).
- Patients should not combine pentazocine hydrochloride and acetaminophen tablets with alcohol or other central nervous system depressants (sleep aids, tranquilizers) except by the orders of the prescribing physician, because dangerous additive effects may occur, resulting in serious injury or death.
- Women of childbearing potential who become or are planning to become pregnant should consult a physician prior to initiating or continuing therapy with pentazocine hydrochloride and acetaminophen tablets.
- Safe use in pregnancy has not been established. Prolonged use of opioid analgesics during pregnancy may cause neonatal physical dependence, and neonatal withdrawal may occur.
- If patients have been receiving treatment with pentazocine hydrochloride and acetaminophen tablets for more than a few weeks and cessation of therapy is indicated, they should be counseled on the importance of safely tapering the dose and that abruptly discontinuing the medication could precipitate withdrawal symptoms. The physician should provide a dose schedule to accomplish a gradual discontinuation of the medication.
- Patients should be advised that pentazocine hydrochloride and acetaminophen tablets are a potential drug of abuse. They should protect it from theft. It should never be given to anyone other than the individual for whom it was prescribed.
- Patients should be instructed to keep pentazocine hydrochloride and acetaminophen tablets in a secure place out of the reach of children. When pentazocine hydrochloride and acetaminophen tablets are no longer needed, please consult your pharmacist for proper disposal instructions.
- As with other opioids, patients taking pentazocine hydrochloride and acetaminophen tablets should be advised of the potential for severe constipation; appropriate laxatives and/or stool softeners as well as other appropriate treatments should be initiated from the onset of opioid therapy.
- Patients should be advised of the most common adverse events that may occur while taking pentazocine hydrochloride and acetaminophen tablets: constipation, nausea, somnolence, lightheadedness, dizziness, sedation, vomiting, and sweating.