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 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.
Smoking tobacco could enhance the metabolic clearance rate of pentazocine reducing the clinical effectiveness of a standard dose of pentazocine.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis, mutagenesis, and impairment of fertility studies have not been done with this combination product.
Studies to evaluate the mutagenic potential of the components of pentazocine hydrochloride and acetaminophen tablets have not been conducted.
Pentazocine, when administered orally or parenterally, had no adverse effect on either the reproductive capabilities or the course of pregnancy in rabbits and rats. Embryotoxic effects on the fetuses were not shown.
The daily administration of 4 mg/kg to 20 mg/kg pentazocine subcutaneously to female rats during a 14 day pre-mating period and until the 13th day of pregnancy did not have any adverse effects on the fertility rate.
Pregnancy Category C
There are no adequate and well-controlled studies in pregnant women. Pentazocine hydrochloride and acetaminophen tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Animal studies with the combination of pentazocine and acetaminophen have not been completed.
In a published report, a single dose of pentazocine administered to pregnant hamsters on gestation day 8 increased the incidence of exencephaly and cranioschisis at a dose of 196 mg/kg, SC (0.2-times the maximum daily human dose of pentazocine via 6 caplets on a mg/m2 basis).
There has been no experience in this regard with the combination pentazocine and acetaminophen. However, there have been rare reports of possible abstinence syndromes in newborns after prolonged use of pentazocine during pregnancy. Frequent use of acetaminophen (defined as most days or daily use) in late pregnancy may be associated with an increased risk of persistent wheezing in the infant which may persist into childhood.
Patients receiving pentazocine during labor have experienced no adverse effects other than those that occur with commonly used analgesics. However, pentazocine can cross the placental barrier and cause central nervous system depression in the newborn and, if used regularly throughout pregnancy, may lead to symptoms of withdrawal in the newborn. Pentazocine hydrochloride and acetaminophen tablets should be used with caution in women delivering premature infants. The effect of pentazocine hydrochloride and acetaminophen tablets on the mother and fetus, the duration of labor or delivery, the possibility that forceps delivery or other intervention or resuscitation of the newborn may be necessary, or the effect of pentazocine hydrochloride and acetaminophen tablets, on the later growth, development, and functional maturation of the child are unknown at the present time.
Pentazocine and acetaminophen are excreted in human milk. Caution should be exercised when pentazocine hydrochloride and acetaminophen tablets are administered to a nursing woman.
Safety and effectiveness in pediatric patients below the age of 12 have not been established.
Clinical studies of pentazocine hydrochloride and acetaminophen tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, 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.
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.
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.
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.
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.
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