Pentazocine and Acetaminophen (Pentazocine Hydrochloride / Acetaminophen) - Drug Interactions, Contraindications, Overdosage

DRUG INTERACTIONS

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis, mutagenesis, and impairment of fertility studies have not been done with this combination product.

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.

There is no evidence in long-term animal studies to demonstrate that pentazocine is carcinogenic.

Pregnancy Category C

Animal reproduction studies have not been conducted with pentazocine hydrochloride and acetaminophen tablets. It is also not known whether pentazocine hydrochloride and acetaminophen tablets can cause fetal harm when administered to pregnant women or can affect reproduction capacity. Pentazocine hydrochloride and acetaminophen tablets should be given to pregnant women only if clearly needed. However, animal reproduction studies with pentazocine have not demonstrated teratogenic or embryotoxic effects.

Nonteratogenic Effects

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.

OVERDOSAGE

Manifestations

Clinical experience with pentazocine hydrochloride and acetaminophen tablets has been insufficient to define the signs of overdosage with this product. It may be assumed that signs and symptoms of pentazocine hydrochloride and acetaminophen tablets overdose would be a combination of those observed with pentazocine overdose and acetaminophen overdose.

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. Marked respiratory depression associated with increased blood pressure and tachycardia have also resulted from excessive doses as have dizziness, nausea, vomiting, lethargy, and paresthesias. The respiratory depression is antagonized by naloxone (see Treatment).

In acute acetaminophen overdosage, dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necrosis, hypoglycemic coma, and thrombocytopenia may also occur.

In adults, a single dose of 10 g to 15 g (200 mg/kg to 250 mg/kg) of acetaminophen may cause hepatotoxicity. A dose of 25 g or more is potentially fatal. The potential seriousness of the intoxication may not be evident during the first two days of acute acetaminophen poisoning. During the first 24 hours, nausea, vomiting, anorexia, and abdominal pain occur. These may persist for a week or more. Liver injury may become evident the second day, initial signs being elevation of the serum transaminase and lactic dehydrogenase activity, increased serum bilirubin concentration, and prolongation of prothrombin time. Serum albumin concentration and alkaline phosphatase activity may remain normal. The hepatotoxicity may lead to encephalopathy, coma, and death. Transient azotemia is evident in a majority of patients and acute renal failure occurs in some.

There have been reports of glycosuria and impaired glucose tolerance, but hypoglycemia may also occur. Metabolic acidosis and metabolic alkalosis have been reported. Cerebral edema and nonspecific myocardial depression have also been noted. Biopsy reveals centrolobular necrosis with sparing of the periportal area. The hepatic lesions are reversible over a period of weeks or months in nonfatal cases.

The severity of the liver injury can be determined by measurement of the plasma halftime of acetaminophen during the first day of acute poisoning. If the halftime exceeds 4 hours, hepatic necrosis is likely and if the halftime is greater than 12 hours, hepatic coma will probably occur. Only minimal liver damage has developed when the serum concentration was below 120 mcg/mL at 12 hours after ingestion of the drug. If serum bilirubin concentration is greater than 4 mg/100 mL during the first 5 days, encephalopathy may occur.

The seven day oral LD₅₀ value for pentazocine hydrochloride and acetaminophen tablets in mice is 3,570 mg/kg.

Treatment

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.

The toxic effects of acetaminophen may be prevented or minimized by antidotal therapy with N-acetylcysteine. In order to obtain the best possible results, N-acetylcysteine should be administered within approximately 16 hours of ingestion of the overdose.

For complete prescribing information for the approved use of acetylcysteine in the treatment of acetaminophen overdose, see the package insert for acetylcysteine.

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. Induction of vomiting or gastric lavage, followed by oral administration of activated charcoal should be done in all cases.

If hemodialysis can be initiated within the first 12 hours, it is advocated for patients with a plasma acetaminophen concentration exceeding 120 mcg/mL at 4 hours after ingestion of the drug.

CONTRAINDICATIONS

Pentazocine hydrochloride and acetaminophen tablets should not be administered to patients who are hypersensitive to either pentazocine or acetaminophen.