Head Injury and Increased Intracranial Pressure

As in the case of other potent analgesics, the potential of pentazocine for elevating cerebrospinal fluid pressure may be attributed to CO2 retention due to the respiratory depressant effects of the drug. These effects may be markedly exaggerated in the presence of head injury, other intracranial lesions, or a preexisting increase in intracranial pressure. Furthermore, pentazocine can produce effects which may obscure the clinical course of patients with head injuries. In such patients, TALACEN must be used with extreme caution and only if its use is deemed essential.

Acute CNS Manifestations

Patients receiving therapeutic doses of pentazocine have experienced hallucinations (usually visual), disorientation, and confusion which have cleared spontaneously within a period of hours. The mechanism of this reaction is not known. Such patients should be closely observed and vital signs checked. If the drug is reinstituted, it should be done with caution since these acute CNS manifestations may recur.

There have been instances of psychological and physical dependence on parenteral pentazocine in patients with a history of drug abuse, and rarely, in patients without such a history. (See DRUG ABUSE AND DEPENDENCE.)

Due to the potential for increased CNS depressant effects, alcohol should be used with caution in patients who are currently receiving pentazocine.

Pentazocine may precipitate opioid abstinence symptoms in patients receiving courses of opiates for pain relief.

Myocardial Infarction

As with all drugs, TALACEN should be used with caution in patients with myocardial infarction who have nausea or vomiting.

Certain Respiratory Conditions

Although respiratory depression has rarely been reported after oral administration of pentazocine, the drug should be administered with caution to patients with respiratory depression from any cause, severely limited respiratory reserve, severe bronchial asthma and other obstructive respiratory conditions, or cyanosis.

Impaired Renal or Hepatic Function

Decreased metabolism of the drug by the liver in extensive liver disease may predispose to accentuation of side effects. Although laboratory tests have not indicated that pentazocine causes or increases renal or hepatic impairment, the drug should be administered with caution to patients with such impairment.

Since acetaminophen is metabolized by the liver, the question of the safety of its use in the presence of liver disease should be considered.

Biliary Surgery

Narcotic drug products are generally considered to elevate biliary tract pressure for varying periods following their administration. Some evidence suggests that pentazocine may differ from other marketed narcotics in this respect (i.e., it causes little or no elevation in biliary tract pressures). The clinical significance of these findings, however, is not yet known.

CNS Effect

Caution should be used when TALACEN is administered to patients prone to seizures; seizures have occurred in a few such patients in association with the use of pentazocine although no cause and effect relationship has been established.

Information for Patients

Since sedation, dizziness, and occasional euphoria have been noted, ambulatory patients should be warned not to operate machinery, drive cars, or unnecessarily expose themselves to hazards. Pentazocine may cause physical and psychological dependence when taken alone and may have additive CNS depressant properties when taken in combination with alcohol or other CNS depressants.

Drug Interactions

Pentazocine is a mild narcotic antagonist. Some patients previously given narcotics, including methadone for the daily treatment of narcotic dependence, have experienced withdrawal symptoms after receiving pentazocine.

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 TALACEN. It is also not known whether TALACEN can cause fetal harm when administered to pregnant women or can affect reproduction capacity. TALACEN 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.

Labor and Delivery

Patients receiving pentazocine during labor have experienced no adverse effects other than those that occur with commonly used analgesics. TALACEN should be used with caution in women delivering premature infants. The effect of TALACEN 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 TALACEN, on the later growth, development, and functional maturation of the child are unknown at the present time.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when TALACEN is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 12 have not been established.

Geriatric Use

Clinical studies of TALACEN 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.

Controlled Substance

TALACEN is a Schedule IV controlled substance.

Abuse and Dependence

There have been some reports of dependence and of withdrawal symptoms with orally administered pentazocine. There have been recorded instances of psychological and physical dependence in patients using parenteral pentazocine. Abrupt discontinuance following the extended use of parenteral pentazocine has resulted in withdrawal symptoms. Patients with a history of drug dependence should be under close supervision while receiving TALACEN. There have been rare reports of possible abstinence syndromes in newborns after prolonged use of pentazocine during pregnancy.

Some tolerance to the analgesic and subjective effects of pentazocine develops with frequent and repeated use.

Drug addicts who are given closely spaced doses of pentazocine (e.g., 60 mg to 90 mg every 4 hours) develop physical dependence which is demonstrated by abrupt withdrawal or by administration of naloxone. The withdrawal symptoms exhibited after chronic doses of more than 500 mg of pentazocine per day have similar characteristics, but to a lesser degree, of opioid withdrawal and may be associated with drug seeking behavior.

Manifestations

Clinical experience with TALACEN has been insufficient to define the signs of overdosage with this product. It may be assumed that signs and symptoms of TALACEN 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 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 non-specific 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 TALACEN 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 TALACEN, 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 as soon as possible.

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.

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.

The usual duration of therapy is dependent upon the condition being treated but in any case should be reviewed regularly by the physician. The effect of meals on the rate and extent of bioavailability of both pentazocine and acetaminophen has not been documented.

Store at 25° C (77° F); excursions permitted between 15° – 30° C (59° – 86° F).