Pentazocine and Acetaminophen

TALACEN is 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 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.

Chemically,  acetaminophen  is  Acetamide, N- (4-hydroxy-phenyl)-.

Pentazocine is an analgesic and acetaminophen is an analgesic and antipyretic.

TALACEN is a pale blue, scored caplet for oral administration.

Inactive Ingredients:   Colloidal Silicon Dioxide, FD&C Blue #1, Gelatin, Microcrystalline Cellulose, Potassium Sorbate, Pregelatinized Starch, Sodium Lauryl Sulfate, Sodium Metabisulfite, Sodium Starch Glycolate, Stearic Acid.

CLINICAL PHARMACOLOGY

TALACEN is an analgesic possessing antipyretic actions.

Pentazocine is an 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.

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. Onset and duration of action and the degree of pain relief are related both to dose and the severity of pretreatment pain. 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.

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 the placental barrier.

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 TALACEN is taken every 4 hours over an extended period of time, accumulation of pentazocine and to a lesser extent, acetaminophen, may occur.

INDICATIONS

TALACEN is 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.

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.

  HOW SUPPLIED

Talacen is available as a pale blue, scored caplet embossed with "Winthrop" on one side and "T37" on the other side.

Bottles of 100 (NDC 0024-1937-04).

Unit Dose Dispenser Package of 250 (NDC 0024-1937-14), 10 sleeves of 25 caplets each.

Store at controlled room temperature 15° C to 30° C (59° F to 86° F).

SIDE EFFECTS

Clinical experience with TALACEN has 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 gastrointestinal: nausea, vomiting, infrequently constipation; and rarely abdominal distress, anorexia, diarrhea. CNS effects: dizziness, lightheadedness, hallucinations, sedation, euphoria, headache, confusion, disorientation; infrequently weakness, disturbed dreams, insomnia, syncope, visual blurring and focusing difficulty, depression; and rarely tremor, irritability, excitement, tinnitus. Autonomic: sweating; infrequently flushing; and rarely chills. Allergic: infrequently rash; and rarely urticaria, edema of the face. Cardiovascular: infrequently decrease in blood pressure, tachycardia. Hematologic: rarely depression of white blood cells (especially granulocytes), which is usually reversible, moderate transient eosinophilia. Other: rarely respiratory depression, urinary retention, paresthesia, serious skin reactions, including erythema multiforme, Stevens-Johnson Syndrome, toxic epidermal necrolysis, and in one instance, an apparent anaphylactic reaction has been reported.

Numerous clinical studies have shown that acetaminophen, when taken in recommended doses, is relatively free of adverse effects in most age groups, even in the presence of a variety of disease states.

A few cases of hypersensitivity to acetaminophen have been reported, as manifested by skin rashes, thrombocytopenic purpura, rarely hemolytic anemia and agranulocytosis. Occasional individuals respond to ordinary doses with nausea and vomiting and diarrhea.

DRUG ABUSE AND DEPENDENCE

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.

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.

WARNINGS

Contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.

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 CO ₂ 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.

PRECAUTIONS

In prescribing TALACEN for chronic use, the physician should take precautions to avoid increases in dose by the patient.

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.