Action And Clinical Pharmacology: Analgesic effects: Pentazocine relieves pain of all degrees, from mild to severe, in patients with acute and chronic disorders, regardless of age or sex. Analgesia usually occurs within 15 to 30 minutes after i.m. or s.c. injection, or 2 to 3 minutes after i.v. injection, and lasts for 3 to 4 hours. A dose of 30 mg administered parenterally is approximately equal in analgesic activity to 10 mg of morphine or 75 to 100 mg of meperidine. 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.
Most authors agree that respiratory depression with pentazocine is equal to or less than opiates after a single dose. With repeated doses, however, the respiratory depressive effects are not cumulative, there being a ceiling effect at a dose of 30 to 60 mg.
Pentazocine does not significantly affect maternal blood pressure or heart rate, nor does it interfere with the progress of labor or uterine contractions. Generally there is minimal effect on Apgar ratings or fetal heart rate.
Indications And Clinical Uses: For the relief of moderate to severe pain. Also for preoperative or preanesthetic medication, and as a supplement to surgical anesthesia.
Contra-Indications: Should not be administered to patients who are hypersensitive to pentazocine.
Manufacturers’ Warnings In Clinical States: Drug Dependence: Special care should be exercised in prescribing pentazocine for emotionally unstable patients and for those with a history of drug misuse. Such patients should be closely supervised when long-term therapy is contemplated. There have been instances of psychological and physical dependence on pentazocine in patients with such a history and, rarely, in patients without such a history. Abrupt discontinuance following the extended use of parenteral pentazocine has resulted in symptoms such as abdominal cramps, elevated temperature, rhinorrhea, restlessness, anxiety, and lacrimation. Even when these occurred, discontinuance has been accomplished with minimal difficulty. In the rare patient in whom more than minor difficulty has been encountered, reinstitution of parenteral pentazocine with gradual withdrawal has ameliorated the patient’s symptoms. Substituting methadone or other narcotics for pentazocine in the treatment of the pentazocine abstinence syndrome should be avoided.
In prescribing parenteral pentazocine for chronic use, particularly if the drug is to be self-administered, the physician should take precautions to avoid increases in dose and frequency of injection by the patient and to prevent the use of the drug in anticipation of pain rather than for the relief of pain. Just as with all medication, the oral form of pentazocine is preferable for chronic administration.
Pregnancy: There have been rare reports of possible abstinence syndromes in newborns after prolonged use of pentazocine during pregnancy.
Precautions: Because pentazocine is a weak narcotic antagonist, occasional patients who are addicted to narcotics and those given methadone for the daily treatment of narcotic dependence, may experience withdrawal symptoms and therefore pentazocine should be given with special caution to such persons. In nonaddicted patients receiving narcotics for a short period, symptoms believed to be related to antagonism may be observed. Intolerance or untoward reactions are usually not observed following administration of pentazocine to patients who have received single doses or who have had limited exposure to narcotics.
Occupational Hazards: 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.
Impaired Renal or Hepatic Function: 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. Extensive liver disease appears to predispose to a higher incidence of side effects (e.g., marked apprehension, anxiety, dizziness, sleepiness) from the usual clinical dose, and may be the result of decreased metabolism of the drug by the liver.
Biliary Surgery: The drug should be used with caution in patients with acute cholecystitis or pancreatitis or in those about to undergo surgery of the biliary tract. 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 marked 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.
Obstructive Uropathy: Because urinary retention has been observed in a few patients receiving pentazocine, caution is advised in administration of the drug to patients with obstructive uropathy.
Children: Since clinical experience in children under 12 years of age is limited, the use of pentazocine in this age group is not recommended.
Pregnancy: Safe use of pentazocine during pregnancy (other than labor) has not been established. Animal reproduction studies have not demonstrated teratogenic or embryotoxic effects. However, pentazocine should be administered to pregnant patients (other than labor) only when, in the judgment of the physician, the potential benefits outweigh the possible hazards. Patients receiving pentazocine during labor have experienced no adverse effects other than those that occur with commonly used analgesics. Pentazocine should be used with caution in women delivering premature infants.
Tissue Damage at Injection Sites: Severe sclerosis of the skin, s.c. tissues and underlying muscle have occurred at the injection sites of patients who have received multiple doses of pentazocine lactate. Constant rotation of injection sites is, therefore, essential. In addition, animal studies have demonstrated that pentazocine is tolerated less well s.c. than i.m.
Myocardial Infarction: Caution should be exercised in the i.v. use of pentazocine for patients with acute myocardial infarction accompanied by hypertension or left ventricular failure. Data suggest that i.v. administration of pentazocine increases systemic and pulmonary arterial pressure and systemic vascular resistance in patients with acute myocardial infarction.
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, pentazocine must be used with extreme caution and only if its use is deemed essential.
Certain Respiratory Conditions: Pentazocine should be administered only with caution and in low dosage to patients with respiratory depression (e.g., from other medication, uremia, or severe infection), severely limited respiratory reserve, obstructive respiratory conditions, or cyanosis.
Acute CNS Manifestations: Patients receiving therapeutic doses have experienced, in rare instances, 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 very closely observed and vital signs checked. If the drug is reinstituted, it should be done with caution since the acute CNS manifestations may recur. Due to the potential for increased CNS depressant effects, alcohol should be used with caution in patients who are currently receiving pentazocine. Caution should be used when pentazocine 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.
Anesthesia: Concomitant use of CNS depressants with parenteral pentazocine may produce additive CNS depression. Adequate equipment and facilities should be available to identify and treat systemic emergencies should they occur.
Adverse Reactions: The most commonly occurring reactions are: nausea, dizziness or lightheadedness, vomiting, euphoria.
Dermatologic: Soft tissue induration, nodules, and cutaneous depression can occur at injection sites. Ulceration (sloughing) and severe sclerosis of the skin and s.c. tissues (and, rarely, underlying muscle) have been reported after multiple doses. Others include diaphoresis, sting on injection, flushed skin including plethora, dermatitis including pruritus.
Infrequently occurring reactions are: Respiratory: respiratory depression, dyspnea, transient apnea in a small number of newborn infants whose mothers received pentazocine during labor.
Cardiovascular: circulatory depression, shock, hypertension.
CNS: 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.
Gastrointestinal: constipation, dry mouth.
Other: urinary retention, headache, paresthesia, alterations in rate or strength of uterine contractions during labor.
Rarely reported reactions include: Neuromuscular and Psychiatric: muscle tremor, insomnia, disorientation, hallucinations.
Gastrointestinal: taste alteration, diarrhea and cramps.
Ophthalmic: blurred vision, nystagmus, diplopia, miosis.
Hematologic: depression of white blood cells (especially granulocytes), which is usually reversible, moderate transient eosinophilia.
Other: tachycardia, weakness or faintness, chills, allergic reactions including edema of the face, toxic epidermal necrolysis (see Acute CNS Manifestations under Precautions, and Drug Dependence under Warnings).
Symptoms And Treatment Of Overdose: Symptoms and Treatment: Like all potent analgesics, pentazocine exhibits some degree of respiratory depression although this has not proved to be a problem clinically. Pentazocine has not produced severe respiratory embarrassment in adults (never apnea), even when large amounts of the drug were used. However, moderate depression of respiration may occur occasionally. Should depression of respiration occur, oxygen, i.v. fluids, vasopressors, and other supportive measures should be employed as indicated. Assisted or controlled ventilation should also be considered. Although nalorphine and levallorphan are not effective antidotes for respiratory depression due to overdosage, parenteral naloxone (Narcan, available through Du Pont Pharma) is a specific and effective antagonist. The recommended adult dose of naloxone is 0.4 mg (1 mL) administered by i.v., i.m. or s.c routes. If the desired degree of counteraction and improvement in respiratory function is not obtained immediately, naloxone may be repeated at 2 to 3 minute intervals. Failure to obtain significant improvement after 2 to 3 doses suggests that causes other than pentazocine overdose may be responsible for the patient’s condition. Apart from this there is no specific treatment for overdosage and the patient should be treated symptomatically.
Pentazocine shares with the narcotic analgesics and narcotic antagonists the potential, at high doses, of producing convulsions in animals and electrocortical dysrhythmia in man or animals.
Dosage And Administration: Adults, Excluding Patients in Labor: the average recommended single dose for adults is 30 mg depending on the needs of the patient. This dose, administered by i.m., s.c. or i.v. injection, may be repeated every 3 to 4 hours. Pain has been controlled in most patients with not more than 3 doses daily. In selected patients, 45 to 60 mg may be administered s.c. or i.m. as required. Total daily dosage should not exceed 360 mg.
Pentazocine has been administered to patients with chronic pain for over 300 days with absence of withdrawal symptoms, even when administration was stopped abruptly. However, since in a few patients, withdrawal symptoms have occurred after frequent, prolonged use (see Warnings, Drug Dependence), it may be of value to reduce the dose gradually when the drug is no longer needed.
Patients in Labor: Although most patients in labor have received a single injection of 30 mg i.m., some have obtained adequate pain relief with an i.v. injection of 20 mg. This latter dose may be repeated 1 or 2 times at 2 to 3 hour intervals as needed.
Compatibility with Other Drugs: Pentazocine has been compatible with other concurrently administered medication, such as diazepoxides, phenothiazines, meprobamate, barbiturates, chloral hydrate, digitalis, digitoxin, aminophylline, antibiotics and oncolytic drugs. Pentazocine did not alter insulin requirements in 5 diabetic patients.
Pentazocine should not be mixed in the same syringe with soluble barbiturates, chlordiazepoxide or diazepam since precipitation will occur.
Availability And Storage: Each mL contains: pentazocine 30 mg as pentazocine lactate. Also contains sodium chloride in water for injection. Alcohol-, bisulfite-, parabens- and tartrazine-free. Ampuls of 1 mL, boxes of 25.
TALWIN® Injection Sanofi Pentazocine Lactate Analgesic