^Description Section
Pentazocine Hydrochloride and Naloxone Hydrochloride Tablets contains pentazocine hydrochloride, USP, equivalent to 50 mg base and is a member of the benzazocine series (also known as the benzomorphan series), and naloxone hydrochloride, USP, equivalent to 0.5 mg base.
Pentazocine Hydrochloride and Naloxone Hydrochloride Tablets, USP is an analgesic for oral administration.
Chemically, pentazocine hydrochloride is (2R*,6R*,11R*)-1,2,3,4,5,6-Hexahydro-6,11dimethyl-3-(3-methyl-2-butenyl)-2,6-methano-3-benzazocin-8-ol hydrochloride, a white, crystalline substance soluble in acidic aqueous solutions, and has the following structural formula:
Chemically, naloxone hydrochloride is Morphinan-6-one,4,5-epoxy-3,14-dihydroxy-17-(2propenyl)-, hydrochloride, (5α)-. It is a slightly off-white powder, and is soluble in water and dilute acids, and has the following structural formula:
^Contraindications Section
Pentazocine hydrochloride and naloxone hydrochloride tablets is contraindicated in patients who are hypersensitive to either pentazocine or naloxone.
^Adverse Reactions Section
Cardiovascular. Hypertension, hypotension, circulatory depression, tachycardia, syncope.
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.
Dependence and Withdrawal Symptoms. (See WARNINGS, PRECAUTIONS, and DRUG ABUSE AND DEPENDENCE Sections).
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.
^Precautions Section
^Boxed Warning Section
WARNING: Pentazocine Hydrochloride and Naloxone Hydrochloride Tablets, USP is intended for oral use only. Severe, potentially lethal, reactions may result from misuse of Pentazocine Hydrochloride and Naloxone Hydrochloride Tablets, USP by injection either alone or in combination with other substances. (See DRUG ABUSE AND DEPENDENCE section.)
^Indications & Usage Section
Pentazocine Hydrochloride and Naloxone Hydrochloride Tablets, USP is indicated for the relief of moderate to severe pain.
Pentazocine Hydrochloride and Naloxone Hydrochloride Tablets, USP is indicated for oral use only.
^Overdosage Section
Manifestations
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 hypertension 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.
Treatment
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. For respiratory depression due to overdosage or unusual sensitivity to pentazocine, parenteral naloxone is a specific and effective antagonist. Initial doses of 0.4 to 2.0 mg of naloxone are recommended, repeated at 2-3 minute intervals, if needed, up to a total of 10 mg. Anti-convulsant therapy may be necessary.
^Drug Abuse And Dependence Section
Pentazocine can cause a physical and psychological dependence. (See DRUG ABUSE AND DEPENDENCE.)
Use In Head Injury and Increased Intracranial Pressure
In the presence of head injury, intracranial lesions or a preexisting increase in intracranial pressure, the possible respiratory depressant effects of pentazocine and its potential to elevate cerebrospinal fluid pressure (resulting from vasodilation following CO2 retention) may be markedly increased. Furthermore, pentazocine can produce effects on pupillary response and consciousness, which may obscure neurologic signs of further increases in intracranial pressure in patients with head injuries. In such patients, pentazocine must be used with extreme caution and only if its use is deemed essential.
Interactions with Alcohol and Drugs of Abuse
Pentazocine may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression because respiratory depression, hypotension, profound sedation, coma or death may result.
Patients Receiving Narcotics
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.
Respiratory Depression
Respiratory depression occurs more frequently in elderly or debilitated patients and in those suffering from conditions accompanied by hypoxia, hypercapnia, or upper airway obstruction, in whom even moderate therapeutic doses may significantly decrease pulmonary ventilation. Use pentazocine hydrochloride and naloxone hydrochloride with extreme caution in patients with chronic obstructive pulmonary disease or cor pulmonale and in patients having a substantially decreased respiratory reserve (e.g., severe kyphoscoliosis), hypoxia, hypercapnia, or pre-existing respiratory depression. Alternative non-opioid analgesics should be considered, and pentazocine hydrochloride and naloxone hydrochloride should be employed only under careful medical supervision at the lowest effective dose in such patients.
Acute CNS Manifestations
Patients receiving therapeutic doses of pentazocine hydrochloride and naloxone hydrochloride 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 very closely observed and vital signs checked. If the drug is reinstituted, it
^Dosage & Administration Section
DOSAGE AND ADMINISTRATION
Adults
The usual initial adult dose is 1 tablet every three or four hours. This may be increased to 2 tablets when needed. Total daily dosage should not exceed 12 tablets.
Discontinuation
Due to the potential for withdrawal symptoms associated with abrupt discontinuation, consideration should be given to tapering patients off pentazocine hydrochloride and naloxone hydrochloride after prolonged periods of treatment with pentazocine hydrochloride and naloxone hydrochloride (See PRECAUTIONS, Drug Abuse and Dependence).
^Package Label.principal Display Panel
^How Supplied Section
Pentazocine Hydrochloride and Naloxone Hydrochloride Tablets, USP is available as light yellow, capsule shaped tablet debossed “NL” on left side and “680” on the right side of the bisect and plain on the other side. Each tablet contains pentazocine hydrochloride equivalent to 50 mg base and naloxone hydrochloride equivalent to 0.5 mg base.
Bottles of 100 (NDC 43386-680-01).
Store at 20° C -25° C (68° - 77° F); See USP Controlled Room Temperature.
Manufactured by:
Novel Laboratories, Inc.
Somerset, NJ 08873
Distributed by:
GAVIS Pharmaceuticals, LLC
Somerset, NJ 08873
GIN-680-01
Rev: 04/2011
^Clinical Pharmacology Section
Pentazocine is a Schedule IV opioid analgesic which when administered orally in a 50 mg dose appears equivalent in analgesic effect to 60 mg of codeine.
Pentazocine weakly antagonizes the analgesic effects of morphine and meperidine; 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.
Onset of significant analgesia usually occurs between 15 and 30 minutes after oral administration, and duration of action is usually three hours or longer.
Pentazocine is well absorbed from the gastrointestinal tract. Concentrations in plasma coincide closely with 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).
Pentazocine is metabolized in the liver and excreted primarily 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 into the fetal circulation.
Naloxone when administered orally at 0.5 mg has no pharmacologic activity. Naloxone hydrochloride administered parenterally at the same dose is an antagonist to pentazocine and a pure antagonist to narcotic analgesics.
Pentazocine hydrochloride and naloxone hydrochloride is a potent analgesic when administered orally. However, the presence of naloxone in Pentazocine hydrochloride and naloxone hydrochloride is intended to prevent the effect of pentazocine if the product is misused by injection.
Studies in animals indicate that the presence of naloxone does not affect pentazocine analgesia when the combination is given orally. If the combination is given by injection the action of pentazocine is neutralized.