Talwin Nx

Patient Information

Patients receiving TALWIN NX (pentazocine and naloxone) should be given the following instructions by the physician:

• Patients should be advised that TALWIN NX (pentazocine and naloxone) is a narcotic pain reliever, and should be taken only as directed.
• The dose of TALWIN NX (pentazocine and naloxone) should not be adjusted without consulting with a physician or other healthcare professional.
• Patients should be advised that TALWIN NX (pentazocine and naloxone) may cause drowsiness, dizziness, or lightheadedness and may impair mental and/or physical ability required for the performance of potentially hazardous tasks (e.g., driving, operating machinery). Patients started on TALWIN NX (pentazocine and naloxone) or patients whose dose has been adjusted should refrain from any potentially dangerous activity until it is established that they are not adversely affected.
• TALWIN NX (pentazocine and naloxone) will add to the effect of alcohol and other CNS depressants (such as antihistamines, sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and monoamine oxidase [MAO]inhibitors).
• Patients should not combine TALWIN NX (pentazocine and naloxone) with alcohol or other central nervous system depressants (sleep aids, tranquilizers) except by the orders of the prescribing physician, because dangerous additive effects may occur, resulting in serious injury or death.
• Women of childbearing potential who become or are planning to become pregnant should consult a physician prior to initiating or continuing therapy with TALWIN NX (pentazocine and naloxone) .
• Safe use in pregnancy has not been established. Prolonged use of opioid analgesics during pregnancy may cause neonatal physical dependence, and neonatal withdrawal may occur.
• If patients have been receiving treatment with TALWIN NX (pentazocine and naloxone) for more than a few weeks and cessation of therapy is indicated, they should be counseled on the importance of safely tapering the dose and that abruptly discontinuing the medication could precipitate withdrawal symptoms. The physician should provide a dose schedule to accomplish a gradual discontinuation of the medication.
• Patients should be advised that TALWIN NX (pentazocine and naloxone) is a potential drug of abuse. They should protect it from theft. It should never be given to anyone other than the individual for whom it was prescribed.
• Patients should be instructed to keep TALWIN NX (pentazocine and naloxone) in a secure place out of the reach of children. When TALWIN NX (pentazocine and naloxone) is no longer needed, please consult your pharmacist for proper disposal instructions.
• As with other opioids, patients taking TALWIN NX (pentazocine and naloxone) should be advised of the potential for severe constipation; appropriate laxatives and/or stool softeners as well as other appropriate treatments should be initiated from the onset of opioid therapy.
• Patients should be advised of the most common adverse events that may occur while taking TALWIN NX (pentazocine and naloxone) : constipation, nausea, somnolence, lightheadedness, dizziness, sedation, vomiting, and sweating.

Description

TALWIN NX (pentazocine and naloxone hydrochlorides, USP) 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.

TALWIN NX (pentazocine and naloxone) is an analgesic for oral administration.

Chemically, pentazocine hydrochloride is (2R*,6R*,11R*)-l,2,3,4,5,6-Hexahydro-6,ll-dimethyl-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:

 

C₁₉H₂₇NO·HCl…………M.W. 321.88

 

Chemically, naloxone hydrochloride is Morphinan-6-one,4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)-, hydrochloride, (5α)-. It is a slightly off-white powder, and is soluble in water and dilute acids, and has the following structural formula:

 

C₁₉H₂₁NO₄·HCl…………..M.W.=363.84

 

Inactive Ingredients: Colloidal Silicon Dioxide, Dibasic Calcium Phosphate, D&C Yellow #10, FD&C Yellow #6, Magnesium Stearate, Microcrystalline Cellulose, Sodium Lauryl Sulfate, Starch.

Indications

TALWIN NX (pentazocine and naloxone hydrochlorides, USP) is indicated for the relief of moderate to severe pain.

TALWIN NX (pentazocine and naloxone) is indicated for oral use only.

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 TALWTN NX after prolonged periods of treatment with TALWIN NX (See PRECAUTIONS, Drug Abuse and Dependence).

How Supplied

TALWIN NX (pentazocine and naloxone hydrochlorides, USP) is available as yellow, scored, oblong tablets, debossed with a “W” surrounded by a box on one side and “T51” on the other. Each tablet contains pentazocine hydrochloride equivalent to 50 mg base and naloxone hydrochloride equivalent to 0.5 mg base.

Bottles of 100 (NDC 0024-1951-04).

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

Manufactured for: sanofi-aventis U.S. LLC Bridgewater, NJ 08807.

Side Effects

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 DependenceSections).

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

Drug Interactions

CNS Depressants

Other central nervous system (CNS) depressants including sedatives, hypnotics, general anesthetics, antiemetics, phenothiazines, or other tranquilizers or alcohol increases the risk of respiratory depression, hypotension, profound sedation, or coma. Use morphine sulfate with caution and in reduced dosages in patients taking these agents.

Opioid Agonist Analgesics

TALWIN NX (pentazocine and naloxone) can antagonize the effects of a pure opioid agonist analgesic and/or may precipitate withdrawal symptoms.

Monoamine Oxidase Inhibitors (MAOIs)

Concomitant use of monoamine oxidase inhibitors (MAOIs) with TALWIN NX (pentazocine and naloxone) may cause CNS excitation and hypertension through their respective effects on catecholamines. Caution should therefore be observed in administering TALWIN NX (pentazocine and naloxone) to patients who are currently receiving MAOIs or who have received them within the preceding 14 days

Anticholinergics

Anticholinergics or other medications with anticholinergic activity when used concurrently with opioid analgesics may result in increased risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.

Tobacco

Smoking tobacco could enhance the metabolic clearance rate of pentazocine reducing the clinical effectiveness of a standard dose of pentazocine.

WarningS

Included as part of the PRECAUTIONS section.

Precautions

Addiction, Abuse, And Misuse

TALWIN contains pentazocine, a Schedule IV controlled substance. As an opioid, TALWIN exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse And Dependence].

Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed TALWIN. Addiction can occur at recommended dosages and if the drug is misused or abused.

Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing TALWIN, and monitor all patients receiving TALWIN for the development of these behaviors or conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as TALWIN, but use in such patients necessitates intensive counseling about the risks and proper use of TALWIN along with intensive monitoring for signs of addiction, abuse, and misuse.

Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing TALWIN. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.

Life-Threatening Respiratory Depression

Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status [see OVERDOSAGE]. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of TALWIN, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with and following dosage increases of TALWIN.

To reduce the risk of respiratory depression, proper dosing and titration of TALWIN are essential [see DOSAGE AND ADMINISTRATION]. Overestimating the TALWIN dosage when converting patients from another opioid product can result in a fatal overdose with the first dose.

Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper [see DOSAGE AND ADMINISTRATION].

Neonatal Opioid Withdrawal Syndrome

Prolonged use of TALWIN during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Use In Specific Populations, PATIENT INFORMATION].

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants

Profound sedation, respiratory depression, coma, and death may result from the concomitant use of TALWIN Injection with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics [see DRUG INTERACTIONS]

If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratory depression and sedation.

Advise both patients and caregivers about the risks of respiratory depression and sedation when TALWIN Injection is used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs [see DRUG INTERACTIONS, PATIENT INFORMATION].

Life-Threatening Respiratory Depression In Patients With Chronic Pulmonary Disease Or In Elderly, Cachectic, Or Debilitated Patients

The use of TALWIN in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.

Patients With Chronic Pulmonary Disease

TALWIN-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of TALWIN [see Life-Threatening Respiratory Depression].

Elderly, Cachectic, Or Debilitated Patients

Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients [see Life-Threatening Respiratory Depression].

Monitor such patients closely, particularly when initiating and titrating TALWIN and when TALWIN is given concomitantly with other drugs that depress respiration [see Life-Threatening Respiratory Depression]. Alternatively, consider the use of non-opioid analgesics in these patients.

Adrenal Insufficiency

Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.

Severe Hypotension

TALWIN may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs  (e.g. phenothiazines or general anesthetics) [see DRUG INTERACTIONS]. Monitor these patients for signs of hypotension after initiating or titrating the dosage of TALWIN. In patients with circulatory shock, TALWIN may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of TALWIN in patients with circulatory shock.

Risks Of Use In Patients With Increased Intracranial Pressure, Brain Tumors, Head Injury, Or Impaired Consciousness

In patients who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), TALWIN may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with TALWIN.

Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of TALWIN in patients with impaired consciousness or coma.

Risks Of Use In Patients With Gastrointestinal Conditions

TALWIN is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.

The pentazocine in TALWIN may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis for worsening symptoms.

Increased Risk Of Seizures In Patients With Convulsive Or Seizure Disorders

The pentazocine in TALWIN may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during TALWIN therapy.

Withdrawal

The use of TALWIN, a mixed agonist/antagonist opioid analgesic, in patients who are receiving a full opioid agonist analgesic may reduce the analgesic effect and/or precipitate withdrawal symptoms. Avoid concomitant use of TALWIN with a full opioid agonist analgesic.

When discontinuing TALWIN in a physically-dependent patient, gradually taper the dosage [see DOSAGE AND ADMINISTRATION]. Do not abruptly discontinue TALWIN in these patients [see Drug Abuse And Dependence].

Risks Of Driving And Operating Machinery

TALWIN may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of TALWIN and know how they will react to the medication [see Patient Counseling Information].

Tissue Damage At Injection Sites

Severe sclerosis of the skin, subcutaneous 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 TALWIN is tolerated less well subcutaneously than intramuscularly [see DOSAGE AND ADMINISTRATION].

Myocardial Infarction

Caution should be exercised in the intravenous use of pentazocine for patients with acute myocardial infarction accompanied by hypertension or left ventricular failure. Data suggest that intravenous administration of pentazocine increases systemic and pulmonary arterial pressure and systemic vascular resistance in patients with acute myocardial infarction.

Impaired Renal Or Hepatic Function

Although laboratory tests have not indicated that TALWIN 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 greater 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

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.

Allergic-Type Reactions To Acetone Sodium Bisulfite

A sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people, is contained in multiple-dose vials. 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. The ampuls in the Uni-Amp™ Pak do not contain acetone sodium bisulfite.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenesis

Long-term animal studies to evaluate the carcinogenic potential of pentazocine have not been conducted.

Mutagenesis

Studies to evaluate the mutagenic potential of pentazocine have not been conducted.

Impairment Of Fertility

Animal studies to evaluate the impact of pentazocine on fertility have not been conducted.

Use In Specific Populations

Pregnancy

Risk Summary

Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome. Available data with TALWIN in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage.

In animal reproduction studies, pentazocine administered subcutaneously to pregnant hamsters during the early gestational period produced neural tube defects (i.e., exencephaly and cranioschisis) at 4.4 times the maximum daily dose [see Data]. Based on animal data, advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth.

Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see WARNINGS AND PRECAUTIONS].

Labor Or Delivery

Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. TALWIN is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including TALWIN, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. Patients receiving TALWIN during labor have experienced no adverse effects other than those that occur with commonly used analgesics.

Data

Animal Data

In a published report, a single dose of pentazocine administered to pregnant hamsters on Gestation Day 8 increased the incidence of neural tube defects (exencephaly and cranioschisis) at a dose of 196 mg/kg, SC (4.4-times the maximum daily dose (MDD) of 360 mg/day pentazocine on a body surface area basis). No evidence of neural tube defects were reported following a dose of 98 mg/kg (2.2 times the MDD).

Lactation

Risk Summary

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for TALWIN and any potential adverse effects on the breastfed infant from TALWIN or from the underlying maternal condition.

Clinical Considerations

Infants exposed to TALWIN through breast milk should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped.

Females And Males Of Reproductive Potential

Infertility

Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible [see ADVERSE REACTIONS].

Pediatric Use

The safety and efficacy of TALWIN as preoperative or preanesthetic medication have been established in pediatric patients 1 to 16 years of age. Use of TALWIN in these age groups is supported by evidence from adequate and controlled studies in adults with additional data from published controlled trials in pediatric patients. The safety and efficacy of TALWIN as a premedication for sedation have not been established in pediatric patients less than one year old. Information on the safety profile of TALWIN as a postoperative analgesic in children less than 16 years is limited.

Geriatric Use

Pentazocine is metabolized in the liver and excreted primarily in the urine. Patients with impaired renal or hepatic function may have slower elimination of the drug, and the risk of adverse reactions to this drug may be greater in these patients. Elderly patients (aged 65 years or older) may have increased sensitivity to pentazocine. In general, use caution when selecting a dosage for an elderly patient, 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.

Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of TALWIN slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression [see WARNINGS AND PRECAUTIONS].Pentazocine is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Overdose

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.

Contraindications

TALWIN NX (pentazocine and naloxone) is contraindicated in patients who are hypersensitive to either pentazocine or naloxone.

Clinical Pharmacology

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.

TALWIN NX (pentazocine and naloxone) is a potent analgesic when administered orally. However, the presence of naloxone in TALWIN NX (pentazocine and naloxone) 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.