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Pentazocine and Acetaminophen (Pentazocine Hydrochloride / Acetaminophen) - Warnings and Precautions

 
 



BOXED WARNING
Hepatotoxicity
Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4000 milligrams per day, and often involve more than one acetaminophen-containing product.

 

WARNINGS

Hepatotoxicity

Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death.  Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4000 milligrams per day, and often involve more than one acetaminophen-containing product. The excessive intake of acetaminophen may be intentional to cause self-harm or unintentional as patients attempt to obtain more pain relief or unknowingly take other acetaminophen-containing products.

The risk of acute liver failure is higher in individuals with underlying liver disease and in individuals who ingest alcohol while taking acetaminophen.

Instruct patients to look for acetaminophen or APAP on package labels and not to use more than one product that contains acetaminophen. Instruct patients to seek medical attention immediately upon ingestion of more than 4000 milligrams of acetaminophen per day, even if they feel well.

Serious skin reactions

Rarely, acetaminophen can cause serious skin reactions such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Patients should be informed about the signs of serious skin reactions, and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.

Hypersensitivity/anaphylaxis

There have been post-marketing reports of hypersensitivity and anaphylaxis associated with use of acetaminophen. Clinical signs included swelling of the face, mouth, and throat, respiratory distress, urticaria, rash, pruritus, and vomiting. There were infrequent reports of life-threatening anaphylaxis requiring emergency medical attention.  Instruct patients to discontinue Pentazocine hydrochloride and Acetaminophen Tablets, USP immediately and seek medical care if they experience these symptoms.  Do not prescribe Pentazocine Hydrochloride and Acetaminophen Tablets, USP for patients with acetaminophen allergy.

Drug Dependence

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 and acetaminophen tablets 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 and acetaminophen tablets 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 and acetaminophen tablets 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 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.

PRECAUTIONS

Drug Abuse and Dependence

Pentazocine and acetaminophen tablets are a Schedule IV controlled substance.

Abuse and addiction are separate and distinct from physical dependence and tolerance. Abuse is characterized by misuse of a drug for non-medical purposes, often in combination with other psychoactive substances. Addiction is a disease of repeated drug abuse. Addiction is a primary, chronic, neurobiologic disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations. Addiction is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. Drug addiction is a treatable disease, utilizing a multidisciplinary approach, but relapse is common. Physical dependence is a state of adaptation that is manifested by a specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist. Tolerance is a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug’s effects over time. Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.

Physicians should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts.  In addition, abuse of opioids can occur in the absence of addiction and is characterized by misuse of the drug for non-medical purposes, and often in combination with other psychoactive substances.

There have been some reports of dependence and of withdrawal symptoms with pentazocine and acetaminophen tablets. Patients with a history of drug dependence should be under close supervision while receiving pentazocine orally. There have been rare reports of possible abstinence syndromes in newborns after prolonged use of pentazocine during pregnancy.

There have been reports of development of addiction and physical dependence in patients receiving parenteral pentazocine. People with a history of drug abuse or alcohol abuse may have a higher chance of becoming addicted to opioid medicines.

Abrupt dose cessation or rapid dose reduction following the extended use of parenteral pentazocine has resulted in withdrawal symptoms such as abdominal cramps, nausea, vomiting, elevated temperature, chills, rhinorrhea, restlessness, anxiety, or lacrimation.  In general opioid therapy should not be abruptly discontinued. When the patient no longer requires treatment with pentazocine and acetaminophen, the drug should be tapered gradually to prevent signs and symptoms of withdrawal in patients who have been receiving opioids for an extended period of time and might have become physically dependent.

In prescribing pentazocine and acetaminophen tablets for chronic use, the physician should take under consideration that proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to identify and decrease misuse and abuse of opioid drugs.

Severe, even lethal, consequences may result from misuse of tablets by injection either alone or in combination with other substances, such as pulmonary emboli, vascular occlusion, ulceration and abscesses, and withdrawal symptoms in narcotic dependent individuals.

CNS Effect

Caution should be used when pentazocine and acetaminophen 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.

Porphyria

Particular caution should be exercised in administering pentazocine to patients with porphyria since it may provoke an acute attack in susceptible individuals.

Cardiovascular Disease

Pentazocine can elevate blood pressure, possibly through the release of endogenous catecholamines. Particular caution should be exercised in conditions where alterations in vascular resistance and blood pressure might be particularly undesirable, such as in the acute phase of myocardial infarction.

Pentazocine and acetaminophen tablets should be used with caution in patients with myocardial infarction who have nausea or vomiting.

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.

Acetaminophen is metabolized by the liver, and has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Therefore, pentazocine and acetaminophen tablets should be administered with caution to patients with hepatic impairment and in individuals who ingest alcohol (See BOXED WARNING  and WARNINGS, Hepatotoxicity).

Other

Caution should also be observed when administering pentazocine and acetaminophen tablets in patients with hypothyroidism, adrenocortical insufficiency, prostate hypertrophy, inflammatory or obstructive bowel disease, acute abdominal syndromes of unknown etiology, cholecystitis, pancreatitis, or acute alcohol intoxication and delirium tremens.

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.

Information for Patients

Patients receiving pentazocine and acetaminophen tablets should be given the following instructions by the physician:

  • Do not take pentazocine and acetaminophen tablets if you are allergic to any of its ingredients.
  • If you develop signs/symptoms of allergy such as a rash, hives, itching, vomiting, swelling of the face or mouth, or difficulty breathing, stop taking pentazocine and acetaminophen tablets and contact your healthcare provider immediately.
  • Do not take more than 4000 milligrams of acetaminophen (alone or in combination with other products containing acetaminophen). Seek medical attention immediately upon ingestion of more than 4000 milligrams of acetaminophen per day, even if you feel well. Look for acetaminophen or APAP on package labels. Do not use more than one product that contains acetaminophen.
  • Contact your healthcare provider if you took more than the recommended dose.
  • Patients should be advised that pentazocine and acetaminophen is a narcotic pain reliever, and should be taken only as directed.
  • The dose of pentazocine and acetaminophen should not be adjusted without consulting with a physician or other healthcare professional.
  • Patients should be advised that pentazocine and acetaminophen tablets 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 pentazocine and acetaminophen tablets or patients whose dose has been adjusted should refrain from any potentially dangerous activity until it is established that they are not adversely affected.
  • pentazocine and acetaminophen 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 pentazocine and acetaminophen tablets 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 pentazocine and acetaminophen.
  • 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 pentazocine and acetaminophen tablets 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 pentazocine and acetaminophen 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 pentazocine and acetaminophen tablets in a secure place out of the reach of children. When pentazocine and acetaminophen tablets are no longer needed, please consult your pharmacist for proper disposal instructions.
  • As with other opioids, patients taking pentazocine and acetaminophen tablets 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 pentazocine and acetaminophen tablets: constipation, nausea, somnolence, lightheadedness, dizziness, sedation, vomiting, and sweating.

Pregnancy

Teratogenic Effects

Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women.  Pentazocine and acetaminophen tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Animal studies with the combination of pentazocine and acetaminophen have not been completed.

In a published report, a single dose of pentazocine administered to pregnant hamsters on gestation day 8 increased the incidence of exencephaly and cranioschisis at a dose of 196 mg/kg, SC (0.2-times the maximum daily human dose of pentazocine via 6 tablets on a mg/m2 basis).

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. Frequent use of acetaminophen (defined as most days or daily use) in late pregnancy may be associated with an increased risk of persistent wheezing in the infant which may persist into childhood.

Labor and Delivery

Patients receiving pentazocine during labor have experienced no adverse effects other than those that occur with commonly used analgesics.  However, pentazocine can cross the placental barrier and cause central nervous system depression in the newborn and, if used regularly throughout pregnancy, may lead to symptoms of withdrawal in the newborn. Pentazocine and acetaminophen tablets should be used with caution in women delivering premature infants.  The effect of pentazocine and acetaminophen tablets 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 pentazocine and acetaminophen tablets on the later growth, development, and functional maturation of the child are unknown at the present time.

Nursing Mothers

Pentazocine and acetaminophen are excreted in human milk.  Caution should be exercised when pentazocine and acetaminophen 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 pentazocine and acetaminophen 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.

Page last updated: 2014-03-14

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