"Nov. 2, 2012 -- Safety steps taken in the wake of the fungal meningitis outbreak have worsened drug shortages, raising questions about whether the U.S. must choose between the safety and the availability of crucial medicines.
(Generic versions may still be available.)
Risk of Overdose
There have been numerous cases of accidental and intentional overdose with propoxyphene products either alone or in combination with other CNS depressants, including alcohol. Fatalities within the first hour of overdosage are not uncommon. Many of the propoxyphene-related deaths have occurred in patients with previous histories of emotional disturbances or suicidal ideation/attempts and/or concomitant administration of sedatives, tranquilizers, muscle relaxants, antidepressants, or other CNS-depressant drugs. Do not prescribe propoxyphene for patients who are suicidal or have a history of suicidal ideation.
Respiratory depression is the chief hazard from all opioid agonist preparations. Respiratory depression occurs most frequently in elderly or debilitated patients, usually following large initial doses in non-tolerant patients, or when opioids are given in conjunction with other agents that depress respiration. Darvocet-N (propoxyphene napsylate and acetaminophen) should be used with extreme caution in patients with significant chronic obstructive pulmonary disease (COPD) or cor pulmonale, and in patients having substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression. In such patients, even usual therapeutic doses of Darvocet-N (propoxyphene napsylate and acetaminophen) may decrease respiratory drive to the point of apnea. In these patients alternative non-opioid analgesics should be considered, and opioids should be employed only under careful medical supervision at the lowest effective dose.
Darvocet-N (propoxyphene napsylate and acetaminophen) , like all opioid analgesics, may cause severe hypotension in an individual whose ability to maintain blood pressure has been compromised by a depleted blood volume, or after concurrent administration with drugs such as phenothiazines or other agents which compromise vasomotor tone. Darvocet-N (propoxyphene napsylate and acetaminophen) may produce orthostatic hypotension in ambulatory patients. Darvocet-N (propoxyphene napsylate and acetaminophen) , like all opioid analgesics, should be administered with caution to patients in circulatory shock, since vasodilatation produced by the drug may further reduce cardiac output and blood pressure.
Head Injury and Increased Intracranial Pressure
The respiratory depressant effects of narcotics and their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions or a pre-existing increase in intracranial pressure. Furthermore, narcotics produce adverse reactions which may obscure the clinical course of patients with head injuries.
The concomitant use of propoxyphene and CNS depressants, including alcohol, can result in potentially serious adverse events including death. Because of its added depressant effects, propoxyphene should be prescribed with caution for those patients whose medical condition requires the concomitant administration of sedatives, tranquilizers, muscle relaxants, antidepressants, or other CNS-depressant drugs.
Usage in Ambulatory Patients
Propoxyphene may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a car or operating machinery. The patient should be cautioned accordingly.
Use with Other Acetaminophen-Containing Agents
Due to the potential for acetaminophen hepatotoxicity at doses higher than the recommended dose, Darvocet-N (propoxyphene napsylate and acetaminophen) should not be used concomitantly with other acetaminophen-containing products.
Use with Alcohol
Hepatotoxicity and severe hepatic failure occurred in chronic alcoholics following therapeutic doses of acetaminophen. Patients should be cautioned about the concomitant use of propoxyphene products and alcohol because of potentially serious CNS-additive effects of these agents that can lead to death.
Tolerance and Physical Dependence
Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Physical dependence is manifested by withdrawal symptoms after abrupt discontinuation of a drug or upon administration of an antagonist. Physical dependence and tolerance are not unusual during chronic opioid therapy.
The opioid abstinence or withdrawal syndrome is characterized by some or all of the following: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other symptoms also may develop, including: irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. In general, opioids should not be abruptly discontinued (see DOSAGE AND ADMINISTRATION: Cessation of Therapy).
If Darvocet-N (propoxyphene napsylate and acetaminophen) is abruptly discontinued in a physically dependent patient, an abstinence syndrome may occur (see Drug Abuse And Dependence). If signs and symptoms of withdrawal occur, patients should be treated by reinstitution of opioid therapy followed by gradual tapered dose reduction of Darvocet-N (propoxyphene napsylate and acetaminophen) combined with symptomatic support (see DOSAGE AND ADMINISTRATION: Cessation of Therapy).
Use in Pancreatic/Biliary Tract Disease
Darvocet-N (propoxyphene napsylate and acetaminophen) may cause spasm of the sphincter of Oddi and should be used with caution in patients with biliary tract disease, including acute pancreatitis. Opioids like Darvocet-N (propoxyphene napsylate and acetaminophen) may cause increases in the serum amylase level.
Hepatic or Renal Impairment
Insufficient information exists to make appropriate dosing recommendations regarding the use of either propoxyphene alone or in combination with acetaminophen in patients with hepatic or renal impairment as a function of degree of impairment. Higher plasma concentrations and/or delayed elimination may occur in case of impaired hepatic function and/or impaired renal function (see CLINICAL PHARMACOLOGY). If the drug is used in these patients, it should be used with caution because of the hepatic metabolism of propoxyphene and acetaminophen and renal excretion of their metabolites.
Information for Patients/Caregivers
- Patients should be advised to report pain and adverse experiences occurring during therapy. Individualization of dosage is essential to make optimal use of this medication.
- Patients should be advised not to adjust the dose of Darvocet-N (propoxyphene napsylate and acetaminophen) without consulting the prescribing professional.
- Patients should be advised that Darvocet-N (propoxyphene napsylate and acetaminophen) may impair mental and/or physical ability required for the performance of potentially hazardous tasks (e.g., driving, operating heavy machinery).
- Patients should not combine Darvocet-N (propoxyphene napsylate and acetaminophen) with central nervous system (CNS) depressants (e.g., sleep aids, tranquilizers) except by the orders of the prescribing physician, because additive effects may occur.
- Patients should be instructed not to consume alcoholic beverages, including prescription and over-the-counter medications that contain alcohol, while using Darvocet-N (propoxyphene napsylate and acetaminophen) because of risk of serious adverse events including death.
- Women of childbearing potential who become, or are planning to become, pregnant should be advised to consult their physician regarding the effects of analgesics and other drug use during pregnancy on themselves and their unborn child.
- Patients should be advised that Darvocet-N (propoxyphene napsylate and acetaminophen) is a potential drug of abuse. They should protect it from theft, and it should never be given to anyone other than the individual for whom it was prescribed.
- Patients should be advised that if they have been receiving treatment with Darvocet-N (propoxyphene napsylate and acetaminophen) for more than a few weeks and cessation of therapy is indicated, it may be appropriate to taper the Darvocet-N (propoxyphene napsylate and acetaminophen) dose, rather than abruptly discontinue it, due to the risk of precipitating withdrawal symptoms. Their physician can provide a dose schedule to accomplish a gradual discontinuation of the medication.
- Instruct patients not to consume any other medication that contain acetaminophen, including acetaminophen-based over-the-counter medications, while taking Darvocet-N (propoxyphene napsylate and acetaminophen) .
Carcinogenesis, Mutagenesis, Impairment of Fertility
The mutagenic and carcinogenic potential of propoxyphene and acetaminophen alone and in combination have not been evaluated.
In animal studies there was no effect of propoxyphene on mating behavior, fertility, duration of gestation, or parturition when rats were fed propoxyphene as a component of their daily diet at estimated daily propoxyphene intake up to 8-fold greater than the maximum human equivalent dose (HED) based on body surface area comparison. At this highest dose, fetal weight and survival on postnatal day 4 was reduced. Acetaminophen has not been studied in animals for effects on fertility and the effects on human fertility are unknown.
Pregnancy category C.
There are no adequate and well-controlled studies of propoxyphene with acetaminophen in pregnant women. While there are limited data in the published literature, adequate animal reproduction studies have not been conducted with propoxyphene or acetaminophen. Therefore, it is not known whether propoxyphene or acetaminophen can affect reproduction or cause fetal harm when administered to a pregnant woman. Propoxyphene with acetaminophen should be given to a pregnant woman only if clearly needed.
Acetaminophen, propoxyphene and its major metabolite, norpropoxyphene, cross the human placenta. Neonates whose mothers have taken opiates chronically may exhibit respiratory depression or withdrawal symptoms.
In published animal reproduction studies, no teratogenic effects occurred in offspring born to pregnant rats or rabbits that received propoxyphene during organogenesis. Pregnant animals received propoxyphene doses approximately 10-fold (rats) and 4-fold (rabbits) the maximum recommended human dose (based on mg/m2 body surface area comparison).
Propoxyphene, norpropoxyphene (major metabolite), and acetaminophen are excreted in human milk. Published studies of nursing mothers using propoxyphene detected no adverse effects in nursing infants. Based on a study of six mother-infant pairs, an exclusively breastfed infant receives approximately 2% of the maternal weight-adjusted dose. Norpropoxyphene is renally excreted and renal clearance is lower in neonates than in adults. Therefore, it is possible that prolonged maternal propoxyphene use could result in norpropoxyphene accumulation in a breastfed infant. Watch breastfeeding infants for signs of sedation including poor feeding, somnolence, or respiratory depression. Caution should be exercised when Darvocet-N (propoxyphene napsylate and acetaminophen) is administered to a nursing woman.
Safety and effectiveness in pediatric patients have not been established.
Clinical studies of Darvocet-N (propoxyphene napsylate and acetaminophen) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, postmarketing reports suggest that patients over the age of 65 may be more susceptible to CNS-related side effects. Therefore, 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. Decreased total daily dosage should be considered (see DOSAGE AND ADMINISTRATION).
Last reviewed on RxList: 12/20/2010
This monograph has been modified to include the generic and brand name in many instances.
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