英文药名: Darvocet(Propoxyphene Pink Tablets)

中文药名: 丙氧芬粉红片

药品介绍

止痛药丙氧芬（propoxyphene）作为止痛药达尔丰（Darvon）出售，与对乙酰氨基酚混和被称为Darvocet。
右丙氧芬是一种弱阿片类止痛药，止痛效果弱于吗啡，与可待因接近。临床常与对乙酰氨基酚组成复方制剂，广泛用于治疗慢性或复发性中度疼痛性疾病。与其他镇痛药相比，右丙氧芬有起效快的特点。在推荐剂量下，右丙氧芬的副作用不如吗啡明显，最常见的不良反应包括：胃肠道反应、眩晕、嗜睡。有肝损害的病例报告。该药物的治疗窗窄，过量可引起严重毒性反应。另外，右丙氧芬在某些国家还是一种戒毒药。
与一般的阿片类药物不同，右丙氧芬对心脏可能有一定的副作用，这种毒性作用是剂量依赖性的，主要导致心电图中QRS波异常。右丙氧芬过量引起死亡发生的速度很快。很多都是在药物过量后一小时内发生，甚至可以在15分钟内发生，约80％的病人还来不及送到医院就已死亡。
早在2004年4月，英国药品和健康产品管理局的药品安全委员会对右丙氧芬进行了风险/效益评估，认为co-proxamol（325mg对乙酰氨基酚和32.5mg盐酸右丙氧芬复合制剂）的有效性不明确，但其过量引发的毒性风险远大于治疗获益。2005年1月，英国药品和健康产品管理局宣布了对co-proxamol的撤市决定。2007年1月17日，英国药品和健康产品管理局再次发布信息，称由于一些患者无法找到其他合适的替代药品，在co-proxamol完全撤市后，还将继续保留一部分供应，由医生负责处方给病人。
在美国，同样的药品曾获FDA批准。美国目前上市的类似药品还有萘磺酸右丙氧芬与对乙酰氨基酚的复合制剂。2006年2月，美国消费者组织“公共市民”以该类药品毒性大、有潜在成瘾性、容易滥用且疗效不佳为由，向FDA建议撤市所有含右丙氧芬的产品。目前，固定剂量(fixed dose)的右丙氧芬和对乙酰氨基酚复方制剂也已经从瑞典和瑞士市场撤出。
在我国，右丙氧芬已列入我国2005年9月颁布的《麻醉药品品种目录》，按麻醉药品管理，但其复方制剂不在此管理范围内，丙氧氨酚复方片作为II类精神药品，按处方药管理。目前世界范围内使用的含右丙氧芬的复方制剂主要包括两类：盐酸右丙氧芬＋对乙酰氨基酚（如英国的co-proxamol）和萘磺酸右丙氧芬＋对乙酰氨基酚（如美国的Darvocet系列和中国的达宁、同必妥）。
中国目前共有两个批准文号的右丙氧芬和对乙酰氨基酚的复合制剂，分别是达宁（萘磺酸右丙氧50mg：对乙酰氨基酚250mg）和同立妥（萘磺酸右丙氧50mg：对乙酰氨基酚250mg），通用名都是丙氧氨酚复方片。自2002年和2003年批准上市后，国家药物不良反应中心病例报告数据库中，有关丙氧氨酚的不良反应报告共43例，主要不良反应为胃肠道反应和头晕，无死亡病例。
 
专家的用药建议
公众对含右丙氧芬的制剂最大恐惧是过量导致的死亡。虽然FDA的一个顾问委员会今年１月底也曾建议FDA对此类镇痛药颁发销售禁令，但本次FDA并没有取缔右丙氧芬类镇痛药，而是加强风险提示，并责令相关机构进一步研究右丙氧芬的安全性，以评估其在超剂量使用时，可能对心脏产生的一些尚不明晰的影响。这说明到目前为止，除滥用和过量应用外，含右丙氧芬的制剂还是相对安全的。
 
药理作用
右丙氧芬主要为μ受体激动剂。其化学结构和药理作用与美沙酮相似。镇痛作用较弱，仅能用于缓解轻度至中度疼痛。几乎没有镇咳作用。
 
药动学
口服吸收快，有首关效应，生物利用度为30％～70％。主要在肝脏代谢为去甲丙氧芬后从尿中排泄。表观分布容积为10～26 L／kg。口服清除率为1.3～3.6 L／min，全身性清除率为O.6～1.2 L／min。代谢产物去甲丙氧芬的半衰期为22.9小时。
 
适应症
本品镇痛作用弱，多与解热镇痛药阿司匹林、氨基比林或对乙酰氨基酚组成复方片剂，适用于慢性风湿性关节炎、偏头痛。
 
用法用量
口服：每次65mg盐酸右丙氧芬或100mg萘磺酸右丙氧芬，4～6小时可重复。
 
不良反应
常见的不良反应有头晕、嗜睡、恶心、呕吐；较少见的有便秘、腹痛、皮疹、头痛，偶见虚弱、欣快、发音困难和轻度视力障碍。过量中毒表现为呼吸抑制、极端困倦乏力，随之昏迷、瞳孔缩小、局部或全身抽搐、心脏传导异常、心律失常、肺水肿，甚至出现呼吸暂停和心脏停搏。过量中毒与去甲丙氧芬蓄积有关。纳洛酮可对抗呼吸抑制等作用，用于解救。

药物相互作用
酒精和其他中枢抑制药可加重其过量中毒效应。
 
注意事项
1.本品不作为注射给药。
2.用药过程中须注意是否有过量中毒表现如呼吸抑制等。

Description
Propoxyphene Napsylate, USP is an odorless, white, crystalline solid with a bitter taste. It is very slightly soluble in water and soluble in methanol, ethanol, chloroform, and acetone. Chemically, it is (αS,1R)-α-[2-(Dimethylamino)-1-methylethyl]-α-phenylphenethyl propionate compound with 2-napthalenesulfonic acid (1:1) monohydrate, which can be represented by the accompanying structural formula:

Propoxyphene napsylate differs from propoxyphene hydrochloride in that it allows more stable liquid dosage forms and tablet formulations. Because of differences in molecular weight, a dose of 100 mg (176.8 mcmol) of propoxyphene napsylate is required to supply an amount of propoxyphene equivalent to that present in 65 mg (172.9 mcmol) of propoxyphene hydrochloride.

The acetaminophen component is 4'-Hydroxyacetanilide, a white, odorless, crystalline powder possessing a slightly bitter taste, and is represented by the following structural formula:

Propoxyphene napsylate and acetaminophen is supplied in tablet form for oral administration.

Propoxyphene Napsylate and Acetaminophen Tablets, USP 50 mg/325 mg

Each tablet contains:

Propoxyphene Napsylate ...........................50 mg
Acetaminophen..........................................325 mg

In addition each tablet contains the following inactive ingredients: carnauba wax, D&C Yellow #10 Aluminum Lake, FD&C Red #40 Aluminum Lake, hypromellose, lactose monohydrate, magnesium stearate, polyethylene glycol, polysorbate 80, sodium starch glycolate and titanium dioxide.

Propoxyphene Napsylate and Acetaminophen Tablets, USP 100 mg/650 mg

Each tablet contains:

Propoxyphene Napsylate ..........................100 mg
Acetaminophen...........................................650 mg

In addition each tablet contains the following inactive ingredients: carnauba wax, hypromellose, lactose monohydrate, magnesium stearate, polyethylene glycol, polysorbate 80, sodium starch glycolate and titanium dioxide. The orange tablets also contain D&C Yellow #10 Aluminum Lake and FD&C Red #40 Aluminum Lake. The pink tablets also contain FD&C Red #40 Aluminum Lake.

Clinical Pharmacology

Propoxyphene is a centrally acting narcotic analgesic agent. Equimolar doses of propoxyphene hydrochloride or napsylate provide similar plasma concentrations. Following administration of 65, 130, or 195 mg of propoxyphene hydrochloride, the bioavailability of propoxyphene is equivalent to that of 100, 200, or 300 mg respectively of propoxyphene napsylate. Peak plasma concentrations of propoxyphene are reached in 2 to 2 1/2 hours. After a 100 mg oral dose of propoxyphene napsylate, peak plasma levels of 0.05 to 0.1 mcg/mL are achieved. As shown in Figure 1, the napsylate salt tends to be absorbed more slowly than the hydrochloride. At or near therapeutic doses, this absorption difference is small when compared with that among subjects and among doses.

Because of this several hundredfold difference in solubility, the absorption rate of very large doses of the napsylate salt is significantly lower than that of equimolar doses of the hydrochloride.

Repeated doses of propoxyphene at 6 hour intervals lead to increasing plasma concentrations, with a plateau after the ninth dose at 48 hours.

Figure 1. Mean plasma concentrations of propopxyphene in 8 human subjects following oral administration of 65 and 130 mg of the hydrochloride salt and 100 mg and 200 mg of the napsylate salt and in 7 given 195 mg of the hydrochloride and 300 mg of the napyslate salt.

Propoxyphene is metabolized in the liver to yield norpropoxyphene. Propoxyphene has a half-life of 6 to 12 hours, whereas that of norpropoxyphene is 30 to 36 hours.

Norpropoxyphene has substantially less central nervous system depressant effect than propoxyphene but a greater local anesthetic effect, which is similar to that of amitriptyline and antiarrhythmic agents such as lidocaine and quinidine.

In animal studies in which propoxyphene and norpropoxyphene were continuously infused in large amounts, intracardiac conduction time (PR and QRS intervals) was prolonged. Any intracardiac conduction delay attributable to high concentrations of norpropoxyphene may be of relatively long duration.

Actions

Propoxyphene is a mild narcotic analgesic structurally related to methadone. The potency of propoxyphene napsylate is from two-thirds to equal that of codeine.

Propoxyphene napsylate and acetaminophen tablets provide the analgesic activity of propoxyphene napsylate and the antipyretic-analgesic activity of acetaminophen.

The combination of propoxyphene and acetaminophen produces greater analgesia than that produced by either propoxyphene or acetaminophen administered alone.

Indications and Usage

Propoxyphene napsylate and acetaminophen tablets are indicated for the relief of mild to moderate pain, either when pain is present alone or when it is accompanied by fever.

Contraindications

Hypersensitivity to propoxyphene or to acetaminophen.

Warnings

• Do not prescribe propoxyphene for patients who are suicidal or addiction-prone.
• Prescribe propoxyphene with caution for patients taking tranquilizers or antidepressant drugs and patients who use alcohol in excess.
• Tell your patients not to exceed the recommended dose and to limit their intake of alcohol.

Propoxyphene products in excessive doses, either alone or in combination with other CNS depressants, including alcohol, are a major cause of drug-related deaths. Fatalities within the first hour of overdosage are not uncommon. In a survey of deaths due to overdosage conducted in 1975, in approximately 20% of the fatal cases, death occurred within the first hour (5% occurred within 15 minutes). Propoxyphene should not be taken in doses higher than those recommended by the physician. The judicious prescribing of propoxyphene is essential to the safe use of this drug. With patients who are depressed or suicidal, consideration should be given to the use of non-narcotic analgesics. Patients should be cautioned about the concomitant use of propoxyphene products and alcohol because of potentially serious CNS-additive effects of these agents. 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. Patients should be advised of the additive depressant effects of these combinations.

Many of the propoxyphene-related deaths have occurred in patients with previous histories of emotional disturbances or suicidal ideation or attempts as well as histories of misuse of tranquilizers, alcohol, and other CNS-active drugs. Some deaths have occurred as a consequence of the accidental ingestion of excessive quantities of propoxyphene alone or in combination with other drugs. Patients taking propoxyphene should be warned not to exceed the dosage recommended by the physician.

Drug Dependence

Propoxyphene, when taken in higher-than-recommended doses over long periods of time, can produce drug dependence characterized by psychic dependence and less frequently, physical dependence and tolerance. Propoxyphene will only partially suppress the withdrawal syndrome in individuals physically dependent on morphine or other narcotics. The abuse liability of propoxyphene is qualitatively similar to that of codeine although quantitatively less, and propoxyphene should be prescribed with the same degree of caution appropriate to the use of codeine.

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.

Precautions

General

Propoxyphene should be administered with caution to patients with hepatic or renal impairment since higher serum concentrations or delayed elimination may occur.

Information for Patients

A Patient Information Sheet is available for this product. See text below.

Drug Interactions

The CNS-depressant effect of propoxyphene is additive with that of other CNS depressants, including alcohol.

As is the case with many medicinal agents, propoxyphene may slow the metabolism of a concomitantly administered drug. Should this occur, the higher serum concentrations of that drug may result in increased pharmacologic or adverse effects of that drug. Such occurrences have been reported when propoxyphene was administered to patients on antidepressants, anticonvulsants, or warfarin-like drugs. Severe neurologic signs, including coma, have occurred with concurrent use of carbamazepine.

Pregnancy

Safe use in pregnancy has not been established relative to possible adverse effects on fetal development. Instances of withdrawal symptoms in the neonate have been reported following usage during pregnancy. Therefore, propoxyphene should not be used in pregnant women unless, in the judgement of the physician, the potential benefits outweigh the possible hazards.

Nursing Mothers

Low levels of propoxyphene have been detected in human milk. In postpartum studies involving nursing mothers who were given propoxyphene, no adverse effects were noted in infants receiving mother's milk. Caution should be exercised when propoxyphene napsylate and acetaminophen tablets are administered to a nursing woman.

Pediatric Use

Propoxyphene is not recommended for use in pediatric patients because documented clinical experience has been insufficient to establish safety and a suitable dosage regimen in the pediatric age group.

Geriatric Use

The rate of propoxyphene metabolism may be reduced in some patients. Increased dosing interval should be considered.

Adverse Reactions

In a survey conducted in hospitalized patients, less than 1% of patients taking propoxyphene hydrochloride at recommended doses experienced side effects. The most frequently reported were dizziness, sedation, nausea, and vomiting. Some of these adverse reactions may be alleviated if the patient lies down. Other adverse reactions include constipation, abdominal pain, skin rashes, lightheadedness, headache, weakness, euphoria, dysphoria, hallucinations, and minor visual disturbances.

Liver dysfunction has been reported in association with both active components of propoxyphene napsylate and acetaminophen tablets. Propoxyphene therapy has been associated with abnormal liver function tests and, more rarely, with instances of reversible jaundice (including cholestatic jaundice). Hepatic necrosis may result from acute overdose of acetaminophen (see Overdosage). In chronic ethanol abusers, this has been reported rarely with short-term use of acetaminophen doses of 2.5 to 10 g/day. Fatalities have occurred.

Renal papillary necrosis may result from chronic acetaminophen use, particularly when the dosage is greater than recommended and when combined with aspirin. Subacute painful myopathy has occurred following chronic propoxyphene overdosage.

Overdosage

In all cases of suspected overdosage, call your regional Poison Control Center to obtain the most up-to-date information about the treatment of overdose. This recommendation is made because, in general, information regarding the treatment of overdosage may change more rapidly than do package inserts. Initial consideration should be given to the management of the CNS effects of propoxyphene overdosage. Resuscitative measures should be initiated promptly.

Symptoms of Propoxyphene Overdosage

The manifestations of acute overdosage with propoxyphene are those of narcotic overdosage. The patient is usually somnolent but may be stuporous or comatose and convulsing. Respiratory depression is characteristic. The ventilatory rate and/or tidal volume is decreased, which results in cyanosis and hypoxia. Pupils, initially pinpoint, may become dilated as hypoxia increases. Cheyne-Stokes respiration and apnea may occur. Blood pressure and heart rate are usually normal initially, but blood pressure falls and cardiac performance deteriorates, which ultimately results in pulmonary edema and circulatory collapse, unless the respiratory depression is corrected and adequate ventilation is restored promptly. Cardiac arrhythmias and conduction delay may be present. A combined respiratory-metabolic acidosis occurs owing to retained CO2 (hypercapnia) and to lactic acid formed during anaerobic glycolysis. Acidosis may be severe if large amounts of salicylates have also been ingested. Death may occur.

Treatment of Propoxyphene Overdosage

Attention should be directed first to establishing a patent airway and to restoring ventilation. Mechanically assisted ventilation, with or without oxygen, may be required, and positive pressure respiration may be desirable if pulmonary edema is present. The narcotic antagonist naloxone will markedly reduce the degree of respiratory depression, and 0.4 to 2 mg should be administered promptly, preferably intravenously. If the desired degree of counteraction with improvement in respiratory functions is not obtained, naloxone should be repeated at 2 to 3 minute intervals. The duration of action of the antagonist may be brief. If no response is observed after 10 mg of naloxone have been administered, the diagnosis of propoxyphene toxicity should be questioned. Naloxone may also be administered by continuous intravenous infusion.

Treatment of Propoxyphene Overdosage in Children

The usual initial dose of naloxone in children is 0.01 mg/kg body weight given intravenously. If this dose does not result in the desired degree of clinical improvement, a subsequent increased dose of 0.1 mg/kg body weight may be administered. If an IV route of administration is not available, naloxone may be administered IM or subcutaneously in divided doses. If necessary, naloxone can be diluted with Sterile Water for injection.

Blood gases, pH, and electrolytes should be monitored in order that acidosis and any electrolyte disturbance present may be corrected promptly. Acidosis, hypoxia, and generalized CNS depression predispose to the development of cardiac arrhythmias. Ventricular fibrillation or cardiac arrest may occur and necessitate the full complement of cardiopulmonary resuscitation (CPR) measures. Respiratory acidosis rapidly subsides as ventilation is restored and hypercapnia eliminated, but lactic acidosis may require intravenous bicarbonate for prompt correction.

Electrocardiographic monitoring is essential. Prompt correction of hypoxia, acidosis, and electrolyte disturbance (when present) will help prevent these cardiac complications and will increase the effectiveness of agents administered to restore normal cardiac function.

In addition to the use of a narcotic antagonist, the patient may require careful titration with an anticonvulsant to control convulsions. Analeptic drugs (for example, caffeine or amphetamine) should not be used because of their tendency to precipitate convulsions.

General supportive measures, in addition to oxygen, include, when necessary, intravenous fluids, vasopressor-inotropic compounds, and when infection is likely, anti-infective agents. Gastric lavage may be useful, and activated charcoal can adsorb a significant amount of ingested propoxyphene. Dialysis is of little value in poisoning due to propoxyphene. Efforts should be made to determine whether other agents, such as alcohol, barbiturates, tranquilizers or other CNS depressants, were also ingested, since these increase CNS depression as well as cause specific toxic effects.

Symptoms of Acetaminophen Overdosage

Shortly after oral ingestion of an overdosage of acetaminophen and for the next 24 hours, anorexia, nausea, vomiting, diaphoresis, general malaise, and abdominal pain have been noted. The patient may then present no symptoms, but evidence of liver dysfunction may become apparent up to 72 hours after ingestion, with elevated serum transaminase and lactic dehydrogenase levels, an increase in serum bilirubin concentrations, and a prolonged prothrombin time. Death from hepatic failure may result 3 to 7 days after overdosage.

Acute renal failure may accompany the hepatic dysfunction and has been noted in patients who do not exhibit signs of fulminant hepatic failure. Typically, renal impairment is more apparent 6 to 9 days after ingestion of the overdose.

Treatment of Acetaminophen Overdosage

Acetaminophen in massive overdosage may cause hepatic toxicity in some patients. In all cases of suspected overdose, immediately call your regional poison center or the Rocky Mountain Poison Center's toll-free number (800-525-6115)  for assistance in diagnosis and for directions in the use of N-acetylcysteine as an antidote.

In adults, hepatic toxicity has rarely been reported with acute overdoses of less than 10 g and fatalities with less than 15 g. Importantly, young children seem to be more resistant than adults to the hepatotoxic effect of an acetaminophen overdose. Despite this, the measures outlined below should be initiated in any adult or child suspected of having ingested an acetaminophen overdose.

Because clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours postingestion, liver function studies should be obtained initially and repeated at 24-hour intervals.

Consider emptying the stomach promptly by lavage or by induction of emesis with syrup of ipecac. Patients' estimates of the quantity of a drug ingested are notoriously unreliable. Therefore, if an acetaminophen overdose is suspected, a serum acetaminophen assay should be obtained as early as possible, but no sooner than 4 hours following ingestion. The antidote, N-acetylcysteine, should be administered as early as possible, preferably within 16 hours of the overdose ingestion for optimal results. Following recovery, there are no residual, structural, or functional hepatic abnormalities.

Dosage and Administration

This products is given orally. The usual dosage is 100 mg propoxyphene napsylate and 500 mg acetaminophen every 4 hours as needed for pain. The maximum recommended dose of propoxyphene napsylate is 600 mg per day.

Consideration should be given to a reduced total daily dosage in patients with hepatic or renal impairment.

How Supplied

Propoxyphene napsylate and acetaminophen tablets contain 50 mg propoxyphene napsylate and 325 mg acetaminophen. They are supplied as orange film coated, unscored, capsule shaped tablets, debossed "5111" and "V" in containers of 10, 100, 500 and 1000 and unit dose packages of 100's.

Propoxyphene napsylate and acetaminophen tablets contain 100 mg propoxyphene napsylate and 650 mg acetaminophen. They are supplied as orange film coated, unscored, capsule shaped tablets, debossed "5112" and "V", in white film coated, unscored capsule shaped tablets, debossed "5113" and "V" and in pink film coated, unscored capsule shaped tablets, debossed "5114" and "V" in containers of 20, 30, 50, 60, 90, 100, 120, 180, 270, 500 and 1000.

Dispense in a tight, light-resistant container as defined in the USP/NF with a child-resistant closure.

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
ANIMAL TOXICOLOGY

The acute lethal doses of the hydrochloride and napsylate salts of propoxyphene were determined in 4 species. The results shown in Figure 2 indicate that, on a molar basis, the napsylate salt is less toxic than the hydrochloride. This may be due to the relative insolubility and retarded absorption of propoxyphene napsylate.

Figure 2

ACUTE ORAL TOXICITY OF PROPOXYPHENE
	LD50 (mg/kg) ± SE LD50 (mmol/kg)
Species	Propoxyphene Hydrochloride	Propoxyphene Napsylate
Mouse	282 ± 39	915 ± 163
	0.75	1.62
Rat	230 ± 44	647 ± 95
	0.61	1.14
Rabbit	ca 82	>183
	0.22	>0.32
Dog	ca 100	>183
	0.27	>0.32

Some indication of the relative insolubility and retarded absorption of propoxyphene napsylate was obtained by measuring plasma propoxyphene levels in 2 groups of 4 dogs following oral administration of equimolar doses of the 2 salts.

As shown in Figure 3, the peak plasma concentration observed with propoxyphene hydrochloride was much higher than that obtained after administration of the napsylate salt.

Although none of the animals in this experiment died, 3 of the 4 dogs given propoxyphene hydrochloride exhibited convulsive seizures during the time interval corresponding to the peak plasma levels. The 4 animals receiving the napsylate salt were ataxic but not acutely ill.

Figure 3. Plasma propoxyphene concentrations in dogs following large doses of the hydrochloride and napsylate salts.

The following information includes the maximum daily dosage and is available to patients receiving propoxyphene napsylate and acetaminophen tablets.

Patient Information Sheet

Your prescription for a propoxyphene product summary.

Products containing Propoxyphene are used to relieve pain.

Limit your intake of alcohol while taking this drug. Make sure your doctor knows if you are taking tranquilizers, sleep aids, antidepressants, antihistamines, or any other drugs that make you sleepy. Combining propoxyphene with alcohol or these drugs in excessive doses is dangerous.

Use care while driving a car or using machines until you see how the drug affects you because propoxyphene can make you sleepy. Do not take more of the drug than your doctor prescribed. Dependence has occurred when patients have taken propoxyphene for a long period of time at doses greater than recommended.

The rest of this leaflet gives you more information about propoxyphene. Please read it and keep it for future use.

Uses for Propoxyphene

Products containing propoxyphene are used for the relief of mild to moderate pain. Products that contain propoxyphene plus acetaminophen are prescribed for the relief of pain or pain associated with fever.

Before Taking Propoxyphene

Make sure your doctor knows if you have ever had an allergic reaction to propoxyphene or acetaminophen.

The effect of propoxyphene in children under 12 has not been studied; therefore, use of the drug in this age group is not recommended.

How to Take Propoxyphene

Follow your doctor's directions exactly. Do not increase the amount you take without your doctor's approval. If you miss a dose of the drug, do not take twice as much the next time.

Pregnancy

Do not take propoxyphene during pregnancy unless your doctor knows you are pregnant and specifically recommends its use. Cases of temporary dependence in the newborn have occurred when the mother has taken propoxyphene consistently in the weeks before delivery. As a general principle, no drug should be taken during pregnancy unless it is clearly necessary.

General Cautions

Heavy use of alcohol with propoxyphene is hazardous and may lead to overdosage symptoms (see "Overdosage" below). Therefore, limit your intake of alcohol while taking propoxyphene.

Combinations of excessive doses of propoxyphene, alcohol, and tranquilizers are dangerous. Make sure your doctor knows if you are taking tranquilizers, sleep aids, antidepressant drugs, antihistamines, or any other drugs that make you sleepy. The use of these drugs with propoxyphene increases their sedative effects and may lead to overdosage symptoms, including death (see "Overdosage" below).

Propoxyphene may cause drowsiness or impair your mental and/or physical abilities; therefore, use caution when driving a vehicle or operating dangerous machinery. DO NOT perform any hazardous task until you have seen your response to this drug.

Propoxyphene may increase the concentration in the body of medications such as anticoagulants ("blood thinners"), antidepressants, or drugs used for epilepsy. The result may be excessive or adverse effects of these medications. Make sure your doctor knows if you are taking any of these medications.

Dependence

You can become dependent on propoxyphene if you take it in higher than recommended doses over a long period of time. Dependence is a feeling of need for the drug and a feeling that you cannot perform normally without it.

Overdosage

An overdose of propoxyphene alone or in combination with other drugs, including alcohol, may cause weakness, difficulty in breathing, confusion, anxiety, and more severe drowsiness and dizziness. Extreme overdosage may lead to unconsciousness and death.

This product contains acetaminophen. Acetaminophen overdosage symptoms include nausea, vomiting, lack of appetite, and abdominal pain. Liver damage may occur even after symptoms disappear. Death can occur days later.

In any suspected overdosage situation, contact your doctor or nearest hospital emergency room. Get emergency help immediately. Keep this drug and all drugs out of the reach of children.

Possible Side Effects

When propoxyphene is taken as directed, side effects are infrequent. Among those reported are drowsiness, dizziness, nausea, and vomiting. If these effects occur, it may help if you lie down and rest.

Less frequently reported side effects are constipation, abdominal pain, skin rashes, lightheadedness, headache, weakness, hallucinations, minor visual disturbances, and feelings of elation or discomfort.

If side effects occur and concern you, contact your doctor.

Other information

The safe and effective use of propoxyphene depends on you taking it exactly as directed. This drug has been prescribed specifically for you and your present condition. Do not give this drug to others who may have similar symptoms. Do not use it for any other reason.

If you would like more information about propoxyphene, ask your doctor or pharmacist. They have a more technical leaflet (professional labeling) you may read.