Vicodin HP

DESCRIPTION

Hydrocodone bitartrate andacetaminophenare supplied in tablet form for oral administration. Hydrocodone bitartrate is anopioidanalgesicand antitussive and occurs as fine, white crystals or as a crystalline powder. It is affected by light. The chemical name is 4,5α-epoxy-3-methoxy-17-methylmorphinan-6-one tartrate (1:1) hydrate (2:5).

It has the following structural formula:

C₁₈H₂₁NO₃.C₄H₆O₆.2½ H₂O M.W. = 494.50

Acetaminophen, 4-hydroxyacetanilide, a slightly bitter, white, odorless, crystalline powder, is a non-opiate, non-salicylate analgesic and antipyretic. It has the following structural formula:

C₈H₉NO₂M.W.= 151.17

Each VICODIN HP (hydrocodone bitrate and acetaminophen tablets) Tablet contains:

Hydrocodone Bitartrate 10 mg
Acetaminophen 660 mg

In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized starch, and stearic acid.

Meets USP Dissolution Test 2.

INDICATIONS

VICODIN HP (hydrocodone bitrate and acetaminophen tablets) Tablets are indicated for the relief of moderate to moderately severe pain.

DOSAGE AND ADMINISTRATION

Dosage should be adjusted according to severity of pain and the response of the patient. However, it should be kept in mind that tolerance to hydrocodone can develop with continued use and that the incidence of untoward effects is dose related.

The usual adult dosage is one tablet every four to six hours as needed for pain. The total daily dosage should not exceed 6 tablets.

HOW SUPPLIED

VICODIN HP® (hydrocodone bitrate and acetaminophen tablets) (hydrocodone bitartrate and acetaminophen, 10 mg/660 mg) is supplied as a white, oval-shaped, tablet bisected on one side and debossed with “VICODIN HP (hydrocodone bitrate and acetaminophen tablets) ” on the other side.

Bottles of 100-NDC#0074-2274-14
Bottles of 500-NDC#0074-2274-54

Storage:Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F). [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP.

Revised March, 2007. Abbott Laboratories, North Chicago, IL 60064, USA

SIDE EFFECTS

The most frequently reported adverse reactions arelightheadedness, dizziness, sedation, nausea and vomiting. These effects seem to be more prominent in ambulatory than in nonambulatory patients, and some of these adverse reactions may be alleviated if the patient lies down.

Other adverse reactions include

Central Nervous System

Drowsiness, mental clouding,lethargy, impairment of mental and physical performance, anxiety, fear,dysphoria, psychic dependence, mood changes.

Gastrointestinal System

Prolonged administration of VICODIN HP (hydrocodone bitrate and acetaminophen tablets) Tablets may produce constipation.

Genitourinary System

Ureteral spasm, spasm ofvesicalsphincters and urinary retention have been reported with opiates.

Respiratory Depression

Hydrocodone bitartrate may produce dose-related respiratory depression by acting directly on thebrain stemrespiratory centers (seeOVERDOSAGE).

Special Senses

Cases of hearing impairment or permanent loss have been reported predominantly in patients with chronic overdose.

Dermatological

Skin rash,pruritus.

The following adverse drug events may be borne in mind as potential effects of acetaminophen: allergic reactions, rash,thrombocytopenia,agranulocytosis.

Potential effects of high dosage are listed in theOVERDOSAGEsection.

Drug Abuse And Dependence

Misuse, Abuse, and Diversion of Opioids

VICODIN HP (hydrocodone bitrate and acetaminophen tablets) contains hydrocodone, an opioidagonist, and is a Schedule III controlled substance. VICODIN HP (hydrocodone bitrate and acetaminophen tablets) , and other opioids, used inanalgesiacan be abused and are subject to criminal diversion.

Addiction is a primary, chronic, neurobiologic disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations. It 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.

“药物寻求“在成瘾行为是很常见的and drug abusers. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing orreferral, repeated “loss” of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating physician(s). “Doctor shopping” to obtain additional prescriptions is common among drug abusers and people suffering from untreated addiction.

滥用和成瘾是分开的,截然不同physical dependence and tolerance. Physical dependence usually assumes clinically significant dimensions only after several weeks of continued opioid use, although a mild degree of physical dependence may develop after a few days of opioid therapy. Tolerance, in which increasingly large doses are required in order to produce the same degree of analgesia, is manifested initially by a shortened duration of analgesic effect, and subsequently by decreases in the intensity of analgesia. The rate of development of tolerance varies among patients. Physicians should be aware that abuse of opioids can occur in the absence of true addiction and is characterized by misuse for non-medical purposes, often in combination with other psychoactive substances. VICODIN HP (hydrocodone bitrate and acetaminophen tablets) , like other opioids, may be diverted for non-medical use. Record-keeping of prescribing information, including quantity, frequency, and renewal requests is strongly advised.

Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

DRUG INTERACTIONS

Patients receiving narcotics,antihistamines, antipsychotics, antianxiety agents, or other CNS depressants (including alcohol) concomitantly with VICODIN HP (hydrocodone bitrate and acetaminophen tablets) Tablets may exhibit an additive CNS depression. When combined therapy is contemplated, the dose of one or both agents should be reduced.

The use of MAO inhibitors ortricyclic antidepressantswith hydrocodone preparations may increase the effect of either theantidepressantor hydrocodone.

Drug/Laboratory Test Interactions

Acetaminophen may produce false-positive test results for urinary 5-hydroxyindoleacetic acid.

警告

Respiratory Depression

At high doses or in sensitive patients, hydrocodone may produce dose-relatedrespiratory depressionby acting directly on the brain stem respiratory center. Hydrocodone also affects the center that controls respiratory rhythm, and may produce irregular andperiodic breathing.

Head Injury and Increased Intracranial Pressure

The respiratory depressant effects of narcotics and their capacity to elevatecerebrospinal fluidpressure may be markedly exaggerated in the presence ofhead injury, other intracranial lesions or a preexisting increase in intracranial pressure. Furthermore, narcotics produce adverse reactions, which may obscure the clinical course of patients with head injuries.

Acute Abdominal Conditions

The administration of narcotics may obscure the diagnosis or clinical course of patients with acute abdominal conditions.

Misuse, Abuse, and Diversion of Opioids

VICODIN HP (hydrocodone bitrate and acetaminophen tablets) contains hydrocodone, an opioid agonist, and is a Schedule III controlled substance. Opioid agonists have the potential for being abused and are sought by abusers and people with addiction disorders, and are subject to diversion.

VICODIN HP (hydrocodone bitrate and acetaminophen tablets) can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing VICODIN HP in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion (seeDrug Abuse And Dependence).

PRECAUTIONS

General

Special Risk Patients

As with anynarcoticanalgesic agent, VICODIN HP (hydrocodone bitrate and acetaminophen tablets) Tablets should be used with caution in elderly or debilitated patients, and those with severe impairment of hepatic or renal function,hypothyroidism, Addison's disease, prostatichypertrophyor urethral狭窄. The usual precautions should be observed and the possibility of respiratory depression should be kept in mind.

Cough Reflex

Hydrocodone suppresses the cough reflex; as with all narcotics, caution should be exercised when VICODIN HP (hydrocodone bitrate and acetaminophen tablets) Tablets are used postoperatively and in patients with pulmonary disease.

Laboratory Tests

In patients with severe hepatic or renal disease, effects of therapy should be monitored with serial liver and/or renal function tests.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No adequate studies have been conducted in animals to determine whether hydrocodone or acetaminophen have a potential for carcinogenesis,mutagenesis, or impairment of fertility.

Pregnancy

Teratogenic Effects

Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. VICODIN HP (hydrocodone bitrate and acetaminophen tablets) Tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects

Babies born to mothers who have been taking opioids regularly prior to delivery will be physically dependent. The withdrawal signs include irritability and excessive crying, tremors, hyperactive reflexes, increasedrespiratory rate, increased stools, sneezing,yawning, vomiting, and fever. The intensity of the syndrome does not always correlate with the duration of maternal opioid use or dose. There is no consensus on the best method of managing withdrawal.

Labor and Delivery

As with all narcotics, administration of VICODIN HP (hydrocodone bitrate and acetaminophen tablets) Tablets to the mother shortly before delivery may result in some degree of respiratory depression in the newborn, especially if higher doses are used.

Nursing Mothers

Acetaminophen is excreted in breast milk in small amounts, but the significance of its effects on nursing infants is not known. It is not known whether hydrocodone is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from hydrocodone and acetaminophen, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in the pediatric population have not been established.

Geriatric Use

Clinical studies of VICODIN HP® (hydrocodone bitrate and acetaminophen tablets) (hydrocodone bitartrate and acetaminophen 10 mg/660 mg) 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.

Hydrocodone and the major metabolites of acetaminophen are known to be substantially excreted by the kidney. Thus the risk of toxic reactions may be greater in patients with impaired renal function due to accumulation of the parent compound and/or metabolites in the plasma. 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.

Hydrocodone may cause confusion and over-sedation in the elderly; elderly patients generally should be started on low doses of hydrocodone bitartrate and acetaminophen tablets and observed closely.

OVERDOSE

Following an acute overdosage, toxicity may result from hydrocodone or acetaminophen.

Signs and Symptoms

Hydrocodone

Serious overdose with hydrocodone is characterized by respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokesrespiration,cyanosis), extremesomnolenceprogressing to stupor or coma,skeletal muscleflaccidity, cold and clammy skin, and sometimesbradycardiaandhypotension. In severe overdosage,apnea,circulatorycollapse, cardiac arrest and death may occur.

Acetaminophen

In acetaminophen overdosage: dose-dependent, potentially fatal hepaticnecrosisis the most seriousadverse effect. Renal tubular necrosis,hypoglycemiccoma, and thrombocytopenia may also occur.

Early symptoms following a potentiallyhepatotoxicoverdose may include: nausea, vomiting, diaphoresis and generalmalaise. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours post-ingestion.

In adults, hepatic toxicity has rarely been reported with acute overdoses of less than 10 grams, or fatalities with less than 15 grams.

Treatment

A single or multiple overdose with hydrocodone and acetaminophen is a potentiallylethalpolydrug overdose, and consultation with a regional poison control center is recommended.

Immediate treatment includes support of cardiorespiratory function and measures to reduce drug absorption. Vomiting should be induced mechanically, or with syrup ofipecac, if the patient is alert (adequatepharyngealandlaryngealreflexes). Oralactivated charcoal(1 g/kg) should followgastricemptying. The first dose should be accompanied by an appropriatecathartic. If repeated doses are used, the cathartic might be included with alternate doses as required. Hypotension is usuallyhypovolemicand should respond to fluids. Vasopressors and other supportive measures should be employed as indicated. A cuffed endo-tracheal tube should be inserted before gastric lavage of theunconsciouspatient and, when necessary, to provide assisted respiration.

Meticulous attention should be given to maintaining adequate pulmonaryventilation. In severe cases of intoxication,peritoneal dialysis, or preferablyhemodialysismay be considered. If hypoprothrombinemia occurs due to acetaminophen overdose,vitamin Kshould be administered intravenously.

Naloxone, an opioidantagonist, can reverse respiratory depression and coma associated with opioid overdose. Naloxone hydrochloride 0.4 mg to 2 mg is given parenterally. Since the duration of action of hydrocodone may exceed that of the naloxone, the patient should be kept under continuous surveillance and repeated doses of the antagonist should be administered as needed to maintain adequate respiration. An opioid antagonist should not be administered in the absence of clinically significant respiratory orcardiovasculardepression.

If the dose of acetaminophen may have exceeded 140 mg/kg,acetylcysteineshould be administered as early as possible. Serum acetaminophen levels should be obtained, since levels four or more hours following ingestion help predict acetaminophen toxicity. Do not await acetaminophen assay results before initiating treatment. Hepatic enzymes should be obtained initially, and repeated at 24-hour intervals.

Methemoglobinemiaover 30% should be treated with methylene blue by slow intravenous administration.

The toxic dose for adults for acetaminophen is 10 g.

CONTRAINDICATIONS

This product should not be administered to patients who have previously exhibited hypersensitivity to hydrocodone or acetaminophen.

Patients known to be hypersensitive to other opioids may exhibit cross-sensitivity to hydrocodone.

CLINICAL PHARMACOLOGY

Hydrocodone is a semisynthetic narcotic analgesic and antitussive with multiple actions qualitatively similar to those of codeine. Most of these involve thecentral nervous systemandsmooth muscle. The precise mechanism of action of hydrocodone and other opiates is not known, although it is believed to relate to the existence ofopiate受体在中央nervous system. In addition to analgesia, narcotics may produce drowsiness, changes in mood and mental clouding.

The analgesic action of acetaminophen involves peripheral influences, but the specific mechanism is as yet undetermined.Antipyreticactivity is mediated through hypothalamic heat regulating centers. Acetaminophen inhibitsprostaglandinsynthetase. Therapeutic doses of acetaminophen have negligible effects on the cardiovascular or respiratory systems; however, toxic doses may cause circulatory failure and rapid, shallow breathing.

Pharmacokinetics

The behavior of the individual components is described below.

Hydrocodone

Following a 10 mg oral dose of hydrocodone administered to five adult male subjects, the mean peak concentration was 23.6 ± 5.2ng/mL. Maximum serum levels were achieved at 1.3 ± 0.3 hours and the half-life was determined to be 3.8 ± 0.3 hours. Hydrocodone exhibits a complex pattern ofmetabolismincluding O-demethylation, N-demethylation and 6-keto reduction to the corresponding 6-α- and 6-β- hydroxy- metabolites. SeeOVERDOSAGEfor toxicity information.

Acetaminophen

Acetaminophen is rapidly absorbed from thegastrointestinaltract and is distributed throughout most body tissues. The plasma half-life is 1.25 to 3 hours, but may be increased by liver damage and following overdosage. Elimination of acetaminophen is principally by liver metabolism (conjugation) and subsequent renal excretion of metabolites. Approximately 85% of an oral dose appears in the urine within 24 hours of administration, most as the glucuronide conjugate, with small amounts of other conjugates and unchanged drug. SeeOVERDOSAGEfor toxicity information.

PATIENT INFORMATION

Hydrocodone, like all narcotics, may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery; patients should be cautioned accordingly.

Alcohol and other CNS depressants may produce an additive CNS depression, when taken with this combination product, and should be avoided.

Hydrocodone may be habit forming. Patients should take the drug only for as long as it is prescribed, in the amounts prescribed, and no more frequently than prescribed.