Norco 5/325 (Hydrocodone Bitartrate and Acetaminophen): Side Effects, Uses, Dosage, Interactions, Warnings (2024)

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NORCO® (Hydrocodone bitartrate and acetaminophen) is supplied in tablet form for oral administration.

Hydrocodone bitartrate is an opioid analgesic and 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:

Acetaminophen, 4´-hydroxy acetani lide, a slightly bitter, white, odorless, crystalline powder, is a nonopiate, non-salicylate analgesic and antipyretic. It has the following structural formula:

NORCO®, for oral administration is available in the following strengths:

Hydrocodone

Bitartrate Acetaminophen

NORCO® 7.5/325 7.5 mg 325 mg
NORCO® 10/325 10 mg 325 mg

In addition, each tablet contains the following inactive ingredients: croscarmellose sodium, crospovidone, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized starch, and stearic acid; the 7.5 mg/325 mg tablets include FD&C Yellow #6 Aluminum Lake, the 10 mg/325 mg tablets include D&C Yellow #10 Aluminum Lake. Meets USP Dissolution Test 1.

Uses for Norco 5/325

NORCO® isindicated for the relief of moderate to moderately severe pain.

Dosage for Norco 5/325

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

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

HOW SUPPLIED

NORCO® 7.5/325 isavailable as capsule-shaped, light orange tablets bisected on one side and debossedwith “NORCO® 729” on the other side.Each tablet contains 7.5 mg hydrocodone bitartrate and 325 mg acetaminophen.They are supplied as follows:

Bottles of 30
Bottles of 100
Bottles of 500

NORCO 10/325 is available as capsule-shaped, yellow tablets bisected on one side and debossed with “NORCO 539” on the other side. Each tablet contains 10 mg hydrocodone bitartrate and 325 mg acetaminophen.They are supplied as follows:

Bottles of 100
Bottles of 500

Store at 20°-25°C (68°-77°F). [See USP controlled roomtemperature.]

Dispense in a tight, light-resistant container with achild resistant closure.

Watson Pharma, Inc., A Subsidiary of Watson, Pharmaceuticals,Inc., Corona, CA 92880 USA 14716. Revised: July 2007. Cardinal Health, Zanesville,OH 43701.

Side Effects for Norco 5/325

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

Other Adverse Reactions Include

Central Nervous System: Drowsi ness, mentalclouding, lethargy, impairment of mental and physical performance, anxiety,fear, dysphoria, psychic dependence, mood changes.

Gastrointestinal System: Prolonged administrationof NORCO® may produce constipation.

Genitourinary System: Ureteral spasm, spasm of vesical sphincters and urinary retention have been reported with opiates.

Respiratory Depression: Hydrocodone bitartrate mayproduce dose-related respiratory depression by acting directly on brain stem respiratory centers (see OVERDOSAGE).

Special Senses : Cases of hearing impairment orpermanent loss have been reported predominantly in patients with chronicoverdose.

Dermatological: Skin rash, pruritus.

The following adverse drug events may be borne in mind aspotential effects of acetaminophen: allergic reactions, rash, thrombocytopenia, agranulocytosis. Potential effects of high dosage are listed in the OVERDOSAGE section.

Drug Abuse And Dependence

Controlled Substance

NORCO® isclassified as a Schedule III controlled substance.

Abuse and Dependence

Psychic dependence, physical dependence, and tolerancemay develop upon repeated administration of narcotics; therefore, this productshould be prescribed and administered with caution. However, psychic dependenceis unlikely to develop when NORCO® isused for a short time for the treatment of pain.

Physical dependence, the condition in which continuedadministration of the drug is required to prevent the appearance of awithdrawal syndrome, assumes clinically significant proportions only afterseveral weeks of continued narcotic use, although some mild degree of physicaldependence may develop after a few days of narcotic therapy. Tolerance, inwhich increasingly large doses are required in order to produce the same degreeof analgesia, is manifested initially by a shortened duration of analgesic effect,and subsequently by decreases in the intensity of analgesia. The rate ofdevelopment of tolerance varies among patients.

Drug Interactions for Norco 5/325

Patients receiving other narcotics, antihistamines,antipsychotics, antianxiety agents, or other CNS depressants (includingalcohol) concomitantly with NORCO® mayexhibit an additive CNS depression. When combined therapy is contemplated, thedose of one or both agents should be reduced.

The use of MAO inhibitors or tricyclic antidepressants with hydrocodone preparations may increase the effect of either the antidepressant or hydrocodone.

Drug/Laboratory Test Interactions

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

Warnings for Norco 5/325

Respiratory Depression

At high doses or in sensitive patients, hydrocodone mayproduce dose -related respiratory depression by acting directly on the brainstem respiratory center. Hydrocodone also affects the center that controls respiratoryrhythm, and may produce irregular and periodic breathing.

Head Injury And Increased Intracranial Pressure

The respiratory depressant effects of narcotics and theircapacity to elevate cerebrospinal fluid pressure may be markedly exaggerated inthe presence of head injury, other intracranial lesions or a pre-existingincrease in intracranial pressure. Furthermore, narcotics produce adversereactions which may obscure the clinical course of patients with head injuries.

Acute Abdominal Conditions

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

Precautions for Norco 5/325

General

Special Risk Patients

As with any narcotic analgesic agent, NORCO® should be used with caution in elderly ordebilitated patients and those with severe impairment of hepatic or renalfunction, hypothyroidism, Addison's disease, prostatic hypertrophy or urethral stricture. The usual precautions should be observed and the possibility ofrespiratory depression should be kept in mind.

Cough reflex

Hydrocodone suppresses the cough reflex; as with allnarcotics, caution should be exercised when NORCO®is used postoperatively and in patients with pulmonary disease.

Laboratory Tests

In patients with severe hepatic or renal disease, effectsof 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 todetermine whether hydrocodone or acetaminophen have a potential forcarcinogenesis, mutagenesis, or impairment of fertility.

Pregnancy

Teratogenic Effects

Pregnancy Category C

There are no adequate and well-controlled studies inpregnant women. NORCO®should be used during pregnancy only if the potential benefit justifies thepotential risk to the fetus.

Nonteratogenic Effects

Babies born to mothers who have been taking opioidsregularly prior to delivery will be physically dependent. The withdrawal signsinclude irritability and excessive crying, tremors, hyperactive reflexes,increased respiratory rate, increased stools, sneezing, yawning, vomiting andfever. The intensity of the syndrome does not always correlate with theduration of maternal opioid use or dose. There is no consensus on the bestmethod of managing withdrawal.

Labor And Delivery

As with all narcotics, administration of this product tothe mother shortly before delivery may result in some degree of respiratorydepression in the newborn, especially if higher doses are used.

Nursing Mothers

Acetaminophen is excreted in breast milk in smallamounts, 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 drugsare excreted in human milk and because of the potential for serious adversereactions in nursing infants from hydrocodone and acetaminophen, a decisionshould 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 pediatric patients have notbeen established.

Geriatric Use

Clinical studies of hydrocodone bitartrate 5 mg andacetaminophen 500 mg did not include sufficient numbers of subjects aged 65 andover to determine whether they respond differently from younger subjects. Otherreported clinical experience has not identified differences in responsesbetween the elderly and younger patients. In general, dose selection for anelderly patient should be cautious, usually starting at the low end of thedosing range, reflecting the greater frequency of decreased hepatic, renal, orcardiac function, and of concomitant disease or other drug therapy.

Hydrocodone and the major metabolites of acetaminophenare known to be substantially excreted by the kidney. Thus the risk of toxicreactions may be greater in patients with impaired renal function due to the accumulationof the parent compound and/or metabolites in the plasma. Because elderlypatients are more likely to have decreased renal function, care should be takenin dose selection, and it may be useful to monitor renal function.

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

Overdose Information for Norco 5/325

Following an acute overdosage, toxicity may result fromhydrocodone or acetaminophen.

Signs And Symptoms

Hydrocodone

Serious overdose with hydrocodone is characterized byrespiratory depression (a decrease in respiratory rate and/or tidal volume,Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stuporor coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse,cardiac arrest and death may occur.

Acetaminophen

In acetaminophen overdosage: dosedependent,potentially fatal hepatic necrosis is the most serious adverse effect. Renaltubular necrosis, hypoglycemic coma, and thrombocytopenia may also occur.

Early symptoms following a potentially hepatotoxic overdose may include: nausea, vomiting, diaphoresis and general malaise.Clinical and laboratory evidence of hepatic toxicity may not be apparent until48 to 72 hours post-ingestion.

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

Treatment

A single or multiple overdose with hydrocodone andacetaminophen is a potentially lethal polydrug overdose, and consultation witha regional poison control center is recommended.

Immediate treatment includes support of cardiorespiratoryfunction and measures to reduce drug absorption. Vomiting should be inducedmechanically, or with syrup of ipecac, if the patient is alert (adequate pharyngeal and laryngeal reflexes). Oral activated charcoal (1 g/kg) shouldfollow gastric emptying. The first dose should be accompanied by an appropriate cathartic. If repeated doses are used, the cathartic might be included withalternate doses as required. Hypotension is usually hypovolemic and shouldrespond to fluids. Vasopressors and other supportive measures should beemployed as indicated. A cuffed endotracheal tube should be inserted beforegastric lavage of the unconscious patient and, when necessary, to provideassisted respiration.

Meticulous attention should be given to maintainingadequate pulmonary ventilation. In severe cases of intoxication, peritoneal dialysis, or preferably hemodialysis may be considered. If hypoprothrombinemiaoccurs due to acetaminophen overdose, vitamin K should be administered intravenously.

Naloxone, a narcotic antagonist, can reverse respiratorydepression and coma associated with opioid overdose. Naloxone hydrochloride 0.4mg to 2 mg is given parenterally. Since the duration of action of hydrocodonemay exceed that of the naloxone, the patient should be kept under continuoussurveillance and repeated doses of the antagonist should be administered asneeded to maintain adequate respiration.

A narcotic antagonist should not be administered in theabsence of clinically significant respiratory or cardiovascular depression.

If the dose of acetaminophen may have exceeded 140 mg/kg, acetylcysteine should be administered as early as possible. Serum acetaminophenlevels should be obtained, since levels four or more hours following ingestionhelp predict acetaminophen toxicity. Do not await acetaminophen assay results beforeinitiating treatment. Hepatic enzymes should be obtained initially, andrepeated at 24-hour intervals.

Methemoglobinemia over 30% should be treated withmethylene blue by slow intravenous administration.

The toxic dose for adults for acetaminophen is 10 g.

Contraindications for Norco 5/325

NORCO® should notbe administered to patients who have previously exhibited hypersensitivity to hydrocodoneor acetaminophen.

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

Clinical Pharmacology for Norco 5/325

Hydrocodone is a semisynthetic narcotic analgesic andantitussive with multiple actions qualitatively similar to those of codeine.Most of these involve the central nervous system and smooth muscle. The precisemechanism of action of hydrocodone and other opiates is not known, although itis believed to relate to the existence of opiate receptors in the centralnervous system. In addition to analgesia, narcotics may produce drowsiness,changes in mood and mental clouding.

The analgesic action of acetaminophen involves peripheralinfluences, but the specific mechanism is as yet undetermined. Antipyretic activity is mediated through hypothalamic heat regulating centers. Acetaminopheninhibits prostaglandin synthetase. Therapeutic doses of acetaminophen havenegligible effects on the cardiovascular or respiratory systems; however, toxicdoses may cause circulatory failure and rapid, shallow breathing.

Pharmaco*kinetics

The behavior of the individual components is describedbelow.

Hydrocodone

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

Acetaminophen

Acetaminophen is rapidly absorbed from the gastrointestinal tract and is distributed throughout most body tissues. Theplasma half-life is 1.25 to 3 hours, but may be increased by liver damage and followingoverdosage. 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 asthe glucuronide conjugate, with small amounts of other conjugates and unchangeddrug. See OVERDOSAGE for toxicity information.

Patient Information for Norco 5/325

Hydrocodone, like all narcotics, may impair mental and/orphysical abilities required for the performance of potentially hazardous taskssuch as driving a car or operating machinery; patients should be cautionedaccordingly.

Alcohol and other CNS depressants may produce an additiveCNS depression, when taken with this combination product, and should beavoided.

Hydrocodone may be habit-forming. Patients should takethe drug only for as long as it is prescribed, in the amounts prescribed, andno more frequently than prescribed.

e drug only for as long as it is prescribed, in the amounts prescribed, and no more frequently than prescribed.