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'-hydroxyacetanilide, a slightly bitter, white, odorless, crystalline powder, is a non-opiate, non-salicylate analgesic and antipyretic. It has the following structural formula:
Each hydrocodone bitartrate and acetaminophen tablet contains:
Hydrocodone Bitartrate 7.5 mg
Acetaminophen 750 mg
In addition each tablet contains the following inactive ingredients: colloidal silicon dioxide, corn starch (pregelatinized), croscarmellose sodium, crospovidone, magnesium stearate, microcrystalline cellulose, povidone and stearic acid.
Meets USP Dissolution Test 2.
Hydrocodone is a semisynthetic narcotic analgesic and antitussive with multiple actions qualitatively similar to those of codeine. Most of these involve the central nervous system and smooth muscle. The precise mechanism of action of hydrocodone and other opiates is not known, although it is believed to relate to the existence of opiate receptors in the central 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. Antipyretic activity is mediated through hypothalamic heat regulating centers. Acetaminophen inhibits prostaglandin synthetase. Therapeutic doses of acetaminophen have negligible effects on the cardiovascular or respiratory systems; however, toxic doses may cause circulatory failure and rapid, shallow breathing.
The behavior of the individual components is described below.
Hydrocodone bitartrate and acetaminophen tablets are indicated for the relief of moderate to moderately severe pain.
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.
At high doses or in sensitive patients, hydrocodone may produce dose-related respiratory depression by acting directly on the brain stem respiratory center. Hydrocodone also affects the center that controls respiratory rhythm, and may produce irregular and periodic breathing.
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 preexisting increase in intracranial pressure. Furthermore, narcotics produce adverse reactions, which may obscure the clinical course of patients with head injuries.
The administration of narcotics may obscure the diagnosis or clinical course of patients with acute abdominal conditions.
Hydrocodone bitartrate and acetaminophen tablets contain 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.
Hydrocodone bitartrate 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 hydrocodone bitartrate and acetaminophen tablets in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion (see DRUG ABUSE AND DEPENDENCE).
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.
In patients with severe hepatic or renal disease, effects of therapy should be monitored with serial liver and/or renal function tests.
Patients receiving other narcotic analgesics, antihistamines, antipsychotics, antianxiety agents, or other CNS depressants (including alcohol) concomitantly with hydrocodone bitartrate and acetaminophen 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 or tricyclic antidepressants with hydrocodone preparations may increase the effect of either the antidepressant or hydrocodone.
Acetaminophen may produce false-positive test results for urinary 5-hydroxyindoleacetic acid.
No adequate studies have been conducted in animals to determine whether hydrocodone or acetaminophen have a potential for carcinogenesis, mutagenesis, or impairment of fertility.
As with all narcotics, administration of hydrocodone bitartrate and acetaminophen tablets to the mother shortly before delivery may result in some degree of respiratory depression in the newborn, especially if higher doses are used.
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.
Safety and effectiveness in the pediatric population have not been established.
Clinical studies of hydrocodone bitartrate 7.5 mg and acetaminophen 750 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.
The most frequently reported adverse reactions include: lightheadedness, 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 hydrocodone bitartrate and acetaminophen tablets may produce constipation.
Genitourinary System: Ureteral spasm, spasm of vesical sphincters and urinary retention have been reported with opiates.
Respiratory Depression: Hydrocodone bitartrate may produce dose-related respiratory depression by acting directly on the brain stem respiratory center (see OVERDOSAGE).
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 uled in the OVERDOSAGE section.
Hydrocodone bitartrate and acetaminophen tablets contain hydrocodone, an opioid agonist, and is a Schedule III controlled substance. Hydrocodone bitartrate and acetaminophen, and other opioids, used in analgesia can 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.
"Drug seeking" behavior is very common in addicts and drug abusers. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, 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.
Abuse and addiction are separate and distinct from 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. Hydrocodone bitartrate and acetaminophen tablets (hydrocodone bitartrate 7.5 mg and acetaminophen 750 mg), 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.
Following an acute overdosage, toxicity may result from hydrocodone or acetaminophen.
A single or multiple overdose with hydrocodone and acetaminophen is a potentially lethal polydrug 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 of ipecac, if the patient is alert (adequate pharyngeal and laryngeal reflexes). Oral activated charcoal (1 g/kg) should follow gastric emptying. The first dose should be accompanied by an appropriate cathartic. If repeated doses are used, the cathartic might be included with alternate doses as required. Hypotension is usually hypovolemic and 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 the unconscious patient and, when necessary, to provide assisted respiration.
Meticulous attention should be given to maintaining adequate pulmonary ventilation. In severe cases of intoxication, peritoneal dialysis, or preferably hemodialysis may be considered. If hypoprothrombinemia occurs due to acetaminophen overdose, vitamin K should be administered intravenously.
Naloxone, a narcotic antagonist, 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. A narcotic antagonist should not be administered in the absence 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 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.
Methemoglobinemia over 30% should be treated with methylene blue by slow intravenous administration.
The toxic dose for adults for acetaminophen is 10 g.
Dosage should be adjusted according to the severity of the 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 5 tablets.
Hydrocodone bitartrate and acetaminophen tablets USP, 7.5 mg/750 mg are white, capsule shaped tablets debossed with “”, “568” on one side and scored on the other side.
Bottles of 100 Tablets NDC 62037-568-01
Bottles of 500 Tablets NDC 62037-568-05