HYDROcodone bitartrate 2.5 MG / acetaminophen 500 MG Oral Tablet
WARNINGS
Respiratory Depression: 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.
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 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: 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 ).
DRUG INTERACTIONS
Drug Interactions: 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.
OVERDOSAGE
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-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or 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: dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect.
Renal tubular 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 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 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 endotracheal 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 acetaminophen for adults is 10 g.
DESCRIPTION
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: Hydrocodone Bitartrate and Acetaminophen Tablets, USP 2.5 mg/500 mg Each tablet contains: Hydrocodone Bitartrate ………….
2.5 mg Acetaminophen …………………….
500 mg In addition each tablet contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, crospovidone, FD&C Red #3, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized corn starch, stearic acid, and sucrose.
Meets USP Dissolution Test 1.
Hydrocodone Bitartrate and Acetaminophen Tablets, USP 5 mg/325 mg Each tablet contains: Hydrocodone Bitartrate ……………..
5 mg Acetaminophen ………………………..
325 mg In addition, each tablet contains the following inactive ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized starch, sodium lauryl sulfate, stearic acid and sugar spheres which are composed of starch derived from corn, FD&C Red #40, FD&C Yellow #6, and sucrose.
Meets USP Dissolution Test 2.
Hydrocodone Bitartrate and Acetaminophen Tablets, USP 5 mg/500 mg Each tablet contains: Hydrocodone Bitartrate ………….
5 mg Acetaminophen …………………….
500 mg In addition each tablet contains the following inactive ingredients: hypromellose, lactose monohydrate, magnesium stearate, and sodium starch glycolate.
Meets USP Dissolution Test 1.
Hydrocodone Bitartrate and Acetaminophen Tablets, USP 7.5 mg/325 mg Each tablet contains: Hydrocodone Bitartrate ………….
7.5 mg Acetaminophen …………………….
325 mg In addition, each tablet contains the following inactive ingredients: croscarmellose sodium, FD&C Red #40 aluminum lake, FD&C Yellow #6 aluminum lake, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized starch, sodium lauryl sulfate, stearic acid.
Meets USP Dissolution Test 2.
Hydrocodone Bitartrate and Acetaminophen Tablets, USP 7.5 mg/500 mg Each tablet contains: Hydrocodone Bitartrate ………….
7.5 mg Acetaminophen …………………….
500 mg In addition each tablet contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, crospovidone, FD&C Blue #1, FD&C Yellow #5, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized corn starch, stearic acid, and sucrose.
Meets USP Dissolution Test 1.
Hydrocodone Bitartrate and Acetaminophen Tablets, USP 7.5 mg/650 mg Each tablet contains: Hydrocodone Bitartrate ………….
7.5 mg Acetaminophen …………………….
650 mg In addition each tablet contains the following inactive ingredients: croscarmellose sodium, crospovidone, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized corn starch, and stearic acid.
Meets USP Dissolution Test 1.
Hydrocodone Bitartrate and Acetaminophen Tablets, USP 7.5 mg/750 mg Each tablet contains: Hydrocodone Bitartrate ………….
7.5 mg Acetaminophen …………………….
750 mg In addition each tablet contains the following inactive ingredients: croscarmellose sodium, crospovidone, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized corn starch, and stearic acid.
Meets USP Dissolution Test 1.
Hydrocodone Bitartrate and Acetaminophen Tablets, USP 10 mg/325 mg Each tablet contains: Hydrocodone Bitartrate …………
10 mg Acetaminophen …………………….
325 mg In addition each tablet contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, crospovidone, D&C Yellow #10 lake, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized corn starch, and stearic acid.
Meets USP Dissolution Test 1.
Hydrocodone Bitartrate and Acetaminophen Tablets, USP 10 mg/500 mg Each tablet contains: Hydrocodone Bitartrate …………
10 mg Acetaminophen …………………….
500 mg In addition each tablet contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, crospovidone, D&C Red #27 aluminum lake, D&C Red #30 aluminum lake, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized corn starch, and stearic acid.
Meets USP Dissolution Test 1.
Hydrocodone Bitartrate and Acetaminophen Tablets, USP 10 mg/650 mg Each tablet contains: Hydrocodone Bitartrate …………
10 mg Acetaminophen …………………….
650 mg In addition each tablet contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, crospovidone, FD&C Blue #1 aluminum lake, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized corn starch, and stearic acid.
Meets USP Dissolution Test 1.
Hydrocodone Bitartrate and Acetaminophen Tablets, USP 10 mg/660 mg Each tablet contains: Hydrocodone Bitartrate …………
10 mg Acetaminophen …………………….
660 mg In addition each tablet contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, crospovidone, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized corn starch, and stearic acid.
Meets USP Dissolution Test 1.
This is an image of the structural formula of Hydrocodone bitartrate.
This is an image of the structural formula of Acetaminophen.
HOW SUPPLIED
Hydrocodone Bitartrate and Acetaminophen Tablets, USP 2.5 mg/500 mg are supplied as white with bright pink specks, capsule-shaped, scored tablets, debossed “3591” on one side and debossed “V” on the reverse side.
The tablets are supplied in containers of: 8 NDC 21695-579-08 16 NDC 21695-579-16 28 NDC 21695-579-28 30 NDC 21695-579-30 60 NDC 21695-579-60 Store at 20°-25°C (68°-77°F) [see USP Controlled Room Temperature].
Dispense in a tight, light-resistant container as defined in the USP/NF with a child-resistant closure.
A Schedule CIII Narcotic.
GERIATRIC USE
Geriatric Use: Clinical studies of hydrocodone bitartrate and acetaminophen tablets 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 the 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.
INDICATIONS AND USAGE
Hydrocodone bitartrate and acetaminophen tablets are indicated for the relief of moderate to moderately severe pain.
PEDIATRIC USE
Pediatric Use: Safety and effectiveness in pediatric patients have not been established.
PREGNANCY
Pregnancy: Teratogenic Effects: Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women.
Hydrocodone bitartrate and acetaminophen 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, increased respiratory 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.
NUSRING MOTHERS
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.
INFORMATION FOR PATIENTS
Information for Patients: 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.
DOSAGE AND ADMINISTRATION
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.
Hydrocodone Bitartrate and Acetaminophen Tablets, USP 2.5 mg/500 mg The usual adult dosage is one or two tablets every four to six hours as needed for pain.
The total daily dosage should not exceed 8 tablets.