Acetaminophen and Hydrocodone

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# Black Box Warning

# Overview
Acetaminophen and Hydrocodone is a opioid/acetaminophen combination that is FDA approved for the {{{indicationType}}} of moderate to moderately severe pain. There is a Black Box Warning for this drug as shown here.  Common adverse reactions include lightheadedness, dizziness, sedation, nausea and vomiting.

# Adult Indications and Dosage

## FDA-Labeled Indications and Dosage (Adult)
- Dosing Information

## Off-Label Use and Dosage (Adult)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Acetaminophen and Hydrocodone in adult patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Acetaminophen and Hydrocodone in adult patients.

# Pediatric Indications and Dosage

## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Acetaminophen and Hydrocodone in pediatric patients.

## Off-Label Use and Dosage (Pediatric)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Acetaminophen and Hydrocodone in pediatric patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Acetaminophen and Hydrocodone in pediatric patients.

# 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.

# Warnings
- Hepatotoxicity  Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4000 milligrams per day, and often involve more than one acetaminophen-containing product. The excessive intake of acetaminophen may be intentional to cause self-harm or unintentional as patients attempt to obtain more pain relief or unknowingly take other acetaminophen-containing products.
- The risk of acute liver failure is higher in individuals with underlying liver disease and in individuals who ingest alcohol while taking acetaminophen.
- Instruct patients to look for acetaminophen or APAP on package labels and not to use more than one product that contains acetaminophen. Instruct patients to seek medical attention immediately upon ingestion of more than 4000 milligrams of acetaminophen per day, even if they feel well.
- Hypersensitivity/anaphylaxis  There have been post-marketing reports of hypersensitivity and anaphylaxis associated with use of acetaminophen. Clinical signs included swelling of the face, mouth, and throat, respiratory distress, urticaria, rash, pruritus, and vomiting. There were infrequent reports of life-threatening anaphylaxis requiring emergency medical attention. Instruct patients to discontinue Hydrocodone Bitartrate and Acetaminophen Tablets USP immediately and seek medical care if they experience these symptoms. Do not prescribe Hydrocodone Bitartrate and Acetaminophen Tablets USP for patients with acetaminophen allergy.
- 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 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.
- 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.

### Precautions
- Special Risk Patients  As with any narcotic analgesic agent, hydrocodone bitartrate and acetaminophen 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, prostatic hypertrophy or urethral stricture. 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 hydrocodone bitartrate and acetaminophen tablets are used postoperatively and in patients with pulmonary disease.

# Adverse Reactions

## Clinical Trials Experience
- 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.
Prolonged administration of hydrocodone bitartrate and acetaminophen tablets may produce constipation.
Drowsiness, mental clouding, lethargy, impairment of mental and physical performance, anxiety, fear, dysphoria, psychic dependence, mood changes.
Hydrocodone bitartrate may produce dose-related respiratory depression by acting directly on the brain stem respiratory center.
Skin rash, pruritus.
Cases of hearing impairment or permanent loss have been reported predominantly in patients with chronic overdose.
Ureteral spasm, spasm of vesical sphincters and urinary retention have been reported with opiates.
- The following adverse drug events may be borne in mind as potential effects of acetaminophen: allergic reactions, rash, thrombocytopenia, agranulocytosis.

## Postmarketing Experience
There is limited information regarding Postmarketing Experience of Acetaminophen and Hydrocodone in the drug label.

# 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.

# Use in Specific Populations

### Pregnancy
Pregnancy Category (FDA):
- 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.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Acetaminophen and Hydrocodone in women who are pregnant.

### Labor and Delivery
- As with all narcotics, administration of this product 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.

### Geriatic 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 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.

### Gender
There is no FDA guidance on the use of Acetaminophen and Hydrocodone with respect to specific gender populations.

### Race
There is no FDA guidance on the use of Acetaminophen and Hydrocodone with respect to specific racial populations.

### Renal Impairment
There is no FDA guidance on the use of Acetaminophen and Hydrocodone in patients with renal impairment.

### Hepatic Impairment
There is no FDA guidance on the use of Acetaminophen and Hydrocodone in patients with hepatic impairment.

### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Acetaminophen and Hydrocodone in women of reproductive potentials and males.

### Immunocompromised Patients
There is no FDA guidance one the use of Acetaminophen and Hydrocodone in patients who are immunocompromised.

# Administration and Monitoring

### Administration
- Oral

### Monitoring
There is limited information regarding Monitoring of Acetaminophen and Hydrocodone in the drug label.

# IV Compatibility
There is limited information regarding IV Compatibility of Acetaminophen and Hydrocodone in the drug label.

# Overdosage

## Acute Overdose

### 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 coagulation defects 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.

### Management
- A single or multiple drug 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. Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated. Assisted or controlled ventilation should also be considered.
- For hydrocodone overdose, primary attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and the institution of assisted or controlled ventilation. The narcotic antagonist naloxone hydrochloride is a specific antidote against respiratory depression which may result from overdosage or unusual sensitivity to narcotics, including hydrocodone. Since the duration of action of hydrocodone may exceed that of the antagonist, the patient should be kept under continued 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.
- Gastric decontamination with activated charcoal should be administered just prior to N-acetylcysteine (NAC) to decrease systemic absorption if acetaminophen ingestion is known or suspected to have occurred within a few hours of presentation. Serum acetaminophen levels should be obtained immediately if the patient presents 4 hours or more after ingestion to assess potential risk of hepatotoxicity; acetaminophen levels drawn less than 4 hours post-ingestion may be misleading. To obtain the best possible outcome, NAC should be administered as soon as possible where impending or evolving liver injury is suspected. Intravenous NAC may be administered when circumstances preclude oral administration.
- Vigorous supportive therapy is required in severe intoxication. Procedures to limit the continuing absorption of the drug must be readily performed since the hepatic injury is dose dependent and occurs early in the course of intoxication.

## Chronic Overdose
There is limited information regarding Chronic Overdose of Acetaminophen and Hydrocodone in the drug label.

# Pharmacology
There is limited information regarding Acetaminophen and Hydrocodone Pharmacology in the drug label.

## Mechanism of Action
- 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.

## Structure
- Hydrocodone Bitartrate and Acetaminophen Tablets are 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: 4,5-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:
- In addition each tablet contains the following inactive ingredients: crospovidone, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized starch, silicon dioxide, and stearic acid.
- The 10 mg/650 mg tablet also contains FD & C Blue No. 1 Aluminum Lake 12%.
- Meets USP Dissolution Test 1.

## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Acetaminophen and Hydrocodone in the drug label.

## 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  5.2 ng/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 of metabolism including O-demethylation, N-demethylation and 6-keto reduction to the corresponding 6-- and 6--hydroxy-metabolites.
- Acetaminophen  Acetaminophen is rapidly absorbed from the gastrointestinal tract 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.

## Nonclinical Toxicology
There is limited information regarding Nonclinical Toxicology of Acetaminophen and Hydrocodone in the drug label.

# Clinical Studies
There is limited information regarding Clinical Studies of Acetaminophen and Hydrocodone in the drug label.

# How Supplied
- Hydrocodone Bitartrate and Acetaminophen Tablets USP are supplied in Unit-of-Use Bottles as follows:
- Dispense in a tight, light-resistant container (as defined in USP) with a child-resistant closure.
- Storage  Store at 20 to 25C (68 to 77F). Protect from light.
- A Schedule III controlled drug substance.

## Storage
There is limited information regarding Acetaminophen and Hydrocodone Storage in the drug label.

# Images

## Drug Images

## Package and Label Display Panel

# Patient Counseling Information
- Do not take Hydrocodone Bitartrate and Acetaminophen Tablets USP if you are allergic to any of its ingredients.
- If you develop signs of allergy such as a rash or difficulty breathing stop taking Hydrocodone Bitartrate and Acetaminophen Tablets USP and contact your healthcare provider immediately.
- Do not take more than 4000 milligrams of acetaminophen per day. Call your doctor if you took more than the recommended dose.
- 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.

# Precautions with Alcohol
- Alcohol-Acetaminophen and Hydrocodone interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

# Brand Names
- HYDROCODONE BIT/APAP

# Look-Alike Drug Names
There is limited information regarding Acetaminophen and Hydrocodone Look-Alike Drug Names in the drug label.

# Drug Shortage Status

# Price