1011 HYDRO/APAP 2.5/325MG

Hydrocodone bitartrate and acetaminophen tablets are indicated for the management of moderate to moderately severe pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

Limitations of Use
Because of the risks of addiction, abuse, and misuse, with opioids, even at recommended doses [seeWARNINGS], reserve hydrocodone bitartrate and acetaminophen tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics]

Have not been tolerated, or are not expected to be tolerated,
Have not provided adequate analgesia, or are not expected to provide adequate analgesia

Important Dosage and Administration Instructions
Initiate the dosing regimen for each patient individually, taking into account the patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see WARNINGS].

Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy and following dosage increases with hydrocodone bitartrate and acetaminophen tablets and adjust the dosage accordingly [see WARNINGS].

Initial Dosage

Initiating Treatment with Hydrocodone Bitartrate and Acetaminophen Tablets

2.5 mg/325 mg

5 mg/325 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.

7.5 mg/325 mg

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.

10 mg/325 mg

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.

Conversion from Other Opioids to Hydrocodone Bitartrate and Acetaminophen Tablets
There is inter-patient variability in the potency of opioid drugs and opioid formulations. Therefore, a conservative approach is advised when determining the total daily dosage of hydrocodone bitartrate and acetaminophen tablets. It is safer to underestimate a patient’s 24-hour hydrocodone bitartrate and acetaminophen tablets dosage than to overestimate the 24-hour hydrocodone bitartrate and acetaminophen tablets dosage and manage an adverse reaction due to overdose.

Titration and Maintenance of Therapy
Individually titrate hydrocodone bitartrate and acetaminophen tablets to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving hydrocodone bitartrate and acetaminophen tablets to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse [see WARNINGS]. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration.

If the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing the hydrocodone bitartrate and acetaminophen tablets dosage. If unacceptable opioid-related adverse reactions are observed, consider reducing the dosage. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

Discontinuation of Hydrocodone Bitartrate and Acetaminophen Tablets
When a patient who has been taking hydrocodone bitartrate and acetaminophen tablets regularly and may be physically dependent no longer requires therapy with hydrocodone bitartrate and acetaminophen tablets, use a gradual downward titration of the dosage to prevent signs and symptoms of withdrawal. Do not stop hydrocodone bitartrate and acetaminophen tablets abruptly [seeWARNINGS, DRUG ABUSE AND DEPENDENCE].

Clinical Presentation
Acute overdose with hydrocodone bitartrate and acetaminophen tablets can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations.

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.

Treatment of Overdose
In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support techniques.

The opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression resulting from opioid overdose. For clinically significant respiratory or circulatory depression secondary to hydrocodone bitartrate and acetaminophen tablets overdose, administer an opioid antagonist. Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to hydrocodone bitartrate and acetaminophen tablets overdose.

Because the duration of opioid reversal is expected to be less than the duration of action of hydrocodone bitartrate and acetaminophen in hydrocodone bitartrate and acetaminophen tablets, carefully monitor the patient until spontaneous respiration is reliably re-established. If the response to an opioid antagonist is suboptimal or only brief in nature, administer additional antagonist as directed by the product’s prescribing information.

In an individual physically dependent on opioids, administration of the recommended usual dosage of the antagonist will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the antagonist should be begun with care and by titration with smaller than usual doses of the antagonist.

Medication Guide

Hydrocodone Bitartrate and Acetaminophen
(hye” droe koe’ done bye tar’ trate and a seet” a min’ oh fen)
Tablets, USP, CII

Hydrocodone bitartrate and acetaminophen tablets are:

A strong prescription pain medicine that contains an opioid (narcotic) that is used to manage moderate to moderately severe pain, when other pain treatments such as non-opioid pain medicines do not treat your pain well enough or you cannot tolerate them.
An opioid pain medicine that can put you at risk for overdose and death. Even if you take your dose correctly as prescribed you are at risk for opioid addiction, abuse, and misuse that can lead to death.

Important information about hydrocodone bitartrate and acetaminophen tablets:

Get emergency help right away if you take too much hydrocodone bitartrate and acetaminophen tablets (overdose). When you first start taking hydrocodone bitartrate and acetaminophen tablets, when your dose is changed, or if you take too much (overdose), serious or life-threatening breathing problems that can lead to death may occur.
Never give anyone else your hydrocodone bitartrate and acetaminophen tablets. They could die from taking them. Store hydrocodone bitartrate and acetaminophen tablets away from children and in a safe place to prevent stealing or abuse. Selling or giving away hydrocodone bitartrate and acetaminophen tablets is against the law.

Do not take hydrocodone bitartrate and acetaminophen tablets if you have:

severe asthma, trouble breathing, or other lung problems.
a bowel blockage or have narrowing of the stomach or intestines.
signs or allergy such as a rash.
are allergic to any of its ingredients.

Before taking hydrocodone bitartrate and acetaminophen tablets, tell your healthcare provider if you have a history of:

head injury, seizures ● liver, kidney, thyroid problems
problems urinating ● pancreas or gallbladder problems
abuse of street or prescription drugs, alcohol addiction, or mental health problems.

Tell your healthcare provider if you are:

pregnant or planning to become pregnant. Prolonged use of hydrocodone bitartrate and acetaminophen tablets during pregnancy can cause withdrawal symptoms in your newborn baby that could be life-threatening if not recognized and treated.
breastfeeding. Hydrocodone bitartrate and acetaminophen passes into breast milk and may harm your baby.
taking prescription or over-the-counter medicines, vitamins, or herbal supplements. Taking hydrocodone bitartrate and acetaminophen tablets with certain other medicines can cause serious side effects that could lead to death.

When taking hydrocodone bitartrate and acetaminophen tablets:

Do not change your dose. Take hydrocodone bitartrate and acetaminophen tablets exactly as prescribed by your healthcare provider.
Take your prescribed dose every four to six hours at the same time every day. Do not take more than your prescribed dose. If you miss a dose, take your next dose at your usual time.
Call your healthcare provider if the dose you are taking does not control your pain.
If you have been taking hydrocodone bitartrate and acetaminophen tablets regularly, do not stop taking hydrocodone bitartrate and acetaminophen tablets without talking to your healthcare provider.
After you stop taking hydrocodone bitartrate and acetaminophen tablets, flush any unused tablets down the toilet.

While taking hydrocodone bitartrate and acetaminophen tablets DO NOT:

Drive or operate heavy machinery, until you know how hydrocodone bitartrate and acetaminophen tablets affects you. Hydrocodone bitartrate and acetaminophen tablets can make you sleepy, dizzy, or lightheaded.
Drink alcohol or use prescription or over-the-counter medicines that contain alcohol. Using products containing alcohol during treatment with hydrocodone bitartrate and acetaminophen tablets may cause you to overdose and die.

The possible side effects of hydrocodone bitartrate and acetaminophen tablets:

constipation, nausea, sleepiness, vomiting, tiredness, headache, dizziness, abdominal pain. Call your healthcare provider if you have any of these symptoms and they are severe.

Get emergency medical help if you have:

trouble breathing, shortness of breath, fast heartbeat, chest pain, swelling of your face, tongue, or throat, extreme drowsiness, light-headedness when changing positions, feeling faint, agitation, high body temperature, trouble walking, stiff muscles, or mental changes such as confusion.

These are not all the possible side effects of hydrocodone bitartrate and acetaminophen tablets. Call your doctor for medical advice about side effects.

You may report side effects to FDA at 1-800-FDA-1088.

For more information go to dailymed.nlm.nih.gov

This Medication Guide has been approved by the U.S. Food and Drug Administration.

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:

[image: img_76cc1259-d6ff-1118-e053-2a91aa0a4267]

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:

[image: img_76cc1259-d700-1118-e053-2a91aa0a4267]

Hydrocodone Bitartrate and Acetaminophen Tablets, USP for oral administration are available in a variety of strengths as described in the following table.

Hydrocodone
Strength Bitartrate Acetaminophen

2.5 mg/325 mg 2.5 mg 325 mg
5 mg/325 mg 5 mg 325 mg

7.5 mg/325 mg 7.5 mg 325 mg

10 mg/325 mg 10 mg 325 mg

In addition, each tablet contains the following inactive ingredients: microcrystalline cellulose, croscarmellose sodium and magnesium stearate. Meets USP Dissolution Test 1.

[image: img_76ce7826-3783-4437-e053-2991aa0a3122]