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TRAMADOL - ORAL USES: This medication is used to relieve moderate pain. It is similar to narcotic pain medications. It works on certain nerves in the brain that control how you experience pain.HOW TO USE: Take this medication by mouth with or without food as directed by your doctor,

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. If you have nausea,

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you may take this drug with food. Consult your doctor or pharmacist about other ways to decrease nausea (e.g., antihistamines, lying down for 1 to 2 hours with as little head movement as possible).

The dosage is based on your medical condition and response to treatment. To reduce the risk of side effects, your doctor may tell you to gradually increase your dose when starting maximum recommended dose is 400 milligrams a day. If you have serious kidney disease (e.g., if you are on dialysis),

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, the maximum recommended dose is 100 milligrams every 12 hours,

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. If you have serious liver disease (e.g.,

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cirrhosis), the maximum recommended dose is 50 milligrams every 12 hours. If you are older than 75 years,

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the maximum recommended dose is 300 milligrams a medications work best if they are used as the first signs of pain (or migraine) occur.

If you wait until the pain has worsened,

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, the medication may not work as ow your doctor's or pharmacist's instruction for the safe use of non-narcotic pain relievers (e.g., acetaminophen,

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ibuprofen). Ask your doctor or pharmacist for more details regarding your treatment.

Tramadol may cause withdrawal reactions, especially if it has been used regularly for a long time or in high doses. In such cases, withdrawal symptoms (such as anxiety, sweating, sleeplessness, shaking, diarrhea, rapid breathing) may occur if you suddenly stop using this medication,

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. To prevent withdrawal reactions, your doctor may reduce your dose gradually. Also,

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,
if you are taking regular doses of narcotic medications for ongoing pain (e.g., cancer pain), starting tramadol may cause a withdrawal reaction.

Consult your doctor or pharmacist for more details, and report any withdrawal reactions ly,

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, abnormal drug-seeking behavior (addiction) is possible with this medication. Do not increase your dose, take it more frequently,

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or use it for a longer time than prescribed,

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. Properly stop the medication when so directed. When used for an extended period, this medication may not work as well and may require different dosing. Talk with your doctor if this medication stops working well.

Fioricet® (Butalbital, Acetaminophen, and Caffeine Tablets USP) is supplied in tablet form for oral administration. 

Each tablet contains the following active ingredients:
butalbital USP . . . . . . . . . ,

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. . .50 mg
acetaminophen USP . . ,

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. . . . 325 mg
caffeine USP . . . . . . . ,

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. . ,

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. ,

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. . .40 mg 

Inactive Ingredients: crospovidone, FD&C Blue #1,

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, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized starch, and stearic acid. 

Butalbital (5-allyl-5-isobutylbarbituric acid),

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, is a short to intermediate-acting barbiturate. It has the following structural formula: 

 


Fioricet® (Butalbital,

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, Acetaminophen, and Caffeine Tablets USP) is indicated for the relief of the symptom complex of tension (or muscle contraction) headache,

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. Evidence supporting the efficacy and safety of this combination product in the treatment of multiple recurrent headaches is unavailable,

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. Caution in this regard is required because butalbital is habit-forming and potentially abusable. 

Fioricet SIDE EFFECTS 



Frequently Observed

The most frequently reported adverse reactions are drowsiness,

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, lightheadedness,

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dizziness, sedation, shortness of breath, nausea,

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vomiting, abdominal pain,

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and intoxicated feeling. 

Infrequently Observed

All adverse events tabulated below are classified as infrequent. 

Central Nervous System: headache, shaky feeling, tingling,

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, agitation, fainting,

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,
fatigue, heavy eyelids,

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,
high energy, hot spells, numbness, sluggishness, seizure. Mental confusion,

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,
excitement, or depression can also occur due to intolerance, particularly in elderly or debilitated patients,

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,
or due to overdosage of butalbital. 

Autonomic Nervous System: dry mouth, hyperhidrosis. 

Gastrointestinal:

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, difficulty swallowing, heartburn, flatulence, constipation. 

Cardiovascular: tachycardia. 

Musculoskeletal: leg pain, muscle fatigue. 

Genitourinary:

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, diuresis. 

Miscellaneous: pruritus, fever, earache, nasal congestion, tinnitus, euphoria, allergic reactions. 

Several cases of dermatological reactions, including toxic epidermal necrolysis and erythema multiforme, have been reported. 

The following adverse drug events may be borne in mind as potential effects of the components of this product. Potential effects of high dosage are listed in the OVERDOSAGE section. 

Acetaminophen: allergic reactions, rash, thrombocytopenia, agranulocytosis. 

Caffeine: cardiac stimulation, irritability, tremor, dependence, nephrotoxicity, hyperglycemia. 

DRUG ABUSE AND DEPENDENCE Abuse and Dependence Butalbital

Barbiturates may be habit-forming: Tolerance, psychological dependence, and physical dependence may occur especially following prolonged use of high doses of barbiturates,

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. The average daily dose for the barbiturate addict is usually about 1500 mg,

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. As tolerance to barbiturates develops, the amount needed to maintain the same level of intoxication increases; tolerance to a fatal dosage, however, does not increase more than two-fold. As this occurs, the margin between an intoxication dosage and fatal dosage becomes smaller,

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. The lethal dose of a barbiturate is far less if alcohol is also ingested. Major withdrawal symptoms (convulsions and delirium) may occur within 16 hours and last up to 5 days after abrupt cessation of these drugs. Intensity of withdrawal symptoms gradually declines over a period of approximately 15 days. Treatment of barbiturate dependence consists of cautious and gradual withdrawal of the drug. Barbiturate-dependent patients can be withdrawn by using a number of different withdrawal regimens,

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. One method involves initiating treatment at the patient's regular dosage level and gradually decreasing the daily dosage as tolerated by the patient. 



Fioricet DRUG INTERACTIONS

The CNS effects of butalbital may be enhanced by monoamine oxidase (MAO) inhibitors. 

Butalbital, acetaminophen, and caffeine may enhance the effects of: other narcotic analgesics,

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, alcohol, general anesthetics,

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tranquilizers such as chlordiazepoxide,

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,
sedative-hypnotics,

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or other CNS depressants, causing increased CNS depression. 

TRAMADOL DRUG INTERACTIONS

CYP2D6 and CYP3A4 Inhibitors

Concomitant administration of CYP2D6 and/or CYP3A4 inhibitors, such as quinidine, fluoxetine, paroxetine and amitriptyline (CYP2D6 inhibitors),

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, and ketoconazole and erythromycin (CYP3A4 inhibitors), may reduce metabolic clearance of tramadol increasing the risk for serious adverse events including seizures and serotonin syndrome. 

Serotonergic Drugs

There have been postmarketing reports of serotonin syndrome with use of tramadol and SSRIs/SNRIs or MAOIs and α2-adrenergic blockers,

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. Caution is advised when ULTRAM® is coadministered with other drugs that may affect the serotonergic neurotransmitter systems,

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such as SSRIs, MAOIs, triptans, linezolid (an antibiotic which is a reversible non-selective MAOI),

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lithium, or St. John's Wort. If concomitant treatment of ULTRAM® with a drug affecting the serotonergic neurotransmitter system is clinically warranted, careful observation of the patient is advised,

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,
particularly during treatment initiation and dose increases. 

Triptans 

Based on the mechanism of action of tramadol and the potential for serotonin syndrome,

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, caution is advised when ULTRAM® is coadministered with a triptan. If concomitant treatment of ULTRAM® with a triptan is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases . 

Use With Carbamazepine

Patients taking carbamazepine may have a significantly reduced analgesic effect of ULTRAM®,

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. Because carbamazepine increases tramadol metabolism and because of the seizure risk associated with tramadol, concomitant administration of ULTRAM® and carbamazepine is not recommended. 

Use With Quinidine

Tramadol is metabolized to M1 by CYP2D6. Quinidine is a selective inhibitor of that isoenzyme, so that concomitant administration of quinidine and ULTRAM® results in increased concentrations of tramadol and reduced concentrations of M1. The clinical consequences of these findings are unknown. In vitro drug interaction studies in human liver microsomes indicate that tramadol has no effect on quinidine metabolism. 

Potential for Other Drugs to Affect Tramadol

In vitro drug interaction studies in human liver microsomes indicate that concomitant administration with inhibitors of CYP2D6 such as fluoxetine,

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, paroxetine, and amitriptyline could result in some inhibition of the metabolism of tramadol. Administration of CYP3A4 inhibitors, such as ketoconazole and erythromycin, or inducers, such as rifampin and St. John's Wort, with Ultram® may affect the metabolism of tramadol leading to alteted tramadol exposure. 

Potential for Tramadol to Affect Other Drugs

In vitro studies indicate that tramadol is unlikely to inhibit the CYP3A4-mediated metabolism of other drugs when tramadol is administered concomitantly at therapeutic doses,

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. Tramadol does not appear to induce its own metabolism in humans, since observed maximal plasma concentrations after multiple oral doses are higher than expected based on single-dose data. Tramadol is a mild inducer of selected drug metabolism pathways measured in animals. 

Use With Cimetidine

Concomitant administration of ULTRAM® with cimetidine does not result in clinically significant changes in tramadol pharmacokinetics,

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. Therefore, no alteration of the ULTRAM® dosage regimen is recommended. 

Use With Digoxin and Warfarin

Post-marketing surveillance has revealed rare reports of digoxin toxicity and alteration of warfarin effect,

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, including elevation of prothrombin times. 





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