Fioricet Clinical Pharmacology

Fioricet is intended as a treatment for tension headache.

It consists of a fixed combination of butalbital, acetaminophen, and caffeine. The role each component plays in the relief of the complex of symptoms known as tension headache is incompletely understood.

Pharmacokinetics

The behavior of the individual components is described below.

Butalbital

Butalbital is well absorbed from the gastrointestinal tract and is expected to distribute to most tissues in the body. Barbiturates in general may appear in breast milk and readily cross the placental barrier. They are bound to plasma and tissue proteins to a varying degree and binding increases directly as a function of lipid solubility.

Elimination of butalbital is primarily via the kidney (59% to 88% of the dose) as unchanged drug or metabolites. The plasma half-life is about 35 hours. Urinary excretion products include parent drug (about 3.6% of the dose), 5-isobutyl-5-(2, 3-dihydroxypropyl) barbituric acid (about 24% of the dose), 5-allyl-5(3-hydroxy-2-methyl-1-propyl) barbituric acid (about 4.8% of the dose), products with the barbituric acid ring hydrolyzed with excretion of urea (about 14% of the dose), as well as unidentified materials. Of the material excreted in the urine, 32% is conjugated.

The in vitro plasma protein binding of butalbital is 45% over the concentration range of 0.5-20 mcg/mL. This falls within the range of plasma protein binding (20%-45%) reported with other barbiturates such as phenobarbital, pentobarbital, and secobarbital sodium. The plasma-to-blood concentration ratio was almost unity, indicating that there is no preferential distribution of butalbital into either plasma or blood cells.

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.

Caffeine

Like most xanthines, caffeine is rapidly absorbed and distributed in all body tissues and fluids, including the CNS, fetal tissues, and breast milk.

Caffeine is cleared through metabolism and excretion in the urine. The plasma half-life is about 3 hours. Hepatic biotransformation prior to excretion results in about equal amounts of 1-methylxanthine and 1-methyluric acid. Of the 70% of the dose that is recovered in the urine, only 3% is unchanged drug.

Mechanism of Action

Butalbital: Barbiturate; elicits generalized CNS depressant effects; depresses sensory cortex; decreases motor activity

Acetaminophen: Nonopioid, nonsalicylate analgesic; acts on hypothalamus to produce analgesia and antipyresis

Caffeine: Vasoconstrictive properties of cerebral blood vessels may be helpful when treating headaches; improves skeletal muscle contraction and medullary respiratory center sensitivity; stimulates central inspiratory drive

Absorption

Butalbital and caffeine: Well absorbed

Bioavailability: 100% acetaminophen

Distribution

Protein bound: Butalbital (45%); acetaminophen (20-50%)

Metabolism

Butalbital

  • Metabolized in liver by CYP450 enzyme system
  • Induces hepatic enzymes, but to lesser degree than phenobarbital

Acetaminophen

  • Metabolized in liver by microsomal enzyme systems
  • 80-85% conjugated principally with glucuronic acid and to a lesser extent with sulfuric acid and cysteine
  • 4% metabolized by CYP450 to toxic metabolite (N acetyl-p-benzoquinoneimine, N-acetylimidoquinone [NAPQI]), which is detoxified by conjugation with glutathione; high doses may deplete fixed amount of glutathione in body, causing NAPQI accumulation

Caffeine

  • Metabolized in liver via CYP1A2 to paraxanthine, theobromine, and theophylline

Elimination

Half-life: 35 hr butalbital; 2-4 hr acetaminophen; 3-7 hr caffeine

Excretion: Butalbital (59-88% in urine); acetaminophen (90-100% in urine, principally as acetaminophen glucuronide with acetaminophen sulfate/mercaptate); caffeine (principally in urine)

 

Fioricet Overdose Signs and Symptoms, and Treatment

Following an acute overdosage of butalbital, acetaminophen, and caffeine, toxicity may result from the barbiturate or the acetaminophen. Toxicity due to caffeine is less likely, due to the relatively small amounts in this formulation.

Fioricet is a combination prescription medication used to treat migraines and tension headaches. Keep the following key points in mind regarding Fioricet:

    • Fioricet includes butalbital, acetaminophen and caffeine
    • Fioricet is a controlled substance and should be taken exactly as prescribed
    • As a depressant, Fioricet can have side effects like feeling sluggish or drowsiness as the body adjusts to the medication. In rare cases, side effects can be more severe.
    • Fioricet can interact with other drugs and health conditions and you should speak to a doctor if you are taking other medications, have any other health conditions or are pregnant
    • Fioricet has some addictive qualities
    • Misusing Fioricet can be dangerous or deadly

 

Signs and Symptoms

Toxicity from barbiturate poisoning include drowsiness, confusion, and coma; respiratory depression; hypotension; and hypovolemic shock.

In acetaminophen overdosage: dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necroses, 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.

Acute caffeine poisoning may cause insomnia, restlessness, tremor, and delirium, tachycardia and extrasystoles.

Treatment

A single or multiple overdose with Fioricet 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. Pressors should be avoided. A cuffed endotracheal tube should be inserted before gastric lavage of the unconscious patient and when necessary, to provide assisted respiration. If renal function is normal, forced diuresis may aid in the elimination of the barbiturate. Alkalinization of the urine increases renal excretion of some barbiturates, especially phenobarbital.

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.

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.

Toxic Doses (for adults)

 Butalbital:

    toxic dose

   1 g

   (20 tablets)

 Acetaminophen:

    toxic dose

   10 g

   (30 tablets)

 Caffeine:

    toxic dose

   1 g

   (25 tablets)

In all cases of suspected overdosage, call your Regional Poison Control Center to obtain the most up-to-date information about the treatment of overdosage. Telephone numbers of certified Regional Poison Control Centers are listed in the Physicians’ Desk Reference®.

Acetaminophen Overdose

Do not take Fioricet along with other medications that contain acetaminophen as it can be toxic to the liver.

In the event of an overdose on Fioricet, call 911 immediately. Emergency treatment is critical to ensure the person remains stable. After the immediate overdose risk is averted, subsequent care is essential to effectively address the drug abuse or addiction issue.

Fioricet rehab treatment normally begins with the detoxification phase. This process reduces the patient’s dosage of Fioricet until they are no longer taking the drug at all. The detoxification phase of the treatment eliminates the patient’s physical dependence on Fioricet. The remainder of a treatment program for Fioricet addiction deals primarily with the psychological aspect of the addiction.

Barbiturate Withdrawal Following Internet Purchase of Fioricet

Who can not buy fioricet in our website online ?

All the pharmacies in our warehouses are US licensed pharmacies and you can get the pharmacy name, the pharmacists name and the doctor name in the bottle we sent you.

You can also get the full prescription profile when you buy the prescription in our online pharmacies. But we do not ship to all patients:

    • The first time buyer. We do not sell to patient who has not seen a local doctors that prescribed him a Fioricet prescription;
    • The patient has a history of mental illness or suicidal thoughts;
    • The patient has liver disease;
    • The patient has heart disease;
    • The patient has kidney disease;
    • The patient has drug or alcohol addiction history;
    • The patient has taken a MAO inhibitor in the past 14 days;
    • The patient is allergic to acetaminophen, butalbital, or caffeine;
    • The patient has cirrhosis disease;
    • The patient has asthma, sleep apnea, or other breathing disorder;
    • The patient has stomach ulcer or bleeding;
    • The patient has a history of skin rash caused by any medication;
    • The patient uses medicine to prevent blood clots
    • The patient is pregnant; life-threatening withdrawal symptoms in the baby after it is born
    • The patient is breastfeeding because this medicine can pass into breast milk and may harm a nursing baby.

You  cannot order in our website if you

    • have not picked up after clicking placing order button;
    • send us a bounced check;
    • send us a check not money order;
    • keep emailing us for a single order ID
    • asked a charge back before

Background  The Internet enables businesses to advertise their pharmaceutical products and services without medical supervision. The Internet also allows for the unsupervised purchase of medications that may have neurologic consequences.

Objective  To describe acute withdrawal delirium following the abrupt discontinuation of Fioricet.

Patient  The patient was a 37-year-old woman with a history of depression and migraine headaches but not drug abuse. She developed a florid withdrawal delirium following the discontinuation of a drug she purchased online. The medication, which contained butalbital, was self-administered in escalating doses for the treatment of chronic headaches. Daily doses of up to 750 mg to 1000 mg were reported.

Results  The patient was admitted to the hospital for the treatment of unexplained seizures that were followed by several days of an intense withdrawal syndrome. Little improvement was noted after the administration of benzodiazepines and phenothiazine. After parenteral phenobarbital administration, her symptoms resolved.

Conclusions  The withdrawal state from barbiturates is similar to that from ethanol. Tolerance can develop with prolonged abuse, leading to escalating drug doses to achieve the desired effect.

The suggested management of both types of withdrawal syndromes is similar, but the relative resistance of the behavioral and autonomic features in patients was remarkable.

Physicians should be aware of the ease with which medications can be purchased without supervision from Internet pharmacies. The magnitude of the number of drugs that are made available through this means creates a proclivity to withdrawal states.

Pregnancy

Case reports of withdrawal seizures in newborns whose mothers had taken butalbital-containing drug during pregnancy

Lactation

Excreted in breast milk in small amounts; not recommended

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.