Worst Pills, Best Pills

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Drug Profile

Do NOT stop taking this or any drug without the advice of your physician. Some drugs can cause severe adverse effects when they are stopped suddenly.

Do Not Use [what does this mean?]
Generic drug name: butalbital, acetaminophen and caffeine (byoo TAL bi tal, a seat a MEE noe fen, and kaf EEN)
Brand name(s): ESGIC PLUS, FIORICET
GENERIC: not available FAMILIES: Barbiturates, Non-Narcotic Painkillers
Find the drug label by searching at DailyMed.

Do Not Use [what does this mean?]
Generic drug name: butalbital, caffeine and aspirin (byoo TAL bi tal, kaf EEN and AS pir in)
Brand name(s): FIORINAL
GENERIC: not available FAMILIES: Barbiturates, Salicylates
Find the drug label by searching at DailyMed.

Do Not Use [what does this mean?]
Generic drug name: butalbital, caffeine, aspirin and codeine (byoo TAL bi tal, kaf EEN, AS pir in, and KO deen)
Brand name(s): FIORINAL WITH CODEINE
GENERIC: not available FAMILIES: Barbiturates, Opiate-containing Painkillers, Salicylates
Find the drug label by searching at DailyMed.

Alternative Treatment [top]

Safety Warnings For This Drug [top]

FDA BLACK-BOX WARNING

WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; ULTRA-RAPID METABOLISM OF CODEINE AND OTHER RISK FACTORS FOR LIFETHREATENING RESPIRATORY DEPRESSION IN CHILDREN; NEONATAL OPIOID WITHDRAWL SYNDROME; and INTERACTIONS WITH DRUGS AFFECTING CYTOCHROME P450 ISOENZYMES

Addiction, Abuse, and Misuse

FIORINAL with CODEINE exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing FIORINAL with CODEINE, and monitor all patients regularly for the development of these behaviors and conditions.

Life-Threatening Respiratory Depression

Serious, life-threatening, or fatal respiratory depression may occur with use of FIORINAL with CODEINE. Monitor for respiratory depression, especially during initiation of FIORINAL with CODEINE or following a dose increase.

Accidental Ingestion

Accidental ingestion of even one dose of FIORINAL with CODEINE, especially by children, can result in a fatal overdose of FIORINAL with CODEINE.

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants

Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.

  • Reserve concomitant prescribing of FIORINAL with CODEINE and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
  • Limit dosages and durations to the minimum required.
  • Follow patients for signs and symptoms of respiratory depression and sedation.

Ultra-Rapid Metabolism of Codeine and Other Risk Factors for Life-Threatening Respiratory Depression in Children

Life-threatening respiratory depression and death have occurred in children who received codeine. Most of the reported cases occurred following tonsillectomy and/or adenoidectomy, and many of the children had evidence of being an ultrarapid metabolizer of codeine due to a CYP2D6 polymorphism. FIORINAL with CODEINE is contraindicated in children younger than 12 years of age and in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see Contraindications (4)]. Avoid the use of FIORINAL with CODEINE in adolescents 12 to 18 years of age who have other risk factors that may increase their sensitivity to the respiratory depressant effects of codeine.

Neonatal Opioid Withdrawal Syndrome

Prolonged use of FIORINAL with CODEINE during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

Death Related to Ultra-Rapid Metabolism of Codeine to Morphine

Respiratory depression and death have occurred in children who received codeine following tonsillectomy and/or adenoidectomy and had evidence of being ultra-rapid metabolizers of codeine due to a CYP2D6 polymorphism.

Interactions with Drugs Affecting Cytochrome P450 Isoenzymes

The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex. Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with FIORINAL with CODEINE requires careful consideration of the effects on codeine, and the active metabolite, morphine.

One hazard of taking these drugs continuously for longer than several weeks is drug-induced dependence. Do not stop taking your drug suddenly. With the help of your doctor, work out a schedule for slowly lowering the amount of the drug you take by about 5 to 10 percent each day. Keep a written record of the dosage reduction schedule with you. These steps will make it much easier to become drug free without developing distressing symptoms of drug withdrawal.

Fiorinal with Codeine can increase the risk of hip fracture.[1]

Warning

There have been a number of case reports of liver damage involving a possible drug interaction between isoniazid, a medication used to prevent and treat tuberculosis (TB), and acetaminophen, an over-the-counter painkiller and the active ingredient in Tylenol. Isoniazid alone, especially as people get older, has been documented to cause liver damage. Acetaminophen, alone in large doses or probably in combination with alcohol, also increases the risk of liver damage. The combination of acetaminophen with isoniazid, according to the authors of these case reports, may also be dangerous.

If you are taking isoniazid for tuberculosis or have a positive TB skin test and are using the drug, consult your physician before using acetaminophen or any combination product containing acetaminophen. Discuss alternatives to acetaminophen with your physician.

Aspirin/Reye's Syndrome Alert

Do not use the aspirin-containing products for treating chicken pox, flu, or flulike illness. They will increase the risk of contracting Reye’s syndrome, a rare but often fatal disease.

Facts About This Drug [top]

Do Not Use: These drugs are irrational combinations that include drugs that are unsafe or ineffective.

Like other fixed-combination products, these combinations curtail the ability to vary doses of each drug — irrationally combining, in the case of Fioricet, an ineffective drug (caffeine), one effective painkiller (acetaminophen) and one excessively dangerous drug (butalbital).

Caffeine has not been proven effective in relieving pain. It can aggravate incontinence, produce insomnia and...

Do Not Use: These drugs are irrational combinations that include drugs that are unsafe or ineffective.

Like other fixed-combination products, these combinations curtail the ability to vary doses of each drug — irrationally combining, in the case of Fioricet, an ineffective drug (caffeine), one effective painkiller (acetaminophen) and one excessively dangerous drug (butalbital).

Caffeine has not been proven effective in relieving pain. It can aggravate incontinence, produce insomnia and lead to dependence-causing withdrawal headaches.

Butalbital is a barbiturate, and because of the serious adverse effects and addictive nature of all barbiturates, older adults should not use it. Barbiturates other than phenobarbital (SOLFOTON, for seizure) have been on a list of drugs that are inappropriate for use in older adults.[2]

Acetaminophen is an effective painkiller that is available separately without a prescription, as is aspirin.

(See also the acetaminophen drug profile.)

Side effects

A high frequency of medication use to manage headache pain may lead to a condition known as medication overuse headache (MOH). According to a review published in the August 2004 issue of the medical journal Lancet Neurology,[3] there is now substantial evidence that all drugs used for the treatment of headache can cause MOH in patients who are using drugs to treat headaches. Combination products containing butalbital, caffeine or aspirin with or without codeine can cause MOH.

The March 2013 issue of Worst Pills, Best Pills News discussed two recent studies dealing with MOH. In the first study, the treatment for MOH was simple: basic information, tailored to the individual patient, including a discussion with the patient’s doctor both of the role of drugs in developing MOH and the likelihood that stopping painkiller overuse would lead to an improvement. The second study involved a review of MOH treatment guidelines, including evidence concerning the manner in which the previously overused painkillers were discontinued.

Based on the results of both studies, patients should discuss with their doctors the important details of MOH and, depending on their individual case, the type of withdrawal from the MOH-causing drugs that is best for them.[4]

Regulatory actions surrounding these fixed-combination drugs

2007: The Food and Drug Administration (FDA) issued a public health advisory with important new information about a very rare but serious side effect in nursing infants whose mothers are taking codeine and are ultra-rapid metabolizers of codeine. When codeine enters the body and is metabolized, it changes to morphine, which relieves pain. Nursing mothers taking codeine may have higher morphine levels in their breast milk. These higher levels of morphine in breast milk may lead to life-threatening or fatal side effects in nursing babies.[5]

2011: In January, the FDA issued an advisory concerning the strength of acetaminophen in prescription-drug products. The FDA requested that drug manufacturers limit the strength of acetaminophen in prescription-drug products to 325 milligrams per tablet. The agency also required that a black-box warning be added to the drug label of all acetaminophen-containing prescription products to highlight the potential for severe liver injury. The agency stated that another warning highlighting the potential for allergic reactions (swelling of the face, mouth and throat; difficulty breathing; itching; or rash) also would be added to the drug label.[6]

The FDA required the addition of a black-box warning to opioid and benzodiazepine drugs stating that profound sedation, depressed breathing, coma and death can occur when these medications are used together.

last reviewed February 28, 2021