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Commonly Observed

The most commonly reported adverse events associated with the use of Fiorinal® with Codeine (Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP) and not reported at an equivalent incidence by placebo-treated patients were nausea and/or abdominal pain, drowsiness, and dizziness.

Associated with Treatment Discontinuation

Of the 382 patients treated with Fiorinal® with Codeine (Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP) in controlled clinical trials, three (0.8%) discontinued treatment with Fiorinal® with Codeine (Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP) because of adverse events. One patient each discontinued treatment for the following reasons: gastrointestinal upset; lightheadedness and heavy eyelids; and drowsiness and generalized tingling.

Incidence in Controlled Clinical Trials

The following table summarizes the incidence rates of the adverse events reported by at least 1% of the Fiorinal® with Codeine (Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP) treated patients in controlled clinical trials comparing Fiorinal® with Codeine (Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP) to placebo, and provides a comparison to the incidence rates reported by the placebo-treated patients.

The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators.

Adverse Events Reported by at Least 1% of Fiorinal® with Codeine (Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP) Treated Patients During Placebo Controlled Clinical Trials Incidence Rate of Adverse Events

Other Adverse Events Reported During Controlled Clinical Trials

The listing that follows represents the proportion of the 382 patients exposed to Fiorinal® with Codeine (Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP) while participating in the controlled clinical trials who reported, on at least one occasion, an adverse event of the type cited. All reported adverse events, except those already presented in the previous table, are included. It is important to emphasize that, although the adverse events reported did occur while the patient was receiving Fiorinal® with Codeine (Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP), the adverse events were not necessarily caused by Fiorinal® with Codeine (Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP).

Adverse events are classified by body system and frequency. "Frequent" is defined as an adverse event which occurred in at least 1/100 (1%) of the patients; all adverse events listed in the previous table are frequent. "Infrequent" is defined as an adverse event that occurred in less than 1/100 patients but at least 1/1000 patients. All adverse events tabulated below are classified as infrequent.

Central Nervous: headache, shaky feeling, tingling, agitation, fainting, fatigue, heavy eyelids, high energy, hot spells, numbness, and sluggishness.

Autonomic Nervous: dry mouth and hyperhidrosis.

Gastrointestinal: vomiting, difficulty swallowing, and heartburn.

Cardiovascular: tachycardia.

Musculoskeletal: leg pain and muscle fatigue.

Genitourinary: diuresis.

Miscellaneous: pruritus, fever, earache, nasal congestion, and tinnitus.

Voluntary reports of adverse drug events, temporally associated with Fiorinal® with Codeine (Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP), that have been received since market introduction and that were not reported in clinical trials by the patients treated with Fiorinal® with Codeine (Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP), are listed below. Many or most of these events may have no causal relationship with the drug and are listed according to body system.

Central Nervous: Abuse, addiction, anxiety, depression, disorientation, hallucination, hyperactivity, insomnia, libido decrease, nervousness, neuropathy, psychosis, sedation, sexual activity increase, slurred speech, twitching, unconsciousness, vertigo.

Autonomic Nervous: epistaxis, flushing, miosis, salivation.

Gastrointestinal: anorexia, appetite increased, constipation, diarrhea, esophagitis, gastroenteritis, gastrointestinal spasm, hiccup, mouth burning, pyloric ulcer.

Cardiovascular: chest pain, hypotensive reaction, palpitations, syncope.

Skin: erythema, erythema multiforme, exfoliative dermatitis, hives, rash, toxic epidermal necrolysis.

Urinary: kidney impairment, urinary difficulty.

Miscellaneous: allergic reaction, anaphylactic shock, cholangiocarcinoma, drug interaction with erythromycin (stomach upset), edema.

The following adverse drug events may be borne in mind as potential effects of the components of Fiorinal® with Codeine (Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP). Potential effects of high dosage are listed in the OVERDOSAGE section of this insert.

Aspirin: occult blood loss, hemolytic anemia, iron deficiency anemia, gastric distress, heartburn, nausea, peptic ulcer, prolonged bleeding time, acute airway obstruction, renal toxicity when taken in high doses for prolonged periods, impaired urate excretion, hepatitis.

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

Codeine: nausea, vomiting, drowsiness, lightheadedness, constipation, pruritus.

Drug Abuse And Dependence

Controlled Substance

Fiorinal® with Codeine (Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP) is controlled by the Drug Enforcement Administration and is classified under Schedule III.

Abuse and Dependence

Codeine

Codeine can produce drug dependence of the morphine type and, therefore, has the potential for being abused. Psychological dependence, physical dependence, and tolerance may develop upon repeated administration and it should be prescribed and administered with the same degree of caution appropriate to the use of other oral narcotic medications.

Butalbital

Barbiturates may be habit-forming:

Tolerance, psychological dependence, and physical dependence may occur especially following prolonged use of high doses of barbiturates. The average daily dose for the barbiturate addict is usually about 1,500 mg. 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 twofold. As this occurs, the margin between an intoxication dosage and fatal dosage becomes smaller. 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. One method involves initiating treatment at the patient's regular dosage level and gradually decreasing the daily dosage as tolerated by the patient.

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

In patients receiving concomitant corticosteroids and chronic use of aspirin, withdrawal of corticosteroids may result in salicylism because corticosteroids enhance renal clearance of salicylates and their withdrawal is followed by return to normal rates of renal clearance.

Fiorinal® with Codeine (Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP) may enhance the effects of:

1. Oral anticoagulants, causing bleeding by inhibiting prothrombin formation in the liver and displacing anticoagulants from plasma protein binding sites.
2. Oral antidiabetic agents and insulin, causing hypoglycemia by contributing an additive effect, if dosage of Fiorinal® with Codeine (Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP) exceeds maximum recommended daily dosage.
3. 6-mercaptopurine and methotrexate, causing bone marrow toxicity and blood dyscrasias by displacing these drugs from secondary binding sites, and, in the case of methotrexate, also reducing its excretion.
4. Non-steroidal anti-inflammatory agents, increasing the risk of peptic ulceration and bleeding by contributing additive effects.
5. Other narcotic analgesics, alcohol, general anesthetics, tranquilizers such as chlordiazepoxide, sedative-hypnotics, or other CNS depressants, causing increased CNS depression.

Fiorinal® with Codeine (Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP) may diminish the effects of:

Uricosuric agents such as probenecid and sulfinpyrazone, reducing their effectiveness in the treatment of gout. Aspirin competes with these agents for protein binding sites.

Drug/Laboratory Test Interactions

Aspirin

Aspirin may interfere with the following laboratory determinations in blood: serum amylase, fasting blood glucose, cholesterol, protein, serum glutamic-oxalacetic transaminase (SGOT), uric acid, prothrombin time and bleeding time. Aspirin may interfere with the following laboratory determinations in urine: glucose, 5-hydroxy-indoleacetic acid, Gerhardt ketone, vanillylmandelic acid (VMA), uric acid, diacetic acid, and spectrophotometric detection of barbiturates.

Codeine: Codeine may increase serum amylase levels.

Last reviewed on RxList: 4/11/2008
This monograph has been modified to include the generic and brand name in many instances.