Fiorinal with Codeine (Codeine Phosphate / Butalbital / Caffeine / Aspirin) - Drug Interactions, Contraindications, Overdosage

DRUG INTERACTIONS

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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Adequate long-term studies have been conducted in mice and rats with aspirin, alone or in combination with other drugs, in which no evidence of carcinogenesis was seen. No adequate studies have been conducted in animals to determine whether aspirin has a potential for mutagenesis or impairment of fertility. No adequate studies have been conducted in animals to determine whether butalbital has a potential for carcinogenesis, mutagenesis, or impairment of fertility.

Usage in Pregnancy

Teratogenic Effects

Pregnancy Category C. Animal reproduction studies have not been conducted with Fiorinal® with Codeine (Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP). It is also not known whether Fiorinal® with Codeine (Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP) can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Fiorinal® with Codeine (Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP) should be given to a pregnant woman only when clearly needed.

Nonteratogenic Effects

Although Fiorinal® with Codeine (Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP) was not implicated in the birth defect, a female infant was born with lissencephaly, pachygyria and heterotopic gray matter. The infant was born 8 weeks prematurely to a woman who had taken an average of 90 Fiorinal® with Codeine (Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP) each month from the first few days of pregnancy. The child’s development was mildly delayed and from one year of age she had partial simple motor seizures.

Withdrawal seizures were reported in a two-day-old male infant whose mother had taken a butalbital-containing drug during the last 2 months of pregnancy. Butalbital was found in the infant’s serum. The infant was given phenobarbital 5 mg/kg, which was tapered without further seizure or other withdrawal symptoms.

Studies of aspirin use in pregnant women have not shown that aspirin increases the risk of abnormalities when administered during the first trimester of pregnancy. In controlled studies involving 41,337 pregnant women and their offspring, there was no evidence that aspirin taken during pregnancy caused stillbirth, neonatal death or reduced birth weight. In controlled studies of 50,282 pregnant women and their offspring, aspirin administration in moderate and heavy doses during the first four lunar months of pregnancy showed no teratogenic effect.

Reproduction studies have been performed in rabbits and rats at doses up to 150 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to codeine.

Therapeutic doses of aspirin in pregnant women close to term may cause bleeding in mother, fetus, or neonate. During the last 6 months of pregnancy, regular use of aspirin in high doses may prolong pregnancy and delivery.

OVERDOSAGE

The toxic effects of acute overdosage of Fiorinal® with Codeine (Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP) are attributable mainly to the barbiturate and codeine components, and, to a lesser extent, aspirin. Because toxic effects of caffeine occur in very high dosages only, the possibility of significant caffeine toxicity from Fiorinal® with Codeine (Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP) overdosage is unlikely.

Signs and Symptoms

Symptoms attributable to acute barbiturate poisoning include drowsiness, confusion, and coma; respiratory depression; hypotension; hypovolemic shock. Symptoms attributable to acute aspirin poisoning include hyperpnea; acid-base disturbances with development of metabolic acidosis; vomiting and abdominal pain; tinnitus, hyperthermia; hypoprothrombinemia; restlessness; delirium; convulsions. Acute caffeine poisoning may cause insomnia, restlessness, tremor, and delirium; tachycardia and extrasystoles. Symptoms of acute codeine poisoning include the opioid triad of: pinpoint pupils, marked depression of respiration, and loss of consciousness. Convulsions may occur.

Treatment

The following paragraphs describe one approach to the treatment of overdose with Fiorinal® with Codeine (Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP). However, because strategies for the management of an overdose continually evolve, consultation with a regional poison control center is strongly encouraged.

Treatment consists primarily of management of barbiturate intoxication, reversal of the effects of codeine, and the correction of the acid-base imbalance due to salicylism. Vomiting should be induced mechanically or with emetics in the conscious patient. Gastric lavage may be used if the pharyngeal and laryngeal reflexes are present and if less than 4 hours have elapsed since ingestion. A cuffed endotracheal tube should be inserted before gastric lavage of the unconscious patient and when necessary to provide assisted respiration. Diuresis, alkalinization of the urine, and correction of electrolyte disturbances should be accomplished through administration of intravenous fluids such as 1% sodium bicarbonate and 5% dextrose in water.

Meticulous attention should be given to maintaining adequate pulmonary ventilation. The value of vasopressor agents such as Norepinephrine or Phenylephrine Hydrochloride in treating hypotension is questionable since they increase vasoconstriction and decrease blood flow. However, if prolonged support of blood pressure is required, Norepinephrine Bitartrate (Levophed®) may be given I.V. with the usual precautions and serial blood pressure monitoring. In severe cases of intoxication, peritoneal dialysis, hemodialysis, or exchange transfusion may be lifesaving. Hypoprothrombinemia should be treated with vitamin K, intravenously.

Methemoglobinemia over 30% should be treated with methylene blue by slow intravenous administration.

Naloxone, a narcotic antagonist, can reverse respiratory depression and coma associated with opioid overdose. Typically, a dose of 0.4-2 mg is given parenterally and may be repeated if an adequate response is not achieved. Since the duration of action of codeine may exceed that of the antagonist, the patient should be kept under continued surveillance and repeated doses of the antagonist should be administered as needed to maintain adequate respiration. A narcotic antagonist should not be administered in the absence of clinically significant respiratory or cardiovascular depression.

Up-to-date information about the treatment of overdose can be obtained from a Certified Regional Poison Control Center. Telephone numbers of Certified Regional Poison Control Centers are listed in the Physicians’ Desk Reference®.

Toxic and Lethal Doses (for adults)

Butalbital:                       toxic dose 1 g (20 capsules); lethal dose 2-5 g
Aspirin:                            toxic blood level greater than 30 mg/100 mL; lethal dose 10-30 g
Caffeine:                         toxic dose greater than 1 g; (25 capsules); lethal dose unknown
Codeine:                         toxic dose 240 mg (8 capsules); lethal dose 0.5-1 g

CONTRAINDICATIONS

Fiorinal® with Codeine (Butalbital, Aspirin, Caffeine, and Codeine Phosphate Capsules, USP) is contraindicated under the following conditions:

1. Hypersensitivity or intolerance to aspirin, caffeine, butalbital or codeine.

2. Patients with a hemorrhagic diathesis (e.g., hemophilia, hypoprothrombinemia, von Willebrand’s disease, the thrombocytopenias, thrombasthenia and other ill-defined hereditary platelet dysfunctions, severe vitamin K deficiency and severe liver damage).

3. Patients with the syndrome of nasal polyps, angioedema and bronchospastic reactivity to aspirin or other nonsteroidal anti-inflammatory drugs. Anaphylactoid reactions have occurred in such patients.

4. Peptic ulcer or other serious gastrointestinal lesions.

5. Patients with porphyria.