GARDENAL

A barbituric acid derivative that acts as a nonselective central nervous system depressant.

It promotes binding to inhibitory gamma-aminobutyric acid subtype receptors, and modulates chloride currents through receptor channels.

It also inhibits glutamate induced depolarizations.

For the treatment of all types of seizures except absence seizures.

Phenobarbital, the longest-acting barbiturate, is used for its anticonvulsant and sedative-hypnotic properties in the management of all seizure disorders except absence (petit mal).

Absorbed in varying degrees following oral, rectal or parenteral administration.

The salts are more rapidly absorbed than are the acids.

The rate of absorption is increased if the sodium salt is ingested as a dilute solution or taken on an empty stomach.

Hepatic (mostly via CYP2C19).

Hover over products below to view reaction partners Phenobarbital p-Hydroxyphenobarbital Phenobarbital O-glucuronide Phenobarbital O-sulfate.

53-118 hours (mean 79 hours).

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and respiratory depression which may progress to Cheyne-Stokes respiration, areflexia, constriction of the pupils to a slight degree (though in severe poisoning they may wshow paralytic dilation), oliguria, tachycardia, hypotension, lowered body temperature, and coma.

Typical shock syndrome (apnea, circulatory collapse, respiratory arrest, and death) may occur.

Phenobarbital may be habit-forming.

Tolerance and psychological and physical dependence may occur with continued use.

Patients who have psychologic dependence on barbiturates may increase the dosage or decrease the dosage interval without consulting a physician and may subsequently develop a physical dependence on barbiturates.

In order to minimize the possibility of overdosage or the development of dependence, the prescribing and dispensing of sedative-hypnotic barbiturates should be limited to the amount required for the interval until the next appointment.

Abrupt cessation after prolonged use in a person who is dependent on the drug may result in withdrawal symptoms, including delirium, convulsions, and possibly death.

Barbiturates should be withdrawn gradually from any patient known to be taking excessive doses over long periods of time. 2.

Caution should be exercised when barbiturates are administered to patients with acute or chronic pain, because paradoxical excitement could be induced or important symptoms could be masked.

However, the use of barbiturates as sedatives in the postoperative surgical period and as adjuncts to cancer chemotherapy is well established. 3.

Barbiturates can cause fetal damage when administered to a pregnant woman.

Retrospective, case-controlled studies have suggested a connection between the maternal consumption of barbiturates and a higher than expected incidence of fetal abnormalities.

Barbiturates readily cross the placental barrier and are distributed throughout fetal tissues; the highest concentrations are found in the placenta, fetal liver and brain.

Fetal blood levels approach maternal blood levels following parenteral administration.

Withdrawal symptoms occur in infants born to women who receive barbiturates throughout the last trimester of pregnancy.

If phenobarbital is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. 4.

Phenobarbital has been reported to be associated with cognitive deficits in children taking it for complicated febrile seizures. 5.

Synergistic Effects The concomitant use of alcohol or other CNS depressants may produce additive CNS depressant effects.

Phenobarbital is contraindicated in patients who are hypersensitive to barbiturates, in patients with a history of manifest or latent porphyria, and in patients with marked impairment of liver function or respiratory disease in which dyspnea or obstruction is evident.

The dose of phenobarbital must be individualized with full knowledge of its particular characteristics.

Factors of consideration are the patient's age, weight, and condition.

ADVERSE REACTIONS The following adverse reactions have been reported: CNS Depression.

• Residual sedation or "hangover," drowsiness, lethargy, and vertigo.

Emotional disturbances and phobias may be accentuated.

In some persons, barbiturates such as phenobarbital repeatedly produce excitement rather than depression, and the patient may appear to be inebriated.

Irritability and hyperactivity can occur in children.

Like other nonanalgesic hypnotic drugs, barbiturates such as phenobarbital, when given in the presence of pain, may cause restlessness, excitement, and even delirium.

Rarely, the use of barbiturates results in localized or diffuse myalgic, neuralgic, or arthritic pain, especially in psychoneurotic patients with insomnia.

The pain may appear in paroxysms, is most intense in the early morning hours, and is most frequently located in the region of the neck, shoulder girdle, and upper limbs.

Symptoms may last for days after the drug is discontinued.

• Respiratory depression, apnea, circulatory collapse.

• Acquired hypersensitivity to barbiturates consists chiefly in allergic reactions that occur especially in persons who tend to have asthma, urticaria, angioedema, and similar conditions.

Hypersensitivity reactions in this category include localized swelling, particularly of the eyelids, cheeks, or lips, and erythematous dermatitis.

Rarely, exfoliative dermatitis (eg, Stevens-Johnson syndrome and toxic epidermal necrolysis) may be caused by phenobarbital and can prove fatal.

The skin eruption may be associated with fever, delirium, and marked degenerative changes in the liver and other parenchymatous organs.

In a few cases, megaloblastic anemia has been associated with the chronic use of phenobarbital.

• Nausea and vomiting, headache, osteomalacia.

The following adverse reactions and their incidence were compiled from surveillance of thousands of hospitalized patients who received barbiturates.

Because such patients may be less aware of the milder adverse effects of barbiturates, the incidence of these reactions may be somewhat higher in fully ambulatory patients.

More than in 100 Patients The most common adverse reaction, estimated to occur at a rate of to 3 patients per 100, is: Nervous System: Somnolence Less than in 100 Patients Adverse reactions estimated to occur at a rate of less than in 100 patients are listed below, grouped by organ system and by decreasing order of occurrence: Nervous System: Agitation, confusion, hyperkinesia, ataxia, CNS depression, nightmares, nervousness, psychiatric disturbances, hallucinations, insomnia, anxiety, dizziness, abnormality in thinking.

Hypoventilation, apnea Cardiovascular System: Bradycardia, hypotension, syncope Digestive System: Nausea, vomiting, constipation Other Reported Reactions: Headache, injection site reactions, hypersensitivity reactions (angioedema, skin rashes, exfoliative dermatitis), fever, liver damage, megaloblastic anemia following chronic phenobarbital use.

For sedation, the drug may be administered in single doses of to 120 mg repeated at intervals; frequency will be determined by the patient's response.

It is generally considered that no more than 400 mg of phenobarbital should be administered during a 24-hour period.

Sedation: 30 to 120 mg daily in to 3 divided doses.

Hypnotic: 100 to 200 mg. Anticonvulsant Use Clinical laboratories reference values should be used to determine the therapeutic anticonvulsant level of phenobarbital in the serum.

To achieve the blood levels considered therapeutic in children, higher per-kilogram dosages are generally necessary for phenobarbital and most other anticonvulsants.

In children and infants, phenobarbital at a loading dose of to 20 mg/kg produces blood levels of about 20 µg/mL shortly after administration.

Phenobarbital has been used in the treatment and prophylaxis of febrile seizures.

However, it has not been established that prevention of febrile seizures influences the subsequent development of epilepsy.

Adults: 60 to 200 mg/day. Children: 3 to 6 mg/kg/day. Special Patient Population Dosage should be reduced in the elderly or debilitated because these patients may be more sensitive to barbiturates.

Dosage should be reduced for patients with impaired renal function or hepatic disease.

0121-0531-05: 5 mL unit dose cup.

Case contains 100 unit dose cups of 5 mL packaged in 10 trays of 10 unit dose cups each.

NDC 0121-0531-07: 7.5 mL unit dose cup.

Case contains 100 unit dose cups of 7.5 mL packaged in 10 trays of 10 unit dose cups each.

NDC 0121-0531-15: 15 mL unit dose cup.

Case contains 100 unit dose cups of 15 mL packaged in 10 trays of 10 unit dose cups each.

NDC 0121-0531-16: 16 fl oz (473 mL) Bottle.

Keep tightly closed.

Store at controlled room temperature, 20°-25°C (68° -77°F).

Barbiturates can cause fetal damage when administered to a pregnant woman.

Retrospective, case-controlled studies have suggested a connection between the maternal consumption of barbiturates and a higher than expected incidence of fetal abnormalities.

Barbiturates readily cross the placental barrier and are distributed throughout fetal tissues; the highest concentrations are found in the placenta, fetal liver and brain.

Fetal blood levels approach maternal blood levels following parenteral administration.

Withdrawal symptoms occur in infants born to women who receive barbiturates throughout the last trimester of pregnancy.

If phenobarbital is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Caution should be exercised when phenobarbital is administered to a nursing woman, because small amounts of barbiturates are excreted in the milk.

Phenobarbital has been reported to be associated with cognitive deficits in children taking it for complicated febrile seizures.