PHENOBARBITAL ORAL SOLUTION

The barbiturates are nonselective central nervous system (CNS) depressants that are primarily used as sedative-hypnotics. In subhypnotic doses, they are also used as anticonvulsants. The barbiturates and their sodium salts are subject to control under the Federal Controlled Substances Act. Phenobarbital is a barbituric acid derivative and occurs as white, odorless, small crystals or crystalline powder that is very slightly soluble in water; soluble in alcohol, in ether, and in solutions of fixed alkali hydroxides and carbonates; sparingly soluble in chloroform. Phenobarbital is 5-ethyl-5-phenylbarbituric acid and has the empirical formula C 12 H 12 N 2 O 3 . Its molecular weight is 232.24. It has the following structural formula: Phenobarbital is a substituted pyrimidine derivative in which the basic structure is barbituric acid, a substance that has no CNS activity. CNS activity is obtained by substituting alkyl, alkenyl, or aryl groups on the pyrimidine ring. Each 5 mL (teaspoon) contains 20 mg Phenobarbital and Alcohol 14.25%. The oral solution also contains Glycerin, Sucrose, Orange Flavor, Hydrogenated Vegetable Oil, FD&C Red#40, Vitamin E and Purified water. image description

INDICATIONS USAGE A. Sedative B. Anticonvulsant - For the treatment of generalized and partial seizures.

DOSAGE & ADMINISTRATION 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. Sedation For sedation, the drug may be administered in single doses of 30 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. Adults: Daytime Sedation: 30 to 120 mg daily in 2 to 3 divided doses. Oral 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 pediatric patients, higher per-kilogram dosages are generally necessary for phenobarbital and most other anticonvulsants. In pediatric patients and infants, phenobarbital at a loading dose of 15 to 20 mg/kg produces blood levels of about 20 mcg/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. Pediatric Patients: 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.

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 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 the 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/Circulatory - Respiratory depression, apnea, circulatory collapse. Allergic - 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. Other - 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 1 in 100 Patients The most common adverse reaction, estimated to occur at a rate of 1 to 3 patients per 100, is: Nervous System: Somnolence Less than 1 in 100 Patients Adverse reactions estimated to occur at a rate of less than 1 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. Respiratory System : 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. To report SUSPECTED ADVERSE REACTIONS, contact BPI Labs, LLC at 1-727-471-0850 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch