Phenobarbital Sodium

Parenteral Sedative. Sedation is obtainable within an hour, and in adequate dosage, the duration of action is more than six hours. Included in the more common conditions in which the sedative action of this class of drugs is desired are anxiety-tension states, hyperthyroidism, essential hypertension, nausea and vomiting of functional origin, motion sickness, acute labyrinthitis, pylorospasm in infants, chorea and cardiac failure.

Phenobarbital is also a useful adjunct in treatment of hemorrhage from the respiratory or gastrointestinal tract. Phenobarbital controls anxiety, decreases muscular activity and lessens nervous excitability in hyperthyroid patients. However, thyrotoxic individuals occasionally react poorly to barbiturates. Hypnotic, for the short-term treatment of insomnia, since it appears to lose its effectiveness for sleep induction and sleep maintenance after 2 weeks (see CLINICAL PHARMACOLOGY ).

Preanesthetic. Long-term anticonvulsant, (phenobarbital, mephobarbital and metharbital) for the treatment of generalized tonic-clonic and cortical focal seizures. And, in the emergency control of certain acute convulsive episodes, e.g., those associated with status epilepticus, cholera, eclampsia, cerebral hemorrhage, meningitis, tetanus, and toxic reactions to strychnine or local anesthetics. Phenobarbital sodium may be administered intramuscularly or intravenously as an anticonvulsant for emergency use.

When administered intravenously, it may require 15 or more minutes before reaching peak concentrations in the brain. Therefore, injecting phenobarbital sodium until the convulsions stop may cause the brain level to exceed that required to control the convulsions and lead to severe barbiturate-induced depression. Phenobarbital is indicated in pediatric patients as an anticonvulsant and as a sedative, including its preoperative and postoperative use.

Barbiturates are contraindicated in patients with known barbiturate sensitivity. Barbiturates are also contraindicated in patients with a history of manifest or latent porphyria, marked impairment of liver functions or with severe respiratory distress where dyspnea or obstruction is evident. Large doses are contraindicated in nephritic subjects. Barbiturates should not be administered to persons with known previous addiction to the sedative-hypnotic group since ordinary doses may be ineffectual and may contribute to further addiction.

Intraarterial administration is contraindicated. Its consequences vary from transient pain to gangrene. Subcutaneous administration produces tissue irritation, ranging from tenderness and redness to necrosis and is not recommended. (See DOSAGE AND ADMINISTRATION, Treatment of Adverse Effects Due to Inadvertent Error in Administration .)

Phenobarbital Sodium Injection contains the preservative benzyl alcohol and is not recommended for use in neonates. There have been reports of fatal 'gasping syndrome' in neonates (children less than one month of age) following the administration of intravenous solutions containing the preservative benzyl alcohol. Symptoms include a striking onset of gasping respiration, hypotension, bradycardia, and cardiovascular collapse.

Habit Forming Barbiturates may be habit forming. Tolerance and psychological and physical dependence may occur with continued use (see DRUG ABUSE AND DEPENDENCE and CLINICAL PHARMACOLOGY ). Patients who are psychologically dependent on barbiturates may increase the dosage or decrease the dosage interval without consulting a physician and may subsequently develop a physical dependence on barbiturates. 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 the dependent person may result in withdrawal symptoms, including delirium, convulsions and possibly death. Barbiturates should be withdrawn gradually from any patient known to be taking excessive dosage over long periods of time (see DRUG ABUSE AND DEPENDENCE ). Dermatologic Reactions Exfoliative dermatitis and Stevens-Johnson syndrome, possibly fatal, are rare hypersensitivity reactions to phenobarbital.

Physicians should be alert to signs which may precede the onset of barbiturate- induced cutaneous lesions, and the drug should be discontinued whenever dermatological reactions occur. Intravenous Administration Too rapid administration may cause severe respiratory depression, apnea, laryngospasm, hypertension or vasodilation with fall in blood pressure. When administered intravenously, it may require 15 or more minutes before reaching peak concentrations in the brain.

Therefore, injecting phenobarbital sodium until the convulsions stop may cause brain levels to exceed that required to control the convulsions and lead to severe barbiturate-induced depression. Acute or Chronic Pain 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.

Use in Pregnancy Barbiturates can cause fetal harm 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. Phenobarbital may cause major fetal malformations. Following oral or parenteral administration, barbiturates readily cross the placental barrier and are distributed throughout fetal tissues with highest concentrations found in the placenta, fetal liver and brain.

Drug Interactions Most reports of clinically significant drug interactions occuring with the barbiturates have involved phenobarbital. However, the application of these data to other barbiturates appears valid and warrants serial blood level determinations of the relevant drugs when there are multiple therapies. Anticoagulants Phenobarbital lowers the plasma levels of dicumarol (bishydroxycoumarin) and causes a decrease in anticoagulant activity as measured by the prothrombin time.

Barbiturates can induce hepatic microsomal enzymes resulting in increased metabolism and decreased anticoagulant response of oral anticoagulants (e.g., warfarin, acenocoumarol, dicumarol and phenprocoumon). Patients stabilized on anticoagulant therapy may require dosage adjustments if barbiturates are added to or withdrawn from their dosage regimen. Corticosteroids Barbiturates appear to enhance the metabolism of exogenous corticosteroids probably through the induction of hepatic microsomal enzymes.

Patients stabilized on corticosteroid therapy may require dosage adjustments if barbiturates are added to or withdrawn from thier dosage regimen. Griseofulvin Phenobarbital appears to interfere with the absorption of orally administered griseofulvin, thus decreasing its blood level. The effect of the resultant decreased blood levels of griseofulvin on therapeutic response has not been established. However, it would be preferable to avoid concomitant administration of these drugs.

Doxycycline Phenobarbital has been shown to shorten the half-life of doxycycline for as long as 2 weeks after barbiturate therapy is discontinued. This mechanism is probably through the induction of hepatic microsomal enzymes that metabolize the antibiotic. If phenobarbital and doxycycline are administered concurrently, the clinical response to doxycycline should be monitored closely. Phenytoin, Sodium Valproate, Valproic Acid The effect of barbiturates on the metabolism of phenytoin appears to be variable.

Some investigators report an accelerating effect, while others report no effect. Because the effect of barbiturates on the metabolism of phenytoin is not predictable, phenytoin and barbiturate blood levels should be monitored more frequently if these drugs are given concurrently. Sodium valproate and valproic acid appear to decrease barbiturate metabolism; therefore, barbiturate blood levels should be monitored and appropriate dosage adjustments made as indicated.

Central Nervous System Depressants The concomitant use of other central nervous system depressants, including other sedatives or hypnotics, antihistamines, tranquilizers or alcohol, may produce additive depressant effects. Monoamine Oxidase Inhibitors (MAOIs) MAOIs prolong the effects of barbiturates probably because metabolism of the barbiturate is inhibited. Estradiol, Estrone, Progesterone and Other Steroidal Hormones Pretreatment with or concurrent administration of phenobarbital may decrease the effect of estradiol by increasing its metabolism.

Pregnancy Teratogenic Effects-Pregnancy Category D Phenobarbital may cause major fetal malformations. (See WARNINGS, Use in Pregnancy .) Nonteratogenic Effects Reports of infants suffering from long-term barbiturate exposure in utero included the acute withdrawal syndrome of seizures and hyperirritability from birth to a delayed onset of up to 14 days. (See DRUG ABUSE AND DEPENDENCE . )

The following adverse reactions and their incidence were compiled from surveillance of thousands of hospitalized patients. Because such patients may be less aware of certain of the milder adverse effects of barbiturates, the incidence of these reactions may be somewhat higher in fully ambulatory patients. Nervous System Somnolence, agitation, confusion, hyperkinesia, ataxia, CNS depression, nightmares, nervousness, psychiatric disturbance, hallucinations, insomnia, anxiety, dizziness, thinking abnormality Respiratory System Hypoventilation, apnea Cardiovascular System Bradycardia, hypotension, syncope Digestive System Nausea, vomiting, constipation Dermatologic Reactions Exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermic necrolysis.

Other Reported Reactions Headache; injection site reactions; hypersensitivity reactions, including but not limited to angioedema and skin rashes; fever; liver damage and megaloblastic anemia following chronic phenobarbital use.