PHENOBARBITAL

PHENOBARBITAL (fee-noe-bar'bi-tal) Solfoton PHENOBARBITAL SODIUM Luminal Classifications: anticonvulsant; sedative-hypnotic; barbiturate; Therapeutic:anticonvulsant; sedative-hypnotic Pregnancy Category: D Controlled Substance: Schedule IV

Availability

15 mg, 16 mg, 30 mg, 60 mg, 90 mg, 100 mg tablets; 16 mg capsules; 15 mg/5 mL, 20 mg/5 mL liquid; 30 mg/mL, 60 mg/mL, 65 mg/mL, 130 mg/mL injection

Action

Long-acting barbiturate. Sedative and hypnotic effects appear to be due primarily to interference with impulse transmission of cerebral cortex by inhibition of reticular activating system. CNS depression may range from mild sedation to coma, depending on dosage, route of administration, degree of nervous system excitability, and drug tolerance. Initially, barbiturates suppress REM sleep, but with chronic therapy REM sleep returns to normal.

Therapeutic Effect

Produces sedative and hypnotic effects with no analgesic properties. Limits spread of seizure activity by increasing threshold for motor cortex stimuli.

Uses

Long-term management of tonic-clonic (grand mal) seizures and partial seizures; status epilepticus, eclampsia, febrile convulsions in young children. Also used as a sedative in anxiety or tension states; in pediatrics as preoperative and postoperative sedation and to treat pylorospasm in infants.

Unlabeled Uses

Treatment and prevention of hyperbilirubinemia in neonates and in the management of chronic cholestasis; benzodiazepine withdrawal.

Contraindications

Hypersensitivity to barbiturates; manifest hepatic or familial history of porphyria; severe respiratory or kidney disease; history of previous addiction to sedative hypnotics; alcohol intoxication; uncontrolled pain; renal failure, anuria; pregnancy (category D), lactation.

Cautious Use

Impaired liver, kidney, cardiac, or respiratory function; sleep apnea; COPD; history of allergies; older adult or debilitated patients; patients with fever; hyperthyroidism; diabetes mellitus or severe anemia; seizure disorders; during labor and delivery; patient with borderline hypoadrenal function; young children and neonates.

Route & Dosage

Anticonvulsant Adult: PO/IV 1–3 mg/kg/d in divided doses Child: PO/IV 4–8 mg/kg/d in divided doses Status Epilepticus Adult: IV 300-800 mg, then 120–240 mg q20min (total max: 1–2 g) Child: IV 10–20 mg/kg in single or divided doses, then 5 mg/kg/dose q15–30min (total max: 40 mg/kg) Neonate: IV 15–20 mg/kg in single or divided doses Sedative/Hypnotic Adult: PO 30–120 mg/d IV/IM/SC 100–320 mg/d Child: PO 2 mg/kg/d in 3 divided doses IV/IM/SC 3–5 mg/kg Renal Impairment Clcr <10 mL/min: dose q12–16h Hemodialysis: 20–50% dialyzed

Administration

Oral

• Make sure patient actually swallows pill and does not "cheek" it.
• Give crushed and mixed with a fluid or with food if patient cannot swallow pill. Do not permit patient to swallow dry crushed drug.

Intramuscular

• Give IM deep into large muscle mass; do not exceed 5 mL at any one site.

Intravenous Note: Verify correct IV concentration and rate of infusion for neonates, infants, children with physician. Use IV route ONLY if other routes are not feasible. PREPARE: Direct: May be given undiluted or diluted in 10 mL of sterile water for injection.   ADMINISTER: Direct: Give 60 mg or fraction thereof over at least 60 sec. Give within 30 min after preparation.   INCOMPATIBILITIES Solution/additive: Ampicillin, cephalothin, chlorpromazine, cimetidine, clindamycin, codeine phosphate, dexamethasone, diphenhydramine, erythromycin, ephedrine, hydralazine, hydrocortisone sodium succinate, hydroxyzine, insulin, kanamycin, levorphanol, meperidine, methadone, methylphenidate, morphine, nitrofurantoin, norepinephrine, tetracyclines, pentazocine, pentobarbital, phytonadione, procaine, prochlorperazine, promazine, promethazine, sodium bicarbonate, streptomycin, vancomycin, warfarin. Y-site: Amphotericin B cholesteryl complex, hydromorphone, TPN with albumin. Be aware that extravasation of IV phenobarbital may cause necrotic tissue changes that necessitate skin grafting. Check injection site frequently.

Adverse Effects (≥1%)

Body as a Whole: Myalgia, neuralgia, CNS depression, coma, and death. CNS: Somnolence, nightmares, insomnia, "hangover," headache, anxiety, thinking abnormalities, dizziness, nystagmus, irritability, paradoxic excitement and exacerbation of hyperkinetic behavior (in children); confusion or depression or marked excitement (older adult or debilitated patients); ataxia. CV: Bradycardia, syncope, hypotension. GI: Nausea, vomiting, constipation, diarrhea, epigastric pain, liver damage. Hematologic: Megaloblastic anemia, agranulocytosis, thrombocytopenia. Metabolic: Hypocalcemia, osteomalacia, rickets. Musculoskeletal: Folic acid deficiency, vitamin D deficiency. Respiratory: Respiratory depression. Skin: Mild maculopapular, morbilliform rash; erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis (rare).

Diagnostic Test Interference

barbiturates may affect bromsulphalein retention tests (by enhancing liver uptake and excretion of dye) and increase serum phosphatase.

Interactions

Drug: Alcohol, cns depressants compound CNS depression; phenobarbital may decrease absorption and increase metabolism of oral anticoagulants; increases metabolism of corticosteroids, oral contraceptives, anticonvulsants, digitoxin, possibly decreasing their effects; antidepressants potentiate adverse effects of phenobarbital; griseofulvin decreases absorption of phenobarbital; quinine increases plasma levels. Herbal: Kava, valerian may potentiate sedation.

Pharmacokinetics

Absorption: 70–90% slowly from GI tract. Peak: 8–12 h PO; 30 min IV. Duration: 4–6 h IV. Distribution: 20–45% protein bound; crosses placenta; enters breast milk. Metabolism: In liver (CYP2C19). Elimination: In urine. Half-Life: 2–6 d.

Nursing Implications

Assessment & Drug Effects

• Observe patients receiving large doses closely for at least 30 min to ensure that sedation is not excessive.
• Chronic use in children or infants requires continuous assessment related to normal cognitive and behavioral functioning.
• Keep patient under constant observation when drug is administered IV, and record vital signs at least every hour or more often if indicated.
• Check IV injection site very frequently to prevent extravasation of phenobarbital. It could result in tissue damage requiring skin grafting.
• Lab tests: Obtain liver function and hematology tests and determinations of serum folate and vitamin D levels during prolonged therapy.
• Monitor serum drug levels. Serum concentrations >50 mcg/mL may cause coma. Therapeutic serum concentrations of 15–40 mcg/mL produce anticonvulsant activity in most patients. These values are usually attained after 2 or 3 wk of therapy with a dose of 100–200 mg/d.
• Expect barbiturates to produce restlessness when given to patients in pain because these drugs do not have analgesic action.
• Be prepared for paradoxical responses and report promptly in older adult or debilitated patient and children [i.e., irritability, marked excitement (inappropriate tearfulness and aggression in children), depression, and confusion].
• Monitor for drug interactions. Barbiturates increase the metabolism of many drugs, leading to decreased pharmacologic effects of those drugs. Whenever a barbiturate is added to an established regimen of another drug, observe for changes in effectiveness of the first drug at least during early phase of barbiturate use.
• Monitor for and report chronic toxicity symptoms (e.g., ataxia, slurred speech, irritability, poor judgment, slight dysarthria, nystagmus on vertical gaze, confusion, insomnia, somatic complaints).

Patient & Family Education

• Be aware that anticonvulsant therapy may cause drowsiness during first few weeks of treatment, but this usually diminishes with continued use.
• Avoid potentially hazardous activities requiring mental alertness until response to drug is known.
• Do not consume alcohol in any amount when taking a barbiturate; it may severely impair judgment and abilities.
• Increase vitamin D-fortified foods (e.g., milk products) because drug increases vitamin D metabolism. A vitamin D supplement may be prescribed.
• Maintain adequate dietary folate intake: fresh vegetables (especially green leafy), fresh fruits, whole grains, liver. Long-term therapy may result in nutritional folate (B₉) deficiency. A supplement of folic acid may be prescribed.
• Adhere to drug regimen (i.e., do not change intervals between doses or increase or decrease doses) without contacting physician.
• Do not stop taking drug abruptly because of danger of withdrawal symptoms (8–12 h after last dose), which can be fatal.
• Report to physician the onset of fever, sore throat or mouth, malaise, easy bruising or bleeding, petechiae, jaundice, rash when on prolonged therapy.
• Avoid pregnancy when receiving barbiturates. Use or add barrier device to hormonal contraceptive when taking prolonged therapy.

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug