phenobarbital

Absorption: Absorption is slow but relatively complete (70–90%).

Distribution: Unknown.

Metabolism/Excretion: 75% metabolized by the liver, 25% excreted unchanged by the kidneys.

Half-Life: Neonates: 1.8–8.3 days; Infants: 0.8–5.5 days; Children: 1.5–3 days; Adults: 2–6 days.

Time/Action Profile ⬆ ⬇

(sedation‡)

ROUTE	ONSET	PEAK	DURATION
PO	30–60 min	unknown	>6 hr
IM, SUBQ	10–30 min	unknown	4–6 hr
IV	5 min	30 min	4–6 hr

‡Full anticonvulsant effects occur after 2–3 wk of chronic dosing unless a loading dose has been used.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Comatose patients or those with pre-existing CNS depression;
Severe respiratory disease with dyspnea or obstruction;
Uncontrolled severe pain;
Known alcohol intolerance (elixir only);
Lactation: Lactation.

Use Cautiously in:

Hepatic impairment;
Severe renal impairment;
History of suicide attempt or drug abuse;
OB: Chronic use during pregnancy results in drug dependency in the infant; may result in coagulation defects and fetal malformation; acute use at term may result in respiratory depression in the newborn;
Geri: Appears on Beers list. Older adults have risk of physical dependence and risk of toxicity at lower doses. If possible, avoid use in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

CV:

hypotension

Derm: photosensitivity, rash, urticaria

GI: constipation, diarrhea, nausea, vomiting

Local: phlebitis at IV site

MS: arthralgia, myalgia

Neuro: hangover, delirium, depression, drowsiness, excitation, lethargy, neuralgia, vertigo

Resp: respiratory depression,

LARYNGOSPASM, bronchospasm

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANGIOEDEMA AND SERUM SICKNESS), physical dependence, psychological dependence

Interactions ⬆ ⬇

Drug-drug:

Additive CNS depression with other CNS depressants, including alcohol, antihistamines, opioid analgesics, and other sedative/hypnotics.
May induce hepatic enzymes that metabolize other drugs, ↓ their effectiveness, including hormonal contraceptives, warfarin, chloramphenicol, cyclosporine, dacarbazine, corticosteroids, tricyclic antidepressants, felodipine, clonazepam, carbamazepine, verapamil, theophylline, metronidazole, and quinidine.
May ↑ risk of hepatic toxicity of acetaminophen.
MAO inhibitors, valproic acid, or divalproex may ↓ metabolism of phenobarbital, ↑ sedation.
Rifampin may ↑ metabolism of and ↓ effects of phenobarbital.
May ↑ risk of hematologic toxicity with cyclophosphamide.

Drug-Natural Products:

Concomitant use of kava-kava, valerian, chamomile, or hops can ↑ CNS depression.
St. John’s wort may ↓ effects.

Route/Dosage ⬆ ⬇

Status Epilepticus

IV (Adults and Children >1 mo): 15–18 mg/kg in a single or divided dose, maximum loading dose 20 mg/kg.
IV (Neonates ): 15–20 mg/kg in a single dose. If clinically indicated, ≥15 minutes after completion of the initial loading dose, a 2nd loading dose may be administered over the subsequent 15 minutes as 20 mg/kg for term infants or 10–20 mg/kg for preterm infants

Maintenance Anticonvulsant

IV PO (Adults and Children >12 yr): 1–3 mg/kg/day as a single dose or 2 divided doses.
IV PO (Children >5 yr): 2–3 mg/kg/day in 1–2 divided doses.
IV PO (Children ≤5 yr): 3–5 mg/kg/day in 1–2 divided doses.

Sedation

PO IM (Adults ): 30–120 mg/day in 2–3 divided doses. Preoperative sedation: 100–200 mg IM 1–1.5 hr before the procedure.
PO (Children ): 2 mg/kg 3 times daily. Preoperative sedation: 1–3 mg/kg PO/IM/IV 1–1.5 hr before the procedure.

Hypnotic

PO SC IV IM (Adults ): 100–320 mg at bedtime.
IV IM SC (Children ): 3–5 mg/kg at bedtime.

Hyperbilirubinemia

PO (Adults ): 90–180 mg/day in 2–3 divided doses.
PO (Children <12 yr): 3–8 mg/kg/day in 2–3 divided doses, doses up to 12 mg/kg/day have been used.

Availability ⬆ ⬇

(Generic available)

Tablets: 15 mg; 16.2 mg; 30 mg; 32.4 mg; 60 mg; 64.8 mg; 97.2 mg; 100 mg
Elixir: 20 mg/5 mL
Lyophilized powder for injection: 100 mg/vial
Solution for injection: 65 mg/mL; 130 mg/mL

Assessment ⬆ ⬇

Monitor respiratory status, pulse, and BP, and signs and symptoms of angioedema (swelling of lips, face, throat, dyspnea) frequently in patients receiving phenobarbital IV. Equipment for resuscitation and artificial ventilation should be readily available. Respiratory depression is dose-dependent.
- Prolonged therapy may lead to psychological or physical dependence. Restrict amount of drug available to patient, especially if depressed, suicidal, or with a history of addiction.
Geri: Older adults may react to phenobarbital with marked excitement, depression, and confusion. Monitor for these adverse reactions.
Seizures: Assess location, duration, and characteristics of seizure activity.
Sedation: Assess level of consciousness and anxiety when used as a preoperative sedative.
- Assess postoperative patients for pain with a pain scale. Phenobarbital may increase sensitivity to painful stimuli.

Lab Test Considerations:

Patients on prolonged therapy should have hepatic and renal function and CBC evaluated periodically.
- Monitor serum folate concentrations periodically during therapy because of increased folate requirements of patients on long-term anticonvulsant therapy with phenobarbital.
- May cause ↓ serum bilirubin concentrations in neonates, in patients with congenital nonhemolytic unconjugated hyperbilirubinemia, and in epileptics.

Toxicity and Overdose:

Serum phenobarbital levels may be monitored when used as an anticonvulsant. Therapeutic blood levels are 10–40 mcg/mL. Symptoms of toxicity include confusion, drowsiness, dyspnea, slurred speech, and staggering.

Implementation ⬆ ⬇

Do not confuse phenobarbital with pentobarbital.
- Supervise ambulation and transfer of patients following administration. Two side rails should be raised and call bell within reach at all times. Keep bed in low position. Institute seizure and fall precautions.
- When changing from phenobarbital to another anticonvulsant, gradually decrease phenobarbital dose while concurrently increasing dose of replacement medication to maintain anticonvulsant effects.
PO: Tablets may be crushed and mixed with food or fluids (do not administer dry) for patients with difficulty swallowing. Oral solution may be taken undiluted or mixed with water, milk, or fruit juice. Use calibrated measuring device for accurate measurement of liquid doses.
IM: Injections should be given deep into the gluteal muscle to minimize tissue irritation. Do not inject >5 mL into any one site, because of tissue irritation.

IV Administration:

IV: Doses may require 15–30 min to reach peak concentrations in the brain. Administer minimal dose and wait for effectiveness before administering 2nd dose to prevent cumulative barbiturate-induced depression.
Intermittent Infusion: Reconstitution: Reconstitute sterile powder for IV dose with 10 mL of 0.9% NaCl.Diluent: Do not use solution that is not absolutely clear within 5 min after reconstitution or that contains a precipitate. Discard powder or solution that has been exposed to air for longer than 30 min. If not administered immediately, place vial in original carton to protect from light. Stable for 8 hr at room temperature or 24 hr if refrigerated.
- Use a large peripheral vein to avoid local tissue toxicity. Solution is highly alkaline; avoid extravasation, which may cause tissue damage and necrosis. If extravasation occurs, injection of 5% procaine solution into affected area and application of moist heat may be ordered.
Concentration: 130 mg/mL (undiluted).
Rate: Do not inject IV faster than 60 mg/min. Infuse over 15–30 min. Infuse large loading doses over 60 min. Titrate slowly for desired response. Rapid administration may result in respiratory depression.

Patient/Family Teaching ⬆ ⬇

Advise patient to take medication as directed. Take missed doses as soon as remembered if not almost time for next dose; do not double doses.
Advise patients on prolonged therapy not to discontinue medication without consulting health care professional. Abrupt withdrawal may precipitate seizures or status epilepticus.
Medication may cause daytime drowsiness. Caution patient to avoid driving and other activities requiring alertness until response to medication is known. Do not resume driving until physician gives clearance based on control of seizure disorder.
Caution patient to avoid taking alcohol or other CNS depressants, including opioids, concurrently with this medication.
Advise patient to notify health care professional if signs and symptoms of angioedema, fever, sore throat, mouth sores, unusual bleeding or bruising, nosebleeds, or petechiae occur.
Teach sleep hygiene techniques (dark room, quiet, bedtime ritual, limit daytime napping, avoid nicotine and caffeine).
Rep: Advise females of reproductive potential using oral contraceptives to use an additional nonhormonal contraceptive during therapy and until next menstrual period. Instruct patient to notify health care professional immediately if pregnancy is planned or suspected or if breastfeeding. Use during third trimester of pregnancy may cause withdrawal symptoms in the neonate, including seizures and hyperirritability; symptoms of withdrawal may be delayed in the neonate up to 14 days after birth. Monitor infant for respiratory depression if used during labor. A registry is available for women exposed to phenobarbital during pregnancy: Pregnant women may enroll themselves into the North American Antiepileptic Drug Pregnancy Registry (1-888-233-2334 or http://www.aedpregnancyregistry.org).
Pedi: Advise parents or caregivers that child may experience irritability, hyperactivity, and/or sleep disturbances, which may diminish in a few days to a few wk or may persist until drug is stopped. An alternative medication can be considered. Instruct parents to monitor for skin rash occurring 7–20 days after treatment begins and to contact a health care provider if rash occurs. Teach family about symptoms of toxicity (staggering, drowsiness, slurred speech).

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇