phenobarbital

fee-noe-BAR-bi-tal

Therapeutic Classification: anticonvulsants, sedative/hypnotics

Pharmacologic Classification: barbiturates

BEERS REMS

Tonic-clonic (grand mal), partial, and febrile seizures in children.
Preoperative sedative and in other situations in which sedation may be required.
Hypnotic (short-term).

Produces all levels of CNS depression.
Depresses the sensory cortex, decreases motor activity, and alters cerebellar function.
Inhibits transmission in the nervous system and raises the seizure threshold.
Capable of inducing (speeding up) enzymes in the liver that metabolize drugs, bilirubin, and other compounds.

Therapeutic effects:

Anticonvulsant activity.
Sedation.

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.

(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.

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.

CV: IVhypotension

Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), photosensitivity, rash, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN), urticaria

GI: constipation, diarrhea, nausea, vomiting

Local: phlebitis

MS: arthralgia, myalgia

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

Resp: respiratory depression, IVLARYNGOSPASM, bronchospasm

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

Drug-drug:

Use with opioid analgesics may result in significant sedation, respiratory depression, coma, and death. Reserve concurrent use of these drugs for patients when alternative treatment options are inadequate; if concurrent use necessary, limit doses and durations to the minimum required.
Additive CNS depression with other CNS depressants, including alcohol, antihistamines, and other sedative/hypnotics.
May ↓ levels and effectiveness of 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 ↑ levels and risk of toxicity.
Rifampin may ↓ levels and effectiveness.
May ↑ risk of hematologic toxicity with cyclophosphamide.

Drug-Natural Products:

Kava-kava, valerian, chamomile, or hops can ↑ risk of CNS depression.
St. John’s wort may ↓ levels and effectiveness.

Status Epilepticus

IV (Adults and Children >1 mo): 15–18 mg/kg in a single or divided dose (max loading dose = 20 mg/kg).
IV (Neonates ): 15–20 mg/kg in a single dose. If clinically indicated, ≥15 min after completion of the initial loading dose, a 2nd loading dose may be administered over the subsequent 15 min 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 in 1–2 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.

(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

Monitor respiratory status, HR, and BP, and signs and symptoms of angioedema (swelling of lips, face, and throat; dyspnea) frequently in patients receiving IV therapy. Equipment for resuscitation and artificial ventilation should be readily available. Respiratory depression is dose-dependent.
Monitor for infusion site reaction (pain, swelling, discoloration, temperature change in limb). If signs/symptoms of infusion site reaction occur, immediately discontinue injection.
Assess for dermatologic toxicity. At 1st sign of drug-related rash, discontinue and do not resume therapy if symptoms suggest SJS or TEN.
Monitor for signs and symptoms of multiorgan hypersensitivity reactions: DRESS (rash, fever, lymphadenopathy). May be associated with other organ involvement (hepatitis, hepatic failure, blood dyscrasias, acute multiorgan failure). If cause cannot be determined, discontinue phenobarbital immediately.
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 ↑ sensitivity to painful stimuli.

Lab Test Considerations:

Monitor hepatic and renal function and CBC periodically during prolonged therapy.
- Monitor serum folate concentrations periodically during therapy because of ↑ folate requirements of patients on long-term anticonvulsant therapy with phenobarbital.
- May ↓ bilirubin in neonates and in patients with congenital nonhemolytic unconjugated hyperbilirubinemia or seizure disorders.

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.

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 ↓ dose while concurrently ↑ dose of replacement anticonvulsant.
PO: Tablets may be crushed and mixed with food or fluids. Oral solution may be taken undiluted or mixed with water, milk, or fruit juice. Use calibrated measuring device for accurate measurement of liquid dose.
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 phenobarbital is a vesicant. Administer into a large vein. If extravasation occurs, immediately stop infusion. Leave needle/cannula in place temporarily but do not flush the line. Gently aspirate extravasated solution; then remove needle/cannula. Elevate patient's extremity and apply dry warm compresses. Initiate hyaluronidase antidote for refractory cases in addition to supportive management. For hyaluronidase, inject a total of 1 mL (15 units/mL) intradermally or SUBQ as five separate 0.2-mL injections (using a tuberculin syringe) around the site of extravasation; if IV catheter remains in place, administer IV through the infiltrated catheter; may repeat in 30–60 min if no resolution.
IV: 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: Lyophilized powder for injection: Reconstitution: Reconstitute vial with 10 mL of 0.9% NaCl. Concentration: 10 mg/mL. 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. Administer solution undiluted. Solution for injection:Administer dose undiluted.
Rate: Infuse over 15–30 min and no faster than 60 mg/min. Infuse large loading doses over 60 min. Titrate slowly for desired response. Rapid administration may result in respiratory depression.
Y-Site Compatibility:
- acyclovir
- amikacin
- aminocaproic acid
- aminophylline
- amphotericin B liposomal
- anidulafungin
- argatroban
- arsenic trioxide
- ascorbic acid
- atropine
- azathioprine
- azithromycin
- aztreonam
- benztropine
- bivalirudin
- bleomycin
- bumetanide
- butorphanol
- caffeine citrate
- calcium chloride
- calcium gluconate
- carboplatin
- cefazolin
- ceftazidime
- ceftriaxone
- chloramphenicol
- chlorothiazide
- cisplatin
- clindamycin
- cyanocobalamin
- cyclophosphamide
- cytarabine
- dacarbazine
- dactinomycin
- daptomycin
- dexamethasone
- dexmedetomidine
- dexrazoxane
- digoxin
- docetaxel
- dopamine
- doxapram
- doxorubicin liposomal
- edetate calcium disodium
- enalaprilat
- epoetin alfa
- eptifibatide
- ertapenem
- etoposide
- etoposide phosphate
- famotidine
- fentanyl
- fluconazole
- fludarabine
- fluorouracil
- folic acid
- foscarnet
- fosphenytoin
- furosemide
- ganciclovir
- gemcitabine
- gentamicin
- glycopyrrolate
- granisetron
- heparin
- hydrocortisone
- ibuprofen lysine
- ifosfamide
- indomethacin
- insulin regular
- irinotecan
- ketorolac
- labetalol
- leucovorin
- linezolid
- lorazepam
- magnesium sulfate
- mannitol
- meropenem
- mesna
- methadone
- methohexital
- methotrexate
- methylprednisolone
- metoclopramide
- metoprolol
- metronidazole
- milrinone
- mitoxantrone
- morphine
- multivitamins
- nafcillin
- naloxone
- nitroglycerin
- nitroprusside
- octreotide
- oxacillin
- oxytocin
- paclitaxel
- palonosetron
- pamidronate
- pemetrexed
- pentobarbital
- phenylephrine
- phytonadione
- piperacillin/tazobactam
- potassium acetate
- potassium chloride
- procainamide
- propofol
- propranolol
- rocuronium
- sodium acetate
- sodium bicarbonate
- sufentanil
- theophylline
- thiotepa
- tigecycline
- tirofiban
- tobramycin
- vancomycin
- vasopressin
- vecuronium
- vinblastine
- vincristine
- voriconazole
- zoledronic acid
Y-Site Incompatibility:
- acetaminophen
- alemtuzumab
- amiodarone
- amphotericin B deoxycholate
- atracurium
- buprenorphine
- carmustine
- caspofungin
- cefotaxime
- cefotetan
- cefoxitin
- cefuroxime
- chlorpromazine
- cyclosporine
- dantrolene
- daunorubicin
- diazepam
- diazoxide
- diltiazem
- diphenhydramine
- dobutamine
- doxorubicin hydrochloride
- doxycycline
- epinephrine
- epirubicin
- esmolol
- gemtuzumab ozogamicin
- haloperidol
- idarubicin
- meperidine
- midazolam
- minocycline
- mitomycin
- mycophenolate
- nalbuphine
- nicardipine
- norepinephrine
- ondansetron
- papaverine
- pentamidine
- phenytoin
- prochlorperazine
- promethazine
- protamine
- pyridoxine
- succinylcholine
- thiamine
- topotecan
- trimethoprim/sulfamethoxazole
- verapamil
- vinorelbine

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Advise patient to take medication as directed. Take missed dose as soon as remembered if not almost time for next dose; do not double doses.
Advise patient on prolonged therapy not to discontinue medication without consulting health care provider. 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 phenobarbital.
Advise patient to notify health care provider if facial swelling, difficulty breathing, rash, skin peeling, 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 women 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 provider immediately if pregnancy is planned or suspected or if breastfeeding. Use during 3rd trimester of pregnancy may cause withdrawal symptoms (seizures, hyperirritability) in the neonate; symptoms of withdrawal may be delayed 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 weeks 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).

Decrease or cessation of seizure activity without excessive sedation. Several wk may be required to achieve maximum anticonvulsant effects.
Preoperative sedation.
Improvement in sleep patterns.
Decrease in serum bilirubin levels.

~~Luminal,~~ Sezaby

Schedule IV (C-IV)

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