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Pronunciation
(fee noe BAR bi tal)
Generic Available (U.S.)
Yes
Index Terms
Controlled Substance
C-IV
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Management of generalized tonic-clonic (grand mal), status epilepticus, and partial seizures; sedative/hypnotic
Note: Use to treat insomnia is not recommended (Schutte-Rodin, 2008)
Use: Unlabeled
Prevention and treatment of neonatal hyperbilirubinemia and lowering of bilirubin in chronic cholestasis; neonatal seizures
Pregnancy Risk Factor
B/D (manufacturer dependent)
Pregnancy Considerations
Barbiturates can be detected in the placenta, fetal liver, and fetal brain. Fetal and maternal blood concentrations may be similar following parenteral administration. An increased incidence of fetal abnormalities may occur following maternal use. The use of folic acid throughout pregnancy and vitamin K during the last month of pregnancy is recommended; epilepsy itself, number of medications, genetic factors, or a combination of these probably influence the teratogenicity of anticonvulsant therapy. When used during the third trimester of pregnancy, withdrawal symptoms may occur in the neonate, including seizures and hyperirritability; symptoms of withdrawal may be delayed in the neonate up to 14 days after birth. Use during labor does not impair uterine activity; however, respiratory depression may occur in the newborn; resuscitation equipment should be available, especially for premature infants.
Lactation
Enters breast milk/use caution (AAP recommends use “with caution”; AAP 2001 update pending)
Breast-Feeding Considerations
Phenobarbital is excreted into breast milk. Infantile spasms and other withdrawal symptoms have been reported following the abrupt discontinuation of breast-feeding.
Contraindications
Hypersensitivity to barbiturates or any component of the formulation; marked hepatic impairment; dyspnea or airway obstruction; porphyria (manifest and latent); intra-arterial administration, subcutaneous administration (not recommended); use in patients with a history of sedative/hypnotic addiction is not recommended; nephritic patients (large doses)
Warnings/Precautions
Concern related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Hypotension: May cause hypotension particularly when administered intravenously; use with caution in hemodynamically unstable patients (hypotension or shock).
• Paradoxical stimulatory response: May cause paradoxical responses, including agitation and hyperactivity, particularly in acute pain and pediatric patients.
• Respiratory depression: May cause respiratory depression particularly when administered intravenously; use with caution patients with respiratory disease.
Disease-related concerns:
• Depression: Use with caution in patients with depression or suicidal tendencies.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Hypoadrenalism: Use with caution in patients with hypoadrenalism.
• Renal impairment: Use with caution in patients with renal impairment.
• Substance abuse: Use with caution in patients with a history of drug abuse; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use.
Concurrent drug therapy issues:
• Sedatives: Effects with other sedative drugs or ethanol may be potentiated.
Special populations:
• Debilitated patients: Use with caution in patients who are debilitated.
• Elderly: Use with caution in the elderly; due to its long half-life and risk of dependence, phenobarbital is not recommended as a sedative in the elderly.
• Pediatrics: Use with caution in children; has been associated with cognitive deficits.
Dosage form specific issues:
• Injection: Intra-arterial administration may cause reactions ranging from transient pain to gangrene and is contraindicated. Subcutaneous administration may cause tissue irritation (eg, redness, tenderness, necrosis) and is not recommended.
Other warnings/precautions:
• Acute pain: Do not administer to patients in acute pain.
• Withdrawal: Anticonvulsants should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.
Adverse Reactions
Frequency not defined.
Cardiovascular: Bradycardia, hypotension, syncope
Central nervous system: Agitation, anxiety, ataxia, CNS excitation or depression, confusion, dizziness drowsiness, hallucinations, “hangover” effect, headache, hyperkinesia, impaired judgment, insomnia, lethargy, nervousness, nightmares, somnolence
Dermatologic: Exfoliative dermatitis, rash, Stevens-Johnson syndrome
Gastrointestinal: Nausea, vomiting, constipation
Hematologic: Agranulocytosis, thrombocytopenia, megaloblastic anemia
Local: Pain at injection site, thrombophlebitis with I.V. use
Renal: Oliguria
Respiratory: Laryngospasm, respiratory depression, apnea (especially with rapid I.V. use), hypoventilation
Miscellaneous: Gangrene with inadvertent intra-arterial injection
Metabolism/Transport Effects
Substrate of CYP2C19 (major), CYP2C9 (minor), CYP2E1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Induces CYP1A2 (strong), CYP2A6 (strong), CYP2B6 (strong), CYP2C8 (strong), CYP2C9 (strong), CYP3A4 (strong)
Drug Interactions
Acetaminophen: Barbiturates may increase the metabolism of Acetaminophen. This may 1) diminish the effect of acetaminophen; and 2) increase the risk of liver damage. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Amphetamines: May decrease the serum concentration of PHENobarbital. Risk C: Monitor therapy
ARIPiprazole: CYP3A4 Inducers may decrease the serum concentration of ARIPiprazole. Management: Double aripiprazole dose when initiating concomitant therapy with a CYP3A4 inducer (e.g., carbamazepine). Monitor response and adjust aripiprazole dose as clinically indicated. If CYP3A4 inducer is discontinued, reduce aripiprazole dose to 10-15 mg/day. Risk D: Consider therapy modification
Axitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Axitinib. Risk X: Avoid combination
Bendamustine: CYP1A2 Inducers (Strong) may decrease the serum concentration of Bendamustine. Concentrations of active metabolites may be increased. Risk C: Monitor therapy
Beta-Blockers: Barbiturates may decrease the serum concentration of Beta-Blockers. Exceptions: Atenolol; Levobunolol; Metipranolol; Nadolol. Risk C: Monitor therapy
Boceprevir: PHENobarbital may decrease the serum concentration of Boceprevir. Risk X: Avoid combination
Bortezomib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Bortezomib. Risk X: Avoid combination
Brentuximab Vedotin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Risk C: Monitor therapy
Calcium Channel Blockers: Barbiturates may increase the metabolism of Calcium Channel Blockers. Management: Monitor for decreased therapeutic effects of calcium channel blockers with concomitant barbiturate therapy. Calcium channel blocker dose adjustments may be necessary. Nimodipine Canadian labeling contraindicates concomitant use with phenobarbital. Exceptions: Clevidipine. Risk C: Monitor therapy
Carbonic Anhydrase Inhibitors: May enhance the adverse/toxic effect of Anticonvulsants (Barbiturate). Specifically, osteomalacia and rickets. Exceptions: Brinzolamide; Dorzolamide. Risk C: Monitor therapy
Chloramphenicol: May decrease the metabolism of Barbiturates. Barbiturates may increase the metabolism of Chloramphenicol. Risk D: Consider therapy modification
Cholestyramine Resin: May decrease the serum concentration of PHENobarbital. Management: Administer phenobarbital at least 1 hour before or 4-6 hours after administration of cholestyramine in order to minimize the risk for any significant interaction. Risk D: Consider therapy modification
Clarithromycin: CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Clarithromycin. CYP3A4 Inducers (Strong) may decrease the serum concentration of Clarithromycin. Clarithromycin may increase the serum concentration of CYP3A4 Inducers (Strong). Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Risk C: Monitor therapy
Contraceptives (Estrogens): Barbiturates may diminish the therapeutic effect of Contraceptives (Estrogens). Contraceptive failure is possible. Management: Use of a non-hormonal contraceptive is recommended. Risk D: Consider therapy modification
Contraceptives (Progestins): Barbiturates may diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible. Management: Use of alternative, nonhormonal contraceptives is recommended. Risk D: Consider therapy modification
Corticosteroids (Systemic): Barbiturates may decrease the serum concentration of Corticosteroids (Systemic). Risk C: Monitor therapy
Crizotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Crizotinib. Risk X: Avoid combination
CycloSPORINE: Barbiturates may increase the metabolism of CycloSPORINE. Risk D: Consider therapy modification
CycloSPORINE (Systemic): Barbiturates may increase the metabolism of CycloSPORINE (Systemic). Risk D: Consider therapy modification
CYP1A2 Substrates: CYP1A2 Inducers (Strong) may increase the metabolism of CYP1A2 Substrates. Risk C: Monitor therapy
CYP2A6 Substrates: CYP2A6 Inducers (Strong) may increase the metabolism of CYP2A6 Substrates. Risk C: Monitor therapy
CYP2B6 Substrates: CYP2B6 Inducers (Strong) may increase the metabolism of CYP2B6 Substrates. Risk C: Monitor therapy
CYP2C19 Inducers (Strong): May increase the metabolism of CYP2C19 Substrates. Risk C: Monitor therapy
CYP2C19 Inhibitors (Moderate): May decrease the metabolism of CYP2C19 Substrates. Risk C: Monitor therapy
CYP2C19 Inhibitors (Strong): May decrease the metabolism of CYP2C19 Substrates. Risk D: Consider therapy modification
CYP2C8 Substrates: CYP2C8 Inducers (Strong) may increase the metabolism of CYP2C8 Substrates. Risk C: Monitor therapy
CYP2C9 Substrates: CYP2C9 Inducers (Strong) may increase the metabolism of CYP2C9 Substrates. Risk C: Monitor therapy
CYP3A4 Substrates: CYP3A4 Inducers (Strong) may increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Cyproterone: May decrease the serum concentration of CYP2E1 Substrates. Risk C: Monitor therapy
Darunavir: PHENobarbital may decrease the serum concentration of Darunavir. Risk X: Avoid combination
Dasatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dasatinib. Management: Avoid when possible. If such a combination cannot be avoided, consider increasing dasatinib dose and monitor clinical response and toxicity closely. Risk D: Consider therapy modification
Deferasirox: PHENobarbital may decrease the serum concentration of Deferasirox. Management: Avoid combination when possible; if the combination must be used, consider an increase in initial deferasirox dose to 30 mg/kg, and monitor serum ferritin concentrations/clinical responses to guide further dosing. Risk D: Consider therapy modification
Dexmethylphenidate: May increase the serum concentration of PHENobarbital. Risk C: Monitor therapy
Diclofenac: CYP2C9 Inducers (Strong) may decrease the serum concentration of Diclofenac. Risk C: Monitor therapy
Disopyramide: Barbiturates may increase the metabolism of Disopyramide. Risk C: Monitor therapy
Divalproex: May decrease the metabolism of Barbiturates. Barbiturates may decrease the serum concentration of Divalproex. Risk C: Monitor therapy
Doxycycline: Barbiturates may decrease the serum concentration of Doxycycline. Risk D: Consider therapy modification
Dronedarone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Dronedarone. Risk X: Avoid combination
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Etoposide: Barbiturates may decrease the serum concentration of Etoposide. Risk C: Monitor therapy
Etoposide Phosphate: Barbiturates may decrease the serum concentration of Etoposide Phosphate. Barbiturates may increase the metabolism, via CYP isoenzymes, of etoposide phosphate. Risk C: Monitor therapy
Etravirine: PHENobarbital may decrease the serum concentration of Etravirine. Management: The manufacturer of etravirine states these drugs should not be used in combination Risk X: Avoid combination
Everolimus: CYP3A4 Inducers (Strong) may decrease the serum concentration of Everolimus. Management: Avoid concurrent use of strong CYP3A4 inducers, but if strong CYP3A4 inducers cannot be avoided, consider gradually (in 5 mg increments) increasing the everolimus dose from 10 mg/day to 20 mg/day (adult doses). Risk X: Avoid combination
Exemestane: CYP3A4 Inducers (Strong) may decrease the serum concentration of Exemestane. Management: Exemestane prescribing information recommends using an increased dose (50 mg/day) in patients receiving concurrent strong CYP3A4 inducers. Monitor patients closely for evidence of toxicity and/or inadequate clinical response. Risk D: Consider therapy modification
Felbamate: PHENobarbital may decrease the serum concentration of Felbamate. Felbamate may increase the serum concentration of PHENobarbital. Management: In patients receiving phenobarbital, initiate felbamate at 1200 mg/day in divided doses 3-4 times daily and reduce phenobarbital dose by 20%. Monitor for increased phenobarbital concentrations/effects and decreased felbamate concentrations/effects. Risk D: Consider therapy modification
Felbamate: May increase the serum concentration of Barbiturates. Barbiturates may decrease the serum concentration of Felbamate. Management: Monitor for elevated barbiturate concentrations/toxicity if felbamate is initiated/dose increased, or reduced concentrations/effects if felbamate is discontinued/dose decreased. Refer to phenobarbital dosing guidelines for patients receiving that agent. Risk C: Monitor therapy
Folic Acid: May decrease the serum concentration of PHENobarbital. Risk C: Monitor therapy
Fosphenytoin: Barbiturates may enhance the CNS depressant effect of Fosphenytoin. Fosphenytoin may increase the serum concentration of Barbiturates. Barbiturates may decrease the serum concentration of Fosphenytoin. Risk C: Monitor therapy
Gefitinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Gefitinib. Management: In the absence of severe adverse drug reactions, consider increasing gefitinib dose to 500 mg daily in patients receiving strong CYP3A4 inducers. Carefully monitor clinical response and development of adverse reactions. Risk D: Consider therapy modification
Griseofulvin: Barbiturates may decrease the serum concentration of Griseofulvin. Risk C: Monitor therapy
GuanFACINE: CYP3A4 Inducers (Strong) may decrease the serum concentration of GuanFACINE. Management: Consider increasing the guanfacine dose (within the labeled dosage range) when such a combination is used. Risk D: Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of Barbiturates. Management: Consider a decrease in the barbiturate dose, as appropriate, when used together with hydroxyzine. With concurrent use, monitor patients closely for excessive response to the combination. Risk D: Consider therapy modification
Imatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Imatinib. Management: Avoid concurrent use of imatinib with strong CYP3A4 inducers when possible. If such a combination must be used, increase imatinib dose by at least 50% and monitor the patient's clinical response closely. Risk D: Consider therapy modification
Irinotecan: PHENobarbital may decrease the serum concentration of Irinotecan. Concentrations of the active metabolite SN-38 may also be reduced. Management: Change to a non-enzyme inducing anticonvulsant, when clinically possible, at least 2 weeks prior to beginning irinotecan. Dosage increases for irinotecan may be needed when used with phenobarbital, but specific dosing guidelines are not available. Risk D: Consider therapy modification
Ixabepilone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ixabepilone. Management: Avoid this combination whenever possible. If this combination must be used, a gradual increase in ixabepilone dose from 40 mg/m2 to 60 mg/m2 (given as a 4-hour infusion), as tolerated, should be considered. Risk D: Consider therapy modification
Ketorolac: May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy
Ketorolac (Nasal): May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy
Ketorolac (Systemic): May diminish the therapeutic effect of Anticonvulsants. Risk C: Monitor therapy
Lacosamide: PHENobarbital may decrease the serum concentration of Lacosamide. Risk C: Monitor therapy
LamoTRIgine: Barbiturates may decrease the serum concentration of LamoTRIgine. Management: See lamotrigine prescribing information for specific age-dependent dosing guidelines regarding concurrent use with a barbiturate, as well as for adjusting lamotrigine dosing if concurrent barbiturate therapy is discontinued. Risk D: Consider therapy modification
Lapatinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lapatinib. Management: If therapy overlap cannot be avoided, consider titrating lapatinib gradually from 1,250 mg/day up to 4,500 mg/day (HER2 positive metastatic breast cancer) or 1,500 mg/day up to 5,500 mg/day (hormone receptor/HER2 positive breast cancer) as tolerated. Risk X: Avoid combination
Leucovorin Calcium-Levoleucovorin: May decrease the serum concentration of PHENobarbital. Risk C: Monitor therapy
Levomefolate: May decrease the serum concentration of PHENobarbital. Risk C: Monitor therapy
Linagliptin: CYP3A4 Inducers (Strong) may decrease the serum concentration of Linagliptin. Management: Strongly consider using an alternative to any strong CYP3A4 inducer in patients who are being treated with linagliptin. If this combination is used, monitor patients closely for evidence of reduced linagliptin effectiveness. Risk D: Consider therapy modification
Lopinavir: PHENobarbital may decrease the serum concentration of Lopinavir. Management: Increased doses of lopinavir may be necessary when using these agents in combination. Do not use a once daily lopinavir/ritonavir regimen together with phenobarbital. Increase monitoring of therapeutic response in all patients using this combination. Risk D: Consider therapy modification
Lurasidone: CYP3A4 Inducers (Strong) may decrease the serum concentration of Lurasidone. Risk X: Avoid combination
Maraviroc: CYP3A4 Inducers (Strong) may decrease the serum concentration of Maraviroc. Management: Increase maraviroc adult dose to 600 mg twice daily when used with strong CYP3A4 inducers. This does not apply to patients also receiving strong CYP3A4 inhibitors. Do not use maraviroc with strong CYP3A4 inducers in patients with Clcr less than 30 mL/min. Risk D: Consider therapy modification
Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. Monitor anticonvulsant concentrations and treatment response closely with concurrent use. Risk D: Consider therapy modification
Meperidine: Barbiturates may enhance the CNS depressant effect of Meperidine. Barbiturates may increase serum concentrations of the active metabolite(s) of Meperidine. Risk C: Monitor therapy
Methadone: Barbiturates may decrease the serum concentration of Methadone. Risk C: Monitor therapy
Methylfolate: May decrease the serum concentration of PHENobarbital. Risk C: Monitor therapy
Methylphenidate: May increase the serum concentration of PHENobarbital. Risk C: Monitor therapy
MetroNIDAZOLE: PHENobarbital may decrease the serum concentration of MetroNIDAZOLE. Risk C: Monitor therapy
MetroNIDAZOLE (Systemic): PHENobarbital may decrease the serum concentration of MetroNIDAZOLE (Systemic). Risk C: Monitor therapy
Nilotinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Nilotinib. Risk X: Avoid combination
OXcarbazepine: PHENobarbital may decrease the serum concentration of OXcarbazepine. Risk C: Monitor therapy
Pazopanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Pazopanib. Risk X: Avoid combination
Phenytoin: May enhance the CNS depressant effect of Barbiturates. Phenytoin may increase the serum concentration of Barbiturates. Barbiturates may decrease the serum concentration of Phenytoin. Risk C: Monitor therapy
Praziquantel: CYP3A4 Inducers (Strong) may decrease the serum concentration of Praziquantel. Management: Avoid concomitant use of praziquantel with strong CYP3A4 inducers. Discontinue rifampin 4 weeks prior to initiation of praziquantel therapy. Rifampin may be resumed the day following praziquantel completion. Risk X: Avoid combination
Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Risk C: Monitor therapy
Primidone: May enhance the adverse/toxic effect of Barbiturates. Primidone is converted to phenobarbital, and thus becomes additive with existing barbiturate therapy. Risk C: Monitor therapy
Propafenone: Barbiturates may decrease the serum concentration of Propafenone. Risk C: Monitor therapy
Pyridoxine: May increase the metabolism of Barbiturates. Apparent in high pyridoxine doses (eg, 200 mg/day) Risk C: Monitor therapy
QuiNIDine: Barbiturates may enhance the hepatotoxic effect of QuiNIDine. Barbiturates may decrease the serum concentration of QuiNIDine. Risk C: Monitor therapy
QuiNINE: May increase the serum concentration of PHENobarbital. PHENobarbital may decrease the serum concentration of QuiNINE. Risk D: Consider therapy modification
Ranolazine: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ranolazine. Risk X: Avoid combination
Rifamycin Derivatives: May increase the metabolism of Barbiturates. Risk C: Monitor therapy
Rilpivirine: PHENobarbital may decrease the serum concentration of Rilpivirine. Risk X: Avoid combination
Rivaroxaban: CYP3A4 Inducers (Strong) may decrease the serum concentration of Rivaroxaban. Risk X: Avoid combination
Roflumilast: CYP3A4 Inducers (Strong) may decrease the serum concentration of Roflumilast. Management: Roflumilast U.S. prescribing information recommends against combining strong CYP3A4 inducers with roflumilast. The Canadian product monograph makes no such recommendation but notes that such agents may reduce roflumilast therapeutic effects. Risk X: Avoid combination
RomiDEPsin: CYP3A4 Inducers (Strong) may decrease the serum concentration of RomiDEPsin. Risk X: Avoid combination
Rufinamide: May increase the serum concentration of PHENobarbital. PHENobarbital may decrease the serum concentration of Rufinamide. Risk C: Monitor therapy
Saxagliptin: CYP3A4 Inducers may decrease the serum concentration of Saxagliptin. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy
SORAfenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of SORAfenib. Risk X: Avoid combination
SUNItinib: CYP3A4 Inducers (Strong) may decrease the serum concentration of SUNItinib. Management: Avoid when possible. If such a combination cannot be avoided, consider increasing sunitinib dose and monitor clinical response and toxicity closely. Risk D: Consider therapy modification
Tadalafil: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tadalafil. Management: Erectile dysfunction: monitor for decreased effectiveness - no standard dose adjustments recommended. Avoid use of tadalafil for pulmonary arterial hypertension in patients receiving a strong CYP3A4 inducer. Risk D: Consider therapy modification
Telaprevir: May decrease the serum concentration of PHENobarbital. Telaprevir may increase the serum concentration of PHENobarbital. PHENobarbital may decrease the serum concentration of Telaprevir. Risk X: Avoid combination
Teniposide: Barbiturates may decrease the serum concentration of Teniposide. Management: Consider alternatives to combined treatment with barbiturates and teniposide due to the potential for decreased teniposide concentrations. If the combination cannot be avoided, monitor teniposide response closely. Risk D: Consider therapy modification
Theophylline Derivatives: Barbiturates may decrease the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Risk C: Monitor therapy
Thiazide Diuretics: Barbiturates may enhance the orthostatic hypotensive effect of Thiazide Diuretics. Risk C: Monitor therapy
Ticagrelor: CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inducers (Strong) may decrease the serum concentration of Ticagrelor. Risk X: Avoid combination
Tipranavir: May decrease the serum concentration of PHENobarbital. PHENobarbital may decrease the serum concentration of Tipranavir. Risk D: Consider therapy modification
Tolvaptan: CYP3A4 Inducers (Strong) may decrease the serum concentration of Tolvaptan. Management: If concurrent use is necessary, increased doses of tolvaptan (with close monitoring for toxicity and clinical response) may be needed. Risk X: Avoid combination
Toremifene: CYP3A4 Inducers (Strong) may decrease the serum concentration of Toremifene. Risk X: Avoid combination
Treprostinil: CYP2C8 Inducers (Strong) may decrease the serum concentration of Treprostinil. Risk C: Monitor therapy
Tricyclic Antidepressants: Barbiturates may increase the metabolism of Tricyclic Antidepressants. Risk D: Consider therapy modification
Ulipristal: CYP3A4 Inducers (Strong) may decrease the serum concentration of Ulipristal. Risk C: Monitor therapy
Valproic Acid: May decrease the metabolism of Barbiturates. Barbiturates may decrease the serum concentration of Valproic Acid. Risk C: Monitor therapy
Vandetanib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vandetanib. Risk X: Avoid combination
Vemurafenib: CYP3A4 Inducers (Strong) may decrease the serum concentration of Vemurafenib. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Barbiturates may increase the metabolism of Vitamin K Antagonists. Risk D: Consider therapy modification
Voriconazole: Barbiturates may decrease the serum concentration of Voriconazole. Risk X: Avoid combination
Zonisamide: PHENobarbital may decrease the serum concentration of Zonisamide. Risk C: Monitor therapy
Zuclopenthixol: CYP3A4 Inducers (Strong) may decrease the serum concentration of Zuclopenthixol. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: May increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Food: May cause decrease in vitamin D and calcium.
Herb/Nutraceutical: Avoid evening primrose (seizure threshold decreased). Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).
Storage
Protect elixir from light. Not stable in aqueous solutions; use only clear solutions. Do not add to acidic solutions; precipitation may occur.
Compatibility
Stable in dextran 6% in dextrose, dextran 6% in NS, D5LR, D51/4NS, D51/2NS, D5NS, D5W, D10W, LR, 1/2NS, NS.
Y-site administration: Compatible: Caffeine citrate, doripenem, enalaprilat, fentanyl, fosphenytoin, levofloxacin, linezolid, meropenem, methadone, morphine, propofol, sufentanil. Incompatible: Amphotericin B cholesteryl sulfate complex, pantoprazole. Variable (consult detailed reference): Doxapram, hydromorphone.
Compatibility in syringe: Compatible: Caffeine citrate, heparin. Incompatible: Hydromorphone, pantoprazole, ranitidine, sufentanil.
Mechanism of Action
Long-acting barbiturate with sedative, hypnotic, and anticonvulsant properties. Barbiturates depress the sensory cortex, decrease motor activity, alter cerebellar function, and produce drowsiness, sedation, and hypnosis. In high doses, barbiturates exhibit anticonvulsant activity; barbiturates produce dose-dependent respiratory depression.
Pharmacodynamics/Kinetics
Onset of action: Oral: Hypnosis: 20-60 minutes; I.V.: ~5 minutes
Peak effect: I.V.: ~30 minutes
Duration: Oral: 6-10 hours; I.V.: 4-10 hours
Absorption: Oral: 70% to 90%
Protein binding: 20% to 45%; decreased in neonates
Metabolism: Hepatic via hydroxylation and glucuronide conjugation
Half-life elimination: Neonates: 45-500 hours; Infants: 20-133 hours; Children: 37-73 hours; Adults: 53-140 hours
Time to peak, serum: Oral: 1-6 hours
Excretion: Urine (20% to 50% as unchanged drug)
Dosage
Children:
Sedation: Oral: 2 mg/kg 3 times/day
Preoperative sedation: Oral, I.M., I.V.: 1-3 mg/kg 1-1.5 hours before procedure
Adults:
Sedation: Oral, I.M.: 30-120 mg/day in 2-3 divided doses
Preoperative sedation: I.M.: 100-200 mg 1-1.5 hours before procedure
Anticonvulsant: Status epilepticus: Loading dose: I.V.:
Infants and Children: 15-20 mg/kg (maximum: 1000 mg/dose, maximum rate ≤30 mg/minute in children <60 kg); may repeat dose after 15 minutes as needed (maximum total dose: 40 mg/kg)
Adults: 10-20 mg/kg (maximum rate ≤60 mg/minute in patients ≥60 kg); may repeat dose in 20-minute intervals as needed (maximum total dose: 30 mg/kg)
Anticonvulsant maintenance dose: Oral, I.V.:
Infants: 5-8 mg/kg/day in 1-2 divided doses
Children:
1-5 years: 6-8 mg/kg/day in 1-2 divided doses
5-12 years: 4-6 mg/kg/day in 1-2 divided doses
Children >12 years and Adults: 1-3 mg/kg/day in divided doses or 50-100 mg 2-3 times/day
Sedative/hypnotic withdrawal (unlabeled use): Initial daily requirement is determined by substituting phenobarbital 30 mg for every 100 mg pentobarbital used during tolerance testing; then daily requirement is decreased by 10% of initial dose
Elderly or debilitated: Initiate at the lowest recommended dose.
Dosing adjustment in renal impairment: Clcr <10 mL/minute: Administer every 12-16 hours
Hemodialysis: Moderately dialyzable (20% to 50%)
Dosing adjustment in hepatic impairment: Reduce dose in patients with hepatic impairment.
Administration: I.M.
Inject deep into muscle. Do not exceed 5 mL per injection site due to potential for tissue irritation.
Administration: I.V.
Avoid rapid I.V. administration >60 mg/minute in adults and >30 mg/minute in children. Avoid extravasation. Intra-arterial injection is contraindicated. Avoid subcutaneous administration.
Administration: I.V. Detail
Parenteral solutions are highly alkaline.
pH: 9.2-10.2
Monitoring Parameters
Phenobarbital serum concentrations, mental status, CBC, LFTs, seizure activity
Reference Range
Therapeutic:
Infants and Children: 15-30 mcg/mL (SI: 65-129 micromole/L)
Adults: 20-40 mcg/mL (SI: 86-172 micromole/L)
Toxic: >40 mcg/mL (SI: >172 micromole/L)
Toxic concentration: Slowness, ataxia, nystagmus: 35-80 mcg/mL (SI: 150-344 micromole/L)
Coma with reflexes: 65-117 mcg/mL (SI: 279-502 micromole/L)
Coma without reflexes: >100 mcg/mL (SI: >430 micromole/L)
Test Interactions
Assay interference of LDH
Dietary Considerations
Vitamin D: Loss in vitamin D due to malabsorption; increase intake of foods rich in vitamin D. Supplementation of vitamin D and/or calcium may be necessary. Injection may contain sodium.
Patient Education
I.V.: Patient instructions and information are determined by patient condition and therapeutic purpose. Oral: Drug may cause physical and/or psychological dependence. While using this medication, do not use alcohol and other prescription or OTC medications (especially pain medications, sedatives, antihistamines, or hypnotics) without consulting prescriber. Maintain adequate hydration unless instructed to restrict fluid intake. You may experience drowsiness, dizziness, blurred vision, nausea, vomiting, loss of appetite, or constipation. Report skin rash or irritation, CNS changes (confusion, depression, increased sedation, suicide ideation, excitation, headache, insomnia, or nightmares), respiratory difficulty or shortness of breath, changes in urinary pattern or menstrual pattern, muscle weakness or tremors, or difficulty swallowing or feeling of tightness in throat.
Geriatric Considerations
Using barbiturates in elderly may induce paradoxical stimulation, cause or aggravate depression and confusion. Due to its long half-life and risk of dependence, phenobarbital is not recommended as a sedative or hypnotic in the elderly. Interpretive guidelines from the Centers for Medicare and Medicaid Services (CMS) discourage the use of this agent as a sedative/hypnotic in long-term care residents.
Additional Information
Injectable solutions contain propylene glycol.
Phenobarbital tablets are also available from some generic manufacturers in strengths that are exactly equivalent to fractional grain strengths: 16.2 mg (1/4 grain), 32.4 mg (1/2 grain), 64.8 mg (1 grain). To avoid medication errors, do not prescribe phenobarbital in grains.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Nursing: Physical Assessment/Monitoring
Assess for history of addiction or suicide ideation; long-term use can result in dependence, abuse, or tolerance; periodically evaluate need for continued use. I.V.: Monitor cardio/respiratory and CNS status; use safety precautions.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Elixir, oral: 20 mg/5 mL (5 mL, 7.5 mL, 15 mL, 473 mL)
Injection, solution, as sodium: 65 mg/mL (1 mL); 130 mg/mL (1 mL)
Tablet, oral: 15 mg, 30 mg, 60 mg, 100 mg
Extemporaneously Prepared
An alcohol-free 10 mg/mL phenobarbital oral suspension may be made from tablets and one of two different vehicles (a 1:1 mixture of Ora-Plus® and Ora-Sweet® or a 1:1 mixture of Ora-Plus® and Ora-Sweet® SF). Crush ten phenobarbital 60 mg tablets in a glass mortar and reduce to a fine powder. Mix 30 mL of Ora-Plus® and 30 mL of either Ora-Sweet® or Ora-Sweet® SF; stir vigorously. Add 15 mL of the vehicle to the powder and mix to a uniform paste. Transfer the mixture to a 2 ounce amber plastic prescription bottle. Rinse mortar and pestle with 15 mL of the vehicle; transfer to bottle. Repeat, then add quantity of vehicle sufficient to make 60 mL. Label "shake well." May mix dose with chocolate syrup (1:1 volume) immediately before administration to mask the bitter aftertaste. Stable for 115 days when stored in amber plastic prescription bottles at room temperature.
Cober M and Johnson CE, “Stability of an Extemporaneously Prepared Alcohol-Free Phenobarbital Suspension,” Am J Health Syst Pharm, 2007, 64(6):644-6.
References
American Academy of Pediatrics Committee on Drugs, "Transfer of Drugs and Other Chemicals Into Human Milk," Pediatrics, 2001, 108(3):776-89.
Amitai Y and Degani Y, “Treatment of Phenobarbital Poisoning With Multiple Dose of Activated Charcoal in an Infant,” J Emerg Med, 1990, 8(4):449-50.
Bleck TB, Seizures, Stroke, and Other Neurologic Emergencies. In: Zimmerman JL, Roberts PR, eds. Multidisciplinary Critical Care Review, Des Plains, IL: Society of Critical Care Medicine; 2003:325-34.
Hegenbarth MA and the American Academy of Pediatrics Committee on Drugs, “Preparing for Pediatric Emergencies: Drugs to Consider,” Pediatrics, 2008, 121(2):433-43.
Jacobsen D, Wiik-Larsen E, Dahl T, et al, “Pharmacokinetic Evaluation of Haemoperfusion in Phenobarbital Poisoning,” Eur J Clin Pharmacol, 1984, 26(1):109-12.
Knott C, Reynolds F, and Clayden G, "Infantile Spasms on Weaning From Breast Milk Containing Anticonvulsants," Lancet, 1987, 2(8553):272-3.
Lin JL and Jeng LB, “Critical, Acutely Poisoned Patients Treated With Continuous Arteriovenous Hemoperfusion in the Emergency Department,” Ann Emerg Med, 1995, 25(1):75-80.
Mockli G, Crowley M, Stern R, et al, “Massive Hepatic Necrosis in a Child After Administration of Phenobarbital,” Am J Gastroenterol, 1989, 84(7):820-2.
Pond SM, Olson KR, Osterloh JD, et al, “Randomized Study of the Treatment of Phenobarbital Overdose With Repeated Doses of Activated Charcoal,” JAMA, 1984, 251(23):3104-8.
Sabo-Graham T and Seay AR, “Management of Status Epilepticus in Children,” Pediatr Rev, 1998, 19(9):306-9.
Schutte-Rodin S, Broch L, Buysse D, et al, "Clinical Guideline for the Evaluation and Management of Chronic Insomnia in Adults," J Clin Sleep Med, 2008, 4(5):487-504.
Treiman DM, Meyers PD, Walton NY, et al, “A Comparison of Four Treatments for Generalized Convulsive Status Epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group,” N Engl J Med, 1998, 339(12):792-8.
International Brand Names
Lexi-Comp.com
Last full review/revision February 2012
Content last modified February 2012
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