Phenobarbital

Strong UGT1A1 inducer that significantly decreases cabotegravir plasma concentrations. Coadministration is contraindicated.

Co-administration decreases doravirine plasma concentrations. At least a 4-week cessation period is recommended prior to initiation of PIFELTRO.

Co-administration decreases doravirine plasma concentrations and is contraindicated. At least a 4-week cessation period is recommended prior to initiation of DELSTRIGO.

Strong CYP3A inducer expected to decrease elexacaftor, tezacaftor, and ivacaftor exposures, reducing TRIKAFTA efficacy.

Strong CYP3A4 inducer substantially reduces exposure to irinotecan and SN-38. Do not administer unless no therapeutic alternatives exist.

CYP3A inducer. Do not use with ranolazine extended-release tablets.

Coadministration is contraindicated due to decreased rilpivirine plasma concentrations and loss of virologic response.

Coadministration is contraindicated. Induces CYP3A, resulting in decreased rilpivirine plasma concentrations and loss of virologic response.

Strong CYP3A inducer that substantially reduces ticagrelor exposure and decreases efficacy.

Long-acting barbiturate CYP450 inducer likely to significantly reduce voriconazole plasma exposure.

Barbiturates induce hepatic microsomal enzymes resulting in increased metabolism and decreased anticoagulant response of oral anticoagulants.

P-gp inducer that decreases tenofovir alafenamide concentrations. Coadministration is not recommended.

Additive depressant effects with phenobarbital; toxic effects and fatalities have occurred with this combination.

Increased risk of methemoglobinemia when concurrently exposed to articaine.

Increased risk of developing methemoglobinemia when concurrently exposed to this anticonvulsant.

Strong CYP3A4/5 inducer reduces axitinib plasma exposure. Co-administration should be avoided.

Increased risk of methemoglobinemia when concurrently exposed to this anticonvulsant oxidizing agent with local anesthetics.

Increased risk of methemoglobinemia when local anesthetics are used concomitantly with anticonvulsants.

Increased risk of methemoglobinemia when concurrently exposed with bupivacaine.

Induces carmustine metabolism, reducing exposure and potentially compromising antitumor activity. Consider alternative drugs.

XCOPRI increases phenobarbital plasma concentrations, increasing risk of adverse reactions; dosage reduction recommended.

Phenobarbital induces clonazepam metabolism, causing approximately 38% decrease in plasma clonazepam levels.

Barbiturates enhance metabolism of exogenous corticosteroids. Dose adjustment may be needed when adding or withdrawing phenobarbital.

Induces methemoglobinemia; concomitant use may increase risk for developing methemoglobinemia.

Concomitant use may increase risk of developing methemoglobinemia. Monitor closely.

Anticonvulsant associated with increased methemoglobinemia risk when used with ropivacaine.

Methylphenidate may inhibit the metabolism of phenobarbital. Downward dose adjustments may be required and plasma drug concentration should be monitored.

Phenobarbital lowers plasma levels of dicumarol and decreases anticoagulant activity. Induction of hepatic microsomal enzymes increases metabolism and reduces anticoagulant response.

Enzyme-inducing drug that can double valproate clearance. Increased monitoring of valproate and phenobarbital concentrations and dosage adjustment indicated.

Can double the clearance of valproate, resulting in lower valproate concentrations and potential loss of therapeutic effect.

CYP3A4 inducer that may decrease doxorubicin concentration and clinical effect.

Phenobarbital shortens the half-life of doxycycline for up to 2 weeks after discontinuation. Clinical response should be monitored closely.

CYP3A4 inducer decreases erlotinib exposure. Increase erlotinib dosage if co-administration is unavoidable.

CYP3A4 inducer decreases erlotinib exposure. Increase erlotinib dosage if co-administration is unavoidable.

Strong CYP 3A4 inducer that significantly decreases exemestane exposure. Dose increase to 50 mg recommended.

Anticonvulsant that considerably reduces felodipine plasma concentrations; alternative antihypertensive therapy should be considered.

Enzyme-inducing anticonvulsant that decreases folate availability through increased hepatic metabolism and inhibition of intestinal folate-processing.

Enzyme-inducing anti-epileptic drug that decreases imatinib AUC by 73%, significantly reducing imatinib exposure.

Potent CYP3A4 enzyme inducer that may decrease itraconazole bioavailability and efficacy. Avoid use 2 weeks before and during itraconazole treatment.

Strong CYP3A inducer. Co-administration not recommended.

Phenobarbital decreases lamotrigine concentrations by approximately 40%, requiring dose adjustment.

Phenobarbital decreases lenacapavir concentration, risking loss of therapeutic effect and resistance. Concomitant use is not recommended.

Increases L-thyroxine metabolism by inducing UGT, leading to lower T4 serum levels and increased levothyroxine requirements. Changes in thyroid status may occur if added or withdrawn.

Increased risk of methemoglobinemia when used concurrently with lidocaine.

Anticonvulsant that may cause methemoglobinemia when used concomitantly with lidocaine patch 5%.

Anticonvulsant that increases risk of methemoglobinemia when used concurrently with lidocaine and capsaicin patch.

Anticonvulsant; increased risk of methemoglobinemia when concurrently exposed.

Increased risk of methemoglobinemia when used concurrently with lidocaine hydrochloride.

Anticonvulsant associated with increased methemoglobinemia risk when used concurrently.

Increased risk of methemoglobinemia when local anesthetic is concurrently exposed to anticonvulsants.

Concurrent exposure increases risk of methemoglobinemia in patients administered local anesthetics.

Increased risk of methemoglobinemia; anticonvulsants associated with methemoglobinemia when used with local anesthetics.

Increased risk of methemoglobinemia when used with lidocaine.

Increased risk of methemoglobinemia when lidocaine is concurrently exposed to anticonvulsants.

Increased risk of methemoglobinemia when local anesthetics are concurrently exposed to anticonvulsants.

Stimulates hepatic microsomal drug-metabolizing enzyme activity, causing increased hepatic degradation of thyroid hormones and increased liothyronine sodium requirements.

MAOIs prolong the effects of barbiturates by inhibiting barbiturate metabolism.

Increased risk of methemoglobinemia when concurrently exposed to anticonvulsants.

Strong CYP3A inducer may decrease medroxyprogesterone acetate concentrations and reduce contraceptive efficacy. Avoid concomitant use or use backup contraception.

Concurrent exposure increases risk of methemoglobinemia in patients administered mepivacaine.

CYP3A4, CYP2B6, CYP2C19, and CYP2C9 inducer decreases methadone plasma concentration, resulting in decreased efficacy or withdrawal symptoms.

MAOIs prolong the effects of barbiturates by inhibiting barbiturate metabolism.

Strong CYP3A inducer reduces the bioavailability and efficacy of nifedipine; careful consideration needed if co-administered.

Phenobarbital increases metabolism of ethinyl estradiol and/or norethindrone, which could result in reduced contraceptive effectiveness.

Phenobarbital increases metabolism of ethinyl estradiol and/or norethindrone, potentially reducing contraceptive effectiveness.

Strong CYP3A4/CYP2B6 inducer may decrease osilodrostat concentration and reduce efficacy. Dose increase may be needed; monitor cortisol.

Increased risk of methemoglobinemia when penicillin is concurrently administered with phenobarbital (an anticonvulsant).

Barbiturates induce hepatic microsomal enzymes resulting in increased metabolism and decreased anticoagulant response.

Increased risk of methemoglobinemia when prilocaine is concurrently exposed to phenobarbital.

Increased risk of methemoglobinemia when used concurrently with prilocaine.

Strong CYP3A4 inducer that decreases regorafenib plasma concentrations and may lead to decreased efficacy.

Strong CYP3A inducer may significantly reduce riociguat exposure. Data are not available to guide dosing.

Strong CYP450 enzyme inducer that decreases roflumilast systemic exposure and may reduce therapeutic effectiveness. Use not recommended.

Increased risk of developing methemoglobinemia when concurrently exposed to Phenobarbital.

May decrease tacrolimus whole blood trough concentrations and increase risk of rejection. Increase tacrolimus dose and monitor concentrations.

Strong CYP3A inducer may decrease tacrolimus concentrations and increase risk of rejection. Increase tacrolimus dose and monitor concentrations.

Strong CYP3A inducer. Co-administration not recommended due to reduced SYMDEKO efficacy.

Strong CYP3A4 inducer that decreases toremifene steady-state concentration and should be avoided.

Strong CYP3A inducer. Avoid concomitant use with trabectedin.

Additive depressant effects with phenobarbital; toxic effects and fatalities have occurred with this combination.

Increased risk of methemoglobinemia when concurrently exposed.

Increased risk of methemoglobinemia when used concurrently with triethanolamine salicylate.

Increased risk of methemoglobinemia when used with Trubrexa Transdermal Patch.

Sodium valproate increases phenobarbital serum levels. Phenobarbital blood levels should be closely monitored and dosage adjustments made as clinically indicated.

Valproic acid increases phenobarbital serum levels. Phenobarbital blood levels should be closely monitored and dosage adjustments made as clinically indicated.

CYP2C9 inducer that decreases warfarin exposure and INR; requires close INR monitoring.

CYP2C9 inducer that decreases warfarin effect and INR; requires closer INR monitoring.

P-glycoprotein inducer that decreases afatinib exposure. Increase GILOTRIF dose by 10 mg per day as tolerated.

Concomitant use of antihistamines with phenobarbital may produce additive CNS depressant effects.

May increase risk of methemoglobinemia when concurrently exposed with bupivacaine.

Increased risk of methemoglobinemia when concurrently exposed.

Increased risk of developing methemoglobinemia when concurrently exposed.

CYP2B6 inducer that may decrease bupropion exposure; dose increase may be necessary but should not exceed maximum recommended dose.

May induce metabolism of bupropion and decrease bupropion exposure; dose increase may be necessary.

CYP2B6 inducer that may decrease bupropion exposure. Dose increase may be necessary but should not exceed maximum recommended dose.

CYP2B6 inducer that may decrease bupropion exposure. Dose increase of bupropion may be necessary but should not exceed maximum recommended dose.

CYP2B6 inducer that may decrease bupropion exposure. Dose increase may be necessary but should not exceed maximum recommended dose.

Strong CYP3A4 inducer. Avoid chronic co-administration or increase COMETRIQ dosage if unavoidable.

Increases caffeine elimination; higher caffeine doses may be needed when coadministered.

Stimulates microsomal hydroxylation and reduces the half-life of calcifediol. Dose adjustment and monitoring of serum 25-hydroxyvitamin D, PTH, and calcium may be required.

May reduce endogenous plasma levels of 25(OH)D3 by accelerating metabolism, potentially requiring higher calcitriol doses.

May reduce endogenous plasma levels of 25(OH)D3 and calcitriol; higher calcitriol doses may be necessary.

UGT enzyme inducer decreases canagliflozin exposure which may reduce effectiveness of INVOKANA. Dosage adjustment may be required.

UGT enzyme inducer that decreases canagliflozin exposure and may reduce effectiveness. May require canagliflozin dose increase.

CYP3A4 inducer that decreases carbamazepine plasma levels. Carbamazepine levels and/or dosage adjustment may be necessary.

Cholestyramine may delay or reduce the absorption of phenobarbital.

Cholestyramine may delay or reduce the absorption of phenobarbital.

Cholestyramine may delay or reduce absorption of phenobarbital.

Clomipramine administration increases plasma levels of phenobarbital when given concomitantly.

Clomipramine increases plasma levels of phenobarbital when given concomitantly.

Concomitant use may produce additive depressant effects when combined with sedatives, hypnotics, antihistamines, tranquilizers, or alcohol.

CYP3A4 inducer may reduce plasma concentrations of estrogens, possibly decreasing therapeutic effects and/or altering uterine bleeding profile.

CYP3A4 and UGT inducer may reduce estrogen and bazedoxifene concentrations, decreasing therapeutic effects and increasing endometrial hyperplasia risk.

Amphetamines may reduce the effects of this drug. Monitor for reduced efficacy.

CYP3A4 inducer that increases diazepam elimination, potentially decreasing efficacy.

High doses of folic acid may decrease serum levels of this anticonvulsant drug.

Enzyme inducer that may enhance the 25-hydroxylation of doxercalciferol. Dose adjustment of doxercalciferol may be necessary.

Can double the clearance of valproate, potentially decreasing valproate concentrations. Monitor valproate levels when introduced or withdrawn.

Induces CYP3A activity, increasing efavirenz clearance and lowering plasma concentrations.

Induces CYP3A activity, increasing efavirenz clearance and lowering plasma concentrations.

Induction of CYP3A activity by phenobarbital may increase clearance of efavirenz resulting in lowered plasma concentrations.

Decreases TAF concentration. Consider alternative anticonvulsant.

Higher dosage of eslicarbazepine acetate may be necessary. Phenobarbital can induce enzymes that metabolize eslicarbazepine acetate and cause decreased plasma concentrations.

CYP3A4 inducer that may reduce plasma concentrations of estradiol, possibly decreasing therapeutic effects and altering uterine bleeding profile.

CYP3A4 inducer may decrease estradiol acetate plasma concentration, resulting in decreased therapeutic effects and/or changes in uterine bleeding profile.

CYP3A4 inducer that may reduce plasma concentrations of estrogens, possibly decreasing therapeutic effects and/or altering uterine bleeding profile.

CYP3A4 inducer that may reduce plasma concentrations of estrogens, possibly decreasing therapeutic effects and/or altering uterine bleeding profile.

CYP3A4 inducer may reduce plasma concentrations of estrogens and progestins, possibly decreasing therapeutic effects and altering uterine bleeding profile.

CYP3A4 inducer that may reduce estradiol plasma concentrations, possibly decreasing therapeutic effects and altering uterine bleeding profile.

CYP3A4 inducer that may reduce estradiol plasma concentrations, possibly decreasing therapeutic effects and/or altering uterine bleeding profile.

CYP3A4 inducer that may reduce plasma concentrations of estradiol valerate, possibly decreasing therapeutic effects and altering uterine bleeding profile.

CYP3A4 inducer that may reduce plasma concentrations of estrogens, possibly decreasing therapeutic effects and altering uterine bleeding profile.

CYP3A4 inducer may reduce plasma concentrations of estrogens, possibly decreasing therapeutic effects and altering uterine bleeding profile.

Phenobarbital may decrease the effect of estrone by increasing its metabolism.

Felbamate increases steady-state phenobarbital plasma concentrations while decreasing felbamate concentrations; phenobarbital dosing adjustment may be necessary.

Enzyme inducer; limited data indicate only 30% increase in flecainide elimination rate.

CYP3A4 inducer; concomitant use may decrease flibanserin exposure and therapeutic effect.

May increase or decrease plasma phenytoin concentrations; effects are unpredictable.

CYP3A4 inducer that decreases ganaxolone exposure and efficacy; ZTALMY dosage may need to be increased but should not exceed maximum daily dosage.

Phenobarbital interferes with absorption of orally administered griseofulvin, decreasing blood levels. Concomitant administration should preferably be avoided.

Microsomal enzyme inducer that reduces guanfacine elimination half-life and plasma concentration, particularly in patients with renal impairment, requiring more frequent dosing.

Microsomal enzyme inducer that significantly reduces guanfacine elimination half-life and plasma concentration, particularly in renal impairment patients, requiring more frequent dosing.

Induces hepatic enzymes and increases clearance of corticosteroids, may require increased corticosteroid dose to achieve desired response.

CYP3A4 inducer may increase metabolism of ifosfamide to active metabolites and increase formation of neurotoxic/nephrotoxic chloroacetaldehyde. Monitor for toxicities and consider dose adjustment.

Decreased lamotrigine concentration approximately 40%.

Decreases lamotrigine concentration approximately 40%.

Folic acid in large amounts may counteract the antiepileptic effect and increase seizure frequency in susceptible children.

Folic acid in large amounts may counteract antiepileptic effect and increase seizure frequency in susceptible children. Monitor patients taking levoleucovorin with this drug.

Folic acid in large amounts may counteract the antiepileptic effect and increase seizure frequency in susceptible children. Unclear if folinic acid has same effects, but they share metabolic pathways. Monitor patients.

Folic acid in large amounts may counteract antiepileptic effect and increase seizure frequency. Monitor patients taking folinic acid with antiepileptic drugs.

Anticonvulsant that increases risk of methemoglobinemia when used concomitantly with lidocaine and tetracaine.

Coadministration led to a reduction of about 20% in the AUC of losartan and its active metabolite.

Coadministration led to a reduction of about 20% in the AUC of losartan and its active metabolite. Monitor blood pressure control.

Increased risk of methemoglobinemia when concurrently exposed to anticonvulsants with bupivacaine.

Moderate CYP3A4 inducer that decreases maribavir concentrations. A dose adjustment of LIVTENCITY is recommended when coadministered.

Mefloquine may reduce seizure control by lowering plasma levels of anticonvulsant. Monitor blood levels and adjust dosage appropriately.

Phenobarbital induces CYP3A4, potentially increasing the rate of elimination of donepezil.

Methsuximide may increase plasma concentrations of phenobarbital; periodic serum level determinations may be necessary.

Methylphenidate may inhibit metabolism of this anticonvulsant. Downward dose adjustments may be required.

Methylphenidate may inhibit metabolism of phenobarbital; downward dose adjustment may be required and plasma concentrations should be monitored.

May increase the clearance of methylprednisolone and require increases in methylprednisolone dose to achieve the desired response.

Phenobarbital induces microsomal liver enzymes, accelerating elimination of metronidazole and reducing plasma levels.

Hepatic enzyme inducer that lowers mexiletine plasma levels; monitoring recommended to avoid ineffective therapy.

CYP3A4 inducer anticonvulsant that may lower mifepristone serum concentrations and reduce efficacy. Verify treatment success through follow-up assessment.

CYP2B6 inducer that may reduce CONTRAVE efficacy by reducing bupropion exposure. Avoid concomitant use.

Phenobarbital decreases plasma levels of MHD (active metabolite) by 25-49%. Monitoring of MHD levels and oxcarbazepine dose adjustment may be necessary.

Barbiturates have variable effects on phenytoin metabolism. Blood levels of both drugs should be monitored frequently during concurrent use.

May increase or decrease phenytoin serum levels; monitoring of phenytoin levels recommended.

Induces hepatic enzymes and may increase clearance of prednisone, requiring increases in prednisone dose to achieve desired response.

Impairs folate absorption and increases metabolism of circulating folate.

High doses of folic acid may result in decreased serum levels of phenobarbital.

Phenobarbital may decrease the effect of progesterone by increasing its metabolism.

Hepatic enzyme inducer that decreases blood levels of propranolol by increasing hepatic metabolism.

Phenobarbital induces cytochrome P450 IIIA4 and accelerates hepatic elimination of quinidine.

Induces cytochrome P450 IIIA4, accelerating hepatic elimination and decreasing quinidine levels.

CYP3A4 inducer that may decrease quinine plasma concentrations. Frequent monitoring of anticonvulsant drug concentrations and adverse reactions is recommended.

CYP3A4 inducer that may decrease quinine plasma concentrations and reduce efficacy.

Strong inducer of drug metabolizing enzymes that may decrease raltegravir levels. Coadministration not recommended.

Weak/moderate CYP3A4/P-gp inducer that may decrease sirolimus concentrations. Monitor and adjust dosage as needed.

Rifapentine may increase metabolism and decrease activity. Dosage adjustment may be necessary.

Phenobarbital decreases rufinamide concentration by 25-46% and rufinamide increases phenobarbital by 8-13%.

May decrease endogenous BH4 levels by inhibiting dihydrofolate reductase, potentially increasing phenylalanine levels.

Phenobarbital is a strong inducer of CYP1A2, CYP3A4, and CYP2C19 and may decrease DIACOMIT concentrations. Concomitant use should be avoided or dosage adjustment made.

One patient exhibited lower steady state serum level of tamoxifen; clinical significance not known.

Phenobarbital increases tiagabine clearance by 60%, which may require dose adjustments to maintain therapeutic efficacy.

Phenobarbital therapy may increase verapamil clearance.

Enzyme-inducing AED that increases zonisamide metabolism and clearance, decreasing its half-life to 27-38 hours.

Caffeine may increase the metabolism of phenobarbital.

Steady-state pharmacokinetic parameters for phenobarbital and gabapentin were identical whether administered alone or together.

Steady-state plasma concentrations of phenobarbital were not affected by concomitant lacosamide at any dose in clinical studies.

Levetiracetam does not influence phenobarbital plasma concentration and phenobarbital does not influence levetiracetam pharmacokinetics.

Prazosin has been administered without adverse drug interaction with phenobarbital in limited clinical experience.

Administered without adverse drug interaction in limited clinical experience.

Hepatic enzyme induction with phenobarbital resulted in 25% increase in total plasma clearance of granisetron, but clinical significance is not known.

Potential interaction with topiramate as a standard antiepileptic drug; specific effect not evaluated.