Phenobarbital Corticosteroids

One chronic adverse effect that is of concern is osteoporosis.32,33 Carbamazepine, phenytoin, phenobarbital, oxcarbazepine, and valproate have all been shown to decrease bone mineral density, even after only 6 months of treatment. Data on the relationship between other AEDs and osteoporosis are not currently available. Multiple studies have shown the risk of osteoporosis due to chronic AED use to be similar to the risk with chronic use of corticosteroids. Patients taking carbamazepine, phenytoin, phenobarbital, or valproate for longer than 6 months should take supplemental calcium and vitamin D. Additionally routine monitoring for osteoporosis should be performed every 2 years, and patients should be instructed on ways to protect themselves from fractures. 

In cases of lead encephalopathy with cerebral edema, edema can be treated with mannitol, corticosteroids, and hypothermia. Convulsions can be treated with diazepam, phenytoin, and/or phenobarbital (Garrettson 1990). 

Drug-induced osteoporosis may result from systemic corticosteroids (prednisone doses greater than 7.5 mg/day), thyroid hormone replacement, some antiepileptic drugs (e.g., phenytoin, phenobarbital), depot medroxyprogesterone acetate, and other agents. 

Drugs that might decrease plasma concentrations of lopinavir/ritonavir include rifampin, phenobarbital, carbamazepine, phenytoin, azole antifungals, delavirdine, rifabutin, St. John s wort, efavirenz, nevirapine, and corticosteroids. 

Drugs that may affect cyclosporine include allopurinol, amiodarone, androgens (eg, danazol, methyltestosterone), anticonvulsants (eg, carbamazepine, phenobarbital, phenytoin), azole antifungals (eg, fluconazole, ketoconazole), beta-blockers, bosentan, bromocriptine, calcium channel blockers, colchicine, oral contraceptives, corticosteroids, fluoroquinolones (eg, ciprofloxacin), foscarnet, HMG-CoA reductase inhibitors, imipenem-cilastatin, macrolide antibiotics, methotrexate, metoclopramide, nafcillin, nefazodone, orlistat, potassium-sparing diuretics, probucol, rifamycins (rifampin, rifabutin), serotonin reuptake inhibitors (SSRIs eg, fluoxetine, sertraline),... 

Phenytoin, carbamazepine, phenobarbital, rifampin, rifabutin Iopanoic acid, ipodate, amiodarone, beta-blockers, corticosteroids, propylthiouracil, cholestyramine, colestipol, aluminium hydroxide, sucralfate, ferrous sulfate, some calcium preparations Interferon-c/, interleukin-2... 

CORTICOSTEROIDS ANTIEPILEPTICS -CARBAMAZEPINE, PHENYTOIN, PHENOBARBITAL 1 plasma concentrations of corticosteroids and risk of poor or inadequate therapeutic response, which would be undesirable if used for e.g. cerebral oedema Due to induction of the hepatic metabolism by the CYP3A4 isoenzymes Closely monitor therapeutic response - clinically, by ophthalmoscopy and radiologically - and t dose of corticosteroids for desired therapeutic effect... 

Clinically important, potentially hazardous interactions with amlodipine, anisindione, anticoagulants, aprepitant, atorvastatin, barbiturates, benzodiazepines, butabarbital, carbamazepine, chlordiazepoxide, clarithromycin, clonazepam, dorazepate, corticosteroids, cyclosporine, dexamethasone, diazepam, dicumarol, erythromycin, ethotoin, felodipine, flurazepam, fluvastatin, fosphenytoin, isradipine, itraconazole, ketoconazole, lorazepam, lovastatin, mephenytoin, mephobarbital, midazolam, nicardipine, nifedipine, nimodipine, nisoldipine, oxazepam, pentobarbital, phenobarbital, pimozide, pravastatin, primidone, quazepam, rifampin, secobarbital, simvastatin, St John s wort, temazepam, warfarin... 

The most common drugs responsible for acneform eruptions are ACTH, androgenic hormones, anticonvulsants (hydantoin derivatives, phenobarbital, trimethadione), corticosteroids, danazol, disulfiram, halogens (bromides, chlorides, iodides), lithium, oral contraceptives, tuberculostatics (ethionamide, isoniazid, rifampin), vitamins B2, B6, and B12. 

Some drugs, for example anticonvulsants phenytoin, phenobarbital and corticosteroids can lead to osteomalacia and rickets by depressing vitamin D dependent calcium uptake in the intestine. 

Phenobarbital is a potent enzyme inducer and as such can reduce the effects of other drugs, for example oral contraceptives, warfarin and corticosteroids. 

Phenobarbital is a recognised potent liver eiKyme inducer that increases the metabolism of corticosteroids, thereby reducing their effects. Pharmacokinetic studies have shown that phenobarbital reduces the half-lives of these corticosteroids and increases their clearances by 40 to 209%. Primidone interacts in a similar way because it is metabolised in the body to phenobarbital. ... 

The interaction between the corticosteroids and phenobarbital is well documented, well established and of clinical importance. Concurrent use need not be avoided but the outcome should be monitored. Increase the corticosteroid dosage as necessary. The extent of the increase is variable. Dex-amethasone, hydrocortisone, " methylprednisolone, prednisone and prednisolone are all known to be affected. Prednisone and prednisolone appear to be less affected than methylprednisolone and may be preferred. Be alert for the same interaction with other corticosteroids and other barbiturates, which also are enzyme-inducers, although direct evidence seems to be lacking. The dexamethasone adrenal suppression test may be expected to be unreliable in those taking phenobarbital, just as it is with pheny-toin, another potent enzyme-inducer. See Corticosteroids + Phenytoin , p.1059. 

Brooks SM, Werk EE, Ackerman SJ, Sullivan I, Thrasher K. Adverse effects of phenobarbital on corticosteroid metabolism in patients with bronchial asthma. NEnglJMed(y972) 286, 1125-8. 

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