Phenobarbital clinical efficacy

IMATINIB 1. ANTIBIOTICS-rifampicin 2. ANTICANCER AND IMMUNOMODULATING DRUGS - dexamethasone 3. ANTIDEPRESSANTS-St John s wort 4. ANTI EPILEPTICS - carbarn azepine, phenobarbital, phenytoin 1 imatinib levels Due to induction of CYP3A4-mediated metabolism of imatinib Monitor for clinical efficacy and adjust dose as required. Avoid co-administration of imatinib and rifampicin... 

PACLITAXEL 1. ANTIBIOTICS-rifampicin 2. ANTIDEPRESSANTS-St John s wort 3. ANTIEPILEPTICS -carbamazepine, phenobarbital, phenytoin 1 plasma concentration of paclitaxel and 1 efficacy of paclitaxel Due to induction of hepatic metabolism of paclitaxel by the CYP isoenzymes Monitor for clinical efficacy and need to T dose if inadequate response is due to interaction... 

VINCA ALKALOIDS - VINBLASTINE, VINCRISTINE 1. ANTIBIOTICS-rifampicin 2. ANTICANCER AND IMMUNOMODULATING DRUGS - dexamethasone 3. ANTIDEPRESSANTS-St John s wort 4. ANTI EPILEPTICS -carbamazepine, phenobarbital, phenytoin 1 of plasma concentrations of vinblastine and vincristine, with risk of inadequate therapeutic response. Reports of 1 AUC by 40% and elimination half life by 35%, and t clearance by 63%, in patients with brain tumours taking vincristine, which could lead to dangerously inadequate therapeutic responses Due to induction of CYP3A4-mediated metabolism Monitor for clinical efficacy, and t dose of vinblastine and vincristine as clinically indicated in the latter case, monitor clinically and radiologically for clinical efficacy in patients with brain tumours and t dose to obtain desired response... 

TAMOXIFEN ANTIEPILEPTICS -CARBAMAZEPINE, PHENYTOIN, PHENOBARBITAL i plasma concentrations of tamoxifen and risk of inadequate therapeutic response Due to induction of metabolism of tamoxifen by the CYP3A isoenzymes by phenytoin Avoid concurrent use if possible. Otherwise monitor for clinical efficacy of tamoxifen by t dose of tamoxifen... 

TEUTHROMYCIN BARBITURATES 1 levels of these drugs, with risk of therapeutic failure Induction of hepatic metabolism 1. Avoid co-administration of telithromycin for up to 2 weeks after stopping phenobarbital 2. With the other drugs, monitor for l clinical efficacy and T dose as required... 

Ebid A-H-I, Abdel-Rahman HM. Pharmacokinetics of phenobarbital during certain enhanced elimination modalities to evaluate their clinical efficacy in management of drug overdose. Ther Drug Monit 2001 23 209-16. 

Major events preceding this work are the fortuitous discovery of phenobarbital as an anticonvulsant agent, stmcture/hypnotic activity studies with barbiturates and hydantoins in the early 1920s by A.W. Dox in the Parke Davis laboratories, and the development of anticonvulsi-vant assay techniques in animals, by a number of laboratories. Phenytoin was the first item on the list of compounds sent to Putnam by Dox and W.G. Bywater in April 1936. It was found to have anticonvulsivants properties in animals late in 1936, but no public reports were issued until the following year. Clinical efficacy was established in 1937, but again no public reports were issued until 1938. Dilantin sodium capsules were prepared by Parke, Davis Co. and were ready for marketing the same year. ... 

An extremely well documented and well established interaction of clinical importance. The incidence seems to be high. The effects of concurrent use should be well monitored and suitable phenobarbital dosage reductions made as necessary to avoid toxicity. The dosage may need to be reduced by a third to a half. The significance of the modest reduction in valproate levels is not clear, especially as valproate levels do not correlate well with efficacy of treatment. Valproate has been associated with serious hepato-toxicity, especially in children aged less than 3 years, and this has been more common in those receiving other anticonvulsants. Valproate monotherapy is to be preferred in tbis group. 

The manufacturers therefore caution the use of exemestane with CYP3A4 inducers such as carbamazepine, phenobarbital, phenytoin and St John s wort. >2 The clinical relevance of these potential interactions is unknown, but it would seem prudent to monitor the outcome of concurrent use to ensure exemestane efficacy. 

What the sum of all these changes is likely to mean is uncertain, but good monitoring for any evidence of reduced efficacy and/or increased toxicity (due to the raised hydroxybupropion) is clearly needed. The same good monitoring would also be appropriate with phenytoin and phenobarbital, which would be expected to interact similarly, but clinical studies appear to be lacking. 

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