Carbamazepine clinical efficacy

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 CARBAMAZEPINE 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 carbamazepine 2. With the other drugs, monitor for 1 clinical efficacy and t dose as required... 

As with carbamazepine, the historical use of valproate for anxiety is not supported by robust clinical trials. A randomised study showed efficacy in panic disorder (Lum et al. 1991) and benefit has been reported in open studies in OCD and PTSD. The major side-effects are tremor, nausea, ataxia and weight gain and there is the potential for drug interactions via inhibition of hepatic enzymes. 

Well known for their clinical role as antimanic agents, anticonvulsants such as carbamazepine and valproate have also been used in both bipolar and unipolar TRD (Post et al. 1994a, 1994b). In one series. Post et al. (1994a) found a greater response in patients with bipolar (15/40) versus those with unipolar (2/17) TRD. Open studies of valproate also suggest limited antidepressant efficacy, but only a paucity of data with anticonvulsants on TRD exists. More recently, in open trials, lamotrigine (a partial anticonvulsant that inhibits glu-... 

Support is scant for the efficacy of anticonvulsant agents in the treatment of OCD (Jenike 1990 Joffe and Swinson 1987). If there is a role for carbamazepine in OCD, it may be in patients with clinical or electroen-cephalographic evidence of a seizure disorder (Jenike and Brotman 1984 Khanna 1988). The anti-OC efficacy of combined SRI-carbamazepine treatment has not been adequately studied. Sodium valproate was found ineffective in two cases of OCD (McElroy and Pope 1988 McElroy et al. 1987). However, one author has suggested that sodium valproate may be a useful pretreatment for patients with OCD who might otherwise tolerate SRIs poorly (Deltito 1994). The anticonvulsant clonazepam is discussed earlier in this chapter. 

Several other therapeutic effects of sodium channel blockers have been suggested. Most of these stem from clinical activities of approved anticonvulsants and antiarrhythmics with sodium channel blocking activity. Beneficial effects of sodium channel blockers for the treatment of bipolar disease are suggested by clinical data with lamotrigine [63-67], phenytoin [68], topiramate [69], and carbamazepine [70,71]. In addition, clinical studies with lidocaine suggest efficacy in the treatment of tinnitus [72] and, as an inhaled formulation, in the suppression of cough [73,74]. 

ALMOTRIPTAN, ELETRIPTAN CARBAMAZEPINE Possible 1 plasma concentrations of almotriptan and risk of inadequate therapeutic efficacy. Risk of serotonin syndrome One of the major metabolizing enzymes of almotriptan - CYP3A4 isoenzymes - is induced by rifampicin. As there are alternative metabolic pathways, the effect may not be significant and can vary from individual to individual. Triptans and carbamazepine are both stimulants of 5-HT receptors, and carbamazepine in addition prevents the reuptake of 5-HT Be aware of possibility of l response to triptan, and consider T dose if considered to be due to interaction. Be aware of the possibility of the occurrence of serotonin syndrome >- For signs and symptoms of serotonin toxicity, see Clinical Features of Some Adverse Drug Interactions, Serotonin toxicity and serotonin syndrome... 

GRAPEFRUIT JUICE ANTI EPILEPTICS -CARBAMAZEPINE t in plasma concentrations of carbamazepine (AUC11.4-fold, maximum concentration t), which is of clinical significance because of the narrow therapeutic index of carbamazepine thus, toxic effects are likely, t efficacy and t adverse effects Grapefruit juice irreversibly inhibits intestinal CYP3A4. Transport via P-gp and MRP-2 efflux pumps is also inhibited Monitor fort side-effects/toxicity and check carbamazepine levels weekly. If levels or control of fits are variable, remove grapefruit and grapefruit juice from the diet... 

The relations between plasma concentrations of carbamazepine and its two major metabolites, carbamazepine-10, 11-epoxide and carbamazepine-10,11-diol, and antimanic efficacy and adverse effects in patients with schizoaffective disorder have been studied in 10 patients (81). There were positive relations between plasma concentrations of the epoxide and the degree of clinical improvement and adverse effects, but not with plasma concentrations of carbamazepine or its diol. 

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. 

The manufacturer says that on a theoretical basis enzyme inducers such as the barbiturates, carbamazepine, phenytoin and rifampicin may accelerate the metabolism of tibolone and thus decrease its efficacy. However, they note that no examples of these interactions have been reported in clinical practice, and pharmacokinetic studies are required to demonstrate this interaction. Nevertheless it would be prudent to monitor concurrent use. 

Drug-drug interactions Carbamazepine and valproate The mood stabilizers carbamazepine and valproate are often used in combination with antidepressants in patients with unipolar or bipolar affective disorder. The effects of valproate and carbamazepine on the steady-state pharmacokinetics of moclobemide and two metabolites have been studied in a non-randomized crossover study in 21 patients with unipolar depression [3 ]. Valproate had no effect, but carbamazepine was associated with a 35% reduction in moclobemide AUC, a 28% reduction in C ,ax, and a 41% reduction in clearance after 4 weeks of co-administration. These changes were interpreted as being due to induction carbamazepine of the metabolism of moclobemide and its main metabolite. However, there was no concurrent loss of efficacy, throwing into doubt the clinical significance of these significant kinetic effects. 

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