Carbamazepine adverse reactions

Adverse reactions to carbamazepine include nystagmus, ataxia, diplopia, particularly if the dosage is raised too fast. Gastrointestinal problems and skin rashes are frequent It exerts an antidiuretic effect (sensitization of collecting ducts to vasopressin water intoxication). 

Lactation Carbamazepine and its epoxide metabolite are transferred into breast milk. Because of the potential for serious adverse reactions, decide whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. 

Askmark H, Wihohn BE. Epidemiology of adverse reactions to carbamazepine as seen in a spontaneous reporting system. Acta Neurol Scand 1990 81(2) 131-40. 

The most frequent CNS adverse reactions of carbamazepine are dizziness, drowsiness, and unsteadiness. In addition, it is known to have caused confusion, headache. 

There appear to be no reports of adverse reactions during the concurrent use of MAOIs and carbamazepine. However, the manufacturers of carbamazepine say that concurrent use should be avoided because of the close structural similarity between carbamazepine and the tricyclic antidepressants (and therefore the theoretical risk of an adverse interaction). They suggest that MAOIs should be discontinued at least 2 weeks before carbamazepine is started. Several reports describe successful use of carbamazepine and MAOIs, namely tranylcypromine, phenelzine, and moclobemide. Bearing in mind that the MAOIs and the tricyclics can be given together under certain well controlled conditions (see MAOIs or RIMAs + Tricyclic and related antidepressants , p.ll49), the warning about the risks may possibly prove to be overcautious. Note that, rarely, the MAOIs have been seen to cause convulsions. 

For mention of carbamazepine toxicity and other adverse reactions following the concurrent use of antipsychotics, see Carbamazepine + Antipsychotics , p.524. 

UK manufacturer lists carbamazepine (see also Clozapine + Anti epileptics , p.744), chloramphenicol, cytotoxics, penicillamine, pyrazolone analgesics (e.g. phenylbutazone), sulphonamides (e.g. co-trimoxazole) and, because they cannot be stopped if an adverse reaction occurs, they advise against the use of depot antipsychotics. There are several cases that confirm the clinical significance of these predicted interactions. 

In an open trial of monotherapy with car-bamazepine, phenytoin, valproate, or lamo-trigine in 505 Chinese patients with newly diagnosed epilepsy [3 ], 18% had adverse reactions carbamazepine (25/168 15%), phenytoin (18/59 31%), valproate (32/192 17%), and lamotrigine (16/86 19%). The... 

Systematic reviews A systematic review has been conducted to evaluate the efficacy and safety of carbamazepine and oxcarbazepine in treatment of alcohol withdrawal syndrome [108 ]. The authors concluded that trials have provided inconclusive evidence of the efficacy of carbamazepine in preventing alcohol withdrawal seizures and delirium tremens in comparison with benzodiazepines, which remain the primary treatment of moderate-to-severe alcohol withdrawal syndrome. Adverse reactions were not a major problem. 

HLA class I has been examined in 15 Japanese patients who fulfilled the diagnostic criteria for carbamazepine-induced cutaneous adverse reactions (mild in 10 and Stevens-Johnson syndrome in 5) [124 ]. HLA-B 1518, HLA-B 5901, and HLA-C 0704 alleles were associated with higher relative risks of severe cutaneous adverse reactions. The haplotype HLA-A 2402-B 5901-C 0102 carried a high relative risk of severe adverse reactions. In patients with severe cutaneous adverse reactions, the frequencies of HLA-A 1101, HLA-A 3303, HLA-B 1501, HLA-B 4403, HLA-B 5101, HLA-B 5201, HLA-C 0702, and HLA-C 1202 alleles were relatively lower than in the general population of Japanese people. The authors suggested that HLA-B 5901 may be a marker of carbamazepine-induced Stevens-Johnson syndrome in Japanese people. 

Environmental toxicity The risk of accidental exposure to meprobamate, carbamazepine, and phenytoin from consumption of stream water and fish has been studied in children and adults the average hazard quotients (i.e. the ratio of chronic daily intake to acceptable daily intake) showed no potential risks of adverse reactions due to exposure to these substances [140. ... 

Duarte AF, Baudrier T, Mota A, Azevedo F. Toxidermia a carbamazepina apresentacao invulgar [Cutaneous adverse reaction to carbamazepine unusual presentation]. Acta Med Port 2010 23(2) 267-72. 

Ikeda H, Takahashi Y, Yamazaki E, Fujiwara T, Kaniwa N, Saito Y, Aihara M, Kashiwagi M, Muramatsu M. HLA class I markers in Japanese patients with carbamazepine-induced cutaneous adverse reactions. Epilepsia 2010 51(2) 297-300. 

The possible association between HLA-B 1502 and carbamazepine- or phenytoin-induced Stevens-Johnson syndrome or maculopapular eruptions has been explored in 31 Thai subjects who had these antiepileptic drug-induced complications between 1994 and 2007 and in 50 antiepileptic drug-tolerant controls [92. There was a strong association between HLA-B 1502 and phenytoin- and carbamazepine-induced Stevens-Johnson syndrome. However, some patients with HLA-B 1502 had had carbamazepine-induced Stevens-Johnson syndrome and were tolerant of phenytoin and vice versa, which suggests that other factors contribute to this adverse reaction. 

Carbamazepine stimulates antidiuretic hormone activity and has been used for the treatment of neurohypophyseal diabetes insipidus. Carbamazepine induces microsomal enzymes and its metabolism is subject to auto-induction. Frequently occurring adverse effects are sedation, dry mouth, dizziness and gastrointestinal disturbances. Photosensitivity reactions, urticaria and Stevens-Johnson syndrome have been described. The elderly are more prone to mental confusion, cardiac abnormalities and problems due to inappropriate ADH secretion. 

Oxcarbazepine is less potent than carbamazepine, both in animal models of epilepsy and in epileptic patients clinical doses of oxcarbazepine may need to be 50% higher than those of carbamazepine to obtain equivalent seizure control. Some studies report fewer hypersensitivity reactions to oxcarbazepine, and cross-reactivity with carbamazepine does not always occur. Furthermore, the drug appears to induce hepatic enzymes to a lesser extent than carbamazepine, minimizing drug interactions. Although hyponatremia may occur more commonly with oxcarbazepine than with carbamazepine, most adverse effects that occur with oxcarbazepine are similar in character to reactions reported with carbamazepine. 

CARBAMAZEPINE H2 RECEPTOR BLOCKERS -CIMETIDINE, FAMOTIDINE, RANITIDINE t plasma concentrations of phenytoin and risk of adverse effects including phenytoin toxicity, bone marrow depression and skin reactions Inhibition of metabolism via CYP2C9 and CYP2C19 Use alternative acid suppression (e.g. ranitidine) or warn patients that effects last about 1 week. Consider monitoring carbamazepine levels, and adjust dose as necessaiy... 

Toxic profiles of the common antiepileptics vary. Of these, phenytoin has the narrowest therapeutic index, and toxicity is likely to cause ataxia, diplopia and dysarthria, Measurement of blood levels is necessary. With carbamazepine, patients and carers should report any skin reactions or eruptions, tremor or weight gain, For adverse effects with add-on antiepileptics, see the relevant sections in the text,... 

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