Haloperidol with carbamazepine

Haverkos HW, Pinsky PF, Drotman DP, etal Disease manifestation among homosexual men with acquired immunodeficiency syndrome a possible role of nitrites in Kaposi s sarcoma. Sex Transm Dis 12 203-208, 1985 Haverkos HW, Kopstein AN, Wilson H, et al Nitrite inhalants history, epidemiology, and possible links to AIDS. Environ Health Perspect 102 858-861, 1994 Hernandez-Avila CA, Ortega-Soto HA, Jasso A, et al Treatment of inhalant-induced psychotic disorder with carbamazepine versus haloperidol. Psychiatr Serv49 812— 815, 1998... 

GFJ has been shown to increase the exposure of carbamazepine (175), cisapride (176-179), fluvoxamine (184), losartan (188), methadone (189), scopolamine (191), and sertraline (192). However, only the interaction of GFJ with carbamazepine and cisapride seems to be clinically relevant. No alteration in exposure was observed for clozapine (180,181), heophylline (195), halo-peridol (196), and omeprazole (190). Reports of increased pharmacokinetic parameters of clozapine, theophylline, and haloperidol suggest that an interaction is unlikely to be clinically relevant. Contradicting results were reported for itraconazole (185-187), digoxin (75,183), and sildenafil (193,194). An increased effect on concomitant use of diclofenac and GFJ was observed in rats (182). Overall, the clinical relevance for this drug class appears to be low. 

Iwahashi K. Significantly higher plasma haloperidol level during cotreatment with carbamazepine may herald cardiac change. Clin Neuropharmacol 1996 19(3) 267-70. 

Three patients treated with various antipsychotics (fluphenazine, ha-loperidol, trifluoperazine, chlorpromazine) developed Stevens-Johnson syndrome within 8 to 14 days of starting to take carbamazepine. All 3 had erythema multiforme skin lesions and at least two mucous membranes were affected. After treatment, all 3 were restarted on all their previous drugs, except carbamazepine, without problems. Another case of Stevens-Johnson syndrome has been reported in a patient taking carbamazepine, lithium carbonate, haloperidol and trihexyphenidyl. The reasons are not understood. Stevens-Johnson syndrome with carbamazepine alone is rare, and the risk appears to be mostly confined to the first 8 weeks of treatment. It may be more common in patients being treated for conditions other than epilepsy. It is not possible to say whether the concurrent use of antipsychotics increases the risk of its development, but until more is known it would be prudent to monitor the outcome, particularly during the first 2 weeks of combined use. 

An isolated report descrihes a woman with schizoaflective disorder successfully treated for 3 years with haloperidol and carhamazepine who was given sertraline 50 mg daily for depression. When she failed to respond, the sertraline dosage was progressively increased to 300 mg daily but her sertraline plasma levels remained low (about 17 to 25% of those predicted). Another patient on carbamazepine similarly failed to respond to the addition of sertraline and had low sertraline levels. In an analysis of plasma sertraline levels the concentration to daily dose ratio of sertraline was significantly lower in patients who had taken sertraline with carbamazepine compared with those who had taken sertraline without carbamazepine, suggesting that carbamazepine lowered sertraline levels. 

Haloperidol plasma levels are roughly halved by carbamazepine, phenobarbital and phenytoin. Bromperidol, fluphenazine and ti-otixene levels are also reduced by carbamazepine. The plasma levels of chlorpromazine and haloperidol do not appear to be affected by oxcarbazepine. Neurotoxicity has been seen with haloperidol and carbamazepine and haloperidol can raise serum carbamazepine levels. Valproate or valproic acid appear not to interact. 

Other studies have similarly found 40 to 60% falls in plasma haloperidol levels in patients taking carbamazepine, " with the occasional patient having undetectable levels. Decreases in plasma haloperidol levels of unspecified amounts have also been described. A study in 9 patients t ing haloperidol 6 mg twice daily who were then given carbamazepine, with the daily dose increased at fortnightly intervals from 100 to 300 and to 600 mg, found a dose-dependent reduction in haloperidol levels. Mean plasma haloperidol levels were reduced by 25%, 61%, and 82%, respectively. A few patients have had clinical worsening or increased adverse effects. " Three patients had two to fivefold increases in plasma haloperidol levels and clinical improvement when carbamazepine 1.2 to 1.4 g daily was stopped, but extrapyramidal adverse effects developed within 1 to 30 days. Three cases of neurotoxicity (drowsiness, slurred speech, confusion) have also been described in patients taking haloperidol and carbamazepine. ... 

Biayley J, Yellowlees P. An interaction between haloperidol and carbamazepine in a patient with cerelxal f lsy. Aust N ZJ Psychiatry (1987) 21,605-7. 

Chronic Agitation. For chronic agitation with physical aggression, sodium divalproex is the preferred treatment. If divalproex is ineffective, haloperidol or an atypical antipsychotic can be added or snbstituted. Other options include trazodone, carbamazepine, and SSRI antidepressants. 

Largactil is a proprietary preparation of chlorpromazine, an aliphatic antipsychotic with marked sedation and moderate antimuscarinic and extrapyramidal side-effects. Serenace is a proprietary preparation of haloperidol, a butyrophenone antipsychotic with marked extrapyramidal side-effects, moderate sedation but not very likely to cause hypotension. Tegretol is a proprietary preparation of carbamazepine, an anti-epileptic drug indicated in partial and secondary generalised tonic-clonic seizures, primary generalised tonic-clonic seizures, trigeminal neuralgia and in the prophylaxis of bipolar disorder unresponsive to lithium. 

Oxcarbazepine is a keto derivative of carbamazepine but offers several advantages over carbamazepine. Oxcarbazepine does not require blood cell count, hepatic, or serum drug level monitoring. It causes less cytochrome P450 enzyme induction than does carbamazepine (but may decrease effectiveness of oral contraceptives containing ethinyl estradiol and levonorgestrel). As opposed to carbamazepine, oxcarbazepine does not induce its own metabolism. These properties, combined with its similarity to carbamazepine, led many clinicians to use this medication for the treatment of bipolar disorder. Randomized controlled trials suggested efficacy in the treatment of acute mania compared with lithium and haloperidol, but these trials were quite small and did not include a placebo control (Emrich 1990). 

Another use of the laboratory is for therapeutic drug monitoring (TDM) of psychotropics with defined optimal ranges, narrow therapeutic indices, or both. Although TDM is not essential for many psychotropics, it is for others, including lithium, several TCAs, valproate, and carbamazepine. It may also be helpful to optimize the use of certain antipsychotics (e.g., haloperidol, clozapine) ( 7). 

Limited evidence indicates that carbamazepine plus an antipsychotic may also benefit some schizophrenic patients. This is an interesting possibility in view of the similar antimanic properties of lithium and carbamazepine (375). This area requires further research, especially to clarify the indications for combining anticonvulsants with an antipsychotic. For example, mania complicated by psychotic features may benefit from lithium, valproate, or carbamazepine augmented by antipsychotics. Because carbamazepine induces the metabolism of at least some antipsychotics (e.g., haloperidol, thiothixene), dose adjustment based on TDM may be necessary to achieve the optimal effect. 

The pharmacologic basis of these disorders is unknown, and there is no satisfactory medical treatment for them. A subset of patients respond well to levodopa medication (dopa-responsive dystonia), which is therefore worthy of trial. Occasional patients with dystonia may respond to diazepam, amantadine, antimuscarinic drugs (in high dosage), carbamazepine, baclofen, haloperidol, or phenothiazines. A trial of these pharmacologic approaches is worthwhile, though often not successful. Patients with focal dystonias such as blepharospasm or torticollis often benefit from injection of botulinum toxin into the overactive muscles. The role of deep brain stimulation for the treatment of these conditions is being explored. 

Identical twin brothers, aged 37 years, had both suffered from bipolar disorder since their early twenties and had been treated with chlorpromazine, haloperidol, lithium, and carbamazepine before developing priapism. One of them developed priapism after taking trazodone 400 mg/day, and in the 2 years after the initial episode he suffered recurrent painless erections. Initially they occurred daily and lasted 4-5 hours. During a relapse of mania at age 37, he was given oral zuclopenthixol 40 mg/day. On the tenth day he presented with priapism of 4 days duration, which persisted despite zuclopenthixol withdrawal, needle aspiration, and phenylephrine instillation, but subsided 2 weeks later with conservative management. The... 

Haloperidol inhibits the metabolism of carbamazepine. In Japanese patients with schizophrenia, serum concentrations of carbamazepine were about 40% lower in the absence of haloperidol (48). 

Clinically important, potentially hazardous interactions with amiodarone, astemizole, bepridil, carbamazepine, chloroquine, cisapride, clarithromycin, dihydroergotamine, disopyramide, ergotamine, grapefruit juice, halofantrine, haloperidol, itraconazole, ketoconazole, methadone, moxifloxacin, phenobarbital, phenytoin, pimozide, procainamide, quinidine, rifampicin, ritonavir, sotalol, St John s wort, telithromycin, terfenadine, voriconazole... 

After first trimester carbamazepine, lamotrigine, oxcarbazepine, or valproate Second choice benzodiazepine (lorazepam) Third choice calcium channel blocker With psychosis first choice adjunctive high-potency typical antipsychotic (haloperidol, perphenazine, thiothixene, or trifluoperazine)... 

A patient with atypical bipolar disorder and panic attacks, given alprazolam 7.5 mg daily, had a reduction of more than 50% in plasma alprazolam levels, from 43 to 19.3 nanograms/mL when given carbamazepine. This was accompanied by a deterioration in his clinical condition, which was managed with haloperidol. ... 

A 59-year-old man who had been diagnosed with encephalopathy and confusion while taking a combination of carbamazepine, haloperidol and lithium (therapeutic lithium level), developed similar symptoms when he was later given lithium with olanzapine. Another elderly patient who had taken lithium for 7 years, developed severe delirium and extrapyramidal... 

When the occurrence of flip-flop kinetics is not recognised it may compromise the interpretation of results from studies on the pharmacokinetic behaviour of slow release dosage forms. Flip-flop pharmacokinetics may occur with any extravascularly administered parenteral slow release dosage form. Intramuscular depot injectimis of antipsychotics such as fluphenazine decanoate, haloperidol decanoate or flupenthixol decanoate show this behaviour. It also occurs after the administration of oral slow release products of active substances such as isoxuptine, carbamazepine, diclofenac, valproic acid, morphine and theophylline. 

Carbamazepine levels are increased by CYP3A4 inhibitors (cimetidine, macrolides, diltiazem, fluoxetine, ketoconazole, verapamil, valproate) levels are decreased by CYP3A4 inducers (cisplatin, doxorubicin, felbamate, phenobarbital, phenytoin, primidone, rifampin, theophylline). Carbamazepine may increase levels of clomipramine, phenytoin, and primidone and lithium toxicity may decrease levels of phenytoin, warfarin, oral contraceptives, doxycycline, theophylline, haloperidol, alprazolam, clozapine, ethosuximide, and valproate may interfere with other anticonvulsants. 

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