Plasma-exchange treatment for severe carbamazepine intoxication: a case study.

Acute poisoning is an important cause of morbidity and mortality during childhood. This manuscript reports the positive outcome of a pediatric case with a history of accidental carbamazepine intake treated using plasma exchange. A 3-year-old male presented with severe carbamazepine intoxication. He was comatose and had generalized tonic clonic seizure, ventricular tachycardia, and hypotension. Although he did not respond to classical therapies, we performed two sessions of plasma exchange. The patient recovered rapidly and was discharged from the hospital six days from the time of carbamazepine ingestion with no complication or neurologic impairment. Plasma exchange can be performed safely in very small children, and it might be the first line treatment, particularly for intoxication with drugs that have high plasma-protein-binding properties.

Probable interaction between trazodone and carbamazepine.

The need to maintain long-term treatment of chronic pathologies makes the appearance of interactions possible when such therapies incorporate other drugs to deal with the aggravation of the same or other intercurrent pathologies. A case is presented in which the addition of trazodone to a chronic treatment with carbamazepine (CBZ) is associated with symptoms typical for intoxication by this antiepileptic, accompanied by a raised serum concentration. When the trazodone was suspended, these symptoms lessened and the concentration of CBZ decreased progressively, suggesting a probable interaction between the 2 drugs.

An experimental design for finding of minimum dosage of carbamazepine and valproate in preventing of seizure attacks.

Previous studies have shown that physicians use high doses of carbamazepine (CBZ) and valproate (VPA) to control of epileptic attacks, while these drugs incur of many side effects include of gastrointestinal, hematologic, psychiatric, cardiac and other side effects. The aim of this study was to determine the minimum therapeutic dose with and an acceptable blood level of these drugs. This semi-experimental study was done in 56 epileptic patients in during of one year. At the first demographic data including of age, sex, weight and the period of drug taking was recorded. Then the drug CBZ and VPA were prescribed to adults (more than 12 years old) 9-11 mg/kg and 12-14 mg/kg respectively, and in children (less than 12 years old) 12-14 and 12-15 mg/kg respectively. Serum levels of CBZ and VPA were measured monthly by gas chromatography method that is separation technique, is mostly employed in chemical analysis. The results indicated that serum levels of CBZ and VPA in adult were 7.4 and 74.7 and serum levels of drugs in children were 8.2 and 66.8 respectively. Also patients have not epilepsy attack in during the period of assessment. These findings showed that with a much lower dosage of the drugs, which is suggested in texts can lead to an appropriate blood level of CBZ and VPA for controlling the epileptic seizures.

Possible Oxcarbazepine Inductive Effects on Aripiprazole Metabolism: A Case Report.

Oxcarbazepine is a cytochrome P450 (CYP) 3A4 inducer, which is structurally similar to carbamazepine. Although lacking Food and Drug Administration approval, oxcarbazepine is sometimes prescribed to treat aggressive behavior in youth with autism spectrum disorder (ASD). These youths may also be taking second-generation antipsychotics, some of which are substrates of the CYP3A4 metabolic pathway. The combination of these medications may result in decreased serum antipsychotic concentrations, potentially reducing effectiveness. A limited number of reports are available which discuss reduced atypical antipsychotic concentrations secondary to oxcarbazepine CYP3A4 induction. We report a young boy taking oxcarbazepine (1200 mg/d) who presented with an unexpectedly low serum aripiprazole concentration. Utilizing therapeutic drug monitoring, pharmacogenetic testing, and a tool to evaluate drug-drug interactions, we estimate that oxcarbazepine possibly reduced his serum aripiprazole concentration by 68%. Our report is important, as it is the first to describe a drug-drug interaction between oxcarbazepine and aripiprazole. This report should encourage the completion of in vitro and clinical studies and the publication of case reports describing the possible inductive effects of oxcarbazepine on atypical antipsychotics (including cariprazine, lurasidone, quetiapine, aripiprazole, brexpiprazole, iloperidone, and risperidone) mediated by induction of the CYP3A4 metabolic pathway.

Rational use of antiepileptic drug levels.

Antiepileptic drug (AED) levels are obtained frequently in clinical practice, but their complex relation to seizures or drug toxicity often makes interpretation of the results difficult. Research studies have not always taken into account clinical, as well as pharmacokinetic and pharmacodynamic, factors which may influence the drug level-effect relationship. AED levels should be drawn at an appropriate time in relation to drug ingestion and clinical symptoms. Systematic investigations in selected patients, during which several levels are obtained, may be more rewarding than routine measurements in a large clinic population.

Pediatric carbamazepine suspension overdose-clinical manifestations and toxicokinetics.

Two toddlers ingested unknown quantities of their older sibling's carbamazepine suspension and rapidly manifested central nervous depression requiring intubation in 1 patient. Coma was the primary clinical finding throughout their care with no anticholinergic syndrome, seizures, or dysrhythmia. Both patients recovered without sequelae within 24 hours. Initial carbamazepine concentrations were 36.6 and 22.7 mg/L. The elimination rates (zero-order kinetic) were approximately 1.4 and 0.75 mg/L per hour. We provide the first toxicokinetic data for carbamazepine suspension overdose in children. We confirm that the oral absorption of suspension carbamazepine is rapid necessitating prompt referral to a health care facility for this exposure.

Absence of carbamazepine-induced hyponatremia among patients also given lithium.

Of 33 chronically psychotic patients in a state hospital, 17 received carbamazepine, 13 received carbamazepine and lithium, and three received carbamazepine and then the combination. There was a significant difference in serum sodium level between the patients receiving carbamazepine alone (mean +/- SD = 138.4 +/- 4.3 meq/liter) and those also receiving lithium (141.8 +/- 1.6 meq/liter). (A similar difference was seen for the patients who received the two treatments serially.) Age, sex, diagnosis, age at diagnosis, seizure disorder, antipsychotic drugs, and serum carbamazepine level did not explain this difference. The protection against hyponatremia provided by the carbamazepine-lithium combination occurred despite lithium's tendency to increase polyuria.

Carbamazepine: prevention of alcohol withdrawal seizures.

Effects of carbamazepine on alcohol withdrawal seizures and symptoms were studied in rats. Carbamazepine was administered during alcohol feeding and continued during alcohol withdrawal. When carbamazepine serum levels were above 3 micrograms per milliliter, alcohol withdrawal seizures were not observed. Carbamazepine also alleviated alcohol withdrawal symptoms, especially heightened spontaneous activity, startle to noise, stereotyped chewing movements, and intermittent body stiffening.

Mood stabilizers during breastfeeding: a review.

BACKGROUND: The postpartum period is an exceptionally high-risk time for recurrence of depression, mania, or psychosis for women with bipolar disorder. Puerperal prophylaxis with mood stabilizers decreases this risk. To allow patients and clinicians to make informed decisions about mood-stabilizer use during breastfeeding, there is a need for a critical review and analysis of the data. DATA SOURCES: A search of MEDLINE (1966-1998) and the Lithium Database, Madison Institute of Medicine, was conducted to obtain articles about lithium, valproate, carbamazepine, gabapentin, or lamotrigine use during lactation. Search terms used were pregnancy, teratogenesis, breastfeeding, lactation, breast milk levels and lithium, anticonvulsants, mood stabilizers. No other search restrictions were used. Unpublished data on gabapentin and lamotrigine were provided by the manufacturers. RESULTS: The search revealed 11 cases of lithium use during breastfeeding, 8 of which reported infant serum levels. Two cases reported symptoms consistent with lithium toxicity in the infants. Thirty-nine cases of valproate use during breastfeeding were found, 8 of which reported infant serum levels. There was 1 report of thrombocytopenia and anemia in an infant. Fifty cases of carbamazepine use during breastfeeding were found, 10 of which reported infant serum levels. Two infants experienced hepatic dysfunction. One unpublished study of gabapentin in breast milk was found. Three reports of lamotrigine use during breastfeeding were found. DISCUSSION: Available information remains limited to uncontrolled studies and case reports. Carbamazepine and valproate, but not lithium, have generally been considered compatible with breastfeeding. The overall paucity of data, data confounded by polypharmacy and infant age differences, and adverse reactions reported with all established mood stabilizers dictate a reassessment of these recommendations. We propose that a woman's historical response to medication and the clinical circumstances be the primary considerations when choosing a mood stabilizer during breastfeeding, rather than strict adherence to categorical assignments.

The treatment of affective disorder with carbamazepine: prophylactic synergism of lithium and carbamazepine combination.

1. In order to examine the prophylactic interaction between lithium and carbamazepine (CBZ), 18 patients who had been treated prophylactically with a combination of lithium and CBZ (combination therapy), lithium alone (Li-therapy), or CBZ alone (CBZ-therapy) were investigated in terms of episode occurrence. 2. The results revealed that the duration of symptoms and the frequency of hospitalization per year were significantly lower in the combination therapy than in both the Li-therapy and the CBZ-therapy. 3. In 7 out of 18 patients, the best prophylactic effect was obtained during combination therapy and none of the parameters measured was definitely inferior to those measured during the two single therapies. 4. During combination therapy, serum lithium level was significantly lower than during Li-therapy in the CBZ responders, and the combination of the two drugs enabled the required concentrations of lithium to be decreased. 5. It was concluded that synergistic action and a decrease in required concentrations of lithium can be expected with the combined use of lithium and CBZ, especially in responders to CBZ.

Two cases of downbeat nystagmus and oscillopsia associated with carbamazepine.

Downbeat nystagmus is often associated with structural lesions at the craniocervical junction, but has occasionally been reported as a manifestation of metabolic imbalance or drug intoxication. We recorded the eye movements of two patients with reversible downbeat nystagmus related to carbamazepine therapy. The nystagmus of both patients resolved after reduction of the serum carbamazepine levels. Neuroradiologic investigations including magnetic resonance imaging scans in both patients showed no evidence of intracranial abnormality. In patients with downbeat nystagmus who are taking anticonvulsant medications, consideration should be given to reduction in dose before further investigation is undertaken.

Short-term impact of the switch from immediate-release to extended-release oxcarbazepine in epilepsy patients on high dosages.

Extended-release oxcarbazepine (OXC) was introduced in Germany in January of 2008. In principle, this formulation should allow a better tolerability due to the less marked serum peak concentration of OXC prior to metabolization to its monohydroxy derivate (MHD) that is the active compound. Twenty-seven in-patients who had been referred to our epilepsy centre because of their difficult-to-treat localization-related epilepsies and had been on immediate-release OXC were abruptly switched to extended-release OXC at identical dosages. The adverse event profile (AEP) and the QOLIE-10 questionnaire were obtained immediately prior to and 5 days after this switch. On both days MHD fasting serum concentrations were also measured. After the switch a significant improvement of tolerability and quality of life was reported according to AEP and QOLIE-10 (p<0.001). Ameliorations were apparent in almost every patient (AEP: 26 of 27 patients, QOLIE-10: 23 of 27 patients). The improvement not explained by a drop of MHD levels. On the contrary and in line with preclinical data, serum levels of MHD rose significantly (p<0.001). We suggest that patients on extended-release OXC experience a lower serum concentration peak of the pro-drug OXC.

[Carbamazepine poisoning in a small child]. / Carbamazepinvergiftung bei einem Kleinkind.

Accidental intoxication with carbamazepine in a non epileptic female infant of two years of age is described. On admission the girl was unconscious, reacting only to painful stimuli, with a tonic extension spasm of the left arm and a tonic spasm of the mastication muscles. After primary care and gastric lavage a general tonic seizure with opisthotonus occurred. CBZ-plasma level 14 hours after ingestion: 19.4 mcg/ml (82.06 micromol/l). After the girl recovered consciousness, 21 hours after ingestion, a period of restlessness was seen. 36 hours after ingestion the patient had recovered completely. Comparison with published cases is made, the analogy to diphenylhydantoin intoxication is pointed out.

Long-term prophylactic effects of carbamazepine in affective disorder.

The prophylactic effects of carbamazepine (CBZP) were studied in 32 patients with affective disorder who were receiving long-term therapy with CBZP. Complete inhibition of both manic and depressive episodes was observed in four cases, reduced incidence of episodes or decreased intensity of symptoms in twenty, and no change in eight. CBZP was significantly more effective in cases with an onset before the age of 20, and subjects showing a continuous pattern of alternating episodes responded better than those with a more intermittent history of mania and depression. Where CBZP had an effect it was generally apparent soon after therapy started. These results suggest that in some cases CBZP is an agent suitable for long-term continuous prophylactic therapy in manic-depressive disorder.

Slow release carbamazepine in treatment of poorly controlled seizures.

Thirty three children with poorly controlled epilepsy, and six new patients, were treated with slow release carbamazepine. Twelve of the former had a reduction in the number of seizures of more than half, and 10 had fewer side effects. Three of the new patients stopped having seizures. Variations in plasma concentrations between doses was significantly less when patients took the slow release preparation (22%) compared with the standard preparation (41%). Slow release carbamazepine may improve the conditions of children whose seizures are poorly controlled.

[Effects of carbamazepine on heart conduction in young patients: a serial study using ambulatory ECG]. / Effetti della carbamazepina sull'eccitoconduzione cardiaca in soggetti giovani: studio seriato con ECG-dinamico.

BACKGROUND: Carbamazepine (CBZ) is a first-line drug in the treatment of epileptic seizures and neuralgia. CBZ is also a cardioactive drug and sometimes induces sinusal dysfunction or AV conduction defects. METHODS: In order to investigate the effect of CBZ on sinus node function and AV conduction, long-term ECG recording (24 hours) and determination of plasma concentration of CBZ were carried out in 10 epileptic patients without heart disorders (5 males and 5 females, mean age 31 years), in the basal state, during steady-state (7th day) and after 30th day of CBZ treatment. The number of total cardiac beats, mean heart rate, P-Q and Q-T interval, sinus-atrial node and atrioventricular dysfunction and intraventricular conduction delay were evaluated. RESULTS: Plasma CBZ concentration was always in the therapeutic range (5-12 micrograms/ml): 9.5 micrograms/ml in the 7th day and 7.8 micrograms/ml in the 30th day. No significant differences in the number of cardiac beats, or P-Q and Q-T intervals were found; there was no depression of sinus node function nor delay of AV conduction. In the basal state, ectopic supraventricular beats (105 +/- 20/24 hours) were observed in 7 patients and repetitive in five of them. In the first Holter ECG recording during CBZ treatment, a strong reduction of ectopic supraventricular beats (6 +/- 3/24 hours) and disappearance of the bursts was observed. In the second control, when the CBZ concentration was lower, the number of ectopic supraventricular beats were moderately increased (30 +/- 8/24 hours) and in one patient supraventricular tachycardia reappeared. CONCLUSIONS: In young epileptic subjects without signs of heart disease, CBZ seems to have no significant effect on conduction, yet has a possible antiarrhythmic effect.

Carbamazepine intoxication with negative myoclonus after the addition of clobazam.

We report a case a carbamazepine (CBZ) intoxication with negative myoclonus that occurred 4 weeks after clobazam (CLB) had been added to a stable regimen of CBZ and topiramate (TPM). Both CBZ and CBZ-epoxide (CBZ-E) blood levels were elevated, and the symptoms resolved quickly when CBZ dosage was reduced and CLB discontinued. CLB was reintroduced a year later with the patient's consent, and the time course of the interaction was studied: CBZ and CBZ-E levels increased slowly over 12 days. The interaction is thus probably related to the progressive increase in Nor-CLB.