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Background: The mechanistic target of rapamycin inhibitors everolimus and sirolimus have activity against multiple manifestations of tuberous sclerosis complex and are approved to treat astrocytomas, angiomyolipomas, lymphangioleiomyomatosis, and epilepsy. Cannabidiol is a novel antiepileptic medication. There is lack of information regarding drug-drug interactions between mechanistic target of rapamycin inhibitors and cannabidiol in clinical practice.Methods: We reviewed patients with tuberous sclerosis complex who were treated with a mechanistic target of rapamycin inhibitor (everolimus, sirolimus) and cannabidiol. Clinical information, mechanistic target of rapamycin inhibitor and cannabidiol dosing, concomitant antiepileptic drugs, as well as laboratory and adverse events were reviewed before and after initiation of cannabidiol.Results: A total of 25 patients were treated with cannabidiol and a mechanistic target of rapamycin inhibitor (18 everolimus, seven sirolimus). All mechanistic target of rapamycin inhibitor levels were drawn as troughs. Levels were significantly higher in 76% patients after cannabidiol treatment (P = 0.0003). Median change from baseline was +9.8 ng/mL for everolimus and +5.1 ng/mL for sirolimus. Adverse events occurred in 40%, with diarrhea being the most frequent adverse event occurring in three patients. No severe adverse events occurred during the treatment period.Conclusions: Cannabidiol resulted in increased serum levels of everolimus and/or sirolimus. Some patients experienced doubling or tripling of their mechanistic target of rapamycin inhibitor trough following the addition of cannabidiol. In some cases, this resulted in clinical toxicity, as well as laboratory abnormalities. Awareness of this interaction can lead clinicians to evaluate serum levels and other safety laboratory studies more closely, and thereby avoid potentially significant adverse effects. In patients known to be prone to mechanistic target of rapamycin inhibitor toxicity, preemptive reduction in dose may be warranted upon initiation of cannabidiol. [ABSTRACT FROM AUTHOR]

Abstract: To determine vigabatrin’s effectiveness and the prevalence of symptomatic visual impairment (i.e., impairment affecting the ability to perform everyday activities) associated with its therapy in pediatric epilepsy, we retrospectively reviewed medical records of 156 patients receiving vigabatrin at Cincinnati Children’s Medical Center from 1998-2010. In addition to demographics and vigabatrin dosing information, data included seizure type/frequency at presentation and subsequent follow-up. Of 156 patients, we excluded 35 because their medical records were insufficient to permit verification of the exact duration or timing of vigabatrin treatment. To evaluate efficacy (n = 121/135), we used a 5-point scale (0-4) to compare seizure frequency at several time points. To evaluate visual impairment (n = 63), we reviewed serial ophthalmologic evaluations at baseline and during treatment for patients in whom they were clinically indicated. Mean age at treatment initiation was 1.8 years (range, 0.1-29.2 years). Treatment duration ranged from 0.7-101.0 months, with an estimated average daily dose of 79 mg/kg/day. Tuberous sclerosis complex was the commonest seizure etiology (83%). Partial-onset seizure, alone or with infantile spasms, was the commonest seizure type (84%). Seizure frequency decreased from 3.7 ± 0.6 S.D. at baseline to 1.8 ± 1.7 S.D. at 6 months (P < 0.001). Responses to vigabatrin did not differ by tuberous sclerosis complex or nontuberous sclerosis complex etiology, and were sustained for 5 years. Sixty-three patients (∼50% of all patients evaluated) underwent clinically indicated ophthalmologic assessments during the review period. In our clinical judgment, no cases of clinically relevant vigabatrin-associated visual impairment occurred. Vigabatrin was effective for refractory childhood partial-onset epilepsy, and was not associated with symptomatic vision loss. [Copyright &y& Elsevier]