Abstracts

Rationale: Cannabidiol (CBD) as add-on therapy is effective for drug resistant epilepsy in tuberous sclerosis complex. Drug interactions with other antiseizure medications are significant, notably clobazam and valproic acid. Data demonstrating elevation of sirolimus serum levels following addition of CBD exist in a very limited number of patients.

Methods: We reviewed patients in our multidisciplinary tuberous sclerosis clinic for children lreviewing patients already on sirolimus to whom Cannabidiol (Epidiolex) was added, looking at serum levels of sirolimus prior to and following introduction of CBD as well as any dosing adjustments.

Results: 2 pts were identified. Patient #1 was an 8-year-old with an average sirolimus level of 6.3 NG/ML prior and average levels were 20.4 NG/ML following CBD. Patient #2 is a 15-year-old with a prior average sirolimus level of 8.1 mg/ML and 23.3 NG/ML following.

Pt#1 * Initial Epidiolex dosing unavailable for first value on treatment

	weight	VCU	LabCorp	Epidiolex dose mg/kg	Sirolimus dose
6/24/2013	11		7.7		0.8
8/5/2013	9.9		1.2		0.8
9/6/2013	9.9		1.9		1
9/18/2013	9.9				2.5
10/4/2013	9.9		3.4		2.5
10/24/2013	9.9				3
12/19/2013	11.5	7.1			3
3/27/2014	12.2	6.4
2/12/2015	13.6	3.4
4/8/2015	14	6.1
12/30/2015	15.9	10.7
2/22/2017	20	7.9
4/28/2017	20	2
10/20/2017	21.8	7.7
12/17/2018	17.8	2
2/13/2019	18.5	9.6
4/22/2019	18.5	19.7
10/15/2019				5
10/18/2019	18.5		5.3	5.405405405
1/22/2020	19.7	12.2		5.076142132
3/12/2020	19.7			10.15228426
6/26/2020	19.7			20.30456853
6/29/2020	19.7		27	20.30456853
7/13/2020	23	30		17.39130435
7/31/2020	23		11.9	17.39130435
12/3/2020	23		22.7	17.39130435
1/22/2021	23		23.5	17.39130435
3/17/2021	23			26.08695652
4/16/2021	23		15.3	26.08695652
Before Epidiolex	6.29	4.942966
After Epidiolex	20.3714286	7.258493

Pt # 2

	weight	VCU	LabCorp	Epidiolex dose mg/kg	Sirolimus dose
1/14/2015	26.9	10.6
5/20/2015	27	13
12/8/2015	27.4		6.3
5/18/2016	28.5	9
11/30/2016	32.9	7.6
7/18/2017	35.4	7.6
1/16/2018	37.6	5.4			3.5
7/13/2018	39.6	5.5			3.5
1/16/2019	42.5	10.1			3.5
4/17/2019	43.1	8.2			3.5
7/23/2019	44.4	6.7			3.5
8/15/2019	43	9.4			3.5
6/4/2020	49.6	6.4			3.5
9/8/2020	49.6			10.08065	3.5
10/16/2020	49.6	27.4		12.09677	3.5
11/9/2020	48.4	24.4		12.39669	3.5
11/27/2020	48.4	21.4		12.39669	3.5
4/16/2021	51.6	19.8		5.813953	3.5
Before Epidiolex	8.138462	2.224687
After Epidiolex	23.25	3.36006

Conclusions: We identified 2 patients on sirolimus who subsequently had cannabidiol (Epidiolex) added to the treatment regimen with marked elevation in sirolimus levels. This effect was seen at low levels of cannabidiol. Higher dosing of cannabidiol further elevated levels of sirolimus modestly. These elevations are more elevated, standing in stark contrast to the case series by Ebrahimi-Fakhari et al where 5 out of 6 patients had changes of < 10 NG/mL. Of note, neither of these patients during this time reported any adverse effects and evaluation in the clinic did not demonstrate any additional complications.

In both instances, patients were on brand name cannabidiol (Epidiolex) limiting the impact of product variability may occur with an artisanal CBD.

Close monitoring is warranted in any patient on this combination therapy.

Funding: Please list any funding that was received in support of this abstract.: No funding was received in support of this abstract.