Chronic overdosage of elagolix may result in greater suppression of estradiol levels and a consequent increased risk of bone loss with long-term therapy. Interactions
Elagolix has a number of potential drug interactions with other medications. Elagolix is a substrate of the cytochrome P450 (CYP450) enzyme CYP3A, and inhibitors and inducers of CYP3A4 may alter the metabolism of elagolix and increase or decrease its circulating levels. The strong CYP3A4 inhibitor ketoconazole has been found to increase peak levels of and total exposure to a single 150 mg dose of elagolix by about 2-fold. Paradoxically, rifampin, a strong inducer of CYP3A4 and other CYP450 enzymes, increased peak levels of and total exposure to a single 150 mg dose of elagolix as well. A single dose of rifampin increased peak levels of elagolix by 4.4-fold and total exposure by 5.6-fold, whereas continuous rifampin therapy increased peak levels of elagolix by 2-fold and total exposure by 1.7-fold. The use of elagolix at 200 mg twice per day concomitantly with rifampin is not recommended, whereas the concomitant use of elagolix at 150 mg once per day with rifampin should be limited to 6 months. No significant changes in exposure to elagolix were observed with concomitant administration of rosuvastatin (a substrate of OATP1B1, OATP1B3, and BCRP), sertraline (a moderate inhibitor of CYP2D6 and CYP2B6), or fluconazole (a strong inhibitor of CYP2C19 and a moderate inhibitor of CYP2C9 and CYP3A4).Elagolix is a substrate of the hepatic OATP1B1 transporter.
Case reports exist to support carbamazepine and levetiracetam; other drugs tried include pimozide, clonidine, and phenobarbitone. Immunosuppression
Immunosuppression is used inconsistently in Sydenhams chorea. The model of an autoimmune disorder would support its use. One randomized controlled trial of steroids from Paz, Brazil in 2006 (22 cases) showed remission reduced to 54 days from 119 days. Various other reports of use of oral or IV steroids from Israel, Italy and Brazil . Immunoglobulin has been used in Holland and South Africa. Some improvement can be seen within a few days of IV steroids. In Italy, prednisolone reduced average duration of symptoms from 9 weeks to 4 weeks, and these were severe cases. South African group found less neuropsychiatric complications at 6 months with IVIG treatment (IVIG preferred due to fear of TB reactivation).A course of penicillin is usually given at diagnosis to definitively clear any remaining streptococci, but there is no evidence that this is an effective treatment. Active infection is usually cleared by diagnosis. Penicillin prophylaxis, on the other hand, is essential to treat cardiac features of rheumatic fever, even if subclinical (American Heart Association guideline). If the case is of isolated chorea, it is arguable whether cardiac risk justifies prophylaxis or not, however it is likely to reduce recurrence. There are several historical case series reporting successful treatment of Sydenhams chorea by inducing fever. Prognosis
Motor problems including chorea settle within an average of 2–3 months. Recurrence seen in 16–40% of cases. Recurrence is more likely with poor compliance with penicillin prophylaxis.