{"entity":{"id":"realgar-indigo-naturalis","kind":"drug","name":"Realgar-indigo naturalis formulation","aka":["realgar-indigo naturalis formula","realgar-indigo naturalis","RIF","tetra-arsenic tetra-sulfide"],"tldr":"Realgar-indigo naturalis is an arsenic medicine taken by mouth, developed in China, for acute promyelocytic leukaemia. It does the same job as arsenic trioxide, which is given by drip, and the WHO lists it as an essential medicine.","summary":"The realgar-indigo naturalis formulation is on the WHO Model List of Essential Medicines among the cytotoxic medicines, as a 270 mg oral tablet containing 30 mg of tetra-arsenic tetra-sulfide, for acute myeloid leukaemia with recurrent genetic abnormalities; it was added in 2019 (TRS 1021). It is an oral form of arsenic used against acute promyelocytic leukaemia. In a multicentre randomised trial of 108 people with non-high-risk acute promyelocytic leukaemia (Haematologica 2025, NCT02899169), consolidation with tretinoin plus the oral formula was non-inferior to tretinoin plus intravenous arsenic trioxide: disease-free survival at two years was 97 per cent and 98 per cent, no deaths were observed after a median follow-up of 29 months, and most side effects were moderate. A mechanism study (PNAS 2008) found tetra-arsenic tetra-sulfide to be the principal component, with indirubin and tanshinone IIA as helpers. The sources read here do not give its national approval history. No regulator's marketing authorisation was read for this page, so its approval status is left open here.","asOf":"2026-11-03","links":[{"label":"WHO eEML: Realgar-indigo naturalis formulation","url":"https://list.essentialmeds.org/medicines/555"},{"label":"ATRA-RIF versus ATRA-ATO in non-high-risk APL (Haematologica 2025)","url":"https://doi.org/10.3324/haematol.2024.285905"},{"label":"Mechanisms of realgar-indigo naturalis in APL (PNAS 2008)","url":"https://doi.org/10.1073/pnas.0712365105"}],"tags":["universe-gap","who-eml"],"related":["arsenic-trioxide","tretinoin-atra","traditional-chinese-herbal-medicine"],"cancers":["apl","aml"],"sections":[],"technologies":[],"targets":["rara"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"provenance":{"editedBy":"OnCo universe gaps (EMA register, FDA novel approvals, WHO eEML)","editedOn":"2026-11-03"},"modality":"Inorganic arsenical (differentiation agent)","mechanism":"Its main active ingredient is tetra-arsenic tetra-sulfide, from the mineral realgar; with indirubin (from Indigo naturalis) and tanshinone IIA (from Salvia miltiorrhiza) it increased the breakdown of the PML-RARα fusion protein (PML joined to the retinoic acid receptor alpha, RARA) that drives acute promyelocytic leukaemia, and pushed the leukaemia cells to mature, in mouse and cell studies (PNAS 2008).","approvals":[{"region":"WHO","year":2019,"indication":"Essential Medicines List, cytotoxic medicines: acute myeloid leukaemia with recurrent genetic abnormalities (acute promyelocytic leukaemia)","note":"WHO EML listing (TRS 1021), not a marketing authorisation"}],"mechanismSteps":[],"toxicity":[],"access":[],"regulatoryEvents":[]},"route":"/drugs/realgar-indigo-naturalis/","neighbours":{"drug":[{"id":"arsenic-trioxide","kind":"drug","name":"Arsenic trioxide","route":"/drugs/arsenic-trioxide/"},{"id":"tretinoin-atra","kind":"drug","name":"Tretinoin (all-trans retinoic acid, ATRA)","route":"/drugs/tretinoin-atra/"}],"technology":[{"id":"traditional-chinese-herbal-medicine","kind":"technology","name":"Traditional Chinese herbal medicine alongside treatment","route":"/technologies/traditional-chinese-herbal-medicine/"}],"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"apl","kind":"cancer","name":"Acute promyelocytic leukaemia","route":"/cancers/apl/"}],"target":[{"id":"rara","kind":"target","name":"Retinoic acid receptor alpha (RARA)","route":"/targets/rara/"}]}}