Pharmacy Compounded Medicines for Patients With Rare Diseases: Lessons Learned From Chenodeoxycholic Acid and Cholic Acid

Abstract

Patients with rare diseases are often confronted with the fact that effective medicines are unavailable or simply not being developed. This situation jeopardizes the health of a large population of vulnerable patients with rare diseases. Pharmacy compounded formulations can provide a safe alternative when authorized treatments are unavailable or unsuitable. Practical guidelines on how to develop and implement pharmacy compounded formulations for patients with rare diseases are limited. The aim of this article is to provide guidance for when and how to apply pharmacy compounded formulations for patients with rare diseases. This is illustrated with two challenging examples: the development and implementation of pharmacy compounding of 1) chenodeoxycholic acid (CDCA) capsules for patients with cerebrotendinous xanthomatosis (CTX) and 2) cholic acid (CA) capsules for patients with rare bile acid synthesis defects (BASD). All critical steps of the development of CDCA and CA capsules are explained and summarized in a practical guideline.

Product Validation and Stability Testing of Pharmacy Compounded Cholic Acid Capsules for Dutch Patients with Rare Bile Acid Synthesis Defects

“…Eur.). Our findings demonstrate that the pharmacy compounded CA capsules within a range of 25–250 mg complies with the EU regulations in regard to quality and product safety [ 26 ]. During the product validation, the capsule content showed some larger variations within one batch in comparison with others (e.g., batch 3, with an AV of 14.7).…”

“…A safe and sustainable alternative to the expensive EU-registered medicinal product can be achieved through pharmacy compounding from CA raw material. We developed a pharmacy formulation for CA capsules that could be easily made by pharmacists with compounding facilities [ 26 ]. The aim of the study is to determine the pharmaceutical quality and stability of our pharmacy compounded CA capsules.…”

Combatting the rising costs of cancer drugs; interventions from a university hospital’s perspective

“…Erasmus MC is not the only Dutch university hospital which makes effort to provide its patients with affordable medicines. Amsterdam UMC has started to produce chenodeoxycholic acid (CDCA) capsules through in-house production—a drug for treatment of the rare metabolic disorder cerebrotendinous xanthomatosis (CTX) which was prescribed off-label–, after the pharmaceutical company had registered this drug in 2017 and increased the price 500 fold ( Polak et al, 2021 ). These examples demonstrate that university hospitals are capable of successfully manufacturing medicines for their patients at lower costs and should be further explored internationally.…”

Cerebrotendinous Xanthomatosis: A practice review of pathophysiology, diagnosis, and treatment

“…Previous studies have also evaluated the possible role of CA therapy in the management of patients with CTX with variable patterns of clinical response, especially regarding neurological involvement (49,74). Through the suppression of endogenous bile acid biosynthesis by negative feedback mechanisms, similar to CDCA, CA supplementation provided significant reduction in the urinary excretion and serum production of intermediate biomarkers of bile acid biosynthesis pathway (75).…”