Drug–drug interactions in patients receiving hematopoietic stem cell transplantation

ABSTRACT

Introduction: Recipients of hematopoietic stem cell transplantation (HSCT) are exposed to numerous drugs in both pre- and post-transplantation period, which creates an opportunity for drug–drug interactions (DDIs); if clinically relevant DDIs happen, the risk of adverse treatment outcomes is increased.

Areas covered: This review is focused on DDIs in recipients of HSCT that were observed and published as clinical trials, case series or case reports. Relevant publications were found by the systematic search of the following online databases: MEDLINE, SCOPUS, EBSCO, and SCINDEX.

Expert opinion: The most important DDIs involve cytostatic or immunosuppressant drug on one side, and antimicrobial drugs on the other. The majority of clinically relevant interactions have pharmacokinetic character, involving drug metabolizing enzymes in the liver. Antifungal azoles inhibit metabolism of many cytostatic and immunosuppressant drugs at cytochromes and increase their plasma concentrations. Macrolide antibiotics and fluoroqunolones should be avoided in HSCT recipients, as they have much larger potential for DDIs than other antibiotic groups. HSCT recipients increasingly receive new immunomodulating drugs, and further observational studies are needed to reveal unsuspected DDIs with clinical relevance.

KEYWORDS:

• Drug–drug interactions
• hematopoietic stem cell transplantation
• prevention
• immunosuppressant drugs
• cytostatic drugs

Article highlights

• There is great potential for DDIs in recipients of HSCT, but clinically relevant interactions are infrequently encountered;

• Majority of clinically relevant interactions are pharmacokinetic in nature, involving drug metabolizing enzymes in the liver;

• Antifungal agents belonging to azoles are frequently given to HSCT recipients, and they increase plasma concentrations of many cytostatic and immunosuppressant drugs due to strong inhibition of their metabolism at cytochromes;

• Macrolide antibiotics and fluoroquinolones should be avoided in HSCT recipients, as they have much larger potential for DDIs than other antibiotic groups;

• Calcium channel blockers and opioids should be used carefully in hemopoietic stem cell transplanted patients as they have potential to increase plasma concentrations of cytostatic and immunosuppressant drugs;

• New immunomodulating drugs are increasingly used for conditioning of HSCT recipients, and further observational studies are needed to reveal unsuspected DDIs with clinical relevance

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

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Additional information

Funding

This paper was funded by Ministry of Education, Science and Technological Development, Republic of Serbia, Grant No 175007.