Oral Drugs Against COVID-19.

Mikus, G; Foerster, KI; Terstegen, T; Vogt, C; Said, A; Schulz, M; Haefeli, WE

Oral Drugs Against COVID-19.

Mikus, G Foerster, KI Terstegen, T Vogt, C Said, A Schulz, M

Haefeli, WE

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Publisher:: DEUTSCHER AERZTE-VERLAG GMBH
Publication Type:: Journal Article
Citation:: Dtsch Arztebl Int, 2022, 119, (15), pp. 263-269
Issue Date:: 2022-04-15

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Field	Value	Language
dc.contributor.author	Mikus, G
dc.contributor.author	Foerster, KI
dc.contributor.author	Terstegen, T
dc.contributor.author	Vogt, C
dc.contributor.author	Said, A
dc.contributor.author	Schulz, M https://orcid.org/0000-0002-5876-7322
dc.contributor.author	Haefeli, WE
dc.date.accessioned	2023-01-23T03:53:27Z
dc.date.available	2022-02-16
dc.date.available	2023-01-23T03:53:27Z
dc.date.issued	2022-04-15
dc.identifier.citation	Dtsch Arztebl Int, 2022, 119, (15), pp. 263-269
dc.identifier.issn	1866-0452
dc.identifier.issn	1866-0452
dc.identifier.uri	http://hdl.handle.net/10453/165362
dc.description.abstract	BACKGROUND: Five-day oral therapies against early COVID-19 infection have recently been conditionally approved in Europe. In the drug combination nirmatrelvir + ritonavir (nirmatrelvir/r), the active agent, nirmatrelvir, is made bioavailable in clinically adequate amounts by the additional administration of a potent inhibitor of its first-pass metabolism by way of cytochrome P450 [CYP] 3A in the gut and liver. In view of the central role of CYP3A in the clearance of many different kinds of drugs, and the fact that many patients with COVID-19 are taking multiple drugs to treat other conditions, it is important to assess the potential for drug interactions when nirmatrelvir/r is given, and to minimize the risks associated with such interactions. METHODS: We defined the interaction profile of ritonavir on the basis of information derived from two databases (Medline, GoogleScholar), three standard electronic texts on drug interactions, and manufacturer-supplied drug information. We compiled a list of drugs and their potentially relevant interactions, developed a risk min - imization algorithm, and applied it to the substances in question. We also compiled a list of commonly prescribed drugs for which there is no risk of interaction with nirmatrelvir/r. RESULTS: Out of 190 drugs and drug combinations, 57 do not need any special measures when given in combination with brief, low-dose ritonavir treatment, while 15 require dose modification or a therapeutic alternative, 8 can be temporarily discontinued, 9 contraindicate ritonavir use, and 102 should preferably be combined with a different treatment. CONCLUSION: We have proposed measures that are simple to carry out for the main types of drug that can interact with ritonavir. These measures can be implemented under quarantine conditions before starting a 5-day treatment with nirmatrelvir/r.
dc.format	Print
dc.language	eng
dc.publisher	DEUTSCHER AERZTE-VERLAG GMBH
dc.relation.ispartof	Dtsch Arztebl Int
dc.relation.isbasedon	10.3238/arztebl.m2022.0152
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	1103 Clinical Sciences, 1117 Public Health and Health Services
dc.subject.mesh	COVID-19
dc.subject.mesh	Cytochrome P-450 CYP3A
dc.subject.mesh	Drug Interactions
dc.subject.mesh	Humans
dc.subject.mesh	Lactams
dc.subject.mesh	Leucine
dc.subject.mesh	Nitriles
dc.subject.mesh	Proline
dc.subject.mesh	Ritonavir
dc.subject.mesh	Humans
dc.subject.mesh	Lactams
dc.subject.mesh	Nitriles
dc.subject.mesh	Ritonavir
dc.subject.mesh	Leucine
dc.subject.mesh	Proline
dc.subject.mesh	Drug Interactions
dc.subject.mesh	Cytochrome P-450 CYP3A
dc.subject.mesh	COVID-19
dc.title	Oral Drugs Against COVID-19.
dc.type	Journal Article
utslib.citation.volume	119
utslib.location.activity	Germany
utslib.for	1103 Clinical Sciences
utslib.for	1117 Public Health and Health Services
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
utslib.copyright.status	closed_access	*
dc.date.updated	2023-01-23T03:53:26Z
pubs.issue	15
pubs.publication-status	Published
pubs.volume	119
utslib.citation.issue	15

Abstract:

BACKGROUND: Five-day oral therapies against early COVID-19 infection have recently been conditionally approved in Europe. In the drug combination nirmatrelvir + ritonavir (nirmatrelvir/r), the active agent, nirmatrelvir, is made bioavailable in clinically adequate amounts by the additional administration of a potent inhibitor of its first-pass metabolism by way of cytochrome P450 [CYP] 3A in the gut and liver. In view of the central role of CYP3A in the clearance of many different kinds of drugs, and the fact that many patients with COVID-19 are taking multiple drugs to treat other conditions, it is important to assess the potential for drug interactions when nirmatrelvir/r is given, and to minimize the risks associated with such interactions. METHODS: We defined the interaction profile of ritonavir on the basis of information derived from two databases (Medline, GoogleScholar), three standard electronic texts on drug interactions, and manufacturer-supplied drug information. We compiled a list of drugs and their potentially relevant interactions, developed a risk min - imization algorithm, and applied it to the substances in question. We also compiled a list of commonly prescribed drugs for which there is no risk of interaction with nirmatrelvir/r. RESULTS: Out of 190 drugs and drug combinations, 57 do not need any special measures when given in combination with brief, low-dose ritonavir treatment, while 15 require dose modification or a therapeutic alternative, 8 can be temporarily discontinued, 9 contraindicate ritonavir use, and 102 should preferably be combined with a different treatment. CONCLUSION: We have proposed measures that are simple to carry out for the main types of drug that can interact with ritonavir. These measures can be implemented under quarantine conditions before starting a 5-day treatment with nirmatrelvir/r.

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http://hdl.handle.net/10453/165362