Carbamazepine Toxicity Induced by Lopinavir/Ritonavir and Nelfinavir
Objective: To present a case of carbamazepine toxicity induced by lopinavir/ritonavir and nelfinavir. Case Summary: A 50-year-old HIV-positive male developed excessive drowsiness secondary to carbamazepine when an antiretroviral regimen containing lopinavir/ritonavir was introduced. The carbamazepin...
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| Veröffentlicht in: | The Annals of pharmacotherapy 2006-06, Vol.40 (6), p.1190-1195 |
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| creator | Bates, Duane E Herman, Robert J |
| description | Objective:
To present a case of carbamazepine toxicity induced by lopinavir/ritonavir and nelfinavir.
Case Summary:
A 50-year-old HIV-positive male developed excessive drowsiness secondary to carbamazepine when an antiretroviral regimen containing lopinavir/ritonavir was introduced. The carbamazepine serum concentration increased 46%. Subsequently, the patient developed a possible adverse skin reaction to his antiretrovirals and was hospitalized. The protease inhibitor was changed to nelfinavir. Within 3 days, the patient again developed excessive drowsiness and became unsteady on his feet. This time, the carbamazepine serum concentration had increased by 53%. In both instances, the carbamazepine dosage was decreased by 33%, which resulted in resolution of symptoms.
Discussion:
Carbamazepine undergoes extensive hepatic metabolism. The major metabolic pathway involves oxidation of carbamazepine via CYP3A4 to an active metabolite, carbamazepine-10,11-epoxide. Protease inhibitors are well-known CYP3A4 inhibitors. Other cases of carbamazepine toxicity secondary to protease inhibitors are reviewed. A MEDLINE search (1966–May 2006) revealed 4 cases of carbamazepine toxicity secondary to antiretrovirals. Carbamazepine serum concentrations increased two- to threefold from baseline. Vertigo, drowsiness, disorientation, ataxia, and vomiting occurred within 12 hours to 2 months, which resolved with reduction of the carbamazepine dosage.
Conclusions:
An objective causality assessment suggests that our patient became drowsy and unsteady on his feet secondary to a carbamazepine–protease inhibitor interaction. Lopinavir/ritonavir and nelfinavir may decrease carbamazepine metabolism, causing an elevation in carbamazepine serum concentrations. Carbamazepine toxicity may be prevented by reducing the carbamazepine dosage by 25–50% when protease inhibitors are introduced. A carbamazepine serum concentration should be repeated 3–5 days after the protease inhibitors are started. |
| doi_str_mv | 10.1345/aph.1G630 |
| format | Article |
| fullrecord | <record><control><sourceid>sage_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1345_aph_1G630</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1345_aph.1G630</sage_id><sourcerecordid>10.1345_aph.1G630</sourcerecordid><originalsourceid>FETCH-LOGICAL-c441t-3d53b7b5f556eec45e3dc693079df97f9a3e7fe8de810e2f2d799670834036383</originalsourceid><addsrcrecordid>eNpt0N9LwzAQB_AgipvTB_8B6YuCD90uTZs0jzJ1CkNB5nNIm2TL6I-RbNb511vXwl58uoP7cMd9EbrGMMYkTiZysxrjGSVwgoY4iaOQRgxO2x4ohBClMEAX3q8BgOOIn6MBpiwCBmSIHqfSZbKUP3pjKx0s6m-b2-0-eK3ULtcqyPbBvG5H8su6yYfd1ocukJUK3nRhusElOjOy8PqqryP0-fy0mL6E8_fZ6_RhHuZxjLchUQnJWJaYJKFa53GiicopJ8C4MpwZLolmRqdKpxh0ZCLFOKcMUhIDoSQlI3Tf7c1d7b3TRmycLaXbCwziLwnRJiEOSbT2prObXVZqdZT96y247YH0uSyMk1Vu_dGxlJLk4O465-VSi3W9c1X7478Xe7iyy1VjnRa-lEXR3seiaZoYBBUYcyC_xbJ_eg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Carbamazepine Toxicity Induced by Lopinavir/Ritonavir and Nelfinavir</title><source>Access via SAGE</source><source>MEDLINE</source><creator>Bates, Duane E ; Herman, Robert J</creator><creatorcontrib>Bates, Duane E ; Herman, Robert J</creatorcontrib><description>Objective:
To present a case of carbamazepine toxicity induced by lopinavir/ritonavir and nelfinavir.
Case Summary:
A 50-year-old HIV-positive male developed excessive drowsiness secondary to carbamazepine when an antiretroviral regimen containing lopinavir/ritonavir was introduced. The carbamazepine serum concentration increased 46%. Subsequently, the patient developed a possible adverse skin reaction to his antiretrovirals and was hospitalized. The protease inhibitor was changed to nelfinavir. Within 3 days, the patient again developed excessive drowsiness and became unsteady on his feet. This time, the carbamazepine serum concentration had increased by 53%. In both instances, the carbamazepine dosage was decreased by 33%, which resulted in resolution of symptoms.
Discussion:
Carbamazepine undergoes extensive hepatic metabolism. The major metabolic pathway involves oxidation of carbamazepine via CYP3A4 to an active metabolite, carbamazepine-10,11-epoxide. Protease inhibitors are well-known CYP3A4 inhibitors. Other cases of carbamazepine toxicity secondary to protease inhibitors are reviewed. A MEDLINE search (1966–May 2006) revealed 4 cases of carbamazepine toxicity secondary to antiretrovirals. Carbamazepine serum concentrations increased two- to threefold from baseline. Vertigo, drowsiness, disorientation, ataxia, and vomiting occurred within 12 hours to 2 months, which resolved with reduction of the carbamazepine dosage.
Conclusions:
An objective causality assessment suggests that our patient became drowsy and unsteady on his feet secondary to a carbamazepine–protease inhibitor interaction. Lopinavir/ritonavir and nelfinavir may decrease carbamazepine metabolism, causing an elevation in carbamazepine serum concentrations. Carbamazepine toxicity may be prevented by reducing the carbamazepine dosage by 25–50% when protease inhibitors are introduced. A carbamazepine serum concentration should be repeated 3–5 days after the protease inhibitors are started.</description><identifier>ISSN: 1060-0280</identifier><identifier>EISSN: 1542-6270</identifier><identifier>DOI: 10.1345/aph.1G630</identifier><identifier>PMID: 16720703</identifier><identifier>CODEN: APHRER</identifier><language>eng</language><publisher>Los Angeles, CA: Harvey Whitney Books</publisher><subject>Anticonvulsants - adverse effects ; Antiretroviral Therapy, Highly Active - adverse effects ; Biological and medical sciences ; Blood Cell Count ; Carbamazepine - adverse effects ; Drug Interactions ; Drug Therapy, Combination ; HIV Protease Inhibitors - adverse effects ; HIV Protease Inhibitors - therapeutic use ; HIV Seropositivity - complications ; HIV Seropositivity - drug therapy ; HIV Seropositivity - virology ; Humans ; Liver Function Tests ; Lopinavir ; Male ; Medical sciences ; Middle Aged ; Nelfinavir - adverse effects ; Nelfinavir - therapeutic use ; Pharmacology. Drug treatments ; Pyrimidinones - adverse effects ; Pyrimidinones - therapeutic use ; Ritonavir - adverse effects ; Ritonavir - therapeutic use ; Sleep Stages - drug effects ; Viral Load</subject><ispartof>The Annals of pharmacotherapy, 2006-06, Vol.40 (6), p.1190-1195</ispartof><rights>Copyright © 2006 Harvey Whitney Books Company</rights><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c441t-3d53b7b5f556eec45e3dc693079df97f9a3e7fe8de810e2f2d799670834036383</citedby><cites>FETCH-LOGICAL-c441t-3d53b7b5f556eec45e3dc693079df97f9a3e7fe8de810e2f2d799670834036383</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1345/aph.1G630$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1345/aph.1G630$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,780,784,21819,27924,27925,43621,43622</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17863503$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16720703$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bates, Duane E</creatorcontrib><creatorcontrib>Herman, Robert J</creatorcontrib><title>Carbamazepine Toxicity Induced by Lopinavir/Ritonavir and Nelfinavir</title><title>The Annals of pharmacotherapy</title><addtitle>Ann Pharmacother</addtitle><description>Objective:
To present a case of carbamazepine toxicity induced by lopinavir/ritonavir and nelfinavir.
Case Summary:
A 50-year-old HIV-positive male developed excessive drowsiness secondary to carbamazepine when an antiretroviral regimen containing lopinavir/ritonavir was introduced. The carbamazepine serum concentration increased 46%. Subsequently, the patient developed a possible adverse skin reaction to his antiretrovirals and was hospitalized. The protease inhibitor was changed to nelfinavir. Within 3 days, the patient again developed excessive drowsiness and became unsteady on his feet. This time, the carbamazepine serum concentration had increased by 53%. In both instances, the carbamazepine dosage was decreased by 33%, which resulted in resolution of symptoms.
Discussion:
Carbamazepine undergoes extensive hepatic metabolism. The major metabolic pathway involves oxidation of carbamazepine via CYP3A4 to an active metabolite, carbamazepine-10,11-epoxide. Protease inhibitors are well-known CYP3A4 inhibitors. Other cases of carbamazepine toxicity secondary to protease inhibitors are reviewed. A MEDLINE search (1966–May 2006) revealed 4 cases of carbamazepine toxicity secondary to antiretrovirals. Carbamazepine serum concentrations increased two- to threefold from baseline. Vertigo, drowsiness, disorientation, ataxia, and vomiting occurred within 12 hours to 2 months, which resolved with reduction of the carbamazepine dosage.
Conclusions:
An objective causality assessment suggests that our patient became drowsy and unsteady on his feet secondary to a carbamazepine–protease inhibitor interaction. Lopinavir/ritonavir and nelfinavir may decrease carbamazepine metabolism, causing an elevation in carbamazepine serum concentrations. Carbamazepine toxicity may be prevented by reducing the carbamazepine dosage by 25–50% when protease inhibitors are introduced. A carbamazepine serum concentration should be repeated 3–5 days after the protease inhibitors are started.</description><subject>Anticonvulsants - adverse effects</subject><subject>Antiretroviral Therapy, Highly Active - adverse effects</subject><subject>Biological and medical sciences</subject><subject>Blood Cell Count</subject><subject>Carbamazepine - adverse effects</subject><subject>Drug Interactions</subject><subject>Drug Therapy, Combination</subject><subject>HIV Protease Inhibitors - adverse effects</subject><subject>HIV Protease Inhibitors - therapeutic use</subject><subject>HIV Seropositivity - complications</subject><subject>HIV Seropositivity - drug therapy</subject><subject>HIV Seropositivity - virology</subject><subject>Humans</subject><subject>Liver Function Tests</subject><subject>Lopinavir</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Nelfinavir - adverse effects</subject><subject>Nelfinavir - therapeutic use</subject><subject>Pharmacology. Drug treatments</subject><subject>Pyrimidinones - adverse effects</subject><subject>Pyrimidinones - therapeutic use</subject><subject>Ritonavir - adverse effects</subject><subject>Ritonavir - therapeutic use</subject><subject>Sleep Stages - drug effects</subject><subject>Viral Load</subject><issn>1060-0280</issn><issn>1542-6270</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0N9LwzAQB_AgipvTB_8B6YuCD90uTZs0jzJ1CkNB5nNIm2TL6I-RbNb511vXwl58uoP7cMd9EbrGMMYkTiZysxrjGSVwgoY4iaOQRgxO2x4ohBClMEAX3q8BgOOIn6MBpiwCBmSIHqfSZbKUP3pjKx0s6m-b2-0-eK3ULtcqyPbBvG5H8su6yYfd1ocukJUK3nRhusElOjOy8PqqryP0-fy0mL6E8_fZ6_RhHuZxjLchUQnJWJaYJKFa53GiicopJ8C4MpwZLolmRqdKpxh0ZCLFOKcMUhIDoSQlI3Tf7c1d7b3TRmycLaXbCwziLwnRJiEOSbT2prObXVZqdZT96y247YH0uSyMk1Vu_dGxlJLk4O465-VSi3W9c1X7478Xe7iyy1VjnRa-lEXR3seiaZoYBBUYcyC_xbJ_eg</recordid><startdate>20060601</startdate><enddate>20060601</enddate><creator>Bates, Duane E</creator><creator>Herman, Robert J</creator><general>Harvey Whitney Books</general><general>SAGE Publications</general><general>Whitney</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20060601</creationdate><title>Carbamazepine Toxicity Induced by Lopinavir/Ritonavir and Nelfinavir</title><author>Bates, Duane E ; Herman, Robert J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c441t-3d53b7b5f556eec45e3dc693079df97f9a3e7fe8de810e2f2d799670834036383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Anticonvulsants - adverse effects</topic><topic>Antiretroviral Therapy, Highly Active - adverse effects</topic><topic>Biological and medical sciences</topic><topic>Blood Cell Count</topic><topic>Carbamazepine - adverse effects</topic><topic>Drug Interactions</topic><topic>Drug Therapy, Combination</topic><topic>HIV Protease Inhibitors - adverse effects</topic><topic>HIV Protease Inhibitors - therapeutic use</topic><topic>HIV Seropositivity - complications</topic><topic>HIV Seropositivity - drug therapy</topic><topic>HIV Seropositivity - virology</topic><topic>Humans</topic><topic>Liver Function Tests</topic><topic>Lopinavir</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Nelfinavir - adverse effects</topic><topic>Nelfinavir - therapeutic use</topic><topic>Pharmacology. Drug treatments</topic><topic>Pyrimidinones - adverse effects</topic><topic>Pyrimidinones - therapeutic use</topic><topic>Ritonavir - adverse effects</topic><topic>Ritonavir - therapeutic use</topic><topic>Sleep Stages - drug effects</topic><topic>Viral Load</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bates, Duane E</creatorcontrib><creatorcontrib>Herman, Robert J</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>The Annals of pharmacotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bates, Duane E</au><au>Herman, Robert J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Carbamazepine Toxicity Induced by Lopinavir/Ritonavir and Nelfinavir</atitle><jtitle>The Annals of pharmacotherapy</jtitle><addtitle>Ann Pharmacother</addtitle><date>2006-06-01</date><risdate>2006</risdate><volume>40</volume><issue>6</issue><spage>1190</spage><epage>1195</epage><pages>1190-1195</pages><issn>1060-0280</issn><eissn>1542-6270</eissn><coden>APHRER</coden><abstract>Objective:
To present a case of carbamazepine toxicity induced by lopinavir/ritonavir and nelfinavir.
Case Summary:
A 50-year-old HIV-positive male developed excessive drowsiness secondary to carbamazepine when an antiretroviral regimen containing lopinavir/ritonavir was introduced. The carbamazepine serum concentration increased 46%. Subsequently, the patient developed a possible adverse skin reaction to his antiretrovirals and was hospitalized. The protease inhibitor was changed to nelfinavir. Within 3 days, the patient again developed excessive drowsiness and became unsteady on his feet. This time, the carbamazepine serum concentration had increased by 53%. In both instances, the carbamazepine dosage was decreased by 33%, which resulted in resolution of symptoms.
Discussion:
Carbamazepine undergoes extensive hepatic metabolism. The major metabolic pathway involves oxidation of carbamazepine via CYP3A4 to an active metabolite, carbamazepine-10,11-epoxide. Protease inhibitors are well-known CYP3A4 inhibitors. Other cases of carbamazepine toxicity secondary to protease inhibitors are reviewed. A MEDLINE search (1966–May 2006) revealed 4 cases of carbamazepine toxicity secondary to antiretrovirals. Carbamazepine serum concentrations increased two- to threefold from baseline. Vertigo, drowsiness, disorientation, ataxia, and vomiting occurred within 12 hours to 2 months, which resolved with reduction of the carbamazepine dosage.
Conclusions:
An objective causality assessment suggests that our patient became drowsy and unsteady on his feet secondary to a carbamazepine–protease inhibitor interaction. Lopinavir/ritonavir and nelfinavir may decrease carbamazepine metabolism, causing an elevation in carbamazepine serum concentrations. Carbamazepine toxicity may be prevented by reducing the carbamazepine dosage by 25–50% when protease inhibitors are introduced. A carbamazepine serum concentration should be repeated 3–5 days after the protease inhibitors are started.</abstract><cop>Los Angeles, CA</cop><pub>Harvey Whitney Books</pub><pmid>16720703</pmid><doi>10.1345/aph.1G630</doi><tpages>6</tpages></addata></record> |
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| ispartof | The Annals of pharmacotherapy, 2006-06, Vol.40 (6), p.1190-1195 |
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| subjects | Anticonvulsants - adverse effects Antiretroviral Therapy, Highly Active - adverse effects Biological and medical sciences Blood Cell Count Carbamazepine - adverse effects Drug Interactions Drug Therapy, Combination HIV Protease Inhibitors - adverse effects HIV Protease Inhibitors - therapeutic use HIV Seropositivity - complications HIV Seropositivity - drug therapy HIV Seropositivity - virology Humans Liver Function Tests Lopinavir Male Medical sciences Middle Aged Nelfinavir - adverse effects Nelfinavir - therapeutic use Pharmacology. Drug treatments Pyrimidinones - adverse effects Pyrimidinones - therapeutic use Ritonavir - adverse effects Ritonavir - therapeutic use Sleep Stages - drug effects Viral Load |
| title | Carbamazepine Toxicity Induced by Lopinavir/Ritonavir and Nelfinavir |
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