The Clinical Guide to Supportive and Palliative Care for HIV/AIDS

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A Clinical Guide to Supportive and Palliative Care for HIV/AIDS • Chapter 27: Pharmacologic Interactions of Clinical SignificanceTable 27-8: Drug Interactions with Anti-PCP AgentsDrug Major Adverse Reactions InteractionsAtavoquone Transaminase elevation Increases levels of zidovudineRashFeverDapsonePentamidinePrimaquineClindamycinTrimethoprimsulfamethoxazoleRashNausea/vomitingAnemiaMethemoglobinemiaNeutropeniaThrombocytopeniaTransaminase elevationNephrotoxicityHyperglycemiaTransaminase elevationHyperkalemiaNeutropeniaThrombocytopeniaPancreatitisPotentially life-threateningventricular arrhythmiasHemolysis(especially in G6PD-deficiency)FeverRashMethemoglobinemiaTransaminase elevationDiarrheaNausea/vomitingPseudomembraneous colitisRashFeverTransaminase elevationSkinErythema multiforme(Stevens-Johnson syndrome, rare)Generalized skin eruptionsEpidermal necrolysisExfoliative dermatitisPhotosensitivityUrticariaPruritusOtherNausea/vomitingTransaminase elevationNeutropeniaThrombocytopeniaFeverIncreases levels of trimethoprimand dapsone, which may increaseboth the pharmacologic and toxiceffects of both drugs. Rifampin increasesmetabolism of dapsonewhile didanosine decreases absorptionof dapsone and may lead to failureof dapsone prophylaxis. Avoid.Foscarnet: increased riskof nephrotoxicity, severehypoglycemia andhypocalcemia. Avoid drugsthat cause or exacerbatepancreatitis, such asdidanosine.Opiates and diphenoxylate mayworsen diarrhea. Kaolin-pectinantidiarrheals decreaseabsorption of clindamycin.Patient needs close monitoring.Increased prothrombin time forpatients on warfarin. Increaseslevels of dapsone and half-life ofphenytoin due to protein binding.Source: Adapted from multiple sources, primarily Pharmacist’s Drug Handbook 2001. Bethesda, MD: American Society of HealthSystems Pharmacists, 2001.564U.S. Department of Health and Human Services • Health Resources and Services Administration • HIV/AIDS Bureau
A Clinical Guide to Supportive and Palliative Care for HIV/AIDS • Chapter 27: Pharmacologic Interactions of Clinical SignificanceSelected Enzyme Inducers of the CYP SystemTable 27-2 lists agents that are inducers of the CYP system, which are discussed here ingreater detail.26 picasIt should be noted that ritonavir is both an inducer and inhibitor of the CYP system; it is presentlyone of the most potent inhibitors known; it also induces CYP1A2, the enzyme system responsiblefor the metabolism of theophylline and caffeine. Other notable inducers of this systemare rifampin, rifabutin, phenytoin, phenobarbital, carbamazepine, nelfinavir, indinavir, efavirenzand nevirapine. Both ritonavir and nevirapine are autoinducers which means that they will induceenzymes that hasten their own metabolism as well. As a result of this, manufacturers ofthese agents suggest that treatment be initiated with doses that are slowly escalated within thefirst two weeks of treatment (always consult the manufacturers’ most recent package inserts foradditional information, updated drug-drug interactions listings and other drug information).Selected Enzyme Inhibitors of the CYP SystemTable 27-3 lists agents that are inhibitors of the CYP system, which are discussed here ingreater detail.As a potent inhibitor of CYP3A both in vitro and in vivo, ritonavir significantly increases thearea under the curve (or, serum concentrations) of drugs that are eliminated primarily throughthis enzyme system, especially the other protease inhibitors such as saquinavir, indinavir,amprenavir and lopinavir. These increases range from 77% to twenty-fold in humans and constitutethe basis for the boosted PI regimens that have been shown to increase plasma levels and inmany instances are able to improve efficacy of salvage regimens in advancing disease.Administering reduced dosages of both PIs reduces pill burden and improves tolerability, whilefood and hydration requirements as well as the incidence of crystalluria due to indinavir aresignificantly reduced. By the same mechanism, enzyme inhibition causes levels of drugs such asclarithromycin, ketoconazole and rifabutin to be greatly increased, leading to unexpected toxicitiesand adverse events; concomitant administration of these agents should therefore beavoided.Other Ritonavir Drug-Drug Interactions of Clinical SignificanceSince ritonavir is also an inducer of several other metabolizing enzymes such as CYP1A4,glucoronyl transferase and possibly CYP2C9 and CYP2C19, the magnitude of ritonavir interactionsis difficult to predict especially for drugs metabolized by multiple enzyme systems or drugsthat have a low intrinsic clearance by CYP3A, such as methadone. Enzyme induction, first recognizedin the 1940s, occurs when hepatic blood flow is increased or the synthesis of moreCYP450 enzymes is stimulated. In early animal models of enzyme induction, phenobarbital wasfound to increase liver weight in a dose-dependent manner. Liver biopsies in human patientstaking anticonvulsants on a chronic basis showed up to a 52% increase in liver size. Enzymeinduction is influenced by age and liver disease. As a general rule, subjects older than 60 yearsof age tend to have decreased capacity for enzyme induction, as shown by reports of differentialinduction of drug metabolism in such elderly, compared to younger subjects, following exposureto polycyclic aromatic hydrocarbons in cigarette smoke. 3XXVIIU.S. Department of Health and Human Services • Health Resources and Services Administration • HIV/AIDS Bureau 565
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DedicationA Clinical Guide to Suppo
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Lynn A Jansen, RN, PhDAssistant Res
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TABLE OF CONTENTSPart IChapter 1Cha
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IChapter 1.26 picasHIV and Palliati
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IA Clinical Guide to Supportive and
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A Clinical Guide to Supportive and
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IIIChapter 3.Assessment of Physical
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Chapter 6.26 picasPulmonary Symptom
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Chapter 8.26 picasOral ProblemsDavi
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Chapter 9.26 picasDermatologic Prob
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Chapter 10.26 picasPsychiatric Prob
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Chapter 11.26 picas Substance Use P
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Chapter 14.26 picasCulture and Care
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Chapter 15.26 picasSpecial Populati
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Chapter 17.26 picasEthical IssuesLy
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Chapter 18.26 picasLegal and Financ
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Chapter 19.Palliative 26 picas Care
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Chapter 23.26 picas Medical Care in
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Chapter 25.26 picas Prevention of S
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