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 SignificanceMore recently, another PI, lopinavir, was added to this list of boosted PIs. Ritonavir and lopinavirwere combined together into a powerful boosted PI combination (Kaletra) that takes advantageof ritonavir’s inhibition of the CYP3A enzyme system to increase levels of lopinavir up to tentimes its normal AUC. This combination can eradicate with a ten-fold increase in potency, forthe most part overcoming PI resistance in heavily experienced patients. Results from the fewstudies so far completed indicate that the profile of drug-drug interactions and drugs that shouldbe avoided for ritonavir are mostly the same for the combination of lopinavir and ritonavir(Kaletra). 1There have been reports of excessive drops in blood pressure following introduction of ritonavirinto the therapy of a hypertensive subject stabilized on a calcium channel blocker such asverapamil. Other drugs to watch out for include the proarrhythmic agents that undergo extensivefirst-pass metabolism such as terfenadine, astemizole and cisapride. Others include theHMG-C0A reductase inhibitors—drugs that are frequently prescribed for patients onantiretroviral therapy who develop lipid abnormalities—as well as triazolam and midazolam,often used to alleviate anxiety or to treat insomnia.Drug-Drug Interactions between Psychotropics and Antiretroviral AgentsSeveral of the medications used to treat mood and anxiety disorders are substrates of thecytochrome P450 enzyme system and as such are prone to interact with protease inhibitors andother drugs used for the treatment of opportunistic infections or the several degenerating neurologicaldisorders that may accompany advancing HIV disease. Some of these psychotropicmedications may be either substrates, inducers or inhibitors of this same system. For patientsreceiving these medications concomitantly, the need for awareness and closer monitoring regardingdrug-drug as well as drug-disease interactions of significance has been heightened. Recently,these concerns, though not limited to people with HIV, have been exacerbated by thereports of sudden cardiac deaths due to unexpected ventricular arrhythmias (torsades despointes) in patients on some antipsychotic medications, who were concomitantly receiving someof the newer antihistamines (terfenadine, astemizole), some of the newer SSRIs, some of thenewer antiarrhythmics (amiodarone, sotalol, fleicanide), some macrolides (erythromycin) andsome newer quinolones. The purpose of this section of the discussion is to clarify some of theissues associated with drug-drug interactions of clinical significance between the antiretroviralagents and drugs used in psychiatry.Specific Interactions between Some Antidepressants,Antipsychotics and Antiretroviral AgentsWhy do interactions occur among some antidepressants, antipsychotic agents and antiretroviralagents? Clinicians prescribing drugs for patients with HIV must be aware of the important potentialfor interactions that exists between some of the PIs (especially ritonavir) and non-nucleosideantiretroviral agents (especially efavirenz) and psychotropic drugs. Protease inhibitors havevarying degrees of inhibition of the cytochrome P450 enzyme system responsible for most of theoxidative metabolism that occurs in the liver. Ritonavir in particular is one of the most potentinhibitors of the various P450 isoenzymes, especially CYP2D6 and CYP34A which are responsiblefor metabolizing the benzodiazepines, some neuroleptics and both the SSRI and triclyclicantidepressants.556U.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 SignificanceTables 27-2, 27-3 and 27-4 give highlights of these ritonavir interactions and classifications ofsubstrates, inducers and inhibitors of the CYP450 enzyme system. Patients on PIs who are receivingtricyclic antidepressants (TCAs) should have their dosages reduced by 50% to 66% initially,with26closepicasmonitoring of blood levels to establish a safe and effective dose. 6Table 27-2: Common Inducers of Cytochrome P450 Enzyme SystemEnzymeCYP3A4CYP1A2CYP2C9CYP2C19CYP2D6CYP2E1Known InducersCarbamazepine (Tegretol), rifampin (Rifadin), phenobarbital, phenytoin(Dilantin), efavirenz (Sustiva), nevirapine (Viramune), prednisone,rifapentine, troglitazone (Rezulin)Cigarette smoke, ritonavir (Norvir), omeprazole (Prilosec), charcoalsmokedfoods, cruciferous vegetablesCarbamazepine (Tegretol), ethanol, phenytoin (Dilantin), rifabutin(Mycobutin), ritonavir (Norvir), rifampin (Rifadin)Rifabutin (Mycobutin), rifampin (Rifadin)PregnancyEthanol, ritonavir (Norvir), isoniazid (INH)Table 27-3: Common Inhibitors of Cytochrome P450 Enzyme SystemEnzymeKnown InhibitorsCYP3A4CYP1A2CYP2C9CYP2C19CYP2D6CYP2E1* the only PI with CYP2D6 inhibitory activityRitonavir (Norvir), nelfinavir (Viracept), amprenavir (Agenerase),indinavir (Crixivan), propoxyphene (Darvon), saquinavir (Fortovase),ketoconazole (Nizoral), itraconazole (Sporonox), erythromycin, grapefruitjuice, nefazodone (Serzone), fluvoxamine (Luvox), fluoxetine (Prozac),diltiazem (Cardizem), verapamil (Calan), clarithromycin (Biaxin),omeprazole (Prilosec)Ciprofloxacin (Cipro), grepafloxacin (Raxar), fluvoxamine (Luvox),fluoxetine (Prozac), nefazodone (Serzone), enoxacin (Penetrex)Amiodarone (Cordarone), clopidrogel (Plavix), fluvastatin (Lescol),fluvoxamine (Luvox), fluoxetine (Prozac), fluconazole (Diflucan),miconazole (Monistat), metronidazole (Flagyl), trimethoprim/sulfamethoxazole (Bactrim/Septra)Ticlopidine (Ticlid), fluvoxamine (Luvox), fluoxetine (Prozac)Ritonavir (Norvir),* sertraline (Zoloft), fluoxetine (Prozac), paroxetine(Paxil), quinidine, thioridazine (Mellaril), cimetidine (Tagamet),amiodarone (Cordarone), diphenhydramine (Benadryl), haloperidol(Haldol), ticlopidine (Ticlid)Cimetidine (Tagamet), isoniazid (INH), watercressXXVIIU.S. Department of Health and Human Services • Health Resources and Services Administration • HIV/AIDS Bureau 557
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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 14.26 picasCulture and Care
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Chapter 17.26 picasEthical IssuesLy
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Chapter 19.Palliative 26 picas Care
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