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 SignificanceDrug Interactions of Clinical SignificanceInvolving HMG-CoA Reductase Inhibitors (Statins)Recent medical and lay literature has raised a number of concerns regarding adverse eventswith the HMG-CoA group of cholesterol-lowering agents, culminating in the removal of at leastone product, cerivastatin (Baycol), from the U.S. market following reports of rhabdomyolysis(destruction of skeletal muscle, leading to renal failure) and myopathy. Clinically significantdrug interactions occur with the statins when these agents, all of which are substrates to theCYP450 enzyme system and so are amenable to the action of these enzymes, are combined withother drugs that cause muscle damage or drugs that interact to give rise to increased statinplasma levels resulting from inhibition of statin metabolism.Numerous interactions between statins metabolized by CYP3A and several CYP3A inhibitors,including the protease inhibitors, the azole antifungals, grapefruit juice, and kaolin/pectin (especiallylovastatin) have been reported. 4 DHHS guidelines specifically suggest avoiding combinationsof protease inhibitors and simvastatin (Zocor) and lovastatin (Mevacor), with fluvastatin(Lescol) and atorvastatin (Lipitor) as alternatives that must be used with caution. 1 Fibratessuch as gemfibrizol may cause myopathy when used alone and also in combination with most ofthe statins, with the exception of fluvastatin (Lescol). An increased incidence of myopathy hasbeen reported when niacin is combined with lovastatin but not with fluvastatin, pravastatin orsimvastatin. 19Despite the increased risk of adverse events, providers are sometimes compelled to continuestatin therapy in order to ward off serious cardiovascular sequalae. In such circumstances, patientsshould be counseled to report immediately any signs or symptoms of myopathy such asmuscle pain, calf tenderness or muscle weakness.Significant Induction Interactions: Estrogens and CorticosteroidsEstrogens and corticosteroids are substrates to the cytochrome P450 enzyme system, henceremain susceptible to the action of these enzymes and can be changed or metabolized by themor by substances that act as inducers or inhibitors on CYP450 enzymes. Protease inhibitors suchas nelfinavir or ritonavir, which can act both as inducers and inhibitors of the CYP450 enzymesystem, have been shown to increase the degradation of ethinyl estradiol, a major component oforal contraceptive pills. 20 Women with HIV taking these PIs should receive additional or alternativecontraceptive methods in order to ensure full protection.As a result of the recent decreases in the estrogen and progestin concentrations of oral contraceptives,reports of unintended pregnancies and episodes of breakthrough bleeding seem to beon the rise. 16 Reports of clinically significant drug interactions secondary to enzyme inductionhave implicated phenobarbital, phenytoin, carbamazepine, ethosuximide, primidone andrifampin. 21,22,23,24 Such reports have not been made for gabapentin, lamotrigine, topiramate andvalproate. When such interactions are suspected, a higher dose oral contraceptive containing50 mg ethinyl estradiol, medroxyprogesterone or a non-hormonal alternative method of contraceptionis usually recommended.Corticosteroids, which often remain the mainstay of management of diseases that occur in palliativecare of advanced HIV infection, have their clearances increased in a similar fashion tothe estrogens by the same agents, when administered concomitantly. Patients receiving steroidsfor chronic diseases should be monitored for exacerbation of symptoms in these situationsand the necessary dosage adjustments made. 24568U.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 SignificanceDRUG INTERACTIONS BETWEEN ILLICIT DRUGSAND ANTIRETROVIRAL AGENTS26 picas■ Interactions between drugs of abuse and other treatment modalities that may be offered inpalliative care, including antiretroviral agents, occur against a background of related eventsand conditions that vary by individual patient. Though patients differ, most patients with longstandingsubstance use will suffer from comorbid conditions that will significantly affect theirresponse to the therapies offered to them at all stages of their HIV disease. It is well establishedthat the abuse of psychoactive substances not only causes a significant number of accidents, butoften is associated with other medical problems and comorbid conditions as shown in Table 27-9. 25 For example, excessive alcohol intake places a patient at risk for various adverse events andconditions including peripheral neuropathy and pancreatitis, cirrhosis, malignancies and psychiatricdisorders. Any of these events and conditions can exacerbate the occurrence as well asthe severity of drug-drug and drug-disease interactions, especially as HIV disease advances andpatients begin to receive palliative care.Table 27-9: Comorbid Conditions Associated with Substance Abuse• Poor nutrition/wasting• Liver disease• Endocarditis• Tuberculosis• Cutaneous abscesses• Pneumonia• Slowed mentation and cognitive dysfunction• HIV/STDs• Cellulitis and septic emboli• Hepatitis (A,B, C, D and G)Source: Adapted from Anderson JR, ed. A Guide to the Clinical Care of Women with HIV. Rockville, MD: U.S. Department of Healthand Human Services, Health Resources and Services Administration (HRSA), 2001.Most Commonly Used Illicit Substances andTheir Interaction with Antiretroviral AgentsRecent reports in the literature have brought more attention to the life-threatening interactions,including deaths, that occurred when protease inhibitors were combined with illicit drugssuch as ecstasy (MDMA) and GHB (gamma hydroxy butyrate). 26Although PIs have dramatically improved the prognosis for many people living with HIV, PIs areassociated with numerous adverse effects including increases in serum glucose, triglycerides,lipodystrophy, hepatitis, nephrolithiasis and a large variety of GI side effects. 27 In addition to thedrug interactions previously discussed, protease inhibitors can cause serious adverse reactionsand interactions when administered in combination with other substances, including illicit drugs,whose metabolism may be altered as a result of the inhibitory effects of the PIs on the cytochromeP450 enzyme system.XXVIIU.S. Department of Health and Human Services • Health Resources and Services Administration • HIV/AIDS Bureau 569
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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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Chapter 6.26 picasPulmonary Symptom
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Chapter 8.26 picasOral ProblemsDavi
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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 19.Palliative 26 picas Care
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Chapter 26.26 picasResourcesMagda B
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