Indinavir adverse effects

Lactation Although it is not known whether indinavir is excreted in breast milk, there exists the potential for adverse effects from indinavir in nursing infants. Instruct mothers to discontinue nursing if they are receiving indinavir. 

The most common adverse effects of indinavir are indirect hyperbilirubinemia and nephrolithiasis due to crystallization of the drug. Nephrolithiasis can occur within days after initiating therapy, with an estimated incidence of approximately 10%. Consumption of at least 48 ounces of water daily is important to maintain adequate hydration. Thrombocytopenia, elevations of serum aminotransferase levels, nausea, diarrhea, insomnia, dry throat, dry skin, and indirect hyperbilirubinemia have also been reported. Insulin resistance may be more common with indinavir than with the other Pis, occurring in 3-5% of patients. There have also been rare cases of acute hemolytic anemia. 

The most common adverse effects associated with nelfinavir are diarrhea and flatulence. Diarrhea often responds to antidiarrheal medications but can be dose-limiting. Nelfinavir is an inhibitor of the CYP3A system, and multiple drug interactions may occur (Tables 49-3 and 49-4). An increased dosage of nelfinavir is recommended when co-administered with rifabutin (with a decreased dose of rifabutin), whereas a decrease in saquinavir dose is suggested with concurrent nelfinavir. Co-administration with efavirenz should be avoided due to decreased indinavir levels. Nelfinavir has a favorable safety and pharmacokinetic profile for pregnant women compared with that of other Pis (Table 49-5) there is no evidence of human teratogenicity. 

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

Indinavir sulfate is a protease inhibitor and is used in combinations for the treatment of viral infection. During the high risk of HIV infection, indinavir is combined with zidovudine and lamivudine.65 Indinavir sulfate should be used with caution in patients with hepatic impairment and avoided in patients with severe liver damage. Caution is needed in diabetic patients and in patients with hemophilia. Adverse effects of indinavir sulfate include nausea, vomiting, diarrhea, fatigue, dizziness, headache, skin rashes, and allergic reactions (hematuria). 

ALMOTRIPTAN, ELETRIPTAN PROTEASE INHIBITORS -INDINAVIR, NELFINAVIR, RITONAVIR Possibly t adverse effects when almotriptan or eletriptan is coadministered with indinavir, ritonavir (with or without lopinavir), or nelfinavir Inhibition of CYP3A4- and possibly CYP2D6-mediated metabolism of eletriptan, and CYP3A4-mediated metabolism of almotriptan Avoid co-administration... 

MODAFINIL 1. ANTIBIOTICS-clarithromycin, telithromycin 2. ANTIFUNGALS-itraconazole, ketoconazole 3. ANTIVIRALS-indinavir, nelfinavir, ritonavir, saquinavir t plasma concentrations of modafinil, with risk of adverse effects Due to inhibition of CYP3A4, which has a partial role in the metabolism of modafinil Be aware. Warn patients to report dose-related adverse effects, e.g. headache, anxiety... 

ALFENTANIL, BUPRENORPHINE, FENTANYL, TRAMADOL PROTEASE INHIBITORS Possibly t adverse effects when buprenorphine is co administered with indinavir, ritonavir (with or without lopinavir) or saquinavir Inhibition of CYP3A4 (CYP2D6 in the case of tramadol) Halve the starting dose and titrate to effect. For single injection of fentanyl, monitor sedation and respiratoiy function closely. If continued use of fentanyl, i dose may be required. Concomitant use of ritonavir and transdermal fentanyl is not recommended... 

CLARITHROMYCIN, ERYTHROMYCIN PROTEASE INHIBITORS Possibly t adverse effects of macrolide with atazanavir, ritonavir (with or without lopinavir) and saquinavir Inhibition of CYP3A4- and possibly CYP1 A2-mediated metabolism. Altered transport via P-gp may be involved. Amprenavir and indinavir are also possibly t by erythromycin Consider alternatives unless there is Mycobacterium avium intracellulare infection if combined, 1 dose by 50% (75% in the presence of renal failure with a creatinine clearance of <30mL/min)... 

RIFABUTIN PROTEASE INHIBITORS t efficacy and t adverse effects of rifabutin Inhibition of CYP3A4-mediated metabolism. Nelfinavir also competitively inhibits 2C19 1 rifabutin dose by at least 50% when given with amprenavir, indinavir or nelfinavir, and by 75% with atazanavir, ritonavir (with or without lopinavir) or tipranavir... 

ITRACONAZOLE, KETOCONAZOLE PROTEASE INHIBITORS Possibly t levels of ketoconazole by amprenavir, indinavir and ritonavir (with or without lopinavir). Conversely, indinavir, ritonavir and saquinavir levels t by itraconazole and ketoconazole Inhibition of, or competition for, CYP3A4-mediated metabolism Use itraconazole with caution and monitor for adverse effects. No dose adjustment is recommended for doses <400 mg/day of ketoconazole... 

ATAZANAVIR INDINAVIR t efficacy and t adverse effects of indinavir t adverse effects of atazanavir, e.g. hyperbilirubinaemia t bioavailability. Inhibition of metabolism via CYP3A4 by atazanavir inhibition of UDGPT by indinavir Avoid co-administration... 

INDINAVIR NELFINAVIR Possibly t efficacy and t adverse effects of both Inhibition of CYP3A4-mediated metabolism Uncertain if interaction is clinically significant however, monitor more closely for adverse effects... 

INDINAVIR RITONAVIR t efficacy and t adverse effects of indinavir. Risk of nephrolithiasis if the dose of indinavir exceeds 800 mg twice a day Inhibition of CYP3A4-mediated metabolism of indinavir Dose of indinavir can be i from 800 mg three times a day to 600 mg twice daily. Adequate hydration and monitoring are essential. Adults must drink at least 1500 mL/24 hours... 

PROTEASE INHIBITORS DUTASTERIDE Possibly t adverse effects of dutasteride with indinavir or ritonavir (with or without lopinavir) Inhibition of CYP3A4-mediated metabolism of dutasteride Monitor closely 1 dosing frequency if side-effects occur... 

Efavirenz is a non-nucleoside reverse transcriptase inhibitor with excellent inhibitory activity against HTV-l. Its most frequent adverse effects involve the central nervous system and the skin (1). At the start of therapy, dizziness, insomnia, or fatigue is observed in most patients, and headache and even psychotic reactions have also been observed. A maculopapular rash is seen in about 10%. These adverse effects usually vanish within the first 2-4 weeks of therapy (2). About 1-2% of individuals stop taking efavirenz because of neurological or dermatological adverse events. Administration of efavirenz at bedtime reduces the incidence of severe adverse effects, and the rash can be managed by short-term antihistamines or topical corticosteroids (1). Nausea and vomiting are less often observed than in patients treated with zidovudine, lamivudine, or indinavir. 

In an open comparison of efavirenz and indinavir (plus two nucleoside analogues) in predominantly treatment-naive patients efavirenz-based triple therapy provided at least similar antiviral effects over 48 weeks (7). Furthermore, fewer patients discontinued efavirenz-based triple therapy than indinavir-based therapy because of adverse events. Adverse effects associated with efavirenz included a maculopapular rash and central nervous system disturbances (dizziness, vivid dreams, poor concentration, sleep disturbances), which generally occurred (but later resolved) within the first weeks of therapy. 

Indinavir has been compared with abacavir in a randomized equivalence trial in 562 patients who were also taking lamivudine and zidovudine (10). The only significant difference in adverse effects was that there was hyperbilirubinemia in 8% of those taking indinavir and 2% of those taking abacavir. It has been postulated that indinavir-induced hyperbilirubinemia is due to inhibition of bilirubin UDP glucuronyl transferase activity, since it is more common in individuals with Gilbert s syndrome (11). 

Since the basic problem in many such cases is probably crystalluria, it should be possible to treat it with rehydration, perhaps supplemented by brief interruption of therapy this has been the conclusion of a study in which the unwanted renal effects of indinavir were prominent (25). Of 74 individuals infected with HIV-1 and taking indinavir 2.4 g/day orally, 15 had indinavir-related urological adverse effects (19 episodes), most commonly dull flank pain and dysuria. Microhematuria occurred in 16 of the 19 episodes. Four patients had urinary tract distension on... 

Although circumoral paresthesia has been a common adverse effect of ritonavir, peripheral neuropathy has not been previously reported with HIV-1 protease inhibitors. There has been a report of painful neuropathy in two patients who took ritonavir and indinavir respectively (4). 

The combination of indinavir + ritonavir 400/400 mg bd plus two NRTIs has been studied in 93 patients in an open, uncontrolled, multicenter trial (7). Raised triglycerides (n = 78) and cholesterol (n = 63) were the commonest adverse effects, followed by nausea (n — 22) and circumoral paresthesia (n = 9). Withdrawal was required in four cases of nausea, four of lipodystrophy, one of diarrhea, and one of osteonecrosis. 

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