Indinavir

Comparative studies

In a randomized comparison of ritonavir-boosted indinavir versus indinavir alone the two regimens resulted in similar efficacy [ ]. However, because of an increase in adverse reactions, drug-withdrawals were more frequent in the boosted indinavir arm (47/161 versus 20/162). The following adverse reactions were significantly more common in the boosted arm: nausea/vomiting, diarrhea, nephrolithiasis and hematuria, dry skin, ingrowing toenails, rash, and oral paresthesia.

In a randomized, open comparison of ritonavir-boosted saquinavir versus indinavir, adverse events were reported significantly more often in the indinavir/ritonavir arm [ ]. While there were no differences in hematological, renal, or hepatic toxicity (except increased bilirubin concentrations with indinavir), there were significantly higher lipid concentrations (total cholesterol, LDL cholesterol, and total triglycerides) in the indinavir arm. Adverse reactions (renal, dermatological, and gastrointestinal) were more frequent in the indinavir/ritonavir arm.

Cardiovascular

A hypertensive crisis caused a secondary reversible posterior leukoencephalopathy in a patient taking indinavir-containing antiretroviral therapy [ ].

• A 40-year-old man, who had taken stavudine 30 mg bd, lamivudine 150 mg bd, and indinavir 800 mg qds, developed an occipital headache, nausea, and vomiting. His blood pressure was 220/140 mmHg and he had bilateral papilledema. His blood pressure was controlled and his symptoms disappeared. An MRI scan of the brain showed lesions in the periventricular white matter; the nuclei semiovale and occipital asta were most severely affected. Indinavir was withdrawn and replaced by nelfinavir; his blood pressure returned to normal and the MRI white matter lesions disappeared.

In a retrospective analysis of 198 normotensive patients in a protease inhibitor comparison study, 30% of those who took indinavir developed stage I or worse hypertension, compared with none of the patients who took nelfinavir, ritonavir, or saquinavir [ ].

Respiratory

Shock and respiratory failure have been attributed to indinavir [ ].

• A 36-year-old HIV-positive man had started to take zidovudine and zalcitabine 9 months earlier together with co-trimoxazole as primary prophylaxis against Pneumocystis jirovecii , but switched to indinavir, stavudine, and lamivudine. Two hours after the first dose of indinavir he developed a high fever, generalized myalgia, and malaise and started to vomit. After the second dose he developed shock and cyanosis. A chest X-ray was compatible with adult respiratory distress syndrome. All cultures were negative for bacterial, viral, mycobacterial, and fungal pathogens. He recovered in 6 days and antiretroviral treatment without indinavir was reintroduced without recurrent problems.

The authors suggested that the severe shock and respiratory distress syndrome had been due to an idiosyncratic reaction to indinavir.

Nervous system

There has been a report of painful neuropathy in two patients who took ritonavir and indinavir respectively [ ].

For a case of paraparesis due to epidural lipomatosis, attributed to indinavir, see below under Metabolic.

Metabolism

Hematologic

Indinavir has been associated with severe hemolytic anemia [ ].

• A 32-year-old Caucasian, who was taking lamivudine, stavudine, and indinavir for HIV infection, presented with pallor following a period of fatigue and headache [ ]. His hemoglobin was 8.2 g/dl and there were no clinical findings to suggest bleeding. The reticulocyte count was 3.5% and a direct Coombs’ test was negative. A diagnosis of hemolytic anemia secondary to indinavir was made, the indinavir was stopped, and he was transfused with concentrated erythrocytes. The other antiretroviral drugs were continued, saquinavir was added, and a normal hemoglobin concentration was maintained.

Indinavir has been associated with thrombocytopenia [ ].

• A man suddenly developed severe thrombocytopenia while taking stavudine + lamivudine + indinavir [ ]. After withdrawal and treatment with glucocorticoids and immunoglobulin, the platelet count recovered and he was treated with stavudine + didanosine + nevirapine. Six months later, after re-exposure to the initial combination, thrombocytopenia immediately occurred and spontaneously recovered after replacing indinavir with efavirenz.

Gastrointestinal

Of 30 patients taking ritonavir + indinavir 400/100 mg in an open pilot study in Mali one reported nausea [ ].

In a prospective study of 70 sub-Saharan African patients taking indinavir, 22 had severe vomiting [ ].