Table 2.
Important considerations for cART management in ICU patients
| Drug | Most common severe toxicities | Main drug–drug interactions to consider in the ICU | Alternatives for administration in the ICU | Dosage adjustment if renal failure |
|---|---|---|---|---|
| Nucleoside/nucleotide reverse transcriptase inhibitors | ||||
| Abacavir | Hypersensitivity syndromes in patients with HLA-B*5701 | – | Liquid formulation | No (avoid if end-stage renal failure) |
| Emtricitabine | Neutropenia | – | Liquid formulation, crushable pills | Yes |
| Lamivudine | Rash | – | Liquid formulation, crushable pills | Yes |
| Zidovudine | Lactic acidosis, myopathy, bone marrow toxicity, hepatitis | Rifamycins, valproic acid, fluconazole | Liquid formulation, crushable pills, IV formulation | Yes |
| Tenofovir | Nephrotoxicity (proximal tubular acidosis with Fanconi-like syndrome, acute renal failure), rash, hepatitis | – | Crushable pills | Yes |
| Nonnucleoside reverse transcriptase inhibitors | ||||
| Efavirenz | Hepatitis, rash | Rifamycins, voriconazole, posaconazole, phenytoin, phenobarbital, carbamazepine, calcium channel blockers, statins, warfarin, midazolam | Crushable pills | No |
| Etravirine | Bone marrow toxicity, hypersensitivity syndromes, hepatitis | Rifamycins, fluconazole, voriconazole, posaconazole, phenytoin, phenobarbital, carbamazepine, digoxin, amiodarone, warfarin, statins, clopidogrel, dexamethasone | Crushable pills | No |
| Nevirapine | Neutropenia, hypersensitivity syndromes, hepatitis | Rifampicin (switch to rifabutin), fluconazole, warfarin | Liquid formulation | Yes |
| Rilpivirine | Bone marrow toxicity, hepatitis, rash | Rifamycins, PPIs, anti-H2, phenytoin, phenobarbital, carbamazepine, dexamethasone | IV formulation | No |
| Integrase inhibitors | ||||
| Raltegravir | Rash | Rifampicin | Liquid formulation, crushable pills | No |
| Dolutegravir | Rash, hepatitis | Rifampicin, phenytoin, phenobarbital, carbamazepine, apixaban, metformin | Crushable pills | No |
| Protease inhibitors (all ritonavir-boosted) | ||||
| Atazanavir | Hyperbilirubinemia, renal lithiasis, QT prolongation | Rifamycins, voriconazole, PPIs, phenytoin, phenobarbital, carbamazepine, fentanyl, midazolam, calcium channel blockers, amiodarone, warfarin, statins | – | No |
| Darunavir | Rash, peripheral neuropathy | Rifamycins, voriconazole, fluconazole, posaconazole, phenytoin, phenobarbital, fentanyl, midazolam, calcium channel blockers, beta-blockers, amiodarone, digoxin, warfarin, apixaban, rivaroxaban, dabigatran, ticagrelor, metformin, statins, salmeterol | Liquid formulation | No |
| Fosamprenavir | Rash | Rifamycins, phenytoin, phenobarbital, fentanyl, midazolam, amiodarone, statins, warfarin | Liquid formulation | No |
| Lopinavir | QT prolongation, bone marrow toxicity, hypersensitivity syndromes, hepatitis | Rifamycins, voriconazole, phenytoin, phenobarbital, valproic acid, fentanyl, midazolam, calcium channel blockers, amiodarone, digoxin, warfarin, rivaroxaban, statins, salmeterol | Liquid formulation | No |
| Tipranavir | Hepatitis, rash | Rifamycins, voriconazole, phenytoin, phenobarbital, carbamazepine, fentanyl, midazolam, PPIs, amiodarone, digoxin, warfarin, statins | Liquid formulation | No |
| Fusion inhibitors | ||||
| Enfuvirtide | Myalgia, lung toxicity, peripheral neuropathy, pancreatitis, renal lithiasis | – | Subcutaneous formulation | No |
| CCR5 inhibitors | ||||
| Maraviroc | Anemia, rash | Rifamycins, phenytoin, phenobarbital, carbamazepine | Liquid formulation | Yes |
Based on Ref. [3] and information obtained from the following sources: http://www.hiv-druginteractions.org, https://liverpool-hiv-hep.s3.amazonaws.com/prescribing_resources/ pdfs/000/000/011/original/ARV_Swallowing_2018_Dec.pdf?1543916096, https://hivclinic.ca/main/drugs_extra_files/Crushing%20and%20Liquid%20ARV%20Formulations.pdf and http://www.eacsociety.org/files/2018_guidelines-9.1-english.pdf. All information refers to licensed use of products and is sourced from individual manufacturers’ Summary of Product Characteristics (emc.medicines.org.uk) and U.S. Prescribing Information. Note that tablet or capsule formulations pooling two or more antiretroviral drugs are not crushable/dissolvable (or available as liquid formulations), except dolutegravir/abacavir/lamivudine, emtricitabine/tenofovir disoproxil fumarate and lamivudine/zidovudine; however, individual components of most of combinations are available with such galenic presentations. Dose adjustment may be necessary in patients with renal or hepatic impairment (see the guidelines of the Centers for Disease Control and Prevention, the National Institutes of Health, and the Infectious Diseases Society of America for the use of antiretroviral agents in adults and adolescents with HIV) [98]
PPIs proton-pump inhibitors