ritonavir and Diarrhea

ModraDoc006 is a novel docetaxel tablet formulation that is co-administrated with the cytochrome P450 3A4 and P-glycoprotein inhibitor ritonavir (r): ModraDoc006/r.. This study evaluated the effect of food consumed prior to administration of ModraDoc006/r on the pharmacokinetics of docetaxel and ritonavir.. Patients with advanced solid tumours were enrolled in this randomized crossover study to receive ModraDoc006/r in a fasted state in week 1 and after a standardized high-fat meal in week 2 and vice versa. Pharmacokinetic sampling was conducted until 48 h after both study drug administrations. Docetaxel and ritonavir plasma concentrations were determined using liquid chromatography with tandem mass spectrometry. Safety was evaluated with the Common Terminology Criteria for Adverse Events, version 4.03.. In total, 16 patients completed the food-effect study. The geometric mean ratio (GMR) for the docetaxel area under the plasma concentration-time curve (AUC). The docetaxel and ritonavir exposure were not bioequivalent, as consumption of a high-fat meal prior to administration of ModraDoc006/r resulted in a slightly higher docetaxel exposure and lower ritonavir C. NCT03147378, date of registration: May 10 2017.

Topics: Administration, Oral; Aged; Antineoplastic Agents; Area Under Curve; Cross-Over Studies; Cytochrome P-450 CYP3A Inhibitors; Diarrhea; Diet, High-Fat; Docetaxel; Drug Combinations; Fasting; Fatigue; Female; Food-Drug Interactions; Humans; Hypokalemia; Male; Middle Aged; Neoplasms; Ritonavir; Tablets; Therapeutic Equivalency

Virologic and safety outcomes of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (OBV/PTV/r ± DSV ± RBV) therapy have shown high sustained virologic response (SVR) rates and good tolerability in most patient populations in pre-registration studies.. To confirm these clinical trial findings in the treatment of genotype 1 and 4 hepatitis C under real-world conditions.. Patients enrolled for treatment with OBV/PTV/r ± DSV ± RBV based on therapeutic guidelines were included, and the regimen was administered according to product characteristics. Clinical and laboratory data, including virologic response, were collected at baseline, end of treatment (EOT) and 12 weeks after EOT.. A total of 209 patients with chronic hepatitis C were enrolled, most were genotype 1b-infected (84.2%) and 119 (56.9%) had liver cirrhosis. Among these, 150 (71.7%) had failed previous anti-viral therapies and 84 (40.2%) were null-responders. At 12 weeks after EOT, SVR was achieved by 207 (99.0%) patients, ranging from 96.4% to 100.0% across subgroups. All Child-Pugh B and post-orthotopic liver transplantation patients achieved SVR. Adverse events occurred in 151 (72.2%) patients and were mostly mild and associated with the use of RBV. Serious adverse events, including hepatic decompensation, renal insufficiency, anaemia, hepatotoxicity and diarrhoea, were reported in eight (3.8%) patients. In five (2.4%) patients, adverse events led to treatment discontinuation. On-treatment decompensation was experienced by seven (3.3%) patients.. The results of our study confirm previous findings. They demonstrate excellent effectiveness and a good safety profile of OBV/PTV/r± DSV±RBV in HCV genotype 1-infected patients treated in the real-world setting.

Topics: 2-Naphthylamine; Adult; Anilides; Antiviral Agents; Carbamates; Cyclopropanes; Diarrhea; Drug Therapy, Combination; Hepacivirus; Hepatitis C, Chronic; Humans; Lactams, Macrocyclic; Liver Cirrhosis; Macrocyclic Compounds; Male; Middle Aged; Proline; Ribavirin; Ritonavir; Sulfonamides; Treatment Outcome; Uracil; Valine

Elvitegravir is a once daily inhibitor of HIV-1 integrase boosted by ritonavir. We aimed to compare the efficacy and safety of elvitegravir with raltegravir, another HIV-1 integrase inhibitor, in patients in whom previous antiretroviral treatment failed.. We conducted a randomised, double-blind, double-dummy, phase 3 study at 234 sites in 13 countries. Eligible patients had plasma HIV RNA of 1000 copies per mL or greater, any CD4 cell count, and resistance to or 6 months' experience with at least two classes of antiretroviral drugs. They received an open-label background regimen of a fully active, ritonavir-boosted protease inhibitor and a second agent. We randomly allocated patients (1:1) by computer with a block size of four to receive either elvitegravir 150 mg once daily (n=361; 85 mg dose if given with atazanavir, or lopinavir with ritonavir) or raltegravir 400 mg twice daily (n=363). Placebo tablets were given to mask the difference in daily dosing. The primary endpoint was achievement and maintenance of virological response (HIV RNA <50 copies per mL) through week 48. Non-inferiority was prespecified with a margin of 10%. We did a modified intention-to-treat analysis. This study is registered with ClinicalTrials.gov, number NCT00708162.. Ten patients allocated elvitegravir and 12 assigned raltegravir were excluded from the analysis (either for protocol violations or because they did not receive treatment). 207 (59%) of 351 patients allocated elvitegravir achieved virological response compared with 203 (58%) of 351 assigned raltegravir (treatment difference 1·1%, 95% CI -6·0 to 8·2), meeting the criterion for non-inferiority (p=0·001). Three patients allocated elvitegravir had serious adverse events related to study drugs compared with seven assigned raltegravir; two and eight patients died, respectively. More individuals assigned elvitegravir reported diarrhoea up to week 48 (p=0·023), and more patients assigned raltegravir had grade 3 or 4 rises in alanine aminotransferase (p=0·020) or aspartate aminotransferase (p=0·009).. Elvitegravir used in combination with a ritonavir-boosted protease inhibitor in treatment-experienced patients has similar efficacy and safety to raltegravir. Since elvitegravir can be given once a day compared with twice a day for raltegravir, elvitegravir might improve patients' adherence.. Gilead Sciences.

Topics: Adult; Alanine Transaminase; Anti-Retroviral Agents; Aspartate Aminotransferases; Atazanavir Sulfate; CD4 Lymphocyte Count; Diarrhea; Double-Blind Method; Drug Therapy, Combination; Female; HIV Infections; HIV Integrase Inhibitors; HIV Protease Inhibitors; HIV-1; Humans; Lopinavir; Male; Middle Aged; Oligopeptides; Pyridines; Pyrrolidinones; Quinolones; Raltegravir Potassium; Ritonavir; RNA, Viral; Treatment Outcome; Viral Load

Sustained viral suppression with antiretroviral therapy improves clinical outcomes for HIV-infected individuals. Study M05-730 evaluated the long-term antiviral activity, safety, tolerability, emergence of resistance, and compliance with once-daily (QD) versus twice-daily (BID) lopinavir/ritonavir (LPV/r) combination therapy in treatment-naïve, HIV-1-infected subjects through 96 weeks. Antiretroviral-naïve subjects with HIV-1 RNA levels >1000 copies/ml were randomized to LPV/r QD (N = 333) or BID (N = 331) with tenofovir DF and emtricitabine. Through 96 weeks, 77 subjects from each group discontinued prematurely; adverse or HIV-related events contributed to discontinuation of 36 subjects overall, with no significant differences between treatment groups. At 96 weeks, 216 QD subjects (64.9%) and 229 BID subjects (69.2%) had HIV-1 RNA <50 copies/ml (p = 0.249) by intent-to-treat analysis. Evaluation of the time to virologic failure indicated that 85.0% and 80.7% of QD and BID subjects, respectively, maintained virologic suppression through 96 weeks (p = 0.638). QD subjects demonstrated greater adherence levels. There were no significant differences in virologic response when subjects were analyzed according to baseline disease state. Emergence of postbaseline resistance mutations occurred at similar low rates in each dosing group. Diarrhea was the most common moderate-to-severe drug-related adverse event reported; the most common Grade 3+ laboratory abnormalities were elevations of total cholesterol and triglycerides, occurring with similar incidence regardless of LPV/r dosing frequency. QD dosing of LPV/r was associated with similar durability of viral suppression and low rates of genotypic resistance and treatment-limiting adverse events as compared with BID dosing in treatment-naïve subjects through 96 weeks of treatment.

Topics: Adenine; Anti-HIV Agents; Deoxycytidine; Diarrhea; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Emtricitabine; HIV Infections; HIV-1; Humans; Lopinavir; Organophosphonates; Pyrimidinones; Ritonavir; Tenofovir

SCH532706 is a novel small molecule chemokine receptor-5 (CCRS) antagonist with high in vitro potency (mean 90% inhibitory concentration [IC90] 0.15-7.0 nM) against diverse HIV type-1 (HIV-1) isolates.. A single arm study was undertaken to examine the safety, antiviral activity and pharmacokinetics (PK) of 10 days of SCH532706 coadministered with ritonavir (RTV). The trial enrolled formerly treated (off therapy >3 months) or untreated HIV-1-infected patients.. The study enrolled 12 males with CD4+ T-cell count >100 cells/microl. Median (range) CD4+ T-cell count was 327 cells/microl (117-1008), HIV-1-RNA was 4.6 log10 copies/ml (3.8-5.5) and patients had phenotypically confirmed R5-tropic HIV-1 only. Mean (95% confidence interval) changes from baseline plasma HIV-1-RNA at days 10 and 15 (4 days off SCH532706) were -1.31 log10 copies/ml (-1.6 - -1.0) and -1.62 log10 copies/ml (-2.0 - -1.3), respectively. Day 10 median (range) time to maximum plasma concentration, mean (+/-SD) effective half-life and mean (+/-SD) trough concentration were 1.4 h (1.0-4.0), 39.4 h (+/-14.5) and 178 ng/ml (+/-34), respectively. All virus isolates remained R5-tropic pre-study, on study and at study end. There were no laboratory or QTc interval changes reportable as adverse events. In total, 11 patients reported > or =1 treatment emergent adverse event, most commonly gastrointestinal upset. One serious adverse event, pericarditis (grade 2), occurred 13 days after drug administration. It was considered to be possibly related to study drug.. Overall, SCH532706 with RTV was safe, generally well tolerated and active against HIV-1 over 10 days of dosing. In this setting, SCH532706 trough concentrations exceed the mean in vitro IC90 (1.1 ng/ml) by >30-fold (after correction for 80% plasma protein binding) and provide a PK rationale for the observed efficacy.

Topics: Abdominal Pain; Administration, Oral; Adult; CCR5 Receptor Antagonists; CD4 Lymphocyte Count; Diarrhea; Drug Administration Schedule; Drug Therapy, Combination; HIV Fusion Inhibitors; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Male; Middle Aged; Pericarditis; Ritonavir; Viral Load

Antiretroviral-naive HIV-1-infected volunteers received zidovudine/lamivudine plus either lopinavir/ritonavir (n=104) or efavirenz (n=51). Lopinavir/ritonavir-treated subjects demonstrating 3 consecutive monthly HIV-1 RNA levels <50 copies/mL started lopinavir/ritonavir monotherapy. In previous-failure=failure analysis, 48% (lopinavir/ritonavir) and 61% (efavirenz) maintained HIV-1 RNA at <50 copies/mL through week 96, (P= .17; 95% confidence interval [CI] for the difference, -29% to 4%); in noncompletion=failure analysis, 60% (lopinavir/ritonavir) and 63% (efavirenz) maintained HIV-1 RNA at <50 copies/mL at week 96 (P= .73; 95% CI for the difference, -19% to 13%). Significant sparing of peripheral lipoatrophy was noted in the lopinavir/ritonavir simplification strategy. This study has provided important information for future studies using treatment simplified to lopinavir/ritonavir monotherapy.

Topics: Acquired Immunodeficiency Syndrome; Alkynes; Anti-HIV Agents; Benzoxazines; Cyclopropanes; Diarrhea; Drug Therapy, Combination; Glucose Tolerance Test; HIV Protease Inhibitors; Humans; Lopinavir; Nausea; Pyrimidinones; Ritonavir; RNA, Viral; Time Factors; Treatment Outcome; Viral Load

Recent data indicate that fosamprenavir/ritonavir as part of an initial antiretroviral regimen in HIV-1-infected patients is associated with favourable efficacy and tolerability and in the KLEAN study (kaletra versus lexiva with epivir and abacavir in antiretroviral-naive patients) it was found to be non-inferior to lopinavir/ritonavir in association with abacavir/lamivudine. In our open-label, observational study conducted in 82 therapy-nasmall yi, Ukrainianve HIV-1-infected patients followed-up for 18 months, virological and immunological efficacy was comparable in subjects receiving a fosamprenavir/ritonavir-based and a lopinavir/ritonavir-based treatment (proportions of patients with HIV RNA <50 copies/mL at month 18 were 76.9% and 74.4%, respectively, when discontinuations were counted as failures). At the same time, frequency of treatment discontinuations and adverse events were similar in both groups, whereas incidence of diarrhoea and hypertriglyceridaemia was significantly higher in lopinavir-treated patients than in fosamprenavir-treated ones (53.5% vs. 25.6% and 69.8% vs. 43.6%, respectively; P < 0.01). In subjects with virological failure, no viral protease resistance mutations were detected by genotype analysis.

Topics: Adult; Anti-HIV Agents; Carbamates; Diarrhea; Drug Administration Schedule; Drug Resistance, Viral; Drug Therapy, Combination; Female; Furans; HIV Infections; HIV Protease; HIV-1; Humans; Hypertriglyceridemia; Lopinavir; Male; Middle Aged; Organophosphates; Pyrimidinones; Reverse Transcriptase Inhibitors; Ritonavir; Sulfonamides; Treatment Failure; Treatment Outcome

To evaluate the efficacy, safety and tolerability of ritonavir-boosted tipranavir (TPV/r) in HIV-1-infected pediatric patients.. Open-label randomized pediatric trial (1182.14/PACTG1051) comparing TPV/r at two doses including an optimized background regimen.. HIV-1-infected patients (2-18 years) with plasma viral load 1500 copies/ml or more were randomized to TPV/r 290/115 or 375/150 mg/m twice-daily oral solution and optimized background regimen. Week 48 efficacy, safety and tolerability results were evaluated.. Children (n = 115; 97% treatment experienced) were randomized to low or high dose therapy. Eighty-eight remained on-treatment through 48 weeks. Baseline characteristics were similar between dose groups. At study entry, half of the HIV-1 isolates were resistant to all protease inhibitors. At 48 weeks, 39.7% low-dose and 45.6% high-dose TPV/r recipients had viral load less than 400 copies/ml and 34.5 and 35.1%, respectively, achieved viral load less than 50 copies/ml. Vomiting, cough and diarrhea were the most frequent adverse events. Grade 3 alanine aminotransferase elevations were observed in 6.3% of patients. No grade 4 alanine aminotransferase or grade 3/4 aspartate aminotransferase elevations were reported.. TPV/r achieved a sustained virologic response, showed a good safety profile and was well tolerated at either dose. In pediatric patients with high baseline resistance profiles, high-dose TPV/r tended to demonstrate a better sustained response.

Topics: Adolescent; Alanine Transaminase; Anti-HIV Agents; Biomarkers; Blood Coagulation Disorders; Child; Child, Preschool; Diarrhea; Drug Administration Schedule; Drug Therapy, Combination; Female; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Logistic Models; Male; Pyridines; Pyrones; Ritonavir; Sulfonamides; Treatment Outcome; Viral Load; Vomiting

Lopinavir/ritonavir (LPV/r) has been the gold standard in first line rescue treatment for many years. No other boosted protease inhibitor (PI/r) has managed to demonstrate that it is superior to LPV/r. In this regard, the TITAN study compared the efficacy and safety of darunavir (DRV/r) in 595 patients, at a dose of 600/100 mg two times a day against the normal LPV/r dose, combined with at least 2 other optimised antiretroviral drugs. The efficacy of the treatment at 48 weeks (VL<400 copies/mL) was significantly higher in the DRV/r goup compared to the LPV/r group, both in the analysis by protocol (77% vs. 68%), the non-inferiority of DRV/r being demonstrated (estimated difference +9%, 95% CI 2-16), and by intention to treat (77% vs. 67%), the superiority of DRV/r being demonstrated (estimated difference 10%, 95% CI 2-17%). The incidence of diarrhoea and increase in triglycerides was higher in the LPV/r group. The differences in efficacy of both treatments in favour of DRV/r started to be seen from a basal primary mutation in the protease, with these differences increasing as the number of these mutations increased. In patients with virological failure, DRV/r protected the protease and reverse transcriptase against mutations, thus preserving future therapeutic options. We have some theoretical and clinical data available that enables us to consider the possibility of administering DRV/r once a day in some patients with a few mutations in the protease and in those where this dosing regime is considered important. With the results of the TITAN study, DRV/r must be considered the new gold standard in first line rescue, at least in those patients with a primary mutation in the protease.

Topics: Adult; Anti-HIV Agents; CD4 Lymphocyte Count; Chemical and Drug Induced Liver Injury; Clinical Trials as Topic; Darunavir; Diarrhea; Drug Resistance, Multiple, Viral; Drug Therapy, Combination; Female; HIV; HIV Infections; HIV Protease Inhibitors; Humans; Hyperlipidemias; Lopinavir; Male; Prognosis; Pyrimidinones; Reverse Transcriptase Inhibitors; Ritonavir; Salvage Therapy; Sulfonamides

Given the limited treatment options for patients with high-level resistance, antiretroviral (ARV) regimens based on concomitant use of 2 ritonavir (RTV)-boosted protease inhibitors (PIs) were considered a therapeutic option.. Boehringer Ingelheim (BI) study 1182.51 examined the pharmacokinetic profile, safety, and efficacy of RTV-boosted tipranavir (TPV/r), alone and in combination with comparator PIs (CPIs) in 315 triple-class-experienced, HIV-infected patients.. Two weeks after single PI therapy, the addition of TPV/r reduced plasma trough levels 52%, 80%, and 56% for lopinavir (LPV), saquinavir (SQV), and amprenavir (APV) recipients, respectively. After 2 weeks, a TPV/r-only regimen reduced HIV viral load (VL) by a median of 1.06 log(10) copies/mL. VL reductions at 2 weeks between single-boosted CPIs were difficult to compare, because the numbers of patients maintaining their previous failing PI after randomization were different. At week 4, patients initiating treatment with TPV-containing regimens sustained VL reduction (median decrease of 1.27 log(10) copies/mL). Patients adding TPV to regimens at week 2 achieved median reductions from a baseline of 1.19 log(10), 0.96 log(10), and 1.12 log(10) copies/mL at week 4 in dual-boosted LPV, SQV, and APV groups, respectively. At 24 weeks, VL reductions (median: -0.24 to -0.47 log(10) copies/mL) were comparable between treatment groups.. The efficacy of a dual PI regimen depended on the presence of TPV, with additional recycled CPIs having limited activity, even in drug-resistant patient populations with plasma trough concentrations regarded as likely to be adequate in this study. No clear guidelines exist about ARV plasma trough concentrations in treatment-experienced patients, however.

Topics: Adolescent; Adult; Anti-HIV Agents; Area Under Curve; Diarrhea; Drug Therapy, Combination; Fatigue; Female; HIV Infections; HIV Protease Inhibitors; Humans; Male; Metabolic Clearance Rate; Middle Aged; Nausea; Pyridines; Pyrones; Ritonavir; Sulfonamides; Treatment Outcome

Brecanavir (BCV, 640385) is a novel, potent protease inhibitor (PI) with low nanomolar 50% inhibitory concentrations against PI-resistant human immunodeficiency virus (HIV) in vitro. This phase I, double-blind, randomized, placebo-controlled, two-part single-dose study (first time with humans) was conducted to determine the safety, tolerability, and pharmacokinetics of BCV administered at 10 mg/ml in a tocopherol-polyethylene glycol succinate-polyethylene glycol 400-ethanol 50:40:10 solution. In part 1 of the study, single oral doses of BCV ranged from 25 mg to 800 mg. In part 2, single oral doses of BCV ranged from 10 mg to 300 mg and were coadministered with 100-mg oral ritonavir (RTV) soft gel capsules. Single doses of BCV and BCV/RTV were generally well tolerated. There were no severe adverse events (SAEs), and no subject was withdrawn due to BCV. The most commonly reported drug-related AEs during both parts of the study combined were gastrointestinal disturbances (similar to placebo) and headache. BCV was readily absorbed following oral administration with mean times to maximum concentration from >1 h to 2.5 h in part 1 and from 1.5 h to 3 h in part 2. Administration of BCV without RTV resulted in BCV exposures predicted to be insufficient to inhibit PI-resistant virus based on in vitro data. Coadministration of 300 mg BCV with 100 mg RTV, however, significantly increased the plasma BCV area under the concentration-time curve and maximum concentration 26-fold and 11-fold, respectively, achieving BCV concentrations predicted to inhibit PI-resistant HIV.

Topics: Administration, Oral; Adult; Area Under Curve; Benzodioxoles; Capsules; Carbamates; Diarrhea; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Flatulence; Gels; Half-Life; Headache; HIV Protease Inhibitors; Humans; Male; Middle Aged; Nausea; Ritonavir

To evaluate the safety and pharmacokinetic interaction between amprenavir (APV) and ritonavir (RTV).. Three open-label, randomized, two-sequence, multiple-dose studies having the same design (7 days of APV or RTV alone followed by 7 days of both drugs together) used 450 or 900 mg APV with 100 or 300 mg RTV every 12 h with pharmacokinetic assessments on days 7 and 14. Safety was monitored as clinical adverse events (AEs) and laboratory abnormalities.. Relative to APV alone, RTV co-administration resulted in a 3.3- to 4-fold and 10.84 to 14.25-fold increase in the geometric least-square (GLS) mean area under the plasma concentration--time curve (AUC(tau,ss)) and minimum concentration (C(min,ss)), respectively. APV 900 mg with RTV 100 mg resulted in a 2.09-fold and 6.85-fold increase in the GLS mean AUC(tau,ss) and C(min,ss), respectively. On day 14, the geometric mean (95% confidence interval) for 450 mg APV AUC(tau,ss) (micro x h/mL) was 23.49 (19.32--28.57) with 300 mg RTV and 35.42 (30.46--44.42) with 100 microg RTV, and for the 900 mg APV with 100 mg RTV 47.11 (39.47--61.24). The 450 mg APV C(min,ss) (microg/ml) were 1.32 (1.05--1.67) and 2.01 (1.70--2.61), and 2.47 (2.08--3.32) for 900 mg APV. The most common AEs were mild and included diarrhea, nausea/vomiting, oral parasthesias, and rash. The triglyceride and cholesterol increased significantly from RTV exposure.. Adding RTV to APV resulted in clinically and statistically significant increases in APV AUC and C(min) with variable effects on maximum concentration. The two RTV doses had similar effects on APV but AEs were more frequent with 300 mg RTV.

Topics: Administration, Oral; Adult; Body Mass Index; Carbamates; Diarrhea; Dose-Response Relationship, Drug; Drug Therapy, Combination; Exanthema; Female; Furans; HIV Protease Inhibitors; HIV Seronegativity; Humans; Male; Middle Aged; Nausea; Ritonavir; Statistics, Nonparametric; Sulfonamides

This study aimed to characterize adverse drug reactions (ADRs) to hydroxychloroquine in the setting of COVID-19, occurring in Italy in the period March to May 2020. The analysis of the combination therapy with azithromycin or/and lopinavir/ritonavir as well as a comparison with ADRs reported throughout 2019 was performed. ADRs collected by the Italian National Network of Pharmacovigilance were analyzed for their incidence, seriousness, outcome, coadministered drugs, and Medical Dictionary for Regulatory Activities classification. A total of 306 reports were gathered for the quarter of 2020: 54% nonserious and 46% serious, and half of the latter required either the hospitalization or its prolongation. However, most of them were either completely recovered (26%) or in the process of recovery (45%), except for 9 fatal cases. Throughout 2019, 38 reports were collected, 53% nonserious and 47% serious, but no deaths had been reported. Diarrhea, prolonged QT interval, and hypertransaminasemia were the most frequently ADRs reported in 2020, significantly higher than 2019 and specific for COVID-19 subjects treated with hydroxychloroquine. The logistic regression analyses demonstrated that the likelihood of serious ADRs, QT prolongation, and diarrhea significantly increased with hydroxychloroquine dosage. Coadministration of lopinavir/ritonavir and hydroxychloroquine showed a positive correlation with diarrhea and hypertransaminasemia and a negative relationship with the ADR seriousness. The combination therapy with azithromycin was another independent predictor of a serious ADR. Off-label use of hydroxychloroquine for COVID-19, alone or in combination regimens, was associated with increased incidence and/or seriousness of specific ADRs in patients with additional risk factors caused by the infection.

Topics: Azithromycin; COVID-19 Drug Treatment; Diarrhea; Drug-Related Side Effects and Adverse Reactions; Humans; Hydroxychloroquine; Long QT Syndrome; Lopinavir; Off-Label Use; Pharmacovigilance; Ritonavir

Since December 2019, severe acute respiratory syndrome coronavirus 2 infection has spread worldwide. We all are concerned about immunocompromised children, especially hematologic and oncologic pediatric patients. We want to share our experience with 2 pediatric cancer patients with severe acute respiratory syndrome coronavirus 2 infection. Both presented mild disease and good outcome. No respiratory symptoms were identified, but both developed diarrhea, one probably secondary to lopinavir/ritonavir. Pediatric cancer patients may have milder disease than adults, but larger studies are needed to make conclusions.

Topics: Adolescent; Betacoronavirus; Child; Child, Preschool; Coronavirus Infections; COVID-19; Diarrhea; Female; Humans; Kidney Neoplasms; Lopinavir; Pandemics; Pneumonia, Viral; Ritonavir; Sarcoma, Ewing; SARS-CoV-2; Spain; Wilms Tumor

In late 2019, a new coronavirus-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-was discovered in Wuhan, China, and the World Health Organization later declared coronavirus disease 2019 (COVID-19) a pandemic. Numerous drugs have been repurposed and investigated for therapeutic effectiveness in the disease, including those from "Solidarity," an international clinical trial (azithromycin, chloroquine, hydroxychloroquine, the fixed combination lopinavir/ritonavir, and remdesivir).. Our objective was to evaluate adverse drug reaction (ADR) reporting for drugs when used in the treatment of COVID-19 compared with use for other indications, specifically focussing on sex differences.. We extracted reports on COVID-19-specific treatments from the global ADR database, VigiBase, using an algorithm developed to identify reports that listed COVID-19 as the indication. The Solidarity trial drugs were included, as were any drugs reported ≥ 100 times. We performed a descriptive comparison of reports for the same drugs used in non-COVID-19 indications. The data lock point date was 7 June 2020.. In total, 2573 reports were identified for drugs used in the treatment of COVID-19. In order of frequency, the most reported ADRs were electrocardiogram QT-prolonged, diarrhoea, nausea, hepatitis, and vomiting in males and diarrhoea, electrocardiogram QT-prolonged, nausea, vomiting, and upper abdominal pain in females. Other hepatic and kidney-related events were included in the top ten ADRs in males, whereas no hepatic or renal terms were reported for females. COVID-19-related reporting patterns differed from non-pandemic reporting for these drugs.. Review of a global database of suspected ADR reports revealed sex differences in the reporting patterns for drugs used in the treatment of COVID-19. Patterns of ADR sex differences need further elucidation.

Topics: Abdominal Pain; Adenosine Monophosphate; Alanine; Antibodies, Monoclonal, Humanized; Antiviral Agents; Azithromycin; Chemical and Drug Induced Liver Injury; Chloroquine; COVID-19 Drug Treatment; Databases, Pharmaceutical; Diarrhea; Drug Combinations; Drug Eruptions; Drug Repositioning; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Hydroxychloroquine; Long QT Syndrome; Lopinavir; Male; Nausea; Oseltamivir; Ritonavir; Sex Distribution; Sex Factors; Vomiting

Topics: Acute Kidney Injury; Adenine; Aged, 80 and over; Anti-HIV Agents; Biopsy; CD4 Lymphocyte Count; Diagnosis, Differential; Diarrhea; HIV Infections; Humans; Hypertension; Immunologic Tests; Kidney; Kidney Function Tests; Male; Monitoring, Physiologic; Organophosphonates; Ritonavir; Tenofovir; Treatment Outcome; Viral Load; Withholding Treatment

To evaluate the drug interaction between fosamprenavir (FPV) and esomeprazole (ESO) after repeated doses in healthy adults.. Subjects received ESO 20 mg once daily (qd) for 7 days followed by either ESO 20 mg qd + FPV 1400 mg twice daily (bid) or ESO 20 mg qd + FPV 700 mg bid + ritonavir (RTV) 100 mg bid for 14 days in arms 1 and 2, respectively. After a 21- to 28-day washout, subjects received either FPV 1400 mg bid for 14 days (arm 1) or FPV 700 mg bid + RTV 100 mg bid for 14 days (arm 2). Pharmacokinetic sampling was conducted on the last day of each treatment.. Simultaneous coadministration of ESO 20 mg qd with either FPV 1400 mg bid or FPV 700 mg bid + RTV 100 mg bid had no effect on steady-state amprenavir pharmacokinetics. The only effect on plasma ESO exposure was a 55% increase in area under the plasma concentration-time curve during a dosing interval, tau[AUC0-tau], after coadministration of ESO 20 mg qd with FPV 1400 mg bid.. FPV 1400 mg bid or FPV 700 mg bid + RTV 100 mg bid may be coadministered simultaneously with ESO without dose adjustment. However, the impact of staggered administration of proton pump inhibitors (PPI) on plasma amprenavir exposure is unknown at present.

Topics: Administration, Oral; Adolescent; Adult; Carbamates; Diarrhea; Drug Administration Schedule; Drug Combinations; Esomeprazole; Female; Furans; Headache; Humans; Male; Middle Aged; Nausea; Organophosphates; Ritonavir; Sulfonamides

To determine and compare rates of diarrhea in patients receiving an antiretroviral regimen containing lopinavir-ritonavir versus nelfinavir and in patients who received these drugs sequentially.. Retrospective cohort analysis.. Hospital-based human immunodeficiency virus (HIV) clinic.. Four hundred one participants in the HIV Atlanta VA Cohort Study who were prescribed lopinavir-ritonavir or nelfinavir from 1996-2002.. Chart review identified episodes of diarrhea that potentially were associated with an antiretroviral agent. Data collected included antidiarrheal agents dispensed, baseline viral load and CD4+ cell counts, demographic variables, and previous therapy Diarrhea associated with an antiretroviral regimen occurred in 175 (49%) of 354 patients receiving nelfinavir and 17 (17%) of 99 patients receiving lopinavir-ritonavir (p < 0.001). Treatment for the diarrhea occurred in 118 (33%) of 354 patients receiving nelfinavir and 9 (9%) of 99 receiving lopinavir-ritonavir (p < 0.001). Patients in the lopinavir-ritonavir group were more likely to have received highly active antiretroviral therapy and azithromycin than patients receiving nelfinavir, and they had lower baseline CD4+ cell counts (p < or = 0.01 for each comparison). The average number of months/person-year of diarrhea treatment was 2.0 for the nelfinavir group and 0.13 for the lopinavir-ritonavir group. Of the 10 antiretroviral-naive patients who received lopinavir-ritonavir, none needed treatment for diarrhea, whereas 78 (36%) of 217 antiretroviral-naive patients who received nelfinavir required treatment for diarrhea. Of the 52 patients who had been taking nelfinavir and were switched to lopinavir-ritonavir, they were more likely to start antidiarrheal treatment while taking nelfinavir (14 [27%]) than while receiving lopinavir-ritonavir (3 [6%]) (p = 0.004).. Patients receiving lopinavir-ritonavir were significantly less likely to have diarrhea or to require treatment for diarrhea than patients receiving nelfinavir. The same results occurred when the drugs were given to the same patients sequentially (nelfinavir followed by lopinavir-ritonavir). The diarrhea associated with lopinavir-ritonavir was less frequent, less severe, and shorter in duration than diarrhea associated with nelfinavir.

Topics: Adult; Anti-Retroviral Agents; Antidiarrheals; Antiretroviral Therapy, Highly Active; Cohort Studies; Diarrhea; Georgia; HIV Infections; Humans; Incidence; Lopinavir; Middle Aged; Nelfinavir; Pyrimidinones; Retrospective Studies; Ritonavir; United States; United States Department of Veterans Affairs

Topics: Acquired Immunodeficiency Syndrome; Colon; Diarrhea; HIV Protease Inhibitors; HT29 Cells; Humans; Indinavir; Intestinal Absorption; Intestinal Mucosa; Nelfinavir; Ritonavir; Saquinavir

A retrospective study was performed to determine whether twice-daily ritonavir 400 mg plus twice-daily saquinavir 400 mg (ritonavir 400/saquinavir 400) was better tolerated than ritonavir 600 mg twice daily (ritonavir 600). A secondary objective was to determine whether the rate of discontinuation due to therapeutic failure differed between the two ritonavir regimens.. The study was a retrospective chart review. Data collected included ritonavir dose; length of ritonavir therapy; reason for discontinuation; HIV-1 RNA prior to and at discontinuation of ritonavir therapy; CD4+ count; and antiretroviral therapy prior to, concomitant with, and initiated after ritonavir therapy.. Patient charts were reviewed in a university teaching hospital clinic.. Patients were identified through a search of the pharmacy database from December 18, 1995, to December 18, 1997. Patients were > 18 years old, but not restricted by gender or race.. The main outcome measures were frequency of discontinuation of ritonavir due to intolerance or due to lack of therapeutic efficacy.. The search identified 116 patients, including 57 patients taking ritonavir 400/saquinavir 400 and 54 patients taking ritonavir 600. Five patients on other ritonavir regimens were excluded. Significantly fewer patients receiving ritonavir 400/saquinavir 400 (14%) discontinued ritonavir due to intolerance compared with ritonavir 600 (37%; p = 0.002). Discontinuations due to therapeutic failure were not significantly different: 8.8% for ritonavir 400/saquinavir 400 and 7.4% for ritonavir 600, despite the fact that ritonavir/saquinavir therapy followed another protease inhibitor in 41 patients (73.2%) compared with 12 patients (24.5%) for ritonavir 600 (p = 0.001).. Ritonavir 400/saquinavir 400 is better tolerated than ritonavir 600.

Topics: Adult; Anti-HIV Agents; Diarrhea; Dose-Response Relationship, Drug; Drug Evaluation; Drug Therapy; Drug Therapy, Combination; Female; Gastrointestinal Diseases; HIV Infections; Humans; Male; Middle Aged; Nausea; Protease Inhibitors; Retrospective Studies; Ritonavir; Saquinavir; Treatment Outcome; Vomiting

Topics: AIDS-Related Opportunistic Infections; Animals; Anti-HIV Agents; Diarrhea; Follow-Up Studies; HIV Protease Inhibitors; Humans; Indinavir; Intestinal Diseases, Parasitic; Male; Microsporida; Microsporidiosis; Remission Induction; Retrospective Studies; Ritonavir

Topics: AIDS-Related Opportunistic Infections; Anti-HIV Agents; Delavirdine; Diarrhea; Didanosine; Drug Interactions; Drug Therapy, Combination; HIV Infections; Humans; Indinavir; Lamivudine; Nelfinavir; Nevirapine; Protease Inhibitors; Reverse Transcriptase Inhibitors; Ritonavir; Saquinavir; Virus Replication; Zalcitabine; Zidovudine