Pierre Giguère

Interactions between protease inhibitors and acid-reducing agents: a systematic review.

The purpose of this article is to provide a systematic review of the available pharmacokinetic and clinical data on drug interactions between protease inhibitors (PIs) and acid‐reducing agents, and their clinical relevance.

Psychiatric treatment considerations with direct acting antivirals in hepatitis C

BackgroundDespite recent advances in hepatitis C (HCV) treatment, specifically the addition of direct acting antivirals (DAAs), pegylated interferon-alpha remains the backbone of HCV therapy. Therefore, the impact of DAAs on the management of co-morbid psychiatric illness and neuropsychiatric sequalae remains an ongoing concern during HCV therapy. This paper provides a review of the neuropsychiatric adverse effects of DAAs and drug-drug interactions (DDIs) between DAAs and psychiatric medications.MethodsWe conducted a Pubmed search using relevant search terms and hand searched reference lists of related review articles. In addition, we searched abstracts for major hepatology conferences and contacted respective pharmaceutical companies for additional studies.ResultsLimited data is available on the neuropsychiatric adverse effects of DAAs; however, data from major clinical trials suggest that DAAs have minimal neuropsychiatric risk. DAAs can potentially interact with a variety of psychotropic agents via cytochrome P450 and p-glycoprotein interactions. Triazolam, oral midazolam, St. John’s Wort, carbamazepine and pimozide, are contraindicated with DAAs. DDIs between DAAs and antidepressants, anxiolytics, hypnotics, mood stabilizers, antipsychotics and treatments for opioid dependence are summarized.ConclusionsAlthough DAAs do not add significant neuropsychiatric risk, the potential for DDIs is high. Consideration of DDIs is paramount to improving medication adherence and mitigating adverse effects during HCV therapy.

Atazanavir-Associated Choledocholithiasis Leading to Acute Hepatitis in an HIV-infected Adult

OBJECTIVE To report a case of atazanavir-associated choledocholithiasis in an HIV-infected individual. CASE SUMMARY A 47-year-old treatment-naïve HIV-positive African female presented to the emergency department with a 3-day history of right epigastric pain. Six weeks prior to this episode, she began antiretroviral therapy with a regimen consisting of atazanavir 400 mg and abacavir/lamivudine 600/300 mg once daily. Alanine aminotransferase (766 U/L), aspartate aminotransferase (876 U/L), γ-glutamyltransferase (588 U/L), alkaline phosphatase (348 U/L), and total bilirubin (3.9 mg/dL) levels were elevated. Abdominal ultrasound revealed obstructive choledocholithiasis as well as intra- and extrahepatic biliary dilatation. She underwent a laparoscopic cholecystectomy, which revealed approximately 50 small calculi present in the gallbladder. Since previous ultrasounds had also shown gallstones, an analysis of the extracted calculi was performed to determine the possible association with atazanavir use; low amounts of atazanavir were detected. DISCUSSION Atazanavir is an inhibitor of the bilirubin-conjugating enzyme UGT1A1 and has been frequently linked to the occurrence of hyperbilirubinemia without complications. This individual experienced hyperbilirubinemia that peaked at hospital presentation after she developed choledocholithiasis and secondary acute hepatitis. Analysis of the extracted gallstones revealed that smaller stones contained a higher content of atazanavir than larger stones, which suggests that atazanavir precipitation may play a role in cholelithiasis, although the mechanism remains unknown. The low yield of atazanavir may be explained by the short, 6-week duration of drug exposure as well as the lack of assay for metabolites. The Naranjo probability scale implicated choledocholithiasis as a possible atazanavir-associated adverse event. This report provides the first published evidence that even short-term use of atazanavir may lead to hyperbilirubinemia with choledocholithiasis and secondary acute hepatitis in HIV-infected adults. CONCLUSIONS Atazanavir should be considered a possible contributor in the development of cholelithiasis or choledocholithiasis, and people with HIV should receive adequate counseling in the recognition of symptoms associated with gallstones. The exact incidence and mechanism still need to be elucidated.

The Efficacy of Calcium Carbonate in the Treatment of Protease Inhibitor-Induced Persistent Diarrhea in HIV-Infected Patients

Abstract Background: Although some evidence exists to support the practice of using calcium carbonate to treat nelfinavir-induced diarrhea, there is a lack of data supporting the role of calcium in diarrhea induced by other protease inhibitors (PIs). Purpose: The objective of this prospective open-label study is to evaluate the efficacy of calcium carbonate in the treatment of PI-induced persistent diarrhea in HIV-infected patients. Method: Along with dietary advice, patients were asked to take oral calcium carbonate 500 mg twice daily for 2 weeks. Visual Analog Scale (VAS) and the National Cancer Institute of Canada (NCIC) scale were used to assess the severity of diarrhea. Data were analyzed using paired t tests to test for differences in VAS and NCIC scores between baseline and 14 days. Pearson correlation was used to explore the relationships between change in diarrhea and patient baseline factors. Results: At day 0, the mean VAS ± standard deviation was 6.6 ± 2.1 and decreased to 5.3 ± 1.9 (p = .01) after 14 days. At day 0, the mean NCIC score was 1.9 ± 0.8 and decreased to 1.2 ± 0.9 (p = .005) after 14 days. No baseline patient factors predicted change in NCIC or VAS grade. Conclusion: Calcium carbonate is associated with a reduction of diarrhea in individuals with diarrhea induced by PI.BACKGROUND Although some evidence exists to support the practice of using calcium carbonate to treat nelfinavir-induced diarrhea, there is a lack of data supporting the role of calcium in diarrhea induced by other protease inhibitors (PIs). PURPOSE The objective of this prospective open-label study is to evaluate the efficacy of calcium carbonate in the treatment of PI-induced persistent diarrhea in HIV-infected patients. METHOD Along with dietary advice, patients were asked to take oral calcium carbonate 500 mg twice daily for 2 weeks. Visual Analog Scale (VAS) and the National Cancer Institute of Canada (NCIC) scale were used to assess the severity of diarrhea. Data were analyzed using paired t tests to test for differences in VAS and NCIC scores between baseline and 14 days. Pearson correlation was used to explore the relationships between change in diarrhea and patient baseline factors. RESULTS At day 0, the mean VAS +/- standard deviation was 6.6 +/- 2.1 and decreased to 5.3 +/- 1.9 (p=.01) after 14 days. At day 0, the mean NCIC score was 1.9 +/- 0.8 and decreased to 1.2 +/- 0.9 (p=.005) after 14 days. No baseline patient factors predicted change in NCIC or VAS grade. CONCLUSION Calcium carbonate is associated with a reduction of diarrhea in individuals with diarrhea induced by PI.

Canadian guideline on HIV pre-exposure prophylaxis and nonoccupational postexposure prophylaxis

KEY POINTS New HIV infections occur every year in Canada,[1][1] highlighting the need for integrated prevention programs. Pre-exposure prophylaxis (PrEP) and nonoccupational postexposure prophylaxis (nPEP) are two important strategies for preventing HIV that should be considered standard of care and

Evaluation of Sodium Polystyrene Sulfonate Dosing Strategies in the Inpatient Management of Hyperkalemia

Background: Hyperkalemia occurs frequently in an inpatient setting, for which sodium polystyrene sulfonate (SPS) is a common treatment modality. Few studies have investigated the dose-response of SPS. Objective: To quantify the change in serum potassium after 15-, 30-, and 60-g oral and 30-g rectal doses of SPS. Secondary objectives were to compare the proportion of patients attaining post–SPS dose normokalemia between dosing groups and to investigate the effect of certain characteristics on SPS dose-response. Methods: The reduction in serum potassium after 15-, 30-, and 60-g oral and 30-g rectal doses of SPS administered to adult inpatients was evaluated through a retrospective chart review. Ottawa Hospital Research Ethics Board approval was obtained prior to data collection. Results: A total of 118 patients were included in the analysis. Serum potassium levels were reduced by 0.39, 0.69, 0.91, and 0.22 mEq/L following 15-, 30-, and 60-g oral doses and a 30-g rectal dose of SPS, respectively. A greater proportion of patients (50% vs 23%) remained hyperkalemic in the 15-g versus the 60-g group (P = 0.018), and all patients in the rectal group remained hyperkalemic. No patient in any group experienced postdose hypokalemia. The influence of all studied interindividual characteristics on SPS dose-response was clinically nonsignificant. Conclusion: Mild hyperkalemia can be effectively treated with a single 60-g oral dose of SPS as monotherapy, with minimal risk of hypokalemia. Moderate to severe hyperkalemic episodes warrant alternative therapy. The potassium-lowering effect is correlated to SPS dose and is independent of interindividual characteristics.

Outcomes Associated with Reducing the Urine Alkalinization Threshold in Patients Receiving High-Dose Methotrexate

Urine alkalinization increases methotrexate (MTX) solubility and reduces the risk of nephrotoxicity. The objectives of this study were to determine whether a reduction in the urine pH threshold from 8 to 7 in patients receiving high‐dose methotrexate (HDMTX) results in a shorter length of hospital stay, delayed MTX clearance, or higher rates of nephrotoxicity; and to determine whether specific factors were associated with prolonged MTX clearance.