Bleeding Complications in a Patient After the Unexpected Interaction between Valproic Acid and Phenprocoumon.

Background: Phenprocoumon is a vitamin K antagonist that is widely prescribed in Europe and Latin America for the prophylaxis and treatment of thromboembolic events.

Case Presentation: A 90-year-old female was admitted to our hospital with tonic-clonic seizures, possibly due to dementia syndrome. Valproic acid (VPA) was prescribed for the treatment of seizures.

The QT interval prolongation potential of anticancer and supportive drugs: a comprehensive overview.

Patients with cancer are prone to prolongation of the corrected QT interval (QTc) due to the use of anticancer drugs with QTc-prolonging potential in combination with electrolyte imbalances caused by, for example, gastrointestinal side-effects. However, most anticancer drugs were approved with little information on their QTc-prolonging potential and the added risk of torsade de pointes. The absence of this information on the drug label poses a considerable challenge to clinicians regarding the measures that need to be taken to safely start anticancer treatment.

Meropenem to Treat Valproic Acid Intoxication.

This therapeutic drug monitoring (TDM) grand round describes a patient with serious valproic acid intoxication. A total valproic acid level of 844 mg/L and an unbound valproic acid level of 604 mg/L were observed. Meropenem was administered to enhance the clearance of valproic acid.

Recommendations for Dosing of Repurposed COVID-19 Medications in Patients with Renal and Hepatic Impairment.

Introduction: In December 2019, an outbreak of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began, resulting in a number of antivirals and immune modulators being repurposed to treat the associated coronavirus disease 2019 (COVID-19). Many patients requiring treatment for COVID-19 may have either pre-existing renal or hepatic disease or experience acute renal/hepatic injury as a result of the acute infection. Altered renal or hepatic function can significantly affect drug concentrations of medications due to impaired drug metabolism and excretion, resulting in toxicity or reduced efficacy.

Effect of Pregnancy and Concomitant Antiretrovirals on the Pharmacokinetics of Tenofovir in Women With HIV Receiving Tenofovir Disoproxil Fumarate-Based Antiretroviral Therapy Versus Women With HBV Receiving Tenofovir Disoproxil Fumarate Monotherapy.

Tenofovir disoproxil fumarate (TDF) is recommended as part of antiretroviral therapy (ART) for pregnant women with HIV and as monotherapy for pregnant women with hepatitis B virus (HBV) monoinfection at high risk of transmitting infection to their infants. Tenofovir (TFV) plasma exposures are reduced during pregnancy; however, concomitant antiretrovirals and the viral infection itself can also influence TFV pharmacokinetics. Our aim was to compare TFV pharmacokinetics in pregnant women receiving TDF-based ART, with or without a ritonavir-boosted protease inhibitor (r/PI), to pregnant women with HBV receiving TDF monotherapy.

SARS-CoV-2 and HIV protease inhibitors: why lopinavir/ritonavir will not work for COVID-19 infection.

Since the beginning of the outbreak of severe acute respiratory syndrome (SARS) coronavirus (CoV) 2, lopinavir/ritonavir was selected for treatment. The recent publication of Cao et al. in the New England Journal of Medicine showed that lopinavir/ritonavir treatment did not accelerate clinical improvement compared with standard of care.

Prospective validation of a model-informed precision dosing tool for vancomycin in intensive care patients.

Aims: Vancomycin is an important antibiotic for critically ill patients with Gram-positive bacterial infections. Critically ill patients typically have severely altered pathophysiology, which leads to inefficacy or toxicity. Model-informed precision dosing may aid in optimizing the dose, but prospectively validated tools are not available for this drug in these patients.

An update on extravasation: basic knowledge for clinical pharmacists.

Extravasation is the leakage of intravenously administered solution into surrounding tissues, which can cause serious damage to the patient. The impact of extravasation is mostly determined by the localisation and volume of extravasation, but the physicochemical properties of the drugs are also important. In this paper a stepwise approach to managing an extravasation is described, with recommendations on the role of the pharmacist.

Pharmacokinetics of oral tenofovir disoproxil fumarate in pregnancy and lactation: a systematic review.

Background: Tenofovir disoproxil fumarate (TDF), the oral prodrug of tenofovir (TFV), is advocated in pregnancy for prevention of mother-to-child transmission (PMCT) with failure of hepatitis B immunoglobulin and vaccination. The pharmacokinetics of TDF monotherapy for PMCT-HBV is important if deployment is to emulate the success of multiple antiretrovirals (ARVs) for PMCT-HIV in resource-constrained settings.

Methods: This systematic review followed a protocol and is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) guidelines.

Review article: clinical pharmacology of current and investigational hepatitis B virus therapies.

Background: Treatment of hepatitis B virus (HBV) infection with current therapy suppresses HBV DNA, but loss of hepatitis B surface antigen (HBsAg; functional cure), is rare. Multiple compounds are under investigation.

Aims: To describe the pharmacology, including drug interactions, efficacy, safety and mechanisms of action of investigational compounds for HBV infection.

Mercaptopurine and Metabolites in Breast Milk.

A 35-year-old pregnant woman visited our outpatient clinical questioning the safety of once daily 50 mg mercaptopurine (MP) during pregnancy and lactation, which was successfully treating her Crohn's disease. We measured MP and its metabolites in plasma and breast milk and found after 4 hours of intake of MP, no MP or its metabolites in breast milk. We concluded that 4 hours after intake of MP, no exposure of the suckling infant to MP and its metabolites was found while being breastfed.

Viral Hepatitis C Therapy: Pharmacokinetic and Pharmacodynamic Considerations: A 2019 Update.

It has been estimated by the World Health Organization (WHO) that over 71 million people were infected with the hepatitis C virus (HCV) in 2015. Since then, a number of highly effective direct-acting antiviral (DAA) regimens have been licensed for the treatment of chronic HCV infection: sofosbuvir/daclatasvir, sofosbuvir/ledipasvir, elbasvir/grazoprevir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir, and sofosbuvir/velpatasvir/voxilaprevir. With these treatment regimens, almost all chronic HCV-infected patients, even including prior DAA failures, can be treated effectively and safely.

Metformin Alters Human Host Responses to Mycobacterium tuberculosis in Healthy Subjects.

Background: Metformin, the most widely administered diabetes drug, has been proposed as a candidate adjunctive host-directed therapy for tuberculosis, but little is known about its effects on human host responses to Mycobacterium tuberculosis.

Methods: We investigated in vitro and in vivo effects of metformin in humans.

Results: Metformin added to peripheral blood mononuclear cells from healthy volunteers enhanced in vitro cellular metabolism while inhibiting the mammalian target of rapamycin targets p70S6K and 4EBP1, with decreased cytokine production and cellular proliferation and increased phagocytosis activity.

Cardiovascular Risk Management and Hepatitis C: Combining Drugs.

Direct-acting antivirals (DAAs) are known victims (substrate) and perpetrators (cause) of drug-drug interactions (DDIs). These DAAs are used for the treatment of hepatitis C virus (HCV) infections and are highly effective drugs. Drugs used for cardiovascular risk management are frequently used by HCV-infected patients, whom also are treated with DAAs.

The Observed Effect of Gastric Bypass Surgery on Direct-acting Antiviral Treatment: a Case Report.

Chronic hepatitis C virus (HCV) infection can be cured with treatment using direct-acting antivirals (DAAs). Although these drugs have been widely studied, information about certain special populations is missing. In this case report we describe a treatment-experienced patient with chronic HCV infection genotype 1b, treated with 150 mg/day simeprevir, 400 mg/day sofosbuvir, and 1,000 mg/ day ribavirin for 24 weeks, after a Roux-and-Y gastric bypass.

Brief Report: High Need to Switch cART or Comedication With the Initiation of DAAs in Elderly HIV/HCV-Coinfected Patients.

Background: To describe the use of nonantiretroviral comedication and combination antiretroviral therapy (cART) in patients coinfected with HIV/hepatitis C virus (HCV) and to predict the potential for drug-drug interactions (DDIs) with direct-acting antivirals (DAAs) against HCV.

Methods: This is a retrospective, cross-sectional study, using the Dutch, nationwide ATHENA observational HIV cohort database. All patients with a known HIV/HCV coinfection on January 1, 2015, were included.

The majority of hepatitis C patients treated with direct acting antivirals are at risk for relevant drug-drug interactions.

Background: Direct-acting antivirals have improved treatment of chronic hepatitis C virus infection significantly. Direct-acting antivirals inhibit/induce and can also be substrates of drug-metabolising enzymes and transporters. This increases the risk for drug-drug interactions.

Metformin and daclatasvir: absence of a pharmacokinetic-pharmacodynamic drug interaction in healthy volunteers.

Aim: The aim of the present study was to evaluate the effect of the proposed organic cation transporter (OCT) inhibitor daclatasvir on the pharmacokinetics and pharmacodynamics of the OCT substrate metformin.

Methods: This was an open-label, two-period, randomized, crossover trial in 20 healthy subjects. Treatment A consisted of metformin and treatment B consisted of metformin + daclatasvir.