What the product label does not tell you about drug–drug interaction management: time for a re‐appraisal

Pharmacolog

Development of immunity in rainbow trout (Oncorhynchus mykiss, Walbaum) to Aeromonas hydrophila after the dietary application of garlic

The development and duration of immune protection against Aeromonas hydrophila infections with garlic as immunostimulant in rainbow trout Oncorhynchus mykiss was studied. Rainbow trout fingerlings of 14 g average weight were fed with 0 g (= Control), 0.5 g and 1.0 g of garlic 100 g-1 of feed for 14 days. Physiological factors, biochemical, immunological, hematological parameters and electrolyte indices were evaluated after a further 14, 21 and 28 days before challenge with Aeromonas hydrophila. Fourteen days after the cessation of feeding with garlic, mortality rates of 12 % (relative percent survival [RPS] = 86 %) and 16 % (RPS = 80 %) were recorded in groups which received 0.5 g and 1.0 g of garlic 100 g-1 of feed, respectively, compared to 84 % mortalities in the controls. The corresponding RPS 21 days after ending the feeding regime was 75 % and 68, respectively. One week later, the RPS had dropped to 55% and 46% in the groups fed with 0.5 g and 1.0 g garlic 100 g-1 of feed, respectively

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

A pharmacist’s contribution to eradicate hepatitis C.

Contains fulltext : 173898.pdf (publisher's version ) (Open Access)Radboud University, 1 december 2017Promotores : Burger, D.M., Drenth, J.P.H. Co-promotor : Kanter, C.T.M.M. d

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

Contains fulltext : 218239.pdf (Publisher’s version ) (Closed access)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. METHODS: Descriptive review using PubMed and Google to identify literature/conference papers on investigational compounds (>/=Phase 2) with data on efficacy and safety in HBV-infected patients. RESULTS: Bulevirtide, JNJ-56136379, ABI-H0731, REP-2139, and inarigivir decrease HBV DNA/RNA, with greater potency than current nucleos(t)ide analogues. REP-2139 (25%-75% of patients, 20-48 weeks treatment) and inarigivir (26% of patients, 12-24 weeks treatment) induce HBsAg loss. ARO-HBV reduced (>1.5 log10 UI/mL) HBsAg in 85% of patients (12 weeks treatment). There are some safety concerns with investigational agents (e.g., increased bile acids with bulevirtide, and liver enzyme flares with REP-2139) which will require a risk benefit assessment compared with current therapies. Single and multidose pharmacokinetic data are available for bulevirtide, JNJ-56136379, ABI-H0731; no such data are available for REP-2139, ARO-HBV, inarigivir. Initial drug interaction assessments have been performed with bulevirtide and inarigivir (only in vitro). CONCLUSIONS: There are promising investigational therapies for HBV infection. Increasing the potential for HBsAg loss may result in more patients achieving functional cure. However, many knowledge gaps remain such as pharmacokinetics in those with HBV, cirrhosis and renal impairment but also the interaction potential between investigational therapies, risk-benefit profiles, and potential for drug interactions with medications used to treat comorbidities associated with aging

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. Therefore, the aim of this review was to describe DDIs between cardiovascular drugs (CVDs) and DAAs. An extensive literature search was performed containing search terms for the marketed DAAs and CVDs (beta-blocking agents, ACE inhibitors, angiotensin II antagonists, renin inhibitors, diuretics, calcium channel blockers, statins/ezetimibe, fibrates, platelet aggregation inhibitors, vitamin K antagonists, heparins, direct Xa inhibitors, nitrates, amiodarone, and digoxin). In particular, the drug labels from the European Medicines Agency and the US Food and Drug Administration were used. A main finding of this review is that CVDs are mostly victims of DDIs with DAAs. Therefore, when possible, monitoring of pharmacodynamics is recommended when coadministering these drugs with DAAs. Nevertheless, it is sometimes better to discontinue a drug on a temporary basis (statins, ezetimide). The DAAs are victims of DDIs in combination with bisoprolol, carvedilol, labetalol, verapamil, and gemfibrozil. Despite there are many DDIs predicted in this review, most of these DDIs can be managed by monitoring the efficacy and toxicity of the victim drug or by switching to another CVD/DAA

Exercise in treating hypertension

BACKGROUND: Little is known about the impact of engineered nanoparticles (ENPs) on skin sensitization caused by chemicals. OBJECTIVES: We determined the ability of different ENPs (TiO2 , Ag and SiO2 ) and aged paint particles containing ENPs to modulate dermal sensitization by a known potent dermal sensitizer. METHODS: The fur of BALB/c mice in the area around the ears was cut with scissors 1 day prior to topical exposure to ENPs (0.4, 4 or 40 mg mL(-1) ), paint particles containing ENPs (4 mg mL(-1) ) or vehicle (day 0). On days 1, 2 and 3, the mice received dermal applications on the back of both ears of 2,4-dinitrochlorobenzene (DNCB) or vehicle. The stimulation index (SI) was calculated on day 6. RESULTS: Topical exposure to TiO2 , Ag or SiO2 ENPs, or aged paint particles followed by vehicle treatment as a control, did not influence the SI. When 4 mg mL(-1) TiO2 ENPs were applied prior to DNCB sensitization, we found an increased SI compared with vehicle-exposed mice prior to DNCB sensitization. Furthermore, an increased titanium concentration was found in the draining lymph node cells of this group. Topical exposure to Ag or SiO2 ENPs or aged paint particles prior to DNCB sensitization did not influence the SI. CONCLUSIONS: We have demonstrated that topical exposure to TiO2 ENPs increases chemical-induced dermal sensitization

A call for a consortium for optimal management of drug-drug interactions in patient care

Contains fulltext : 176982.pdf (publisher's version ) (Closed access)During clinical development of medicines, manufacturers are obliged to assess the risk of drug-drug interactions (DDIs) with their new drug. There is no doubt that product labels of drugs that are nowadays introduced to the market contain much more information on DDIs than in the past. Indeed, the drug label is often the first source for DDIs available to physicians and pharmacists. But how informative are the data presented in the drug labels