De-simplifying antiretroviral therapy from a single-tablet to a two-tablet regimen: Acceptance, patient-reported outcomes, and cost savings in a multicentre study.

BACKGROUND: Antiretroviral therapy (ART), which is increasingly used by people with HIV, accounts for significant care costs, particularly because of single-tablet regimens (STRs). This study explored de-simplification to a two-tablet regimen (TTR) for cost reduction. The objectives of this study were: (1) acceptance of de-simplification, (2) patient-reported outcomes, and (3) cost savings. METHODS: All individuals on Triumeq®, Atripla® or Eviplera® in five HIV clinics in the Netherlands were eligible. Healthcare providers informed individuals of this study. After inclusion, individuals were free to de-simplify. An electronic questionnaire was sent to assess study acceptance, adherence, quality of life (SF12) and treatment satisfaction (HIVTSQ). After 3 and 12 months, questionnaires were repeated. Cost savings were calculated using Dutch drug prices. RESULTS: In total, 283 individuals were included, of whom 55.5% agreed to de-simplify their ART, with a large variability between treatment centres: 41.1-74.2%. Individuals who were willing to de-simplify tended to be older, had a longer history of HIV diagnosis, and used more co-medication than those who preferred to remain on an STR regimen. Patient-reported outcomes, including quality of life and treatment satisfaction, showed no significant difference between people with HIV who switched to a TTR and those who remained on an STR regimen. Furthermore, we observed a 17.8% reduction in drug costs in our cohort of people with HIV who were initially on an STR. CONCLUSIONS: De-simplification from an STR to a TTR within the Dutch healthcare setting has been demonstrated as feasible, leads to significant cost reductions and should be discussed with every eligible person with HIV in the Netherlands.

Monitoring of tobramycin serum concentrations in selected critically ill patients receiving selective decontamination of the digestive tract: a retrospective evaluation.

INTRODUCTION: Selective decontamination of the digestive tract (SDD) is a strategy in mechanically ventilated patients to reduce mortality. Treatment consists of enterally administered non-absorbable antibiotics, i.e., tobramycin. However, most intensive care unit (ICU) patients with SDD appear to have detectable tobramycin serum concentrations. The Rijnstate Hospital implemented a protocol for therapeutic drug monitoring (TDM) of tobramycin in patients at risk. The aim of this study was to evaluate the necessity of TDM in these patients and to optimize the current protocol. METHODS: This retrospective observational study included ICU patients with SDD treatment for ≥ 7 days and renal failure. These patients were considered eligible for monitoring of tobramycin. Tobramycin serum concentrations, relevant laboratory parameters (i.e., renal function, lactate), and patient data were extracted from the National Intensive Care Evaluation database and the hospital electronic patient data system. RESULTS: In 23 subjects, a total of 43 tobramycin serum concentrations was determined. The median tobramycin serum concentration was 0.33 (IQR 0.17-0.49) mg/L of which 12 (27.9%) samples had concentrations < 0.2 mg/L, 30 (69.8%) had concentrations 0.2-1.0 mg/L and 1 (2.3%) had a toxic concentration > 1.0 mg/L. In 3 (7.0%) cases, an intervention was conducted based on the tobramycin serum concentration. CONCLUSION: The majority (83.7%) of samples had detectable tobramycin serum concentrations. Monitoring of tobramycin serum concentrations can be considered necessary in patients at risk. However, the current protocol should be optimized to intercept patients more precise.

Pharmacokinetics of the combination raltegravir/atazanavir in HIV-1-infected patients.

OBJECTIVES: To evaluate the use of raltegravir with unboosted atazanavir in combination with one nucleoside reverse transcriptase inhibitor (NRTI) (lamivudine or emtricitabine) as a potentially well-tolerated once-daily (qd) maintenance regimen. METHODS: We compared the pharmacokinetics of raltegravir 400 mg twice daily (bid) with raltegravir 800 mg qd in HIV-infected patients (n=17) on unboosted atazanavir (600 mg qd) in combination with lamivudine or emtricitabine. RESULTS: The area under the plasma concentration vs. time curve for a dose interval t (AUC0 -t ) of 800 mg qd divided by 2 was not significantly different from the AUC0 -t of 400 mg bid (P=0.664) but the minimum concentration (C min ) was 72% lower with the qd regimen (P=0.002). The regimen was well tolerated and the viral load remained undetectable in all patients during the 6 weeks of the study follow-up. CONCLUSIONS: A qd regimen of raltegravir 800 mg, atazanavir 600 mg and lamivudine or emtricitabine resulted in favourable pharmacokinetic profiles and good short-term safety and efficacy data. Larger phase IIb studies are needed to explore this novel regimen.

Reality of severe metformin-induced lactic acidosis in the absence of chronic renal impairment.

BACKGROUND: Lactic acidosis in metformin use is a widely recognised but rare side effect. Case reports usually describe elderly patients with conditions which in themselves can cause lactic acidosis or with known contraindications to metformin. We present cases of an elderly woman, a younger woman and a man who developed serious metformin-induced lactic acidosis in the absence of chronic renal impairment. RESULTS: Laboratory results showed acute renal failure in all patients. The pH was 6.77, 6.98 and 6.7, respectively, and lactate levels were 18.2, 18.4 and 11.7 mmol/l, respectively. Metformin plasma levels were 58, 57 and 39 mg/l. All patients received continuous veno-venous haemofiltration (CVVH), using bicarbonate as a buffer solution shortly after arrival on our ICU. In the subsequent hours, a steep decline in the plasma levels was observed, with a concomitant increase in pH. No other diagnoses were made, so we concluded that all patients were suffering from metformin-induced lactic acidosis. Despite the severity of the metabolic acidosis, both female patients survived. Our male patient died after a prolonged stay in the ICU, but this was not related to metformin. CONCLUSION: Metformin-induced lactic acidosis does exist. Metformin-induced lactic acidosis may occur in patients with previously normal renal function, even in young patients. Patients with extreme (lactic) metabolic acidosis caused by metformin can survive when CVVH treatment is initiated rapidly. Intercurrent symptoms or diseases that affect renal perfusion can precipitate lactic acidosis.

[Acute caffeine intoxication after intake of 'herbal energy capsules']. / Acute coffeïne-intoxicatie na het innemen van 'herbal energy'-capsules.

Two males, 15 and 17 years old respectively, presented at the Emergency Department complaining of cramping abdominal pain, nausea and vomiting after ingestion of energy capsules. Physical examination revealed sinus tachycardia and slight abdominal pain. Laboratory examination showed substantial hypokalaemia and mild hyperglycaemia. Questioning revealed that they had taken 5 and 3 'herbal energy capsules' respectively and that these capsules supposedly contained 200 mg of caffeine each. Toxicological analysis showed a greatly increased serum caffeine concentration in both patients. The peak concentrations calculated were in the highly toxic range and could have led to severe acute complications such as convulsions. Pharmaceutical analysis demonstrated that these 'Supercap Xtreme'-capsules contained 700 mg caffeine or more. All symptoms presented were compatible with caffeine intoxication. The content of these capsules is not reliable and could lead to life-threatening intoxication.

[Metformin-associated lactic acidosis: an insufficiently recognised problem]. / Metformine-geassocieerde lactaatacidose.

Metformin-associated lactic acidosis (MALA) is a rare but potentially fatal condition that can easily be avoided. As metformin is known to facilitate the production of lactate, predisposing factors can accelerate this process. In situations of infection or dehydration, metformin can accumulate due to kidney failure, hereby increasing the risk of MALA. Despite controversy in the literature about the presence of a relationship between metformin and lactic acidosis, the severity of the condition is cause for concern and allows for preventive measurements. Awareness of this condition among patients and clinicians is insufficient, resulting in many patients continuing metformin in situations where there is an increased risk of developing MALA. Metformin can easily be discontinued temporarily without causing any harm. We emphasize the importance of temporarily discontinuing metformin in situations where the risk of lactic acidosis is increased, such as severe infection, dehydration and acute kidney insufficiency. This requires increased awareness and adequate counselling by clinicians as well as pharmacists.