Clinical Pharmacokinetics and Pharmacodynamics of Anti-Tubercular Drugs in Pregnancy.

The objectives of this qualitative review were to critically evaluate and summarize the currently available data on the use of anti-tuberculosis (TB) drugs during pregnancy, with a focus on treatment outcomes, safety, and pharmacokinetics. This qualitative, narrative review was based on literature searches in Medline, Pubmed, Embase, and Google Scholar (from their inception to 13 August 2020). Our search identified 22 papers related to treatment outcomes and 14 papers related to pharmacokinetic exposures and fetal distributions. While it is challenging to study this patient population, current evidence supports treatment of drug-susceptible TB, multidrug-resistant TB and latent TB infections. However, decisions regarding initiating, continuing, or discontinuing anti-tubercular medications while pregnant should be individualized and discussed with a specialist. Similarly, the pharmacokinetic data of anti-TB agents were mainly derived from small scale, observational studies many of which lacked high quality controls. Based on these data, it does not appear that pregnancy has an extensive impact on the pharmacokinetics of the majority of first-line and second-line agents, although caution (discussed in the review) should be exercised in data interpretation. Fetal drug exposure can also be significant and should be considered when selecting an anti-TB agent for longer term treatment. Overall, it is generally difficult to predict pregnancy-associated pharmacokinetic changes based only on drug's physiochemical characteristics.

Medication Discrepancies Associated With a Medication Reconciliation Program and Clinical Outcomes After Hospital Discharge.

STUDY OBJECTIVE: To identify the frequency of unintended medication discrepancies 30 days postdischarge from medicine wards with interprofessional medication reconciliation processes and clinical import. METHODS: Prospective cohort study of adults discharged between October 2013 and November 2014 from two teaching hospitals in Edmonton, Canada. The Best Possible Medication Discharge Plan (BPMDP) was prepared for all patients. Patients were called 30 days postdischarge to determine the medication discrepancy rate from the BPMDP and whether this was intentional or unintentional; three clinicians used standardized criteria to determine if the discrepancy was inconsequential. Electronic health records and patient contact were used to ascertain death, hospital readmissions, and emergency department (ED) visits at 90 days. RESULTS: Of 433 patients (mean age 64 yrs, 52% female, median discharge prescriptions 6 [interquartile range 4-9]), 168 (38.8%) had at least one unintentional medication discrepancy at 30 days (325 total discrepancies; median one [interquartile range 1-2 discrepancies per patient]). Patients with unintentional medication discrepancies were older (65.9 vs 61.9 yrs, p=0.03) with more discharge medications (7 vs 6, p=0.03). Most unintentional discrepancies (91.1%) were judged inconsequential. The presence of an unintentional medication discrepancy was not associated with 90-day readmission or death (42/167 [25.1%] vs 64/263 [24.3%], adjusted odds ratio 0.96 [95% confidence interval 0.60-1.54]) or ED visits (69 [41.3%] vs 101 [38.4%], adjusted odds ratio 1.11 [95% confidence interval 0.74-1.67]. CONCLUSION: Despite the presence of an interprofessional medication reconciliation process, over one-third of patients had a medication discrepancy within 30 days of discharge, although most were inconsequential and there was no association between unintended medication discrepancies and risk of readmission, ED visit, or death 3 months after discharge.

Dosing and monitoring of methadone in pregnancy: literature review.

BACKGROUND: The pharmacokinetics of methadone is altered during pregnancy, but the most appropriate dosing and monitoring regimen has yet to be identified. OBJECTIVE: To review dosing and monitoring of methadone therapy in pregnancy. METHODS: A literature search was performed in several databases (PubMed, MEDLINE, Embase, International Pharmaceutical Abstracts, and the Cochrane Database of Systematic Reviews) from inception to May 2012. The search terms were "methadone", "pregnancy", "pharmacokinetic", "clearance", "metabolism", "therapeutic drug monitoring", and "methadone dosing". Additional papers were identified by searching the bibliographies of primary and review articles. All English-language primary articles related to methadone pharmacokinetics in pregnancy were included. Articles not related to maternal outcomes were excluded. RESULTS: The literature search yielded 1 case report and 10 studies discussing use of methadone by pregnant women. Methadone pharmacokinetics in pregnancy has been studied in 3 pharmacokinetic trials, and split dosing of methadone in pregnant women has been described in 1 case report and 3 dosing trials. Only 4 trials evaluated monitoring of methadone concentration in pregnancy. The studies included in this review confirm that methadone pharmacokinetics is altered in pregnancy and is potentially correlated with increases in maternal withdrawal symptoms. Insufficient evidence is available to warrant routine monitoring of serum methadone concentrations in pregnant women with opioid dependence. CONCLUSIONS: Few studies of methadone pharmacokinetics and therapeutic drug monitoring are available for pregnant women with opioid dependence. Although it is known that methadone pharmacokinetics is altered in pregnancy, there is insufficient evidence to guide dosage adjustments and serum concentration monitoring. Until further studies are available, regular follow-up of maternal withdrawal symptoms and empiric dosage adjustments throughout pregnancy are still recommended.

Frequency of intensive statin therapy in patients with acute coronary syndrome admitted to a tertiary care center.

Intensive statin therapy (IST) has been shown to decrease cardiovascular events in patients with acute coronary syndrome (ACS). Numerous studies have described statin use for secondary prevention; however, few data have highlighted IST use after ACS. The objective of the present study was to describe IST use in an ACS population before hospitalization, on discharge, and during early follow-up after discharge. A retrospective chart review was conducted of randomly selected patients admitted to a tertiary care center from November 1, 2007 to October 31, 2008. Eligible patients included adults admitted to cardiology with a most responsible diagnosis of ACS (International Classification of Diseases code 20-25). The exclusion criteria included transfer to another hospital or cardiovascular surgery ward and in-hospital death. Phase 1 included an inpatient chart review. Phase 2 was a follow-up cardiologist clinic letter review that included only patients who started IST in-hospital. Of 234 charts reviewed, 111 (47%) patients met the inclusion criteria (mean age 65 ± 11.7 years, 76% men). Most patients (93%) were discharged with a statin. However, although 72% of the study population were eligible for IST, only 52% had IST during hospitalization. Of the patients who started IST with clinic letters available (n = 31), 68% continued IST (mean interval to follow-up 85 days, range 33 to 208). In conclusion, although statin use is good, IST use after ACS is suboptimal. Additionally, newly initiated IST demonstrates poor persistence after discharge.

Pseudohyperphosphatemia associated with high-dose liposomal and lipid complex amphotericin B when tested with Synchron LX 20 (Beckman/Coulter) phosphorous assay.

Although case reports of hyperphosphatemia have been previously described in patients receiving liposomal amphotericin B, this has not been reported in patients receiving the lipid complex formulation. We report a case of hyperphosphatemia that persisted despite switching from liposomal to lipid complex amphotericin B in a child with invasive zygomycosis. This case suggests that in the context of acute renal dysfunction, hyperphosphatemia may also be observed with lipid complex amphotericin B. This case highlights the importance of differentiating between pseudohyperphosphatemia and hyperphosphatemia to prevent complications.