Complementary medicine (CM) is used by one third to one half of cancer patients throughout the world. The objective of this study was to describe the prevalence of CM use and the potential for ...interactions with cancer treatments in an academic oncology centre. A cross-sectional study was conducted among patients undergoing current cancer treatment. Among 132 included patients, 56% had used CM since their cancer diagnosis and 45% were using CM during cancer treatment at the time of the survey. The main CM used were green tea (35%), herbal tea (35%), homeopathy (27%), dietary supplements (27%), and herbal medicines (27%). A small majority of patients (58%) spontaneously mentioned the use of CM to their oncologist. Of 42 identified combinations of concomitant use of biologically based CM and anticancer agents among the study patients, the potential for pharmacokinetic interactions of clinical relevance was not expected in 17 combinations (40%), hypothetical and deemed unlikely in 23 (55%), and of probable low clinical relevance in 2 (5%). Considering the high prevalence of CM use, active enquiries should be made by healthcare professionals to detect symptoms that may relate to CM tolerance and effects or that suggest interactions between CM and cancer treatments.
To investigate pregnancy outcomes following maternal use of pregabalin.
This multicenter, observational prospective cohort study compared pregnancy outcomes in women exposed to pregabalin with those ...of matched controls (not exposed to any medications known to be teratogenic or to any antiepileptic drugs). Teratology Information Services systematically collected data between 2004 and 2013.
Data were collected from 164 exposed pregnancies and 656 controls. A significantly higher major birth defect rate in the pregabalin group was observed after exclusion of chromosomal aberration syndromes, and when cases with exposure during first trimester of pregnancy were analyzed separately (7/116 6.0% vs 12/580 2.1%; odds ratio 3.0, 95% confidence interval 1.2-7.9, p = 0.03). The rate of live births was lower in the pregabalin group (71.9% vs 85.2%, p < 0.001), primarily due to a higher rate of both elective (9.8% vs 5.0%, p = 0.02) and medically indicated (5.5% vs 1.8%, p = 0.008) pregnancy terminations. In the Cox proportional cause specific hazards model, pregabalin exposure was not associated with a significantly higher risk of spontaneous abortion.
This study demonstrated a signal for increased risk of major birth defects after first trimester exposure to pregabalin. However, several limitations such as the small sample size, differences across groups in maternal conditions, and concomitant medication exposure exclude definitive conclusions, so these results call for confirmation through independent studies.
To gain medical insight into the clinical course and safety of otolaryngologic disorders following immunisation with severe acute respiratory coronavirus (SARS-CoV-2) mRNA-based vaccines.
Case ...description.
We report four cases of transient audio-vestibular symptoms, which occurred shortly after inoculation of two BNT162b2 (Pfizer-BioNTech
®
) and mRNA-1273 (Moderna®) vaccines.
Hearing loss was unilateral in all cases and recovered at least partially: it was associated with persistent gait instability in two cases, after 1 and 7 months. Trigger mechanisms underpinning audio-vestibular impairment remain uncertain. Immune tolerance mechanisms with off-target innate activation of T-lymphocytes may be involved in vestibulocochlear nerve disorders, as for other cranial nerves involvement.
The occurrence of audio-vestibular manifestations following mRNA-based vaccines needs ENT monitoring to support their causality in such rare vaccine-related adverse events. Audio-vestibular disorders appeared of transitory nature, including hearing loss, and should not deter further efforts in large-scale vaccination campaigns against SARS-CoV-2.
Aims
TNF‐α inhibitors are considered relatively safe in pregnancy but experience is still limited. The aim of this study was to evaluate the risk of major birth defects, spontaneous abortion, preterm ...birth and reduced birth weight after first trimester exposure to TNF‐α inhibitors.
Methods
Pregnancy outcomes of women on adalimumab, infliximab, etanercept, certolizumab pegol or golimumab were evaluated in a prospective observational cohort study and compared with outcomes of a non‐exposed random sample. The samples were drawn from pregnancies identified by institutes collaborating in the European Network of Teratology Information Services.
Results
In total, 495 exposed and 1532 comparison pregnancies were contributed from nine countries. The risk of major birth defects was increased in the exposed (5.0%) compared with the non‐exposed group (1.5%; adjusted odds ratio (ORadj) 2.2, 95% CI 1.0, 4.8). The risk of preterm birth was increased (17.6%; ORadj 1.69, 95% CI 1.1, 2.5), but not the risk of spontaneous abortion (16.2%; adjusted hazard ratio HRadj 1.06, 95% CI 0.7, 1.7). Birth weights adjusted for gestational age and sex were significantly lower in the exposed group compared to the non‐exposed cohort (P = 0.02). As a diseased comparison group was not possible to ascertain, the influence of disease and treatment on birth weight and preterm birth could not be differentiated.
Conclusions
TNF‐α inhibitors may carry a risk of adverse pregnancy outcome of moderate clinical relevance. Considering the impact of insufficiently controlled autoimmune disease on the mother and the unborn child, TNF‐α inhibitors may nevertheless be a treatment option in women with severe disease refractory to established immunomodulatory drugs.
Ivermectin has been used since the 1980s as an anthelmintic and antiectoparasite agent worldwide. Currently, the only available oral formulation is tablets designed for adult patients. A ...patient-friendly orodispersible tablet formulation designed for pediatric use (CHILD-IVITAB) has been developed and is entering early phase clinical trials. To inform the pediatric program of CHILD-IVITAB, 16 healthy adults were enrolled in a phase I, single-center, open-label, randomized, 2-period, crossover, single-dose trial which aimed to compare palatability, tolerability, and bioavailability and pharmacokinetics of CHILD-IVITAB and their variability against the marketed ivermectin tablets (STROMECTOL) at a single dose of 12 mg in a fasting state. Palatability with CHILD-IVITAB was considerably enhanced as compared to STROMECTOL. Both ivermectin formulations were well tolerated and safe. Relative bioavailability of CHILD-IVITAB compared to STROMECTOL was estimated as the ratios of geometric means for C
, AUC
, and AUC
, which were 1.52 90% CI: 1.13-2.04, 1.27 0.99-1.62, and 1.29 1.00-1.66, respectively. Maximum drug concentrations occurred earlier with the CHILD-IVITAB formulation, with a median T
at 3.0 h range 2.0-4.0 h versus 4.0 h range 2.0-5.0 h with STROMECTOL (P = .004). With CHILD-IVITAB, variability in exposure was cut in half (coefficient of variation: 37% vs 70%) compared to STROMECTOL. Consistent with a more controlled absorption process, CHILD-IVITAB was associated with reduced variability in drug exposure as compared to STROMECTOL. Together with a favorable palatability and tolerability profile, these findings motivate for further clinical studies to evaluate benefits of such a patient-friendly ODT formulation in pediatric patients with a parasitic disease, including infants and young children <15 kg.
Effect of dronedarone on renal function in healthy subjects Tschuppert, Yvonne; Buclin, Thierry; Rothuizen, Laura E. ...
BJCP. British journal of clinical pharmacology/British journal of clinical pharmacology,
December 2007, Letnik:
64, Številka:
6
Journal Article
Recenzirano
Odprti dostop
What is already known about this subject
• Creatinine clearance (CL) is used to assess glomerular filtration rate (GFR). However, it is known to slightly overestimate the true GFR, due to renal ...tubular secretion of creatinine.
• During phase I‐III clinical trials, a 10–15% increase in serum creatinine has been observed both in healthy subjects and patients receiving the new antiarrhythmic agent dronedarone.
What this study adds
• Dronedarone affects the renal handling of creatinine and N‐methylnicotinamide, two cations, while leaving unchanged GFR, assessed through sinistrin CL, and renal plasma flow and anion secretion, assessed through para‐amino‐hippurate CL.
• This suggests a specific action of dronedarone on renal organic cation transport explaining the limited, reversible effect of dronedarone on serum creatinine, which must not be interpreted as reflecting an impairment of renal function, but which may indicate an interaction potential with cationic drugs.
Aims
To assess the effects of dronedarone on renal function and tubular cation handling.
Methods
Twelve healthy males were enrolled in a randomized, cross‐over, placebo‐controlled, double‐blind study. They received 400 mg dronedarone or placebo twice daily for 7 days. Baseline and on‐treatment renal function tests were performed under strict standardization of intakes, by assessing creatinine, sinistrin, para‐amino‐hippurate (PAH) and N‐methylnicotinamide (NMN) CLs, and electrolyte excretion.
Results
Compared with placebo, dronedarone significantly decreased renal creatinine CL (mean 138–119 ml min−1 after dronedarone vs. 142–149 ml min−1 after placebo) and NMN CL (448–368 ml min−1vs. 435–430 ml min−1), but did not alter renal sinistrin CL, PAH CL and other renal parameters.
Conclusions
Dronedarone reduces renal creatinine and NMN clearance by about 18%, without evidence of an effect on GFR, renal plasma flow or electrolyte exchanges. This suggests a specific partial inhibition of tubular organic cation transporters (OCT). A limited increase in serum creatinine is therefore expected with dronedarone treatment, but does not mean there is a decline in renal function.
Aims
Metformin is used to treat type 2 diabetes, polycystic ovary syndrome associated infertility, and gestational diabetes. This study aims to evaluate the safety of metformin in early pregnancy.
...Method
We evaluated the risk of major birth defects and pregnancy losses in a cohort of pregnant women exposed to metformin during the first trimester for different indications relative to a matched unexposed reference group.
Results
The risk of major birth defects was 5.1% (20/392) in pregnancies exposed to metformin during the first trimester and 2.1% (9/431) in the reference group adjusted odds ratio (OR) 1.70; 95% CI 0.70–4.38. Among metformin users, this risk was 7.8% (17/219) in patients with pre‐gestational diabetes and 1.7% (3/173) in those without this diagnosis. Compared to the unexposed reference, the OR for metformin user with diabetes was 3.95 (95% CI 1.77–9.41) and for metformin with other indications it was 0.83 (95% CI 0.18–2.81). The risk of pregnancy losses (spontaneous abortions and stillbirths) was 20.8% in women on metformin during the first trimester and 10.8% in the reference group adjusted hazard ratio (HR) 1.57; 95% CI 0.90–2.74. The risks for women on metformin with and without pre‐gestational diabetes were 24.0% and 16.8% respectively, with adjusted HR of 2.51 (95% CI 1.44–4.36) and 1.38 (95% CI 0.74–2.59) when compared to the reference.
Conclusion
Pregnant women with pre‐gestational diabetes on metformin are at a higher risk for adverse pregnancy outcomes than the general population. This appears to be due to the underlying diabetes since women on metformin for other indications do not present meaningfully increased risks.
This prospective multicentre cohort study investigated pregnancy outcomes after fingolimod use for multiple sclerosis during pregnancy. Pregnancy outcomes of 63 fingolimod and 62 interferon-β-exposed ...pregnancies were compared. Rates of major congenital anomalies (MCA) were 4.8% (2/42) in the fingolimod group versus 2.3% (1/44) in the interferon-β group (odds ratio, 2.2; 95% confidence interval, 0.2–24.6). The adjusted hazard ratio for spontaneous abortion in fingolimod versus interferon-β-exposed pregnancies was 0.6 (95% confidence interval, 0.2–1.8). Further studies are needed to definitely rule out a moderately increased MCA risk after fingolimod exposure during pregnancy.
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