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Background and objective: Lornoxicam is an NSAID used to obtain short-term relief of acute mild to moderate pain and symptomatic relief of pain and inflammation in rheumatoid arthritis and osteoarthritis. The aim of this study was to compare and evaluate the pharmacokinetic parameters of lornoxicam 8 mg as quick-release (QR) tablet, standard tablet (ST) and intramuscular injection (IM). Methods: Eighteen healthy volunteers (9 male, 9 female; average age 26.9 (SD 3.0) years; average body mass index 21.8 (SD 2.3) kg/m2 were randomized to three different treatment groups. Subjects received a single 8-mg dose of each lornoxicam formulation in a three-way crossover design on days 1, 8 and 15. Lornoxicam plasma concentrations were obtained from baseline to 24 hours using high-pressure liquid chromatography. The pharmacokinetic parameters area under the plasma concentration-time curve from zero to infinity (AUC∞), maximum plasma concentration (Cmax), time to maximum plasma concentration (tmax), terminal half-life (t1/2) and mean residence time (MRT) were calculated. Results: Lornoxicam-QR was comparable with lornoxicam-ST and lornoxicam-IM regarding AUC∞, t1/2 and MRT. The AUC∞ ratio (90% CI) was 1.07 (0.94, 1.20) for lornoxicam-QR/lornoxicam-ST and 1.10 (0.97, 1.24) for lornoxicam-QR/lornoxicam-IM. Cmax and tmax did not differ between lornoxicam-QR and lornoxicam-IM (p = 0.66 and 0.07, respectively). Both lornoxicam-QR and lornoxicam-IM showed significantly shorter tmax and significantly higher Cmax values than lornoxicam-ST. Conclusion: Lornoxicam-QR and lornoxicam-IM did not differ with respect to AUC∞, Cmax and tmax, but both lornoxicam-QR and lornoxicam-IM showed significantly shorter tmax and significantly higher Cmax values than lornoxicam-ST.

The presence of liver cirrhosis affects the selection and dosing of drugs metabolised by the liver as doses have to be adjusted to the remaining liver function. This is a major challenge in clinical practice as specific guidelines are lacking. The aim of this study was to identify drugs for which recommendations on selection and dose adjustments for patients with cirrhosis exist by assessing the literature according to certain quality standards, paying particular attention to the suitability of these recommendations for clinical practice. A systematic literature review included peer-reviewed publications that were published by October 2020 in PubMed in the English language and aimed to generate recommendations on dose adjustment in patients with liver cirrhosis. Subsequently, the identified publications were checked for reporting quality against the relevant reporting guidelines and the Oxford Centre for Evidence-Based Medicine Levels of Evidence. Finally, all specific dose recommendations were extracted, compared with the specifications of the Summaries of Product Characteristics and mapped according to the Anatomical Therapeutic Chemical/Defined Daily Dose Index. Eighteen publications covering a total of 1145 dose recommendations for 481 active substances were identified. There were 706 recommendations for 316 substances sufficiently specific for application in clinical practice. For 22 active substances, the specific recommendations were consistent across multiple publications, of which only six were also consistent with the respective Summaries of Product Characteristics. As the majority of dose recommendations were not sufficiently specific or even contradictory, there is an urgent need for the definition of standard parameters for a uniform assessment of drugs in liver cirrhosis. In addition, dose recommendations should be aligned by suitable methods.

For specific immunotherapy to pollen allergy, a pre-seasonal start of treatment is recommended by international guidelines. In a placebo-controlled clinical trial with adults, an intra-seasonal start of therapy with the SQ-standardised grass allergy immunotherapy tablet (AIT) was well-tolerated. The objective of our study was to investigate the feasibility of an intra-seasonal start of grass AIT administered during routine treatment by practising allergists. In a multicentre, prospective, open-label, uncontrolled, non-interventional observational study, data on routine treatment with grass AIT were recorded in patients who started administration of tablets within the 2010 grass pollen season in Germany. Adverse events (AEs) were recorded by the physician at visits for the first administration in the clinic and at the end of the 1- to 3-month observation period. AEs and daily administration of the tablet were recorded by the patients in diaries for the first 14 days. Treatment satisfaction, global tolerability and perceived effect of treatment were assessed by the patient and physician at the end of the study. A total of 662 patients were treated with 1 tablet daily by 286 physicians. Grass AIT was started intra-seasonally in 620 patients and post-season in 42. The average treatment period was 51.6 days. AEs were recorded in 52.1 % of all patients and in 35.6 % at first administration, with throat irritation (21.3 %), paraesthesia oral (19.9 %), oral pruritus (14.0 %) and ear pruritus (10.3 %) being the most frequent AEs related to grass AIT. The intensity of the AEs was assessed as mild or moderate in 42.1 % of patients and severe in 8.0 %; AEs related to grass AIT were classified as serious in two patients. Grass AIT was discontinued due to AEs in 7.7 % of patients. Diaries were evaluable for 77.0 % of patients; the average rate of patients with AEs decreased continuously from 44.7 % (day 1) to 26.9 % (day 14) and the average daily rate of patients who forgot to take their tablet was about 5 %. Overall tolerability was assessed by 87.2 % of patients and 91.4 % physicians as “very good” or “good” and effectiveness of treatment was assessed as “very good” or “good” in 81.4 % of patients and 85.8 % of physicians. More than 90 % of patients and physicians were satisfied with the treatment. The tolerability data for an intra-seasonal start of grass AIT during routine treatment confirm the safety profile from the previous controlled trial. Tolerability was assessed as good in combination with high satisfaction with the treatment and compliance.

Background and methods: A higher degree of clinical efficacy with olmesartan compared with other angiotensin receptor blockers, has been reported by several sources. In this study of 31 examples of cases of essential hypertension, Holter electrocardiogram, ambulatory blood pressure monitoring and pulse wave velocity (PWV) measurements were performed before and after substituting olmesartan 20 mg for candesartan 8 mg antihypertensive drug therapy. Results: Following the therapeutic change, daily average systolic and diastolic blood pressures were decreased by 6.7 ± 9.3 mmHg and 3.6 ± 8.3 mmHg, respectively, with olmesartan 20 mg; PWV was also significantly decreased. Holter electrocardiogram heart rate variability spectral analysis demonstrated that none of the very low frequency (VLF), high frequency (HF) and low frequency (LF)/HF components were significantly altered. However, a significant correlation was observed between the LF/HF component and blood pressure difference, when blood pressure and heart rate variability components in each individual case were studied. Conclusion: This study shows that olmesartan has a stronger antihypertensive effect in comparison to candesartan, and does not generate reflex sympathoexcitatory activity.

There are limited data on the adverse events of d-penicillamine in Wilson's disease (WD) that can result in dose modification or treatment discontinuation. The objective of this study was to observe the adverse events related to d-penicillamine in patients with hepatic WD. A retrospective audit of prospectively registered hepatic WD patients at a tertiary care center between December 2006 and January 2020 was carried out. Demographic variables, laboratory parameters, and details of treatment were noted. Adverse events (AEs) related to d-penicillamine treatment, the timing and management of these AEs were analysed. The study included 112 patients with hepatic WD on d-penicillamine. d-penicillamine intolerance was seen in 28/112 (25%) over 179 person-years. Of the 28 AEs, severe AEs leading to permanent d-penicillamine discontinuation occurred in 16 (57%) [never reintroduced 12 (43%), discontinued after intolerant to rechallenge, 4 (14%)], temporary cessation followed by reintroduction to initial dose 13 (46%) and continuation with reduced dose in 3 (11%) patients. Overall, most common AEs were hematological [16, 57% (pancytopenia n = 8, bicytopenia n = 5 and hemolytic anemia n = 3)] while renal adverse events (n = 7, 25%) constituted the most common indication for permanent discontinuation. Cytopenias developed beyond 12 months of d-penicillamine initiation whereas hemolytic anemia developed within first 3 months. Following d-penicillamine discontinuation in 25 patients, it was reintroduced to initial dose in 13/25 (52%), switched to trientine due to neurological worsening in 2/25 (8%) and switched to zinc in 10/25 (40%). In patients with reintroduction, gradual dose escalation was tolerated in 9/13 (69%) with a recurrence of AEs leading to permanent discontinuation in 4/13 (31%). D-penicillamine treatment is associated with significant AEs mainly related to blood, kidney, and skin. Temporary cessation of drug with reintroduction at a lower dose is an effective and safe option.

Background and objective: The use of low levels of visible or near infrared light for reducing pain, inflammation and oedema, promoting healing of wounds, deeper tissue and nerves, and preventing tissue damage has been known for almost 40 years since the invention of lasers. The HairMax LaserComb® is a hand-held Class 3R lower level laser therapy device that contains a single laser module that emulates 9 beams at a wavelength of 655 nm (±5%). The device uses a technique of parting the user’s hair by combs that are attached to the device. This improves delivery of distributed laser light to the scalp. The combs are designed so that each of the teeth on the combs aligns with a laser beam. By aligning the teeth with the laser beams, the hair can be parted and the laser energy delivered to the scalp of the user without obstruction by the individual hairs on the scalp. The primary aim of the study was to assess the safety and effectiveness of the HairMax LaserComb® laser phototherapy device in the promotion of hair growth and in the cessation of hair loss in males diagnosed with androgenetic alopecia (AGA). Methods: This double-blind, sham device-controlled, multicentre, 26-week trial randomized male patients with Norwood-Hamilton classes IIa-V AGA to treatment with the HairMax LaserComb® or the sham device (2: 1). The sham device used in the study was identical to the active device except that the laser light was replaced by a non-active incandescent light source. Results: Of the 110 patients who completed the study, subjects in the HairMax LaserComb® treatment group exhibited a significantly greater increase in mean terminal hair density than subjects in the sham device group (p <0.0001). Consistent with this evidence for primary effectiveness, significant improvements in overall hair regrowth were demonstrated in terms of patients’ subjective assessment (p < 0.015) at 26 weeks over baseline. The HairMax LaserComb® was well tolerated with no serious adverse events reported and no statistical difference in adverse effects between the study groups. Conclusions: The results of this study suggest that the HairMax LaserComb® is an effective, well tolerated and safe laser phototherapy device for the treatment of AGA in males.