Papers by Katharina Hartmann
This chapter elaborates the drugs acting on the respiratory tract. Overall safety data show that ... more This chapter elaborates the drugs acting on the respiratory tract. Overall safety data show that the use of inhaled glucocorticoids is associated with systemic ad-verse effects in clinical practice, encompassing an approximately twofold increased risk of skin bruising and diminished bone mineral density in patients with COPD using moderate to high doses of inhaled triamcinolone, and reduced short-term growth velocity in children using budesonide 200 μg/day. Oropharyngeal candidiasis has an incidence of up to 70% in users of inhaled glucocorticoids, depending on the diagnostic criteria. The use of breath-actuated metered-dose inhalers leads to high oropharyngeal deposition of glucocorticoids, which can be 80% of the delivered dose. The effects of budesonide aqueous nasal spray on adrenal function was studied in a 6-week double-blind, placebo-controlled study in 78 patients with allergic rhinitis aged 2–5 years. The pulmonary and extra-pulmonary effects of cumulative doses of formoterol and salbutamol have also been compared.
... a large, ran-domized, controlled trial using standardized allergenextracts confirmed its effe... more ... a large, ran-domized, controlled trial using standardized allergenextracts confirmed its effectiveness and safety.REFERENCES 1. Van Ganse E, van der Linden PD, Leufkens HGM, Herings RMC, Vincken W ... Maesen FPV, Smeets JJ, Sledsens TJH, Wald FDM, Cornelissen PJG. ...
Side Effects of Drugs Annual, 2005
... a large, ran-domized, controlled trial using standardized allergenextracts confirmed its effe... more ... a large, ran-domized, controlled trial using standardized allergenextracts confirmed its effectiveness and safety.REFERENCES 1. Van Ganse E, van der Linden PD, Leufkens HGM, Herings RMC, Vincken W ... Maesen FPV, Smeets JJ, Sledsens TJH, Wald FDM, Cornelissen PJG. ...
Vaccine, 2008
Immediate passive immune prophylaxis as part of rabies post-exposure prophylaxis (PEP) often cann... more Immediate passive immune prophylaxis as part of rabies post-exposure prophylaxis (PEP) often cannot be provided due to limited availability of human or equine rabies immunoglobulin (HRIG and ERIG, respectively). We report first clinical data from two phase I studies evaluating a monoclonal antibody cocktail CL184 against rabies.
Vaccine, 2009
Background: Despite the established benefit of intramuscular (i.m.) influenza vaccination, new ad... more Background: Despite the established benefit of intramuscular (i.m.) influenza vaccination, new adjuvants and delivery methods for comparable or improved immunogenicity are being explored. Intradermal (i.d.) antigen administration is hypothesized to initiate an efficient immune response at reduced antigen doses similar to that observed after i.m. full dose vaccination. Methods: In a randomized, partially blinded phase II study 224, healthy adults aged ≥18 to ≤60 years were randomly assigned to four groups and received trivalent influenza vaccine at single doses of 3.0, 4.5 and 6.0 g hemagglutinin (HA) antigen of each influenza virus strain via i.d. injection or 15.0 g HA of each influenza strain via i.m. delivery. Serum anti-influenza virus antibodies were determined by hemagglutination inhibition (HI) assay before and 3 weeks after vaccination. Safety assessments were made at baseline and at the follow-up visit by the investigators and for a 4-day period post-vaccination by the subjects themselves. Results: The EMEA requirements for re-licensing of influenza vaccines were fulfilled in all groups 3 weeks after vaccination, irrespective of dose and mode of administration. High seroconversion rates were observed in all study groups and for all strains ranging from 50.9 to 85.5% and 70.4 to 87.0% after i.d. and i.m. vaccination, respectively. Seroprotection rates for the A strains A/Solomon Islands and A/Wisconsin were generally higher compared to the B/Malaysia strain and ranged from 89.1 to 98.2% across the i.d. groups. Similar rates of 96.3% for the A/Solomon Islands and 94.4% for the A/Wisconsin strain were observed in the i.m. group. Seroprotection rates for the B/Malaysia strain were 65.5, 83.0 and 72.7% after i.d. administration of 3.0, 4.5, and 6.0 g HA of each strain, respectively, compared to a seroprotection rate of 85.2% in the i.m. group. In addition, marked increases in geometric mean titer (GMT) were observed across the groups for all influenza virus strains ranging from 6.9 to 70.5 for i.d. and from 16.9 to 56.5 for i.m. antigen delivery. Both routes of administration were well tolerated. Systemic reactions were broadly similar across the groups. With respect to local reactions the frequency of injection site pain and ecchymosis were significantly lower following i.d. vaccination, while other local reactions such as erythema occurred at higher rates with i.d. than with i.m. vaccine administration, as expected due to the mechanism of action for the i.d. route. Conclusions: The virosomal adjuvanted influenza vaccine (Inflexal ® V) was shown to be overall highly immunogenic and well tolerated when given i.d. at reduced doses to healthy adults, eliciting an immune response similar to that observed with full dose i.m. administration and thus suggesting a promising antigen-sparing strategy for universal influenza vaccination against endemic influenza. Trial registration: ISRCTN registry number: 33950739.
Vaccine, 2009
Since the introduction to the Swiss market in 1997, Crucell (former Berna Biotech Ltd.), has sold... more Since the introduction to the Swiss market in 1997, Crucell (former Berna Biotech Ltd.), has sold over 41 million doses worldwide of the virosomal adjuvanted influenza vaccine, Inflexal ® V. Since 1992, 29 company sponsored clinical studies investigating the efficacy and safety of Inflexal ® V have been completed in which 3920 subjects participated. During its decade on the market, Inflexal ® V has shown an excellent tolerability profile due to its biocompatibility and purity. The vaccine contains no thiomersal or formaldehyde and its purity is reflected in the low ovalbumin content. By mimicking natural infection, the vaccine is highly efficacious. Inflexal ® V is the only adjuvanted influenza vaccine licensed for all age groups and shows a good immunogenicity in both healthy and immunocompromised elderly, adults and children. This review presents and discusses the experience with Inflexal ® V during the past decade.
Respiration, 2001
The Swiss Drug Monitoring Center (SANZ) uses a systematic approach to the collection of spontaneo... more The Swiss Drug Monitoring Center (SANZ) uses a systematic approach to the collection of spontaneously reported individual cases on suspected adverse drug reactions (ADRs). Spontaneous reporting schemes are designed to detect new, rare and unexpected ADRs and to act as an early warning system but there is a tendency to overreport severe reactions. The aim of the study was to determine drug-induced episodes of bronchospasm, their seriousness and predisposing risk factors. An ADR is classified as serious if the reaction results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity. From 1986 to 1995 SANZ received 8,191 case reports of suspected ADRs. In 187 cases (2%) bronchospasm was reported. In 55% of these cases the reaction was regarded as serious. Analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) were reported most frequently and were involved in 24% of the cases of which 64.5% were classified as serious. In three cases a lethal outcome was reported after intravenous administration of metamizol. Anti-infectious agents were implicated in 18% (52% serious), cardiovascular drugs in 11% (50% serious), drug formulation agents in 9% (41% serious), vaccines and immunoglobulins in 5.5% (50% serious), and plasma volume expanders in 5.5% (80% serious). Other drug groups were involved in 27% of the cases. About 50% of patients experiencing bronchospasm after NSAIDs, pharmaceutical formulation agents, vaccines and immunoglobulins had predisposing risk factors such as asthma, atopy or drug allergy. In other drug groups a predisposing factor was identified in 27% or less. Drug-induced bronchospasm is frequently reported with NSAIDs, anti-infective agents, cardiovascular drugs and excipients with a high proportion of serious reactions.
Pharmacoepidemiology and Drug Safety, 1999
From 1995 until June 1998 123 new chemical entities (NCEs) were launched in Switzerland. In this ... more From 1995 until June 1998 123 new chemical entities (NCEs) were launched in Switzerland. In this time period 250 reports of adverse reactions (ADRs) involving 56 different NCEs were reported to the Swiss Drug Monitoring Center SANZ directly by physicians within the voluntary spontaneous reporting scheme (SRS). No cases from observational or clinical postmarketing studies were included. Of the reports 88% were suspected to be drug-related and 20% of them were serious. In 64% the ADRs were unlabelled and not notified to the health professionals. Disorders of the central nervous system (CNS) were reported in 32% and cardiovascular disorders in 26% of the unlabelled and serious cases. The non-serious cases accounted for 80% of the reported NCE-ADRs and 60% of them were unlabelled. Skin reactions were reported most frequently (18%), followed by psychic (15%), gastrointestinal (10%), cardiovascular and CNS disorders (8% each). In the labelled non-serious cases gastrointestinal and skin reactions were reported in 25% and 24% respectively. The other system organ classes were involved to a much smaller extent (<8%). (1) Spontaneous reports are of great value in optimizing postmarketing safety information. (2) Early reports give rise to a different ADR profile than expected from premarketing safety information. (3) Spontaneous reports have a strong signalling function especially for drugs used by general practitioners. (4) Sensitive signal detection systems are of great value in detecting non-labelled and serious ADRs in an early phase.
Vaccine, 2007
Bell&... more Bell's palsy has been reported as an adverse event following immunization (AEFI). Review of the published literature reveals that several characteristics have been used to describe Bell's palsy, which differ significantly from author to author. Evidently, the definition of "Bell's palsy" remains controversial, and consensus between different medical subspecialties is urgently needed. The Brighton Collaboration has formed an international working group with representatives of neurology, otorhinolaryngology, pediatrics, electrophysiology, pharmacology, pharmaceutical and biotech industry as well as regulatory agencies to create a case definition of Bell's palsy as an AEFI.
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Papers by Katharina Hartmann