Kaloba: 30 Tablets

Product Information

The liquid placebo was designed to match the appearance of the liquid herbal medicinal product. This was achieved by using the identical solvent composition (water, glycerol, ethanol) and by replacing the herbal active ingredient with colouring and flavouring. The placebo tablets were also designed to match the appearance of the active tablets, by using the identical film-coating composition and a coloured granulation for manufacturing of the uncoated tablets matching the tablet core of the herbal medicinal product. Baars EW, Zoen EBV, Breitkreuz T, Martin D, Matthes H, Schoen-Angerer TV, et al. The Contribution of Complementary and Alternative Medicine to Reduce Antibiotic Use: A Narrative Review of Health Concepts, Prevention, and Treatment Strategies. Evidence-based Complementary and Alternative Medicine. 2019;2019 (no pagination). Although patients only received one formulation (liquid or tablets) they were asked which they would prefer to receive. Six patients said that they would not mind either. Four patients said that they would prefer the liquid (because there is less pharmaceutical processing involved than in manufacturing tablets, and the liquid felt soothing for the throat). Fifteen said that they would prefer tablets, because they were already taking other tablets, tablets were easy to swallow, they were more convenient, one is less likely to take the wrong dose, there is no problem with spillage, they can be put in a weekly container and they are easier to carry out. The main reason for disliking the liquid was its taste. Several patients reported problems in measuring the liquid dose in drops and thought they may sometimes have taken the wrong dose; they would have preferred to measure the dose using a spoon. Two health professionals expressed similar concerns about dosing the liquid, but one reported that “ I perceived a problem but it wasn’t, it didn’t come to fruition actually… it’s to do with number of drops and things, isn’t it, but it wasn’t a problem” (HP02, GP). Study diaries

Macfarlane J, Holmes W, Gard P, Macfarlane R, Rose D, Weston V, et al. Prospective study of the incidence, aetiology and outcome of adult lower respiratory tract illness in the community. Thorax. 2001;56(2):109–14.

10 Date of revision of the text

In rare cases (≥1/10,000 to ≤ 1/1,000), mild bleeding from the gums or nose may occur. Furthermore, hypersensitivity reactions (e.g. exanthema, urticaria, pruritus of skin and mucous membranes) have been described in rare cases. Such reactions may occur after the first intake of the product. Bao Y, Gao Y, Koch E, Pan X, Jin Y, Cui X. Evaluation of pharmacodynamic activities of EPs(R) 7630, a special extract from roots of Pelargonium sidoides, in animals models of cough, secretolytic activity and acute bronchitis. Phytomedicine. 2015;22(4):504–9. Whitehead A, Simpson C, Willcox M, Webley F, Hay AD, Butler C, et al. HATRIC: a study of Pelargonium sidoides root extract EPs®7630 (Kaloba®) for the treatment of acute cough due to lower respiratory tract infection in adults—study protocol for a double blind, placebo-controlled randomised feasibility trial. Pilot and Feasibility Studies. 2019;5(1):98. Gastro-intestinal complaints such as stomach pain, heartburn, nausea, vomiting, difficulty swallowing (dysphagia) or diarrhoea. Of 543 patients screened, 261 were eligible, of whom 134 (51%) were recruited and 103 (77%) returned a completed diary. Overall, 41% (41/100) of patients took antibiotics (Kaloba® liquid group: 48% [15/31]; placebo liquid group: 23% [6/26]; Kaloba® tablet group: 48% [9/21]; placebo tablet group: 50% [11/22]). Most patients adhered to the study medication (median 19 out of 21 doses taken in week 1, IQR 18–21 - all arms combined). There were no serious adverse events relating to treatment. Most patients interviewed found study recruitment to be straightforward, but some found the diary too complex. Conclusions

Kaloba is a traditional herbal medicinal product used to relieve the symptoms of upper respiratory tract infections such as the common cold, sore throats and coughs exclusively based on long standing use as a traditional remedy. Herbal medicine is another option for relieving symptoms and so reducing inappropriate use of antibiotics [ 12]. Qualitative research has shown that herbal medicine is widely used and accepted as a viable option for treatment of mild respiratory infections, especially by ethnic minorities, but very few studies have included white Caucasian adults [ 13, 14, 15, 16]. Many patients feel that they need trustworthy advice on whether to use alternative treatments, which to use, and when [ 17]. Several strategies have attempted to reduce inappropriate use of antibiotics. “Delayed” prescriptions (which patients are advised to take only if they are not starting to improve after a certain time) reduce consumption of antibiotics while maintaining patient satisfaction [ 9], but many patients would still like to take medication to relieve their symptoms because a moderately bad cough is known to persist for around three weeks on average [ 6, 10]. Commonly recommended treatments like steam and ibuprofen make little or no difference to symptom severity [ 11]. Other potential symptomatic treatments in adults (the expectorant guaifenesin, mucolytics and antihistamine-decongestant combinations) have not been shown to have consistent benefit in a recently updated Cochrane systematic review [ 7].

3 Pharmaceutical form

Little P, Rumsby K, Kelly J, Watson L, Moore M, Warner G, et al. Information leaflet and antibiotic prescribing strategies for acute lower respiratory tract infection: a randomized controlled trial. JAMA. 2005;293(24):3029–35. The liquid herbal medicinal product used in the study (Kaloba® manufactured by Dr. Willmar Schwabe GmbH & Co. KG, Germany) is tested and released compliant with drug GMP and the European Pharmacopoeia according to written, authorized and validated analytical procedures with respect to identity, content (ethanol, glycerin, extract; HPLC) and microbiological quality. The film-coated tablets are tested with the same methods, adapted to the respective dosage form with respect to extract content (HPLC), uniformity, disintegration and microbiological purity. The respective placebo preparation is tested with the same procedures, except for herbal drug content (i.e. absence of active ingredient) and in addition for visual appearance in comparison to the batch of herbal drug product used as medication. The quality testing is performed by the Quality Control laboratory of Dr. Willmar Schwabe GmbH & Co. KG, Germany by a laboratory technician with extensive long-term experience in the testing of herbal medicinal products. Personnel manufacturing or performing quality tests on investigational medicinal products including placebo preparations have been specifically skilled and trained in this field. Conrad A, Hansmann C, Engels I, Daschner FD, Frank U. Extract of Pelargonium sidoides (EPs 7630) improves phagocytosis, oxidative burst, and intracellular killing of human peripheral blood phagocytes in vitro. Phytomedicine. 2007;14(Suppl 6):46–51. This medicinal product does not require any special storage conditions. 6.5 Nature and contents of container

Feasibility outcomes were: recruitment rate, withdrawal rate from the study, return rate of patient diaries, percentage of completion of patient diaries, compliance with medication according to diary data and returned medication, type of antibiotic prescription given (i.e. immediate/delayed/not given), percentage of patients who took antibiotics, time to antibiotic usage, mean symptom severity (at days 2–4), percentage of patients resolved, time to resolution of symptoms and duration of treatment with herbal medication. The minimum key outcome dataset from the diaries was considered to be [ 1] antibiotic use in the 28 days post randomisation, [ 2] no longer experiencing moderate symptoms for two consecutive days and [ 3] study medication use. A health economic study was a part of the feasibility study which aimed to develop the methods of data collection both for quality of life and for usage of key resources for the design of the future phase III trial.Kayser O, Kolodziej H, Kiderlen AF. Immunomodulatory principles of Pelargonium sidoides. Phytotherapy research: PTR. 2001;15(2):122–6. This is the first feasibility trial to be conducted on the use of a herbal medicine for acute bronchitis in UK primary care. A strength of this trial is the use of both quantitative and qualitative methods to explore several feasibility aspects. The trial was not powered to detect effectiveness, so we are unable to comment on the effectiveness of the herbal medicine. However, there was no evidence of any serious side-effects due to the intervention and the patient withdrawal rate was low. Although the study was only open for 9 months as opposed to the 12 months initially planned, we recruited at a faster rate than anticipated.