Eucalyptus – Eucalyptus leaf (Eucalypti folium)
|Latin name of the genus:||Eucalyptus|
|Latin name of herbal substance:||Eucalypti folium|
|Botanical name of plant:||Eucalyptus globulus labill.|
|English common name of herbal substance:||Eucalyptus leaf|
Latin name of the genus: Eucalyptus
Latin name of herbal substance: Eucalypti folium
Botanical name of plant: Eucalyptus globulus Labill.
English common name of herbal substance: Eucalyptus leaf
- 1. Introduction
- 2. Historical data on medicinal use
- 3. Non-Clinical Data
- 3.1. Overview of available pharmacological data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
- 3.2. Overview of available pharmacokinetic data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
- 3.3. Overview of available toxicological data regarding the herbal substance(s)/herbal preparation(s) and constituents thereof
- 3.4. Overall conclusions on non-clinical data
- 4. Clinical Data
- 4.1. Clinical Pharmacology
- 4.1.1. Overview of pharmacodynamic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
- 4.1.2. Overview of pharmacokinetic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
- 4.2. Clinical Efficacy
- 4.2.1. Dose response studies
- 4.2.2. Clinical studies (case studies and clinical trials)
- 4.2.3. Clinical studies in special populations (e.g. elderly and children)
- 4.3. Overall conclusions on clinical pharmacology and efficacy
- 5. Clinical Safety/Pharmacovigilance
- 6. Overall conclusions
1.1. Description of the herbal substance(s), herbal preparation(s) or combinations thereof
Eucalypti folium consists of the dried leaves of Eucalyptus globulus Labill. (Myrtaceae).
Definition of the herbal substance:
European Pharmacopoeia 7th ed. 2011 (7.1), British Herbal Compendium 2006 [Bradley 2006], Real Farmacopea Espanola 2002 and according to the Deutsches Arzneibuch DAB 10 (German Pharmacopoeia): “Eucalyptus leaves are the whole or cut dried leaves of older branches of Eucalyptus globulus Labill. Content: minimum 20 ml/kg of essential oil for the whole drug (anhydrous drug) and minimum 15 ml/kg of essential oil for the cut drug (anhydrous drug).”
Pharmacopée française X (10ème édition): “Eucalyptus defined as dried leaves of Eucalyptus globulus Labill. It contains a minimum of 2% V/m essential oil.”
Eucalyptus is indigenous to Tasmania and
Eucalyptus is an evergreen tree with leathery leaves. The leaves are ensiform or
The leaves are studded with brown lenticels and colourless glands containing a fragrant volatile oil.
There are several varieties of Eucalyptus. Eucalyptus globulus is the most popular in terms of cultivation and medicinal use. The trees with the highest cineole content
Powdered plant material is a
The herbal substance (dried leaves) contains
phloroglucinol derivates such as euglobals and macrocarpals [Wichtl 2004]. The leaves of Eucalyptus globulus have smaller amounts of tannins than many other Eucalyptus species [Duke 1985]. Tannin content can depend on the methods of drying leaves [Cork & Krockenberger 1991].
Recent investigations made by
A further constituent of the leaves is the plant cuticle that consists of
The regular usage of the herbal tea in Germany led to the publication of a standard license in 1996 which is used by pharmacies and applicants. No further specific medicinal product was mentioned in the market overview with Eucalyptus leaf or preparation thereof as a single active substance.
There are many reports on herbal preparations in literature and monographs (see also section 2):
−Dried leaf infusion; the hot infusion may also be used for inhalation [Bradley 2006]
−Tincture (1:5)*, extraction solvent: ethanol 70% (V/V) [DAC 2004]
−Tincture (1:5)*, extraction solvent: diluted wine spirit [Ergänzungsbuch zum Deutschen Arzneibuch EB6 1951]. “Diluted wine spirit” contains ethanol
−Tincture (1:5)*, extraction solvent: ethanol 80% (V/V) [Pharmacopée Française IX 1976]
−Eucalyptus tincture (1:5)*, extraction solvent ethanol 80% (V/V) [Pharmacopée Belge V 1962]
−Tincture (1:5)*, extraction solvent: ethanol 45% [Bradley 2006]
−Syrup 10%, without further specification [Pharmacopée Française IX 1976, Madaus 1938]
−Powdered whole drug, herbal tea, aqueous alcoholic extracts of “low strength” prepared with ethyl alcohol of a strength with less than or equal to 30% (V/V), of “high strength” prepared with ethyl alcohol of more than 30% (V/V) [Cahier N°3 de l’Agence du Médicament 1998].
*ratio of herbal substance to extraction solvent
•Combinations of herbal substance(s) and/or herbal preparation(s) including a description of vitamin(s) and/or mineral(s) as ingredients of traditional combination herbal medicinal products assessed, where applicable.
Eucalyptus leaves are often marketed as a combination with other herbal substances/preparations for the treatment of cough associated with cold e.g. Peppermint oil, Juniper oil, Fennel oil, Turpentine oil, Pine oil, extract of pigmenta radicis curcumae, frangulaemodin, Calendula tincture, Abietis sibiricae oil, Hippophae oil, Citrus sinensis, Lagerstroemia, Citrus limonum or other active substances such as levomenthol, thymol, menthol, camphor, guaiazulene, benzalkonium chloride, methyl salicylate, magnesium salicylate and alpha tocopherol acetate.
1.2. Information about products on the market in the Member States
Regulatory status overview
MA: Marketing Authorisation TRAD: Traditional Use Registration
Other TRAD: Other national Traditional systems of registration Other: If known, it should be specified or otherwise add ’Not Known’
This regulatory overview is not legally binding and does not necessarily reflect the legal status of the products in the MSs concerned.
1.3. Search and assessment methodology
Data bases PubMed (April 2011) and DIMDI – DB (Deutsche Institut für medizinische Dokumentation und Information) were searched using the terms: “Eucalyptus folium, Eucalyptus leaves, Eucalyptus globulus, Cineole”. Additional handbooks and textbooks as cited in the references list were used.
Only articles found to be relevant for assessment are included in the list of references.
2. Historical data on medicinal use
2.1. Information on period of medicinal use in the Community
The usage of Eucalyptus leaf as herbal tea has a long history and the importance is underlined by the release of a standard license in Germany. Furthermore, a traditional use can be regarded as established because a lot of monographs on Eucalyptus folium are included in handbooks and the Pharmacopoeias of the European Union (EU) (see sections 2.2. and 2.3.).
Already in 1873, Köhler described the use in South Europe and the benefits on health of Eucalyptus preparations. As an example, he described effects on fever, neuralgic pain, asthma, lung tuberculosis, and antisepsis. In 1938, Madaus described the use of Eucalyptus leaves and its volatile oil as follows: “The oil stimulates the excretion of saliva and gastric juice. It enhances the appetite. Oral application of a syrup is described for whooping cough and external use of the leaves as an antiseptic agent. Additionally it is used as an inhalation for the treatment of catarrh and inflammatory diseases of respiratory tract and in cases of asthma. It is also used as a remedy for fever, catarrh of the urinary tract, influenza, rheumatism, neuralgias, malaria, fevered diarrhoea, gum bleeding and as an anthelmintic. Beside an oral application of Eucalyptus leaf, topical treatments as an antiseptic agent have been described.”
A survey, filled in by parents of children and adolescents, was conducted in Germany in 2007. Its results showed that 43.9% of the children were given Eucalyptus preparations in the last 6 years [Hümer et al. 2010]. No further information about the applied products or their indication was given. However it confirmed the use and the tradition of Eucalyptus in the EU as a medicinal product.
2.2. Information on traditional/current indications and specified substances/preparations
In folk medicine, it is used internally for the treatment of asthma, fever, flu, whooping cough, loss of appetite, dyspeptic complaints, inflammatory and infectious diseases of kidneys and bladder, diabetes, rheumatic complaints. It is used externally for wounds, acne, poorly healing ulcers, stomatitis, bleeding gums, rheumatism, neuralgia and gonorrhoea. All these applications have not been confirmed scientifically [Blaschek et al. 2007].
Diepenbrock’s Gehes Codes  reports on the use of a distillate of the leaves as an inhalant for treatment of disorders of respiratory tract and bronchial asthma.
Penso  listed Eucalyptus preparations for the treatment of respiratory diseases. No particular wording for indication is given.
The Pharmacopée Française monograph “Eucalyptus”  listed the following indication: ”antiseptic agent in the lung and
The Cahier N°3 de l’Agence du Médicament  listed the following traditional indications:
−oral use: “Traditionally used during benign acute bronchial conditions. N.B. if the condition persists, consult a doctor”.
−topical use: ”Traditionally used during benign acute bronchial conditions. N.B. if the condition persists, consult a doctor” and ”Traditional use in case of nasal congestion and common cold”.
Wichtl  mentioned the following indication: “catarrhal disorders of the respiratory tract”.
The monograph of the Commission E approves Eucalyptus leaves as a medicinal product for the treatment of diseases of the respiratory tract [Blumenthal et al. 1998].
In Martindale [Sweetman 2007], it has been referred: “Eucalyptus leaf has been used in oral preparations for coughs and associated
The WHO monograph  referred to the Commission E monograph and to the African pharmacopoeia 1985. According to the latter, Eucalyptus is used for the symptomatic treatment of asthma, fever and inflammation of the throat.
Traditional use of Eucalyptus leaf (powdered herbal substance and herbal substance) was reported by Spain (see sections 1.2. and 2.3.).
Traditional use outside the EU
In Australia, it is used for the treatment of headache and in South Africa for the treatment of stomach ache [Blaschek et al. 2007]. None of these indications are supported by scientific data.
An inquiry of 100 adults yielded that, in Oregon (USA), Eucalyptus and its preparations was used for the treatment of cough, colds, sore throat and sinusitis.
A survey, conducted by Otoom et al. , confirmed the use of Eucalyptus leaves as a traditional medicine used by diabetic patients in Jordan. No further information on posology or side effects was given.
Eucalyptus leaves have been listed as a Mexican traditional medicine used for treatment of common infections such as bronchial affections, cough, asthma, pharyngitis, cold, fever and wounds [Navarro et al. 1996].
As some reported indications require a supervision of a physician, they cannot be listed in the monograph as a traditional indication.
In response to the public call for scientific data, data on the traditional use of Eucalyptus leaf and its preparations in India have been submitted. Submitted data included the traditional use of the powdered leaves as a febrifuge, carminative, stimulant (no further information), expectorant, diaphoretic and antiseptic. As a single oral dose for adults
Handbooks, Gehes Codes and Pharmacopée Française as well as Penso (1980) support the traditional use of Eucalyptus as a medicinal product in the EU for more than 30 years. Traditional use for the treatment of several medical conditions has been reported. Some of the cited therapeutic indications are insufficiently described and not supported by scientific data, thus it is recommended to list only the indications that are appropriate for traditional use without the supervision of a medical
practitioner for diagnostic purposes or for prescription or monitoring of treatment. Because bronchial asthma should be supervised by a medical practitioner, it is not included as a traditional indication.
2.3. Specified strength/posology/route of administration/duration of use for relevant preparations and indications
The monograph on Eucalypti folium of the Commission E for herbal medicinal products [Blumenthal et al. 1998] gives a daily dose for oral use as follows: corresponding to
Additionally a topical use for the same indication is listed, but information on the posology is missing.
For the treatment of diseases of respiratory tract, the traditional daily oral posology is 3 cups of about 1.8 g herbal substance in 150 ml boiling water, steeping time
The British Herbal Compendium gives the following posology: Hot infusion corresponding to
According to “Médicaments traditionnels à base de plantes: Liste des indications acceptées pour une mise devant le comptoir” published by the Afssaps in July 2008 referring to the indications found in the Cahier N°3 de l’Agence du Médicament, the administration should be limited to one week and to adults and children aged 6 years and older. Concerning the posology, reference is made to the Pharmacopée Française monograph “Tisanes” . It recommends an oral dosage of
Penso  described in the “Piante medicinali nella terapia medica” some oral antiseptics for treatment of respiratory diseases, including 0.5 g powdered Eucalyptus leaves 6 times a day, 200 ml herbal tea (prepared with 10 g leaves/1,000 ml water) every 3 h, 100 drops of tincture (prepared with 200 g leaves macerated 10 days with 1,000 g ethanol 80%) in a cup of warm honeyish water every 4 hours, or 2 to 5 table spoons of a syrup (prepared with 100 g powdered leaves and 1,500 g water, and subsequent added sugar 180 g per 100 ml infusion) per day. This corresponds to 0.2 to 8 g herbal substance as a daily dose.
Schmid et al.  summarised the common posologies for Eucalyptus preparations. For Eucalyptus leaves they gave a common single dose of 1.5 g and for Eucalyptus tincture a single dose of 2.5 g. A later edition of their book gave as a single dose for Eucalyptus leaves 2 g and for Eucalyptus tincture 2.5 g. For Eucalyptus leaves, a daily dose is
Spain reported the traditional use of Eucalyptus leaf as herbal tea/vapour for inhalation and as hard capsules for the treatment of common cold and cough. Reported posology ranged from 230 to
690 mg powdered herbal substance as single dose and 1.8 to 2 g as daily dose, and 3 to 9 g daily as herbal tea (3 g/250 ml water)/inhalant (3 g in boiling water).
In conclusion, the use of Eucalyptus leaf and its preparations for the treatment of disorders of upper respiratory tract and colds has been known for a long time. Based on the listed indications of European monographs and the documented usual dosage, only the following indication is proposed for a traditional use without the supervision of a medical practitioner for diagnostic purposes or for prescription or monitoring of treatment:
Oral use and as an inhalant: “Traditional herbal medicinal product used for relief of cough associated with cold.”
This indication is not supported by sufficient pharmacological and clinical data (see section 4.) to consider a
Reported dosages vary in wide range and are inconsistent.
For infusions for oral use, single dosages range from 1.5 to 3 g herbal substance and daily doses range from 2.5 to 20 g herbal substance. The most common posology is about 4 to 9 g herbal substance per day. The posology given in the Pharmacopée Française i.e. a daily dose of: up to 4 times a day a cup of herbal tea prepared with 1.5 to 3 g Eucalyptus leaves in 150 ml boiling water, steeping time 10 to 15 minutes, is appropriate for the Community herbal monograph.
The hot infusion may also be used as an inhalation. For the inhalant, the posology ranges from 2 to 3 g single dose up to 3 times a day. Bradley 2006 and Spain cite that the infusion preparation can also be used as an inhalant, with a single dose of 3 g herbal substance in boiling water, without further information.
For tinctures for oral use, the posology varies from 1 to 10 g a day. But the most cited dosage is 2.5 g tincture 1 to 4 times a day that corresponds to 0.5 g herbal substance as a single dose and 0.5 to 2 g herbal substance a day.
The posologies given in the monograph reflect the wide ranges found in the literature or tradition. A footnote in section 4.2. of the monograph points out that the posology applied for an individual medicinal product has to be specified in a tighter range and should be consistent concerning the single and daily dosages.
The posology of the syrup as well as that for the topical use are not sufficiently and comprehensively described. Therefore, these traditional uses cannot be regarded as sufficiently supported by the literature and are not listed in the monograph.
3.1. Overview of available pharmacological data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
Pharmacological information on Eucalyptus leaves and/or their preparations is limited. Most publications deal with the effects of Eucalyptus oil. As Eucalyptus oil is extracted from fresh leaves of
Eucalyptus globulus Labill., Eucalyptus fructicetorum F.V. Mueller (syn. Eucalyptus polybractea) and
Eucalyptus smithii R.T. Baker, the data cannot be transferred to dried leaves.
Antibacterial, antifungal and antiviral effects
Many studies deal with the antibacterial effects of plants or plant extracts. For Eucalyptus globulus leaves extracts a high inhibition activity on bacteria and fungi growth has been described. Although Cimanga et al.  found no correlation between the amount of
The following comments refer mainly to the extracts, with less emphasis on the purified compounds.
Eucalyptus globulus leaves and preparations
Brantner & Grein  tested an aqueous extract (50 ml boiling water to 5 g air dried, powdered drug and heated under reflux for 5 minutes) for its antibacterial potential by using
Osawa et al.  showed that eucalyptone, an isolated compound of an ethanolic extract of Eucalyptus leaves (50% ethanolic extract from dried leaves), inhibited the enzyme glucosyltransferase and has an antibacterial activity against cariogenic bacteria (different
Navarro et al.  investigated the antimicrobial activity against S. aureus, E. coli, Pseudomonas aeruginosa and Candida albicans. Eucalyptus globulus dry extracts (100 g dried material macerated with 1500 ml methanol, distilled to dry extracts and subsequent dilution in 10% Tween 80 to different concentrations) showed a general antimicrobial effect against all the microorganisms tested (108 CFU/ml) at concentrations of 10 mg/ml or below.
Salari et al.  investigated the antimicrobial activity of Eucalyptus globulus leaf extracts (methanolic extract dissolved in
Caceres et al.  found that an ethanolic maceration of 10 g powdered dried leaves with 100 ml 50% ethanol showed only an unclear inhibition on C. albicans and E. coli.
The same author found that an aqueous extract of leaves (40 g powdered plant material boiled 5 minutes with 200 ml water, then concentrated on 1 g/ml of dry material) inhibits the growth of
Epidermophyton floccosum. Six dermatophyte strains were tested. An inhibition effect of Eucalyptus extract on the other strains was not found [Caceres et al. 1991].
In order to compare the antibacterial activity with six antibiotics,
aeruginosa was the predominant pathogen followed by S. aureus which was isolated from 92 cases of burn infections. The Eucalyptus extracts gave comparable effects on bacterial growth of
P. aeruginosa to penicillin G (10 units), kannamycin (30 mg), cephalexin (30 mg), tetracycline (30 µg), neomycin (30 µg) and gentamicin (10 mg).
May & Willuhn  examined aqueous extracts (1 part substance to 10 parts water infusion) from 178 plants, for their virustatic activity. Results were given in mm zone of inhibition. For Eucalyptus infusions, a
Takasaki et al. [1990, 1995] examined the inhibitory effects on
Amakura et al.  isolated and identified constituents of Eucalyptus leaves extracts.
Bokaeian et al.  investigated Eucalyptus and its effect on systemic infection with Candida albicans in diabetic rats. Sixty normoglycaemic male Wistar rats were selected and divided into 6 groups. In three groups (each n=10) diabetes was induced by injection of streptozotocin. Four groups were inoculated with C. albicans 15 days after diabetes induction. Eucalyptus (dried and
powdered leaves) was added to the diet (62.5 g/kg, pellets made from powdered leaves mixed with distilled water and subsequently drying at 45°C) and to the drinking water (2.5 g/l, 2.5 g powdered leaves mixed with 100 ml distilled water, brought to boil, then removed after 15 minutes, filtered and diluted with tap water) for 4 weeks. Eucalyptus lowered C. albicans concentration in liver and kidney homogenates in both diabetic group and control group. Additionally, Eucalyptus administration improved the hyperglycaemia and it compensated weight loss of diabetic rats.
Effects on bronchitis, asthma, cold and cough
Ikawati et al.  studied ethanolic and hexane plant extracts of several Indonesian medicinal plants, including Eucalyptus globulus leaves. The dried powdered plant material was extracted with
Laude et al.  studied the antitussive effects of cineole in conscious
Zänker et al.  investigated the effect of vapours of
Eucalyptus globulus has been reported as a therapeutic plant in airway inflammatory diseases. Considering that reactive oxygen species and reactive nitrogen species may be implicated in the pathogenesis of airway inflammatory diseases such as asthma and chronic obstructive pulmonary diseases (COPD), Almeida et al.  investigated an effective scavenging activity against these reactive species of Eucalyptus globulus leaf extract (2 g dried leaves were extracted 10 minutes with 5 times 50 ml
Thymus vulgaris extracts.
Juergens et al. investigated the
A study [1998a] showed that
A study in 2001 yielded an increased lung function due to an inhibition of cytokine production. 600 µg
authors found that
Santos & Rao  demonstrated that
showed an antinociceptive activity comparable to that of morphine in male Wistar rats and male Swiss mice. It showed a significant effect at 30 minutes and 60 minutes in the
Antioxidant activities of Eucalyptus leaves extracts and its compounds were evaluated by the linoleic acid peroxidation assay, the superoxide anion radical generation assay and DPPH
Already in 1902, Faulds described the traditional use of Eucalyptus for the treatment of diabetes. In order to investigate a possible antidiabetic effect, several
Studies in streptozotocin
Eucalyptus (6.25% by weight of diet) and a decoction of Eucalyptus leaves in the drinking water (1 g substance/400 ml water) lowered plasma glucose concentrations significantly in
Already in 1964, Lin et al. investigated the hypoglycaemic activity of medicinal herbs on alloxan- treated rabbits. But oral administration of 1 g/kg body weight (Eucalyptus dry residue of the ethanolic extract) showed no effect on the blood sugar levels.
In contrast to that by Lin et al., other studies showed a significant effect. Perez et al.  investigated the effect of different Mexican plants on mice with
A significant reduced blood glucose level in
Two published studies by Sugimoto et al. [2005, 2010] deal with the effects of Eucalyptus aqueous extracts on sugar metabolism in Wistar rats. The results indicated that Eucalyptus extracts inhibit intestinal fructose absorption and can suppress adiposity.
Although Eucalyptus oil and
Studies on the effects on several bacterial strains, viruses and fungi may be seen to confirm an antimicrobial, antifungal and antiviral effect of Eucalyptus leaves preparations. But in most studies, the extract is not exactly defined. Therefore, it is difficult to give a defined concentration that may be effective against defined strains.
Studies on the effects on cough and cold have not been performed for Eucalyptus leaves preparations. One study dealt with an inhibition effect of histamine release that might be of importance for asthmatic patients. But asthma is not of interest in this context, because it cannot be regarded as a disease that should be treated with products on the basis of their
Studies on diabetic animals and the use as repellent are not supported by a traditional use; therefore these data are not relevant here.
3.2. Overview of available pharmacokinetic data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
No data are available for the herbal substance or its preparations. Limited data are available on Eucalyptus oil, but it has to be taken into account that it is made from fresh leaves of different species. The main component of the essential oil of Eucalyptus leaves is
There are only a few studies on the pharmacokinetics of
A maximum concentration of
Cineole has been found to increase significantly the activity of the microsomal enzyme system [Jori et al. 1969]. Rats were treated by subcutaneous (s.c.) injection (cineole 500 mg/kg daily for 4 days) or aerosol inhalation (4 days, twice 15 minutes and twice 30 minutes; 50 mg/minutes).
The effect of
An inhibitory effect on
Saify et al.  investigated the skin penetration enhancer effect of
3.3. Overview of available toxicological data regarding the herbal substance(s)/herbal preparation(s) and constituents thereof
Only scarce data are available on the herbal substance and preparations thereof. Therefore data on
Aswal et al.  cited a LD50 of 652 mg/kg i.p. on mice for the Eucalyptus tincture (1:5) that was produced by extraction with wine spirit. No further information on the study was given.
The LD50 oral dose found by Jenner et al.  on
De Vincenzi et al.  summarised the toxicity data of
2,400 mg/kg/day showed 50% of mortality in both sexes. Cineole given in encapsulated form corresponding to 0, 381, 766, 1,740 and 3,342 mg/kg showed a
Kristiansen & Madsen  found that the treatment of Wistar rats with
Schimmer et al.  evaluated Eucalyptus tincture (according to the German Pharmacopoeia 6th ed. supplement; manufactured with wine spirit), beside other plant extracts, in an AMES mutagenicity test. Salmonella typhimurium strains TA 98 and TA 100 were used with and without S9 mix (from induced rat liver microsomes) as indicator cells. At the maximum dose of 80 µl/plate, Eucalyptus tincture showed a toxicity that was reduced in the presence of S9 mix. Nevertheless, mutagenicity could not be detected. A possible effect of the ethanolic component of the extract on the results has not been discussed.
Sasaki et al.  treated Chinese hamster ovary cells with 0.15 µm mitomycin C for 21 hours and
No data on Eucalyptus leaf preparations are available.
Stoner et al.  examined the ability of
The treatment of male Wistar rats with
phenomenon, which is exclusively found in adult male rats.
A comparable concentration of
In order to investigate the possibility of stimulating drug metabolism in foetal and neonatal periods, pregnant and lactating rats were treated with cineole (500 mg/kg s.c. daily for 4 days between day 10 and 14 of pregnancy or during the last 4 days of pregnancy or between day 2 and 6 after delivery). Cineole increased liver microsomal enzyme activity of mothers (for all experiments) and foetuses, but not in suckling newborn rats. Nursing mother rats, treated with cineole, showed an increased liver enzymatic activity, too. The authors concluded that cineole cannot cross the blood- milk barrier, but it is able to penetrate the placenta tissue [Jori & Briatico 1973].
3.4. Overall conclusions on
In summary, effects on a broad spectrum of bacteria, fungi and viruses reported by
According to Whitman & Ghazizadeh , the therapeutic effects of Eucalyptus based medications, in settings of pharyngitis and pharyngeal inflammation, may be due to the presence of
As shown in section 2., Eucalyptus globulus leaves and their preparations have a long tradition with benefits for diseases of the upper respiratory tract. Nevertheless,
Another benefit is that cineole causes a sensation of cold and this is accompanied with a facilitated respiration [Saller et al. 1988].
For the herbal substance or herbal preparations thereof, no sufficient data are available. Therefore, no statements on the pharmacokinetics of Eucalyptus globulus leaves preparations can be made.
Despite this fact the published data on cineole should be taken into account.
No toxicological information on the herbal substance or herbal preparations thereof is available. Results for cineole are of limited value for the monograph on Eucalyptus globulus, folium. Therefore, a Community list entry cannot be recommended from a
4. Clinical Data
4.1. Clinical Pharmacology
4.1.1. Overview of pharmacodynamic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
Clinical data on Eucalyptus leaves or preparations thereof are missing. But the effects of
The increased relaxation feeling, due to
4.1.2. Overview of pharmacokinetic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
The uptake of
Inhalation and oral
Kohlert et al.  reviewed the published data on bioavailability and pharmacokinetics of volatile terpenes. Concerning the
4.2. Clinical Efficacy
Studies on efficacy of Eucalyptus globulus leaves and preparations thereof have only been performed for the treatment of dental and oral diseases or for the treatment of wound infections [Sato et al. 1998; Sherry et al. 2001]. All studies supported an antimicrobial and
Sato et al.  studied the effect of chewing gum with Eucalyptus extract on plaque formation. Eucalyptus significantly reduced plaque compared to control gum. The authors attributed this effect to the antibacterial activity of macrocarpals (constituents of Eucalyptus) against S. mutans and P. gingivalis. No information about the Eucalyptus extract or about the amounts in gum were given. Sherry et al.  reported that a medicinal product called Polytoxinol®, which is a complex formulation of Eucalyptus plant extracts, was administered percutaneously to orthopaedic patient
with wound infections. Polytoxinol® was more effective against a broad range of aerobic bacteria (e.g. MRSA) than antibiotics such as flucloxacillin.
Some (pilot) studies have been performed for different indications. The data available are not sufficient to assess efficacy. Moreover,
Several studies on the efficacy of cineole have been published.
Kehrl et al.  compared efficacy and safety of cineole capsules with placebo in 152 patients with acute rhinosinusitis. A dosage of 100 mg 3 times a day was administrated for 7 days (75 placebo, 75 cineole). Significant differences were seen from beginning to the end of treatment for amelioration of headache on bending, sensitivity of pressure points of trigeminal nerve, nasal obstruction, secretion quantity and viscosity and rhinological secretion as well as for redness of mucosa. After 7 days, the differences between both groups were statistically significant in the same parameters. No significant differences were found according to clinical findings of inflammation such as conjunctivitis, tracheitis, pharyngitis and bronchitis. No differences have been found for parameters of leukocyte count and erythrocyte sedimentation rate. The authors concluded that the early treatment of sinusitis with cineole can avoid antibiotic treatment. Mild side effects were observed in two patients as heartburn and exanthema.
In another study, 150 patients with acute and viral rhinosinusitis were treated with cineole or a herbal combination product (Gentianae radix, Primulae flos, Ramicis herba, Sambuci flos, Verbenae herba). Both treated groups showed an improvement in all relevant characteristics for rhinosinusitis within 7 days. A significant benefit after treatment with cineole could be detected for bronchitis but not for pharyngitis, tracheitis and conjunctivitis. Scores for headache on bending, frontal headache, sensitivity of pressure points of trigeminal nerve, nasal obstruction and
Sinusitis and its symptoms are difficult to score because of the individual perception. Image studies (such as ultrasonic or computed tomography) have not been performed.
Worth et al.  studied the effects of cineole (200 mg 3 times a day for 6 months as concomitant therapy) in comparison with placebo in a
In order to compare the effects of oral therapy with cineole (3 times 200 mg/day) and ambroxol (3 times 30 mg/day) after treatment over one week, a randomised
Another combination product was studied by Böhlau & Schildwächter . Aerosol administration of the combination of cineole, thymol, anis oil, azulene and propylenglycol showed a decrease of cough intensity and amount of sputum, but no improvement of pulmonary function could be detected.
Several studies dealt with effects of cineole on pulmonary diseases, but none with Eucalyptus leaves preparations. Due to the small number of treated patients, results failed to be significant or cineole treatment was only a concomitant one. Therefore, these results are not clear enough to apply them to Eucalyptus leaves.
4.2.1. Dose response studies
No dose response studies on Eucalyptus leaves or preparation thereof have been published.
4.2.2. Clinical studies (case studies and clinical trials)
In contrast to its widespread use, clinical studies on Eucalyptus leaves containing preparations are missing. Due to its characteristic taste and smell, it may almost be impossible to conduct a blinded study.
4.2.3. Clinical studies in special populations (e.g. elderly and children)
No studies on special populations such as children or elderly have been performed.
4.3. Overall conclusions on clinical pharmacology and efficacy
Despite the popularity of Eucalyptus and its long usage for treatment of diseases of upper respiratory tracts, there has been little clinical research on their effects on cough and cold.
Studies on cineole showed that it is well absorbed from inhalation and from oral administration. Studies on clinical efficacy of cineole showed that it has some effects in rhinosinusitis and obstructive pulmonary diseases.
The content of cineole may contribute to the effects of Eucalyptus leaves preparations. Dried Eucalyptus leaves contain 1 to 3.5% essential oil. The essential oil contains about 54 to 95% of the major constituent
A daily dose of 300 mg
Additionally, it should be taken into account that the pass over rates from the herbal substance into the infusion or the tincture might not be 100%. For an infusion made from Salvia officinalis, for example, a transfer rate of
100 mg i.e. a maximum of 33% of the dosages in the published clinical studies.
5. Clinical Safety/Pharmacovigilance
5.1. Overview of toxicological/safety data from clinical trials in humans
No relevant data on Eucalyptus leaves preparations are available.
5.2. Patient exposure
Mild side effects such as heartburn and exanthema were observed in 2 out of 75 patients treated with
5.3. Adverse events and serious adverse events and deaths
The Commission E monograph lists nausea, vomiting and diarrhoea as possible side effects. As contraindications, inflammatory diseases of the gastrointestinal tract, gall bladder disease or impaired liver function are given. Additionally, Eucalyptus preparations for external use should not be
applied to the face, especially the nose, of infants or young children. The oil may induce liver enzymes that are involved in drug metabolism. Therefore, the effects of other drugs may influence concomitant administrations [WHO monographs 2002, Blumenthal et al. 1998].
Saller et al. 1988 cited a lethal dose for adults of 4 to 5 ml Eucalyptus oil. For Eucalyptus leaves, they stated that poisoning by oral intake is very unlikely, because dried and comminuted Eucalyptus leaves contain only 1.5% essential oil (minimum according to European Pharmacopoeia 2011) – that corresponds to 267 to 333 g dried leaves. Reported maximum content is about 3.5%, that corresponds to 114 to 143 g dried comminuted leaves. The uptake of a single dose of more than 100 g dried leaves is almost not possible.
One case report by Vidal & Cabeza 1992 described a development of localized erythema and pruritus after contact with Eucalyptus leaves
A number of intoxication reports are available in the literature following accidental exposure to high doses of Eucalyptus oil. De Vincenzi et al.  summarised the case reports. The amounts ingested ranged from 1 ml to 220 ml. The described effects were gastrointestinal symptoms, followed by CNS depression, transient coma; one subject collapsed with rapid shallow respiration and a rapid and feeble pulse. Two patients survived after dialysis
Melis et al.  reported the following symptoms of poisoning with
5.4. Laboratory findings
5.5. Safety in special populations and situations
It has been described that the inhalation of essential oils, observed also for menthol and camphor, may lead to an irritation of the nasal mucosa, which can lead to a closure of glottis in infants
Due to the cooling effect and strong odour of Eucalyptus preparations it is recommended that ointments should not be applied to or near the face of babies and very young children because of the risk of reflex spasm of the glottis [ESCOP monographs 2003, Blumenthal et al. 1998]. Even apnoea may occur [Blaschek et al. 2007].
Since essential oils are steam volatile components, the use as an oral fluid or an inhalant could also generate the risk of reflex spasm for babies and very young children. Their use should therefore also be contraindicated in babies and very young children.
In order to investigate whether
5.6. Overall conclusions on clinical safety
The monograph of the Commission E “Eucalyptus leaves” gives some side effects and contraindications. Considering the history of development of this monograph, it appears that this information is based on the content of essential oil and cineole. Separate studies for the leaves, case reports or reports of unexpected drug interactions with preparations containing the leaves have not been published. Reporting system in Germany listed the following side effects for Eucalyptus oil containing medicinal products for adults:
allergic skin reaction (1), shock (1), tremor (1), decreased blood pressure and increased pulse (1), cold sweat (1), dizziness (3), tiredness (1), coordination abnormal (1), ataxia (1), aphasia (1), syncope (1), vomiting (1), urticaria (1)
skin disorders such as pustular rash (2).
These were considered for possible inclusion in the HMPC monograph; however Eucalyptus oil is only a small fraction of Eucalyptus leaf preparations. Dried and comminuted Eucalyptus leaves contain 1.5% essential oil (minimum according to European Pharmacopoeia 2011), therefore the reported side effects of Eucalyptus oil were considered irrelevant for the specified traditional use of Eucalyptus leaf preparations.
The results of Jori et al.  correspond to the
6. Overall conclusions
As summarised in section 3.1, the effects of Eucalyptus globulus leaves on the upper respiratory tract can be regarded as sufficiently supported by
No clinical data on the efficacy of Eucalyptus leaves preparations are available, thus a well- established use is not supported. From the clinical data on cineole, an effect on upper respiratory diseases is anticipated. But the actual cineole content of an herbal infusion or a tincture prepared from Eucalyptus globulus leaves is not known. Due to the widespread and
The preparations are herbal infusion (oral or as inhalant) and tincture (oral), in suitable pharmaceutical forms. Some authors and handbooks described a syrup and an ointment, but, for
both, no comprehensive posologies were reported. Therefore, a traditional use with a specified strength and posology for such syrup and ointment cannot be provided.
A posology of about 2 to 3 g herbal substance as a single dose and 6 to 9 g herbal substance as a daily dose is sufficiently supported by literature.
Relevant data on an application for children under 12 years of age are not available. Therefore, they are excluded from this therapy. The use in adolescents between 12 and 18 years of age could be accepted in accordance to the data available for Eucalyptus oil. However, having considered the amount of alcohol intake from the use of the tincture at the highest posology, the HMPC decided to restrict the use of the tincture to adults and elderly.
In line with the recommendation found in the Cahier N°3 de l’Agence du Médicament, the duration of use is limited to one week.
Based on the data on Eucalyptus oil, several contraindications were listed in the Commission E monograph. Due to an oil content of only 1.5 to 3.5%, they are irrelevant to the use of Eucalyptus leaf preparations as specified in the HMPC monograph. But since essential oils used as an oral fluid or an inhalant could generate the risk of reflex spasm for babies and very young children, the use in children under 2 years of age should be contraindicated. After discussion (meeting January 2013), the HMPC decided that the use must be contraindicated in children below 30 months.
For tinctures containing ethanol, the appropriate labelling for ethanol, taken from the ‘Guideline on excipients in the label and package leaflet of medicinal products for human use’, has to be included.
Drug interactions are possible, because a lot of
Safety during pregnancy and lactation has only been established on rats. The studies indicate that cineole can cross the placenta barrier, but not the
No relevant toxicological information on the herbal substance or herbal preparations thereof is available.
Due to the lack of toxicity data, a Community list entry cannot be supported.