Diuretic herbal tea combinations – Combination: Species diureticae (Combination: maximum 4 out of 13 possible plants)

Latin name of the genus: Combination: species diureticae
Latin name of herbal substance: Combination: maximum 4 out of 13 possible plants
Botanical name of plant: Herbalref.com
English common name of herbal substance: Diuretic herbal tea combinations

Latin name of the genus: Combination: Species diureticae
Botanical name of plant: Combination: maximum 4 out of 13 possible plants
English common name of herbal substance: Diuretic herbal tea combinations

1. Introduction

1.1. Description of the herbal substance(s), herbal preparation(s) or combinations thereof

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.

This assessment report refers to herbal tea combinations used in the therapeutic area ‘urinary tract disorders’. Herbal substances contained in such combinations for which an assessment by the HMPC has been performed are Betulae folium, Equiseti herba, Graminis rhizoma (Agropyri repentis rhizoma), Juniperi galbulus (Juniperi pseudo-fructus), Levistici radix, Mate folium, Ononidis radix, Orthosiphonis folium, Phaseoli fructus, Polygoni avicularis herba, Solidaginis virgaureae herba, Urticae folium, Urticae herba and Uvae ursi folium.

Herbal substances linked to the therapeutic area but not yet assessed by the HMPC (e.g. Herniariae herba, Solidaginis giganteae herba) are not considered in this assessment report.

Additional herbal substances which may be combination partners but which are not linked to the therapeutic area are considered as excipients.

For the description of the herbal substances, their constituents, relevant pharmacopoeia monographs, non-clinical and clinical data please refer to the assessment reports of the single herbal substances.

1.2. Search and assessment methodology

The information regarding herbal tea combinations in the therapeutic area ‘urinary tract disorders’ was gathered from EU member states and the information provided by interested parties.

Standard handbooks of Phytotherapy were screened manually for relevant information.

Search in scientific databases for combinations did not provide any results.

For the scientific data on safety and efficacy of the single herbal substances contained in the combinations please refer to the assessment reports of the single herbal substances.

2. Data on medicinal use

2.1. Information about products on the market

2.1.1. Information about products on the market in the EU/EEA Member States

Information on medicinal products marketed in the EU/EEA

Not applicable

Information on relevant combination medicinal products marketed in the EU/EEA

Table 1: Overview of data obtained from marketed medicinal products

Herbal substances mentioned in brackets are considered as excipient (no plausible contribution to the traditional indication).

This overview is not exhaustive. It is provided for information only and reflects the situation at the time when it was established.

Belgium: list of tea combinations provided, but no clear diuretic tea among them.

Information on other products marketed in the EU/EEA (where relevant)

Not applicable

2.1.2. Information on products on the market outside the EU/EEA

Not applicable

2.2. Information on documented medicinal use and historical data from literature

Calculation of the mass of the single dose / daily dose when ‘spoon’ is referred:

Based on information from pharmaceutical industry the bulk density of herbal teas depends on the individual components as well as on the particle size. Cut herbal teas have a lower bulk density (e.g. less than 1 g for a traditional diuretic tea combination according to a German Standard Marketing Authorisation) compared to fine cut material for tea bags. However, the official information for the German Standard Marketing Authorisation mentions an equivalence of 1 teaspoon with 2-4 g of herbal tea combination. A similar calculation is cited in Fischer (1978). Therefore, as a mean 1 teaspoon is calculated as 2 grams.

Table 2: Overview of historical data

Herbal substances mentioned in brackets are considered as excipient (no plausible contribution to the traditional indication).

2.3. Overall conclusions on medicinal use

Table 3: Betulae folium in combinations

grey: no European Union herbal monograph developed so far

Combination Graminis rhizoma – Polygoni avicularis herba: Data regarding the single and daily dose of the combination are not clearly reported in the literature. Therefore this combination is not taken up into the monograph. The acceptable range for the monograph is therefore 10‒25%.

Table 6: Juniperi galbulus in combinations

Daily dose: up to 6 g

Frequency: up to 2 times daily

Dosage frequency: although the monograph on Levistici radix as single active ingredient states a dosage frequency of up to 2 times daily the proposed frequency of 3‒4 times daily is acceptable due to the considerable lower posology in combinations.

Table 8: Mate folium in combinations

grey: no European Union herbal monograph developed so far

Combination Polygoni avicularis herba – Graminis rhizoma: Data regarding the single and daily dose of the combination are not clearly reported in the literature. Therefore this combination is not taken up into the monograph. Therefore the evidence of traditional medicinal use is demonstrated for 12% only.

Table 13: Solidaginis virgaureae herba in combinations

grey: no European Union herbal monograph developed so far

Table 16:

Numbers indicate the percentage of a herbal substance (left row) in a combination with other herbal substances (excipients excluded) based on documented traditional medicinal use. (Instructions and an example how to apply the table are given on the following page.)

Example: When Betulae folium is combined with Ononidis radix then 10‒35% of Betulae folium is traditionally used in combinations. This combination contains 10‒30% Ononidis radix.

How to use the information on traditional medicinal use of these combinations?

Evidence for combination: the grey shaded fields in table 16 indicate combinations with evidence of traditional medicinal use. Example: Solidaginis virgaureae herba has evidence of combination with Betulae folium, Equiseti herba, Juniperi galbulus, Orthosiphonis folium and Uvae ursi folium. Out of these documented combinations the combination partners for an application for a traditional herbal medicinal product may be chosen.

Number of combination partners: The number of active substances in a herbal tea combination should be limited to a maximum of 4 based on the corresponding products and the references used for assessment. Further herbal substances may be added as excipients, their number, amount and function should be justified.

Amount of each herbal substance in the combination: The very right column indicates the traditional percentages of the herbal substance in the combinations. The calculation is based on those combination partners only, which are mentioned in the table. The amount in a traditional herbal medicinal product should be within this range. The sum of active ingredients should end up with 100%. Excipients are not considered in this range. Usually the sum of all excipients should not exceed 10% in the final combination.

Example:

Combination of Solidaginis virgaureae herba + Betulae folium + Orthosiphonis folium. The combination should contain 1829% Solidaginis virgaureae herba, 10‒57% Betulae folium and 10‒50% Orthosiphonis folium. Therefore a combination of 25% Solidaginis virgaureae herba, 40% Betulae folium and 35% Orthosiphonis folium is covered by this assessment and by the European Union monograph. Excipients: e.g. Menthae piperitae folium may be added for flavouring purposes.

Information from published European Union herbal monographs

Indication:

Assessment for combinations: According to the indications of medicinal products on the market and according to the terminology of the herbal tea combinations in pharmacopoeias and text books the first indication appears suitable to all combinations.

Posology:

Assessment for combinations:

Based on the information from marketed products the single dose of herbal tea combinations is in the range between 1.3 and 2 g, in some combinations up to 4 g. With the exception of Uvae ursi folium, where the maximum daily dosage reported from marketed products is equal to the one stated in the European Union herbal monograph, the single and daily dosages of all other herbal substances are clearly below the dosages states in the monographs for the single herbal substances. The single dose for new combinations should be set to about 1.5–2 g (active herbal substances, excluding excipients).

The mean dosage frequency is 3‒5 times daily. Only one combination product is recommended up to 6 times daily. Many references do not report a concrete dosage frequency. It can be assumed that the traditional use of herbal teas in general is linked to a ‘3 times daily’ dosage frequency. Particularly in the case of ‘Species diureticae’ a higher frequency can be assumed as in literature the sufficient uptake of fluid was related with the traditional efficacy. Considering the European Union herbal monographs for the single herbal substances the dosage frequency is set to 3‒4 times daily for all combinations.

The possible daily dosages of the herbal substances in combination products is clearly below the maximum posology as given in the HMPC monographs for the single active substances:

Table 17: Comparison of the daily dose in the combinations with the upper limit according to the HMPC monographs

Age limits:

Assessment for combinations:

Tea combinations containing Juniperi galbulus, Levistici radix, Mate folium, Orthosiphonis folium, Phaseoli fructus or Uvae ursi folium are restricted to the use in adults and elderly. Other combinations may be used in adolescents.

The restriction of combinations containing Uvae ursi folium to female adults is not applicable due to the indication.

Duration of use:

Assessment for combinations:

The restriction to 1 week in case of Uvae ursi folium in the European Union herbal monograph is justified by the indication. As the indication for the combinations is different no such restriction applies.

As a suitable compromise duration of use of 2 weeks is justified.

Contraindications:

All combinations have to include the contraindications:

Hypersensitivity to the active substance.

Conditions where a reduced fluid intake is recommended (e.g. severe cardiac or renal disease).

Combinations including Betulae folium:

Additionally: Hypersensitivity to birch pollen.

Combinations including Juniperi galbulus:

According to the data obtained Juniperi galbulus is included in herbal tea combinations with a single dose of up to 0.22 g and a daily dose of up to 1.3 g. This considerably reduced posology compared to the traditional use as single active ingredient justifies that the special contraindications are not taken into account for herbal tea combinations.

Combinations containing Levistici radix:

Additionally: Hypersensitivity to other plants of the Apiaceae family or to anethole.

Combinations containing Mate folium:

According to the data obtained Mate folium is contained in an amount of 10% in traditional herbal tea combinations. A mean single dose of 2 g herbal tea combination would result in a single dose of 0.2 g

Mate folium which is 5‒10% of the recommended dose of Mate folium as only active ingredient. This considerably reduced posology compared to the traditional use as single active ingredient justifies that the special contraindications are not taken into account for herbal tea combinations.

Combinations containing Uvae ursi folium:

The general contraindication ‘kidney disorders’ is summarised in the contraindication related to conditions where a reduced fluid intake is recommended.

Special warnings and precautions for use:

Assessment for combinations:

All combinations have to include the warning statements:

If urinary tract complaints worsen or symptoms such as fever, dysuria, spasm, or blood in the urine occur during the use of medicinal product, a doctor or a qualified health care practitioner should be consulted.

Based on the age limit specified above the respective warning has to be given:

“The use in children under 12 years of age has not been established due to lack of adequate data.” or “The use in children and adolescents under 18 years of age has not been established due to lack of adequate data.”

Combinations containing Uvae ursi folium:

The warning related to the use in men is not relevant due to the different indication.

Interactions:

All combinations have to include the statement: None reported

Combinations containing Mate folium:

According to the data obtained Mate folium is contained in an amount of 10% in traditional herbal tea combinations. A mean single dose of 2 g herbal tea combination would result in a single dose of 0.2 g Mate folium which is 5‒10% of the recommended dose of Mate folium as only active ingredient. This considerably reduced posology compared to the traditional use as single active ingredient justifies that the special interactions are not taken into account for herbal tea combinations.

Fertility, pregnancy and lactation:

All combinations not containing Uvae ursi folium have to include the statement:

Safety during pregnancy and lactation has not been established. In the absence of sufficient data, the use during pregnancy and lactation is not recommended. No fertility data available.

Combinations containing Uvae ursi folium:

As Uvae ursi folium may be contained in herbal tea combinations up to 50% the wording of the European Union herbal monograph on Uvae ursi folium should be used:

Safety during pregnancy and lactation has not been established. The use should be avoided during pregnancy. In the absence of sufficient data the use during lactation is not recommended. No fertility data available.

Effects on ability to drive and use machines

Assessment for combinations:

All combinations have to include the statement:

No studies on the effect on the ability to drive and use machines have been performed. Undesirable effects:

The section ‘Undesirable effects’ should contain the combined information taken from the European Union herbal monographs for the single ingredients.

For all combinations: The frequency is not known.

Overdose:

Assessment for combinations:

All combinations should include the statement:

No case of overdose has been reported.

Combinations containing Juniperi galbulus:

According to the data obtained Juniperi galbulus is included in herbal tea combinations with a single dose of up to 0.22 g and a daily dose of up to 1.3 g. This considerably reduced posology compared to the traditional use as single active ingredient justifies that the special wording related to prolonged use and overdose is not taken into account for herbal tea combinations.

Preclinical safety data:

All combinations not containing Uvae ursi folium have to include the statement:

Adequate tests on reproductive toxicity, genotoxicity and carcinogenicity have not been performed.

Combinations containing Uvae ursi folium:

As Uvae ursi folium may be contained in herbal tea combinations up to 50% the wording of the European Union herbal monograph on Uvae ursi folium should be used:

Available tests on genotoxicity of water and ethanolic extracts of Uvae ursi folium are inadequate. Reproductive toxicity has not been studied. Available carcinogenicity studies have been negative. Arbutin, the principal component of Uvae ursi folium, displayed some maternal and fetal toxicity in rats after subcutaneous administration of 400 mg/kg/day. No effect on reproduction has been observed at doses of 100 mg/kg/day. Toxicity tests with hydroquinone, a hydrolysis product of arbutin, have

demonstrated some evidence of genotoxicity and carcinogenicity. Risks posed by the exposure of hydroquinone during the short-term treatment with Uvae ursi folium preparations are considered minimal.

3. Non-Clinical Data

Please refer to the assessment reports of the individual herbal substances.

4. Clinical Data

Please refer to the assessment reports of the individual herbal substances.

5. Clinical Safety/Pharmacovigilance

Please refer to the assessment reports of the individual herbal substances.

6. Overall conclusions (benefit-risk assessment)

The herbal substances Betulae folium, Equiseti herba, Graminis rhizoma (Agropyri repentis rhizoma), Juniperi galbulus (Juniperi pseudo-fructus), Levistici radix, Mate folium, Ononidis radix, Orthosiphonis folium, Phaseoli fructus, Polygoni avicularis herba, Solidaginis virgaureae herba, Urticae folium, Urticae herba and Uvae ursi folium, for which a EU herbal monograph has been established, are traditionally used in herbal tea combinations with the indication ‘Traditional herbal medicinal product to increase the amount of urine to achieve flushing of the urinary tract as an adjuvant in minor urinary complaints‘.

The evidence on traditional medicinal use of the single herbal substances is discussed and justified in the assessment reports. The evidence on traditional medicinal use of the combinations is based on marketed products in the member states, on monographs in national pharmacopoeias, on standard marketing authorisations and on publications.

Based on the composition of traditionally used combinations a matrix is developed indicating what herbal substances are traditionally combined and in what percentage they are traditionally combined. This matrix can be used as basis for evidence of traditional medicinal use for individual applications for registration as traditional herbal medicinal product.

The traditional medicinal use is plausible due to the longstanding medicinal use in the proposed indication.

The safety of the individual herbal substances has been assessed in the assessment reports published together with the respective European Union monographs. Potential risks and undesirable effects are properly addressed in the proposed European Union monograph for the combinations. Based on the longstanding medicinal use no potentiation of undesirable effects due to the combination is to be expected.

Depending on the safety data of the individual herbal substances the medicinal use of the combinations is restricted to adults or adolescents and adults.

A European Union list entry is not supported due to lack of adequate data on genotoxicity.

Annex

List of references