Spiny restharrow

Spiny Restharrow (Ononis spinosa L.): A Comprehensive Reference

1. Identity and Botanical Description

Taxonomy and Nomenclature

Ononis spinosa L. (family Fabaceae), commonly known as spiny restharrow, is a widely distributed medicinal plant traditionally used in European and Middle Eastern phytotherapy, particularly for the management of urological and inflammatory conditions. It is taxonomically classified within the kingdom Plantae, clade Tracheophytes, clade Angiosperms, order Fabales, family Fabaceae, subfamily Faboideae, genus Ononis, and species O. spinosa.

It is closely related to Ononis repens (common restharrow); the two are considered conspecific by the Plants of the World Online database, with O. repens treated as a subspecies of O. spinosa as Ononis spinosa subsp. procurrens. The Botanical Society of Britain and Ireland treats them as separate species.

The herbal drug derived from its dried root is known in pharmacopoeial literature as Ononidis radix (Restharrow Root). In older literature, both Ononis spinosa L. and Ononis arvensis L. have been mentioned as botanical sources of Ononidis radix. According to information from EU Member States, only products containing Ononis spinosa L. radix are available on the European market. In many well-known European handbooks and pharmacopoeias only Ononis spinosa L. is mentioned as the source of Ononidis radix. Ononis arvensis L. can be mainly found in the literature from the former USSR, for instance in the Pharmacopoeia of the former USSR [1990].

Common names in various languages include: Arabic: Shabraq; English: restharrow, spiny restharrow, thorny restharrow; German: Dornige Hauhechel; Swedish: busktörne; Turkish: kayıskıran. The German name "Hauhechel" likens the plant to a spiky tool, the hackle, which was used to comb through flax.

The English name "spiny restharrow" is formed by "spiny" (because of the long spines of this plant) and "restharrow" (from "rest" and "harrow," meaning plough). According to the Spanish doctor and botanist Andrés Laguna (1499–1559), the scientific name of the genus "Ononis" comes from the Greek "onos," meaning "donkey," because these animals felt a special appreciation toward the plant. "Spinosa" comes from the Latin "spinosus," meaning "having spines," and refers to the thorns of its stems.

Morphology

Ononis spinosa L. is a perennial, spiny subshrub up to 80 cm tall. The branches of the plant are spreading, villous, and densely covered with short shoots, which terminate in straight thorns. The lower leaves are ternate while the upper ones are single, and papilionaceous, pinkish-white flowers generally bloom from June to July, followed by small seed pods.

The root is more or less flattened, twisted, and bent, with a grayish-brown to dark-brown outer surface and deep longitudinal grooves. Characteristic of the transversely cut surface is the conspicuously radiate structure of the xylem due to the unequal width of the medullary rays. The fracture of the root is short and fibrous. It has a bitter taste resembling that of liquorice and is regarded as an aperitive, diuretic, anti-inflammatory, and astringent.

Geographic Distribution and Habitat

The plant is distributed in Africa (Algeria, Libya, Morocco, Tunisia), Asia (Afghanistan, Iran, Iraq, Palestine, Jordan, Lebanon, Syria, Turkey, Armenia, Azerbaijan, India), and Europe (Denmark, Norway, Sweden, United Kingdom, Austria, Belgium, Czechoslovakia, Germany, Hungary, Netherlands, Poland, Switzerland, Estonia, Lithuania, Moldova, Russian Federation — European part, Albania, Bulgaria, former Yugoslavia, Greece, Italy, Romania, France, Portugal, and Spain).

Its typical habitat is lime-rich but nutrient-poor grassland on chalk and heavy, calcareous soils. Restharrow is to be found in dry meadows and pastures, by fields and waysides, and also in peat areas and sand dunes. It favours sunny locations with weak loamy or chalky soils. Fertilizing causes it to disappear.

Pharmacopoeial Status and Common Preparations

Ononidis radix has been monographed by several commissions (Commission E, ESCOP) and is used in herbal medicinal products. The drug consists of whole or cut, dried roots of the plant. Restharrow root is the common name for the root of the plant Ononis spinosa L. The HMPC conclusions cover restharrow root preparations obtained by drying and comminuting (reducing into tiny pieces) the root. Herbal medicines containing this preparation are usually available as herbal tea to be drunk. Restharrow root preparations may also be found in combination with other herbal substances in some herbal medicines.

In the USA, restharrow root is a dietary supplement, and in Canada it is an approved active ingredient in a few OTC traditional herbal medicines and homeopathic medicines.

2. Traditional and Historical Use

Classical Antiquity

In the 4th century BC, Theophrastus produced the first botanical description of restharrow. In the first century AD, Dioscorides and Pliny described the use of the plant as a remedy for urinary complaints and stones. In the later writings of Roman antiquity, Galen referred to the effect of ononis on increasing urine flow and decreasing the size of urinary stones.

The herbalist Lonicerus wrote that the herb is "the most excellent of stone-herbs which flushes out the stone and urine in man and animals." "Bark and root soaked in wine, or marinated in wine and drunk, drive out the stone with force. They also drive out hidden warts (pointed condylomata) and heal them."

European Folk and Phytotherapy Traditions

The roots, leaves, and flowers were used as antitussive, aperient, diuretic, and lithotriptic. The plant infusion was used in the treatment of dropsy, urinary tract infections, inflammations, and rheumatism. Externally, it was used for the healing of wounds, eczema, and other skin disorders.

Many folk names point to its use as a diuretic for man and animals (particularly horses) to combat the swelling in the legs caused by dropsy.

Traditional use includes irrigation therapy for inflammatory diseases of the lower urinary tract and its supportive use in urinary tract infections, as well as urinary tract inflammation as reported in Iranian ethnomedicine.

Turkish Folk Medicine

Ononis spinosa L. has been used in Turkish folk medicine for the treatment of inflammatory diseases of the lower urinary tract and kidney stones. It was reported to possess pharmacological activities due to its aperient, diuretic, antibacterial, analgesic, antiviral, cytotoxic, and antifungal effects. Externally, it is used for the healing of wounds, eczema, other skin disorders, and gout. Ethnobotanical data from Turkish folk medicine record root decoctions of O. spinosa administered twice daily for 5–10 days to induce diuresis and facilitate kidney stone elimination.

Iraqi Traditional Medicine

In Iraq, the aerial part decoction was used as a diuretic and mild laxative, and the roots were used as a diuretic and blood purifier.

Regulatory Recognition of Traditional Use

The European Medicines Agency's HMPC conclusions on the use of these restharrow root medicines for minor urinary complaints are based on "traditional use." This means that although there is insufficient evidence from clinical trials, the effectiveness of these herbal medicines is plausible and there is evidence that they have been used safely in this way for at least 30 years (including at least 15 years within the EU). Moreover, the intended use does not require medical supervision.

3. Phytochemistry: Key Constituents and Active Compounds

Overview

Phytochemical analyses indicate that O. spinosa contains a wide range of secondary metabolites, primarily derived from the phenylpropanoid biosynthetic pathway. The most abundant constituents are flavonoids, especially isoflavones, which occur in both free and glycosylated forms.

Isoflavonoids (Dominant Class)

Identified isoflavone compounds include ononin (formononetin 7-O-glucoside), genistin (genistein 7-O-β-D-glucoside), formononetin, biochanin A (4′-methylgenistein), and biochanin A 7-O-glucoside 6″-O-malonate. The ESCOP monograph additionally lists as main compounds the isoflavones trifolirhizin, formononetin together with its 7-O-β-D-glucoside-6″-malonate and 7-O-β-D-glucoside (ononin), biochanin A-7-O-β-D-glucoside and the pterocarpan medicarpin; additionally, the root contains triterpenes, notably α-onocerin, phytosterols (especially β-sitosterol), deoxybenzoines (especially ononetin), and phenolic acids.

More recently, onogenin, sativanone, calycosin, and the norneolignan clitorienolactone B have been additionally identified from a restharrow root extract.

Isoflavonoids are phytoestrogens due to their structural similarity to estradiol and possess antioxidant activity. Moreover, isoflavonoids can play an important role in the prevention and treatment of hormone-dependent cancers, osteoporosis, cardiovascular diseases, and diseases of civilization like metabolic syndrome or polycystic ovary syndrome.

Triterpenes

Phytosterols, phenolic acids, essential oil, and a specific triterpene, α-onocerin, alongside isoflavonoids and their glucosides, are the major constituents in restharrow root. α-Onocerin is regarded as a characteristic triterpene of the genus Ononis.

Phenolic Acids

Phenolic acids derived from hydroxybenzoic and hydroxycinnamic acid pathways have been reported, including p-hydroxybenzoic, vanillic, caffeic, salicylic, and gentisic acids. Other classes of secondary metabolites such as tannins further contribute to the polyphenolic profile of the plant.

Volatile Oil, Sterols, and Other Constituents

The presence of phytosterols (especially β-sitosterol), deoxybenzoines (especially ononetin), phenolic acids, minerals, and volatile oil (0.02%) with trans-anethole, carvone, and menthol as main compounds has been reported.

The glucoside spinonin, a glucoside with an unusual structure, has been detected, as well as medicarpin, a pterocarpan derivative.

Phytochemical studies on O. spinosa also reveal sterols (β-sitosterol, campesterol, stigmasterol, stigmastan-3,5-dien) and terpenic substances (β-amyrin, α-onocerin).

4. Mechanisms of Action

Diuretic Activity: Multiple Proposed Mechanisms

The precise mechanism underlying the diuretic activity of restharrow extracts remains unclear; it may be caused by the amount of essential oil in the extracts, by flavonoid glycosides, or by the content of potassium salts.

A further explanation for the diuretic activity of restharrow extracts is based on the inhibition of human hyaluronidase-1 (Hyal-1) by the isoflavone sativanone, as renal Hyal-1 contributes at least in part to the control of renal fluid regulation in the kidney cells.

Studies show that exogenous administration of low-molecular-weight hyaluronic acid (LMW-HA) or increased endogenous HA breakdown was associated with enhanced renal fluid excretion, possibly through alterations in tubular water permeability and interstitial matrix dynamics. Conversely, pharmacological inhibition of Hyal-1 has been linked to increased urine output, an effect attributed to the preservation of high-molecular-weight HA within the renal interstitium, which may influence water reabsorption processes.

Bioassay-guided fractionation of the dichloromethane extract yielded four isoflavonoids with anti-Hyal-1 activity: onogenin, sativanone, medicarpin, and calycosin-D, with inhibition rates of 25.4%, 61.2%, 22.4%, and 23.0% respectively at a test concentration of 250 μM. The IC50 of sativanone, the most active compound, was determined at 1501 μM.

Anti-inflammatory Mechanisms

Different extracts and compounds from restharrow roots influence the inflammatory process in a pleiotropic manner: the methanolic extract and the pterocarpan medicarpin inhibit the 5-lipoxygenase and subsequently leukotriene formation.

A dichloromethane extract (OS1), mainly composed of isoflavonoids and triterpenes, showed a concentration-dependent (25–100 μg/ml) inhibition of IL-8 and TNF-α release from LPS-stimulated human neutrophils. Significant inhibition was also found for the triterpene α-onocerin and the norneolignan clitorienolactone B.

In vitro experiments with restharrow root extracts demonstrate inhibition of leukotriene formation.

Gastroprotective Mechanisms

The extract from O. spinosa was demonstrated to be able to protect gastric mucosa from ethanol injury by at least two mechanisms: the induction of COX-2 and the reduction of oxidative stress in the stomach.

Phytoestrogenic and Antioxidant Mechanisms

Isoflavonoids are phytoestrogens due to their structural similarity to estradiol and possess antioxidant activity. Isoflavonoids are found to possess several biological activities, especially estrogenic, antimicrobial, antioxidant, and anti-inflammatory activities. It is also known that these compounds may be used for the prevention of cardiovascular diseases and cancer.

5. Scientific Evidence by Area of Use

5.1 Urinary Tract and Diuretic Effects

Traditional/regulatory classification: Restharrow root is classified as a traditional herbal medicinal product used to increase the amount of urine to achieve flushing of the urinary tract as an adjuvant in minor urinary complaints.

Preclinical evidence: In vivo experiments with animals demonstrated moderate diuretic and saluretic properties, increased urinary output, and showed analgesic effects.

Human clinical evidence: In its assessment, the HMPC considered laboratory studies showing restharrow root increases urine production. No studies in patients have been carried out with restharrow root. The evidence base for urinary flushing effects therefore rests entirely on preclinical (animal) studies and the regulatory plausibility standard associated with traditional use — not on controlled clinical trials in humans. As the diuretic activity of restharrow extracts seems to be only moderate, its traditional use against urinary tract infections might also be based on an anti-inflammatory potential of the herbal material.

Evidence strength: Preclinical (animal/in vitro) and traditional use only. No human clinical trials available. Regulatory status is "traditional use" under the EMA framework.

5.2 Anti-inflammatory Effects

In vitro and animal evidence: Anti-inflammatory effects are described under in vitro conditions for a methanolic extract of O. spinosa roots and for the pterocarpan medicarpin, isolated from the extract, by inhibition of leukotriene and 5-lipoxygenase formation. In the carrageenan-induced rat paw edema assay, a methanolic extract of O. spinosa roots significantly reduced edema formation after intraperitoneal application.

A 2020 study published in Frontiers in Pharmacology investigated the TLR4 pathway: A dichloromethane extract (OS1) showed a concentration-dependent (25–100 μg/ml) inhibition of IL-8 and TNF-α release from LPS-stimulated human neutrophils. Significant inhibition was also found for the triterpene α-onocerin and the norneolignan clitorienolactone B. This supports a further explanation for the diuretic activity of restharrow extracts based on the inhibition of human hyaluronidase-1 (Hyal-1) by the isoflavone sativanone.

Evidence strength: Preliminary; in vitro and animal studies only. No human clinical trials.

5.3 Wound Healing and Dermatological Effects

Dermatological applications of O. spinosa are supported by evidence from in vitro and in vivo studies, antimicrobial assays, ethnobotanical reports, and limited clinical evidence, consistent with both its traditional use and modern pharmacological potential in skin repair, inflammation control, and infection management. Studies investigating the roots of O. spinosa have provided evidence for wound-healing ability. In vivo wound closure was enhanced by the ethyl acetate extract obtained from the roots of O. spinosa, particularly its active fraction (Fr-E5), which contains isoflavonoids such as trifolirhizin, ononin, medicarpin-3-O-glucoside, onogenin-7-O-glucoside, and sativanone-7-O-glucoside.

A study using a Turkish subspecies (O. spinosa subsp. leiosperma) showed: Results showed that O. spinosa subsp. leiosperma roots ethyl acetate extract exhibited remarkable wound healing activity, with a 42.6% tensile strength value on the linear incision wound model and 60.1% reduction of the wound area at day 12 on the circular excision wound model. Hydroxyproline content of the tissue treated by O. spinosa subsp. leiosperma roots ethyl acetate extract was found to be 41.3 μg/mg.

Evidence strength: In vitro and animal studies (rodent wound models). Traditional use across multiple cultures is consistent with these findings. No controlled human clinical trials on wound healing.

5.4 Antimicrobial and Antifungal Activity

A PMC-indexed study investigated the chemical composition and antifungal potential of the methanolic extract obtained from O. spinosa herb. Chemical analyses regarding phenolic compounds were performed by LC-DAD-ESI/MSn, and antifungal activity, antibiofilm properties, antifungal mode of action, and cytotoxicity were evaluated. Chemical analyses revealed the presence of flavonoids, isoflavonoids, and phenolic acids in O. spinosa, with kaempherol-O-hexoside-pentoside being the most abundant compound (5.1 mg/g extract). The methanolic extract was active against all of the tested microfungi, with Penicillium aurantiogriseum being the most sensitive at 0.02 mg/mL.

Evidence strength: Preliminary; in vitro antimicrobial and antifungal studies. No human clinical trials on antimicrobial use.

5.5 Gastroprotective Effects

The gastroprotective properties of O. spinosa were evaluated in a rat model of ethanol-induced gastric ulcers. Methanolic leaf extract (0.5–1 g/kg) administered orally significantly decreased ulcer indices by 80.39% and 98.71%, respectively, outperforming esomeprazole. Histological analysis showed reduced leukocyte infiltration, hemorrhage, submucosal edema, and mucosal necrosis in extract-treated groups. Treatment also increased COX-2 expression and gastric glutathione levels, suggesting the involvement of prostaglandin-mediated cytoprotective mechanisms and antioxidant activity. LC–MS analysis identified ononin as the major compound, followed by trifolirhizin, myricitrin, gentisic acid, cycloartenol, and quercetin.

Evidence strength: Animal study only (rat model). No human clinical trials.

5.6 Anti-adipogenic and Metabolic Effects

The ethnopharmacological use of Ononis spinosa L. roots (OSR) for treatment of obesity and metabolic disorders has prompted scientific evaluation. A study examined the anti-adipogenic capacity of OSR and its secondary metabolites ononin and maackiain in human adipocytes as an in vitro model of obesity.

Evidence strength: In vitro only (human adipocyte cell model). No in vivo or clinical evidence.

5.7 Anticancer Properties

Formononetin, one of the most known isoflavones in the Ononis species, has revealed anticancer activity against various types of cancers, such as colon, breast, prostate, and nasopharyngeal cancers. These findings are attributed to the isoflavone constituents shared with other Fabaceae plants and are not specific to clinical investigations of O. spinosa preparations as a whole.

Evidence strength: Preliminary, based on the constituent formononetin studied in isolation. No clinical trials with O. spinosa for cancer.

5.8 Renal Gravel and Urolithiasis

The ESCOP monograph lists the therapeutic indications as irrigation of the urinary tract, especially in cases of inflammation and renal gravel, and as an adjuvant in treatment of bacterial infections of the urinary tract. An in vivo animal study reported that it causes shrinkage of stone size independently of the diuretic effect.

Evidence strength: Traditional and preclinical (animal) only. No human clinical trials specifically for urolithiasis.

6. Body Systems and Health Areas

• Urinary/Renal System: Ononis spinosa was traditionally used as a diuretic and lithotriptic. Infusion was used in the treatment of dropsy and urinary tract infections.
• Musculoskeletal/Inflammatory: Ononis species are used for gout, rheumatic complaints, and externally for skin disorders and wound healing as folk remedies in Turkey.
• Gastrointestinal System: Traditional use as an aperient (mild laxative); modern preclinical studies demonstrate gastroprotective effects in animal models.
• Skin and Dermatology: Externally, it is used for the healing of wounds, eczema, other skin disorders, and gout.
• Respiratory System: Traditionally used as an antitussive (cough suppressant).
• Metabolic/Hormonal: Isoflavone content gives phytoestrogenic potential; preclinical evidence exists for anti-adipogenic effects in cell models.

7. Dosage Forms and Reported Dosages

Official Monograph Dosage (EMA/HMPC Community Herbal Monograph, 2014)

For adolescents, adults, and the elderly: herbal tea using 2–3 g of comminuted herbal substance in 150 ml of boiling water as a herbal infusion, up to 3–4 times daily, corresponding to a maximum daily dose of 12 g.

Preparation method: brew 2 heaped teaspoons of Hauhechel root with 150 ml boiling water and leave to steep for approximately 30 minutes.

The usual daily dose is between 6 and 12 g and is used for infusions or other galenic preparations for ingestion.

Duration of Use

Restharrow root infusions should be given on a short-term basis, as the diuretic effect will decrease with continued use. If urinary tract complaints worsen and symptoms such as fever or blood in the urine occur during 7 days of use of the medicinal product, a doctor or a qualified health care practitioner should be consulted.

Pediatric Use

The use in children under 12 years of age is not recommended.

Dosages Used in Preclinical Research

In the rat gastric ulcer study, rats received 0.5 and 1 g/kg of O. spinosa extract orally, with gastric ulcer induced by absolute ethanol (5 mL/kg) orally to all groups.

In anti-inflammatory in vitro work, the dichloromethane extract (OS1) showed a concentration-dependent (25–100 μg/ml) inhibition of IL-8 and TNF-α release from LPS-stimulated human neutrophils.

For hyaluronidase-1 inhibition, hot water and hydroalcoholic extracts showed moderate inhibiting effects (IC50 1.36 resp. 0.73 mg/mL), while the dichloromethane extract exerted an IC50 of 190 μg/mL.

8. Safety Considerations and Interactions

General Safety Profile

Oral administration of Ononidis radix can be regarded as safe at traditionally described and used doses in elderly, adults, and adolescents. Preclinical safety for restharrow root extract was assessed in toxicity studies. There were no toxic effects reported.

At the time of the HMPC assessment, no side effects had been reported with these medicines. There are no known adverse effects.

Contraindications

Restharrow root medicines must not be taken by patients with conditions where reduced fluid intake is recommended, such as severe heart or kidney disease. Contraindication exists in case of oedema due to impaired heart and kidney function.

Other contraindications include allergy to any of the ingredients, children under 12 years, and the absence of data for lactation and pregnancy.

Pregnancy and Lactation

Safety during pregnancy and lactation has not been established. In the absence of sufficient data, the use of restharrow root during pregnancy and lactation is not recommended.

Drug Interactions

Interactions with other drugs and adverse events are reported as unknown. No clinically documented herb-drug interactions appear in the EMA assessment record.

Overdose and Abuse

No case of overdose has been reported. There are no reports on drug abuse of Ononis spinosa preparations, and there are no reports on withdrawal of Ononis spinosa preparations.

Driving and Cognitive Impairment

No studies on the ability to drive and use machines have been performed. There are no reports on impairment of mental ability. No concerns arise regarding the ability to drive or operate machinery.

Phytoestrogenic Considerations

The isoflavone content of O. spinosa, including formononetin, biochanin A, and genistein derivatives, gives the plant phytoestrogenic properties. Isoflavonoids can play a role in conditions related to hormone-dependent cancers, osteoporosis, cardiovascular diseases, and metabolic syndrome. The clinical relevance of these phytoestrogenic effects specifically from O. spinosa preparations at monograph-recommended doses has not been established in human studies.

9. Summary Assessment of Evidence Quality

The overall evidence base for spiny restharrow is characterized by a long and well-documented ethnomedicinal history across European, Middle Eastern, and Central Asian traditions, primarily for urological complaints. The EMA's HMPC has formally recognized this traditional use, classifying Ononidis radix as a traditional herbal medicinal product for urinary flushing under Directive 2001/83/EC. Although there is insufficient evidence from clinical trials, the effectiveness of these herbal medicines is plausible and there is evidence that they have been used safely in this way for at least 30 years. Modern pharmacological research has identified plausible mechanisms — particularly Hyal-1 inhibition by isoflavonoids, 5-lipoxygenase inhibition by medicarpin, and TLR4-mediated anti-inflammatory effects — but virtually all current evidence remains at the in vitro or animal level. A systematic literature search across four electronic databases (PubMed, Scopus, Web of Science, and SpringerLink) covering studies published between 1997 and 2024 yielded 308 records; after duplicate removal and eligibility screening, only 34 studies met inclusion criteria, underscoring that the total research volume remains modest. No controlled human clinical trials specific to Ononis spinosa as a single-ingredient preparation have been published at this time.

References

• Phytochemical Constituents and Biological Activities of Ononis spinosa: A Comprehensive Review — Plants (MDPI), 2026
• Ononidis radix — herbal medicinal product: European Medicines Agency (EMA)
• Final Assessment Report on Ononis spinosa L., radix — EMA/HMPC (2014)
• Community Herbal Monograph on Ononis spinosa L., radix — EMA/HMPC/138316/2013
• Ononidis radix (Restharrow Root) ESCOP Monograph — ESCOP, 2015
• Root Extracts From Ononis spinosa Inhibit IL-8 Release via Interactions With Toll-Like Receptor 4 and Lipopolysaccharide — Frontiers in Pharmacology, 2020
• Isoflavonoids with inhibiting effects on human hyaluronidase-1 and norneolignan clitorienolactone B from Ononis spinosa L. root extract — PubMed (2018)
• Characterization and identification of isoflavonoid glycosides in the root of Spiny restharrow (Ononis spinosa L.) by HPLC-QTOF-MS, HPLC–MS/MS and NMR — Journal of Pharmaceutical and Biomedical Analysis, 2016
• Efficacy of extract from Ononis spinosa L. on ethanol-induced gastric ulcer in rats — PubMed / Journal of Traditional Chinese Medicine, 2021
• Methanolic Extract of the Herb Ononis spinosa L. Is an Antifungal Agent with no Cytotoxicity to Primary Human Cells — PMC, 2020
• Wound healing and anti-inflammatory activity of some Ononis taxons — PubMed / Biomedicine & Pharmacotherapy, 2017
• Isoflavonoids as wound healing agents from Ononidis Radix — Journal of Ethnopharmacology, 2017
• The Traditional Uses, Constituents and Pharmacological Effects of Ononis spinosa — IOSR Journal of Pharmacy, 2020
• Ononidis radix — Altmeyers Encyclopedia, Department Phytotherapy
• Assessment Report on Species diureticae — EMA/HMPC