Pelargonium: Liver Injury Reports and Safety

Table of Contents

1. The Safety Picture in Brief
2. Side Effects Reported in Trials
3. The German Liver-Injury Reports
4. The Causality Re-Analyses
5. The Warning in the EU Monograph
6. Ten Years of Periodic Safety Reports
7. Liver Enzymes in Young Children
8. Allergic Reactions
9. Bleeding, Coumarins and Warfarin
10. Pregnancy, Breastfeeding and Young Children
11. What Is Still Unknown
12. Key Research Papers
13. Connections

The Safety Picture in Brief

• In trials: side effects were more common than on placebo but mostly mild, chiefly digestive complaints; no serious adverse events attributed to the extract were reported in the placebo-controlled trials summarised by the Cochrane review.
• Liver: spontaneous reports of hepatitis, jaundice and liver injury, including one liver transplant; causality was judged at least possible by the German regulator and could not be confirmed by independent re-analysis. The EU monograph lists hepatotoxicity and hepatitis with unknown frequency.
• Allergy: hypersensitivity reactions, rarely severe, are listed.
• Bleeding: nosebleeds and gum bleeding are listed as side effects; an interaction with warfarin is considered theoretical and has not been seen in a rat study or reported in trials.
• Pregnancy, breastfeeding, under-threes: safety not established.

A 2014 review of the plant's medicinal properties summed up the background problem: despite favourable trials, there is a lack of adequate information on the safety evaluation of the plant.

Side Effects Reported in Trials

Individual trials reported their adverse events in detail:

• In a 468-patient adult bronchitis trial, adverse events occurred in 20 of 233 patients on the extract and 16 of 235 on placebo, all non-serious.
• In a 124-patient adult trial, 15 of 64 on the extract and 10 of 60 on placebo had adverse events, all non-serious.
• In a 406-patient tablet trial, adverse events were of mild to moderate intensity and their frequency was dose-dependent — more side effects at higher doses. None were serious.
• In the two children's trials, tolerability was similar on the extract and placebo, and all adverse events were non-serious.
• In the 2026 Swiss pragmatic trial, adverse events were reported by 32.3 per cent of patients on the extract and 21.5 per cent on usual care; all adverse drug events were mild.
• In a 2024 Korean trial comparing pelargonium tablets with an ivy-leaf combination syrup, adverse reactions occurred at similar rates in both groups, with no serious events.

Pooled analyses agree. The Cochrane review found adverse events more common with the extract than placebo, but none serious. A 2018 meta-analysis in children found no significant difference in the proportion of patients with adverse events (risk ratio 1.06). A pooled safety analysis cited by the EMA found a slightly higher rate of digestive complaints (stomach pain, nausea, diarrhoea), skin reactions, gum bleeding and nosebleeds on the extract than on placebo.

The German Liver-Injury Reports

Rare drug reactions usually show up only after a product has been used by large numbers of people, through "spontaneous reports" sent by doctors, pharmacists and patients to regulators. Trials of a few hundred people each are too small to detect them.

According to the EMA's 2024 assessment report, by June 2012 the German Federal Institute for Drugs and Medical Devices (BfArM) had received 30 spontaneous reports of liver problems associated with pelargonium products: 26 from Germany, 2 from Switzerland, 1 from Italy and 1 from Singapore. They comprised 11 cases of hepatitis, 8 of jaundice (icterus) and 3 of liver injury. One patient with hepatitis underwent a liver transplant. In 19 of the 30 cases the patient was taking other medicines at the same time.

The BfArM rated the strength of each link. For hepatitis, the association was judged possible in 7 cases, possible-to-probable in 1 and probable in 1; for jaundice, possible in 6 and probable in 2; for liver injury, possible in 2 of 3. The regulator concluded that there was "at least a possible association" between pelargonium use and liver toxicity, introduced a risk-minimisation procedure, and requested a post-authorisation safety study.

A separate Italian pharmacovigilance report described acute liver disease in a patient with several serious illnesses who was taking many medicines including a pelargonium product. The liver problem improved after stopping, but given the other illnesses and medicines a cause could not be established; the report was treated as a signal only.

The Causality Re-Analyses

Two 2012 publications by Teschke and colleagues, summarised in the EMA assessment report, re-examined spontaneous reports using structured, liver-specific causality methods:

• 15 German cases. The analysis found numerous final diagnoses unrelated to pelargonium and poor data quality in several cases. Basic checks were often missing: biliary imaging was available in only 3 patients, and tests to exclude hepatitis A–C virus in only 4. Pelargonium hepatotoxicity could not be confirmed as the final diagnosis in any of the 15.
• 13 further cases from Germany, Switzerland, Italy and Singapore, assessed with the CIOMS scale (a standard liver-causality score). Causality could not be established in any case. Alternative explanations included liver injury from other medicines, pancreatitis, gallbladder and bile-duct inflammation, viral and bacterial infections, autoimmune hepatitis and pre-existing liver disease.

These re-analyses and the regulator's assessment are not necessarily contradictory. Spontaneous reports are often incomplete, and "possible" in a causality scale means a link cannot be ruled out rather than that it has been shown. Infections themselves can disturb liver tests, and the EMA's assessment attributes raised liver enzymes seen in one children's study to the underlying viral infections (see below). The regulator's response was to warn and to keep monitoring, which is what the monograph reflects.

The Warning in the EU Monograph

Following the German assessment, product information in Germany had to carry a liver warning, and the same wording is in the EU herbal monograph (Revision 2, 2024). Under "Special warnings and precautions for use" it states:

"Hepatotoxicity and hepatitis cases were reported in association with the administration of the medicinal product. In case signs of hepatotoxicity occur, the administration of the medicinal product should be stopped immediately, and a medical doctor should be consulted."

Under "Undesirable effects" it lists hepatotoxicity and hepatitis with frequency "not known". Signs of liver injury in general include yellowing of the skin or eyes, dark urine, pale stools, itching, and pain in the upper right abdomen; these are reasons people seek medical attention regardless of what medicines they take.

The 2024 revision was adopted by 23 of the 27 votes on the EMA's herbal committee, and three members recorded divergent positions in the committee's published opinion. Finland objected that liver warnings do not exclude risk, because liver disease often causes symptoms only late, and that any risk of severe reactions is not acceptable for a non-life-threatening condition such as a cold. Ireland did not support use in children under 12 for self-medication. Italy objected to the use in children aged three to five because of the potential risk of liver toxicity in an age group whose metabolism is not fully mature, and because exposure seemed unjustified for a benign, self-limiting condition.

Ten Years of Periodic Safety Reports

Because of the possible liver link, pelargonium root was placed on the EU list of substances requiring regular periodic safety update reports from marketing-authorisation holders. The EMA's 2024 assessment covers two five-year periods from June 2013 to June 2023. In that time 1,097 individual case safety reports were received for medicines containing the extract. Liver disorders such as drug-induced liver injury, acute hepatitis and hepatotoxicity continued to be reported, though in a very low number — 9 serious cases — compared with exposure of several million patient-days. The EMA concluded that the balance of benefit and risk remained positive when the products are used as authorised.

Liver Enzymes in Young Children

The EMA's assessment report describes an open-label randomised study (Kamin and colleagues, 2023) in 591 children aged one to five with acute bronchitis, comparing a syrup with an alcohol-based solution of the extract for seven days. Liver enzymes (ALT, AST and gamma-GT) were measured before and after. At the end of treatment, at least one enzyme was raised in 4.1 per cent of children, compared with 5.7 per cent at the start; mean values did not rise, and all elevations were below five times the upper limit of normal, the threshold usually used to indicate liver injury. The EMA report notes that all the raised values may be related to the underlying or accompanying viral infections.

The study had no placebo group and was not designed to detect rare reactions; a rare idiosyncratic liver injury would not be expected to appear in a few hundred children.

Allergic Reactions

The EU monograph lists hypersensitivity, including anaphylactic reactions, and rash, itching, hives and angioedema (swelling of deeper skin layers, such as the lips or tongue), all with unknown frequency. The EMA assessment report describes two serious cases:

• A 20-year-old woman developed life-threatening acute hives and circulatory failure after taking pelargonium extract for a cold; she had taken no other drugs, and a positive skin-prick test confirmed the extract as the cause. The reaction subsided within four hours of emergency treatment.
• A 71-year-old man developed breathlessness and swelling of the lips and tongue within a day of first taking the extract and needed hospital treatment.

The only contraindication in the monograph is hypersensitivity to the active substance.

Bleeding, Coumarins and Warfarin

Pelargonium root contains coumarins, and warfarin and related blood thinners are coumarin derivatives. That raised the question of whether the root could increase bleeding or strengthen warfarin's effect. The EMA's assessment summarises what is known:

• Chemistry: coumarins need a hydroxyl group in position 4 and a non-polar group in position 3 to act as anticoagulants. None of the coumarins identified in the extract has those features.
• Animal study: in rats given the extract for two weeks at up to 500 mg/kg, clotting tests were unchanged, and giving it with warfarin did not change warfarin's effect or its blood levels.
• Trials: no case in the clinical trials definitely proved an increased bleeding tendency attributable to the extract.
• Monograph: lists no interactions ("None reported").

Against that, nosebleeds and gum bleeding appear among the listed side effects, and no study has tested the extract in people taking warfarin or other anticoagulants. The interaction question is therefore theoretical and unresolved rather than disproven in humans.

Pregnancy, Breastfeeding and Young Children

• Pregnancy and breastfeeding: the monograph states that safety has not been established, that there are no fertility data, and that in the absence of sufficient data use during pregnancy and lactation is not recommended.
• Children under three: the monograph states that oral use under three years is not recommended "because of concerns requiring medical advice"; under six, only liquid dosage forms are listed.
• Alcohol content: liquid extracts are made with ethanol, and the monograph requires the standard ethanol labelling.
• Liver or kidney disease: the EMA notes that no safety studies have been done in people with liver or kidney disease. In the Italian case discussion it suggested alcohol-free preparations where there is a history of liver disorder.

What Is Still Unknown

1. How often liver injury occurs, if it is caused by the extract at all. Spontaneous reports cannot give a rate.
2. Whether any particular group — young children, people with existing liver disease, people taking other liver-affecting medicines — is at higher risk.
3. Whether the extract interacts with warfarin or other blood thinners in people.
4. Safety in pregnancy and breastfeeding.
5. Safety of products other than the studied extracts, including teas, tinctures and products of unknown composition.
6. Effects of use for longer than the one-week courses typical of the trials.

Liver symptoms during or after taking any herbal product are a reason to seek medical attention, and telling a clinician about every supplement taken helps them consider herb-induced liver injury.

Key Research Papers

1. Timmer A, Günther J, Motschall E, et al. Pelargonium sidoides extract for treating acute respiratory tract infections. The Cochrane database of systematic reviews. 2013;2013(10):CD006323. PubMed PMID: 24146345
2. Timmer A, Günther J, Rücker G, et al. Pelargonium sidoides extract for acute respiratory tract infections. The Cochrane database of systematic reviews. 2008;(3):CD006323. PubMed PMID: 18646148
3. Anheyer D, Cramer H, Lauche R, et al. Herbal Medicine in Children With Respiratory Tract Infection: Systematic Review and Meta-Analysis. Academic pediatrics. 2018;18(1):8-19. PubMed PMID: 28610802
4. Matthys H, Eisebitt R, Seith B, et al. Efficacy and safety of an extract of Pelargonium sidoides (EPs 7630) in adults with acute bronchitis. A randomised, double-blind, placebo-controlled trial. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2003;10 Suppl 4:7-17. PubMed PMID: 12807337
5. Chuchalin AG, Berman B, Lehmacher W. Treatment of acute bronchitis in adults with a pelargonium sidoides preparation (EPs 7630): a randomized, double-blind, placebo-controlled trial. Explore (New York, N.Y.). 2005;1(6):437-45. PubMed PMID: 16781588
6. Matthys H, Lizogub VG, Malek FA, et al. Efficacy and tolerability of EPs 7630 tablets in patients with acute bronchitis: a randomised, double-blind, placebo-controlled dose-finding study with a herbal drug preparation from Pelargonium sidoides. Current medical research and opinion. 2010;26(6):1413-22. PubMed PMID: 20387996
7. Kamin W, Maydannik V, Malek FA, et al. Efficacy and tolerability of EPs 7630 in children and adolescents with acute bronchitis - a randomized, double-blind, placebo-controlled multicenter trial with a herbal drug preparation from Pelargonium sidoides roots. International journal of clinical pharmacology and therapeutics. 2010;48(3):184-91. PubMed PMID: 20197012
8. Kamin W, Ilyenko LI, Malek FA, et al. Treatment of acute bronchitis with EPs 7630: randomized, controlled trial in children and adolescents. Pediatrics international : official journal of the Japan Pediatric Society. 2012;54(2):219-26. PubMed PMID: 22360575
9. Bourqui A, Corpataux O, Bonofiglio F, et al. Pelargonium sidoides extract (EPs® 7630) versus usual care for acute bronchitis in Swiss primary care (PHYTOBRONCH): a pragmatic, open-label, randomised controlled trial. NPJ primary care respiratory medicine. 2026;36(1). PubMed PMID: 42014704
10. Han KI, Kim TH, Ra SW, et al. Efficacy and safety of mixture of ivy leaf extract and coptidis rhizome in the treatment of acute bronchitis: multicenter, randomized, double-blinded, active-controlled, parallel, therapeutic confirmatory clinical trial. Current medical research and opinion. 2024;40(7):1235-1243. PubMed PMID: 38889376
11. Kamin W, Funk P, Seifert G, et al. EPs 7630 is effective and safe in children under 6 years with acute respiratory tract infections: clinical studies revisited. Current medical research and opinion. 2018;34(3):475-485. PubMed PMID: 29119837
12. Moyo M, Van Staden J. Medicinal properties and conservation of Pelargonium sidoides DC. Journal of ethnopharmacology. 2014;152(2):243-55. PubMed PMID: 24463034
13. Agbabiaka TB, Guo R, Ernst E. Pelargonium sidoides for acute bronchitis: a systematic review and meta-analysis. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2008;15(5):378-85. PubMed PMID: 18222667

PubMed Topic Searches

1. PubMed: Pelargonium hepatotoxicity
2. PubMed: Teschke re-analyses of Pelargonium liver cases
3. PubMed: Herb-induced liver injury causality assessment

Regulatory Sources

1. European Medicines Agency, Committee on Herbal Medicinal Products. European Union herbal monograph on Pelargonium sidoides DC; Pelargonium reniforme Curt., radix. Final, Revision 2. EMA/HMPC/648100/2022, 2024. EMA monograph (PDF)
2. European Medicines Agency, Committee on Herbal Medicinal Products. Assessment report on Pelargonium sidoides DC; Pelargonium reniforme Curt., radix. Revision 2. EMA/HMPC/765656/2022, 2024. EMA assessment report (PDF)
3. European Medicines Agency, Committee on Herbal Medicinal Products. Opinion of the HMPC on a European Union herbal monograph on Pelargonium sidoides DC; Pelargonium reniforme Curt., radix, with divergent positions. EMA/HMPC/319732/2024. HMPC opinion (PDF)
4. US National Library of Medicine. LiverTox: clinical and research information on drug-induced liver injury. LiverTox

Back to Table of Contents

Connections

• All Herbs
• Pelargonium (Pelargonium sidoides) — the main topic page
• Pelargonium Benefits Deep Dive — the hub for all four articles
• Acute Bronchitis Trials — the trials these side-effect figures come from
• Sinusitis, Sore Throat and Colds — the other indications
• Umckaloabo History and Wild Harvest — the plant's history
• Kava — another herb with a European liver-safety history
• Black Cohosh Benefits — liver reports and causality debates for another herb
• Turmeric: Liver Injury and Who Is at Risk — herb-induced liver injury from a common supplement
• He Shou Wu: Hepatotoxicity Warning — a regulator-led herbal liver warning
• Cinnamon: Cassia, Ceylon and Coumarin — a different coumarin question
• Skullcap: Germander Adulteration and Liver Safety — when the wrong plant causes liver injury

Back to Table of Contents