Butterbur by NOW

POSSIBLY EFFECTIVE

• Allergic rhinitis (hay fever). A specific butterbur leaf extract may be effective for symptoms of allergic rhinitis when taken orally, but a specific butterbur root extract appears to lack these effects. Details: Clinical research shows that taking a specific butterbur leaf extract called Ze 339 (Tesalin, Zeller AG), up to 6 tablets daily in up to three divided doses for 1-2 weeks, seems to decrease nasal inflammatory mediators and nasal symptoms in patients with allergic rhinitis (7595,10336,14414,19383,19384). Some evidence also suggests that this extract might be as effective as cetirizine 10 mg daily (7595) or fexofenadine 180 mg daily (11941,14414). Taking whole butterbur root extract (Petaforce, Bioforce) 50 mg twice daily for 2 weeks seems to reduce the response to an adenosine monophosphate challenge in patients with allergic rhinitis when compared with placebo (10337,11941). However, taking this extract for 2 weeks does not seem to improve peak nasal inspiratory flow, nasal and eye symptoms, or quality of life (11942).
• Migraine headache. A specific butterbur rhizome extract seems to prevent migraine headache in adults and children when taken orally. Details: Clinical research shows that taking a specific butterbur rhizome extract, which is pyrrolizidine alkaloid (PA)-free and standardized to 15% petasin and isopetasin (Petadolex, Weber & Weber, GmbH & Co), 75 mg once or twice daily for up to 16 weeks, reduces the frequency of migraine headache by about 48%. It also reduces the intensity and duration of the headaches (7230,12840,13003,19381). Clinical studies in children aged 6-17 years show that taking this specific butterbur rhizome extract for up to 4 months decreases the frequency of migraine headache when compared with placebo (13121,19382). Doses used in one study were 50-75 mg daily in divided doses for ages 8-9 years, and 100-150 mg daily in divided doses for ages 10-12 years (19382).

POSSIBLY INEFFECTIVE

• Atopic dermatitis (eczema). Oral butterbur root extract does not seem to improve atopic symptoms. Details: Clinical research shows that taking a specific whole butterbur root extract (Petaforce, Bioforce Ltd) 50 mg by mouth twice daily for one week does not reduce histamine wheal and flare responses when compared with placebo in atopic patients (19388).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Anxiety. Although there is interest in using oral butterbur for anxiety, there is insufficient reliable information about the clinical effects of butterbur for this condition.
• Asthma. It is unclear if oral butterbur is beneficial in patients with asthma. Details: Clinical research shows that taking butterbur root extract (Petaforce, Bioforce Ltd.) 25 mg twice daily for 1 week reduces measures of inflammation in patients with asthma when compared with placebo (19385). Taking a different butterbur root extract (Petadolex, Weber & Weber, GmbH & Co.) daily for 2-4 months reduces the number, duration, and severity of asthma attacks when compared with baseline. The extract was taken as 150 mg daily in 3 divided doses by adults, or 50-150 mg daily in 3 divided doses by children aged 6-17 years (19386). The validity of these findings is limited by the lack of a comparator group.
• Chronic bronchitis. Although there is interest in using oral butterbur for chronic bronchitis, there is insufficient reliable information about the clinical effects of butterbur for this condition.
• Cough. Although there is interest in using oral butterbur for cough, there is insufficient reliable information about the clinical effects of butterbur for this purpose.
• Insomnia. Although there is interest in using oral butterbur for insomnia, there is insufficient reliable information about the clinical effects of butterbur for this purpose.
• Peptic ulcers. Although there is interest in using oral butterbur for peptic ulcers, there is insufficient reliable information about the clinical effects of butterbur for this condition.
• Somatic symptom disorder. Adding oral butterbur to a combination of other herbs may reduce anxiety and depression associated with somatic symptom disorder. Details: Clinical research shows that taking a specific combination product called Ze 185 (Relaxane, Max Zeller Söhne AG), containing butterbur root extract 90 mg, valerian root 90 mg, lemon balm leaf 60 mg, and passionflower herb 90 mg, two to three times daily for 2 weeks improves anxiety and depression in people with somatoform disorders when compared with a product containing the same ingredients, but without butterbur (19701). More evidence is needed to rate butterbur for these uses.

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POSSIBLY EFFECTIVE

• Migraine headache. Oral feverfew seems to reduce the frequency of migraines and improve migraine-related symptoms. Details: Most clinical research shows that taking feverfew can reduce the frequency of migraine headaches and reduce symptoms of pain, nausea, vomiting, and sensitivity to light and noise (5080,6959,6960,6961,12384,13239,19358,90607). It may be more effective in patients with more frequent migraine attacks (12384). Combination products containing feverfew and other ingredients have also been evaluated, with promising results in most studies (12389,19357,19359,22602,96531,96532,103009,107473). However, some conflicting evidence exists (727,6938,12153,12384). These conflicting findings may reflect differences in the harvested feverfew plants or differences in the bioavailability of commercially prepared feverfew products (12153). Dosing regimens with evidence of benefit include feverfew powder 50-150 mg once daily for up to 4 months (6959,6960,6961,90607) and a carbon dioxide extract of feverfew (MIG-99, Schaper & Brümmer GmbH & Co) 2.08-18.75 mg three times daily for 3 to 4 months (12384,13239).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Prurigo nodularis. It is unclear if topical feverfew is beneficial for patients with this skin condition. Details: Preliminary clinical research in people with prurigo nodularis shows that applying a topical cream containing feverfew (Aveeno Ultra-Calming Cream, Johnson & Johnson) modestly improves pruritus in about 90% of affected patients. However, the cream does not appear to cause complete remission of skin lesions (22601).
• Psoriasis. Although there has been interest in using oral feverfew for psoriasis, there is insufficient reliable information about the clinical effects of feverfew for this purpose.
• Rheumatoid arthritis (RA). It is unclear if oral feverfew is beneficial for patients with RA. Details: Preliminary clinical research in a small number of women with RA shows that taking dried chopped feverfew 70-86 mg daily for 6 weeks does not seem to reduce the symptoms of RA, including pain, stiffness, or grip strength, when compared with placebo (6933).
• Tension headache. Oral feverfew has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Observational research in children and adolescents with tension headache has found that taking a specific combination supplement (Partena) containing feverfew dry extract 150 mg (standardized to 1.2 mg of parthenolides), magnesium 169 mg, coenzyme Q10 20 mg, riboflavin 4.8 mg, and andrographis 100 mg twice daily for 4 weeks and then once daily for 12 weeks is associated with reduced headache frequency, but not pain intensity, when compared to baseline (103009). More evidence is needed to rate feverfew for these uses.

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POSSIBLY SAFE ...when pyrrolizidine alkaloid (PA)-free butterbur products are used orally and appropriately. Although there are some rare cases of liver injury associated with extracts that are reported to be free of PA constituents (102700), rhizome and leaf extracts that are free of PAs seem to be generally safe when used for up to 16 weeks (7230,7595,10336,10337,12840,13003,14414,19381,19383,19384,19385). Tell patients not to use butterbur products that are not certified and labeled as PA-free.

LIKELY UNSAFE ...when products containing pyrrolizidine alkaloid (PA) constituents are used orally. Repeated exposure to low concentrations of PAs can cause hepatotoxicity and severe veno-occlusive disease. PAs might also be carcinogenic and mutagenic (12841,12842). ...when products containing PAs are used topically on abraded or broken skin. Absorption of PAs through broken skin can lead to systemic toxicity (12841).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately. There is some evidence that a specific pyrrolizidine alkaloid (PA)-free butterbur rhizome extract (Petadolex, Weber & Weber, GmbH & Co) can be used with apparent safety in children aged 6-17 years for up to 4 months (13121,19382,19386).

PREGNANCY: LIKELY UNSAFE
when butterbur preparations containing pyrrolizidine alkaloid (PA) constituents are used orally. These constituents might be teratogenic and hepatotoxic (12841,12842). There is insufficient reliable information available about the safety of using butterbur products that do not contain PAs during pregnancy.

LACTATION: LIKELY UNSAFE
when butterbur preparations containing pyrrolizidine alkaloid (PA) constituents are used orally. PAs are excreted in breast milk (12841,12842). There is insufficient reliable information available about the safety of using butterbur products that do not contain PAs during lactation.

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LIKELY SAFE ...when used orally and appropriately, short-term. Feverfew has been used safely in studies lasting up to 4 months (6959,6960,6961,13239).

POSSIBLY UNSAFE ...when fresh feverfew leaves are chewed. Chewing raw or unprocessed feverfew leaves can cause oral inflammation, ulceration, swelling of the lips, and sometimes loss of taste (6959).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Feverfew might cause uterine contractions and abortion (12); avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

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CYTOCHROME P450 3A4 (CYP3A4) INDUCERS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, CYP3A4 inducers might increase the toxicity of butterbur.  Details The pyrrolizidine alkaloid (PA) constituents found in some butterbur products are substrates of CYP3A4 (12841,12860). Theoretically, drugs that induce CYP3A4 might increase the conversion of PAs to toxic metabolites.

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, feverfew might have additive effects and increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.  Details Laboratory research suggests that feverfew may inhibit platelet aggregation (6935,6936,6942,6943,6944,6945,6951). Additionally, in one case report, a 36-year-old patient taking feverfew 2400 mg daily for 3 months experienced vaginal bleeding and a prolonged menstrual cycle, with a modest increase in partial thromboplastin time (PTT) and prothrombin time (PT) (107472).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, feverfew might increase levels of drugs metabolized by CYP1A2.  Details Laboratory research shows that feverfew might inhibit CYP1A2 (12479). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, feverfew might increase levels of drugs metabolized by CYP2C19.  Details Laboratory research shows that feverfew might inhibit CYP2C19 (12479). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2C8 (CYP2C8) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, feverfew might increase levels of drugs metabolized by CYP2C8.  Details Laboratory research shows that feverfew might inhibit CYP2C8 (12479). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, feverfew might increase levels of drugs metabolized by CYP2C9.  Details Laboratory research shows that feverfew might inhibit CYP2C9 (12479). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, feverfew might increase levels of drugs metabolized by CYP2D6.  Details Laboratory research shows that feverfew might inhibit CYP2D6 (12479). So far, this interaction has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, feverfew might increase levels of drugs metabolized by CYP3A4.  Details Laboratory research shows that feverfew might inhibit CYP3A4 (12479,19361). So far, this interaction has not been reported in humans.

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General ...Orally, butterbur seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Belching, diarrhea, drowsiness, fatigue, headache, itchy eyes, pruritus, rash, and stomach upset.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity due to the presence of pyrrolizidine alkaloids (PAs), although there are also rare reports of liver injury associated with butterbur supplements labeled as PA-free.

Dermatologic ...Orally, butterbur may cause pruritus and rash (12386,19382).

Gastrointestinal ...Orally, butterbur may cause abdominal pain, belching, nausea, diarrhea, regurgitation, and stomach upset (12386,13121,19382,19383).

Hepatic ...The butterbur plant contains hepatotoxic pyrrolizidine alkaloid (PA) constituents which have been associated with veno-occlusive disease, liver enlargement, and gastrointestinal symptoms (4021,12386,12841,12842). However, there is some evidence to suggest that even PA-free butterbur preparations might cause liver injury. Of 48 cases of liver injury with a specific PA-free butterbur product (Petadolex), three cases were considered likely related and 13 cases possibly related to butterbur use. An additional 12 cases of mild liver injury suspected to be related to use of butterbur have been reported in clinical trials. Of a total of 10 severe cases of liver injury, one was considered likely related and 5 were considered possibly related to butterbur use. While most patients experienced quick recovery after butterbur discontinuation, one required liver transplantation (102700).

Musculoskeletal ...Orally, butterbur may cause pain, including arthralgias and limb pain (19382).

Ocular/Otic ...Orally, butterbur causes itchy eyes (12386).

Pulmonary/Respiratory ...Orally, butterbur may cause asthmatic symptoms (12386). Also, butterbur theoretically might cause an allergic reaction in individuals sensitive to the Asteraceae/Compositae family. Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs (12841).

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General ...Orally, feverfew is generally well tolerated. Chewing fresh feverfew leaves is more likely to cause mouth ulceration and other adverse effects of the mouth, lips, and tongue when compared with commercial feverfew preparations.
Most Common Adverse Effects:
Orally: Abdominal pain, bloating, constipation, diarrhea, flatulence, heartburn, and nausea. Skin rash may occur in sensitive individuals.
Topically: Dermatitis in sensitive individuals.

Cardiovascular ...Orally, feverfew has been associated with palpitations in one patient in a clinical study (6959).

Dermatologic ...Orally, feverfew can cause skin rash (12383). Topically, allergic contact dermatitis can occur (6958,42856,42891). Allergic reactions to feverfew may be more likely in individuals sensitive to the Asteraceae/Compositae family. Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.

Gastrointestinal ...Orally, feverfew can cause gastrointestinal symptoms such as heartburn, nausea, diarrhea, constipation, abdominal pain and bloating, and flatulence (6938,6959,12383,22602). Oral numbness has also been reported when feverfew has been taken sublingually in combination with ginger (22602). The traditional method of feverfew administration-chewing fresh feverfew leaves-can result in mouth ulceration, inflamed oral mucosa and tongue, swelling of the lips, and occasionally, loss of taste (6935,6959). Mouth ulceration might result from direct contact with feverfew leaves during chewing, possibly attributable to the sesquiterpene lactone constituent (6959). Some researchers suggest that mouth ulceration is a systemic effect, but one study using dried feverfew capsules reported a higher incidence of mouth ulcers in subjects taking placebo than feverfew (6935,6959,6960).

Genitourinary ...Orally, feverfew has been associated with menstrual changes in one patient in a clinical study (6959) and in one case report involving a 36-year-old patient taking 800 mg of feverfew three times daily for 3 months (107472).

Immunologic ...Orally and topically, feverfew may cause an allergic reaction in individuals sensitive to the Asteraceae/Compositae family. Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.

Musculoskeletal ...Orally, feverfew has been associated with joint stiffness in two patients in a clinical study (6959). Discontinuation of oral feverfew after long-term use may cause "post-feverfew syndrome", which includes symptoms such as muscle and joint stiffness (6959,12153).

Neurologic/CNS ...Discontinuation of oral feverfew after long-term use may cause "post-feverfew syndrome", which includes symptoms such as anxiety, headaches, and insomnia (6959,12153).

Other ...Orally, feverfew may cause weight gain (12383).

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