Petadolex Pro-Active [Discontinued] by Enzymatic Therapy

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 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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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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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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