Feverfew 125 mg [Discontinued] by Natural Factors Nutritional Products Inc

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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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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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, 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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