Feverfew

Feverfew/Drug Interactions:

  • AbortifacientsAbortifacients: Traditional use suggests that feverfew may have abortifacient effects. According to a systematic review, feverfew treatment has been associated with abnormal menstruation (57).
  • AnalgesicsAnalgesics: Oral administration of feverfew extract has produced significant dose-dependent antinociceptive effects in rodents (99). Parthenolide has also produced antinociceptive effects. Naloxone, an opiate antagonist, failed to reverse feverfew and parthenolide-induced antinociception. Feverfew extract in higher doses (40-60mg/kg orally) neither altered the locomotor activity nor potentiated pentobarbitone-induced sleep time in mice. Feverfew has been shown to interact with aspirin (64).
  • AnestheticsAnesthetics: According to a review, feverfew may cause complications when used concomitantly with anesthetics (25). These complications may include increased risk of bleeding in the perioperative period, as well as insomnia.
  • Antiangiogenic drugsAntiangiogenic drugs: Theoretically, feverfew may have additive effects when taken concomitantly with antiangiogenic drugs (26).
  • Antianxiety agentsAntianxiety agents: According to a systematic review, anxiety and insomnia have been reported when feverfew treatment was discontinued (9). In addition, nervousness, tension headaches, insomnia, and tiredness have been reported with feverfew treatment.
  • Antiarthritic agentsAntiarthritic agents: Laboratory and animal studies have shown that feverfew possesses anti-inflammatory activity (30; 100; 101; 102; 103; 99; 104; 105; 106; 107). In human research, feverfew lacked a significant effect on joint pain and stiffness in rheumatoid arthritis patients, but significantly improved grip strength compared to placebo treatment (14). Side effects including muscle stiffness and joint pain have been reported in patients when feverfew was discontinued after chronic use (17; 9; 8; 57).
  • AntibioticsAntibiotics: In laboratory research, the essential oil of feverfew (Tanacetum parthenium) demonstrated bactericidal activities against most of the microorganisms tested, with Gram-positive species exhibiting significantly lower sensitivity relative to Gram-negative species. (108). With respect to Gram-positive species, the essential oil exhibited strong bactericidal effects on only Bacillus species, but exhibited strong bactericidal action against nearly all Gram-negative species.
  • Anticoagulant and antiplateletsAnticoagulant and antiplatelets: Feverfew has been shown to inhibit platelet secretory and aggregation activity and may theoretically increase the risk of bleeding if used concomitantly with anticoagulant or antiplatelet agents (19; 20; 21; 40; 23; 24; 25). It has been demonstrated that feverfew inhibits prostaglandins (97; 98). It has also been shown to interact with aspirin (64).
  • Antidepressant agents, selective serotonin reuptake inhibitors (SSRIs)Antidepressant agents, selective serotonin reuptake inhibitors (SSRIs): According to animal research, it has been suggested that feverfew may worsen symptoms of depression or reduce the effectiveness of antidepressants. Serotonin 5-HT receptor-blocking effects have been suggested as a possible mechanism of action for feverfew in the treatment of migraine headaches (60). The feverfew constituent parthenolide was theorized to inhibit serotonin release as a mechanism for migraine prophylaxis (109).
  • AntifungalsAntifungals: In laboratory research, the essential oil of feverfew (Tanacetum parthenium) demonstrated fungicidal activities (108). A strong antifungal effect was noted in five of the eight fungal species investigated, and the essential oil exhibited strong effects against the molds and dermatophytes tested in the study. In other laboratory research, feverfew extract inhibited phagocytosis and degranulation of Candida guilliermondii (106).
  • AntihistaminesAntihistamines: Feverfew extract has demonstrated a dose-dependent inhibition of histamine release from stimulated rat peritoneal mast cells (110). However, Tanacetum parthenium has been shown to cause airborne contact allergy (61), and according to a systematic review, respiratory disorders have been reported in clinical trials (7). Also, there have been multiple reports of allergic reactions to feverfew in Europe, Asia, and the United States (68; 69; 70; 71; 72; 73; 74; 75; 76; 77; 78; 45; 46; 90; 91).
  • Anti-inflammatory agentsAnti-inflammatory agents: Laboratory, animal, and human research has shown that feverfew possesses anti-inflammatory activity (30; 100; 101; 102; 103; 99; 104; 105; 106; 107; 111; 112; 113; 114; 115; 116; 117; 15). In laboratory research, feverfew acted as an inhibitor of prostaglandin synthesis (97; 118; 102), with observed inhibition of cyclooxygenase and lipoxygenase activity (100; 101). Feverfew has been shown to interact with aspirin (64).
  • Antimalarial agentsAntimalarial agents: In laboratory research, concomitant treatment of parthenolide and artemisinin inhibited nuclear factor (NF)-kappaB, which, according to the authors, may reduce the cytotoxicity or the efficacy of doxorubicin on colon cancer cells (62).
  • Antineoplastic agentsAntineoplastic agents: In laboratory and animal research, parthenolide, a constituent of feverfew, inhibited the activity of various cancer cell lines (28; 33; 119; 120; 36; 29; 121), delayed the onset of cancer in animals (122), and enhanced the chemotherapy activity of paclitaxel (27). However, when administered with artemisinin, inhibition of nuclear factor (NF)-kappaB occurred, which may reduce the cytotoxicity or the efficacy of doxorubicin on colon cancer cells (62).
  • Antiobesity agentsAntiobesity agents: According to a systematic review, treatment with feverfew may be associated with weight gain (57).
  • AntiprotozoalsAntiprotozoals: In laboratory research, parthenolide showed significant activity against the promastigote form of Leishmania amazonensis (37).
  • BarbituratesBarbiturates: In animal research, feverfew extract administered in higher doses (40-60mg/kg orally) neither altered the locomotor activity nor potentiated pentobarbitone-induced sleep time in mice (99).
  • Cardiovascular agentsCardiovascular agents: A small study on migraine patients reported a significant increase in mean heart rate from baseline (17). However, these results were skewed by two patients whose heart rates increased by 20-26 beats/minute each. Palpitations were also reported by one patient. However, according to a systematic review, feverfew lacked a significant effect on blood pressure or heart rate (57).
  • CNS depressantsCNS depressants: According to a systematic review, anxiety and insomnia have been reported when feverfew treatment was discontinued (9). In addition, nervousness, tension headaches, insomnia, and tiredness have been reported in human trials with feverfew treatment. In animal research, feverfew extract administered in higher doses (40-60mg/kg orally) neither altered the locomotor activity nor potentiated pentobarbitone-induced sleep time in mice (99). According to a review, feverfew may cause complications when used concomitantly with anesthetics, due to its potential to cause insomnia (25).
  • Cytochrome P450-metabolized agentsCytochrome P450-metabolized agents: Feverfew has been seen to possess inhibitory effects on the CYP enzymes. Specific isoenzymes studied were CYP1A2, 2C8, 2C9, 2C19, 2D6, and 3A4 (63).
  • Dermatologic agentsDermatologic agents: In human research, feverfew caused contact eczema (45; 46) and contact dermatitis (47; 48; 49; 50; 51; 52; 53; 54; 55; 56; 96; 79; 91), which sometimes developed into erythroderma (79), seborrheic dermatitis (93), or chronic actinic dermatitis (94). However, in animal research, treatment with parthenolide resulted in a delayed onset of papilloma incidence following ultraviolet B (UVB) exposure (122).
  • DoxorubicinDoxorubicin: In vitro, artemisinin with parthenolide inhibited nuclear factor (NF)-kappaB, which may reduce the cytotoxicity of doxorubicin on colon cancer cells (62).
  • Gastrointestinal agents, miscellaneousGastrointestinal agents, miscellaneous : Feverfew may cause oral inflammation and ulceration, swelling of the lips, loss of taste (17), tongue soreness (14), gingival bleeding, indigestion, nausea, flatulence, constipation, diarrhea, abdominal bloating, heartburn, colicky pain in the abdomen, and diarrhea (59; 18; 11; 8; 7; 57).
  • Hematologic agentsHematologic agents: In laboratory studies and reviews, feverfew has been shown to inhibit platelet secretory and aggregation activity and may theoretically increase the risk of bleeding if used concomitantly with anticoagulant or antiplatelet agents or if used with surgical medications, including anesthesia (25; 20; 21; 40; 23; 24; 19). It has been demonstrated that feverfew inhibits prostaglandins (97; 98).
  • Neurologic agentsNeurologic agents: According to animal research, feverfew may worsen symptoms of depression or reduce the effectiveness of antidepressants. Serotonin 5-HT receptor-blocking effects have been suggested as a possible mechanism of action for feverfew, in the treatment of migraine headaches (60). In one study, rebound headaches were reported in two patients when feverfew was discontinued after chronic use (17; 9). Oral administration of feverfew extract has produced significant dose-dependent antinociceptive effects in rodents (99). Parthenolide has also produced antinociceptive effects. Naloxone, an opiate antagonist, failed to reverse feverfew and parthenolide-induced antinociception. Feverfew extract in higher doses (40-60mg/kg orally) neither altered the locomotor activity nor potentiated pentobarbitone-induced sleep time in mice.
  • PaclitaxelPaclitaxel: In laboratory research, parthenolide, a constituent of feverfew, enhanced the chemotherapeutic activity of paclitaxel (27).
  • Photosensitizing agentsPhotosensitizing agents: In animal research, treatment with parthenolide resulted in a delayed onset of papilloma incidence following UVB exposure (122).
  • SalicylatesSalicylates: Feverfew has been shown to interact with aspirin (64).
  • SedativesSedatives: According to a systematic review, anxiety and insomnia have been reported when feverfew treatment was discontinued (9). In addition, nervousness, tension headaches, insomnia, and tiredness have been reported in human trials with feverfew treatment. In animal research, feverfew extract administered in higher doses (40-60mg/kg orally) neither altered the locomotor activity nor potentiated pentobarbitone-induced sleep time in mice (99). According to a review, feverfew may cause complications when used concomitantly with anesthetics due to its potential to cause insomnia (25).
  • VasoconstrictorsVasoconstrictors: Extracts of feverfew and parthenolide have been reported to inhibit smooth muscle contractility (65) and strongly inhibit responses to phenylephrine, 5-hydroxytryptamine, thromboxane mimetic, and angiotensin II (123). Blockade of open potassium channels has been suggested in animal studies (66; 67).

    • Feverfew/Herb/Supplement Interactions:

  • AbortifacientsAbortifacients: Traditional use suggests that feverfew may have abortifacient effects. According to a systematic review, feverfew treatment has been associated with abnormal menstruation (57).
  • AnalgesicsAnalgesics: Oral administration of feverfew extract has produced significant dose-dependent antinociceptive effects in rodents (99). Parthenolide has also produced antinociceptive effects. Naloxone, an opiate antagonist, failed to reverse feverfew and parthenolide-induced antinociception. Feverfew extract in higher doses (40-60mg/kg orally) neither altered the locomotor activity nor potentiated pentobarbitone-induced sleep time in mice. Feverfew has been shown to interact with aspirin (64).
  • AnestheticsAnesthetics: According to a review, feverfew may cause complications when used concomitantly with anesthetics (25). These complications may include increased risk of bleeding in the perioperative period, as well as insomnia.
  • Antiangiogenic agentsAntiangiogenic agents: Theoretically, feverfew may have additive effects when taken concomitantly with antiangiogenic agents (26).
  • Antianxiety agentsAntianxiety agents: According to a systematic review, anxiety and insomnia have been reported when feverfew treatment was discontinued (9). In addition, nervousness, tension headaches, insomnia, and tiredness have been reported with feverfew treatment.
  • AntiarthriticsAntiarthritics: Laboratory and animal studies have shown that feverfew possesses anti-inflammatory activity (30; 100; 101; 102; 103; 99; 104; 105; 106; 107). In human research, feverfew lacked a significant effect on joint pain and stiffness in rheumatoid arthritis patients but significantly improved grip strength compared to placebo treatment (14). Side effects including muscle stiffness and joint pain have been reported in patients when feverfew was discontinued after chronic use (17; 9; 8; 57).
  • AntibacterialsAntibacterials: In laboratory research, the essential oil of feverfew (Tanacetum parthenium) demonstrated bactericidal activities against most of the microorganisms tested, with Gram-positive species exhibiting significantly lower sensitivity relative to Gram-negative species (108). With respect to Gram-positive species, the essential oil exhibited strong bactericidal effects only on Bacillus species, but exhibited strong bactericidal action against nearly all Gram-negative species.
  • Anticoagulants and antiplatelets herbsAnticoagulants and antiplatelets herbs: Feverfew has been shown to inhibit platelet secretory and aggregation activity and may theoretically increase the risk of bleeding if used concomitantly with anticoagulant or antiplatelet agents (19; 20; 21; 40; 23; 24; 25). It has been demonstrated that feverfew inhibits prostaglandins (97; 98).
  • Antidepressants, selective serotonin reuptake inhibitors (SSRIs)Antidepressants, selective serotonin reuptake inhibitors (SSRIs): According to animal research, feverfew may worsen the symptoms of depression or reduce the effectiveness of antidepressants. Serotonin 5-HT receptor-blocking effects have been suggested as a possible mechanism of action for feverfew in the treatment of migraine headaches (60). The feverfew constituent parthenolide was theorized as inhibiting serotonin release as a mechanism for migraine prophylaxis (109).
  • AntifungalsAntifungals: In laboratory research, the essential oil of feverfew (Tanacetum parthenium) demonstrated fungicidal activities (108). A strong antifungal effect was noted in five of the eight fungal species investigated, and the essential oil exhibited strong effects against the molds and dermatophytes tested in the study. In other laboratory research, feverfew extract inhibited phagocytosis and degranulation of Candida guilliermondii (106).
  • AntihistaminesAntihistamines: Feverfew extract has demonstrated a dose-dependent inhibition of histamine release from stimulated rat peritoneal mast cells (110). However, Tanacetum parthenium has been shown to cause airborne contact allergy (61), and according to a systematic review, respiratory disorders have been reported in clinical trials (7). Also, there have been multiple reports of allergic reactions to feverfew in Europe, Asia, and the United States (68; 69; 70; 71; 72; 73; 74; 75; 76; 77; 78; 45; 46; 90; 91).
  • Anti-inflammatory herbsAnti-inflammatory herbs: Laboratory, animal, and human research has shown that feverfew possesses anti-inflammatory activity (30; 100; 101; 102; 103; 99; 104; 105; 106; 107; 111; 112; 113; 114; 115; 116; 117; 15). In laboratory research, feverfew acted as an inhibitor of prostaglandin synthesis (97; 118; 102), with observed inhibition of cyclooxygenase and lipoxygenase activity (100; 101). Feverfew has been shown to interact with aspirin (64).
  • Antimalarial agentsAntimalarial agents: In laboratory research, concomitant treatment of parthenolide and artemisinin inhibited nuclear factor (NF)-kappaB, which, according to the authors, may reduce the cytotoxicity or the efficacy of doxorubicin on colon cancer cells (62).
  • AntineoplasticsAntineoplastics: In laboratory and animal research, parthenolide, a constituent of feverfew, inhibited the activity of various cancer cell lines (28; 33; 119; 120; 36; 29; 121), delayed the onset of cancer in animals (122), and enhanced the chemotherapy activity of paclitaxel (27). However, when administered with artemisinin, inhibition of nuclear factor (NF)-kappaB occurred, which may reduce the cytotoxicity or the efficacy of doxorubicin on colon cancer cells (62).
  • AntiparasiticsAntiparasitics: In laboratory research, parthenolide showed significant activity against the promastigote form of Leishmania amazonensis (37).
  • Cardiovascular herbs and supplementsCardiovascular herbs and supplements: A small study on migraine patients reported a significant increase in mean heart rate from baseline (17). However, these results were skewed by two patients whose heart rates increased by 20-26 beats/minute each. Palpitations were also reported by one patient. However, according to a systematic review, feverfew lacked a significant effect on blood pressure or heart rate (57).
  • Cytochrome P450 substratesCytochrome P450 substrates: Feverfew has been seen to possess inhibitory effects on the CYP enzymes; the specific isoenzymes studied were CYP1A2, 2C8, 2C9, 2C19, 2D6, and 3A4 (63).
  • Dermatologic agentsDermatologic agents: In human research, feverfew caused contact eczema (45; 46) and contact dermatitis (47; 48; 49; 50; 51; 52; 53; 54; 55; 56; 96; 79; 91), which sometimes developed into erythroderma (79), seborrheic dermatitis (93), or chronic actinic dermatitis (94). However, in animal research, treatment with parthenolide resulted in a delayed onset of papilloma incidence following UVB exposure (122).
  • Garlic(Allium sativum)Garlic(Allium sativum): In theory, feverfew may increase the risk of bleeding when taken with garlic.
  • Gastrointestinal herbs and supplementsGastrointestinal herbs and supplements: Feverfew may cause oral inflammation and ulceration, swelling of the lips, loss of taste (17), tongue soreness (14), gingival bleeding, indigestion, nausea, flatulence, constipation, diarrhea, abdominal bloating, heartburn, colicky pain in the abdomen, and diarrhea (59; 18; 11; 8; 7; 57).
  • Ginkgo(Ginkgo biloba)Ginkgo(Ginkgo biloba): In theory, feverfew may increase the risk of bleeding when taken with ginkgo.
  • Hematologic herbs and supplementsHematologic herbs and supplements: In laboratory studies and reviews, feverfew has been shown to inhibit platelet secretory and aggregation activity and may theoretically increase the risk of bleeding if used concomitantly with anticoagulant or antiplatelet agents, as well as if used with surgical medications, including anesthesia (25; 20; 21; 40; 23; 24; 19). It has been demonstrated that feverfew inhibits prostaglandins (97; 98).
  • Neurologic herbs and supplementsNeurologic herbs and supplements: According to animal research, it has been suggested that feverfew may worsen symptoms of depression or reduce the effectiveness of antidepressants. Serotonin 5-HT receptor-blocking effects have been suggested as a possible mechanism of action for feverfew, in the treatment of migraine headaches (60). In one study, rebound headaches were reported in two patients when feverfew was discontinued after chronic use (17; 9). Oral administration of feverfew extract has produced significant dose-dependent antinociceptive effects in rodents (99). Parthenolide has also produced antinociceptive effects. Naloxone, an opiate antagonist, failed to reverse feverfew and parthenolide-induced antinociception. Feverfew extract in higher doses (40-60mg/kg orally) neither altered the locomotor activity nor potentiated pentobarbitone-induced sleep time in mice.
  • PhotosensitizersPhotosensitizers: However, in animal research, treatment with parthenolide resulted in a delayed onset of papilloma incidence following UVB exposure (122).
  • Salicylate-containing agentsSalicylate-containing agents: Feverfew has been shown to interact with aspirin (64).
  • SedativesSedatives: According to a systematic review, anxiety and insomnia have been reported when feverfew treatment was discontinued (9). In addition, nervousness, tension headaches, insomnia, and tiredness have been reported in human trials with feverfew treatment. In animal research, feverfew extract administered in higher doses (40-60mg/kg orally) neither altered the locomotor activity nor potentiated pentobarbitone-induced sleep time in mice (99). According to a review, feverfew may cause complications when used concomitantly with anesthetics due to its potential to cause insomnia (25).
  • VasoconstrictorsVasoconstrictors: Extracts of feverfew and parthenolide have been reported to inhibit smooth muscle contractility (65) and strongly inhibit responses to phenylephrine, 5-hydroxytryptamine, thromboxane mimetic, and angiotensin II (123). Blockade of open potassium channels has been suggested in animal studies (66; 67).
  • Weight loss agentsWeight loss agents: According to a systematic review, treatment with feverfew may be associated with weight gain (57).

    • Feverfew/Food Interactions:

  • Insufficient available evidence.

    • Feverfew/Lab Interactions:

  • Coagulation panelCoagulation panel: Feverfew has been shown to inhibit platelet secretory and aggregation activity and may theoretically increase the risk of bleeding if used concomitantly with anticoagulant or antiplatelet agents (19; 20; 21; 40; 23; 24). It has been demonstrated that feverfew inhibits prostaglandins (97; 98). It has also been shown to interact with aspirin (64).
  • CytokinesCytokines: In vivo and in vitro, parthenolide inhibited NF-kappaB activation, IL-8 secretion, IkappaB kinase complex activity, IkappaB-alpha degradation, PMN influx, and production of cytokines and chemokines (30; 116). In vitro, parthenolide-depleted (PD) feverfew inhibited macrophages from releasing TNF-alpha, nitric oxide, and prostaglandin (PG)-E(2); human peripheral blood mononuclear cells from releasing IFN-gamma, TNF-alpha, IL-2, and IL-4; and human skin equivalents from releasing TPA-induced PGE(2) (15). In laboratory research, parthenolide exerted anti-inflammatory properties via inhibition of lipopolysaccharide-induced proinflammatory production (104). The inhibition was by means of blocking the induction of interleukin-6 (IL-6) and tumor necrosis factor-alpha.
  • Heart rateHeart rate: A small study on migraine patients reported a significant increase in mean heart rate from baseline (17). However, these results were skewed by two patients whose heart rates increased by 20-26 beats/minute each. Palpitations were also reported by one patient.
  • HistamineHistamine: Feverfew extract has demonstrated dose-dependent inhibition of histamine release from stimulated rat peritoneal mast cells (110).
  • Vascular adhesion molecule-1 (VCAM-1)Vascular adhesion molecule-1 (VCAM-1): Parthenolide was shown to block more than 90% of interleukin-4-induced expression of the endothelial vascular cell adhesion molecule (VCAM)-1 (107).