Gas & Bloating [Discontinued] by Gaia Herbs RapidRelief

POSSIBLY EFFECTIVE

• Poisoning. Oral activated charcoal taken after ingestion of certain drugs reduces systemic drug exposure. However, it is unclear if it affects clinical endpoints such as morbidity or mortality. Details: Taking activated charcoal orally appears to be effective when used as part of standard treatment for some, but not all, acute poisonings (12392,12393,93198,93606,93607,93613,94730). Single doses of activated charcoal, 25-100 grams in adults (10-50 grams in children, depending on age), are effective for preventing absorption of some drugs, including acetaminophen, aminophylline, amiodarone, aspirin, atenolol, carbamazepine, digoxin, fluoxetine, indomethacin, phenytoin, valproate, and verapamil, especially if taken within one hour of ingestion (93602,93610,93612,93613,94730,108852). A single dose reduces drug exposure by 38% to 52% when given within 1 hour, by 21% to 35% when given 2-4 hours after ingestion, and by about 14% when given 6 hours after ingestion. These late effects, occurring after oral absorption is complete, are due to enhanced elimination via interruption of enterohepatic circulation and binding of drug that has been actively or passively transported back into the gastrointestinal tract (105543). Multiple-dose activated charcoal, 50-100 grams initially followed by doses of 25 grams every 2 hours or 50 grams every 4 hours, or 10-25 grams per dose in children, is recommended for patients who ingest life-threatening amounts of carbamazepine, dapsone, phenobarbital, quinine, or theophylline. This is based on clinical, animal, and in vitro research showing increased elimination of these drugs (12392,105543). This increased elimination can also reduce levels of drugs that have been given intravenously, with the median half-life being decreased by an average of 45% and the median area under the concentration/time curve (AUC) by an average of 47% (105543). Additional research suggests that multiple-dose activated charcoal may be useful for increasing the elimination of amitriptyline, digoxin, imipramine, moxifloxacin, nadolol, phenytoin, piroxicam, and sotalol. Evidence supporting the use of multiple-dose activated charcoal in aspirin, doxepin, tobramycin, valproate, or vancomycin overdose is limited or conflicting (12392,105543). While activated charcoal may reduce absorption of some toxic agents, there is contradictory evidence about whether it improves clinical outcomes (12392,93200,93601,93613,94730). Administering activated charcoal 50 grams every 6 hours for carbamazepine poisoning decreases the duration of coma by 9 hours, the duration of mechanical ventilation by 12 hours, and the length of hospital stay by 9 hours. However, activated charcoal does not reduce the duration of hospitalization, intensive care admission, vomiting, or mortality when compared with control after oral overdose of benzodiazepines, acetaminophen, or selective serotonin reuptake inhibitors (93200). Other preliminary clinical research in patients with phenytoin toxicity shows that taking activated charcoal 50 grams orally every 4 hours reduces the time to return to therapeutic levels by about 22 hours when compared with control, but without reducing symptoms (93609). In patients with pesticide or yellow oleander seed toxicity, neither single-dose nor multi-dose regimens of activated charcoal reduce mortality, seizures, or the need for intubation when compared with control (93601).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Celiac disease. Although there is interest in using activated charcoal for acute gluten exposure in those with celiac disease, there is insufficient reliable information about the clinical effects of activated charcoal for this purpose.
• Chemotherapy-induced diarrhea. It is unclear if oral activated charcoal is beneficial in patients with chemotherapy-induced diarrhea. Details: Preliminary clinical research in children treated with irinotecan shows that taking activated charcoal 250 mg the night before the first infusion and every 8 hours thereafter until the end of the cycle reduces the risk of diarrhea by 60% when compared with no treatment. Activated charcoal also appears to reduce the risk of severe diarrhea by 92% and to decrease chemotherapy discontinuation by 87% in these patients (93608).
• Cholestasis. It is unclear if oral activated charcoal is beneficial in patients with pregnancy-induced cholestasis. Details: Preliminary clinical research in pregnant patients with cholestasis shows that taking activated charcoal 50 grams orally three times daily for 8 days decreases bile acid levels by about 50%, compared with an increase in those not taking activated charcoal. However, itching was not significantly improved with activated charcoal when compared with control (126).
• Constipation. Oral activated charcoal has only been evaluated in combination with other ingredients; its effects when used alone are unclear. Details: A clinical study in patients with chronic constipation shows that a specific combination product (Nucarb; Wilshire Laboratories Ltd) containing activated charcoal 180 mg, calcium sennosides 50 mg, peppermint oil 0.5 mg, fennel oil 0.5 mg, rhubarb extract 250 mg, and sulfur 50 mg, taken as two tablets at bedtime for one week, followed by 1 tablet at bedtime for 1 week, reduces passing gas, abdominal pain, and sensation of bloating by 81%, 73%, and 72% respectively, when compared with baseline. Sensation of straining, severity of constipation, and feeling of incomplete evacuation were reduced by 69%, 67%, and 54% respectively, when compared with baseline (108853). The validity of this finding is limited by the lack of a comparator group.
• Dyspepsia. Oral activated charcoal has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with functional dyspepsia shows that taking a specific combination product containing activated charcoal 280 mg, simethicone 90 mg, and magnesium oxide 180 mg (Carbosymag, Laboratoires Grimberg) three times daily for one month reduces symptoms of dyspepsia, such as postprandial fullness, epigastric pain, and abdominal bloating, when compared with placebo (93199). Other preliminary clinical research in patients with dyspepsia shows that taking another specific combination product containing activated charcoal 280 mg and simethicone 90 mg (Carbosylane, Laboratoires Grimberg) three times daily for 3 months does not improve overall symptoms of dyspepsia or nausea, but does improve abdominal fullness by 20%, bloating by 20%, and slow digestion by 30%, when compared with placebo (93604).
• Flatulence. It is unclear if oral activated charcoal is beneficial for reducing the occurrence of flatulence. Details: Some preliminary clinical research shows that taking activated charcoal (Requa Charcocaps) 582 mg after a gas-producing meal significantly decreases the number of flatus events when compared with placebo. On average, subjects taking activated charcoal reported less than 3 flatus events over 8 hours, compared with more than 14 flatus events in those taking placebo (12395). However, other preliminary clinical research shows that taking activated charcoal 520 mg at breakfast, lunch, dinner, and bedtime for 7 days does not significantly reduce excessive gas or total flatus events when compared with baseline (12396).
• Hangover. There is no reliable evidence that activated charcoal prevents or treats hangover. Details: Activated charcoal is included in some hangover remedies. However, ethanol adsorbs poorly to activated charcoal (12400).
• Hypercholesterolemia. It is unclear if oral activated charcoal is beneficial in patients with hypercholesterolemia. Details: Some preliminary clinical research in patients with hypercholesterolemia shows that taking activated charcoal 4-32 grams daily for 3 weeks decreases total cholesterol by up to 29% and low-density lipoprotein (LDL) cholesterol by up to 41% when compared with control. The effects of activated charcoal appear to be dose-dependent. Additional clinical research shows that taking activated charcoal 20 grams twice daily for 3 weeks is as effective as cholestyramine 8 grams twice daily for treating hypercholesterolemia (12398), but the combined use of activated charcoal and cholestyramine does not appear to confer additional benefit when compared with either agent alone (12397). However, other research suggests that activated charcoal is not effective for treating hypercholesterolemia (12399). Reasons for the discrepancies are unclear but may relate to the small size of the latter study, and the inclusion of some patients without hyperlipidemia.
• Hyperphosphatemia. Oral activated charcoal might reduce the incidence of hyperphosphatemia in patients with kidney disease. Details: Preliminary clinical research in a small number of patients with stage 3 or 4 chronic kidney disease (CKD) shows that taking activated charcoal 0.6-1.2 grams three times daily for 12 months reduces the risk of hyperphosphatemia by 64% when compared with placebo. Additionally, in CKD patients who develop hyperphosphatemia, use of activated charcoal at the same dose for up to 24 months seems to delay the development of vascular calcification when compared with calcium carbonate, but not when compared with lanthanum carbonate (103193). Other preliminary clinical research in patients on hemodialysis shows that taking activated charcoal for 24 weeks, at a starting dose of 600 mg three times daily, increasing by 300 mg three times daily every 4 weeks until the goal phosphate level is reached, reduces phosphate levels to the goal in over 90% of patients when compared with baseline (93611). The lack of a control group limits the validity of these findings.
• Tooth whitening. It is unclear if toothpaste containing activated charcoal is beneficial for tooth whitening. Details: A small clinical study in adults with dental stains due to factors such as coffee or tobacco use shows that using a toothpaste containing activated charcoal (Blanx Black, Coswell SpA) twice daily for 3 months reduces visible staining, dental plaque, and bleeding when compared to baseline, but not when compared with a micro-cleaning crystal toothpaste (Sensation White, Colgate) (111718).
• Wound healing. Research on the use of activated charcoal-containing dressings for wound healing is limited and conflicting. Details: One preliminary clinical study shows that treating chronic venous leg ulcers with activated charcoal-containing dressings (Actisorb, Systagenix) for 6 weeks reduces ulcer size by 17% when compared with control occlusive or semi-occlusive dressings containing antibacterial or antiseptic agents (94731). However, other preliminary clinical research shows that treating pressure ulcers or venous leg ulcers with activated charcoal-containing dressings (Actisorb and Actisorb Silver 220, Systagenix) for 4 weeks does not significantly improve wound healing when compared with a hydrocolloid dressing (93603). More evidence is needed to rate activated charcoal for these uses.

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POSSIBLY EFFECTIVE

• Dysmenorrhea. Taking fennel oil or extract by mouth may reduce pain in patients with primary dysmenorrhea. This benefit may be similar to ibuprofen or mefenamic acid. Details: Two separate meta-analyses in patients with primary dysmenorrhea show that taking fennel oil or fennel extract for 1-6 menstrual cycles reduces dysmenorrhea pain when compared with placebo. Improvement in pain was similar when compared with ibuprofen or mefenamic acid. In the included studies, doses of fennel oil ranged from 3-30 drops every 4-8 hours, and doses of fennel extract ranged from 30-230 mg daily (104196,108972). However, most studies included in these meta-analyses were small and low-quality, and all studies were conducted in Iran. Higher quality studies in other geographic locations are needed to confirm these findings.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Anxiety. Although there has been interest in using oral fennel for anxiety, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Bronchitis. Although there has been interest in using oral fennel for bronchitis, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Cancer. Although there has been interest in using oral fennel for cancer prevention, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Cholera. Although there has been interest in using oral fennel for cholera, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Colic. Small clinical studies suggest that oral fennel may reduce crying time in infants with colic. However, most research to date has evaluated fennel in combination with other ingredients. Details: A meta-analysis of three small clinical studies shows that giving fennel to infants with colic can reduce crying time by about 72 minutes daily when compared with placebo (97497). However, the studies included in this meta-analysis were at medium to high risk of bias, and the placebo response rate was high in all of the included studies. Additionally, two of the three studies evaluated combination products (16735,19715,49428). In the one study that used fennel alone, administering 5-20 mL of fennel seed oil 0.1% emulsion daily for one week led to colic relief in 65% of infants, compared with 24% of infants receiving placebo (49428). The other studies evaluated fennel in combination with lemon balm and German chamomile (ColiMil) or in combination with chamomile, vervain, licorice, and lemon balm (Calma-Bebi, Bonomelli). These combination products produced a response in 57% to 85% of infants, compared with 26% to 49% of infants receiving placebo (16735,19715).
• Constipation. Oral fennel has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small crossover trial in patients with constipation shows that drinking an herbal tea containing 3 grams of a combination of fennel, anise, elderberry, and senna daily for 5 days can decrease colonic transit time, increase the number of daily evacuations, and improve the perception of bowel function when compared with placebo (49494). Another small clinical study in elderly patients with constipation shows that drinking a specific tea (Smooth Move, Traditional Medicinals) containing fennel, senna, licorice, orange peel, cassia cinnamon, coriander, and ginger for 28 days can increase the number of bowel movements when compared to baseline (46196). The validity of this finding is limited by the lack of a comparator group. Additionally, a small clinical study in patients aged 60-65 years with functional constipation shows that taking a traditional Iranian combination product containing 5 grams each of fennel seed and rose flower, dissolved in water twice daily before meals for 4 weeks, improves constipation severity and stool consistency when compared with polyethylene glycol 10 grams. Improvements in constipation severity persisted in both groups 4 weeks after treatment completion (108973). However, polyethylene glycol is usually taken at a higher dose of 17 grams daily, limiting the validity of these findings.
• Cough. Although there has been interest in using oral fennel for cough, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Dementia. Although there has been interest in using oral fennel for dementia, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Diabetes. Although there has been interest in using oral fennel for diabetes, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Dyspepsia. Although there has been interest in using oral fennel for dyspepsia, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Flatulence. Although there has been interest in using oral fennel for flatulence, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Hirsutism. It is unclear if topical fennel is beneficial in patients with hirsutism. Details: A small clinical study in females with male pattern body hair due to unknown causes shows that applying a fennel 2% cream twice daily for 12 weeks can reduce hair diameter by approximately 19% when compared with placebo (49429).
• Insomnia. Although there has been interest in using oral fennel for insomnia, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Irritable bowel syndrome (IBS). Oral fennel has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in adults with either diarrhea- or constipation-predominant IBS shows that taking two capsules containing fennel essential oil 25 mg and curcumin 42 mg per capsule (CU-FEO, Alfa Wassermann S.p.A.) twice daily for 30 days improves overall ratings of abdominal pain, abdominal distention, and quality of life by 24% when compared with placebo (97422).
• Lactation. Although there has been interest in using oral fennel to stimulate breastmilk production, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Menopausal symptoms. Small clinical studies suggest that oral fennel oil or fennel seed powder may modestly improve menopausal symptoms. Details: One small clinical trial in adults with medium severity menopausal symptoms shows that taking fennel essential oil 60 mg daily for 8 weeks improves scores on the Menopause Rating Scale when compared with a sunflower oil placebo (97498). Another small clinical study in postmenopausal adults shows that taking fennel seed powder 2 grams daily for 8 weeks improves scores on the Kupperman Menopausal Index when compared with placebo (104198). Fennel has also been evaluated in combination with other ingredients. One small clinical study shows that taking a combination of fennel 120 mg, chamomile 1000 mg, and saffron 60 mg daily for 12 weeks reduces physical, psychological, and urogenital symptom scores on the Menopause Rating Scale when compared with placebo or lower doses of the combination (103628). Additionally, a moderate-sized clinical study in postmenopausal women conducted in Iran shows that taking combined fennel and valerian extract 500 mg twice daily for 8 weeks modestly improves self-reported scores for frequency and severity of hot flashes but does not improve sleep quality or duration of hot flashes when compared with placebo (112369). However, it is unclear if these benefits are due to fennel, other ingredients, or the combination.
• Nausea and vomiting. Although there has been interest in using oral fennel for nausea and vomiting, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Nocturnal enuresis. Although there has been interest in using oral fennel for nocturnal enuresis, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Osteoarthritis. It is unclear if oral fennel extract is beneficial in patients with knee osteoarthritis. Details: A small clinical trial in females with osteoarthritis of the knee shows that taking powdered fennel extract 800 mg daily for 2 weeks reduces pain and disability scores, but not stiffness, when compared with placebo (104199).
• Polycystic ovary syndrome (PCOS). It is unclear if oral fennel is beneficial in patients with PCOS. Details: A small clinical study in patients with PCOS shows that taking two fennel capsules, containing anethole 21-27 mg per capsule, daily along with a hypocaloric standard diet or a hypocaloric high-protein diet for 3 months does not reduce body weight or improve androgenic parameters such as testosterone levels, sex hormone-binding globulin levels, or free androgen index, when compared with these diets plus placebo (104197). Fennel has also been evaluated in combination with other ingredients. A clinical study in patients with oligomenorrhea due to PCOS shows that taking a traditional combination product (Aslagh) containing equivalent amounts of essential oils of fennel, wild carrot seeds, and Vitex agnus-castus fruit for 3 months, either alone or in combination with metformin, improves rates of menstrual bleeding and menstrual cyclicity similarly to metformin alone. All three groups experienced a significant improvement from baseline. Aslagh was taken as two, 500-mg capsules twice daily, except during menses; metformin was titrated over one week to a dose of 500 mg three times daily (108974). Additionally, a moderate-sized clinical study in patients with PCOS shows that taking fennel 60 mg and Elwendia persica 25 mg twice daily for 4 months modestly improves number of ovarian follicles and body mass index when compared with placebo; however, when compared to baseline, the combination also improves hirsutism scores and menstrual cycle duration and interval (112370). It is unclear if these effects are due to fennel, other ingredients, or the combination.
• Rheumatoid arthritis (RA). Although there has been interest in using oral fennel for RA, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Sexual desire. It is unclear if oral fennel is beneficial for improving sexual desire. Details: A small clinical study in postmenopausal adults shows that taking fennel seed powder 2 grams daily for 8 weeks does not improve scores on the Hurlbert Index of Sexual Desire when compared with placebo (104198).
• Sunburn. It is unclear if topical fennel emulsion is beneficial for preventing sunburn. Details: A small clinical study shows that applying a fennel 5% emulsion topically prior to ultraviolet (UV) exposure can reduce sunburn by 65% when compared with a control (49518).
• Upper respiratory tract infection (URTI). Although there has been interest in using oral fennel for upper respiratory tract infections, there is insufficient reliable information about the clinical effects of fennel for this purpose.
• Vaginal atrophy. It is unclear if intravaginal application of fennel cream is beneficial in patients with vaginal atrophy. Details: A small clinical study in postmenopausal adults shows that applying 5 grams of a fennel 5% cream to the vagina once daily for 8 weeks seems to reverse vaginal thinning, improve vaginal pH, and reduce symptoms of vaginal atrophy such as itching, dryness, and pain with intercourse when compared with placebo (92509). Patients in the fennel group also rated their sexual function to be improved when compared with those receiving placebo (97496). More evidence is needed to rate fennel for these uses.

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LIKELY SAFE ...when used orally, short-term (12392,12393,93200,93609,93610,93611,93613). ...when activated charcoal-containing wound dressings are used topically (93603,94731).

POSSIBLY SAFE ...when used orally, long-term. Activated charcoal has been used with apparent safety in doses up to 1.2 grams three times daily for up to 3 years (103193).

PREGNANCY AND LACTATION: POSSIBLY SAFE
when used orally short-term. Activated charcoal 50 grams three times daily for 8 days has been used with apparent safety in pregnancy (126).

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LIKELY SAFE ...when used orally in amounts commonly found in foods. Fennel has Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when fennel essential oil or extract is used orally and appropriately, short-term. Twenty-five drops (about 1.25 mL) of fennel fruit extract standardized to fennel 2% essential oil has been safely used four times daily for 5 days (49422). Also, two 100 mg capsules each containing fennel 30% essential oil standardized to 71-90 mg of anethole has been safely used daily for 8 weeks (97498). Powdered fennel extract has been used with apparent safety at a dose of 800 mg daily for 2 weeks (104199). ...when creams containing fennel 2% to 5% are applied topically (49429,92509).

CHILDREN: POSSIBLY SAFE
when combination products containing fennel are used to treat colic in infants for up to one week. Studied products include up to 20 mL of a fennel seed oil emulsion; a specific product (ColiMil) containing fennel 164 mg, lemon balm 97 mg, and German chamomile 178 mg; and up to 450 mL of a specific tea (Calma-Bebi, Bonomelli) containing fennel, chamomile, vervain, licorice, and lemon balm (16735,19715,49428).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Observational research has found that regular use of fennel during pregnancy is associated with shortened gestation (100513).

LACTATION: POSSIBLY UNSAFE
when used orally. Case reports have linked consumption of an herbal tea containing extracts of fennel, licorice, anise, and goat's rue to neurotoxicity in two breast-feeding infants. The adverse effect was attributed to anethole, a constituent of fennel and anise (16744). However, levels of anethole were not measured in breastmilk, and the herbal tea was not tested for contaminants. Furthermore, other adverse effects related to use of fennel during lactation have not been reported. However, until more is known, avoid using.

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ALCOHOL (Ethanol) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D The binding action of activated charcoal may be reduced by alcohol.  Details Alcohol may lower the adsorptive capacity of activated charcoal (12400).

CONTRACEPTIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Activated charcoal may reduce the clinical effects of oral contraceptives.  Details Activated charcoal, taken in a dose of 5 grams four times daily for 3 days, may bind to, and reduce the absorption of, oral contraceptives, thereby limiting their effectiveness and increasing the risk of contraceptive failure. However, some clinical research shows that the risk for this interaction is minimal when activated charcoal is taken either 3 hours after or at least 12 hours before oral contraceptives (103192).

ORAL DRUGS Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B Activated charcoal reduces systemic exposure to many drugs, including those that undergo enterohepatic recirculation, regardless of the route of administration.  Details Activated charcoal adsorbs various drugs and may reduce their absorption and/or half-life. Examples of affected drugs include acetaminophen, aminophylline, amiodarone, atenolol, carbamazepine, dapsone, digoxin, disopyramide, fluoxetine, indomethacin, moxifloxacin, nadolol, phenytoin, phenobarbital, piroxicam, quinine, sotalol, theophylline, tricyclic antidepressants, valproate, and verapamil (12392,12400,93198,93602,93610,93612,93613,94730,105543). Avoid co-administration, except after drug overdose.

SYRUP OF IPECAC Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = C Syrup of ipecac is inactivated by activated charcoal.  Details Activated charcoal adsorbs and inactivates syrup of ipecac (12394). Avoid co-administration.

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, fennel might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.  Details Animal research suggests that fennel oil has antithrombotic and antiplatelet effects (31415,49445).

CIPROFLOXACIN (Cipro) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, fennel might decrease the levels and clinical effects of ciprofloxacin.  Details Animal research shows that fennel reduces ciprofloxacin bioavailability by nearly 50%, possibly due to the metal cations such as calcium, iron, and magnesium contained in fennel. This study also found that fennel increased tissue distribution and slowed elimination of ciprofloxacin (6135).

CONTRACEPTIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking large amounts of fennel might decrease the effects of contraceptive drugs due to competition for estrogen receptors.  Details Some constituents of fennel have estrogenic activity (11).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, fennel might increase levels of drugs metabolized by CYP3A4.  Details In vitro research suggests that fennel inhibits CYP3A4 enzyme activity (38375,49468). This effect has not been reported in humans.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking large amounts of fennel might interfere with hormone replacement therapy due to competition for estrogen receptors.  Details Some constituents of fennel have estrogenic activity (11).

TAMOXIFEN (Nolvadex) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking large amounts of fennel might decrease the antiestrogenic effect of tamoxifen.  Details Some constituents of fennel have estrogenic activity (11), which may interfere with the antiestrogenic activity of tamoxifen.

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General ...Orally, activated charcoal is generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, black stools, bloating, constipation, and flatulence.
Serious Adverse Effects (Rare):
Orally: Gastrointestinal obstruction and pulmonary aspiration.

Gastrointestinal ...The most common adverse reactions reported with activated charcoal are gastrointestinal in nature. Constipation appears to be the most frequent complaint, but is typically transient. Black stools, abdominal pain, bloating, and flatulence have also been reported (12392,12398,93611,103193). Rarely, activated charcoal may lead to gastrointestinal obstruction (12392).

Pulmonary/Respiratory ...Rarely, pulmonary aspiration has been reported in patients taking activated charcoal orally. This may happen if activated charcoal is regurgitated or if a misplaced nasogastric tube delivers activated charcoal to the lungs rather than the stomach (12392).

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General ...Orally and topically, fennel seems to be well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal discomfort, photosensitivity, and allergic reactions in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Seizures.

Dermatologic ...Advise patients to avoid excessive sunlight or ultraviolet light exposure while using fennel (19). Allergic reactions affecting the skin such as atopic dermatitis and photosensitivity may occur in patients who consume fennel (6178,49507).

Gastrointestinal ...Orally, fennel may cause gastrointestinal complaints, including nausea and vomiting (19146,104196).

Hematologic ...Methemoglobinemia has been reported in four infants following intoxication related to ingestion of a homemade fennel puree that may have been made from improperly stored fennel (49444).

Immunologic ...A case report describes an 11-year-old male who developed an allergy to fennel-containing toothpaste. Immediately after using the toothpaste, the patient experienced sneezing, coughing, itchy mouth, rhinorrhea, nasal congestion, wheezing, difficulty breathing, and palpitations, which resolved within 10 minutes of spitting out the toothpaste and rinsing the mouth. In challenge tests, the patient reacted to chewing fresh fennel root, but not ground fennel seeds (103822).

Neurologic/CNS ...Orally, fennel oil has been associated with tonic clonic and generalized seizures (12868). New-onset cluster headaches are reported in a 24-year-old female while using a toothpaste containing fennel and camphor for 3 months. The headaches resolved upon stopping the toothpaste (112368). It is unclear if this adverse effect can be attributed to fennel, camphor, or the combination.

Pulmonary/Respiratory ...Orally, fennel and fennel seed have been reported to cause bronchial asthma (49478).

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