Arsenicum album 30.0 D • Belladonna 30.0 D • Capsicum annuum leaf 30.0 D • Ferrum Phosphoricum 30.0 D • Pyrogenium 30.0 D. Other Ingredients: Grape Fragrance, Potassium Benzoate, Potassium Sorbate, Purified Water, Raspberry Arome, Sorbitol.
Brand name products often contain multiple ingredients. To read detailed information about each ingredient, click on the link for the individual ingredient shown above.
In 2004, Canada began regulating natural medicines as a category of products separate from foods or drugs. These products are officially recognized as "Natural Health Products." These products include vitamins, minerals, herbal preparations, homeopathic products, probiotics, fatty acids, amino acids, and other naturally derived supplements.
In order to be marketed in Canada, natural health products must be licensed. In order to be licensed in Canada, manufacturers must submit applications to Health Canada including information about uses, formulation, dosing, safety, and efficacy.
Products can be licensed based on several criteria. Some products are licensed based on historical or traditional uses. For example, if an herbal product has a history of traditional use, then that product may be acceptable for licensure. In this case, no reliable scientific evidence is required for approval.
For products with non-traditional uses, some level of scientific evidence may be required to support claimed uses. However, a high level of evidence is not necessarily required. Acceptable sources of evidence include at least one well-designed, randomized, controlled trial; well-designed, non-randomized trials; cohort and case control studies; or expert opinion reports.
Finished products licensed by Health Canada must be manufactured according to Good Manufacturing Practices (GMPs) as outlined by Health Canada.
This is a homeopathic preparation. Homeopathy is a system of medicine established in the 19th century by a German physician named Samuel Hahnemann. Its basic principles are that "like treats like" and "potentiation through dilution." For example, in homeopathy, diarrhea would be treated with an extreme dilution of a substance that normally causes diarrhea when taken in high doses.
Practitioners of homeopathy believe that more dilute preparations are more potent. Many homeopathic preparations are so diluted that they contain little or no active ingredient. Therefore, most homeopathic products are not expected to have any pharmacological effects, drug interactions, or other harmful effects. Any beneficial effects are controversial and cannot be explained by current scientific methods.
Dilutions of 1 to 10 are designated by an "X." So a 1X dilution = 1:10, 3X=1:1000; 6X=1:1,000,000. Dilutions of 1 to 100 are designated by a "C." So a 1C dilution = 1:100; 3C = 1:1,000,000. Dilutions of 24X or 12C or more contain zero molecules of the original active ingredient.
Homeopathic products are permitted for sale in the US due to legislation passed in 1938 sponsored by a homeopathic physician who was also a Senator. The law still requires that the FDA allow the sale of products listed in the Homeopathic Pharmacopeia of the United States. However, homeopathic preparations are not held to the same safety and effectiveness standards as conventional medicines. For more information, see the Homeopathy monograph.
Below is general information about the effectiveness of the known ingredients contained in the product Otite. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product Otite. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
LIKELY SAFE ...when organic arsenic is consumed in normal food amounts. Organic forms of arsenic normally found in foods have not been linked to toxicity (7135,16309). ...when arsenic trioxide is used intravenously and appropriately under the guidance of a healthcare provider. Arsenic trioxide (Trisenox) is an FDA-approved prescription drug (15).
LIKELY UNSAFE ...when inorganic arsenic is used orally, especially when used long-term or in high doses. Taking large doses acutely, or in small doses for prolonged periods of time, can cause serious side effects. Chronic intake of 10 mcg/kg daily has been associated with symptomatic arsenicism. Acute doses of 5 mg, or sometimes less, can cause gastrointestinal symptoms. Higher doses can cause severe poisoning and death (7135,16310,16312,16313,16316,102892). Prolonged exposure to inorganic arsenic in drinking water and other sources has been linked to an increased risk of cardiovascular disease, diabetes, cancer, hypertension, and mortality (99824,99827,99829,99830,99832,99834,99835,109108,109110). Inorganic arsenic is classified as a human carcinogen (16312,16316). The maximum permissible level of arsenic in drinking water is 10 mcg/L (16316).
CHILDREN: LIKELY SAFE
when organic arsenic is consumed in food amounts.
Organic forms of arsenic found in a normal diet have not been linked to toxicity (7135,16309).
CHILDREN: LIKELY UNSAFE
when inorganic arsenic is used orally, especially when used long-term or in high doses.
Large doses acutely, or in small doses for prolonged periods of time, can cause serious side effects. Prolonged exposure to inorganic arsenic in drinking water has been linked to reduced scores on intelligence tests, developmental delays, impaired verbal comprehension, decreased memory and attention, and higher blood pressure in children (16319,99826,99828,99836,102898).
PREGNANCY AND LACTATION: LIKELY SAFE
when organic arsenic is consumed in food amounts.
Organic forms of arsenic found in a normal diet have not been linked to toxicity (7135,16309).
PREGNANCY AND LACTATION: LIKELY UNSAFE
when inorganic arsenic is taken orally, especially when used long-term or in high doses.
While exposure to inorganic arsenic in drinking water does not seem to increase the risk of neural tube defects (102897), it has been associated with an increased risk for spontaneous abortion, stillbirth, and neonatal mortality (99833). Exposure to inorganic arsenic in drinking water and other sources while pregnant has also been linked to changes in birth weight, length, and head circumference (102895), with one study showing that higher maternal blood arsenic levels are associated with 44% greater odds of delivering a small for gestational age infant and 103% greater odds of delivering a large for gestational age infant (102895,102896). Avoid arsenic supplements and water contaminated with arsenic during pregnancy or lactation.
POSSIBLY UNSAFE ...when used rectally. It is not known whether significant amounts of the toxic alkaloids are absorbed from the rectum (106909). ...when used topically. It is not known whether significant amounts of the toxic alkaloids are absorbed through the skin (106909).
LIKELY UNSAFE ...when used orally. Belladonna contains toxic alkaloids and has been linked to reports of serious adverse effects (12,553,34144).
CHILDREN: LIKELY UNSAFE
when used orally.
Fatalities in children may occur at doses of belladonna providing atropine 0.2 mg/kg (34168). Two belladonna berries, which contain 2 mg atropine per fruit, may be lethal for a small child (34144). Severe adverse effects and fatalities have been reported in infants treated with topical homeopathic teething products containing belladonna (17493,34142,34146,93537).
PREGNANCY: LIKELY UNSAFE
when used orally.
Belladonna contains toxic alkaloids and has been linked to reports of serious adverse effects (12,553,34144).
LACTATION: LIKELY UNSAFE
when used orally.
Belladonna can reduce milk production and is secreted into breast milk (15).
LIKELY SAFE ...when used orally in amounts typically found in food. Capsicum has Generally Recognized as Safe (GRAS) status in the US (4912). ...when used topically and appropriately (7038,10650,105345). The active capsicum constituent capsaicin is an FDA-approved ingredient used in certain over-the-counter, topical preparations (272).
POSSIBLY SAFE ...when used orally and appropriately, short-term in medicinal amounts. A specific sustained-release chili extract (Capsifen) has been used safely in doses of up to 200 mg daily, for up to 28 days (105196). ...when used intranasally and appropriately, short-term. Capsicum-containing nasal sprays, suspensions, and swabs seem to be safe when applied multiple times over 24 hours or when applied daily or every other day for up to 14 days. Although no serious side effects have been reported in clinical trials, intranasal application of capsicum-containing products can be very painful (14322,14324,14328,14329,14351,14352,14353,14356,14357) (14358,14359,14360,15016,105204). POSSIBLY UNSAFE when used orally, long-term or in high doses. There is concern that long-term use or use of excessive doses might be linked to hepatic or kidney damage, as well as hypertensive crisis (12404,40569,40606). There is insufficient reliable information available about the safety of capsicum when injected.
CHILDREN: POSSIBLY UNSAFE
when used topically in children under 2 years old (272).
There is insufficient reliable information available about the safety of capsicum when used orally in children.
PREGNANCY: LIKELY SAFE
when used topically and appropriately (272).
PREGNANCY: POSSIBLY SAFE
when used orally and appropriately, short-term.
Capsicum 5 mg daily has been used for up to 28 days during the latter half of the second trimester and the third trimester (96457).
LACTATION: LIKELY SAFE
when used topically and appropriately (272).
LACTATION: POSSIBLY UNSAFE
when used orally.
Dermatitis can sometimes occur in infants when foods heavily spiced with capsicum peppers are ingested during lactation (739). Also, observational research suggests that intake of raw capsicum peppers during pregnancy is associated with an increased risk of sensitization to inhalant allergens in children by the age of 2 years (41021).
LIKELY SAFE ...when used orally and appropriately. For people age 14 and older with adequate iron stores, iron supplements are safe when used in doses below the tolerable upper intake level (UL) of 45 mg per day of elemental iron. The UL is not meant to apply to those who receive iron under medical supervision (7135,96621). To treat iron deficiency, most people can safely take up to 300 mg elemental iron per day (15). ...when used intravenously and appropriately. Ferric carboxymaltose 200 mg and iron sucrose 200 mg have been given intravenously for up to 10 doses with no reported serious adverse effects (91179). A meta-analysis of clinical studies of hemodialysis patients shows that administering high-dose intravenous (IV) iron does not increase the risk of hospitalization, infection, cardiovascular events, or death when compared with low-dose IV iron, oral iron, or no iron treatment (102861). A more recent meta-analysis of clinical studies of all patient populations shows that administering IV iron does not increase the risk of hospital length of stay or mortality, although the risk of infection is increased by 16% when compared with oral iron or no iron (110186). Despite these findings, there are rare reports of hypophosphatemia and/or osteomalacia (112603,112608,112609,112610).
LIKELY UNSAFE ...when used orally in excessive doses. Doses of 30 mg/kg are associated with acute toxicity. Long-term use of high doses of iron can cause hemosiderosis and multiple organ damage. The estimated lethal dose of iron is 180-300 mg/kg; however, doses as low as 60 mg/kg have also been lethal (15).
CHILDREN: LIKELY SAFE
when used orally and appropriately (7135,91183,112601).
CHILDREN: LIKELY UNSAFE
when used orally in excessive amounts.
Tell patients who are not iron-deficient not to use doses above the tolerable upper intake level (UL) of 40 mg per day of elemental iron for infants and children. Higher doses frequently cause gastrointestinal side effects such as constipation and nausea (7135,20097). Iron is the most common cause of pediatric poisoning deaths. Doses as low as 60 mg/kg can be fatal (15).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately.
Iron is safe during pregnancy and breast-feeding in patients with adequate iron stores when used in doses below the tolerable upper intake level (UL) of 45 mg daily of elemental iron (7135,96625,110180).
PREGNANCY AND LACTATION: LIKELY UNSAFE
when used orally in high doses.
Tell patients who are not iron deficient to avoid exceeding the tolerable upper intake level (UL) of 45 mg daily of elemental iron. Higher doses frequently cause gastrointestinal side effects such as nausea and vomiting (7135) and might increase the risk of preterm labor (100969). High hemoglobin concentrations at the time of delivery are associated with adverse pregnancy outcomes (7135,20109).
Below is general information about the interactions of the known ingredients contained in the product Otite. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Arsenic trioxide can prolong the QT interval.
 Details
Up to 40% of patients treated with prescription arsenic trioxide have a prolonged QT interval on their electrocardiogram (ECG) (15). Theoretically, non-prescription arsenic could have an additive effect when combined with drugs that prolong the QT interval.
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Belladonna may increase the risk of adverse effects when used concomitantly with anticholinergic drugs.
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Theoretically, belladonna might reduce the effects of cisapride.
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Belladonna contains atropine. In vivo evidence suggests that atropine can prevent cisapride from increasing motility in the gastrointestinal tract (25191).
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Theoretically, using topical capsaicin may increase the risk of ACE inhibitor-induced cough.
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There is one case report of a topically applied capsaicin cream contributing to the cough reflex in a patient using an ACEI (12414). However, it is unclear if this interaction is clinically significant.
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Theoretically, capsicum may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
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In vitro research shows that capsicum might increase the effects of antiplatelet drugs (12406,12407). Also, population research shows that capsicum is associated with an increased risk of self-reported bleeding in patients taking warfarin (12405,20348). However, clinical research shows that taking a single dose of capsaicin (Asian Herbex Ltd.), the active ingredient in capsicum, 400-800 mcg orally in combination with aspirin 500 mg does not decrease platelet aggregation when compared with taking aspirin 500 mg alone. Also, there was no notable effect on measures of platelet aggregation with capsaicin (92990). It is unclear whether capsaicin must be used in more than a single dose to affect platelet aggregation.
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Theoretically, taking capsicum with antidiabetes drugs might increase the risk of hypoglycemia.
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Preliminary clinical research shows that consuming capsicum 5 grams along with a glucose drink attenuates the rise in plasma glucose after 30 minutes by 21%, decreases the 2-hour postprandial area under the curve of plasma glucose by 11%, and increases the 2-hour postprandial area under the curve of plasma insulin by 58% in healthy individuals when compared with placebo (40453,40614). Other clinical research shows that taking capsicum 5 mg daily for 28 days significantly reduces postprandial blood glucose and insulin levels, but not fasting blood glucose and insulin levels, in patients with gestational diabetes (96457).
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Theoretically, taking capsicum with aspirin might reduce the bioavailability of aspirin.
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Animal research shows that acute or chronic intake of capsicum pepper reduces oral aspirin bioavailability (22617). This has not been shown in humans.
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Theoretically, taking capsicum with ciprofloxacin might increase levels and adverse effects of ciprofloxacin.
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Animal research shows that concomitant use of capsaicin, the active constituent of capsicum, and ciprofloxacin increases the bioavailability of ciprofloxacin by up to 70% (22613).
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Theoretically, taking capsicum with theophylline might increase the levels and adverse effects of theophylline.
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Iron reduces the absorption of bisphosphonates.
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Advise patients that doses of bisphosphonates should be separated by at least two hours from doses of all other medications, including supplements such as iron. Divalent cations, including iron, can decrease absorption of bisphosphonates by forming insoluble complexes in the gastrointestinal tract (15).
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Theoretically, taking chloramphenicol with iron might reduce the response to iron therapy in iron deficiency anemia.
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Iron might decrease dolutegravir levels by reducing its absorption.
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Advise patients to take dolutegravir at least 2 hours before or 6 hours after taking iron. Pharmacokinetic research shows that iron can decrease the absorption of dolutegravir from the gastrointestinal tract through chelation (93578). When taken under fasting conditions, a single dose of ferrous fumarate 324 mg orally along with dolutegravir 50 mg reduces overall exposure to dolutegravir by 54% (94190).
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Theoretically, taking iron along with integrase inhibitors might decrease the levels and clinical effects of these drugs.
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Iron is a divalent cation. There is concern that iron may decrease the absorption of integrase inhibitors from the gastrointestinal tract through chelation (93578). One pharmacokinetic study shows that iron can decrease blood levels of the specific integrase inhibitor dolutegravir through chelation (94190). Also, other pharmacokinetic research shows that other divalent cations such as calcium can decrease the absorption and levels of some integrase inhibitors through chelation (93578,93579).
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Iron might decrease levodopa levels by reducing its absorption.
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Advise patients to separate doses of levodopa and iron as much as possible. There is some evidence in healthy people that iron forms chelates with levodopa, reducing the amount of levodopa absorbed by around 50% (9567). The clinical significance of this hasn't been determined.
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Iron might decrease levothyroxine levels by reducing its absorption.
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Advise patients to separate levothyroxine and iron doses by at least 2 hours. Iron can decrease the absorption and efficacy of levothyroxine by forming insoluble complexes in the gastrointestinal tract (9568).
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Iron might decrease methyldopa levels by reducing its absorption.
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Theoretically, iron might decrease mycophenolate mofetil levels by reducing its absorption.
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Advise patients to take iron 4-6 hours before, or 2 hours after, mycophenolate mofetil. It has been suggested that a decrease of absorption is possible, probably by forming nonabsorbable chelates. However, mycophenolate pharmacokinetics are not affected by iron supplementation in available clinical research (3046,20152,20153,20154,20155).
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Iron might decrease penicillamine levels by reducing its absorption.
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Advise patients to separate penicillamine and iron doses by at least 2 hours. Oral iron supplements can reduce absorption of penicillamine by 30% to 70%, probably due to chelate formation. In people with Wilson's disease, this interaction has led to reduced efficacy of penicillamine (3046,3072,20156).
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Iron might decrease levels of quinolone antibiotics by reducing their absorption.
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Iron might decrease levels of tetracycline antibiotics by reducing their absorption.
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Advise patients to take iron at least 2 hours before or 4 hours after tetracycline antibiotics. Concomitant use can decrease absorption of tetracycline antibiotics from the gastrointestinal tract by 50% to 90% (15).
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Below is general information about the adverse effects of the known ingredients contained in the product Otite. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
General
...Orally, organic forms of arsenic found in the diet are well tolerated, with no clear links to adverse effects.
However, high doses or chronic intake of inorganic arsenic is associated with potentially serious adverse effects.
Serious Adverse Effects (Rare):
Orally: With the acute ingestion of inorganic arsenic, anemia, arrhythmias, bruising, gastrointestinal irritation or damage, hepatotoxicity, and peripheral neuropathy.
With chronic intake of inorganic arsenic, arsenicism can occur, including anorexia, cancer, skin hyperpigmentation and hyperkeratosis, and toxicity of the cardiovascular and neurological systems.
Cardiovascular
...Orally, doses of inorganic arsenic 1 mg/kg daily can cause hematopoietic depression including anemia, arrhythmias, and blood vessel damage leading to bruising (7135,16309,16312).
Acute ingestion of inorganic arsenic 10 mg/kg daily or more causes vasodilation and myocardial depression leading to myocardial injury, shock, and circulatory failure (17,7135,16313,16316,102892). Chronic intake of 10 mcg/kg daily of inorganic arsenic produces arsenicism, characterized in part by cardiomyopathy and arrhythmias (17,7135,16309,16310,16316). Prolonged exposure to inorganic arsenic in drinking water at levels greater than or equal to 20 mcg/L has been linked, in a dose-dependent manner, to a 9% to 43% greater risk of cardiovascular disease, 11% to 55% greater risk of coronary heart disease, and 16% to 90% greater risk of cardiovascular-related death (99827). Also, each interquartile increase in urinary inorganic arsenic levels is associated with an increased risk of both cardiovascular and all-cause mortality in a specific area of the US (109110). A metabolite of arsenic, monomethylarsonic acid, has also been positively linked to stroke risk (99831). Increased exposure to inorganic arsenic has also been linked to the development of left ventricular hypertrophy (99835). The cardiovascular adverse effects of inorganic arsenic appear to be more profound in males with hypertension (99829).
The association between arsenic exposure and hypertension has also been investigated. A meta-analysis of observational research has found that the odds of having hypertension and risk of hypertension were increased by 14% and 30%, respectively, in those with the highest arsenic exposure when compared with the lowest. Exposure was determined based on intake of rice and rice products, as well as exposure in water, or levels in urine, hair, or toenails (109108). Additionally, increased exposure to inorganic arsenic in drinking water has been linked to higher blood pressure in children (102898).
Dermatologic ...Orally, chronic intake of 10 mcg/kg daily of inorganic arsenic produces arsenicism, characterized in part by skin hyperpigmentation, hyperkeratosis, alopecia, and occlusive peripheral vascular disease leading to gangrene (17,7135,16309,16310,16316,102894). In one case, chronic intake of inorganic arsenic 30 ng daily has reportedly caused eczema of the hands, arms, and legs (102893).
Endocrine ...Orally, prolonged exposure to inorganic arsenic in drinking water has been associated with a 23% to 75% increase in the risk for diabetes (99830,99834). For every 100 mcg/L increase in inorganic arsenic levels in drinking water, the associated risk for diabetes increases by 13% (99834). A small meta-analysis has found that overall exposure to arsenic, including organic and inorganic arsenic, is associated with an increased risk of developing gestational diabetes (106539).
Gastrointestinal ...Orally, acute ingestion of inorganic arsenic 5 mg, or sometimes less, can cause vomiting, diarrhea, stomach cramps, and flatulence (16316,102893). These effects usually resolve in about 12 hours without treatment (16316). Doses of inorganic arsenic 1 mg/kg daily can cause gastrointestinal irritation (7135,16309,16312). Acute ingestion of inorganic arsenic 10 mg/kg daily or more causes severe gastrointestinal symptoms including bloody rice-water diarrhea (17,7135,16313,16316,102892). Chronic intake of 10 mcg/kg daily of inorganic arsenic produces arsenicism, characterized in part by anorexia and gastrointestinal disturbances (17,7135,16309,16310,16316).
Genitourinary ...Orally, chronic intake of inorganic arsenic 30 ng daily has reportedly caused irregular menstruation (102893). A long-term observational study in adults has found that exposure to inorganic arsenic from consumption of contaminated milk powder during infancy is associated with increased mortality from genitourinary diseases (106541).
Hematologic ...Orally, chronic intake of 10 mcg/kg daily of inorganic arsenic produces arsenicism, characterized in part by anemia, leukopenia, and occlusive peripheral vascular disease (17,7135,16309,16310,16316).
Hepatic
...Orally, doses of inorganic arsenic 1 mg/kg daily can cause hepatotoxicity (7135,16309,16312).
The homeopathic remedy, arsenicum album, has been associated with three cases of acute liver injury. In one case, a 70-year-old male with pre-existing non-alcoholic steatohepatitis (NASH) cirrhosis died following the acute liver injury associated with use of this compound for about 12 weeks. High levels of arsenic were found in his hair and nail samples. Symptoms in the two other individuals resolved upon discontinuation of homeopathic arsenic and use of corticosteroids (109114).
Musculoskeletal ...Orally, chronic intake of inorganic arsenic 30 ng daily has reportedly caused leg cramps in one patient (102893).
Neurologic/CNS
...Orally, doses of inorganic arsenic 1 mg/kg daily can cause peripheral neuropathy and encephalopathy (7135,16309,16312).
In one case, chronic intake of inorganic arsenic 30 ng daily has reportedly caused headache, dizziness, and difficulty concentrating (102893). Acute ingestion of inorganic arsenic 10 mg/kg daily or more can cause cerebral edema, leading to encephalopathy, convulsions, coma, and death (17,7135,16313,16316). Chronic intake of 10 mcg/kg daily of inorganic arsenic produces arsenicism, characterized in part by sensory disturbances, peripheral neuropathy, encephalopathy, confusion, and memory loss (17,7135,16309,16310,16316). A long-term observational study in adults has found that exposure to inorganic arsenic from consumption of contaminated milk powder during infancy is associated with increased mortality from nervous system diseases (106541).
In children, prolonged exposure to inorganic arsenic in drinking water has been linked to reduced scores on intelligence tests, developmental delays, impaired verbal comprehension, and decreased memory and attention (16319,99826,99828,99836).
Ocular/Otic ...Orally, chronic intake of inorganic arsenic 30 ng daily has reportedly caused conjunctivitis in one patient (102893). A long-term observational study in adults has found that exposure to inorganic arsenic from consumption of contaminated milk powder during infancy is associated with increased mortality from traffic accidents. This is suggested to be related to a higher prevalence of visual field narrowing due to macular degeneration, as well as motor or sensory dysfunction, in those exposed to arsenic during infancy (106541).
Oncologic ...Inorganic arsenic is classified as a human carcinogen (16312,16316). Orally, chronic intake of 10 mcg/kg daily of inorganic arsenic produces arsenicism, which can result in cancers of the skin, lungs, liver, kidneys, and bladder (17,7135,16309,16310,16316). Chronic ingestion of lower doses of inorganic arsenic, as a contaminant in well water, has also been linked to cancers of the skin, bladder, kidneys, and lungs (7135,99824,99832,106540). More specifically, levels of inorganic arsenic greater than 200 mcg/L in drinking water have been linked to lung cancer (99824). Levels of inorganic arsenic greater than 10 mcg/L in drinking water are also dose-dependently linked to an increased risk for bladder and kidney cancers (99832). A meta-analysis of observational research has found that arsenic exposure, especially from water and soil, is associated with prostate cancer risk (109109). A long-term observational study in adults has found that exposure to inorganic arsenic from consumption of contaminated milk powder during infancy is associated with increased mortality from liver cancer (106541).
Psychiatric ...Orally, chronic intake of inorganic arsenic 30 ng daily has reportedly caused insomnia and anxiety in one patient (102893).
Pulmonary/Respiratory ...A long-term observational study in adults has found that exposure to inorganic arsenic from consumption of contaminated milk powder during infancy is associated with increased mortality from respiratory diseases (106541).
Other
...Orally, high doses of inorganic arsenic can cause death.
In one case, a 24-year-old female receiving a combination of arsenic trioxide, realgar, and mung bean flour from an illegal medical provider died within days of taking the compounded preparation. Laboratory analysis revealed the amount of arsenic consumed to be around 1.1 grams on day 1 and 0.9 grams on day 4. Researchers concluded that arsenic as the source of poisoning was clear based on the amount of arsenic ingested and the patient's clinical presentation prior to death, which included vomiting, diarrhea, reduced urine output, liver and kidney abnormalities, and myocardial injury (102892).
A long-term observational study in adults has found that exposure to inorganic arsenic from consumption of contaminated milk powder during infancy is associated with increased all-cause mortality (106541).
General
...Orally, belladonna can cause anticholinergic side effects even at low doses, and is considered poisonous.
Most Common Adverse Effects:
Orally: Anticholinergic side effects, including blurred vision, constipation, delirium, dilated pupils, dizziness, dry mouth, fever, headache, hypertension, muscle rigidity and tremor, psychosis, respiratory failure, and slurred speech.
Cardiovascular ...Orally, belladonna can cause anticholinergic side effects such as hypertension, hypotension, tachycardia, and ventricular premature beats (553,34168,34180).
Dermatologic
...Orally, belladonna can cause anticholinergic side effects such as dry, red skin and decreased perspiration (553,34146,34152).
One case of rash and another case of hives have been reported in patients taking belladonna with phenobarbital and ergotamine orally; it is unclear if the adverse effects were due to belladonna or the other ingredients (34154).
Topically, belladonna plaster (Cuxon Gerrard) can cause contact dermatitis (34152).
Gastrointestinal ...Orally, belladonna can cause anticholinergic side effects such as dry mouth and constipation (553,34162,34163,34176,34180,34181).
Genitourinary ...Orally, belladonna can cause anticholinergic side effects such as urinary retention (553,34145,34150,34163).
Neurologic/CNS ...Orally, belladonna can cause anticholinergic side effects such as memory and attention impairment, headache, and confusion (553,34163,34180).
Ocular/Otic ...Orally and topically, belladonna can cause anticholinergic side effects such as dilation of pupils and blurred vision (553,34157,34168,34169,34180). A case report describes anisocoria (unequal pupil sizes) in a 70-year-old female who used homeopathic pink eye relief drops (Similasan) containing belladonna, eyebright, and hepar sulphuris (calcium sulfide) in one eye for 3 days. The pupil dilation lasted more than 2 weeks and did not respond to bright light or pilocarpine (106907). Another report describes a case of acute angle closure glaucoma, requiring referral to an ophthalmologist, in a 55-year-old female who used these eye drops for 2 days (106906).
General
...Orally, capsicum is generally well tolerated in amounts typically found in food or when the extract is used in doses of up to 200 mg daily.
Topically and intranasally, capsaicin, a constituent of capsicum, is generally well tolerated.
Most Common Adverse Effects:
Orally: Belching, bloating, burning, diarrhea, dyspepsia, gas, headache, mild constipation, nausea, rhinorrhea, skin flushing, and sweating.
Serious Adverse Effects (Rare):
Orally: Cases of myocardial infarction and hypertensive crisis have been reported.
Cardiovascular
...Orally, palpitation was reported in one clinical trial (105196).
One case of myocardial infarction has been reported in a 41-year-old male without cardiovascular risk factors; the event was attributed to the use of an oral capsicum pepper pill that the patient had been taking for weight loss (40768). Another case of coronary vasospasm and acute myocardial infarction has been reported for a healthy 29-year-old male; the event was attributed to the use of a topical capsicum-containing patch that the patient had been applying to the middle of the back for 6 days (40658). Two cases of arterial hypertensive crisis have been reported for individuals who ingested a large amount of peppers and chili peppers the day before. One of the patients also had an acute myocardial infarction, and the other had high levels of thyroid stimulating hormone (40569,40606).
Dermatologic
...Orally, capsicum or its constituent capsaicin may cause urticaria and skin wheals in rare cases (96457,105203).
Topically, capsicum can cause a prickling sensation, itching, pain, burning, edema, stinging, irritation, rash, and erythema. About 1 in 10 patients who use capsaicin topically discontinue treatment because of adverse effects. These effects seem to occur more often with topical formulations containing higher concentrations of capsaicin, the active constituent of capsicum. Side effects tend to diminish with continued use (12401,15260,15261,40358,40439,40483,40547,40676,40682,40719)(40784,40847,92979,92983,92984,96453,105193,105197,105202,111514). In one case, application of a capsaicin 8% patch (Qutenza) for 60 minutes caused a second-degree burn, characterized by burning, erythema, severe pain, and blistering at the administration site. The burn was treated with topical corticosteroids, but 9 months later neuropathic pain persisted, resulting in limited mobility. It is unclear whether the mobility sequalae were caused by topical capsaicin or the patient's pre-existing neurological disorders (111514). Skin contact with fresh capsicum fruit can also cause irritation or contact dermatitis (12408).
Intranasally, capsaicin can cause nasal burning and pain in most patients. It also often causes lacrimation, sneezing, and excessive nasal secretion; however, these side effects appear to diminish with repeat applications (14323,14329,14358). In some cases, the burning sensation disappears after 5-8 applications (14351,14358). In some cases, patients are pretreated with intranasal lidocaine to decrease the pain of intranasal capsaicin treatment. However, even with lidocaine pretreatment, patients seem to experience significant pain (14324).
Gastrointestinal
...Orally, capsicum can cause upper abdominal discomfort, including irritation, fullness, dyspepsia, gas, bloating, nausea, epigastric pain and burning, anal burning, diarrhea, mild constipation, and belching (12403,12410,40338,40427,40456,40503,40560,40584,40605,40665)(40718,40725,40745,40808,40828,96456,96457,105194,105196).
There is a case report of a 3-year-old female who experienced a burning and swollen mouth and lips after touching the arm of a parent that had been treated with a capsaicin patch and then placing the fingers in the mouth (105199). Excessive amounts of capsaicin can lead to gastroenteritis and hepatic necrosis (12404). In a case report, a 40-year-old male with diabetes consumed white wine daily and chewed cayenne which was thought to result in black teeth stains and loss of enamel (40809). Some preliminary research links ingestion of capsaicin with stomach and gallbladder cancer; however the link may be due to contamination of capsaicin products with carcinogens (40771).
Topically, capsaicin can cause diarrhea and vomiting (105202).
Immunologic ...In a case report, a 34-year-old female had anaphylaxis involving difficulty breathing and stupor and also urticaria after consuming a red bell pepper, which is in the capsicum genus. The causal chemical was theorized to be 1,3-beta-glucanase (92978). In another case report, a 33-year-old female experienced angioedema, difficulty breathing and swallowing, and urticaria after ingesting raw green and red peppers (92982).
Neurologic/CNS ...Orally, capsicum can cause sweating and flushing of the head and neck, lacrimation, headache, faintness, and rhinorrhea (7005,12410,105196,105203). Topically, applying capsaicin can cause headache (96450,105202). Injection of capsaicin into the intermetatarsal space has also been associated with headache (96454).
Ocular/Otic
...Topically, capsicum can be extremely irritating to the eyes and mucous membranes.
Capsicum oleoresin, an oily extract in pepper self-defense sprays, causes intense eye pain. It can also cause erythema, blepharospasm, tearing, shortness of breath, and blurred vision. In rare cases, corneal abrasions have occurred (12408,12409,40345,40348,40383,40720,40857).
Inhalation of capsicum can cause eye irritation, and allergic alveolitis (5885). In a case report, a 38-year-old female had acute anterior uveitis that developed about 12 hours after using a specific patch (Isola Capsicum N Plus) that contained capsaicin 1.5 mg per patch and methyl salicylate 132 mg per patch for neck pain. The uveitis was controlled with topical steroids and did not recur (92977).
Oncologic ...Population research suggests that moderate to high intake of capsaicin, the active constituent of capsicum, is associated with an increased risk of gastric cancer, while low intake is associated with a decreased risk. It is not clear from the study what amount of capsaicin is considered high versus low intake (92988). Additionally, some research suggests that any link may be due to contamination of capsaicin products with carcinogens (40771).
Pulmonary/Respiratory
...Orally, difficulty breathing was reported in a clinical trial (105196).
Topically, nasopharyngitis related to the use of a cream containing capsaicin has been reported (105202).
Inhalation of capsicum and exposure to capsicum oleoresin spray can cause cough, dyspnea, pain in the nasal passages, sneezing, rhinitis, and nasal congestion (5885,15016,40522,40546,40647). In rare cases, inhalation of the capsicum oleoresin or pepper spray has caused cyanosis, apnea, respiratory arrest and death in people. Death was caused by asphyxiation probably due to acute laryngeal edema and bronchoconstriction from inhalation of the capsicum oleoresin spray (40546,40672,40837,40879).
In a case report, a 47-year-old female who was exposed to capsaicin gas for more than 20 minutes experienced acute cough, shortness of breath, short-term chest pain, wheezing, and difficulty breathing for months afterwards (92980). In rare cases, exposure to capsicum oleoresin spray resulted in apnea, pulmonary injury, cyanosis, and even respiratory arrest (40383,40546).
General
...Orally or intravenously, iron is generally well tolerated when used appropriately.
Most Common Adverse Effects:
Orally: Abdominal pain, constipation, diarrhea, gastrointestinal irritation, nausea, and vomiting.
Serious Adverse Effects (Rare):
Orally: Case reports have raised concerns about oral or gastric ulcerations.
Intravenously: Case reports have raised concerns about hypophosphatemia and osteomalacia.
Cardiovascular
...There is debate regarding the association between coronary heart disease (CHD) or myocardial infarction (MI) and high iron intake or high body iron stores.
Some observational studies have reported that high body iron stores are associated with increased risk of MI and CHD (1492,9542,9544,9545,15175). Some observational studies reported that only high heme iron intake from dietary sources such as red meat are associated with increased risk of MI and CHD (1492,9546,15174,15205,15206,91180). However, the majority of research has found no association between serum iron levels and cardiovascular disease (1097,1099,9543,9547,9548,9549,9550,56469,56683).
There is one case of Kounis syndrome, also referred to as allergic angina or allergic myocardial infarction, in a 39-year-old female patient without previous coronary artery disease given intravenous ferric carboxymaltose. The patient experienced anaphylactic symptoms, including headache, abdominal pain, and breathing difficulties, 3 minutes after starting the infusion. She was further diagnosed with non-ST-elevation myocardial infarction (112607).
Dermatologic ...Cutaneous hemosiderosis, or skin staining, has been reported following intravenous iron infusion in various case reports. Most of these cases are due to extravasation following iron infusion (112605,112611). In one case, extravasation has occurred following iron derisomaltose infusion in a 41-year-old female with chronic kidney disease (112605). Rarely, diffuse cutaneous hermosiderosis has occurred. In one case, a 31-year-old female with excessive sweating developed cutaneous hemosiderosis in the armpits following an intravenous iron polymaltose infusion (112611).
Endocrine ...Population research in females shows that higher ferritin levels are associated with an approximately 1. 5-fold higher odds of developing gestational diabetes. Increased dietary intake of heme-iron, but not non-heme iron, is also associated with an increased risk for gestational diabetes. The effects of iron supplementation could not be determined from the evaluated research (96618). However, in a sub-analysis of a large clinical trial in pregnant adults, daily supplementation with iron 100 mg from 14 weeks gestation until delivery did not affect the frequency or severity of glucose intolerance or gestational weight gain (96619).
Gastrointestinal
...Orally, iron can cause dry mouth, gastrointestinal irritation, heartburn, abdominal pain, constipation, diarrhea, nausea, or vomiting (96621,102864,104680,104684,110179,110185,110188,110189,110192).
These adverse effects are uncommon at doses below the tolerable upper intake level (UL) of 45 mg per day of elemental iron in adults with normal iron stores (7135). Higher doses can be taken safely in adults with iron deficiency, but gastrointestinal side effects may occur (1095,20118,20119,56698,102864). Taking iron supplements with food seems to reduce gastrointestinal side effects (7135). However, food can also significantly reduce iron absorption. Iron should be taken on an empty stomach, unless it cannot be tolerated.
There are several formulations of iron products such as ferrous sulfate, ferrous gluconate, ferrous fumarate, and others. Manufacturers of some formulations, such as polysaccharide-iron complex products (Niferex-150, etc), claim to be better tolerated than other formulations; however, there is no reliable evidence to support this claim. Gastrointestinal tolerability relates mostly to the elemental iron dose rather than the formulation (17500).
Enteric-coated or controlled-release iron formulations might reduce nausea for some patients, however, these products also have lower absorption rates (17500).
Liquid oral preparations can blacken and stain teeth (20118).
Iron can also cause oral ulcerations and ulcerations of the gastric mucosa (56684,91182,96622,110179). In one case report, an 87-year-old female with Alzheimer disease experienced a mucosal ulceration, possibly due to holding a crushed ferrous sulfate 80 mg tablet in the mouth for too long prior to swallowing (91182). The ulceration was resolved after discontinuing iron supplementation. In another case report, a 76-year old male suffered gastric mucosal injury after taking a ferrous sulfate tablet daily for 4 years (56684). In a third case report, a 14-year-old female developed gastritis involving symptoms of upper digestive hemorrhage, nausea, melena, and stomach pain. The hemorrhage was attributed to supplementation with ferrous sulfate 2 hours after meals for the prior 2 weeks (96622). In one case report, a 43-year old female developed atrophic gastritis with non-bleeding ulcerations five days after starting oral ferrous sulfate 325 mg twice daily (110179).
Intravenously, iron can cause gastrointestinal symptoms sch as nausea (104684,110192).
Immunologic
...Although there is some clinical research associating iron supplementation with an increased rate of malaria infection (56796,95432), the strongest evidence to date does not support this association, at least for areas where antimalarial treatment is available (95433,96623).
In an analysis of 14 trials, iron supplementation was not associated with an increased risk of malaria (96623). In a sub-analysis of 7 preliminary clinical studies, the effect of iron supplementation was dependent upon the access to services for antimalarial treatment. In areas where anemia is common and services are available, iron supplementation is associated with a 9% reduced risk of clinical malaria. In an area where services are unavailable, iron supplementation was associated with a 16% increased risk in malaria incidence (96623). The difference in these findings is likely associated with the use of malaria prevention methods.
A meta-analysis of clinical studies of all patient populations shows that administering IV iron, usually iron sucrose and ferric carboxymaltose, increases the risk of infection by 16% when compared with oral iron or no iron. However, sub-analyses suggest this increased risk is limited to patients with inflammatory bowel disease (IBD) (110186).
Intravenously, iron has rarely resulted in allergic reactions, including anaphylactoid reactions (110185,110192,112606,112607). There is one case of Kounis syndrome, also referred to as allergic angina or allergic myocardial infarction, in a 39-year-old female patient without previous coronary artery disease given intravenous ferric carboxymaltose. The patient experienced anaphylactic symptoms, including headache, abdominal pain, and breathing difficulties, 3 minutes after starting the infusion. She was further diagnosed with non-ST-elevation myocardial infarction (112607).
Musculoskeletal ...Intravenously, iron rarely results in osteomalacia related to hypophosphatemia (112609). At least 2 cases exist of hypophosphatemic osteomalacia. In one case, a 70-year-old male with a genetic hemorrhagic disorder infused with ferric carboxymaltose developed lower limb pain with hypophosphatemia and diffuse bone demineralization in the feet (112609). In a second case, a 61-year-old male developed femoral neck insufficiency fractures following repeated ferric carboxymaltose transfusions for anemia related to vascular malformation in the bowel (112603). Severe hypophosphatemia requiring intravenous phosphate in the absence of osteomalacia has also occurred following intravenous ferric carboxymaltose (112608,112610).
Oncologic
...There is a debate regarding the association between high levels of iron stores and cancer.
Data are conflicting and inconclusive (1098,1099,1100,1102). Epidemiological studies suggest that increased body iron stores may increase the risk of cancer or general mortality (56703).
Occupational exposure to iron may be carcinogenic (56691). Oral exposure to iron may also be carcinogenic. Pooled analyses of population studies suggest that increasing the intake of heme iron increases the risk of colorectal cancer. For example, increasing heme iron intake by 1 mg/day is associated with an 11% increase in risk (56699,91185).
Other ...Intravenously, sodium ferric gluconate complex (SFGC) caused drug intolerance reactions in 0. 4% of hemodialysis patients including 2 patients with pruritus and one patient each with anaphylactoid reaction, hypotension, chills, back pain, dyspnea/chest pain, facial flushing, rash and cutaneous symptoms of porphyria (56527).
