| Ingredients | Each Ampoule Contains |
|---|---|
|
(Zn)
(Zinc Gluconate)
|
0.067 mg |
|
(Nickel Gluconate)
|
0.073 mg |
|
(Co)
(Cobalt Gluconate)
|
0.073 mg |
purified Water, Glucose
Below is general information about the effectiveness of the known ingredients contained in the product Gammadyn Zn-Ni-Co. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
There is insufficient reliable information available about the effectiveness of cobalt.
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 Gammadyn Zn-Ni-Co. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Cobalt chloride 1 mg daily has been used with apparent safety for up to 90 days in two small clinical studies (102081,102082).
POSSIBLY UNSAFE ...when used orally, long-term or in large amounts. ...when inhaled due to occupational exposure. Cobalt exposure has been linked to reports of cardiomyopathy, dermatitis, hypothyroidism, interstitial lung disease, and neurotoxicity, including vision and hearing loss (102066,102067,102068,102070,102071,102072,102073,102074,102076,102077).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally and appropriately. Nickel is safe for most adults when used in doses less than the tolerable upper intake level (UL) of 1 mg daily (7135).
POSSIBLY UNSAFE ...when used in high doses and for prolonged periods. Taking nickel in doses above the tolerable upper intake level (UL) of 1 mg daily increases the chance of adverse effects (7135). Taking high doses of nickel is associated with acute toxicity. Prolonged industrial exposure to nickel is also associated with hypersensitivity disorders, lung disorders, and cancer (7135,16307,16311).
CHILDREN: LIKELY SAFE
when used orally and appropriately.
Nickel is safe in children when used in daily doses less than the tolerable upper intake level (UL) of 0.2 mg daily in children 1-3 years, 0.3 mg daily in children 4-8 years, and 0.6 mg daily in children 9-13 years (7135).
CHILDREN: POSSIBLY UNSAFE
when used orally in high doses.
Taking nickel in doses above the UL might not be safe (7135).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately.
Nickel is safe to use during pregnancy and lactation in doses below the tolerable upper intake level (UL) of 1 mg daily (7135). There is insufficient reliable information available about the safety of nickel when taken in doses above the UL during pregnancy and lactation.
LIKELY SAFE ...when used orally and appropriately. Zinc is safe in amounts that do not exceed the tolerable upper intake level (UL) of 40 mg daily (7135). ...when used topically and appropriately (2688,6538,6539,7135,8623,11051,111291).
POSSIBLY SAFE ...when used orally and appropriately in doses higher than the tolerable upper intake level (UL). Because the UL of zinc is based on regular daily intake, short-term excursions above 40 mg daily are not likely to be harmful. In fact, there is some evidence that doses of elemental zinc as high as 80 mg daily in combination with copper 2 mg can be used safely for approximately 6 years without significant adverse effects (7303,8622,92212). However, there is some concern that doses higher than the UL of 40 mg daily might decrease copper absorption and result in anemia (7135).
POSSIBLY UNSAFE ...when used intranasally. Case reports and animal research suggest that intranasal zinc might cause permanent anosmia or loss of sense of smell (11155,11156,11703,11704,11705,11706,11707,16800,16801,17083). Several hundred reports of anosmia have been submitted to the US Food and Drug Administration (FDA) and the manufacturer of some intranasal zinc products (Zicam) (16800,16801). Advise patients not to use intranasal zinc products.
LIKELY UNSAFE ...when taken orally in excessive amounts. Ingestion of 10-30 grams of zinc sulfate can be lethal in adults (7135). Chronic intake of 450-1600 mg daily can cause multiple forms of anemia, copper deficiency, and myeloneuropathies (7135,17092,17093,112473). This has been reported with use of zinc-containing denture adhesives in amounts exceeding the labeled directions, such as several times a day for several years (17092,17093). Advise patients to follow the label directions on denture adhesives that contain zinc.
CHILDREN: LIKELY SAFE
when used orally and appropriately (7135).
Zinc is safe in amounts that do not exceed the tolerable upper intake level (UL). The UL for children is based on age: 4 mg daily for 0-6 months, 5 mg daily for 7-12 months, 7 mg daily for 1-3 years, 12 mg daily for 4-8 years, 23 mg daily for 9-13 years, and 34 mg daily for 14-18 years (7135,97140).
CHILDREN: POSSIBLY UNSAFE
when used orally in high doses.
Taking amounts greater than the UL can cause sideroblastic anemia and copper deficiency (7135). ...when used topically on damaged skin. An infant treated with 10% zinc oxide ointment for severe diaper rash with perianal erosions developed hyperzincemia. Absorption seemed to occur mainly via the erosions; plasma levels dropped after the erosions healed despite continued use of the ointment (106905).
PREGNANCY: LIKELY SAFE
when used orally and appropriately.
Zinc is safe in amounts that do not exceed the tolerable upper intake level (UL) of 34 mg daily during pregnancy in those 14-18 years of age and 40 mg daily in those 19-50 years of age (7135).
PREGNANCY: LIKELY UNSAFE
when used orally in doses exceeding the UL (7135).
LACTATION: LIKELY SAFE
when used orally and appropriately.
Zinc is safe in amounts that do not exceed the tolerable upper intake level (UL) of 34 mg daily during lactation in those 14-18 years of age, and 40 mg daily for those 19-50 years of age (7135).
LACTATION: POSSIBLY UNSAFE
when used orally in doses exceeding the UL.
Higher doses can cause zinc-induced copper deficiency in nursing infants (7135).
Below is general information about the interactions of the known ingredients contained in the product Gammadyn Zn-Ni-Co. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Disulfiram can reduce the absorption and clinical effects of nickel.
 Details
Disulfiram can chelate nickel, preventing its absorption. This interaction has been used therapeutically to reduce eczema in people with severe nickel hypersensitivity (16322).
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Amiloride can modestly reduce zinc excretion and increase zinc levels.
Details
Clinical research shows that amiloride can reduce urinary zinc excretion, especially at doses of 10 mg per day or more. This zinc-sparing effect can help to counteract zinc losses caused by thiazide diuretics, but it is unlikely to cause zinc toxicity at usual amiloride doses (830,11626,11627,11634). The other potassium-sparing diuretics, spironolactone (Aldactone) and triamterene (Dyrenium), do not seem to have a zinc-sparing effect.
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Zinc modestly reduces levels of atazanavir, although this effect does not seem to be clinically significant.
Details
Clinical research shows that zinc might decrease serum atazanavir levels by chelating with atazanavir in the gut and preventing its absorption (93578). Although a single dose of zinc sulfate (Solvazinc tablets) 125 mg orally does not affect atazanavir concentrations in patients being treated with atazanavir/ritonavir, co-administration of zinc sulfate 125 mg daily for 2 weeks reduces plasma levels of atazanavir by about 22% in these patients. However, despite this decrease, atazanavir levels still remain at high enough concentrations for the prevention of HIV virus replication (90216).
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Zinc might decrease cephalexin levels by chelating with cephalexin in the gut and preventing its absorption.
Details
A pharmacokinetic study shows that zinc sulfate 250 mg taken concomitantly with cephalexin 500 mg decreases peak levels of cephalexin by 31% and reduces the exposure to cephalexin by 27%. Also, taking zinc sulfate 3 hours before cephalexin decreases peak levels of cephalexin by 11% and reduces the exposure to cephalexin by 18%. By decreasing cephalexin levels, zinc might increase the risk of treatment failure. This effect does not occur when zinc is taken 3 hours after the cephalexin dose (94163). To avoid an interaction, advise patients take zinc sulfate 3 hours after taking cephalexin.
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Theoretically, zinc might interfere with the therapeutic effects of cisplatin.
Details
Animal research suggests that zinc stimulates tumor cell production of the protein metallothionein, which binds and inactivates cisplatin (11624,11625). It is not known whether zinc supplements or high dietary zinc intake can cause clinically significant interference with cisplatin therapy. Cisplatin might also increase zinc excretion.
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Theoretically, taking zinc along with integrase inhibitors might decrease the levels and clinical effects of these drugs.
Details
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Zinc might reduce the levels and clinical effects of penicillamine.
Details
By forming an insoluble complex with penicillamine, zinc interferes with penicillamine absorption and activity. Zinc supplements reduce the efficacy of low-dose penicillamine (0.5-1 gram/day), but do not seem to affect higher doses (1-2.75 gram/day), provided dosing times are separated (2678,4534,11605). Advise patients to take zinc and penicillamine at least 2 hours apart.
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Zinc can decrease the levels and clinical effects of quinolones antibiotics.
Details
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Zinc modestly reduces levels of ritonavir.
Details
Clinical research shows that zinc might reduce serum ritonavir levels by chelating with ritonavir in the gut and preventing its absorption (93578). In patients with HIV, ritonavir is taken with atazanavir to prevent the metabolism and increase the effects of atazanavir. A pharmacokinetic study shows that, in patients being treated with atazanavir/ritonavir, co-administration of zinc sulfate (Solvazinc tablets) 125 mg as a single dose or as multiple daily doses for 2 weeks reduces plasma levels of ritonavir by about 16% (90216). However, atazanavir levels still remains high enough to prevent HIV virus replication. Therefore, the decrease in ritonavir levels is not likely to be clinically significant.
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Zinc might reduce levels of tetracycline antibiotics.
Details
Tetracyclines form complexes with zinc in the gastrointestinal tract, which can reduce absorption of both the tetracycline and zinc when taken at the same time (3046,4945). Taking zinc sulfate 200 mg with tetracycline reduces absorption of the antibiotic by 30% to 40% (11615). Demeclocycline and minocycline cause a similar interaction (4945). However, doxycycline does not seem to interact significantly with zinc (11615). Advise patients to take tetracyclines at least 2 hours before, or 4-6 hours after, zinc supplements to avoid any interactions.
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Below is general information about the adverse effects of the known ingredients contained in the product Gammadyn Zn-Ni-Co. 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, cobalt seems to be well-tolerated when taken for up to 90 days in small amounts. Taking cobalt orally long-term or in high doses may cause cardiomyopathy, hearing loss, and vision loss (102066,102068,102077). Topically, cobalt-containing products can cause allergic contact dermatitis in some patients (102070,102071,102072,102073). Occupational exposure to cobalt dust may cause cardiomyopathy, interstitial lung disease, and hearing and vision loss in some people (102066,102067,102068,102077). Exposure to cobalt from cobalt-containing prosthetic joints has been linked to cardiomyopathy, dermatitis, hypothyroidism, hearing loss, and vision loss (102066,102068,102070,102074,102076,102077).
Cardiovascular ...Oral, occupational, and systemic exposure to cobalt may cause cardiomyopathy. While rare, this adverse effect has been reported in patients taking cobalt for anemia, consuming cobalt-fortified beer, working in industries with exposure to cobalt dust, and those with cobalt-containing prosthetic joints (102066,102076). Patients who consume a low protein diet, are thiamine deficient, or who have hypothyroidism appear to be at a greater risk of cobalt-induced cardiomyopathy. Cobalt-related cardiomyopathy can be distinguished from non-cobalt-related cardiomyopathy by its rapid onset and progression (102066).
Dermatologic ...Topically, cobalt can cause allergic contact dermatitis. Numerous cases of allergic skin reactions have been reported after contact with cobalt in leather goods, jewelry, nail polishes, cobalt blue tattoo ink, and cement (102069,102070,102071,102072). Dermatitis has also been reported in patients with occupations that involve the production or handling of ceramics, enamel, glass, heavy metals, pigments, or electrical components, as cobalt is extensively used in these industries (102070,102073). Exposure to cobalt found in prosthetic joints and other metallic surgical implants has also been reported to cause generalized dermatitis in some patients (102070).
Endocrine ...Exposure to cobalt-containing prosthetic joints may cause hypothyroidism in some patients (102074,102076).
Neurologic/CNS ...Exposure to cobalt may cause reversible neurologic adverse effects in some patients (102074,102076,102077). Demyelinating neuropathy, cognitive decline, headaches, depression, convulsions, and forgetfulness have been reported in patients with cobalt-containing hip joint prostheses (102074,102077). Vertigo and impairment in memory and attention have been reported after occupational exposure to cobalt (102077).
Ocular/Otic ...Oral, occupational, and systemic exposure to cobalt may cause adverse ocular and otic effects. While rare, reversible and irreversible vision loss, optic neuropathy and atrophy, signs of abnormal retinal functioning, hearing loss, bilateral deafness, and tinnitus have been reported in patients taking cobalt for anemia, working in industries with exposure to cobalt dust, and those with cobalt-containing prosthetic joints (102068,102074,102077).
Pulmonary/Respiratory ...Occupational exposure to cobalt can cause interstitial lung disease (ILD). Patients with subacute cobalt-related ILD may present with dyspnea, cough, fevers, chills, and weight loss a few months to years after exposure, and symptoms typically resolve after removal of the exposure. Patients with chronic cobalt-related ILD experience a more gradual development of dyspnea and cough which generally do not improve after removal of the exposure. Chronic cobalt-related ILD can progress to end-stage fibrosis and death. While removal of exposure is the mainstay of treatment, some case reports show that inhaled or systemic corticosteroids can improve symptoms and radiographic signs of cobalt-related ILD (102067).
Other ...Exposure to cobalt-containing prosthetic joints may cause pseudotumor formation near the replaced joints (102074,102075,102076). In one study, around 54% of patients with metal-on-metal total hip arthroplasty developed pseudotumors, while 22% with conventional metal-on-polyethylene articulations developed pseudotumors. Women with metal-on-metal articulations and elevated serum cobalt levels were at the greatest risk of developing pseudotumors (102075).
General
...Orally, nickel is well tolerated when taken in amounts found in foods, which are typically below the tolerable upper intake level (UL).
However, doses above the UL can cause serious adverse effects.
Most Common Adverse Effects:
All routes of administration: Contact dermatitis.
Serious Adverse Effects (Rare):
Orally: Chronic consumption of large quantities of nickel might increase the risk of cancers of the lung, nose, larynx, and prostate.
Cardiovascular ...Particulate matter-associated nickel exposures have been associated with cardiopulmonary diseases (65021). Nickel exposure may also cause variable degrees of cardiovascular system poisoning (16333). In one case report, a 45-year-old male developed leukocytosis, low-grade fevers, dyspnea, and fatigue after implantation of a cardioverter-defibrillator (ICD). The patient eventually developed fulminant hypereosinophilia and eosinophilic myocarditis, resulting in cardiogenic shock and multiorgan failure. After the patient had been medically stabilized, the ICD was removed, leading to symptom resolution (99670).
Dermatologic
...Orally and topically, nickel can cause dermatitis and other hypersensitivity reactions in sensitized individuals (65045).
Nickel exposure may cause systemic contact dermatitis (65017). Orally, nickel sulfate has been associated with classic systemic allergic contact eczema (64916). Topical exposure can occur from the use of common equipment containing nickel. There are at least four case reports of allergic contact dermatitis of the hand due to the use of a nickel-containing electronic cigarette device. Patients with nickel allergy should be advised to avoid devices that contain nickel (99665,99669). There is also a case report of a 21-year-old female who developed recurrent rash on her upper chest and thighs due to exposure to nickel via weightlifting equipment at her gym (99671).
"Nickel itch" may occur up to seven days before skin eruption occurs. The primary skin eruption is follicular, which may be followed by skin ulceration. Nickel may cause Baboon syndrome, characterized by a clinical presentation of systemic contact dermatitis with a pruritic and confluent maculopapular, light red eruption, localized in the gluteal area and the major flexures and developing several hours or days after nickel contact (64963,65092).
Individuals with mutations in the filaggrin gene may be especially susceptible to hand eczema caused by additive effects from irritants and nickel exposure (65012). Nickel exposure may lead to cross-sensitivity dermatitis reaction in individuals who are allergic to other metals, especially palladium, cobalt, and aluminum (65023,64939,65099,65028,64968,65026).
Gastrointestinal ...Orally, consuming high doses of nickel 0. 5-2.5 grams has been reported to cause nausea, vomiting, abdominal pain, and diarrhea. Patients with systemic nickel allergy syndrome (SNAS) can experience colic and diarrhea after consumption of nickel-rich foods (99663).
Genitourinary ...Nickel has been shown to cross the placenta and to have embryotoxic and teratogenic properties (65068,65091). Nickel may upset the hormonal balance of the mother and may impair development of the preimplantation embryo (65061).
Hepatic ...Orally, nickel has been reported to cause hepatotoxicity (65009).
Immunologic
...Orally and topically, nickel can cause hypersensitivity reactions in sensitized individuals (64916,65017,65045).
Nickel sensitivity, which can cause dermatologic and gastrointestinal symptoms, has an estimated prevalence of 11% in the general population, with a higher overall incidence in females than in males (99668). About 10% of nickel-sensitive people react to ingestion of 550-1300 mcg. Nickel sensitivity, once acquired, may persist indefinitely (64994). Some clinical research suggests that daily consumption of nickel 30 ng, 0.3 mcg, or 1.5 mcg for one year can hyposensitize individuals and reduce symptoms of nickel sensitivity (99663).
In sensitive individuals, dermal or systemic exposure to nickel can induce a type I immediate (anaphylactic) reaction and a type IV delayed hypersensitivity reaction, mediated by secreted cytokines and allergen-specific T lymphocytes (64989,65002). Nickel exposure may cause a cross-sensitivity reaction in individuals who are allergic to other metals, especially palladium, cobalt, and aluminum (65023,64939,65099,65028,64968,65026).
Implantation of devices containing nickel have been reported to cause localized and systemic reactions. A 59-year-old male with a hip arthroplasty, who later tested positive for nickel allergy, experienced hip pain, aseptic implant loosening, and contact allergic dermatitis in the inguinal regions, necessitating multiple surgeries (99664). In another case, a 45-year-old male developed leukocytosis, low-grade fevers, dyspnea, fatigue, and edema immediately and during the two months after implantation of a cardioverter-defibrillator (ICD). The patient eventually developed fulminant hypereosinophilia and eosinophilic myocarditis, resulting in cardiogenic shock and multiorgan failure. Once the patient was stabilized, the ICD was removed and all symptoms resolved. The patient tested positive for nickel allergy (99670).
There have been at least two case reports of hypersensitivity reactions to the nickel contained in implanted cardiac rings. One 57-year-old male experienced severe urticaria and angioedema two weeks after implantation of a mitral valve annuloplasty ring. The patient tested positive for nickel allergy and, although there was no evidence of nickel in his blood, symptoms resolved upon removal of the nickel-containing ring (99667). A 56-year-old male experienced persistent urticarial rash and multiple episodes of anaphylactic shock within the first month after implantation of a mitral ring. The patient tested positive to nickel upon skin prick testing; symptoms resolved after removal of the mitral ring (99666).
Neurologic/CNS ...Orally, consuming large quantities of nickel can lead to acute nickel toxicity, which may cause cerebral edema (16334).
Oncologic
...The International Agency for Research on Cancer has classified nickel compounds as carcinogenic to humans (65046).
Occupational exposure to nickel and nickel compounds in nickel refining, cutlery factories, and alkaline battery manufacturing plants is associated with an increased incidence of lung, bronchial, and nasal cancers (39918,65029,16334,65056,64962,65075,64912,65006,64974). It is unclear if one specific lung cancer cell type is associated with nickel exposure (65054). Nickel fumes present in nickel and some steel refineries are associated with undifferentiated and squamous histologies of the nose and paranasal sinuses (65040,65050,65101,64898,65093,64909,64984,65031,64969). Occupational changes in industrial processes that have eliminated or reduced exposures to nickel compounds have reduced the risk of lung cancer (64966); however, experts believe that further preventive measures are needed to decrease or eliminate occupational nickel exposure time (65010). Exposure to nickel concentrate or metallic nickel through the metallurgical refining process has not been associated with an increase in respiratory cancer risk (64918).
Although clinical and epidemiologic research show that sparingly soluble nickel compounds, and possibly also soluble nickel compounds, may be linked to an increased risk for lung and nasal cancers, there is conflicting evidence as to whether inhalation exposure to soluble nickel alone is carcinogenic (42782,64940). According to some researchers, these opposing positions may be resolved by the hypothesis that high concentrations of inhaled nickel may induce chronic lung inflammation, enhancing carcinogenic risks associated with inhalation exposure to other substances (64938). Therefore, it has been suggested that if exposures are kept below levels that cause chronic respiratory toxicity, carcinogenic effects may be avoided.
There is concern that exposure to nickel in conjunction with another metal might increase the risk for certain forms of cancer. In the art glass industry, an association was found between an increased risk for stomach cancer and the use of a mixture of arsenic, copper, nickel, and manganese (65086). Based on epidemiological data and genotoxicity testing, the combination of nickel and chromium in the fumes from the welding of stainless and high alloy steels may contribute to an additive risk of respiratory tract cancer (65064). Additionally, co-exposure to nickel and cadmium may increase the risk of lung cancer (64945).
Epidemiological studies that have found an association between nickel and an increased risk for cancer might be confounded by the presence of cigarette smoking and asbestos exposure (65087,65106). Nickel occurs in mainstream cigarette smoke in the range of 0-0.51 mg per cigarette (65096). The high prevalence of prostate cancer in smokers may be related to the nickel in cigarettes (65109).
Implantation of nickel-containing hardware has also been reported to induce the development of cancer (64913,65032,65039). In one case, a 65-year-old female developed osteogenic sarcoma at the site of a nail that had been implanted for nine years for fixation of a femoral neck fracture. A concentration of 14 ppm of nickel was detected within the tumor tissue, indicating neoplastic induction by nickel (65032). In a different case, a malignant fibrous histiocytoma of the bone developed 20 years after a femoral fracture treated by plate-screw fixation. Nickel was present in the tumor tissue, indicating the metabolism of corrosion products (64913).
Pulmonary/Respiratory
...Inhalation of nickel carbonyl has been reported to cause nickel toxicity, including pulmonary edema, acute tracheobronchitis, or diffuse interstitial pneumonitis (16334,64905,61495).
Occupational exposure to nickel has been reported to cause chronic rhinitis, sinusitis, airway narrowing, asthma, bronchitis, reduced lung function, lung fibrosis, nasal polyposis, perforation of the nasal septum, and cancer of the lungs and nasal sinuses (65045,64933,65077). Bronchiolitis induced by nickel and nitric acid have also been reported (64948).
Renal ...Orally, nickel has been reported to cause nephrotoxicity (16333,65009), especially when consumed in excessive amounts (65104).
Other
...Orally, nickel toxicity can occur after the consumption of large quantities of nickel.
The level of toxicity caused by nickel exposure seems to depend on its chemical form. Insoluble nickel compounds, including metallic nickel, nickel sulfides, and nickel oxides, seem to have a higher carcinogenic potential than water-soluble nickel salts (chloride, nitrate, sulfate) (64902). Conversely, it has been reported that nickel compounds, other than nickel carbonyl, are essentially nontoxic after ingestion due to their low absorption from the gastrointestinal tract (65052).
The treatment of nickel toxicity is not well studied. In some reports, antioxidants, such as ascorbic acid, may protect against nickel toxicity (65009,64991). Chelating drugs have been used as an antidote in nickel poisoning (65045,64979). Sodium diethyldithiocarbamate and disulfiram have also been proposed as effective nickel chelators in the treatment of acute nickel carbonyl poisoning; however, adequate clinical studies are not available to assess the effectiveness of these options (65003).
General
...Orally, zinc is well tolerated in doses below the tolerable upper intake level (UL), which is 40 mg daily for adults.
Topically, zinc is well tolerated.
Most Common Adverse Effects:
Orally: Abdominal cramps, diarrhea, metallic taste, nausea and vomiting (dose-related).
Topically: Burning, discoloration, itching, stinging, and tingling when applied to irritated tissue.
Intranasally: Bad taste, dry mouth, headache, irritation, reduced sense of smell.
Serious Adverse Effects (Rare):
Orally: There have been cases of acute renal tubular necrosis, interstitial nephritis, neurological complications, severe vomiting, and sideroblastic anemia after zinc overdose.
Intranasally: There have been cases where intranasal zinc caused permanent loss of smell (anosmia).
Dermatologic
...Topically, zinc can cause burning, stinging, itching, and tingling when applied to inflamed tissue (6911,8623,87297).
Zinc oxide can be deposited in the submucosal tissue and cause dark discoloration of the skin. This can occur with prolonged topical application to intact skin, application to eroded or ulcerated skin, or penetrating traumatic exposure, and also parenteral administration (8618).
In rare cases, oral zinc has resulted in worsened acne (104056), skin sensitivity (6592), a leishmanial reaction with a macular rash that occurred on exposed parts of the body (86935), eczema (104055), systemic contact dermatitis (109457), and the development of severe seborrheic dermatitis (86946).
Gastrointestinal
...Orally, zinc can cause nausea (338,2663,2681,6592,6700,18216,106230,106233,106227), vomiting (2663,2681,6519,6592,96069,96074), a metallic or objectionable taste in the mouth (336,338,6700,11350,18216,106902), abdominal cramping (6592,96069), indigestion (87227), heartburn (96069), dry mouth (87533), and mouth irritation (336,2619).
When used orally in amounts above the tolerable upper intake level, zinc may cause irritation and corrosion of the gastrointestinal tract (331,86982,87315,106902), watery diarrhea (1352), epigastric pain (2663,2681), and severe vomiting (2663,2681).
Intranasally, zinc can cause bad taste, dry mouth, and burning and irritation of the throat (8628,8629).
When used topically as a mouth rinse, zinc may cause tooth staining (90206).
Hematologic ...There is concern that high daily doses of zinc, above the tolerable upper intake level (UL) of 40 mg per day, might increase the risk of copper deficiency, potentially leading to anemia and leukopenia (7135,112473). To prevent copper deficiency, some clinicians give a small dose of copper when zinc is used in high doses, long-term (7303).
Hepatic ...There are two cases of liver deterioration in patients with Wilson disease following initiation of treatment with zinc 50-200 mg three times daily. The mechanism of action is not understood, and the event is extremely uncommon (86927,87470).
Immunologic ...Daily doses of 300 mg of supplemental zinc for 6 weeks appear to impair immune response (7135). A case of erythematosus-like syndrome, including symptoms such as fever, leg ulcers, and rash, has been reported following intake of effervescent tablets (Solvezink) containing zinc 45 mg (87506). In another case, severe neutropenia was reported after taking supplemental zinc 900 mg daily for an unknown duration (112473).
Neurologic/CNS
...Zinc-containing denture adhesives can cause toxicity if used more frequently than recommended for several years.
Case reports describe hyperzincemia, low copper levels, blood dyscrasias, and neurological problems, including sensory disturbances, numbness, tingling, limb weakness, and difficulty walking in patients applying denture adhesive multiple times daily for several years (17092,17093,90205,90233). Due to reports of zinc toxicity associated with use of excessive amounts of zinc-containing denture adhesives for several years, GlaxoSmithKline has reformulated Polygrip products to remove their zinc content (17092,17093).
Intranasally (8628) and orally (87534), zinc can cause headache. When used orally in amounts above the tolerable upper intake level (UL), zinc may cause central nervous system (CNS) symptoms including lethargy, fatigue, neuropathy, dizziness, and paresthesia (2663,2681,87369,87470,87533,87534,112473).
Oncologic ...There is concern that zinc might worsen prostate disease. For example, some preliminary evidence suggests that higher dietary zinc intake increases the risk for benign prostatic hyperplasia (6908). Epidemiological evidence suggests that taking more than 100 mg of supplemental zinc daily or taking supplemental zinc for 10 or more years doubles the risk of developing prostate cancer (10306). Another large-scale population study also suggests that men who take a multivitamin more than 7 times per week and who also take a separate zinc supplement have a significantly increased risk of prostate cancer-related mortality (15607). However, a large analysis of population research suggests that there is no association between zinc intake and the risk of prostate cancer (96075).
Pulmonary/Respiratory
...There are several hundred reports of complete loss of sense of smell (anosmia) that may be permanent with use of zinc gluconate nasal gel, such as Zicam (11306,11155,11707,16800,16801,17083,86999,87535).
Loss of sense of smell is thought to be dose related but has also been reported following a single application (11306,11155,11707,16800). Patients often report having sniffed deeply when applying the gel, then experiencing an immediate burning sensation, and noticing anosmia within 48 hours (17083). On June 16, 2009, the US Food and Drug Administration (FDA) advised patients not to use a specific line of commercial zinc nasal products (Zicam) after receiving 130 reports of loss of smell (16800). The manufacturer of these products had also received several hundred reports of loss of smell related to its intranasal zinc products (16801). Zinc sulfate nasal spray was used unsuccessfully for polio prophylaxis before the polio vaccine was developed. It caused loss of smell and/or taste, which was sometimes permanent (11713). Animal studies suggest that zinc sulfate negatively affects smell, possibly by damaging the olfactory epithelium and neurons (11156,11703,11704,11705,11706). Zinc gluconate nasal spray has not been tested for safety in animals or humans. The clinical studies of intranasal zinc have not described anosmia as an adverse effect, but testing was not done to see if zinc use adversely affected sense of smell (6471,8628,8629,10247). Also, these clinical studies reported tingling or burning sensation in the nostril, dry nose, nose pain, and nosebleeds.
When used in amounts above the tolerable upper intake level (UL), zinc may cause flu-like symptoms including coughing (2663).
Renal ...In overdose, zinc can cause acute renal tubular necrosis and interstitial nephritis (331,1352,87338).
Other ...Occupational inhalation of zinc oxide fumes can cause metal fume fever with symptoms including fatigue, chills, fever, myalgias, cough, dyspnea, leukocytosis, thirst, metallic taste, and salivation (331).
