Medically reviewed by Kovalenko Svetlana Olegovna, PharmD. Last updated on 2020-04-06
Attention! Information on this page is intended only for medical professionals! Information is collected in open sources and may contain significant errors! Be careful and double-check all the information on this page!
Top 20 medicines with the same components:
Treatment of Wilson's disease.
Zinc acetate therapy is indicated for maintenance treatment of patients with Wilson's disease who have been initially treated with a chelating agent (See PRECAUTIONS: Monitoring Patients).
Zink beta treatment should be initiated under the supervision of a physician experienced in the treatment of Wilson's disease. Zink beta is a life-long therapy.
There is no difference in dose between symptomatic and presymptomatic patients.
Zink beta is available in hard capsules of 25 mg or 50 mg.
The usual dose is 50 mg 3 times daily with a maximum dose of 50 mg 5 times daily.
- Children and adolescents:
Data are very limited in children under 6 years but since the disease is fully penetrant, prophylactic treatment should be considered as early as possible. The recommended dose is as follows:
- from 1 to 6 years: 25 mg twice daily
- from 6 to 16 years if bodyweight under 57 kg: 25 mg three times daily
- from 16 years or if bodyweight above 57 kg: 50 mg three times daily.
- Pregnant women:
A dose of 25 mg 3 times daily is usually effective but the dose should be adjusted to copper levels.
In all cases, dose should be adjusted according to therapeutic monitoring.
Zink beta must be taken on an empty stomach, at least 1 hour before or 2-3 hours after meals. In case of gastric intolerance, often occurring with the morning dose, this dose may be delayed to mid-morning, between breakfast and lunch. It is also possible to take Zink beta with a little protein, such as meat.
In children who are unable to swallow capsules, these should be opened and their content suspended in a little water (possibly sugar or syrup flavoured water).
When switching a patient on chelating treatment to Zink beta for maintenance therapy, the chelating treatment should be maintained and co-administered for 2 to 3 weeks since this is the time it takes for the zinc treatment to induce maximum metallothionein induction and full blockade of copper absorption. The administration of the chelating treatment and Zink beta should be separated by at least 1 hour.
The recommended adult dose is 50 mg as zinc three times daily (See Clinical Trials).
Since 25 mg t.i.d. is also an effective dose in children 10 years of age or older or in women who are pregnant, it may be advisable to use a dose of zinc to 25 mg three times a day, as long as the patient is compliant with therapy. The dose can be raised to 50 mg t.i.d. if monitoring indicates a lessening of control (see PRECAUTIONS: Monitoring Patients).
Patients should take zinc acetate on an empty stomach, at least one hour before or two to three hours after meals. For additional information, see PRECAUTIONS.
Hypersensitivity to the active substance or to any of the excipients.
Zinc Acetate Capsules are contraindicated in patients with known hypersensitivity to any of the components of the formulation.
Zinc acetate dihydrate is not recommended for the initial therapy of symptomatic patients because of its slow onset of action. Symptomatic patients must be initially treated with a chelating agent; once copper levels are below toxic thresholds and patients are clinically stable, maintenance treatment with Zink beta can be considered.
Nevertheless, while awaiting zinc induced duodenal metallothionein production and consequential effective inhibition of copper absorption, zinc acetate dehydrate could be administered initially in symptomatic patients in combination with a chelating agent.
Although rare, clinical deterioration may occur at the beginning of the treatment, as has also been reported with chelating agents. Whether this is related to mobilisation of copper stores or to natural history of the disease remains unclear. A change of therapy is recommended in this situation.
Caution should be exercised when switching patients with portal hypertension from a chelating agent to Zink beta, when such patients are doing well and the treatment is tolerated. Two patients of a series of 16 died from hepatic decompensation and advanced portal hypertension after being changed from penicillamine to zinc therapy.
The aim of the treatment is to maintain the plasma free copper (also known as non-ceruloplasmin plasma copper) below 250 microgram/l (normal: 100-150 microgram/l) and the urinary copper excretion below 125 microgram/24 h (normal: < 50 microgram/24 h). The non-ceruloplasmin plasma copper is calculated by subtracting the ceruloplasmin-bound copper from the total plasma copper, given that each milligram of ceruloplasmin contains 3 micrograms of copper.
The urinary excretion of copper is an accurate reflection of body loading with excess copper only when patients are not on chelation therapy. Urinary copper levels are usually increased with chelation therapy such as penicillamine or trientine.
The level of hepatic copper cannot be used to manage therapy since it does not differentiate between potentially toxic free copper and metallothionein bound copper.
In treated patients, assays of urinary and/or plasma zinc may be a useful measure of treatment compliance. Values of urinary zinc above 2 mg/24 h and of plasma zinc above 1250 microgram/l generally indicate adequate compliance.
Like with all anti-copper agents overtreatment carries the risk of copper deficiency, which is especially harmful for children and pregnant women since copper is required for proper growth and mental development. In these patient groups, urinary copper levels should be kept a little above the upper limit of normal or in the high normal range (i.e. 40 - 50 microgram/24 h).
Laboratory follow-up including haematological surveillance and lipoproteins determination should also be performed in order to detect early manifestations of copper deficiency, such as anaemia and/or leukopenia resulting from bone marrow depression, and decrease in HDL cholesterol and HDL/total cholesterol ratio.
As copper deficiency may also cause myeloneuropathy, physicians should be alert to sensory and motor symptoms and signs which may potentially indicate incipient neuropathy or myelopathy in patients treated with Zink beta.
No information provided.
Zinc acetate is not recommended for the initial therapy of symptomatic patients because of the delay required for zinc-induced increase in enterocytic metallothionein and blockade of copper uptake. Symptomatic patients should be treated initially, using chelating agents. During initial therapy, neurological deterioration may occur as stores of copper are mobilized. Once initial therapy has been completed, and the patient is clinically stable, maintenance treatment with zinc acetate can be considered, but patients may be continued on initial therapy as clinically indicated.
Patients should be monitored primarily by assessment of existing signs and symptoms of Wilson's disease and 24-hour urine copper. Neuropsychiatric evaluations including speech as well as liver function tests including bilirubin and aminotransferases, should be done as appropriate.
The urinary excretion of copper is an accurate reflection of the body status of copper when patients are not on chelation therapy. The clinician should be aware that urinary copper levels are usually increased with chelation therapy such as penicillamine or trientine. Adequate zinc therapy will eventually decrease urinary copper excretion to 125 μg per 24 hours or less. A significant trend upward indicates impending loss of copper control. The non-ceruloplasmin plasma copper (also known as free copper) is obtained by subtracting the ceruloplasmin-bound copper from the total plasma copper. Each mg of ceruloplasmin contains 3 μg of copper. In the United States study, non-ceruloplasmin plasma copper concentration was kept below 20 μg/dL. Urine and plasma for copper determinations should be collected in copper-free containers and assayed with equipment capable of accurately measuring copper at levels as low as 0.01 μg/mL.
An additional monitoring tool, if available, is the amount of radioactivity measured in the plasma 1 or 2 hours after orally administered 64copper. In adequately controlled patients, the amount is less than 1.2% of the administered dose. The level of hepatic copper should not be used to manage therapy since it does not differentiate between potentially toxic free copper and safely bound copper.
In all treated patients, 24-hour urinary zinc levels may be a useful measure of compliance with the zinc acetate regimen.
Zinc does appear in breast milk and zinc-induced copper deficiency in the nursing baby may occur.
Therefore, it is recommended that women on zinc therapy not nurse their babies.
Results of observations in a small number of patients in the two clinical trials suggest that pediatric patients aged 10 years and above can be adequately maintained at doses between 75 to 150 mg elemental zinc daily in divided doses. No patients below the age of 10 years have been studied.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Zinc acetate has not been tested for its carcinogenic potential in long-term animal studies, for its mutagenic potential or for its effect on fertility in animals.
However, testing with other salts of zinc (zinc oxide, zinc stearate, zinc sulfate) did not reveal a mutagenicity potential in in vitro Ames assays, and human embryonic lung cell chromosomal aberration assay, and in in vivo rat dominant lethal assay, and rat bone marrow cell chromosomal aberration assay.
Other salts of zinc (zinc oxide, zinc chloride, zinc citrate, zinc maleate, zinc carbonate, zinc sulfate) and pure zinc dust at oral doses up to 326 mg/Kg/day (18 times the recommended human dose based on body surface area) were found to have no effect on fertility and reproductive performance of male and female rats.
Pregnancy Category A.
Studies in pregnant women have not shown that zinc acetate or zinc sulfate increases the risk of fetal abnormalities if administered during all trimesters of pregnancy. If this drug is used during pregnancy, the possibility of fetal harm appears remote. Because studies cannot rule out the possibility of harm, however, zinc acetate should be used during pregnancy only if clearly needed. While zinc acetate should be used during pregnancy only if clearly needed, copper toxicosis can develop during pregnancy if anti-copper therapy is stopped.
Oral teratology studies have been performed with zinc sulfate in pregnant rats at doses up to 42.5 mg/Kg/day (2 times the recommended human dose based on body surface area), mice at doses up to 30 mg/Kg/day (1 time the recommended human dose based on body surface area), rabbits at doses up to 60 mg/Kg/day (6 times the recommended human dose based on body surface area) and hamsters at doses up to 88 mg/Kg/day (5 times the recommended human dose based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to zinc sulfate. (See Clinical Trials).
No studies on the effects on the ability to drive and use machines have been performed.
Reported adverse reactions are listed below, by system organ class and by frequency.
Frequencies are defined as: very common (> 1/10), common (> 1/100 to < 1/10), uncommon (> 1/1,000 to < 1/100), rare (> 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
System organ class
Adverse drug reactions
Blood and lymphatic system disorders
sideroblastic anaemia, leukopenia
blood amylase, lipase and alkaline phosphatase increased
Anaemia may be micro-, normo- or macrocytic and is often associated with leukopenia. Bone marrow examination usually reveals characteristic "ringed sideroblasts" (i.e. developing red blood cells containing iron-engorged paranuclear mitochondria). They may be early manifestations of copper deficiency and may recover rapidly following reduction of zinc dosage. However, they must be distinguished from haemolytic anaemia which commonly occurs where there is elevated serum free copper in uncontrolled Wilson's disease.
The most common undesirable effect is gastric irritation. This is usually worst with the first morning dose and disappears after the first days of treatment. Delaying the first dose to mid-morning or taking the dose with a little protein may usually relieve the symptoms.
Elevations of serum alkaline phosphatase, amylase and lipase may occur after a few weeks of treatment, with levels usually returning to high normal within the first one or two years of treatment.
Yellow Card Scheme
Health Products Regulatory Authority
Tel: +353 1 6764971
Fax: +353 1 6762517
e-mail: [email protected]
Clinical experience with zinc acetate has been limited. The following adverse reactions have been reported in patients with Wilson's disease on zinc therapy: a death following overdosage with zinc sulfate (See OVERDOSAGE) and a death in a patient with advanced liver disease and hemolytic crisis where zinc sulfate was used as initial treatment; gastric irritation; elevations of serum alkaline phosphatase, amylase and lipase lasting from weeks to months suggesting pancreatitis. The levels usually return to high normal within the first one or two years of zinc therapy.
Drug Abuse And Dependence
Zinc acetate has no potential for abuse, and it is not related pharmacologically or structurally to any other drug known to have abuse potential.
Three cases of acute oral overdose with zinc salts (sulphate or gluconate) have been reported in the literature. Death occurred in a 35 year-old woman on the fifth day after ingestion of 6 g of zinc (40 times the proposed therapeutic dose) and was attributed to renal failure and haemorrhagic pancreatitis with hyperglycaemic coma. The same dose did not produce any symptoms except for vomiting in an adolescent who was treated by whole-bowel irrigation. Another adolescent who ingested 4 g of zinc had serum zinc level of about 50 mg/l 5 hours later and only experienced severe nausea, vomiting and dizziness.
Treatment of overdose should be with gastric lavage or induced emesis as quickly as possible to remove unabsorbed zinc. Heavy metal chelation therapy should be considered if plasma zinc levels are markedly elevated (> 10 mg/l).
Acute oral overdosage with inorganic salts of zinc in humans is reported rarely. In the event of overdosage, the unabsorbed zinc salt should be removed from the stomach by lavage as quickly as possible. The plasma level of zinc should be measured, and heavy metal chelation therapy should be considered if the plasma level of zinc is elevated markedly ( > 1000 μg/dL). In addition, any signs or symptoms of toxicity should be treated as medically indicated.
One fatality associated with overdosage of zinc sulfate has been reported. The death of this adult woman followed the accidental ingestion of approximately 28 g of zinc sulfate. Death occurred on the fifth day after ingestion and was attributed to renal failure. Hemorrhagic pancreatitis and hyperglycemic coma resulted from the overdose. The amount ingested was 500 mg/Kg of zinc sulfate, a value that is in the same order of magnitude as that found to be lethal in animals.
Pharmacotherapeutic group: various alimentary tract and metabolism products, ATC code: A16AX05.
Wilson's disease (hepatolenticular degeneration) is an autosomal recessive metabolic defect in hepatic excretion of copper in the bile. Copper accumulation in the liver leads to hepatocellular injury and eventual cirrhosis. When the liver capacity of storing copper is exceeded copper is released into the blood and is taken up in extra hepatic sites, such as the brain, resulting in motor disorders and psychiatric manifestations. Patients may present clinically with predominantly hepatic, neurologic, or psychiatric symptoms.
The active moiety in zinc acetate dihydrate is zinc cation, which blocks the intestinal absorption of copper from the diet and the reabsorption of endogenously secreted copper. Zinc induces the production of metallothionein in the enterocyte, a protein that binds copper thereby preventing its transfer into the blood. The bound copper is then eliminated in the stool following desquamation of the intestinal cells.
Pharmacodynamic investigations of copper metabolism in patients with Wilson's disease included determinations of net copper balance and radiolabelled copper uptake. A daily regimen of 150 mg of Zink beta in three administrations was shown to be effective in significantly reducing copper absorption and inducing a negative copper balance.
Since the mechanism of action of zinc is an effect on copper uptake at the level of the intestinal cell, pharmacokinetic evaluations based on blood levels of zinc do not provide useful information on zinc bioavailability at the site of action.
Zinc is absorbed in the small intestine and its absorption kinetics suggest a tendency to saturation at increasing doses. Fractional zinc absorption is negatively correlated with zinc intake. It ranges from 30 to 60% with usual dietary intake (7-15 mg/d) and decreases to 7% with pharmacological doses of 100 mg/d.
In the blood, about 80% of absorbed zinc is distributed to erythrocytes, with most of the remainder being bound to albumin and other plasma proteins. The liver is the main storage for zinc and hepatic zinc levels are increased during maintenance therapy with zinc.
The plasma elimination half-life of zinc in healthy subjects is around 1 hour after a dose of 45 mg. The elimination of zinc results primarily from faecal excretion with relatively little from urine and sweat. The faecal excretion is in the greatest part due to the passage of unabsorbed zinc but it is also due to endogenous intestinal secretion.
Because the proposed site of action of zinc is an effect on copper uptake at the level of the intestinal cell, pharmacokinetic evaluations based on blood levels of zinc do not provide useful information on zinc bioavailability at the site of action. Determinations of zinc content in the liver and the plasma zinc concentration after the oral administration of zinc acetate have yielded inconsistent results. However, foods and beverages have been shown to decrease the uptake of zinc thereby decreasing the levels of zinc in the plasma of healthy volunteers. For this reason, the oral dose of zinc should be separated from food and beverages, other than water, by at least one hour.
Preclinical studies have been conducted with zinc acetate and with other zinc salts. Pharmacological and toxicological data available showed large similarities between zinc salts and among animal species.
The oral LD50 is approximately 300 mg zinc/kg body weight (about 100 to 150 times the human therapeutic dose). Repeat-dose toxicity studies have established that the NOEL (No Observed Effect Level) is about 95 mg zinc/kg body weight (about 48 times the human therapeutic dose).
The weight of evidence, from in vitro and in vivo tests, suggests that zinc has no clinically relevant genotoxic activity.
Reproduction toxicology studies performed with different zinc salts showed no clinically relevant evidence of embryotoxicity, foetotoxicity or teratogenicity.
No conventional carcinogenicity study has been conducted with zinc acetate dihydrate.
No special requirements
However, we will provide data for each active ingredient