Drugs List

Therapeutic Indications

Uses

Wilson's disease

Administration

Zinc acetate must be taken on an empty stomach, at least 1 hour before, or 2 to 3 hours after a meal. If gastric irritation occurs, the morning dose may be delayed until mid-morning. The capsules may also be taken with a little protein, such as meat.

In patients unable to swallow capsules, the contents may be dispersed in a little water.

Contraindications

Children under 1 year
Breastfeeding

Precautions and Warnings

Portal hypertension
Pregnancy

Treatment to be initiated and supervised by a specialist
Some brands contain Sunset Yellow (E110) - can trigger allergic reactions
Advise patient to have no food for 2 hours before and 1 hour after dose
Monitor cholesterol and triglyceride levels
Monitor full blood count regularly
Monitor patients for copper deficiency
Monitor serum zinc levels
Monitor urinary copper
Monitor urinary zinc

Not recommended for initial treatment of symptomatic cases due to slow onset of action. A chelating agent is advised for initial management, followed by zinc acetate once the patient is stable and copper levels are below toxic thresholds. However, while awaiting zinc induced duodenal metallothionein production and effective inhibition of copper absorption, zinc acetate could be used initially in symptomatic patients in combination with a chelating agent.

There is a risk of hepatic decompensation when switching from a chelating agent to zinc acetate in patients with portal hypertension.

Overtreatment - risk of copper deficiency, especially in children and pregnant women. In these patient groups, urinary copper levels should be kept a little above the upper limit of normal or in the high normal range (40 to 50 microgram/24 hours).

Urinary excretion of copper is an accurate reflection of body loading with excess copper only when patients are not on chelation therapy. 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.

Pregnancy and Lactation

Pregnancy

Use with caution in pregnancy.

Limited data of exposed pregnancies gave no indication of any harmful effects to embryo/foetus and mother from zinc. Pregnant Wilson's disease patients must continue their therapy during pregnancy. Their physician should decide which treatment, zinc or chelating agent, to use. Dose adjustments must be made in order to guarantee that the foetus does not become copper deficient, and close monitoring of the patient is essential.

For dosage guidance during pregnancy see Additional Dosage

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Contraindicated in breastfeeding.

Zinc is excreted in human breast milk so zinc induced copper deficiency may occur in the breast fed infant.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Elevated amylase levels
Elevated serum lipase
Gastric irritation
Increase in alkaline phosphatase
Leukopenia
Sideroblastic anaemia

Presentation

Oral formulations containing zinc acetate

Drugs List

Therapeutic Indications

Uses

Wilson's disease

Dosage

Dosage should be adjusted according to therapeutic monitoring.

Adults

Elderly

Children

Additional Dosage Information

Administration

Zinc acetate must be taken on an empty stomach, at least 1 hour before, or 2 to 3 hours after a meal. If gastric irritation occurs, the morning dose may be delayed until mid-morning. The capsules may also be taken with a little protein, such as meat.

In patients unable to swallow capsules, the contents may be dispersed in a little water.

Therapeutic Drug Monitoring

The aim of the treatment is to maintain the plasma free copper below 250 microgram/l (normal 100 to 150 microgram/l) and the urinary copper excretion below 125 microgram/24 hours (normal less than 50 microgram/24 hours).

Values of urinary zinc above 2 mg/24 hours and of plasma zinc above 1250 microgram/l generally indicate adequate compliance.

Contraindications

Children under 1 year
Breastfeeding

Precautions and Warnings

Portal hypertension
Pregnancy

Treatment to be initiated and supervised by a specialist
Some brands contain Sunset Yellow (E110) - can trigger allergic reactions
Advise patient to have no food for 2 hours before and 1 hour after dose
Monitor cholesterol and triglyceride levels
Monitor full blood count regularly
Monitor patients for copper deficiency
Monitor serum zinc levels
Monitor urinary copper
Monitor urinary zinc

Not recommended for initial treatment of symptomatic cases due to slow onset of action. A chelating agent is advised for initial management, followed by zinc acetate once the patient is stable and copper levels are below toxic thresholds. However, while awaiting zinc induced duodenal metallothionein production and effective inhibition of copper absorption, zinc acetate could be used initially in symptomatic patients in combination with a chelating agent.

There is a risk of hepatic decompensation when switching from a chelating agent to zinc acetate in patients with portal hypertension.

Overtreatment - risk of copper deficiency, especially in children and pregnant women. In these patient groups, urinary copper levels should be kept a little above the upper limit of normal or in the high normal range (40 to 50 microgram/24 hours).

Urinary excretion of copper is an accurate reflection of body loading with excess copper only when patients are not on chelation therapy. 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.

Pregnancy and Lactation

Pregnancy

Use with caution in pregnancy.

Limited data of exposed pregnancies gave no indication of any harmful effects to embryo/foetus and mother from zinc. Pregnant Wilson's disease patients must continue their therapy during pregnancy. Their physician should decide which treatment, zinc or chelating agent, to use. Dose adjustments must be made in order to guarantee that the foetus does not become copper deficient, and close monitoring of the patient is essential.

For dosage guidance during pregnancy see Additional Dosage

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Contraindicated in breastfeeding.

Zinc is excreted in human breast milk so zinc induced copper deficiency may occur in the breast fed infant.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Counselling

Zinc acetate capsules must be taken on an empty stomach - one hour before or two to three hours after meals.

Any combined therapy with a chelating agent should be dosed at least one hour apart.

Side Effects

Elevated amylase levels
Elevated serum lipase
Gastric irritation
Increase in alkaline phosphatase
Leukopenia
Sideroblastic anaemia

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: September 2014

Reference Sources

Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press [Accessed on 25 September 2014].

Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications [Accessed on 25 September 2014].

Summary of Product Characteristics: Wilzin 25mg capsules. Orphan Europe (UK) Ltd. Revised January 2014

Summary of Product Characteristics: Wilzin 50mg capsules. Orphan Europe (UK) Ltd. Revised January 2014