AuSPEN GUIDELINES

FOR INTRAVENOUS TRACE ELEMENTS AND VITAMINS

1999

Dr David Russell Department of Gastroenterology Royal Melbourne Hospital Grattan Street ParkviIle Victoria 3050

CONTENTS

1. Introduction

2. Background information on requirements for intravenous Trace Elements and Vitamins

3. New guidelines for Intravenous Trace Elements & Vitamins

4. Composition of Additrace and Peditrace

5. Conclusion

1. INTRODUCTION

At the 22 nd Annual Conference of AuSPEN in 1996 there was a Micro­ Nutrient Workshop reviewing the current AuSPEN recommendations for Intravenous Trace Elements and Vitamins in Total Parenteral Nutrition (TPN).

Dr Alan Shenkin, from the Department of Clinical Chemistry University of Liverpool UK, and Dr Michael Barnett, The Welsh School of Pharmacy, University of Wales, Cardiff were active advisors to the Workshop. Together with a panel of Australian members of AuSPEN the following updated guidelines are presented.

The majority of the workshop focused on recent research into changes in Trace Element requirements during acute illness & TPN. Prevention of trace element deficiencies is clearly critical, and modification of trace element requirements as a consequence of the acute­phase response is now better understood. No significant new recommendations were made regarding intravenous vitamin dosages.

A key reference forming the basis of these recommendations is found in a supplement to NUTRITION Jan/Feb 1995 Vol II No1: "The Trace Elements: Their Role and Function in Nutritional Support".

2. BACKGROUND INFORMATION ON INTRAVENOUS TRACE ELEMENT AND VITAMIN REQUIREMENTS

Note:

1. The following tables summarise the recommendations from previous publications by well­respected authors. A review of these recommendations formed the basis of the new guidelines (see references)

2. In trace elements & vitamin tables AMA = American Medical Association GRI = Glasgow Royal Infirmary AAP = American Academy of Paediatrics

3. Molecular weights of some trace elements n = m /MW Chromium 52 Copper 63.55 lodide (I) 126.9 Manganese 54.94 Selenium 78.96 Zinc 65.38

4. Vitamins: Conversion International Units (IU) to weight Vitamin A 1 IU = 0.344microgram Vitamin D 1 IU = 25 nanogram Vitamin E 1 IU =1 milligram

TRACE ELEMENTS: Adults micromol per day

AuSPEN Shenkin Fleming Elia Leung AMA GR I

Copper 16 0­30 5.7­7.9 8­24 8­ 24 9.1­27.3 20 Chromium 0.4 0.2­0.3 0.2­0.4 0.19­0.29 0.19­0.29 0.19­0.29 0.2 Iron 20 20 Fluoride 50­150 50 lodide 0.4 0.8­1.6 1 Molybdenum 0.2 0.15­0.3 0.2 Manganese 8 5 2.7­14 2.7­14.5 5 Selenium 1.5 1.5 0.5­1 0.4­0.8 0.5­1 0.4 Zinc 30 >50 36­61 38­61 38­61 38­61 100

TRACE ELEMENTS: Children 1 ­15 year micromol/kg/day

AuSPEN 2­16yr Greene AMA Copper 0.4 0.3 0.031 Chromium 0.002 0.004 0.003 ­ 0.004 lodide 0.01 0.007 Manganese 0.15 0.018 0.03 ­ 0.18 Selenium 0.03 0.025 Zinc 0.4 0.77

TRACE ELEMENTS: Infants 0­1 year micromol/kg/day

AuSPEN 0­2yrs Greene Canadian PS Ricour Copper 0.6 0.3 0.3 0.3 Chromium 0.005 0.004 0.004 0.004 Iron 1.8 50µg Fluoride 0.007 1.7 lodide 0.05 0.008 0.04 Molybdenum 0.018 0.0026 Manganese 0.04 0.025 0.02 0.09­0.18 Selenium 0.04 1.5­3.8 0.02­0.025 0.04 Zinc 1.4 6.5 1.5 Cobalt 15 µg

TRACE ELEMENTS: Preterm micromol/kg/day

Shils Zlotkin Leung Greene Canadian PS

Copper 0.3 0.99 0.3­0.55 0.3 1.1­1.9 Chromium 0.002­0.004 0.004 0.001­0.002 Iodine 0.007 0.2 Molybdenum 0.002­0.004 Manganese 0.04­0.18 0.018 0.01­0.02 Selenium 0.025 0.04­0.06 Zinc 4.5 6.7 3.8­6.1 6.15 6.5

VITAMINS: Adults per day

AMA GRI AuSPEN MVI 12 (10ml) A (µg) 1000 1000 324 1135 D (µg) 5 5 1.4 5 E (mg) 10 10 2.9 10 K (µg) 150 C (mg) 100 100 64 100 Thiamine (mg) 3 3 8 3 Riboflavin (mg) 3.6 3.6 3.9 3.6 Pyridoxine (mg) 4 4 2.9 4 Niacin (mg) 40 40 47 40 B12 (µg) 5 5 1.4 5 Pantothenic acid (mg) 15 15 7.5 15 Biotin (µg) 60 60 17.1 60 Folic Acid (µg) 400 400 2143 400

VITAMINS: Children per day

AAP Greene AuSPEN MVI Paed (5ml) A (µg) 400­700 700 1400 700 D (µg) 10 10 20 10 E (mg) 5­8 7 14 7 K (µg) 15­60 200 400 200 C (mg) 45 80 160 80 Thiamine (mg) 0.7­1.2 1.2 2.4 1.2 Riboflavin (mg) 0.8­1.4 1.4 2.8 1.4 Pyridoxine (mg) 0.9­1.6 1 2 1 Niacin (mg) 9­16 17 34 17 B12 (µg) 2­3 1 2 1 Pantothenic acid (mg)

3­5 5 10 5

Biotin (µg) 65­120 20 40 20 Folic Acid (µg) 100­300 140 280 140

VITAMINS: Infants per day

AAP 0­1yrs MVI Paed (5ml) A (µg) 400­420 700 D (µg) 10 10 E (mg) 3­4 10 K (µg) 12­20 200 C (mg) 35 80 Thiamine (mg) 0.3­0.5 1.2 Riboflavin (mg) 0.4­0.6 1.4 Pyridoxine (mg) 0.3­0.6 1 Niacin (mg) 6­8 17 B12 (µg) 0.5­1.5 1 Pantothenic acid (mg) 2­3 5 Biotin (µg) 35­50 20 Folic Acid (µg) 30­45 140

VITAMINS: Preterm

Greene per kg

MVI Paed (2ml)

A (µg) 500 316 D (µg) 4 4 E (mg) 2.8 2.8 K (µg) 80 80 C (mg) 25 32 Thiamine (mg) 0.35 0.48 Riboflavin (mg) 0.15 0.56 Pyridoxine (mg) 0.18 0.4 Niacin (mg) 6.8 6.8 B12 (µg) 0.3 0.4 Pantothenic acid (mg) 2 2 Biotin (µg) 6 8 Folic Acid (µg) 56 56

3. 1999 GUIDELINES FOR INTRAVENOUS TRACE ELEMENTS & VITAMINS

1. TRACE ELEMENTS Previous AuSPEN guidelines for trace element dosages in adult and paediatric practice, meant that pharmacists compounded individual elements or purchased a "trace element mixture" composing a selection of elements. The new AuSPEN guidelines are in line with the internationally published literature and recommended by the expert panel (AuSPEN Micronutrient Workshop 1996). The new guidelines in adult practice recommend routine administration of intravenous iron, whereas its use in paediatric practice is not defined. The commercially available multi­element solutions Additrace and Peditrace meet the new AuSPEN dosage guidelines.

2. VITAMINS Recent Australia­wide shortage of intravenous multivitamins (MVI12 and MVI­paediatric) has meant that other commercially available products (Cernevit, Vitalipid­N and Soluvit) have been assessed and the TGA has been approached for licensing.

Adult & Children over 11 years of age An alternative to MVI­12 is Cernevit. Cernevit is a multivitamin preparation of both water and fat soluble vitamins. The recommended dose is 5ml/d.

Children <11 yrs of age including infants and neonates An alternative to MVI­Paediatric is a combination of Soluvit­N (water soluble vitamin preparation) and Vitalipid­N (fat soluble vitamin preparation). The suggested dose of Soluvit­N is 1ml/kg/day to a maximum dose of 10 ml/day and Vitalipid­N is 4ml/kg/day to a maximum dose of 10ml/day.

1999 AUSPEN TRACE ELEMENTS GUIDELINES

ADULT µmols/day

CHILDREN (1­15yrs)

µmols/kg/day

INFANTS (0­1yr)

µmols/kg/day

PRETERM µmols/kg/day

Zinc (Zn) * 50­100 0.4­3.0 1.5­3.8 3.0­6.5 Copper (Cu) # 5­20 0.3­0.4 0.3 0.3 Selenium (Se) 0.4­1.5 0.03 0.025­0.04 0.016­0.025 Iron (Fe) 20 Not Defined Not Defined Not Defined Manganese (Mn)^ 5 0.018 0.018 0.014­0.018 Chromium (Cr) 0.2­0.4 0.001 Molybdenum (Mo) 0.4 lodide 1.0 0.004­0.008 0.007 0.004­0.007

*Increased zinc supplements may be required with diarrhoea, or increased losses from an intestinal fistula or stoma

# Increased copper supplements may be required with abnormal gastrointestinal fluid loss. Reduced copper supplements should be given in the presence of liver or biliary tract disease

^ Reduced manganese supplements should be given in the presence of cholestasis

1999 ADULT VITAMIN GUIDELINES

AuSPEN (Dose/day)

MV1­12 (10ml)

CERNEVIT (5ml)

INTRAVITE (2ml)

A (µg) 1000 1135 1204 D (µg) 5 5 5.5 E (mg) 10 10 11.2 K (µg) None None None C (mg) 100 100 125 50 Thiamine (mg) 3 3 3.52 10 Riboflavin (mg) 3.6 3.6 4.14 5 Pyridoxine (mg) 4 4 4.54 5 Niacin (mg) 40 40 46 50 B12 (µg) 5 5 6 Pantothenic acid(mg) 15 15 17.25 5 Biotin (µg) 60 60 69 Folic Acid (µg) 400 400 414

1999 PAEDIATRIC VITAMIN GUIDELINES

AuSPEN (Dose/kg/day)

MVI PAED (Dose/ml)

SOLUVIT­N (1ml/kg/day)

VITALIPID­N (4ml/kg/day)

A (µg) 500 460 920 D (µg) 4 2 4 E (mg) 2.8 1.4 2.8 K (µg) 80 40 80 C (mg) 25 16 10 Thiamine (mg)

0.35 0.24 0.32

Riboflavin (mg)

0.35 0.28 0.36

Pyridoxine (mg)

0.15 0.2 4

Niacin (mg) 0.18 0.34 4 B12 (µg) 0.3 0.2 1.5 Pantothenic acid (mg)

2 1 6

Biotin (µg) 6 4 40 Folic Acid (µg)

56 28 0.5

Recommended daily doses of MVI Paed/kg

<0.750 kg 1 ml/d 0.750 – 1 kg 1.5 ml/d 1 – 1.5 kg 2 mls/d 1.5 – 2 kg 3 mls/d 2 – 3 kg 4 mls/d >3 kg to <12 yrs 5 mls/d

4. COMPOSITION OF ADDITRACE AND PEDITRACE

Several commercial preparations of multi­element solutions are now available. The formulations of Additrace and Peditrace are very similar to the new AuSPEN Guidelines. Indeed, Alan Shenkin and Michael Barnett were key advisers to Pharmacia in this product formulation.

Consequently 10ml of Additrace per day in most adult patients on TPN is optimal replacement. However, modification of dosage may be required in hepatic or renal dysfunction (see product contraindications and warnings).

Peditrace (1ml/kgm) is appropriate in the paediatric patients to a maximum of 15ml/day.

DATA SHEET ADDITRACE

Pharmacia & Upjohn Limited Davy Avenue Milton Keynes MK5 8PH United Kingdom

January 1997

PRESENTATION:

A clear, almost colourless solution containing trace elements for addition to Vamin amino acid solutions in the intravenous nutrition of adults. Additrace corresponds to the following formula:

Ferric chloride 6H2O 0.54 mg Zinc chloride 1.36 mg Manganese chloride 4H2O 99.0 micrograms Copper chioride 2H2O 0.34 mg Chromic chloride 5.33 micrograms Sodium selenite 5H2O 10.5 micrograms Sodium molybdate 2H2O 4.85 micrograms Sodium fluoride 0.21 mg Potassium iodide 16.6 micrograms Xylitol 300 mg Water for injections to 1 ml pH 2.2

One ampoule (10 ml Additrace) contains the following amounts of trace elements:

Fe 3+ 20 micromol Zn 2+ 100 micromol Mn 2+ 5 micromol Cu 2+ 20 micromol Cr 3+ 0.2 micromol Se 4+ 0.4 micromol Mo 6+ 0.2 micromol F ­ 50 micromol I ­ 1 micromol

One ampoule of Additrace contains less than 1 mmol of both, potassium and sodium.

USES:

Additrace is used as part of a complete intravenous nutrition regimen providing a source of trace elements for adults and children over 40 kg.

DOSAGE AND ADMINISTRATION:

Recommended dosage for adults:

1 ampoule (10 ml) of Additrace is added to either 500 ml or 1000 ml of a solution listed in the table below. Where higher amounts of trace elements are considered necessary, 2 ampoules of Additrace may be added to 1000 ml solution. Additrace should not be added to Vamin 9 amino acid solution. Where a regimen includes Vamin 9, Additrace should be added to the glucose infusion.

Additrace does not contain calcium, magnesium or phosphate. These minerals should be added to the intravenous nutrition regimen if appropriate. (Vamin 9 Glucose and Vamin 14 contain calcium and magnesium. See appropriate data sheet/SPC.) Similarly Additrace does not contain significant amounts of potassium or sodium (see 'Presentation' above) since the requirements for these electrolytes vary with different clinical conditions. Potassium and sodium salts should therefore be added as appropriate to the individual patient's regimen. (Vamin 9 Glucose and Vamin 14 contain potassium and sodium. See appropriate data sheet/SPC.)

Infusion solution Volume to which 10ml Additrace may be added (ml)

Vamin 9 Glucose 500­1000 Infusion should be Vamin 14 500­1000 completedwithin Vamin 14 El~ctrolyte­Free 500­1000 24 hours of Vamin 18 Electrolyt ­ Free 500­1000 addition. Glucose 5 50% 500­1000

Additrace must only be added to solutions where compatibility is known.

The above mixtures containing Vamin should be infused at an appropriate rate for the amino acid solution and the infusion completed not more than 24 hours after preparation. If Additrace is added to a solution other than those listed above, then ensure that the solution is administered over a period of not less than 2 hours, so as to minimise renal losses.

Recommended dosage for infants and children under 40kg:

The trace element solution Peditrace should be used.

CONTRA­INDICATIONS, WARNINGS, ETC.

Contra­indications: Should not be administered undiluted

Use in pregnancy and lactation: Additrace is a solution of trace elements indicated as a supplement in TPN regimens. It contains the following elements: Fe 3+ , Zn 2+ , Mn 2+ , Cu 2+ , Cr 3+ , Se 4+ , Mo 6+ , F ­ , I ­ in amounts per ampoule not exceeding daily recommended requirements where these exist. No hazard is expected if used in pregnancy at the recommended dosage. No animal studies have been performed. There are, however, published reports on safe and successful use of trace elements as part of a TPN regimen during pregnancy in the human.

Other special warnings and precautions: Care should be taken in the administration of Additrace to patients with impaired liver function (especially cholestasis). Manganese toxicity is more likely to occur in patients with impaired liver function and cholestasis as manganese is almost entirely dependent on the biliary route for excretion. Manganese blood levels and liver function should be monitored regularly (monthly) in such patients. Additrace should be stopped if manganese levels rise into

the potentially toxic range (please refer to appropriate reference ranges for the testing laboratory).

Additrace should be used with caution in patients with impaired renal function when the excretion of some trace elements (zinc, selenium, fluoride, chromium and molybdenum) may be significantly decreased.

Overdosage:

In general overdosage with Additrace is extremely unlikely as the quantity of trace elements per ampoule lies well below known toxic levels of administration

Chronic overdosage may very rarely occur secondary to an unsuspected idio­ syncratic deficiency in metabolism or excretion for a specific trace element. In this case, signs may be observed such as nail dystrophy with insidious onset of symptoms secondary to haematological changes or tissue deposition Diagnosis would be confirmed by biochemical and haematological tests and treatment should be withdrawal of Additrace.

PHARMACEUTICAL PRECAUTIONS: No other additions should be made to solutions containing Additrace unless compatibility is known. 1. Store at room temperature (25°C or below). 2. The addition of Additrace should be performed aseptically immediately before the

start of the infusion and the solution should be used within 24 hours.

LEGAL CATEGORY: POM.

PACKAGE QUANTITIES: Boxes of 20 x 10 ml polypropylene ampoules.

FURTHER INFORMAT1ON: The manufacturer can be consulted for full information on complete and balanced­intravenous nutrition regimens.

PRODUCT LICENCE NUMBER: 0022/0064

PRODUCT LICENCE HOLDER: Pharmacia Laboratories Limited.

DATE OF PREPARATION: January 1997

PEDITRACE

Summary of Product Characteristics

Pharmacia & Upjohn Limited Davy Avenue Knowlhill Milton Keynes MK5 8PH United Kingdom

July 1995 1. NAME OF PROPRIFEARY MEDICINAL PRODUCT – Peditrace

2. QUALITATlVE AND QUANTITATIVE COMPOSITION 1 ml of Peditrace contains:

Active Quantity Reference Ingredients to standard

Zinc chloride 521 µg Ph Eur Copper chloride 53.7 µg USP

2H2O Manganese 3.60 µg USP

chloride 4H2O Sodium selenite 6.66 µg 87/84

5H2O Sodium fluoride 126 µg BP Potassium iodide 1.31 µg Ph Eur

The active ingredients in 1 ml correspond to: Zn 250 µg 3.82 µmol Cu 20 µg 0.315 µmol Mn 1 µg 18.2 nmol Se 2 µg 25.3 nmol F 57 µg 3.00 µmol I 1 µg 7.88 nmol

Other Quantity Reference ingredients to standard Hydrochloric to pH 2 0 Ph Eur

acid Water for to 1 ml Ph Eur

injections

3. PHARMACEUTICAL FORM A 10 ml polypropylene vial of a sterile, clear, colourless solution containing trace elements for addition to certain infusion fluids in the intravenous nutrition of paediatric patients.

4. CLINICAL PARTICULARS 4.1 Therapeutic indications

Peditrace is an integral part of the complete intravenous nutrition of infants and children. It is intended to meet basal requirements for trace elements and should be used in conjunction with Vaminolact, Vamin 14 Electrolyte­Free (at physician's discretion: see data sheet) or a glucose solution.

As the requirements of trace elements may vary in different clinical conditions, these substances may have to be added as appropriate in the individual patient.

Peditrace administration should not be started until kidney function is established usually during the second day of life.

It is not to be given undiluted.

4.2. Posology and method of administration Adults and elderly: Peditrace is designed for paediatric use. ­ Additrace should be used in adults and elderly.

Infants and children (weighing 15 kg or less): Basal requirements of the included trace elements are covered by 1 ml Peditrace per kg body weight per day to a maximum dose of 15ml.

Children (weighing 15 kg or more): A daily dose of 15ml Peditrace should meet basic trace element requirements. However, for patients weighing more than 40 kg the adult preparation Additrace should be used.

Patients who are likely to lose higher than average amounts of trace elements, or those requiring prolonged intravenous nutrition should be monitored biochemically to confirm that requirements are being appropriately met. Peditrace can be added to either an amino acid solution or glucose solution and in these cases, up to 6 ml Peditrace can be added to 100 ml Vaminolact@, Vamin 14~Electrolyte­Free (at physician's discretion: see data sheet) or glucose solution (50­500 mg/ml). It may also be administered as a paediatric admixture but only admixtures in which compatibility has been documented are to be used.

The infusion should be given at a very slow rate (minimum infusion period 8 hours) and is best done with an appropriate pump or an automatic drop rate counter.

The requirements of potassium and sodium vary with different patient conditions. Peditrace is not intended to meet these requirements.

4.3. Contra­indications: Should not be given undiluted.

4.4. Special warnings and special precautions for use: Administration should be carried out only under specialist surveillance especially in patients with pre­existing imbalances, in renal failure or in hepatic disease.

Peditrace should be used with caution in conditions where excretion in the bile is reduced particularity when cholestatic liver disease is present and/or when urinary excretion is markedly reduced. Patients with such conditions require careful biochemical monitoring as the excretion of trace elements may also be significantly decreased. (Copper and manganese being normally excreted in bile; selenium and zinc especially in patients receiving parenteral nutrition being excreted mainly in the urine).

Patients requiring long term total parenteral nutrition (TPN) (defined as longer than one month) should have a baseline whole blood or serum manganese level within or below the normal range and normal liver function before receiving Peditrace.

Manganese levels and liver function should be monitored regularly (monthly) whole the patient is maintained on Peditrace.

Peditrace should be stopped if manganese levels rise into the potentially toxic range (please refer to appropriate reference ranges for the testing laboratory) or if cholestasis develops.

Addition of other drugs to be avoided due to the risk of precipitation.

A cloudy solution or one containing a precipitate must not be used.

The addition of Peditrace must be done aseptically within one hour before the start of infusion. To minimise the risk of infection the infusate should be used within 24 hours.

4.5. Interaction with other medicaments and other forms of interaction: No interactions with other drugs have been observed

4.6. Pregnancy and lactation: Not appropriate to the use of this product.

4.7. Effects on ability to drive and use machines: Not appropriate to the use of this product.

4.8. Undesirable effects Impaired renal or hepatic excretion may lead to chronic overdose of one or more trace elements.

4.9. Overdose: In recommended doses Peditrace supplies trace elements at the level of normal daily requirements. Acute Acute overdose of these trace elements is unlikely to be hazardous.

Chronic Chronic overdose of manganese has been recorded as causing Parkinsonism and Psychosis.

Chronic overdosage may very rarely occur secondary to an unsuspected idiosyncratic deficiency in metabolism or excretion for a specific trace element. In this case, signs may be observed such as nail dystrophy with insidious onset of symptoms secondary to haematological changes or tissue deposition. Diagnosis would be confirmed by biochemical and haematological tests and treatment should be withdrawal of Peditrace.

5. PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties:

Peditrace is a concentrated trace element solution formulated to cover the requirements of neonates and infants receiving total parenteral nutrition. Potassium, magnesium and calcium are not included in the formulation as individual requirements vary from patient to patient.

5.2 Pharmacokinetic properties: The trace elements in Peditrace when infused in physiological amounts should be utilised in the same way as elements absorbed from an oral diet. No pharmacokinetic studies with Peditrace have been performed.

5.1 Preclinical safety data. No toxic effects were observed during the preclinical studies.

6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients:

Hydrochloric acid Ph Eur Water for injections Ph Eur

6.2 Incompatibilities: Do not add drugs with Peditrace to infusion solution unless the compatibility profile is satisfactory.

Do not add Peditrace to infusion solutions other than those recommended unless the compatibility profile is satisfactory.

6.3 Shelf life: The shelf life is 24 months when stored in room temperature (below 25°C).

6.4 Special precautions for storage: Do not freeze. Protect vials from light. Store below 25°C.

6.5 Nature and contents of container: Peditrace is supplied in 10ml polypropylene plastic vials for injection, which fulfil the tests according to Ph Eur. The vials are sealed with a chlorobutyl rubber stopper coated with a steel blue fluoropolymer and flip­off caps.

6.6 Instructions for use/handling: Must not be given undiluted. Peditrace can be added to either an amino acid solution or glucose solution (see below) and given during a minimum infusion period of 8 hours. The infusion should be given at a very slow rate and is best done with an appropriate pump or an automatic drop rate counter. Only admixtures in which compatibility has been documented are to be used.

The addition of Peditrace must be done aseptically within one hour before the start of infusion. To minimise the risk of infection the infusate should be used within 24 hours.

Compatibility

Up to 6 ml of Peditrace can be added to 100 ml Vaminolact, Vamin 14 Electrolyte­Free or glucose solution (5500 mg/ml).

7. MARKETING AUTHORISATION HOLDER Pharmacia Limited Davy Avenue Milton Keynes MK5 8PH

8. MARKET1NG AUTHORISATTION NUMBER 0022/0160

9. DATE OF FIRST AUTHORISATION/ RENEWAL OF AUTHORISATION Not applicable.

10.DATE OF (PARTIAL) REVISION OF THE TEXT Not applicable.

Date of preparation: July 1995

5. CONCLUSION

Discussion has already commenced with the Therapeutics Goods Association (TGA) and Baxter Health Care Australia in association with Fresenius­Kabi about licensing Additrace, Peditrace, Cernevit, Soluvit­N and Vitalipid­N in Australia.

REFERENCES

1. Shils ME, Burke AW, Green HL et al: Guidelines for essential trace element preparations for parenteral use. (AMA Dept of Foods and Nutrition, a statement by an expert panel) JAMA 1979;241:2051­4

2. Zlotkin SH, Buchanan BE: Meeting zinc and copper intake requirements in the parenterally fed preterm and full­term infant. J Paediatr 1983;103:441­6

3. Leung FY: Trace elements in parenteral micronutrition. Clin Biochem 1995;28:561­6

4. Greene HL, Hambridge MD, Schanler R, Tsang RC: Guidelines for the use of vitamins, trace elements, calcium, magnesium and phosphorous in infants and children receiving total parenteral nutrition: report of the Subcommittee on Paediatric Parenteral Nutrient requirements from the Committee on Clinical Practice Issues of the American Society for Clinical Nutrition. Am J Clin Nutr 1988;48:1324­42

5. Nutrition Committee, Canadian Paediatric Society: Nutrition needs and feeding of premature infants. Can Med Assoc J 1995;152:1765­84

6. Nutrition needs of the preterm infant. Williams and Wilkins, New York, 1993

7. Vitamin and trace mineral supplements for total parenteral nutrition. AuSPEN Therapeutic Sub­Committee IDRR 3/86

8. Ricour C, Navarro J, Duhamel JF: Trace elements and vitamin requirements in infants on total parenteral nutrition. Acta Chir Scand Suppl 1980;498:67­9

9. AMA Department of Foods and Nutrition: Guidelines for essential trace element preparations for parenteral use. JAMA 1979;241:2051­4

10. Shenkin A, Fell GS, Halls DJ et al. Essential trace element provision to patients receiving home intravenous nutrition in the United Kingdom. Clin Nutr 1986;5:91­7

11. Fleming CR: Trace element metabolism in adult patients requiring total parenteral nutrition. Am J Clin Nutr 1989;49:573­9

12. Elia M: Changing concepts of nutrient requirements in disease: implications for artificial nutritional support. Lancet 1995;345:1279­84

13. Shenkin A. Vitamin and essential trace element recommendations during intravenous nutrition: theory and practice. Proc Nutr Soc 1986;45:383­90 (GRI)

14. American Academy of Paediatrics, Committee on Nutrition: Nutritional needs of low birth weight infants. Pediatrics 1985;75:976­84

15. Supplement to NUTRITION Jan/Feb 1~995 Vol II No1: "The Trace Elements: Their Role and Function in Nutritional Support''

16. Tsang RC, Lucas A, Vavy R, Zlotkin S. Nutritional needs of the preterm infant, Williams & Wilkins, New York 1993. Am J Clin Nutri 1988;48:1324­42