Consumer medicine information

Glamin

Amino acids

BRAND INFORMATION

Brand name

Glamin

Active ingredient

Amino acids

Schedule

Unscheduled

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Glamin.

What is in this leaflet

This leaflet answers some common question about Glamin. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you being given Glamin against the benefits this medicine is expected to have for you.

If you have any concerns about this medicine, ask your doctor or pharmacist.

Keep this leaflet. You may need to read it again.

What Glamin is used for

Glamin is a 13.4% amino acid/dipeptide intravenous infusion, which is given as a part of intravenous nutritional therapy. When the intake of nutrients or food into the mouth or directly into the gut is not possible or it is not enough to supply the body’s needs then intravenous nutrients or foods can be given. This is especially important for people whose bodies are under physical stress from illness or recent surgery. During illness or after surgery the body requires nutrition or food. Amino acids are the building blocks used by the body to make proteins. Glamin is usually given together with carbohydrates, fats, salts, trace elements and vitamins to provide a complete intravenous diet.

Your doctor may have prescribed Glamin for another reason. Ask your doctor if you have any questions about why Glamin has been prescribed for you.

Before you are given Glamin

You should NOT be given Glamin if

  • You have an allergy to Glamin or any of the ingredients listed at the end of this leaflet.
  • You have an inability to break down amino acids, for example an inherited condition known as phenylketonuria.
  • You have severe liver failure.
  • You have severe kidney failure (if dialysis facilities are not available).
  • You are suffering from a very serious problem with your blood circulation.
  • You have too much fluid in your body.
  • You have too much acid in your blood, also called metabolic acidosis.
  • There is not enough oxygen being supplied to your cells.
  • You have low potassium levels in your body.
  • You have too low sodium levels in your body.
  • You have too much lactic acid in your body.
  • Your blood is very concentrated
  • You have a build up of fluid in your lungs
  • You have certain untreated heart problems.

If you are not sure whether any of these apply to you, check with your doctor.

You must tell your doctor before being given Glamin;

  • If you have any allergies to any other medicines or any other substances, such as foods, preservatives or dyes.
  • If you are pregnant or intend to become pregnant. Your doctor will discuss the risks and benefits of using Glamin during pregnancy.
  • If you are breastfeeding or plan to breastfeed. Your doctor will discuss the risks and benefits of using Glamin when breastfeeding.
  • If you are under 18 years old.

If you have not told your doctors about any of the above, tell them before you are given Glamin.

Taking other medicines.

Some medicines can interact or interfere with each other. There are currently no known medicines, which can interfere or be affected by Glamin.

Use in Children

There is currently not enough information to recommend the use of Glamin in patients less than 18 years of age.

How is Glamin given

Glamin is given as a continuous infusion into a central vein. An electronic pump may be used to control the speed of the infusion. Glamin is usually given as a mixture with glucose, fats, salts, trace elements and vitamins. Glamin must only be given by a doctor or nurse.

How much is given

Your doctor will decide what dose you will receive. This will depend on your condition, any other diseases you may have and your body weight. The usual dose is 7-14mL of Glamin for each kilogram of body weight each day. This is usually given as an infusion running at 0.6-0.7mL for each kilogram of body weight each hour.

Your doctor will also calculate your requirements for energy, salts, trace elements and vitamins.

How long it is given

The infusion will be continued for as long as your condition requires. At the moment there is no experience with the use of Glamin for more than 2 weeks.

Side Effects

Glamin, like all other nutrient solutions which are given intravenously, may cause side effects in some people. All the side effects associated with Glamin may not yet have been detected.

The common side effects of Glamin (this occurs in 1% to less than 10% of people who use it) are fever, chills or hot flushes

Other less common side effects (in less than 1% of people who use it) include nausea and vomiting; confusion, agitation or hallucination; hiccups; breathlessness; gastric reflux; dizziness; lung problems; headache or migraine.

Reports of other side effects caused by Glamin are extremely rare.

If you have these or any other side effects during treatment, tell your doctor.

If you are given too much (overdose)

This rarely happens as Glamin is administered under the care of a trained professional in a hospital or clinic setting.

However, if you are given Glamin too quickly or too much, you may experience the following side effects: feeling sick (nausea and vomiting) or become flushed and sweaty.

Your doctor has information on how to recognise and treat an overdose. Ask your doctor if you have any concerns.

Otherwise, immediately contact the Poisons Information Centre in your country.

Australia: 13 11 26
New Zealand: 0800 764 766

While you are using Glamin

Your doctor will order blood and urine tests while you are given Glamin to monitor your progress. From the results, your dose of Glamin may be adjusted.

Storage

Glamin will be stored in the pharmacy or on the ward. The infusion solution is kept in a cool dry place, where the temperature stays below 25°C.

Product Description

What it looks like

Glamin is a clear, colourless to slightly yellow solution, which is supplied in glass bottles.

It may be supplied from the pharmacy as a mixture of Glamin, glucose, fats and vitamins. In this case it would be a milky white mixture in a plastic bag.

Ingredients

Glamin contains the active ingredients alanine, arginine, aspartic acid, glutamic acid, glycylglutamine monohydrate, glycyltyrosine dihydrate, histidine, isoleucine, leucine, lysine acetate, methionine, phenylalanine, proline, serine, threonine, tryptophan and valine.

Glamin also contains the inactive ingredients citric acid and water for injections.

1000mL of Glamin supplies 134g of amino acids and dipeptides, 22.4g of nitrogen and 2300kJ (550kcal) energy.

Glamin comes in three pack sizes and can be identified by

AUST R numbers:
250 mL: AUSTR 77749
500 mL: AUSTR 77750
1000 mL: AUSTR 77751

Glamin does not contain gluten, lactose, sucrose, tartrazine or any other azo dyes

Further Information

If you have any more questions or are not sure about anything, please ask your doctor or pharmacist.

Sponsor

Fresenius Kabi Australia Pty Limited
Level 2, 2 Woodland Way
Mount Kuring-gai NSW 2080
Australia
Telephone: 1300 361 004

Fresenius Kabi New Zealand Limited
60 Pavilion Drive
Airport Oaks, Auckland 2022
New Zealand
Freecall: 0800 144 892

® = Registered Trademark

Date of Information

This leaflet was prepared 9th August 2016.

Published by MIMS February 2017

BRAND INFORMATION

Brand name

Glamin

Active ingredient

Amino acids

Schedule

Unscheduled

 

1 Name of Medicine

Alanine, arginine, aspartic acid, glutamic acid, glycylglutamine monohydrate, glycyltyrosine dihydrate, histidine, isoleucine, leucine, lysine acetate, methionine, phenylalanine, proline, serine, threonine, tryptophan, valine.

2 Qualitative and Quantitative Composition

Glamin is an amino acid/dipeptide 13.4% solution for intravenous infusion.
Glamin is an electrolyte-free, clear and colourless to slightly yellow amino acid solution which contains glutamine and tyrosine as glycyl dipeptides for total parenteral intravenous nutrition. See Table 1.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Injection, intravenous infusion.

4 Clinical Particulars

4.1 Therapeutic Indications

Glamin provides amino acids as part of parenteral nutrition therapy, when oral or enteral nutrition is impossible, insufficient or contraindicated especially in patients with a moderate to severe catabolic status.

4.2 Dose and Method of Administration

Dosage.

The dosage of Glamin will depend on the patient's amino acid requirements. Generally, 1-2 g amino acids/ dipeptides (corresponding to 0.17-0.34 g N) per kg bodyweight per day are recommended. This corresponds to 7-14 mL Glamin per kg bodyweight per day or to 500-1000 mL Glamin per day for a patient weighing 70 kg.
The recommended infusion rate is 0.6-0.7 mL (corresponding to 0.08-0.09 g amino acids/ dipeptides) per kg bodyweight per hour. This corresponds to 500 mL in 10-12 hours or 1000 mL in 20-24 hours for a patient weighing 70 kg.
In patients with mild to moderate hepatic or renal impairment, dosage should be adjusted individually (see Section 4.4 Special Warnings and Precautions for Use).

Method of administration.

Glamin should be administered by the central venous route due to its osmolarity above 800 mOsm/L.
Use only clear solutions in intact containers.
The safety and efficacy of using Glamin for periods greater than two weeks has not been established.

Compatibility.

Compatibility with Glamin 1000 mL has been documented for the following: 20% fat emulsion (up to 1000 mL Intralipid 20%*), glucose 40% (up to 1000 mL), 80 mmol NaCl, 5 mmol CaCl2, 60 mmol KCl, 3.5 mmol Mg-L-hydrogen-glutamate, fat soluble vitamins (10 mL Vitalipid N Adult*) and water soluble vitamins (1 vial Soluvit N*).
*These have been used for compatibility testing.
Addition of individual supplements, e.g. phosphate supplements or trace elements, is possible but requires compatibility testing in each case.
Additions should be performed aseptically immediately before the start of the infusion.
Discard any residual contents. All steps of admixing must be performed under strictly aseptic conditions, e.g. using laminar air flow technique, by professionally trained personnel according to individual hospital policy.

Recommended admixing sequence.

1. Add trace elements and phosphate free electrolyte solutions to Glamin.
2. Add phosphate-containing electrolytes to the glucose solution.
3. Transfer the solutions produced in steps 1 and 2 into the ethylvinylacetate (EVA) bag.
4. Reconstitute Soluvit N with Vitalipid N and add to Intralipid.
5. Transfer Intralipid/ vitamin mixture to the EVA bag.
6. Mix the contents of the bag by gentle agitation.

Note.

Glucose solutions should not be added directly to Intralipid, but should be mixed with Glamin first. Electrolytes should never be added directly to Intralipid, but should be diluted in Glamin and glucose solution before being mixed with the emulsion.
When a mixture must be stored in the refrigerator for up to 24 hours before use, the vitamins and trace elements should be added just prior to administration.
The use of EVA bags for compounding should follow the manufacturer's instructions under strictly aseptic conditions.

4.3 Contraindications

Glamin is contraindicated in patients with inborn errors of amino acid metabolism (e.g. phenylketonuria), severe liver failure and severe renal failure.
General contraindications of parenteral nutrition are: unstable life threatening circulatory conditions (shock), metabolic acidosis, insufficient cellular oxygen supply, hyperhydration, hyponatraemia, hypokalaemia, hyperlactataemia, increased serum osmolarity, pulmonary oedema, decompensated cardiac insufficiency and known hypersensitivity to any of the ingredients.

4.4 Special Warnings and Precautions for Use

Amino acids solutions should not be used as carrier solutions for drugs. Glamin may only be mixed with other solutions where compatibility is documented.
Only clear solutions in intact containers should be used.

Caloric requirements.

It is essential to provide for appropriate caloric supply concurrently if parenterally administered amino acids are to be retained by the body and utilised maximally for protein synthesis. Concentrated glucose solutions or fat emulsions are effective sources of such calories.

Monitoring.

Frequent clinical evaluation and laboratory testing are necessary for proper monitoring during administration. Electrolytes, osmolarity, glucose, fluid balance, acid-base status, renal and liver function and full blood count should all be monitored.

Use in hepatic impairment.

There is no clinical trial experience with the use of Glamin in patients with mild or moderate impairment of hepatic function. Administration of amino acid solutions to patients with hepatic insufficiency may result in serum amino acid imbalances, hyperammonaemia, stupor and coma. Glamin should be used with caution in these patient populations. Glamin is contraindicated in patients with severe liver failure.

Use in renal impairment.

There is no clinical trial experience with the use of Glamin in patients with mild or moderate impairment of renal function. Glamin is contraindicated in patients with renal failure (if dialysis or hemofiltration is not available).

Use in the elderly.

No data available.

Paediatric use.

There is no experience with the use of Glamin solution in patients less than 18 years of age and it therefore cannot be recommended for use in children.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

In rats it has been shown that glutamine decreases the clearance of methotrexate. However, in humans there are no known drug interactions.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

The effect of Glamin on fertility has not been investigated in animal or clinical studies.
(Category: Exempt)
There were no abnormalities or embryotoxic effects in rabbits when the animals were dosed during embryofoetal development with Glamin at intravenous dose levels similar (1.2 times) to the maximum recommended clinical doses (14 mL/kg/day), based on body surface area. The effect of Glamin on peri- and postnatal development has not been investigated.
There are no adequate and well controlled studies in pregnant women. As animal studies are not always predictive of human response, Glamin should only be used during pregnancy if the benefit to the mother outweighs the risks to the foetus.
No data on the effects of Glamin during lactation are available. Caution should be exercised when Glamin is administered to a nursing woman and should only be used if clearly needed.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

A meta-analysis for a combined 12 trials of Glamin versus Vamin 18 EF showed the number of patients with clinical adverse events was 28.6% (50/175) versus 32.0% (55/172), respectively. Clinical adverse events regardless of causal relationship for the entire sample of 12 studies grouped according to organ classes are presented in Table 2.
The most common adverse events based on the 12 clinical studies with Glamin sorted by CIOMS III categories of frequency and COSTART (5th edition, 1995) body system and terms (not assessed as being necessarily related to Glamin) are as follows.

Incidence of frequency ≥ 1% - < 10%.

Fever, chills or hot flushes.

Incidence of frequency ≥ 0.1% - < 1%.

Nausea or vomiting, confusion, agitation or hallucination, hiccups, dyspnoea, pneumonia, hypertension or hypertonia, anastomosis insufficiency, gastrooesophageal reflux, dizziness or vertigo, pulmonary complication, headache or migraine.

Laboratory parameters.

Incidence of frequency ≥ 1% - < 10%.

Increases of gamma-GT, ALAT, AP, ASAT, glucose, bilirubin, urea; decreases of leucocytes, cholinesterase, haemoglobin.

Incidence of frequency ≥ 0.1% - < 1%.

Increases of ESR, uric acid, triglyceride, creatinine; decreases of albumin, sodium, potassium, leucocytes, total protein, RBP, haemotocrit/ PCV, calcium, chloride, prealbumin, phosphate; urinary glucose, urinary blood and urinary protein.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

When infusion rates exceed the recommended maximum rate, signs of intolerance may occur such as nausea, vomiting, flushing and sweating in combination with renal excretion of amino acids and dipeptides.
If symptoms of overdose occur, therapy includes reduction of the infusion rate or, if necessary, interruption of the infusion.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Glamin is an infusion solution for parenteral nutrition containing 18 essential and nonessential amino acids, two of which are in the form of the dipeptides glycylglutamine and glycyltyrosine.
The solution is suitable to support protein synthesis and to improve nitrogen balance during intravenous nutrition. In order to ensure optimal utilisation of the infused amino acids and dipeptides, the patient's requirements of energy (carbohydrates, fat), electrolytes, trace elements and vitamins should be covered.
Pharmacological effects, except nutritive ones, are not expected from amino acid solutions as long as they are infused according to the recommended dosage for parenteral nutrition.

Clinical trials.

Clinical trials carried out to date have compared Glamin to Vamin 18 EF (an amino acid solution containing 11.4% amino acids, but no dipeptides). A series of 13 clinical trials involving a total of 374 patients, 189 of whom were treated with Glamin, have shown that Glamin is as well tolerated as Vamin 18 EF. The findings also demonstrate that Glamin is as efficacious as Vamin 18 EF when given to patients after moderate to major abdominal surgery. Even though the results are strictly valid only for the studied patient groups, they can most likely be extended to other groups requiring intravenous nutrition and support of protein metabolism.
In the studies, plasma amino acid concentrations showed small to moderate changes during infusion of Glamin or Vamin 18 EF. The combined data of all the clinical trials indicated a slightly higher concentration of glutamine in the Glamin group. However, all plasma amino acid concentrations were well within the normal range in both study groups and there was no accumulation of amino acids in plasma during the study period. The urinary excretion of both amino acids and dipeptides was also low, in the case of glycylglutamine it amounted to 3-4% of the administered amount and the corresponding value for glycyltyrosine was 2-3%. Taken together, the combined data indicates that the dipeptides of Glamin are rapidly hydrolysed, and the amino acids are efficiently utilised in a manner similar to that for Vamin 18 EF.
The short life proteins of the liver, primarily prealbumin, were chosen as efficacy variables. No differences were observed between the two study groups with regard to changes in these variables during the postoperative period. Urea, nitrogen excretion and cumulative nitrogen balance were also measured. The results were similar for both groups.
The incidence of clinical adverse events was similar in both groups of patients. The majority of the observed adverse events were most likely related to the patients' basic disorder or to the surgical procedure (fever, dyspnoea, rupture of the wound, insufficiency of intestinal anastomosis, etc). The appearance of clinical symptoms such as nausea, vomiting, dizziness, etc. may possibly be related to the infusion of amino acid solutions besides being a frequent occurrence in the postoperative period, but the incidence of these events was not different in the two groups.

5.2 Pharmacokinetic Properties

Pharmacokinetics of dipeptides.

The two dipeptides glycylglutamine and glycyltyrosine are rapidly and quantitatively hydrolysed to their constituent amino acids when infused intravenously in animals and humans. Several tissues participate in the hydrolysis of the dipeptides, but the kidneys play the quantitatively most important role. The liver, skeletal muscle and intestine also participate in the clearance of the dipeptides. Finally, hydrolysis of the dipeptides also takes place in the plasma.
The half-life of the dipeptides is short, with a value of less than 30 minutes for glycylglutamine and less than 10 minutes for glycyltyrosine. For glycylglutamine, the volume of distribution approximated that of the blood volume and mean clearance was 91 mL/min. Less than 2% of the dipeptides were excreted unchanged in the urine.

5.3 Preclinical Safety Data

Genotoxicity.

The genotoxic potential of the dipeptides has not been investigated in vivo, however, assays of the dipeptides for gene mutations and chromosomal damage in vitro were negative. The genotoxic potential of Glamin has not been investigated.

Carcinogenicity.

The carcinogenic potential of Glamin or the individual dipeptides has not been investigated in animal studies.

6 Pharmaceutical Particulars

6.1 List of Excipients

Citric acid (2.53 g per 1000 mL), water for injections (to 1000 mL).

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

Glass bottle: 250 mL (AUST R 77749), 500 mL (AUST R 77750), 1000 mL (AUST R 77751).

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

CAS numbers.

Alanine: 56-41-7, arginine: 74-79-3, aspartic acid: 6899-03-2, glutamic acid: 56-86-0, glycylglutamine monohydrate: 13115-71-4, glycyltyrosine dihydrate: 658-79-7, histidine: 71-00-1, isoleucine: 73-32-5, leucine: 61-90-5, lysine acetate: 57282-49-2, methionine: 63-68-3, phenylalanine: 63-91-2, proline: 147-85-3, serine: 56-45-1, threonine: 72-19-5, tryptophan: 73-22-3, valine 72-18-4.

7 Medicine Schedule (Poisons Standard)

Unscheduled.

Summary Table of Changes