Human albumin 20%, Solution for infusion Taj Pharma

Human albumin 20%, Solution for infusion

1. Name of the medicinal product

Human albumin 20%, solution for infusion Taj Pharma

2. Qualitative and quantitative composition

Human albumin 20% is a solution containing 200g/l of total protein of which at least 96% is human albumin.

One vial of 50 ml contains 10g of human albumin.

One vial of 100 ml contains 20g of human albumin.

Human albumin 20% is hyperoncotic to normal plasma.

Excipient with known effect:

Human albumin 20% contains approximately 3.2mg sodium per ml of solution (140 mmol/l).

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Solution for infusion.

A clear, slightly viscous liquid; it is almost colourless, yellow, amber or green.

4. Clinical particulars

4.1 Therapeutic indications

Restoration and maintenance of circulating blood volume where volume deficiency has been demonstrated, and use of a colloid is appropriate.

The choice of albumin rather than artificial colloid will depend on the clinical situation of the individual patient, based on official recommendations.

4.2 Posology and method of administration

The concentration of the albumin preparation, dosage and the infusion rate should be adjusted to the patient’s individual requirements.

Posology

The dose required depends on the size of the patient, the severity of trauma or illness and on continuing fluid and protein losses. Measures of adequacy of circulating volume and not plasma albumin levels should be used to determine the dose required.

If human albumin is to be administered, haemodynamic performance should be monitored regularly; this may include:

• arterial blood pressure and pulse rate
• central venous pressure
• pulmonary artery wedge pressure
• urine output
• electrolyte
• haematocrit / haemoglobin

Paediatric population

The posology in children and adolescents (0-18 years) should be adjusted to the patient’s individual requirements.

Method of administration

Human albumin can be directly administered by the intravenous route, or it can also be diluted in an isotonic solution (e.g. 5% glucose or 0.9 % sodium chloride).

The infusion rate should be adjusted according to the individual circumstances and the indication.

In plasma exchange the infusion rate should be adjusted to the rate of removal.

4.3 Contraindications

Hypersensitivity to albumin preparations or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Suspicion of allergic or anaphylactic type reactions requires immediate discontinuation of the infusion. In case of shock, standard medical treatment for shock should be implemented.

Albumin should be used with caution in conditions where hypervolaemia and its consequences or haemodilution could represent a special risk for the patient. Examples of such conditions are:

• decompensated cardiac insufficiency
• hypertension
• oesophageal varices
• pulmonary oedema
• haemorrhagic diathesis
• severe anaemia
• renal and post-renal anuria

The colloid-osmotic effect of human albumin 200g/l is approximately four times that of blood plasma. Therefore, when concentrated albumin is administered, care must be taken to assure adequate hydration of the patient. Patients should be monitored carefully to guard against circulatory overload and hyperhydration.

200–250g/l human albumin solutions are relatively low in electrolytes compared to the 40–50g/l human albumin solutions. When albumin is given, the electrolyte status of the patient should be monitored (see section 4.2) and appropriate steps taken to restore or maintain the electrolyte balance.

Albumin solutions must not be diluted with water for injections as this may cause haemolysis in recipients.

If comparatively large volumes are to be replaced, controls of coagulation and haematocrit are necessary. Care must be taken to ensure adequate substitution of other blood constituents (coagulation factors, electrolytes, platelets and erythrocytes).

Hypervolaemia may occur if the dosage and infusion rate are not adjusted to the patient’s circulatory situation. At the first clinical signs of cardiovascular overload (headache, dyspnoea, jugular vein congestion), or increased blood pressure, raised venous pressure and pulmonary oedema, the infusion is to be stopped immediately.

Human albumin 20% contains approximately 3.2mg sodium per ml of solution (140 mmol/l).

That should be taken into consideration for patients on a controlled sodium diet.

Transmissible agents

Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of viruses. Despite this, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens.There are no reports of virus transmissions with albumin manufactured to European Pharmacopoeia specifications by established processes.

It is strongly recommended that every time that Human albumin 20% is administered to a patient, the name and batch number of the product are recorded in order to maintain a link between the patient and the batch of the product.

4.5 Interaction with other medicinal products and other forms of interaction

No specific interactions of human albumin with other medicinal products are known.

4.6 Fertility, pregnancy and lactation

Pregnancy

No animal reproduction studies have been conducted with Human albumin 20%.

Its safety for use in human pregnancy has not been established in controlled clinical trials and therefore it should only be given with caution to pregnant women. However, clinical experience with albumin suggests that no harmful effects on the course of pregnancy, or on the foetus and the neonate are to be expected.

Breast-feeding

It is unknown whether Human albumin 20% is excreted in human milk. Since human albumin is a normal constituent of human blood, treatment of the nursing mother with Human albumin 20% is not expected to present a risk to the breastfed newborn/infant.

Fertility

No animal reproduction studies have been conducted with Human albumin 20%. However, human albumin is a normal constituent of human blood and harmful effects on fertility are not expected.

4.7 Effects on ability to drive and use machines

No effects on the ability to drive and use machines have been observed.

4.8 Undesirable effects

Summary of the safety profile

Mild reactions with human albumin solutions such as flush, urticaria, fever and nausea occur rarely. These reactions normally disappear rapidly when the infusion rate is slowed down or the infusion is stopped. Very rarely, severe allergic reactions such as anaphylactic shock may occur. In these cases, the infusion should be stopped immediately and an appropriate treatment should be initiated.

Tabulated list of adverse reactions

The summary table below presents the adverse reactions which have been observed with Human albumin during the post-marketing phase, according to the MedDRA system organ classification (SOC and Preferred Term Level).

As the post-marketing reporting of adverse reactions is voluntary and from a population of uncertain size, it is not possible to reliably estimate the frequency of these reactions.

Hence the frequency category “not known (cannot be estimated from the available data)” is used.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product.

For safety information with respect to transmissible agents, see section 4.4.

4.9 Overdose

Hypervolaemia may occur if the dosage and infusion rate are too high. At the first clinical signs of cardiovascular overload (headache, dyspnoea, jugular vein congestion) or increased blood pressure, raised central venous pressure and pulmonary oedema, the infusion should be stopped immediately and the patient’s haemodynamic parameters carefully monitored.

5. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: plasma substitutes and plasma protein fractions,

Human albumin accounts quantitatively for more than half of the total protein in the plasma and represents about 10% of the protein synthesis activity of the liver.

Physico-chemical data: human albumin 200g/l has a corresponding hyperoncotic effect.

The most important physiological functions of albumin results from its contribution to oncotic pressure of the blood and transport function. Albumin stabilises circulating blood volume and is a carrier of hormones, enzymes, medicinal products and toxins.

5.2 Pharmacokinetic properties

Distribution

Under normal conditions, the total exchangeable albumin pool is 4–5g/kg body weight, of which 40–45% is present intravascularly and 55–60% in the extravascular space. Increased capillary permeability will alter albumin kinetics and abnormal distribution may occur in conditions such as severe burns or septic shock.

Elimination

Under normal conditions, the average half-life of albumin is about 19 days. The balance between synthesis and breakdown is normally achieved by feedback regulation. Elimination is predominantly intracellular and due to lysosome proteases.

In healthy subjects, less than 10% of infused albumin leaves the intravascular compartment during the first 2 hours following infusion. There is considerable individual variation in the effect on plasma volume. In some patients the plasma volume can remain increased for some hours. However, in critically ill patients, albumin can leak out of the vascular space in substantial amounts at an unpredictable rate.

5.3 Preclinical safety data

Human albumin is a normal constituent of human plasma and acts like physiological albumin.

In animals, single dose toxicity testing is of little relevance and does not permit the evaluation of toxic or lethal doses or of a dose-effect relationship.

Repeated dose toxicity testing is impracticable due to the development of antibodies to heterologous protein in animal models.

To date, human albumin has not been reported to be associated with embryo-foetal toxicity, oncogenic or mutagenic potential.

No signs of acute toxicity have been described in animal models.

6. Pharmaceutical particulars

6.1 List of excipients

Sodium N-acetyltryptophanate 16 mmol/l

Sodium caprylate 16 mmol/l

Sodium chloride q.s.to a sodium content of 140 mmol/l

Water for injections q.s. to 1 litre

6.2 Incompatibilities

Human albumin must not be mixed with other medicinal products, whole blood and packed red cells.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

Do not store above 25 °C. Do not freeze. Keep the vial in the outer carton in order to protect from light.

6.5 Nature and contents of container

50 ml of solution in a single vial (glass type II) with a stopper (halogenated synthetic elastomer).

100 ml of solution in a single vial (glass type II) with a stopper (halogenated synthetic elastomer).

1 vial per pack (10g/50 ml, 20g/100 ml).

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

The solution can be directly administered by the intravenous route, or it can also be diluted in an isotonic solution (e.g. 5% glucose or 0.9 % sodium chloride).

Albumin solutions must not be diluted with water for injections as this may cause haemolysis in recipients.

If large volumes are administered, the product should be warmed to room or body temperature before use.

Do not use solutions which are cloudy or have deposits. This may indicate that the protein is unstable or that the solution has become contaminated.

Once the vial has been opened, the contents should be used immediately.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7. Manufactured By:
   Taj Pharmaceuticals Ltd.
   at: Plot. No. 220, Mahagujarat
   Industrial Estate, At & Post-Moraiya,
   Tal-Sanand, Dist- Ahmedabad Gujarat (India)

Human albumin 20%, Solution for infusion

Package leaflet: Information for the user

Human albumin

Read all of this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or healthcare professional.
• If you get any side effects, talk to your doctor or healthcare professional. This includes any possible side effects not listed in this leaflet.

What is in this leaflet:

1. What Human albumin is and what it is used for
   2. What you need to know before you are given Human albumin
   3. How to use Human albumin
   4. Possible side effects
   5. How to store Human albumin
   6. Contents of the pack and other information
2. What Human albumin is and what it is used for

What Human albumin is

Human albumin is a plasma substitute.

How Human albumin works

Albumin stabilises the circulating blood volume. It is a carrier of hormones, enzymes, medicines and toxins. The albumin protein in Human albumin is isolated from human blood plasma. Therefore the albumin works exactly as if it was your own protein.

What Human albumin is used for

Human albumin is used to restore and stabilise the circulating blood volume. It is normally used under intensive care situations, when your blood volume has decreased critically. This may be the case e.g.:

• due to severe loss of blood after an injury, or
• due to a large surface burn

The choice of using Human albumin will be made by your doctor. It will depend on your individual clinical situation.

2. What you need to know before you are given Human albumin

• Read this section carefully. The information given should be taken into consideration by you and your doctor before you are given Human albumin.

Do NOT use Human albumin

• If you are allergic (hypersensitive) to human albumin or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

• Talk to your doctor or healthcare professional before you are given Human albumin.

Which circumstances increase the risk of having side effects?

Your doctor or healthcare professional will take special care if an abnormal increase in blood volume (hypervolaemia) or blood dilution (haemodilution) could be dangerous for you. Examples of such conditions are:

• heart insufficiency which needs to be treated with medicines (decompensated cardiac insufficiency)
• high blood pressure (hypertension)
• expansion of the gullet vein (oesophageal varices)
• abnormal accumulation of liquid in the lung (pulmonary oedema)
• predisposition for bleeding (haemorrhagic diathesis)
• severe decrease of red blood cells (severe anaemia)
• severe decrease of urine excretion because of renal impairment or outflow impairment (renal and post-renal anuria)
  • Tell your doctor or healthcare professional before treatment if at least one of these conditions applies to you.

When stopping the infusion may be required?

• Allergic reactions (hypersensitivity reactions) may occur and may very rarely be severe enough to cause shock (see also section 4 ‘Possible side effects’).
  • Tell your doctor or healthcare professional immediately if you notice such reactions during the infusion of Human albumin. He or she will decide to stop the infusion completely and start the appropriate treatment.
• An abnormal increase in blood volume (hypervolaemia) may occur if the dosage and infusion rate are not adequately adjusted to your condition. This may lead to an overload of the heart and circulatory system (cardiovascular overload). First signs of such an overload are headache, breathing difficulty or swelling of your neck veins (jugular vein congestion).
  • Tell your doctor or healthcare professional immediately if you notice such signs. He or she will stop the infusion and monitor your circulation as necessary.

Information on safety with respect to infections

When medicines are made from human blood or plasma, certain measures are put in place to prevent infections being passed on to patients. These include:

• careful selection of blood and plasma donors to make sure those at risk of carrying infections are excluded,
• the testing of each donation and pools of plasma for signs of virus/infections.
• The inclusion of steps in the processing of the blood or plasma that can inactivate or remove viruses.

Despite these measures, when medicines prepared from human blood or plasma are administered, the possibility of passing on infection cannot be totally excluded. This also applies to any unknown or emerging viruses and other types of infections.

There are no reports of virus infections with albumin manufactured to European Pharmacopoeia requirements by established processes.

It is strongly recommended that every time you are given a dose of Human albumin the name and batch number of the product are recorded, in order to maintain a record of the batches used.

Other medicines and Human albumin

No specific interactions of Human albumin with other medicines are known.

• However, always tell your doctor or healthcare professional before treatment if you are taking, have recently taken or might take any other medicines.

Pregnancy, breast-feeding and fertility

• Tell your doctor or healthcare professional if you are pregnant, plan to become pregnant or are breast-feeding. Your doctor will decide whether you can receive Human albumin during your pregnancy or while you are breast-feeding.

The use of Human albumin in pregnant or breast-feeding women has not been studied separately. Nevertheless, medicines containing human albumin have been used in pregnant or breast-feeding women. The experience showed that no harmful effects on the course of pregnancy, or on the foetus and the newborn are to be expected.

Driving and using machines

No effects of Human albumin on the ability to drive and use machines have been observed.

Human albumin contains sodium

This medicine contains approximately 3.2 mg sodium per ml of solution (140 mmol/l).

Your doctor or healthcare professional will take that into consideration if you are on a controlled sodium diet.

3. How to use Human albumin

Human albumin is given to you by your doctor or healthcare professional.

It is intended only for infusion into your veins (intravenous infusion). The product should be warmed to room or body temperature before it is given.

Your doctor decides how much Human albumin you will receive. The amount and infusion rate depends on your individual requirements.

Your doctor or healthcare professional will regularly monitor important blood flow values like:

• your blood pressure,
• your pulse rate,
• your urine output,
• your blood tests.

These values are monitored to determine the right dose and infusion rate.

Human albumin 20% must not be mixed with other medicinal products (except dilution solvents such as 5% glucose and 0.9% sodium chloride) and blood-derived products.

If you are given more Human albumin than you should

Human albumin is administered under medical supervision only. An overdosage is therefore very unlikely to occur. An abnormal increase in blood volume (hypervolaemia) may occur if the dosage and infusion rate are too high. This may lead to an overload of the heart and circulatory system (cardiovascular overload).

First signs of such an overload include:

• headache,
• breathing difficulty,
• swelling of your neck veins (jugular vein congestion).
  • Tell your doctor or healthcare professional immediately if you notice such symptoms.

Your doctor or healthcare professional may also detect signs like

• an increased blood pressure,
• a raised central venous pressure,
• an abnormal accumulation of liquid in the lung (pulmonary oedema).

In all these cases, he or she will stop the infusion and monitor your circulation as necessary.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Such side effects may occur even when you have previously received Human albumin and had tolerated it well.

General experience with human albumin solutions showed that the following side effects may be observed.

Allergic reactions (hypersensitivity reactions) may occur and may very rarely (less than 1 in 10,000 persons treated) be severe enough to cause shock.

Symptoms of an allergic reaction may include any, some or many of the following:

• skin reactions, e.g. redness, itching, swelling, blistering, rash or hives (itchy bumps)
• difficulty breathing, e.g. wheezing, chest tightness, shortness of breath or cough
• swelling of the face, eyelids, lips, tongue or throat
• cold-like symptoms, e.g. stuffy or runny nose, sneezing, red, itchy, swollen or watery eyes
• headache, stomach ache, nausea, vomiting or diarrhoea.
  • Tell your doctor or healthcare professional immediately if you notice such reactions during the infusion of Human albumin. In this case, he or she will stop the infusion and start the appropriate treatment.

The following mild side effects may occur rarely (between 1 in 1,000 and 1 in 10,000 persons treated):

• flushing
• itchy rash (urticaria)
• fever
• nausea

They will normally disappear rapidly when the infusion is slowed down or the infusion is stopped.

The same side effects have been observed with Human albumin since the product is on the market. However, the exact frequency of these side effects is not known.

Reporting of side effects

If you get any side effects, talk to your doctor or healthcare professional. This includes any possible side effects not listed in this leaflet.

By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Human albumin

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the outer carton and the vial label after the abbreviation «EXP». The expiry date refers to the last day of that month.
• Once the vial has been opened, the contents should be used immediately.
• Do not store above 25 °C.
• Do not freeze.
• Keep the vial in the outer carton in order to protect from light.
• Do not use this medicine if you notice that the solution is cloudy or has particles.
• Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Human albumin contains

• The active substance is human albumin.

Human albumin 20% is a solution containing 200 g/l of total protein, of which at least 96% is human albumin.

One vial of 50 ml contains 10 g of human albumin.

One vial of 100 ml contains 20 g of human albumin.

• The other ingredients are sodium N-acetyltryptophanate, sodium caprylate, sodium chloride, and water for injections.

What Human albumin looks like and contents of the pack

Human albumin is a solution for infusion. The solution is clear and slightly viscous. It may be almost colourless or yellow, amber or green.

Pack sizes:

Human albumin 20%: 1 vial per pack (10 g/50 ml, 20 g/100 ml)

Not all pack sizes may be marketed.

7. Manufactured By:
   Taj Pharmaceuticals Ltd.
   at: Plot. No. 220, Mahagujarat
   Industrial Estate, At & Post-Moraiya,
   Tal-Sanand, Dist- Ahmedabad Gujarat (India)