Product Monograph - Octalbin 25%
RECENT MAJOR LABEL CHANGES
Not applicable
TABLE OF CONTENTS
Sections or subsections that are not applicable at the time of authorization are not listed.
RECENT MAJOR LABEL CHANGES .......................................................................... 2
TABLE OF CONTENTS ................................................................................................ 2
PART I: HEALTH PROFESSIONAL INFORMATION ................................................... 4
1 INDICATIONS ..................................................................................................... 4
1.1 Pediatrics .................................................................................................. 4
1.2 Geriatrics .................................................................................................. 4
2 CONTRAINDICATIONS...................................................................................... 4
3 SERIOUS WARNINGS AND PRECAUTIONS BOX ........................................... 4
4 DOSAGE AND ADMINISTRATION .................................................................... 4
4.1 Dosing Considerations ............................................................................. 4
4.2 Recommended Dose and Dosage Adjustment ......................................... 5
4.4 Administration ........................................................................................... 5
4.5 Missed Dose ............................................................................................. 5
5 OVERDOSAGE .................................................................................................. 6
6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ............ 6
7 WARNINGS AND PRECAUTIONS .................................................................... 6
7.1 Special Populations .................................................................................. 8
7.1.1 Pregnant Women...................................................................................... 8
7.1.2 Breast-feeding .......................................................................................... 8
7.1.3 Pediatrics .................................................................................................. 8
7.1.4 Geriatrics ................................................................................................. 8
8 ADVERSE REACTIONS ..................................................................................... 9
8.1 Adverse Reaction Overview ..................................................................... 9
8.2 Clinical Trial Adverse Reactions ............................................................... 9
8.3 Less Common Clinical Trial Adverse Reactions ....................................... 9
8.4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data ...................................................................................... 9
8.5 Post-Market Adverse Reactions ............................................................... 9
9 DRUG INTERACTIONS .................................................................................... 10
9.2 Drug Interactions Overview ..................................................................... 10
9.3 Drug-Behavioural Interactions ................................................................ 10
9.5 Drug-Food Interactions ........................................................................... 10
9.6 Drug-Herb Interactions ............................................................................ 10
9.7 Drug-Laboratory Test Interactions .......................................................... 10
10 CLINICAL PHARMACOLOGY .......................................................................... 10
10.1 Mechanism of Action .............................................................................. 10
10.2 Pharmacodynamics ................................................................................ 10
10.3 Pharmacokinetics ................................................................................... 10
11 STORAGE, STABILITY AND DISPOSAL ........................................................ 11
12 SPECIAL HANDLING INSTRUCTIONS ........................................................... 11
PART II: SCIENTIFIC INFORMATION ........................................................................ 12
13 PHARMACEUTICAL INFORMATION .............................................................. 12
14 CLINICAL TRIALS ............................................................................................ 12
16 NON-CLINICAL TOXICOLOGY ........................................................................ 12
PATIENT MEDICATION INFORMATION .................................................................... 13
OCTALBIN 25%
Albumin (Human) 250 mg/mL
PART I: HEALTH PROFESSIONAL INFORMATION
1 INDICATIONS
Octalbin 25% (Albumin (Human) 250 mg/mL) is indicated for:
- 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, according to current therapeutic recommendations.
1.1 Pediatrics
Pediatrics (< 12 years of age): Data on the use of Octalbin 25% in children including premature babies are very limited. The product should only be administered to these individuals if the likely benefits clearly outweigh potential risks.
1.2 Geriatrics
Geriatrics (>65 yeas of age): No subgroup analysis was performed and therefore no safety or tolerability data regarding a geriatric population can be presented.
2 CONTRAINDICATIONS
Octalbin 25% is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.
3 SERIOUS WARNINGS AND PRECAUTIONS BOX
Serious Warnings and Precautions
| This product is prepared from large pools of human plasma, which may contain the causative agents of hepatitis and other viral diseases. The physician should discuss the risks and benefits of this product with the patient before prescribing or administering to the patient (see 7. WARNINGS AND PRECAUTIONS – General). |
4 DOSAGE AND ADMINISTRATION
4.1 Dosing Considerations
Human albumin should always be directly administered by the intravenous route. Octalbin 25% may also be diluted in an isotonic solution (e.g. 5% glucose or 0.9% sodium chloride).
The concentration of the albumin preparation, dosage and the infusion-rate should be adjusted to the patient's individual requirements.
4.2 Recommended Dose and Dosage Adjustment
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
This product is suitable for premature infants and dialysis patients.
The infusion rate should be adjusted according to the individual circumstances and the indication, but should normally not exceed 1 to 2 mL/minute.
In plasma exchange the infusion rate may be higher and should be adjusted to the rate of removal.
4.4 Administration
The solution should 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 product should be warmed to room or body temperature before use.
The solution should be clear or slightly opalescent. 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 infusion container has been opened the content should be used immediately. Any unused solution should be disposed of in accordance with local requirements.
Do not use after expiry date given on the label.
Solutions which have been frozen should not be used.
Do not begin administration more than four hours after the container has been entered.
Vials which are cracked or have been previously entered or damaged should not be used, as this may have allowed the entry of microorganisms.
The 25% solution contains no preservative.
Incompatibilities
Albumin solutions must not be diluted with water for injections as this may cause haemolysis in recipients.
4.5 Missed Dose
Not applicable because Octalbin 25% is administered in a hospital setting by health care professionals.
5 OVERDOSAGE
Hypervolaemia may occur if the dosage and rate of infusion 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.
For management of a suspected drug overdose, contact your regional poison control centre.
6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING
To help ensure the traceability of biologic products, including biosimilars, health professionals should recognise the importance of recording both the brand name and the non-proprietary (active ingredient) name as well as other product-specific identifiers such as the Drug Identification Number (DIN) and the batch/lot number of the product supplied.
Table 1 – Dosage Forms, Strengths, Composition and Packaging
Octalbin 25% is human albumin from human plasma source and it contains 250 mg/mL of protein, of which at least 96% is human albumin.
Octalbin 25% contains no preservative. Octalbin 25% is a clear, slightly viscous liquid; it is almost colorless or slightly yellow or green.
Nature and contents of container
Glass bottles are made of glass quality type II (Ph.Eur.) and are closed with bromobutyl rubber stoppers quality type I (Ph.Eur.).
Package sizes:
Single pack:
1 infusion bottle with 50 mL
1 infusion bottle with 100 mL
Multiple pack:
10 x 1 infusion bottle with 50 mL
10 x 1 infusion bottle with 100 mL
7 WARNINGS AND PRECAUTIONS
Please see 3 SERIOUS WARNINGS AND PRECAUTIONS BOX.
This product is prepared from large pools of human plasma. Thus, there is a possibility it may contain causative agents of viral or other undetermined diseases.
| Route of Administration | Dosage Form / Strength / Composition | Non-medicinal Ingredients |
| Intravenous use | Solution for infusion Each mL contains 250 mg protein, of which ≥ 96% is human albumin | 1000 mL solution contain: Aluminium max. 200 µg Caprylic acid max. 21 mmol N-acetyl-DL-tryptophan max. 21 mmol Potassium max. 2.0 mmol Sodium 142.5-157.5 mmol Water for injections ad 1000 mL |
General
Standard measure 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.
Albumin is a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extreme remote risk for transmission of viral diseases. A theoretical transmission of Creutzfeldt-Jakob Disease (CJD), including variant Creutzfeldt-Jakob Disease (vCJD), also is considered remote. No cases of transmission of viral diseases or CJD, including vCJD, have ever been identified for albumin.
Albumin manufactured to European Pharmacopoeia specifications by established processes has a reassuring viral safety record.
The physician should discuss the risks and benefits of the product with the patient, before prescribing or administering to the patient.
If allergic or anaphylactic-type reactions occur, the infusion should be stopped immediately and appropriate treatment instituted. In case of shock, the current medical standards for shock-treatment should be observed.
Albumin solutions must not be diluted with water for injection as this may cause haemolysis in recipients.
Individuals who receive infusions of blood or plasma products may develop signs and/or symptoms of some viral infections, particularly hepatitis C. In the interest of the patient, it is recommended that, whenever possible, every time that Octalbin 25% (Albumin (Human) 250 mg/mL) is administered to them, the name and batch number of the product is recorded.
Albumin solutions must not be used in patients at high risk of developing circulatory overload (e.g. congestive cardiac failure, renal insufficiency) or severe deficiency of oxygen carrying capacity (severe anemia).
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 25% 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.
Hypervolaemia may occur if the dosage and rate of infusion are not adjusted to the patients 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.
20-25% Human albumin solutions are relatively low in electrolytes compared to the 4-5% human albumin solutions. When albumin is given, the electrolyte status of the patient should be monitored (see section 4 DOSAGE AND ADMINISTRATION) and appropriate steps taken to restore or maintain the electrolyte balance.
Octalbin 25% contains 3.28-3.62 mg sodium and 0.078 mg potassium per mL solution (See 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING), which should be taken into consideration for patients on a controlled sodium or potassium intake.
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).
7.1 Special Populations
7.1.1 Pregnant Women
The safety of Octalbin 25% for use in human pregnancy has not been established in controlled clinical trials. While it is not known if it can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity, it should be given to a pregnant woman only if clearly needed.
No animal reproduction studies have been conducted with Octalbin 25%. However, human albumin is a normal constituent of human blood.
7.1.2 Breast-feeding
There is no information regarding the presence of Octalbin 25% in human milk, the effect on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Octalbin 25% and any potential adverse effects on the breastfed infant from Octalbin 25% or from the underlying maternal condition.
7.1.3 Pediatrics
Pediatrics (< 12 years of age):
Data on the use of Octalbin 25% in children including premature babies are very limited. The product should only be administered to these individuals if the likely benefits clearly outweigh potential risks.
7.1.4 Geriatrics
Geriatrics (> 65 years of age):
No subgroup analysis was performed and therefore no safety or tolerability data regarding a geriatric population can be presented.
8 ADVERSE REACTIONS
8.1 Adverse Reaction Overview
Adverse reactions for Octalbin 25% are rare. These reactions normally disappear rapidly when the infusion rate is slowed down or the infusion is stopped. In case of severe reactions, the infusion should be stopped and an appropriate treatment should be initiated.
8.2 Clinical Trial Adverse Reactions
Not applicable.
8.3 Less Common Clinical Trial Adverse Reactions
Not applicable.
8.4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data
There were no particular issues raised for any laboratory parameters in any of the published studies.
8.5 Post-Market Adverse Reactions
The following adverse reactions have been observed for human albumin during the post-marketing phase. Therefore, these reactions can also be expected for Octalbin 25%.
Table 2 – adverse reactions for human albumin observed during post-marketing phase
| System Organ Class | Rare (>1/10,000, <1/1,000) | Very rare (<1/10,000) |
| Immune system disorders | hypersensitivity | anaphylactic shock anaphylactic reaction |
| Psychiatric disorders | confusional state | |
| Nervous system disorders | headache | |
| Cardiac disorders | tachycardia bradycardia | |
| Vascular disorders | hypotension | hypertension flushing |
| Respiratory, thoracic and mediastinal disorders | dyspnoea | |
| Gastrointestinal disorders | nausea | |
| Skin and subcutaneous tissue disorders | urticaria angioneurotic edema rash erythematous hyperhidrosis pruritus | |
| General disorders and administration site conditions | pyrexia chills |
9 DRUG INTERACTIONS
9.2 Drug Interactions Overview
No specific interactions of human albumin with other medicinal products are known.
Human albumin solution must not be mixed with other medicinal products, whole blood and packed red cells.
9.3 Drug-Behavioural Interactions
No effects on ability to drive and use machines have been observed.
9.5 Drug-Food Interactions
Interactions with food have not been established.
9.6 Drug-Herb Interactions
Interactions with herbal products have not been established.
9.7 Drug-Laboratory Test Interactions
Interactions with laboratory tests have not been established.
10 CLINICAL PHARMACOLOGY
10.1 Mechanism of Action
Albumin is the predominant product of hepatic protein synthesis and one of the more abundant plasma proteins. Among its multiple physiologic roles that include binding and transport of molecules, free radical scavenging, inhibition of platelet function and antithrombotic effects, and effects on the capillary membrane permeability, human albumin plays an essential part in the generation of colloid-oncotic pressure.
10.2 Pharmacodynamics
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.
The most important physiological functions of human albumin result 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.
10.3 Pharmacokinetics
Under normal conditions the total exchangeable albumin pool is 4-5 g/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.
Under normal conditions, the average half-life of albumin is about 19 days. The balance between synthesis and breakdown is normally achieved by feed-back 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.
11 STORAGE, STABILITY AND DISPOSAL
Special precautions for storage:
Store and transport at +2 °C to +25 °C.
Store in the original container in order to protect from light.
Do not use after expiry date.
Do not freeze.
Keep out of the reach of children!
Any unused product or waste material should be disposed of in accordance with local requirements.
12 SPECIAL HANDLING INSTRUCTIONS
Please see section 4.4 Administration.
PART II: SCIENTIFIC INFORMATION
13 PHARMACEUTICAL INFORMATION
Drug Substance
Proper name: Octalbin 25%
Chemical name: Human Albumin
Molecular formula and molecular mass: not applicable
Structural formula: not applicable
Physicochemical properties: Human serum albumin (HSA) is a monomeric protein, made up only of amino acids without prosthetic or carbohydrate groups. Albumin has a high percentage of ionic amino acids, glutamic acid and lysine, which confer a relatively high solubility to the protein.
Product Characteristics
Octalbin 25% is a solution containing plasma proteins in a concentration of 250 mg/mL with a content of human albumin of at least 96%. It is manufactured according to the cold ethanol fractionation method.
Viral Inactivation
The plasma used for the manufacture of Octalbin 25% is obtained from collection centres that are inspected by national health authorities and audited by Octapharma.
The product is manufactured by the cold ethanol fractionation process followed by ultra- and diafiltration. The manufacturing process includes final container pasteurisation and an additional bulk pasteurisation at 60 ± 0.5°C for 10 – 11 hours. The Octalbin 25% manufacturing process provides a significant viral reduction in in vitro studies. These reductions are achieved through a combination of process steps including cold ethanol fractionation and final container pasteurisation.
14 CLINICAL TRIALS
Not applicable.
16 NON-CLINICAL TOXICOLOGY
No long-term animal studies have been performed to evaluate carcinogenic or mutagenic potential or whether Octalbin 25% affects fertility in males or females.
Albumin is a normal constituent of the human organism. In animals, single dose toxicity testing is of no relevance, since the high doses required would result in Albumin overload. Repeated dose toxicity testing, and embryo-fetal toxicity studies with albumin preparations are impracticable due to the induction of, and the interference with antibodies. Effects of the preparation on the immune system of new-born animals have not been studied.
Since the clinical experience does not provide any evidence of tumorigenic or mutagenic effects of Albumin, experimental studies, particularly in heterologous species, are not considered to be necessary.