ALUSTAL Pollen Extract of Five Grasses^®

MIMS Revision Date: 01 June 2025

1 Name of Medicine

Alustal Pollen Extract of Five Grasses (5G) (Dactylis glomerata/ Poa pratensis/ Lolium perenne/ Anthoxanthum odoratum/ Phleum pratense pollen extracts).

2 Qualitative and Quantitative Composition

Alustal is prepared from freeze dried allergen extracts adsorbed onto aluminium hydroxide gel. The freeze dried allergen extracts are prepared by ammonium bicarbonate extraction of the allergen source materials, e.g. pollen, mites. Specific allergen(s) are selected by the physician for specific immunotherapy treatment (SIT) for the individual patient.
Each 5 mL vial contains specific allergen extract(s) in suspension and are available in various concentrations. Different concentrations are identified by different coloured caps on the vials.
Yellow cap: 0.1 IR/mL.
Green cap: 1.0 IR/mL.
Blue cap: 10.0 IR/mL.
IR (index of reactivity). The IR unit has been defined to measure the allergenicity of an allergen extract. The allergen extract contains 100 IR/mL when, on a skin prick test using a Stallerpoint, it induces a wheal diameter of 7 mm in 30 patients sensitized to this allergen (geometric mean). The cutaneous reactivity of these patients is simultaneously demonstrated by a positive skin prick-test to 10 mg/mL histamine dihydrochloride. The IR unit of Stallergenes is specific and not comparable to the units used by other allergen manufacturers.
When the family does not contain any standardized reference extract, the value 100 IR/mL corresponds to an extract where the dilution ratio is established according to medical experience.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Suspension for injection.

4 Clinical Particulars

4.1 Therapeutic Indications

Alustal treatment is indicated for patients with type 1 allergy (Gell and Coombs classification), particularly presenting as seasonal or perennial rhinitis, conjunctivitis, rhinoconjunctivitis with or without associated asthma.

4.2 Dose and Method of Administration

The use of Alustal 5G should be supervised by a physician experienced in allergology and allergen immunotherapy (AIT). See Section 4.4 Special Warnings and Precautions for Use.
Treatment is given in two phases: an initiation phase with dose escalation (weekly injections);
a maintenance phase with constant dose (monthly injections).
AIT is more effective if treatment is initiated at an early age. Thus, in children AIT may be started from the age of 5 years. It should be administered to children or young adults as soon as it is justified by the severity of the allergic symptoms. When immunotherapy is contemplated for young children, consultation with a specialist paediatric immunologist/allergist is essential. The physician who administers the injections should be able to treat a systemic reaction appropriately. In adults aged over 50 years, AIT remains indicated in cases of recent sensitisation.
The dosage for children is the same as for adults. Because of the smaller size of children larger volumes of solution may produce excessive discomfort. Therefore in order to achieve the total dose required, the volume of the dose may need to be divided into more than one injection.
Dosage does not vary with age, but must be adjusted to the reactivity of the individual patient.
Duration of treatment. As a general rule, AIT with Alustal should be continued for between 3 and 5 years.
1. Initiation phase: dose escalation. The product is injected exclusively by the deep subcutaneous route, at progressively escalating dosage, at a rate of one injection per week up to the maximum tolerated, according to the following treatment schedule (Table 1).

Important note. This treatment schedule is a guideline only. It must be modified depending on the patient's condition and any reactions that occur. Ideally, AIT with pollen allergens should begin before pollen season.
2. Maintenance phase: constant dose. (Maintenance: 1 vial 10 IR/mL (blue cap)). The highest tolerated dose (max 0.8 mL) in the initial treatment course is then repeated at interval of two weeks, then monthly or at longer intervals, not exceeding 6 weeks, between successive injections. If the interval is longer, the dose should be readjusted. It should be remembered that the above treatment schedule is a guideline only. It must be modified depending on the patient's condition and any reactions that occur. When changing vials for a patient on maintenance therapy, the first dose of the new vial should be 50% of the last dose (i.e. last dose given at 0.8 mL of 10.0 IR/mL, new vial dose should be 0.4 mL of 10.0 IR/mL; then followed by regular monthly doses of 0.8 mL). For pollen allergens, it may be necessary to reduce the maintenance dosage by half during pollen season but only if reactions occur.
Important note. Administer maintenance therapy only after treatment with the initial allergen set has been completed and within 6 weeks of the previous final dose.
Method of administration. Before each injection:
the expiry date on the vial should be checked;
it should be confirmed that the vial to be used is the same as that prescribed (composition, patient's name, concentration). The vial should be shaken gently before the quantity to be injected is withdrawn;
the normal rules of asepsis should be observed;
disposable 1 mL "tuberculin" syringes with 1/100 graduations should be used;
the injection should be precisely the required dose.
Inject slowly by the deep subcutaneous route. Do not inject into a blood vessel or intramuscularly.
The patient should remain under medical supervision for 30 minutes after each injection.
Concomitant treatment with more than one allergen. As per guidelines, in case of treatment with more than one allergen concomitantly, the injections should be given in different locations. In order to evaluate possible allergic reactions caused by the specific allergen it is recommended to give the injections with a time interval of at least 30 minutes.
Factors that could trigger allergic reactions. Patients should be instructed to avoid factors that could trigger allergic reactions on the day of the injection such as: high-intensity physical exercise, hot baths, heavy meals and excessive alcohol consumption.
Infection and atopic dermatitis. In patients with acute febrile illness, inflammatory and infective diseases or clinical signs of chronic infection, subcutaneous immunotherapy (SCIT) should be postponed until the infection has resolved. In patients with worsened atopic dermatitis, SCIT should be postponed.

4.3 Contraindications

Refer to the patient verification table provided at the end of this document.
Hypersensitivity to any excipient (see Section 6.1 List of Excipients);
patients with active or poorly controlled autoimmune disease, immune defects, immunodeficiencies, immunosuppression or malignant neoplastic diseases with current disease relevance;
patients with severe, uncontrolled or unstable asthma (FEV₁ < 70% of predicted value) or severe exacerbation of asthma within the last 3 months;
initiation of allergen immunotherapy treatment during pregnancy (see Section 4.6 Fertility, Pregnancy and Lactation);
renal insufficiency patients on treatment with beta-blockers (see Section 4.4 Special Warnings and Precautions for Use);
patients with a bleeding tendency.

4.4 Special Warnings and Precautions for Use

Before starting treatment symptoms of allergy should be stabilised with appropriate symptomatic therapy if necessary.
Before considering immunotherapy for patients with asthma, establish serial baseline lung function values. If there has been a recent exacerbation of asthma, as assessed clinically and/or by measurement of peak expiratory flow rate (PEFR), treatment should be halted and restarted after symptomatic improvement.
Always ask the patient and record any local or systemic reaction that occurred after leaving the clinic after the previous injection. If necessary, adjust the dose of the next injection appropriately.
As systemic allergic reactions (that could be life-threatening when very severe) might occur, treatment must be performed in presence of or by a physician with experience in allergen immunotherapy and in conditions allowing immediate emergency treatment if necessary (including adrenaline).
Severe allergic reactions. As with any allergen immunotherapy, severe allergic reactions including systemic allergic reactions may occur.
Patients should be made aware of the signs and symptoms of severe allergic reactions. In case of severe allergic reactions, a physician has to be consulted immediately and the treatment should be discontinued.
Previous systemic allergic reaction to allergen immunotherapy. Initiation of SCIT in patients who have previously had a systemic allergic reaction to previous allergen immunotherapy should be carefully considered, and measures to treat potential reactions should be available.
Asthma. Asthma is a known risk factor for severe systemic allergic reactions. The asthma status should be carefully evaluated before each injection (see Section 4.3 Contraindications).
Patients with associated asthma should be controlled at the initiation and during all the duration of SCIT treatment. Patients with asthma must be supervised by a specialist with expertise and experience with the administration of immunotherapy to those with asthma.
In many patients with asthma lung function is worst in the morning and therefore in such patients it may be preferable to give the injection in the afternoon.
In case of a recent asthma attack that is confirmed clinically and/or by expiratory peak flow measurement, the treatment should be suspended and restarted after improvement and after the advice of a physician experienced in allergen immunotherapy.
Abrupt discontinuation of asthma controller medication after initiation of SCIT treatment is not recommended.
Patients with concomitant asthma should be informed of the need to seek medical attention immediately if their asthma deteriorates suddenly.
Cardiovascular diseases. Patients with cardiovascular disease may be at increased risk in case of systemic allergic reactions. This should be taken into consideration prior to initiating SCIT.
Beta-adrenergic blockers. Patients taking beta-adrenergic blockers may be unresponsive to the usual doses of adrenaline used to treat serious systemic reactions, including anaphylaxis. Specifically, beta-adrenergic blockers antagonize the cardiostimulating and bronchodilating effects of adrenaline.
If beta-adrenergic blockers are required and no effective substitute is available, treatment initiation should be evaluated carefully based on an individual risk/benefit assessment.
MAOIs, tricyclic antidepressants and COMT inhibitors. Allergen immunotherapy in patients treated with tricyclic antidepressants, mono amine oxidase inhibitors (MAOIs) or catechol-O-methyltransferase (COMT) inhibitors should be considered carefully as these treatments could potentiate the effect of adrenaline.
Local allergic reactions. In case of enlarged local adverse reactions (redness and/or swelling > 10 cm in diameter) occurring at the injection site, the dosing schemes can be temporarily adjusted.
When local adverse effects occur, premedication with an H₁-antihistamine can be used to reduce the frequency and severity of adverse reactions.
Autoimmune diseases in remission. Caution should be exercised when prescribing allergenic immunotherapy to patients with an autoimmune disorder including patient with autoimmune disorder in remission.
Respect of AIT good practices is absolutely necessary to avoid possible incidents that are linked to:
errors with the vials;
errors with the dose;
accidental intravascular injections;
modifications of the interval between 2 injections;
poor evaluation of patient's clinical condition.
Those risks should be considered before initiation of allergen immunotherapy.
This medicine contains 4 mg aluminium (5 mL vial). Risk of accumulation of aluminium into tissues (central nervous system, bones) should be kept in mind, especially in case of renal insufficiency.
Effects of long-term use of aluminium on immune system are unknown.
Concomitant administration of medicine containing aluminium should be avoided (e.g. anti-acid drugs).
Use in the elderly. No data available.
Paediatric use. No data available.
Effects on laboratory tests. No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No interaction studies have been performed.
No interactions were reported in clinical trials with Alustal 5 Grasses.
Concomitant therapy with symptomatic anti-allergic medications may increase the tolerance level of the patient to immunotherapy. This should be considered at discontinuation of such medications.
There are no data available on possible risks of simultaneous immunotherapy with other allergens during treatment with Alustal 5 Grasses.
Vaccines. Clinical experience concerning simultaneous vaccination during Alustal 5 Grasses treatment is missing. Vaccination may be given without Alustal 5 Grasses discontinuation after medical evaluation of the general condition of the patient.
The time interval between a SCIT injection and a vaccination should be at least 1 week.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility. There are no clinical data regarding the effect of Alustal 5 Grasses on fertility.
No animal fertility study was conducted with freeze dried extracts included in Alustal 5 Grasses. However no microscopic changes in male or female reproductive organs to indicate likely impairment of fertility were observed in a repeat-dose oral toxicity study with 5-grass pollen allergen extracts, in rats up to 1000 IR/kg/day.
Use in pregnancy. (Category B2)
No clinical data are available for the use of Alustal 5 Grasses in pregnant women.
No adverse effects on embryofetal development were observed with oral administration of 5-grass pollen extracts to pregnant rats and rabbits.
No animal studies were conducted to investigate reproductive toxicity of allergen extracts other than those of house dust mites (Dermatophagoides pteronyssinus and Dermatophagoides farinae) and 5 grasses.
The risk of systemic reaction occurrence could not be excluded, during initiation phase as well as maintenance phase.
In any case, allergen immunotherapy should not be initiated during pregnancy.
A close medical evaluation should assess the relevance of the continuation of the treatment during pregnancy.
Use in lactation. It is not known whether Alustal 5 Grasses is excreted in human breast milk.
No animal study was conducted to investigate the excretion of Alustal 5 Grasses into milk.
A risk to the newborns/infants cannot be excluded.
A decision must be made whether to discontinue breast-feeding or to discontinue Alustal 5 Grasses therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

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)

During treatment with Alustal 5 Grasses, patients are exposed to allergens that may cause injection site reactions and/or systemic allergic symptoms which can occur immediately after administration or be delayed.
Tolerance of a given dose in a patient may vary over time depending on the patient's condition and the environment.
Pre-treatment with anti-allergic agents (for example antihistamines) may reduce frequency and severity of adverse reactions.
Cases of delayed serum sickness-like syndrome including arthralgia, myalgia, urticaria, nausea, adenopathy and fever can occur. Inform patients of the associated signs and symptoms and discontinue therapy should these occur.
Concomitant administration of allergy symptomatic drugs (such as antihistamines) may be used to improve the tolerance of allergen immunotherapy.
Tabulated summary of adverse reactions. Tables 2 and 3 of adverse reactions are based on data from solicited reporting in 529 patients enrolled in clinical studies with frequencies as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100).

As with all forms of hyposensitisation therapy, local and/or systemic reactions may occur. Injections of Alustal may be associated with some itching and redness at the injection site. Prolonged pain or pain radiating up the arm is usually the result of intramuscular injection. The tolerated dose is not necessarily constant, but may vary over time, depending on the individual's specific reactivity and environment.
Generally, injection site reactions do not necessitate modification of the therapeutic scheme (see Section 4.4 Special Warnings and Precautions for Use).
Description of selected adverse reactions. As with any allergen immunotherapy, allergic reactions including anaphylactic reactions (i.e. acute onset of an illness with involvement of the skin, mucosal tissue, or both, respiratory compromise, persistent gastrointestinal symptoms, or reduced blood pressure and/or associated symptoms) have been reported. Cases of anaphylactic shock with sudden circulatory collapse requiring rapid administration of adrenaline can occur. Inform patients of the associated signs and symptoms and have them seek immediate medical care and discontinue therapy should these occur. Treatment should only be resumed at the instruction of a physician. (See Table 4).
In any case, a patient should inform his physician of the occurrence of undesirable effect while receiving this medicine.
Paediatric population. Clinical data in children 5 years of age and older are limited. Safety data do not indicate a greater risk in children older than 5 years compared to adults (see Section 4.2 Dose and Method of Administration).
Management of adverse reactions. Local reactions. Skin reactions due to aluminium hydroxide have been reported. Some regress spontaneously, while others, much more rarely, can progress to the formation of subcutaneous nodules. Local reactions (> 2 to 3 cm in diameter) with erythema, oedema and pruritus are relatively common, and do not invariably necessitate modification of the treatment schedule. However, they may still act as a reminder that caution is required.
A major local reaction (≥ 5 cm in diameter) should be treated with an oral antihistamine. Supervision of the patient should be extended, reduce the next dose to that previously tolerated. If necessary, increase the subsequent doses by smaller increments. Another dose should never be given until all local reaction resulting from the previous dose has disappeared.
Discontinue injections if reaction size increases.
Other reactions. Immediate type reactions. A patient experiencing asthma after an injection must be observed until stable.
If an asthma attack occurs after an injection, bronchodilators must be used, if necessary together with a parenteral corticosteroid.
Systemic reactions (pruritus, giant urticaria or angioedema) should be treated by intramuscular injection of 0.5 to 1 mL of 1/1000 epinephrine (adrenaline), if necessary together with an intravenous corticosteroid. In view of the possibility of progression to shock, intensive and prolonged monitoring in a hospital setting is required.
Laryngeal dyspnoea should also be treated with intramuscular injection of epinephrine (adrenaline); admission to hospital is advisable.
In case of anaphylactic shock, the treatment should be administered as in an emergency and the patient should be admitted to a specialised unit (see Anaphylaxis, below).
Severe delayed reactions. A serum sickness type of reaction may occur, with arthralgia, myalgia, urticarial rashes, nausea, lymphadenopathy and fever. This is extremely rare, however, SIT should be discontinued if any of these occur.
Anaphylaxis. Anaphylactic shock consists of some of the following: widespread urticaria, angioedema of the face and glottis, pallor, cough, wheezing, bronchospasm, faintness and hypotension, bradycardia, hyperemesis, shock.
i. Lay patient flat and elevate the legs. Treat immediately.
ii. Give 0.5 mL 1/1000 epinephrine (adrenaline) intramuscularly near the injection site at once. If necessary, repeat 1/1000 epinephrine (adrenaline) intramuscularly at 3-5 minute intervals to a maximum of 2.0 mL in 15 minutes.
iii. Ensure maintenance of adequate airway.
iv. Give antihistamine.
v. If necessary use full supportive measures such as, intravenous saline or plasma expanders for hypotension, oxygen, external cardiac massage.
vi. If bronchospasm is severe, isoprenaline sulphate or salbutamol inhaler may also be used and, if necessary, 10-20 mL of Aminophylline Injection BP by slow intravenous injection at a rate of 2 mL/minute.
vii. A parenteral steroid such as 200-600 mg Hydrocortisone Injection BP, intravenously, may help to prevent persistent bronchospasm.
viii. Patients experiencing an anaphylaxis reaction should be admitted to hospital for close monitoring for at least 24 hours.
Stop treatment in patients with severe reactions.
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

In case of injection of a dose higher than the prescribed one, the risk and severity of undesirable reaction might be increased.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: V (various); C1 allergy (desensitization); P1 allergens and antigens.
ATC classification: V01.
The following biological changes have been demonstrated:
Appearance of specific antibodies (IgG) which act as blocking antibodies;
Reduction of specific plasma IgE levels in some cases;
Change in the behaviour of cells involved in allergic reaction;
Favourable change in TH2 and TH1 lymphocyte activities, leading to the production of cytokines (decrease in IL-4 and increase in IFNγ) that regulate IgE production.
At the same time specific immunotherapy stimulates an immune response which is maintained over long periods by immunological memory.
AIT acts directly upon the patient's immune system, providing lasting hyposensitisation and preventing progression of the allergy to more severe forms.
Mechanism of action. The precise mechanism of AIT is not known.
Clinical trials. No data available.

5.2 Pharmacokinetic Properties

No data available.

5.3 Preclinical Safety Data

Genotoxicity. No data available.
Carcinogenicity. No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Aluminium hydroxide hydrate, sodium chloride, phenol, mannitol and water for injections.

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 at 2-8°C. (Refrigerate. Do not freeze.).
The vial may be stored for up to 24 weeks opened. Do not use after the expiry date.

6.5 Nature and Contents of Container

Initial treatment set: 3 vials, each vial containing either 0.1, 1.0 and 10.0 IR/mL.
Maintenance: a single vial containing 10.0 IR/mL.
Available concentrations: vial containing 5 mL of suspension.
Yellow cap: 0.1 IR/mL.
Green cap: 1.0 IR/mL.
Blue cap: 10.0 IR/mL.
The ARTG details for the Alustal Five grasses are:
Alustal Pollen Extract of Five Grasses Initial Treatment injection suspension vial composite pack - AUST R 132848.
Alustal Pollen Extract of Five Grasses Maintenance 10 IR/mL injection suspension vial - AUST R 132847.
See Table 5.

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

Chemical structure. No data available.
CAS number. No data available.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine - S4.

Date of First Approval

03 October 2006

Date of Revision

10 April 2025

Summary Table of Changes