Phostal

CHARACTERISTICS OF THE MEDICINAL PRODUCT

1. NAME OF THE MEDICINAL PRODUCT

PHOSTALPlant allergen extracts
PHOSTALAnimal allergen extracts
PHOSTALHouse dust mite allergen extracts
PHOSTALFungal allergen extracts (mold fungi, dermatophytes, yeast)
PHOSTALMixtures of allergen extracts (of plant, animal, mite, and fungal origin)
0.01 IR or IC/ml; 0.1 IR or IC/ml; 1 IR or IC/ml; 10 IR or IC/ml
Suspension for injection

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

The active substance consists of allergen extracts or their mixtures in combination with mannitol. The amount of mannitol does not exceed 40 mg/ml.
1 vial (5 ml) of the suspension contains allergen extracts (according to Annex 1) at a concentration of:
0.01; 0.1; 1; 10 IR*/ml (standardized allergen extract)
or
0.01; 0.1; 1; 10 IC**/ml (non-standardized allergen extract)
The qualitative composition of the active substance can be individually tailored for the patient within the range of allergens listed in Annex 1.
A full list of excipients, see section 6.1.
* IR (reactivity index): the allergen extract has an activity equal to 100 IR/ml if, in a prick test using a Stallerpoint needle, it causes the formation of a wheal with a diameter of 7 mm (geometric mean) in 30 individuals sensitized to the given allergen.
In addition, the sensitivity of the tested individuals is confirmed by a positive reaction to 9% codeine phosphate or 10 mg/ml histamine dihydrochloride in a prick test.
** IC (concentration index): the allergen extract has an activity equal to 100 IC/ml when its concentration corresponds to the concentration of 100 IR of the reference, standardized allergen belonging to the same group.
If there is no standardized extract for a given family of allergens, the value of 100 IC/ml corresponds to the degree of dilution determined based on clinical experience.

3. PHARMACEUTICAL FORM

Suspension for injection
A white or slightly yellow-brown suspension, depending on the type of allergen and its concentration

4. CLINICAL PARTICULARS

4.1 Therapeutic Indications

Allergic diseases of a seasonal or perennial nature (Type I allergy according to the Gell and Coombs classification), manifested by rhinitis, conjunctivitis, rhinoconjunctivitis, or asthma (of mild to moderate severity).

4.2 Posology and Method of Administration

The use of allergen immunotherapy should be considered in both adult and pediatric patients, on the explicit indication of a doctor. Specific immunotherapy is more effective the earlier it is started. Treatment can be initiated in children from the age of 5.
The dose does not depend on age, but on the degree of individual reactivity of the patient.
Treatment is divided into two stages:

• Basic treatment - with gradual dose increase;
• Maintenance treatment - using a constant dose.

In the case of seasonal allergies, it is recommended to start therapy 3-4 months before the pollen season.
In the case of perennial allergies, it is recommended to continue treatment throughout the year.
Before each administration of this medicinal product, it is necessary:

• to carefully check the information on the vial (patient's name, composition, concentration, expiry date),
• to shake the vial before withdrawing the suspension,
• to follow the rules of asepsis during the injection,
• to use single-dose tuberculin syringes with a capacity of 1 ml, scaled according to the 1/100 scale,
• to measure the dose very accurately.

The patient should remain under close medical supervision for 30 minutes after the injection.
On the day of the injection, the patient should avoid physical exertion.
Basic treatment with dose increase
This medicinal product is administered deep subcutaneously, once a week.
The dose should be gradually increased until the maintenance dose (the maximum dose well tolerated) is reached, in accordance with the following scheme:

The above dosing scheme should be considered as a guideline and example of treatment. Treatment can be modified depending on the patient's condition and their reaction to treatment.
Maintenance treatment - constant dose
The maximum, well-tolerated dose should be repeated every 15 days, and then every month or less frequently. The interval between injections should not exceed 6 weeks. If the time between injections is longer than 6 weeks, the dose should be reduced.
It is recommended to reduce the dose by half if a new vial is started and possibly during the pollen season.
Duration of treatment
Usually, desensitization treatment is used for 3 to 5 years.
In the event of no significant improvement in symptoms after one year (perennial allergy) or after the first pollen season (seasonal allergy), the treatment scheme should be re-evaluated.
Discontinuation of treatment
In the event of treatment discontinuation or extension of the interval between two injections (not related to adverse effects), according to clinical experience after the product was introduced to the market, the following scheme should be followed:

Break in treatment from

Treatment stage Last injection dose

2 weeks
continue basic treatment with the last used dose
2 weeks to 1 month
resume treatment from 0.1 ml of the vial with the same concentration and continue basic treatment

Basic treatment

longer than 1 month
resume basic treatment using 10 times lower concentration (if possible*), and then continue basic treatment
shorter than 6 weeks
continue treatment with the last dose (at the same concentration

Maintenance treatment

restart basic treatment from 0.1 ml of the 1 IR/ml (or 1 IC/ml) vial until the maximum tolerated dose is reached. Then, continue maintenance treatment.
6 weeks to 6 months
* For patients treated with the lowest concentration suspension, basic treatment should be restarted with the suspension of the same concentration.

4.3 Contraindications

• Hypersensitivity to any of the excipients listed in section 6.1
• Uncontrolled or severe asthma (FEV1 <70% of the target value)
• Malignant disease
• Immunodeficiency or active autoimmune disease

4.4 Special Warnings and Precautions for Use

Medicinal products for desensitization should only be used by specialist allergists with experience in desensitization treatment.
Before each administration of this product, it should be ensured that an appropriate resuscitation set (containing adrenaline) is available due to the possibility of systemic allergic reactions, including life-threatening anaphylactic shock.
Before starting treatment, it is necessary to stabilize the symptoms of allergy using appropriate symptomatic treatment, if necessary.
Caution should be exercised when using allergen immunotherapy in patients taking tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs).
Caution should be exercised when starting desensitization treatment with the PHOSTAL product in patients taking beta-blockers, as they may antagonize the action of epinephrine. In the event of severe allergic reactions in patients taking beta-blockers, the action of epinephrine may be less effective.
Patient should be informed that in the event of any adverse effects after injection, such as severe itching of the hands and soles of the feet, urticaria, swelling of the mouth, throat swelling causing difficulty in swallowing and breathing, or changes in voice, nausea, and vomiting, they should immediately contact their doctor.
In the event of fever or an asthma attack that occurred recently and was clinically confirmed and/or measured by peak expiratory flow, treatment should be discontinued and restarted after consultation with the attending physician.
Before administering the product, it should be confirmed that a resuscitation set containing adrenaline, intravenously administered corticosteroids, antihistamines, and beta-adrenergic agents is available.
It is necessary to strictly follow the rules of good practice for specific immunotherapy in order to avoid possible errors related to errors in vial and dose selection, accidental intravenous administration, and changes in the intervals between injections.
PHOSTAL contains 45 mg of sodium chloride per vial (5 ml vial), which should be taken into account when administering to patients on a sodium-restricted diet, especially in children.

4.5 Interaction with Other Medicinal Products and Other Forms of Interaction

No interaction studies have been conducted with other drugs.
No interactions have been reported in clinical trials in which PHOSTAL was used.
Before starting treatment, it is necessary to consider the need to use epinephrine in the event of severe allergic reactions. In patients taking tricyclic antidepressants or monoamine oxidase inhibitors (MAOIs), there is a higher risk of adverse effects due to the use of epinephrine, even with a fatal outcome.
There is no clinical experience regarding concurrent prophylactic vaccination during treatment with PHOSTAL.
Prophylactic vaccination can be performed during maintenance treatment. It is recommended that the interval between injections be at least 1 week, except in life-threatening situations.

4.6 Fertility, Pregnancy and Lactation

Pregnancy
There are no clinical data on the use of PHOSTAL in pregnant women.
No studies have been conducted on the toxic effects on fertility in animals.
It cannot be excluded that systemic reactions may occur during initial and maintenance treatment.
Immunotherapy should not be initiated during pregnancy under any circumstances.
The decision to continue treatment is made by the doctor.
Breast-feeding
It is not known whether PHOSTAL passes into breast milk.
No studies have been conducted on the passage of PHOSTAL into breast milk in animals.
It cannot be excluded that there is a risk to newborns or infants.
The decision to discontinue breast-feeding or discontinue treatment should be made taking into account the benefits of breast-feeding for the child and the benefits of treatment for the mother.
Fertility
No fertility studies have been conducted with PHOSTAL.

4.7 Effects on Ability to Drive and Use Machines

PHOSTAL does not affect the ability to drive and use machines.

• 4.8

Undesirable Effects

During treatment, patients are exposed to allergens that can cause local and/or systemic reactions.
As with any allergen immunotherapy, severe allergic reactions, including anaphylaxis (e.g., acute onset of skin and mucosal tissue involvement, or both, respiratory failure, persistent gastrointestinal symptoms, or hypotension and associated symptoms), have been reported. Anaphylactic shock with cardiovascular collapse requiring the use of adrenaline may occur. Patients should be informed about the associated symptoms and the need for immediate medical attention and discontinuation of treatment in the event of their occurrence. Treatment should only be resumed on the doctor's instructions.
Tolerance to a given dose by the patient may change over time, depending on the patient's health and environment.
Pretreatment with antiallergic products (e.g., antihistamines) may reduce the frequency and severity of adverse effects.
Delayed symptoms of serum sickness may occur: joint pain, muscle pain, urticaria, nausea, lymphadenopathy, and fever. Patients should be informed about the associated subjective and objective symptoms and treatment should be discontinued in the event of their occurrence.
The following table presents adverse effects reported in clinical trials in which 369 patients participated. The frequency of adverse effects was defined as follows: very common (≥1/10), common (≥1/100 to <1>

Most reactions at the injection site do not require a change in the treatment scheme.
Additionally, after the product was introduced to the market, the following adverse effects have been reported spontaneously (frequency not known): angioedema, laryngeal edema, wheezing, vomiting, malaise, injection site granuloma, generalized erythema, arthralgia, myalgia, serum sickness, lymphadenopathy, fever, and anaphylactic shock.

Reporting of Suspected Adverse Reactions

After the medicinal product has been authorized, it is important to report any suspected adverse reactions. This allows for the continuous monitoring of the benefit/risk ratio of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Department of Adverse Reaction Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products:
Aleja Jerozolimskie 181C
02-222 Warsaw, Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309, e-mail: [email protected] Adverse reactions can also be reported to the marketing authorization holder.

• Adverse reactions should be reported using the Adverse Reaction Reporting Form, which can be found on the website of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products (https://www.urpl.gov.pl). The completed form should be sent to the address above.

4.8 Overdose

In the event of injection of a dose higher than recommended, the risk and severity of adverse effects may increase.
In the event of overdose, the observation period for the patient should be extended.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic Properties

Therapeutic group: allergen extracts
ATC code: V01AA
The exact mechanism of action of allergens administered during specific immunotherapy is not fully understood.
It has been shown that immunotherapy induces changes in the response of T lymphocytes, increases the level of specific IgG4 and/or IgG1 antibodies, and sometimes IgA, and reduces the level of specific IgE antibodies. Early and probably also late immune response is characterized by changes in T lymphocyte activity.

5.2 Pharmacokinetic Properties

There are no available data on pharmacokinetic properties in animals and humans.

5.3 Preclinical Safety Data

Non-clinical data, obtained from conventional toxicity studies after repeated administration and genotoxicity studies, do not reveal any special hazard for humans.
Long-term subcutaneous administration of high doses of mite extracts contained in the PHOSTAL product did not show toxic effects in rats. Genotoxicity studies conducted with several extracts contained in the PHOSTAL product did not show any mutagenic, aneugenic, or clastogenic effects.

6 PHARMACEUTICAL PARTICULARS

6.1 List of Excipients

Calcium phosphate
Sodium chloride
Phenol
Glycerol
Water for injections

6.2 Incompatibilities

None known.

6.3 Shelf Life

1 year

6.4 Special Precautions for Storage

Store in a refrigerator (2°C - 8°C).
Do not freeze!

6.5 Nature and Contents of Container

Vials made of type I glass with chlorobutyl rubber stoppers and colored caps (different color for each concentration).
Basic treatment set:
4 vials of 5 ml (concentration from 0.01 IR/ml to 10 IR/ml or from 0.01 IC/ml to 10 IC/ml)
gray cap
concentration: 0.01 IR/ml or 0.01 IC/ml
yellow cap
concentration: 0.1 IR/ml or 0.1 IC/ml
green cap
concentration: 1 IR/ml or 1 IC/ml
blue cap
concentration: 10 IR/ml or 10 IC/ml
Maintenance treatment set:
1 vial of 5 ml (concentration 10 IR/ml or 10 IC/ml) - blue cap

6.6 Special Precautions for Disposal

No special requirements.
Any unused product or waste material should be disposed of in accordance with local regulations.

7 MARKETING AUTHORIZATION HOLDER

RESPONSIBLE FOR BATCH RELEASE

STALLERGENES
6 rue Alexis de Tocqueville
92160 Antony, France

8 MARKETING AUTHORIZATION NUMBERS

PHOSTAL - Plant allergen extracts (plant pollen)
8201
PHOSTAL - Animal allergen extracts
8202
PHOSTAL - House dust mite allergen extracts
8203
PHOSTAL - Fungal allergen extracts (mold fungi, dermatophytes, yeast)
8204
PHOSTAL - Mixtures of allergen extracts (of plant, animal, mite, and fungal origin)
8205

9 DATE OF FIRST AUTHORIZATION/RENEWAL OF THE AUTHORIZATION

Date of first authorization: July 14, 2000
Date of last renewal: August 31, 2010 (8201, 8202, 8203, 8205); September 9, 2010 (8204)

10 DATE OF REVISION OF THE TEXT

CHARACTERISTICS OF THE MEDICINAL PRODUCT

PHOSTAL ANNEX 1

I. PLANT ALLERGEN EXTRACTS

WEEDS

641 Alfalfa (Medicago sativa)
IC/ml
664 Dandelion (Taraxacum vulgare)
IC/ml
623 Fat hen (Chenopodium album)
IC/ml
673 Goldenrod (Solidago canadensis)
IC/ml
636 Hop (Humulus lupulus)
IC/ml
605 Mugwort (Artemisia vulgaris)
IR/ml
646 Black mustard (Brassica nigra)
IC/ml
654 Nettle (Urtica dioica)
IC/ml
643 Ox-eye daisy (Chrysanthemum leucanthemum)
IC/ml
665 Plantain (Plantago)
IC/ml
604 Ragweed (Ambrosia elatior)
IR/ml
625 Oilseed rape (Brassica oleifera)
IC/ml
710 Russian thistle (Salsola kali)
IC/ml
655 Sorrel (Rumex acetosa)
IC/ml
678 Sunflower (Helianthus annus)
IC/ml
657 Parietaria (Parietaria officinalis)
IR/ml

GRASSES

601 Red fescue (Agrostis vulgaris)
IC/ml
705 Bermuda grass (Cynodon dactylon)
IR/ml
627 Orchard grass (Dactylis glomerata)
IR/ml
624 Couch grass (Agropyron repens)
IC/ml
630 Meadow fescue (Festuca elatior)
IC/ml
658 Meadow grass (Poa pratensis)
IR/ml
638 Perennial ryegrass (Lolium perenne)
IR/ml
631 Sweet vernal grass (Anthoxantum odoratum)
IR/ml
661 Timothy grass (Phleum pratense)
IR/ml
637 Yorkshire fog (Holcus lanatus)
IC/ml

CEREALS

652 Barley (Hordeum vulgare)
IC/ml
642 Maize (Zea mays)
IC/ml
610 Oat (Avena sativa)
IC/ml
671 Rye (Secale cereale)
IR/ml
614 Wheat (Triticum vulgare)
IC/ml
106 Wheat flour
IC/ml

TREES

609 Alder (Alnus glutinosa)
IR/ml
632 Ash (Fraxinus excelsior)
IC/ml
635 Beech (Fagus sylvatica)
IC/ml
615 Birch (Betula alba)
IR/ml
620 Chestnut (Castanea vulgaris)
IC/ml
626 Cypress (Cupressus sempervirens)
IC/ml
675 Elder (Sambucus nigra)
IC/ml
653 Elm (Ulmus campestris)
IC/ml
667 Robinia (Robinia pseudoacacia)
IC/ml
649 Hazel (Corylus avellana)
IR/ml
619 Hornbeam (Carpinus betulus)
IR/ml
644 Horse chestnut (Aesculus hippocastanum)
IC/ml
634 Juniper (Juniperus communis)
IC/ml
677 Lime (Tilia platyphyllos)
IC/ml
629 Sycamore (Acer pseudoplatanus)
IC/ml
645 Silver fir (Abies alba)
IC/ml
647 White mulberry (Morus alba)
IC/ml
621 English oak (Quercus robur)
IC/ml
651 Olive tree (Olea europea)
IR/ml
662 Scots pine (Pinus sylvestris)
IC/ml
666 Plane tree (Platanus vulgaris)
IC/ml
659 White poplar (Populus alba)
IC/ml
680 Privet (Ligustrum vulgare)
IC/ml
650 Walnut (Juglans regia)
IC/ml
669 White willow (Salix caprea)
IC/ml

TOBACCO

904 Tobacco (leaves)
IC/ml
II. ANIMAL ALLERGEN EXTRACTS(dander, epithelium, insects)

ANIMALS

507 Cat
IR/ml
509 Dog
IC/ml
508 Goat
IC/ml
510 Guinea pig
IC/ml
511 Hamster
IC/ml
516 Horse
IC/ml
512 Rabbit
IC/ml
505 Wool
IC/ml

INSECTS

301 Cockroach
IC/ml
303 Grain weevil
IC/ml
310 Horsefly
IC/ml
307 Mosquito
IC/ml

III. HOUSE DUST MITE ALLERGEN EXTRACTS

325 Acarus siro
IC/ml
314 Dermatophagoides farinae
IR/ml
315 Dermatophagoides pteronyssinus
IR/ml
326 Euroglyphus maynei
IC/ml
324 Glycyphagus domesticus
IC/ml
317 Lepidoglyphus destructor
IC/ml
318 Tyrophagus putrescentiae
IC/ml
IV. FUNGAL ALLERGEN EXTRACTS(mold fungi, yeast, dermatophytes)
402 Botrytis cinerea
IC/ml
403 Candida albicans
IC/ml
407 Chaetomium globosum
IC/ml
409 Epicoccum
IC/ml
410 Epidermophyton
IC/ml
411 Fusarium
IC/ml
413 Helminthosporium
IC/ml
447 Merulius lacrymans
IC/ml
417 Mucor racemosus
IC/ml
425 Pullularia pullulans
IC/ml
426 Rhizopus nigricans
IC/ml
432 Stemphylium botryosum
IC/ml
435 Trichophyton
IC/ml
405 Trichothecium roseum (Cephalothecium)
IC/ml

V. MIXTURES OF ALLERGEN EXTRACTS * of animal origin

506 Feather mixture (duck, goose, chicken)
IC/ml
* of plant origin
a) weeds
719 Mixture I - Compositae (Goldenrod, Dandelion, Ragweed, Ox-eye-daisy) IC/ml
714 Mixture II - Chenopodiaceae (Fat hen, Rough pigweed)
IC/ml
706 Mixture III - Weed mixtures (Alfalfa, Red clover, Mustard, Nettle, Sorrel) IC/ml
b) grasses
701 3 grasses- (Orchard grass, Perennial ryegrass, Timothy grass)
IR/ml
688 5 grasses- (Orchard grass, Meadow grass, Perennial ryegrass, Sweet vernal grass, Timothy grass)
IR/ml
689 12 grasses- (Red fescue, Bermuda grass, Bromus, Orchard grass, Meadow fescue, Meadow grass, Perennial ryegrass, Sweet vernal grass, Timothy grass, Wild oats, Yorkshire fog)
IR/ml
690 5 grasses/4 cereals- (Orchard grass, Meadow grass, Perennial ryegrass, Sweet vernal grass, Timothy grass)/(Barley, Maize, Oat, Wheat)
IR/ml
687 4 cereals- (Barley, Maize, Oat, Wheat)
IR/ml
c) trees
702 Betulaceae (Alder, Birch, Hazel, Hornbeam)
IR/ml
696 Fagaceae (Beech, Chestnut, Oak)
IC/ml
716 Cupressaceae (Cypress, Juniper)
IC/ml
715 Oleaceae (Ash, Olive tree, Privet)
IC/ml
717 Salicaceae (Poplar, Willow)
IC/ml
718 Tree mixture (Sycamore, Horse chestnut, Plane tree, Robinia, Lime)
IC/ml
917 Wood dust (Oak, Beech, Cherry, Pine)
IC/ml
* mites
350 D. pteronyssinus + D. farinae
IR/ml
330 Storage mites (Acarus siro, Glycyphagus domesticus, Lepidoglyphus destructor, Tyrophagus putrescentiae)
IC/ml
* fungi
400 Alternaria (alternata, longipes)
IC/ml
414 Cladosporium (cladosporoides, herbarum)
IC/ml
401 Aspergillus (fumigatus, nidulans, niger)
IC/ml
422 Penicillium (digitatum, expansum, notatum)
IC/ml
445 Yeast mixture (Saccharomyces cerevisiae, minor)
IC/ml
446 Corn smut mixture (Ustilago avenae, tritici, holci, zeae)
IC/ml