PHARMALGEN WASP VENOM POWDER AND SOLVENT FOR SOLUTION FOR INJECTION - patient leaflet, side effects, dosage

- If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet:

1. What Pharmalgen is and what it is used for

2. What you need to know before you use Pharmalgen

3. How to use Pharmalgen

4. Possible side effects

5. How to store Pharmalgen

6. Contents of the pack and other information

1. what pharmalgen is and what it is used for

Pharmalgen Bee Venom and Pharmalgen Wasp Venom can be used in two ways:

For treatment

• Pharmalgen Bee Venom and Pharmalgen Wasp Venom are treatments to reduce your body’s reaction to bee or wasp stings. In the rest of this leaflet, these medicines will be called Pharmalgen.

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For diagnosis

• Pharmalgen is also used to test if a person will react too strongly to bee or wasp stings.
• No specific indication for children can be made.

2. what you need to know before you use pharmalgen

Do not use Pharmalgen if:

• If you are allergic to any of the ingredients of this medicine apart from the active substance (listed in section 6)
• You have a disease of, or a problem with, your immune system
• You have chronic heart or lung disease or severe arterial hypertension or are being treated with B-blockers
• You are being treated with tricyclic antidepressants or monoamine oxidase inhibitors

(MAOIs)

• You currently have cancer
• You have severe asthma (seasonal or chronic)
• You are being treated with ACE inhibitors (medicines for heart or blood pressure)

Warnings and precautions

Talk to your doctor or nurse before using

Pharmalgen if:

• You have had a test for a reaction to bee or wasp venom
• You have ever had a bad reaction to this injection or any medicines containing bee or wasp venom
• You suffer from asthma
• You have recurrent or frequent infections

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Other medicines and Pharmalgen

Tell your doctor if you are using, have recently used or might use any other medicines.

In particular tell your doctor if you are taking:

• Antihistamines to reduce allergic reactions
• Medicines to help you breathe (bronchodilators)
• Medicines for travel sickness
• Medicines for heart or blood pressure (beta-blockers and ACE inhibitors)
• Antidepressants (tricyclics and monoamine oxidase inhibitors (MAOIs)
• Or if you are being treated with other allergens
• Or if you have recently received any vaccines

Pregnancy and breast-feeding

Treatment with Pharmalgen should not be started if you are already pregnant. If you are likely to become pregnant or you get pregnant during your treatment, talk to your doctor for advice. If you are breast-feeding, ask your doctor for advice.

Take special care with Pharmalgen

Avoid alcohol, hot baths, and strenuous physical exercise on the days you receive your injection.

Special care should be given if children younger than 5 years of age are treated with Pharmalgen.

Your doctor will carefully weight the risk-benefit for the individual child. For children > 5 years of age clinical data of efficacy are sparse, however data on safety do not reveal a higher risk as for adults.

If levels of tryptase in your blood are increased and/or you are suffering from mastocytosis, the risk of side effects may be increased.

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If you are suffering from mastocytosis you may expect less efficacy compared with general insect venom allergic population.

Driving and using machines

Pharmalgen is not expected to affect your ability to drive or operate machinery.

3. how to use pharmalgen

• Your diagnosis and treatment will be carried out by an experienced doctor.
• There are no fixed doses. All patients are treated individually. The doctor will work out which dose is correct for you
• You will be looked after in hospital or clinic for at least 60 minutes after the injections.

Diagnosis

Pharmalgen is dissolved in Albumin Diluent by the healthcare professional before the product is ready to be used. Healthcare professionals should see section at the end of the technical information leaflet for detailed instruction on how to dissolve and dilute Pharmalgen.

Before treatment starts, you will have a test using Pharmalgen to make sure that it is bee venom or wasp venom that is responsible for producing your allergy. This is the diagnosis. This test will probably be a skin prick test but may be an injection under the skin. Alternatively, your allergy may be confirmed by testing your blood.

Treatment

Treatment of your bee or wasp venom allergy is in two phases, the initial phase and the

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maintenance phase. Pharmalgen will be given to you as an injection under the skin. It will not be injected into a vein.

• Initial phase

In the initial phase, the dose of Pharmalgen is increased by small amounts until the maximum dose suitable for you (maintenance dose) has been reached.

The injections in the initial phase will usually be 3–7 days apart. If necessary, your doctor may decide to give you 2–4 injections, 30 minutes apart, once a week until the maximum dose is reached. If you are already in hospital, your doctor may decide to give you up to 4 injections a day, 2 hours apart.

• Maintenance phase

You will be given an injection containing the maintenance dose each month for at least three years.

4. possible side effects

Like all medicines, this medicine can cause side effects although not everybody gets them. If symptoms of side effects occur they usually occur within the first 30 minutes after the injection, but they may occur up to 24 hours after the injection.

Very common side effects (affecting more than 1 person out of 10):

• A continuously spreading weal may be formed at the site during the first 10–20 minutes after the application of the allergen.

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25.04.2017 ALK-Madrid

• Local widespread swelling and redness may happen 6–24 hours after the application of the allergen.
• Swelling, redness, pain, itching and local nettle rash where the injection needle entered the skin may appear within 30 minutes and may last for up to 6 hours.

Common side effects (affecting more than 1 person out of 100): please tell your doctor if long or severe

• Nettle rash, tiredness, wheezing, chest tightness and flushing
• Headache, sneezing, coughing, itching, stuffy and runny nose, itchy eyes, asthma and general discomfort

Most local side effects are mild in nature and can be treated with medication if needed. Please talk to your doctor for advice.

Rare side effects (affecting more than 1 person out of 10,000): please get doctor’s help straight away

Anaphylactic reaction

In very rare cases (less than 1 in 10,000 patients) an anaphylactic reaction (a severe allergic reaction) may occur after skin-prick test with active allergens, within the first minutes after treatment.

An anaphylactic reaction is a severe reaction throughout the body and the onset is characterised by flushing, intense itching of the skin (like palms of hands and soles of feet or other areas of the body), raised rash (like a nettle rash).

In addition, symptoms of an anaphylactic reaction may include swelling of the lips, throat and tongue; shortness of breath; wheezing; hoarseness; nausea; diarrhoea; vomiting; stomach cramp; low blood pressure; fast heart beat; disturbances of the heart rhythm and loss of consciousness.

If this happens your doctor or health professional will have an emergency kit available with a ‚ready for use‘ adrenaline syringe.

This is the reason why you are kept in hospital or clinic for at least one hour after having had your injection.

TELL YOUR DOCTOR/NURSE IMMEDIATELY IF YOU FEEL ANY OF THESE CHANGES. He or she will be able to give you the right treatment at once to make you feel well.

If any of the side effects get serious, of if you notice any side effects not listed in this leaflet, please tell your doctor.

Reporting of side effects

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the MHRA Yellow Card Scheme at

5. how to store pharmalgen

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 bottle after EXP. The expiry date refers to the last day of that month.

Shelf life after reconstitution and dilution with Albumin Diluent:

The hospital or clinic will store Pharmalgen for you in the refrigerator (2°C – 8°C) in the outer carton.

6. contents of the pack and other information

What Pharmalgen contains

Pharmalgen contains an extract of specific allergen. Pharmalgen Bee Venom contains bee venom and Pharmalgen Wasp Venom contains wasp venom. The allergen is the active substance that causes the allergic reaction to either bee or wasp stings.

Pharmalgen is dissolved in Albumin Diluent before being injected into you. The Albumin Diluent contains only inactive ingredients: human serum albumin, phenol, sodium chloride and water for injections.

What Pharmalgen looks like and contents of the pack

Pharmalgen is available in a Treatment Set containing: four glass bottles, which when diluted with Albumin Diluent give a 100 pg/ml solution and four glass bottles of 5.0 ml sterile Albumin Diluent.

Marketing Authorisation Holder and Manufacturer:

ALK-Abell6 A/S

B0ge Alle 6–8

DK-2970 H0rsholm

Denmark

Distributor:

ALK-Abell6 Ltd.

1 Manor Park, Manor Farm Road, Reading, Berkshire. RG2 0NA.

This leaflet was last revised in April 2017

For information in Large Print, tape, CD or Braille, please phone 0118 903 7940

SXLK

1046344 (042017)_Pil_­UK_PH_170425_PH UK 1046344 (022014) 25–04–2017 11:53 Side 1

Technical Information Leaflet

This leaflet contains important information for the prescribing doctor about Pharmalgen Bee Venom and Pharmalgen Wasp Venom.

In this leaflet:

• 1. Declaration

• 2. Indication

• 3. Posology and Method of Administration

• 4. Contraindi­cations

• 5. Special Warnings and Precautions for use

• 6. Interactions with Other Medical Products

• 7. Pregnancy and Lactation

• 8. Effects on the Ability to Drive and Use Machines

• 9. Undesirable Effects

• 10. Shelf life and Storage

• 11. Packages

• 12. Marketing Authorisation Holder and Distributor

The patient should be clearly informed about the benefits and risks of the treatment, before treatment with Pharmalgen Bee Venom or Pharmalgen Wasp Venom is initiated. In the rest of this leaflet, these medicines will be referred to as Pharmalgen.

• 1. Declaration

Pharmalgen is a powder and solvent for solution for injection.

The active ingredient is freeze-dried Apis mellifera (Honey Bee venom) or Vespula spp. (Wasp venom) which is to be reconstituted with Albumin Diluent before use. For instructions on reconstitution and dilution of the product before administration, see the end of this leaflet.

Each vial of Pharmalgen Venom contains 120 |ig of raw freeze-dried venom.

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After reconstitution with 1.2 ml Albumin

Diluent, the vials contain 100 |ig venom/ml.

Only reconstitute the freeze-dried substance required.

Series of 10-fold dilutions should be prepared from the reconstituted solution.

Pharmalgen must not be mixed with other medicinal products except those mentioned above.

Excipients

Powder for solution for injection:

Mannitol

Human serum albumin

This medical product contains less than 1 mmol sodium (23mg) per dose, i.e. essentially ‘sodium free’.

Albumin Diluent:

Human serum albumin

Sodium chloride

Phenol

Water for injection

• 2. Indication

Pharmalgen Bee Venom and Pharmalgen Wasp Venom are indicated for diagnosis and treatment of IgE-mediated allergy to bee or wasp allergy, respectively.

No specific indication for children can be made.

• 3. Posology and Method of Administration

Diagnosis

Diagnosing allergy to bee or wasp venom using Pharmalgen should be carried out using either a skin prick test or an intracutaneous test.

Skin Prick Test:

A concentration of 100 |ig venom/ml is recommended for use in a skin prick test. However,

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for extremely sensitive patients, testing with a lower concentration (e.g. 1 or 10 |ig venom/ml) is advisable. For instructions on reconstitution and dilution of the product before administration, see the end of this leaflet.

Alternatively, an end-point titration test can be used to determine individual starting concentrations for specific immunotherapy. The end-point titration test is performed using concentrations of venom from 0.01 |ig venom/ml up to 100 |ig venom/ml if necessary. If a positive reaction is observed at 0.01 |ig venom/ml, retesting must be performed using a lower concentration. The lowest concentration resulting in a positive reaction is used as the end-point.

The reaction is read after 15–20 minutes.

A reaction is considered positive when a weal with a diameter of more than 3 mm is observed.

Albumin Diluent should be used for dilution and as control.

Intracutaneous Test:

The intracutaneous test is 100 – 1000 times more sensitive than the skin prick test.

The intracutaneous test should always be performed as an end-point titration test. It is recommended to start with a concentration of 0.0001 |ig venom/ml and increase the concentration stepwise by a factor ten every 20 minutes until a positive reaction is observed. If a positive reaction is observed at 0.0001 |ig venom/ml, retesting must be performed using a lower concentration. The lowest concentration causing a positive reaction is taken as the endpoint.

Concentrations of > 1 |ig venom/ml are not recommended for the intracutaneous test as these may cause unspecific reactions.

The reaction is read after 15 – 20 minutes. A reaction is considered positive if a weal with a

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diameter of more than 5 mm and with erythema is observed.

Albumin Diluent should be used for dilution and as control.

Treatment

IgE-mediated allergy to bee or wasp venom must be confirmed by case history and by in vivo and/or in vitro diagnosis prior to initiating treatment with Pharmalgen Bee Venom or Pharmalgen Wasp Venom, respectively.

Treatment with Pharmalgen must be performed using subcutaneous injections. Intravenous administration must be avoided due to an increased risk of potentially fatal anaphylactic reactions.

The dosage of Pharmalgen must be individually adjusted. The dosage should depend on the patient's general condition, the allergenic anamnesis and the patient's sen­sitivity to the specific allergen used.

The patient’s pre­disposition for an allergic reaction may be reduced by prophylactic treatment with antihistamines. However, care should be taken as the use of antihistamines is likely to mask initial warning signs of anaphylaxis, e.g. rash and pruritus.

Treatment with Pharmalgen is in two phases, the Initial Phase and the Maintenance Phase.

Initial Phase:

In the Initial Phase, the dose of Pharmalgen is increased stepwise until the maximum tolerated (maintenance dose) has been reached.

The initial dose is defined as 0.1 ml of the concentration which is 1000 times lower than the end-point concentration obtained in the skin prick test and 10 times lower than the endpoint concentration obtained in the intracuta-neous test.

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For every further injection, the dose should be increased by a factor of ten until a final concentration of 0.01 |ig venom/ml has been reached. From this point, further injections should be given according to recommendations shown in Table I, II or III.

Three dosage schedules intended as general guidelines in establishing a maintenance dose are shown in the tables below.

Each dose must be adapted to the individual patient’s reac­tivity and should only be increased if the previous injection was well tolerated. In all other cases, including interruptions in therapy (infections, vaccinations, holidays, etc.), the dose must be reduced accordingly.

Table Ia: Conventional Dosage Schedule One injection every 3–7 days

• * Dose may be lower, depending on the patient's sen­sitivity.

• * * To reduce the risk of secondary reactions, each dose of 5–100 |ig/ml venom may be divided into halves and given as 2 injections with an interval of 30 minutes.

Table Ib:

Recommended dose reduction if an interval between 2 injections has been exceeded while following the Conventional Dosage Schedule.

• Table II: Modified Rush (Clustered) Dosage Schedule

The patient is given 2 – 4 injections per week at intervals of 30 minutes. If necessary the treatment period may be extended up to 2 weeks.

* Dose may be lower depending on the patient's sen­sitivity.

• Table III: Rush Dosage Schedule

The patient is given an injection every 2 hours with a maximum of 4 injections per day. The patient must be hospitalised.

* Dose may be lower depending on the patient's sen­sitivity.

Maintenance Phase:

The recommended concentration for the maintenance dose is 100 |ig/ml venom administered in a volume of 1 ml. However, the strength of the maintenance dose depends on the patient’s sen­sitivity toward the allergen and should be determined individually on the basis of the patient's response during the Initial Phase.

If allergic reactions are observed after bee or wasp stings in patients who have achieved the maximum dose of 100 |ig Pharmalgen Bee Venom or Pharmalgen Wasp Venom, respectively, the dose can be cautiously increased up to 200 |ig.

When the maintenance dose has been attained, the interval between the injections is increased stepwise to two, three and four weeks. The maintenance dose is then administered every four weeks for a period of at least three years.

Table IV: Dose Reduction for Maintenance Phase Dosage Schedule Recommended dose reduction if an interval between two injections has been exceeded while following the Maintenance Phase.

Dose reduction when systemic reactions are observed

If a severe, systemic reaction occurs after injection, the treatment with Pharmalgen should only be continued after careful consideration. If treatment is continued, it may be considered to reduce the following dose to 10% of the dose provoking the reaction.

Table V: Dose reduction when large injection site reactions are observed If an injection site reaction with a diameter of 8 cm or more for adults (5 cm or more for children) occurs and is present for more than 6 hours, the subsequent dose should be reduced according to the table below.

Concomitant treatment of more than one allergy

Pharmalgen venom extracts must not be mixed. Patients who are allergic to more than one type of venom should initiate treatment with one type of venom first. When the maintenance dose has been attained, treatment with the other type of venom may be initiated. The maintenance injections of the two types of venom should be given with an interval of 2 – 3 days.

4. Contraindi­cations

• Pharmalgen is contraindicated in patients: allergic to any of the ingredients of this medicine apart from the active substance with immune pathologic conditions such as immune complex and immunodeficiency diseases
• with diseases or conditions preventing the treatment of possible anaphylactic reactions, e.g. chronic heart and lung diseases, severe arterial hypertension and treatment with B-blockers
• treated with tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs), as the effects of adrenaline, used in case of

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