Sublivac Tree

What Is Sublivac Tree and What Is It Used For?

Quick Answer: Sublivac Tree is a sublingual allergen immunotherapy containing a standardized extract of tree pollen from birch, alder, and hazel. It is prescribed to treat allergic rhinitis, allergic rhinoconjunctivitis, and associated allergic asthma symptoms caused by tree pollen in patients whose symptoms are inadequately controlled by standard allergy medications.

Sublivac Tree belongs to a class of treatments known as sublingual allergen immunotherapy (SLIT). Unlike antihistamines, nasal corticosteroids, and decongestants, which only suppress the outward signs of allergic inflammation, immunotherapy targets the underlying immunological mechanism that drives the allergy itself. The active substance is a standardized, natural allergen extract obtained from the pollen of the most clinically important spring-flowering trees in temperate climates: silver birch (Betula verrucosa), European alder (Alnus glutinosa), and common hazel (Corylus avellana). These three species share a common major allergen, Bet v 1, which is highly cross-reactive, making combined extracts an effective strategy for patients sensitized to multiple tree pollens.

The treatment is indicated for patients with clinically relevant IgE-mediated allergic rhinitis or rhinoconjunctivitis caused by tree pollen, confirmed by a positive skin prick test and/or a positive specific IgE blood test, together with a clear seasonal symptom history. According to the European Academy of Allergy and Clinical Immunology (EAACI), allergen immunotherapy should be considered for patients with moderate to severe symptoms that are insufficiently controlled by optimal pharmacotherapy, for patients who experience medication side effects, and for those who wish to modify the natural course of their allergic disease. Sublingual therapy is particularly suitable for patients who prefer a convenient home-based treatment over regular clinic visits for injections.

The mechanism of action involves daily exposure of the sublingual mucosa to tree pollen allergens. The oral mucosa contains a dense network of dendritic cells that take up the allergen and transport it to regional lymph nodes. There, the allergen stimulates a shift away from a pro-allergic T-helper type 2 (Th2) immune response toward a regulatory T-cell response, accompanied by increased production of blocking IgG4 antibodies and reduced production of allergen-specific IgE. These immunological changes translate into a reduction in mast cell and basophil reactivity, decreased eosinophilic tissue inflammation during allergen exposure, and, ultimately, clinically meaningful improvement in symptoms. Crucially, these changes are durable: clinical tolerance persists for years after discontinuation of a full three-year course.

Sublivac Tree is manufactured by HAL Allergy B.V., a Dutch specialty pharmaceutical company with more than 60 years of experience in allergen immunotherapy. The product is formulated as an aqueous sublingual solution without aluminium adjuvant, which differentiates it from injectable immunotherapy products. Sublivac Tree is approved and distributed across several European countries under nationally authorised formulations. The 40,000 AUN/ml (Allergen Unit Native per millilitre) concentration represents the maintenance strength; lower-strength vials are used during the dose-escalation phase to improve tolerability.

What Should You Know Before Taking Sublivac Tree?

Quick Answer: Sublivac Tree must not be used in patients with severe or uncontrolled asthma, active autoimmune disease, severe immunodeficiency, malignancy, severe oral inflammation, or known allergy to any component of the formulation. Several precautions apply, including pregnancy considerations, recent dental procedures, and potential drug interactions. Always provide your physician with a complete medical history before starting therapy.

Contraindications

Sublivac Tree should not be used if you have any of the following conditions:

• Hypersensitivity to excipients: Known allergy to any of the inactive ingredients in the formulation, including glycerol, sodium chloride, or the preservative system.
• Severe or uncontrolled asthma: Active asthma exacerbation, forced expiratory volume in 1 second (FEV1) below 70% of predicted after adequate pharmacological treatment, or any recent severe asthma attack. Sublingual immunotherapy is contraindicated during periods of poor asthma control due to an elevated risk of bronchospasm.
• Active autoimmune disorders: Conditions such as systemic lupus erythematosus, multiple sclerosis, or untreated Hashimoto’s thyroiditis, where ongoing immunological stimulation may worsen the primary disease.
• Primary or severe secondary immunodeficiency: Including patients on high-dose immunosuppressive therapy or with conditions such as HIV with low CD4 counts, as the treatment relies on a functional immune system to achieve efficacy.
• Active or poorly controlled malignancy: Cancer patients should not begin immunotherapy, as the effect of sustained immune modulation on tumour behaviour is unpredictable.
• Severe oral inflammation or injury: Including oral ulcers, lichen planus, gingivitis with open wounds, periodontitis flare, loose teeth, fungal oral infections, or recent oral surgery. These conditions can facilitate systemic absorption of the allergen and increase the risk of severe reactions.
• Chronic inflammatory bowel disease: During active flare, due to altered mucosal permeability.

Warnings and Precautions

Inform your physician before starting Sublivac Tree if any of the following apply to you:

• Controlled asthma: Even well-controlled asthma is a risk factor for severe reactions. Spirometry should be performed before starting treatment, and asthma control should be assessed at every follow-up visit. Treatment should be paused during any asthma exacerbation.
• Previous adverse reactions to immunotherapy: If you have previously experienced systemic allergic reactions to any allergen immunotherapy product, your physician will weigh the risks carefully and may adjust the dose-escalation schedule.
• Tooth extraction, oral surgery, or oral wounds: Treatment should be interrupted for at least 7 days before and after oral surgery (including tooth extraction), and until any oral wounds or ulcers have fully healed.
• Acute respiratory infection: In case of severe upper or lower respiratory tract infection, treatment should be temporarily discontinued until recovery.
• Gastroenteritis: Discontinue temporarily in case of severe gastroenteritis to minimise systemic absorption.
• Atopic dermatitis flare: Active severe eczema may indicate heightened immune reactivity and warrant dose modification.
• Elevated baseline tryptase or mastocytosis: Patients with mastocytosis or baseline tryptase above 11.4 ng/ml have a significantly increased risk of systemic reactions and require specialist evaluation.
• Cardiovascular disease: Patients with significant cardiovascular comorbidities should be evaluated for their ability to tolerate epinephrine if a systemic reaction were to occur.
• Current treatment with beta-blockers: These medications can interfere with emergency treatment of anaphylaxis and may require review of the risk-benefit balance.

Children and Adolescents

Sublingual tree pollen immunotherapy can be used in children aged 5 years and older with a clear indication. Clinical trials of sublingual allergen immunotherapy have demonstrated a favourable safety profile in paediatric populations, with efficacy comparable to or better than that observed in adults. Younger children may be more prone to local oral side effects initially but typically tolerate the treatment well after the first 1 to 2 weeks.

In children under 5 years of age, data are more limited, and the decision to initiate immunotherapy should be made on a case-by-case basis by a paediatric allergist. The ability of the child to cooperate with the sublingual administration procedure (holding the drops under the tongue and not swallowing immediately) is an important practical consideration. Parents or caregivers should supervise all doses in young children and be trained to recognise early symptoms of an allergic reaction.

Pregnancy and Breastfeeding

Sublivac Tree should not be initiated during pregnancy due to the increased risk of systemic reactions during the dose-escalation phase. If you are on established maintenance therapy and become pregnant, continuation of treatment can usually be discussed with your allergist, who will weigh the benefit of symptom control and prevention of severe allergic reactions against any theoretical foetal risks. There is no evidence that established sublingual immunotherapy harms the foetus.

During breastfeeding, the allergen extract is unlikely to pass into breast milk in clinically relevant quantities given the sublingual route of administration and the low systemic bioavailability of the active ingredients. Ongoing maintenance immunotherapy may generally be continued during breastfeeding when the clinical benefit outweighs any theoretical concerns, but this decision should be confirmed with the prescribing physician.

Driving and Operating Machinery

Sublivac Tree is not expected to have a significant influence on the ability to drive or operate machinery. However, during the first weeks of treatment, some patients experience mild dizziness or fatigue that could impair alertness. If you notice such effects, avoid driving and operating heavy machinery until the symptoms have fully resolved.

How Does Sublivac Tree Interact with Other Drugs?

Quick Answer: Sublivac Tree has few direct pharmacokinetic interactions, but several classes of medication can affect the safety or efficacy of treatment. Beta-blockers and ACE inhibitors can worsen anaphylaxis and impair emergency treatment; systemic corticosteroids and immunosuppressants may reduce immunotherapy efficacy; antihistamines and omalizumab can mask early warning symptoms.

Drug interactions with allergen immunotherapy matter because they can influence either the likelihood of an adverse reaction or the ability to treat one effectively. Patients receiving sublingual immunotherapy must therefore inform their physician and pharmacist of every prescription medication, over-the-counter product, and dietary supplement they use. Below are the clinically most relevant interactions that have been reported or are considered plausible on a pharmacological basis.

Major Interactions

Minor Interactions and Considerations

What Is the Correct Dosage of Sublivac Tree?

Quick Answer: Sublivac Tree is taken once daily as sublingual drops under the tongue, held in place for 2 to 3 minutes before swallowing. Treatment begins with a short dose-escalation phase, then continues with a daily maintenance dose of the 40,000 AUN/ml strength for three consecutive years. Treatment should be started 12 to 16 weeks before the expected tree pollen season and continued year-round.

Sublivac Tree is a self-administered treatment, but the very first dose is always given in a medical setting so that the patient’s reaction can be observed. Subsequent doses are taken at home once daily, preferably in the morning on an empty stomach. The prescribed number of drops is placed under the tongue from the dropper bottle, held there for two to three minutes to allow mucosal absorption, and then swallowed. For the five minutes following each dose, patients should avoid eating, drinking, rinsing the mouth, or brushing the teeth.

Initiation (Dose-Escalation) Phase

During the dose-escalation phase, the daily dose is gradually increased over one to two weeks until the full maintenance dose is reached. The allergist typically prescribes a starter pack containing progressively higher concentrations of the extract. Starting doses are lower to minimise the risk of initial oral side effects. If a dose causes marked local reactions (persistent itching or swelling lasting more than several hours), the physician may slow the up-titration or prescribe a short course of antihistamines.

Maintenance Phase

Once the maintenance dose of the 40,000 AUN/ml strength is reached, the patient continues the same daily dose for the remainder of the three-year treatment course. Treatment is given continuously throughout the year, not just during the pollen season. Year-round dosing is essential to maintain the sustained immunological changes required for long-term clinical tolerance. Randomised trials of sublingual allergen immunotherapy have consistently shown that continuous, multi-year regimens produce stronger and more durable treatment effects than seasonal-only regimens.

The full clinical benefit typically becomes apparent during the first tree pollen season after starting treatment, with further gains in efficacy over the second and third years. Patients should not discontinue the treatment just because symptoms improve early; the immunological changes that provide long-term benefit require the full three-year exposure to be firmly established. Evidence summarised by the EAACI and in the AllergoOncology / ARIA guidelines indicates that treatment effects persist for at least several years after discontinuation, whereas shorter courses are associated with a higher rate of symptom relapse.

Children

In children aged 5 years and older, the same dose-escalation and maintenance schedule is generally used. Paediatric studies of sublingual allergen immunotherapy have demonstrated similar efficacy and a favourable safety profile compared with adults. Parents should supervise administration for young children and ensure that the drops are held under the tongue rather than swallowed immediately. Children under 5 years are treated only in specialist centres on a case-by-case basis.

Elderly Patients

No specific dose adjustment is required based on age alone. However, elderly patients are more likely to have comorbidities (particularly cardiovascular disease) and to use medications (such as beta-blockers and ACE inhibitors) that influence the risk-benefit profile of allergen immunotherapy. A thorough medical assessment is therefore recommended before starting treatment in patients over 65 years.

Missed Dose

If you forget a daily dose, take it as soon as you remember on the same day. If more than one day has passed, skip the missed doses and resume the normal daily regimen the next morning. Do not double the dose to compensate for missed days. If the treatment has been interrupted for more than 7 days, contact your allergist before restarting, as a partial re-escalation schedule may be required to safely resume maintenance dosing.

Overdose

Taking a larger than prescribed dose increases the risk of local oral reactions (itching, swelling, pain) and can potentially trigger systemic allergic symptoms (generalised itching, urticaria, angioedema, wheezing, gastrointestinal upset, dizziness, hypotension). If an overdose is suspected, rinse the mouth with water, do not take the next scheduled dose, and contact a healthcare provider. In the case of severe symptoms such as difficulty breathing, widespread hives, or a sudden feeling of faintness, seek emergency medical attention and, if prescribed, use an epinephrine auto-injector.

What Are the Side Effects of Sublivac Tree?

Quick Answer: The most common side effects of Sublivac Tree are mild to moderate local reactions in the mouth and throat, including oral itching, tongue swelling, throat irritation, and ear itching, typically occurring during the first one to two weeks of treatment. Systemic reactions such as generalised urticaria or wheezing are uncommon, and severe anaphylaxis is rare.

Like all medicines, Sublivac Tree can cause side effects, although not everyone experiences them. The majority of side effects are expected consequences of the local immune response to the allergen at the sublingual mucosa and tend to decrease or disappear after the first one to two weeks of continuous treatment. Patients can be reassured that local reactions usually indicate appropriate local immune engagement, not a dangerous allergic reaction. Nevertheless, persistent, severe, or systemic symptoms should prompt medical review.

According to pooled analyses of sublingual tree pollen immunotherapy trials, approximately 40–75% of patients experience at least one local oral reaction during the first two weeks of treatment, but fewer than 4% discontinue treatment because of side effects. Severe systemic reactions occur in fewer than 1 in 1,000 patient-years of treatment, and fatal reactions to sublingual immunotherapy are exceptionally rare. In comparison, subcutaneous injection immunotherapy carries a significantly higher rate of systemic reactions, which is a key reason why sublingual therapy can be safely self-administered at home after the first in-clinic dose.

For mild local reactions, simple measures such as applying a cold compress to the lips, sipping cold water 5 minutes after the dose, or taking a non-sedating antihistamine 30 minutes before the dose can improve tolerability. Persistent or worsening local symptoms should prompt review by the prescribing allergist. Rarely, some patients develop eosinophilic oesophagitis during sublingual immunotherapy, characterised by difficulty swallowing and chest pain; this possibility should be considered if such symptoms develop and does not resolve on pausing treatment.

How Should You Store Sublivac Tree?

Quick Answer: Sublivac Tree must be stored in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze. Keep the bottle in its original carton to protect from light, and always store the cap tightly closed. Once opened, the bottle remains usable for the period specified on the label, typically up to 6 months. Keep out of reach and sight of children.

Correct storage is essential to maintain both the potency and the safety of Sublivac Tree. The active allergen extract consists of natural proteins that are sensitive to heat, freezing, and light. Exposure to adverse conditions can alter the allergen content and lead to unpredictable clinical effects – either reduced efficacy or, in some cases, unexpected reactions.

• Refrigerated storage: Store at 2°C to 8°C (36°F to 46°F) in the main compartment of the refrigerator. Avoid storing directly next to the freezer compartment or on the door, where temperature fluctuations are greater.
• Do not freeze: Freezing can denature the protein allergens and damage the dropper mechanism.
• Light protection: Keep the bottle in its original carton. The packaging is designed to protect the suspension from degradation by light.
• After opening: The bottle typically remains usable for up to 6 months after first opening, provided it is stored correctly. Check the specific in-use shelf life stated on the label or carton.
• Transport: When travelling, use a cool bag with freezer packs (not in direct contact with the bottle) to maintain the correct temperature. Short-term exposure to room temperature (up to a few hours) is unlikely to damage the product, but repeated or prolonged warming should be avoided.
• Expiry date: Do not use after the expiry date printed on the label (EXP). The date refers to the last day of the stated month.
• Child safety: Store in a location where children cannot see or reach the bottle. Accidental ingestion by a child could trigger an allergic reaction.
• Disposal: Do not dispose of unused medication in household waste or pour it down the drain. Return unused or expired medication to a pharmacy for appropriate disposal in accordance with local regulations.

Before each use, gently invert the bottle once or twice to ensure the solution is uniformly mixed, although the product is typically a clear aqueous solution rather than a suspension. Do not use if the solution has changed colour, become cloudy, or contains visible particles. Any damaged bottle or dropper should be returned to the pharmacy and replaced before resuming treatment. If you are unsure whether a temperature excursion has compromised the product, contact the prescribing pharmacy or allergist for advice rather than administering a potentially degraded dose.

What Does Sublivac Tree Contain?

Quick Answer: The active ingredient of Sublivac Tree is a standardized allergen extract of tree pollen from silver birch (Betula verrucosa), European alder (Alnus glutinosa), and hazel (Corylus avellana) at a concentration of 40,000 AUN/ml. Inactive ingredients include glycerol as a stabilizer, sodium chloride, and water for injections.

Active Ingredient

The active substance in Sublivac Tree is a purified, standardized allergen extract prepared from the pollen of the three most important early-flowering trees in the birch family (Betulaceae):

• Silver birch (Betula verrucosa): The dominant tree allergen in most temperate regions. Its major allergen, Bet v 1, is responsible for most cases of birch pollen allergy.
• European alder (Alnus glutinosa): Typically flowers in late winter, shares extensive cross-reactivity with birch via homologous Bet v 1-type proteins.
• Common hazel (Corylus avellana): Often the earliest pollen trigger of the year, sharing the Bet v 1 homologue Cor a 1.

Potency is expressed in Allergen Units Native per millilitre (AUN/ml), a manufacturer-specific standardization unit that reflects both major allergen content and overall allergenic activity measured in validated bioassays. The 40,000 AUN/ml strength corresponds to the maintenance concentration for daily dosing once the initiation phase is complete.

Inactive Ingredients (Excipients)

• Glycerol (glycerine): Stabilizer that preserves the native conformation of the allergen proteins and extends shelf life.
• Sodium chloride: Maintains isotonicity of the solution.
• Sodium hydrogen carbonate (buffering agent): Maintains a physiological pH.
• Water for injections: Solvent.

The product does not contain lactose, gluten, or aluminium adjuvants. Patients with rare hereditary intolerances to any excipient should review the complete formulation with the prescribing pharmacist. Unlike some injectable allergen immunotherapy products, Sublivac Tree is formulated as a non-adjuvanted aqueous solution, which is a key reason it is suitable for sublingual administration.

Packaging

Sublivac Tree is typically supplied in amber glass bottles of 10 ml, fitted with an integrated dropper for accurate sublingual dosing. The initiation (starter) pack contains lower-strength bottles (1,000 AUN/ml and 10,000 AUN/ml) for dose escalation. Maintenance packs contain one or more 40,000 AUN/ml bottles. The outer carton includes batch number and expiry date, and the detailed patient leaflet provides full prescribing information.