F25

Dosage for Aesculus Hippocastanum Flower is highly individualized and is never a 'one-size-fits-all' regimen. Because it is a non-standardized extract, potency is often expressed in Protein Nitrogen Units (PNU) or as a Weight/Volume (w/v) ratio (e.g., 1:10, 1:20).

• Diagnostic Testing: For skin prick testing, a concentration of 1:10 or 1:20 w/v is typically used. A single drop is applied to the skin, followed by a prick through the drop. For intradermal testing, a much more dilute solution (e.g., 0.02 mL of a 100 PNU/mL or 1000 PNU/mL solution) is injected.
• Immunotherapy (Maintenance): Patients typically begin with a very low dose (e.g., 0.05 mL of a 1:100,000 dilution) and gradually increase the dose over several months. The target maintenance dose often ranges between 0.2 mL and 0.5 mL of a 1:100 or 1:20 w/v concentration, administered once every 2 to 4 weeks.

Aesculus Hippocastanum Flower may be used in children, but extreme caution is required.

• Children (Ages 5 and older): Dosing follows a similar escalation pattern to adults but often starts at even lower concentrations. The safety and efficacy in children under the age of 5 have not been extensively established for this specific floral extract.
• Note: Pediatric patients are at a higher risk for systemic reactions and must be monitored more closely during the 30 minutes following administration.

Renal Impairment

No specific dosage adjustments are typically required for patients with kidney disease, as the systemic load of the extract is generally low. However, clinicians should monitor for potential accumulation of metabolites if high-dose immunotherapy is used over a long period.

Hepatic Impairment

Patients with severe liver disease (e.g., Child-Pugh Class C) should be approached with caution. While hepatic metabolism is not the primary clearance route for the allergenic proteins, any systemic adrenergic effects may be prolonged if hepatic clearance of sympathomimetic components is reduced.

Elderly Patients

Geriatric patients (65 years and older) should be dosed conservatively. This population is more likely to have underlying cardiovascular disease, which could be exacerbated by the adrenergic agonist properties of the extract or by the epinephrine required to treat a potential allergic reaction.

This medication is almost exclusively administered in a clinical setting by a healthcare professional.

• Subcutaneous Injection: The injection should be given in the outer aspect of the upper arm. The site should be rotated between the left and right arms for each visit.
• Observation Period: You must remain in the doctor's office for at least 30 minutes after receiving an injection. This is the period when life-threatening anaphylaxis is most likely to occur.
• Storage: Extracts should be stored in a refrigerator between 2°C and 8°C (36°F to 46°F). Do not freeze. Protect from light.

If you miss an immunotherapy appointment, contact your allergist immediately.

• If the delay is short (e.g., 1 week), the previous dose may be repeated.
• If the delay is significant (e.g., 4 weeks or more), the dose may need to be reduced significantly to prevent a reaction when resuming treatment.
• Never try to 'double up' on doses to make up for a missed appointment.

An overdose of Aesculus Hippocastanum Flower usually manifests as an exaggerated allergic response or systemic adrenergic stimulation.

• Symptoms: Severe swelling at the injection site, hives (urticaria), rapid heart rate (tachycardia), palpitations, or difficulty breathing.
• Emergency Measures: If an overdose occurs, immediate administration of epinephrine (0.3 mg IM for adults) is the primary treatment. Supportive care with antihistamines, corticosteroids, and oxygen may be necessary.

> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose without medical guidance. Always inform your doctor if you are feeling unwell on the day of your scheduled injection.

Most patients receiving Aesculus Hippocastanum Flower, especially during the 'build-up' phase of immunotherapy, will experience local reactions. These are generally not dangerous but can be uncomfortable.

• Local Swelling and Redness: A 'wheal' or hard bump at the injection site that may be accompanied by redness (erythema). This typically resolves within 24 to 48 hours.
• Itching (Pruritus): Intense itching at the site of administration.
• Tenderness: The arm may feel sore or heavy for a day or two following the injection.

These side effects indicate a mild systemic response to the extract.

• Generalized Hives: Itchy red welts appearing on parts of the body away from the injection site.
• Nasal Congestion: Sneezing or a runny nose shortly after administration.
• Fatigue: A feeling of tiredness or 'brain fog' that can last for several hours after the appointment.
• Mild Tachycardia: A slightly elevated heart rate, likely due to the adrenergic agonist components of the flower extract.

• Angioedema: Deep swelling, particularly around the eyes, lips, or throat. This is a medical emergency.
• Bronchospasm: Tightness in the chest and wheezing, similar to an asthma attack.
• Hypotension: A sudden drop in blood pressure, which may cause dizziness or fainting.
• Gastrointestinal Distress: Nausea, abdominal cramping, or diarrhea shortly after an injection.

> Warning: Stop taking Aesculus Hippocastanum Flower and call your doctor immediately if you experience any of these.

• Anaphylaxis: A life-threatening, whole-body allergic reaction. Symptoms include a rapid, weak pulse; skin rash; and nausea and vomiting.
• Laryngeal Edema: Swelling of the throat that makes it difficult to breathe or swallow. This can progress rapidly to airway obstruction.
• Cardiac Arrhythmias: Irregular heartbeats, which may be triggered by the beta-1 adrenergic activity of the extract in sensitive individuals.
• Seizures: Extremely rare, but systemic reactions can occasionally lead to neurological symptoms if oxygen levels drop or if there is a severe autonomic response.

With prolonged immunotherapy (3 to 5 years), most patients see a decrease in sensitivity. However, some may develop:

• Persistent Local Nodules: Small, hard lumps under the skin at frequent injection sites.
• Chronic Immunological Changes: While the goal is 'tolerance,' some patients may develop new sensitivities to other components in the extract over many years.
• Adrenergic Desensitization: Theoretically, long-term exposure to adrenergic agonists could lead to receptor down-regulation, though this has not been clinically significant with the low doses used in allergenic extracts.

As of 2026, the FDA requires a class-wide warning for all allergenic extracts, including Aesculus Hippocastanum Flower.

WARNING: RISK OF SEVERE ALLERGIC REACTIONS

• Aesculus Hippocastanum Flower can cause severe, life-threatening systemic reactions, including anaphylaxis.
• This product must only be administered by healthcare providers prepared to manage such reactions.
• Patients with unstable asthma or those taking beta-blockers are at increased risk for severe outcomes.
• Patients must be observed for at least 30 minutes following administration.

Report any unusual symptoms to your healthcare provider immediately. Even a 'late' reaction occurring several hours after you leave the clinic should be reported before your next dose.

Aesculus Hippocastanum Flower is a potent biological agent. Its use is restricted to diagnostic and therapeutic purposes under the direct supervision of medical specialists. Patients must be aware that every injection carries a small but real risk of a systemic allergic reaction. It is vital to communicate your current health status, including any new medications or changes in asthma symptoms, before every dose.

No FDA black box warnings specifically for Aesculus Hippocastanum Flower exist beyond the general class warning for allergenic extracts. This warning emphasizes the risk of anaphylaxis and the requirement for administration in a facility equipped with emergency resuscitation equipment, including oxygen, IV fluids, and epinephrine.

• Allergic Reactions / Anaphylaxis Risk: This is the primary concern. Patients with a history of severe reactions to other allergens or those with highly sensitive skin (dermographism) must be monitored with extreme vigilance.
• Cardiovascular Risk: Due to its alpha and beta-adrenergic agonist properties, this extract can stimulate the heart and constrict blood vessels. Patients with pre-existing hypertension, coronary artery disease, or arrhythmias may be at higher risk for cardiovascular events during a systemic reaction or if the extract is absorbed rapidly.
• Asthma Stability: If your asthma is flaring up or your 'peak flow' meter readings are low, your doctor will likely postpone your injection. Administering an allergen to a patient with active asthma significantly increases the risk of a fatal reaction.
• Epinephrine Preparedness: Patients on immunotherapy should carry an unexpired epinephrine auto-injector (e.g., EpiPen) at all times, as delayed reactions can occur after leaving the clinic.

• Pre-Injection Assessment: Your provider will check your vitals and ask about any 'late' reactions from the previous dose.
• Post-Injection Observation: Mandatory 30-minute wait in the clinic.
• Lung Function: For patients with asthma, a quick spirometry or peak flow test may be required before each dose.
• Skin Checks: Monitoring the size of the local reaction (the 'wheal') helps the doctor decide if the next dose can be increased safely.

Most patients can drive themselves to and from appointments. However, if you experience dizziness, fatigue, or a mild systemic reaction, you should not drive until the symptoms have completely resolved. If you are given an antihistamine or epinephrine for a reaction, you should arrange for someone else to drive you home.

Alcohol should be avoided for several hours before and after your injection. Alcohol can cause vasodilation (widening of blood vessels), which may speed up the absorption of the allergen and potentially increase the severity of a systemic reaction.

Immunotherapy is usually a long-term commitment. Stopping suddenly will not cause 'withdrawal' in the traditional sense, but your allergy symptoms will likely return to their baseline levels. If you need to stop treatment due to pregnancy or a new medical condition, discuss a tapering or pause strategy with your allergist.

> Important: Discuss all your medical conditions with your healthcare provider before starting Aesculus Hippocastanum Flower.

• Beta-Blockers (Non-selective and Selective): Drugs like Propranolol, Atenolol, or Metoprolol are strictly contraindicated or used with extreme caution. If a patient on beta-blockers has an anaphylactic reaction to Aesculus Hippocastanum Flower, the epinephrine used to save their life may not work effectively. This can lead to 'refractory' (untreatable) anaphylaxis.
• MAO Inhibitors (MAOIs): Drugs used for depression (e.g., Phenelzine, Selegiline) can dangerously potentiate the adrenergic agonist effects of the flower extract, leading to a hypertensive crisis (dangerously high blood pressure).

• Tricyclic Antidepressants (TCAs): Similar to MAOIs, TCAs (e.g., Amitriptyline) can increase the body's sensitivity to the adrenergic components of the extract, potentially causing heart palpitations or high blood pressure.
• Other Adrenergic Agonists: Taking medications like pseudoephedrine (Sudafed) or asthma rescue inhalers (Albuterol) on the day of your injection can have an additive effect on your heart rate and blood pressure.

• Antihistamines: While not dangerous, taking antihistamines (e.g., Cetirizine, Loratadine) before a diagnostic skin test will suppress the reaction, leading to a 'false negative' result. You must typically stop these 3 to 7 days before testing.
• Corticosteroids: Long-term use of high-dose steroids may slightly dampen the immune response to immunotherapy, potentially reducing its effectiveness.

• Caffeine: High intake of caffeine (coffee, energy drinks) on the day of treatment can worsen the tachycardia (fast heart rate) associated with the extract's beta-adrenergic properties.
• High-Fat Meals: There is no direct evidence that food affects the absorption of injected extracts, but heavy meals can sometimes complicate the management of gastrointestinal symptoms during an allergic reaction.

• St. John's Wort: May interact with the metabolism of the adrenergic components.
• Ephedra / Ma Huang: These contain natural ephedrine and should be strictly avoided, as they significantly increase the risk of cardiovascular side effects when combined with an adrenergic extract.
• Ginkgo Biloba: May have mild anti-platelet effects; while not a direct interaction, it's worth mentioning to your doctor if you experience bruising at the injection site.

• Skin Prick Tests: As mentioned, antihistamines and certain antidepressants can interfere with skin test results.
• Serum Tryptase: If you have a severe reaction, your doctor may draw blood to test for tryptase levels, which confirm that anaphylaxis has occurred. The extract itself does not interfere with the test but triggers the physiological state the test measures.

For each major interaction, the mechanism usually involves either a pharmacodynamic clash (e.g., beta-blockers blocking the rescue medicine) or a synergistic effect (e.g., MAOIs preventing the breakdown of adrenergic compounds). The clinical consequence is either increased toxicity (hypertension, tachycardia) or reduced safety (inability to treat anaphylaxis).

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, especially any new heart or blood pressure medications.

• Severe, Unstable Asthma: Patients whose asthma is not well-controlled (FEV1 consistently below 70% of predicted) should NEVER receive Aesculus Hippocastanum Flower injections. The risk of a fatal bronchospasm during a reaction is too high.
• Recent Myocardial Infarction (Heart Attack): Within the last 3-6 months. The adrenergic stress of a potential reaction could trigger another cardiac event.
• History of Severe Anaphylaxis to this Specific Extract: If a patient has previously had a near-fatal reaction to Horse Chestnut flower extract, the risks of continuing immunotherapy outweigh the benefits.
• Beta-Blocker Therapy: In many clinical guidelines, the use of beta-blockers is an absolute contraindication for starting new immunotherapy because it renders epinephrine ineffective during emergencies.

• Autoimmune Diseases: Patients with active systemic lupus erythematosus (SLE) or rheumatoid arthritis may have unpredictable immune responses to allergenic extracts.
• Malignancy: Patients undergoing active chemotherapy or radiation may have compromised immune systems that make immunotherapy less effective or more risky.
• Severe Atopic Dermatitis: Extensive skin disease can make diagnostic skin testing impossible to interpret and may increase the risk of systemic absorption.
• Age (Under 5 years): Generally avoided due to the difficulty of the child communicating early symptoms of a reaction.

Patients who are allergic to Aesculus Hippocastanum Flower may also react to:

• Other members of the Sapindaceae family: Such as Maple trees or Lychee fruit.
• Latex: Some studies suggest a cross-reactivity between Horse Chestnut proteins and Hevea brasiliensis (latex) proteins, known as the 'latex-fruit syndrome' or 'latex-tree syndrome.'
• Honey: If the honey contains significant amounts of Horse Chestnut pollen.

> Important: Your healthcare provider will evaluate your complete medical history and current health status before prescribing or administering Aesculus Hippocastanum Flower.

Aesculus Hippocastanum Flower is generally classified as Pregnancy Category C.

• Risk Summary: There are no adequate and well-controlled studies in pregnant women. The primary risk is not direct teratogenicity (birth defects) from the extract itself, but rather the danger that maternal anaphylaxis poses to the fetus. Anaphylaxis can cause severe maternal hypotension, leading to fetal hypoxia (lack of oxygen) and potential fetal death or neurological injury.
• Clinical Guidance: Most allergists will NOT start a new regimen of Aesculus Hippocastanum Flower during pregnancy. However, if a patient is already on a stable maintenance dose and is tolerating it well, the treatment may be continued at that same dose (without further increases) throughout the pregnancy.

It is not known whether the components of Aesculus Hippocastanum Flower are excreted in human milk. Because the allergenic proteins are large and the doses are small, it is unlikely that significant amounts reach the infant through breastfeeding. However, the mother should be monitored for any systemic reactions that could interfere with her ability to care for the infant. The risk-benefit ratio is generally favorable for continuing maintenance immunotherapy while nursing.

• Approved Age: Immunotherapy with this extract is typically reserved for children 5 years of age and older.
• Special Considerations: Children have a smaller blood volume, meaning a systemic reaction can progress to shock more quickly than in an adult. Dosing must be meticulous, and the child must be able to follow instructions regarding the 30-minute wait period.
• Growth Effects: There is no evidence that allergenic extracts like Aesculus Hippocastanum Flower affect growth or development in children.

• Cardiovascular Reserve: Older adults often have less cardiovascular reserve to survive a severe anaphylactic event.
• Polypharmacy: The elderly are more likely to be on medications (like beta-blockers or ACE inhibitors) that complicate the treatment of allergic reactions.
• Renal Function: Natural age-related decline in kidney function may slightly slow the clearance of the extract's metabolic byproducts, though this is rarely clinically significant.

In patients with chronic kidney disease (CKD), no specific dose reduction is mandated by the FDA. However, clinicians should be aware that the systemic stress of an allergic reaction may be harder for a patient with end-stage renal disease to manage. Dialysis does not effectively clear the large allergenic proteins.

There are no specific guidelines for Aesculus Hippocastanum Flower in hepatic impairment. However, since the liver produces many of the proteins involved in the 'complement' and 'clotting' cascades—which are activated during anaphylaxis—patients with severe liver failure may have more unpredictable or severe reactions.

> Important: Special populations require individualized medical assessment and often more frequent monitoring during the course of treatment.

Aesculus Hippocastanum Flower functions through two distinct pathways:

1. 1Immunological Pathway: The extract contains various glycoproteins and proteins that act as antigens. Upon exposure, these antigens bind to IgE antibodies on mast cells. This triggers a signal transduction pathway involving tyrosine kinases (like Syk and Lyn), leading to the release of pre-formed mediators (histamine) and the synthesis of new mediators (leukotrienes). In immunotherapy, repeated low-dose exposure shifts the immune response from a Th2 (allergic) profile to a Th1 or Treg (tolerant) profile, increasing the production of IgG4 'blocking' antibodies.
2. 2Adrenergic Pathway: The extract contains compounds that act as direct agonists at alpha-1, alpha-2, beta-1, and beta-2 adrenergic receptors.

• Alpha-1: Activates phospholipase C, increasing intracellular calcium and causing smooth muscle contraction.
• Beta-2: Activates adenylate cyclase, increasing cAMP and causing smooth muscle relaxation (bronchodilation).

• Onset of Action: For skin testing, the 'wheal and flare' reaction peaks at 15-20 minutes. For adrenergic effects, the onset is rapid (5-10 minutes) if systemic absorption occurs.
• Duration of Effect: Local skin reactions subside within hours. The immunological 'desensitization' effect from immunotherapy can last for years after a full 3-5 year course is completed.
• Tolerance: Unlike many drugs, 'tolerance' in this context is the desired therapeutic outcome—where the immune system stops overreacting to the pollen.

| Parameter | Value |

|---|---|

| Bioavailability | Low (Subcutaneous), Very Low (Oral) |

| Protein Binding | Variable (Albumin binding for small components) |

| Half-life | Proteins: Hours to Days; Adrenergic components: 1-2 hours |

| Tmax | 15-30 minutes (systemic peak) |

| Metabolism | Proteolysis (Proteins), Hepatic (Adrenergic components) |

| Excretion | Renal (Metabolites) |

• Molecular Formula: Complex mixture (contains proteins, flavonoids like quercetin, and tannins).
• Molecular Weight: Ranges from <10 kDa to >70 kDa for various protein fractions.
• Solubility: Soluble in aqueous solutions and glycerin-water mixtures.
• Structure: A heterogeneous biological extract containing various peptide chains and secondary plant metabolites.

Aesculus Hippocastanum Flower is classified as a Non-Standardized Plant Allergenic Extract. It shares therapeutic space with other tree pollen extracts (e.g., Oak, Birch) but is unique due to its specific Adrenergic Agonist [EPC] properties, which distinguish it from simpler allergenic proteins.