F04

Dosage for Aesculus X Carnea Flower extract is highly individualized and must be determined by an allergist based on the patient's sensitivity levels.

Diagnostic Dosing

• Skin Prick Test (SPT): One drop of the extract (typically 1:10 or 1:20 w/v) is applied to the skin, followed by a prick with a sterile lancet. A positive control (histamine) and negative control (saline) are used simultaneously.
• Intradermal Test: If the SPT is negative, 0.02 to 0.05 mL of a 1:100 or 1:1000 w/v dilution may be injected into the dermis to form a small bleb.

Immunotherapy Dosing

Immunotherapy follows a two-phase schedule:

1. 1Build-up Phase: Starting with a very dilute concentration (e.g., 0.05 mL of a 1:100,000 w/v dilution), doses are increased weekly or bi-weekly until the 'maintenance dose' is reached.
2. 2Maintenance Phase: Once the effective dose is reached (often 0.5 mL of a 1:100 or 1:10 w/v concentration), the interval between injections is increased to every 2–4 weeks. Treatment usually continues for 3 to 5 years.

Aesculus X Carnea Flower extract may be used in children, generally starting at age 5. The dosing logic is similar to adults (weight-based dosing is not typically used for allergenic extracts), but the physician may choose a more conservative build-up schedule to monitor for systemic reactions. Safety and efficacy in children under the age of 5 have not been extensively established.

Renal Impairment

No specific dosage adjustments are provided in the manufacturer labeling for patients with renal impairment. However, since systemic absorption is low, significant accumulation is unlikely. Caution is advised in patients with severe renal disease who may have a reduced ability to clear the inflammatory mediators released during a potential systemic reaction.

Hepatic Impairment

No dosage adjustments are required for hepatic impairment. The metabolism of the protein components occurs via general proteolytic pathways throughout the body, not solely in the liver.

Elderly Patients

Elderly patients (over 65) should be evaluated for cardiovascular stability before starting immunotherapy. If a systemic reaction occurs, the use of epinephrine may pose a higher risk in patients with pre-existing heart disease.

Aesculus X Carnea Flower extract is NOT for self-administration. It must be administered by a healthcare professional in a clinical setting equipped to handle emergency reactions.

• Administration: Subcutaneous injection (SCIT) is the standard for immunotherapy. It is usually given in the posterior aspect of the upper arm.
• Observation: Patients MUST remain in the clinic for at least 30 minutes following any injection to monitor for signs of anaphylaxis.
• Storage: Vials must be stored in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze. Freezing can denature the proteins, rendering the extract ineffective or potentially dangerous.

In immunotherapy, consistency is vital. If a dose is missed:

• Short Delay (1-2 weeks): The dose may be repeated or slightly reduced.
• Long Delay (over 4 weeks): The dose may need to be significantly reduced, and the build-up phase may need to be partially restarted to ensure safety.
• Never double a dose to catch up.

An 'overdose' in the context of allergenic extracts usually refers to an injection of a concentration higher than the patient's current tolerance level.

• Signs: Rapid onset of hives (urticaria), swelling of the throat (angioedema), wheezing, drop in blood pressure, or loss of consciousness.
• Emergency Measures: Immediate administration of epinephrine (1:1000), oxygen, IV fluids, and potentially corticosteroids or antihistamines. Emergency medical services (911) should be contacted immediately if a reaction occurs outside the clinic.

> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose without medical guidance.

Most patients undergoing skin testing or immunotherapy with Aesculus X Carnea Flower will experience local reactions. These are generally not dangerous but can be uncomfortable.

• Injection Site Redness (Erythema): A red patch at the site of the injection or skin test, usually appearing within minutes and resolving within hours.
• Local Swelling (Wheal): A raised, itchy bump at the injection site. For immunotherapy, a local reaction smaller than the size of a half-dollar is considered normal.
• Pruritus (Itching): Intense itching at the site of administration.
• Tenderness: The area may feel sore or 'bruised' for 24 hours after the injection.

• Large Local Reactions: Swelling that exceeds 5-10 cm in diameter. This may require a dose adjustment for the next scheduled injection.
• Fatigue: Some patients report feeling unusually tired for several hours after receiving an allergy shot.
• Mild Rhinitis: Sneezing or a runny nose shortly after the administration of the extract.

• Generalized Urticaria: Hives appearing on parts of the body away from the injection site.
• Vasovagal Reaction: Fainting or lightheadedness, often due to the needle stick rather than the extract itself.
• Persistent Granuloma: A small, firm lump under the skin at the injection site that may last for weeks.

> Warning: Stop taking Aesculus X Carnea Flower and call your doctor immediately if you experience any of these symptoms of a systemic allergic reaction (anaphylaxis).

• Respiratory Distress: Difficulty breathing, wheezing, or a feeling of tightness in the chest.
• Laryngeal Edema: A 'lump in the throat,' hoarseness, or difficulty swallowing, indicating swelling of the airway.
• Hypotension: A sudden drop in blood pressure, which may manifest as severe dizziness, confusion, or fainting.
• Tachycardia: A rapid, pounding heartbeat.
• Cyanosis: Bluish tint to the lips or fingernails, indicating a lack of oxygen.

There are no known long-term 'toxic' effects of Aesculus X Carnea Flower extract when used as directed. Because it is a biological protein extract, it does not accumulate in organs like synthetic drugs. The primary long-term consideration is the successful modulation of the immune system, which is the intended therapeutic effect. However, repeated injections in the same site over years can occasionally cause localized thickening of the skin (lichenification).

Aesculus X Carnea Flower, like all allergenic extracts, carries a significant warning regarding the risk of severe systemic reactions.

FDA-Style Warning Summary:

• Anaphylaxis Risk: This product can cause severe, life-threatening systemic allergic reactions, including anaphylaxis.
• Supervision: Must only be administered by healthcare professionals prepared to manage life-threatening reactions.
• Observation: Patients must be observed for at least 30 minutes after administration.
• Contraindications: May be contraindicated in patients with severe or unstable asthma or those taking medications that could mask or complicate the treatment of anaphylaxis (e.g., beta-blockers).

Report any unusual symptoms to your healthcare provider.

Aesculus X Carnea Flower extract is a potent biological agent. Its use requires a careful balance between the benefit of allergy relief and the risk of induced allergic reactions. Patients must be fully informed of the signs of anaphylaxis and must have access to emergency care during and immediately after administration.

No FDA black box warnings for Aesculus X Carnea Flower specifically exist as a unique entity, but it falls under the General Class Warning for Allergenic Extracts. The class warning states that allergenic extracts can cause severe systemic reactions, including death. Treatment should only be initiated by physicians experienced in the diagnosis and treatment of allergic diseases.

• Anaphylaxis Risk: This is the primary concern. Reactions can occur even in patients who have previously tolerated the extract. The risk is higher during the 'build-up' phase or when starting a new vial (which may be more potent than an older, degraded vial).
• Asthma Status: Patients with symptomatic or unstable asthma are at a much higher risk for a fatal systemic reaction. Immunotherapy should be withheld if the patient is experiencing an asthma flare-up.
• Cardiovascular Health: Patients with pre-existing heart disease may be less able to tolerate the physiological stress of a systemic reaction or the effects of epinephrine used to treat it.
• Infection/Illness: Injections should be deferred if the patient has a fever or a significant respiratory infection, as this can lower the threshold for a systemic reaction.

• Wait Time: A mandatory 30-minute post-injection wait time in the clinic.
• Peak Flow: For asthmatic patients, a peak flow meter may be used before the injection to ensure lung function is stable.
• Skin Assessment: The injection site should be checked before the patient leaves the clinic and the patient should report any 'delayed' local reactions (occurring 6-24 hours later) at their next visit.

Most patients can drive after the 30-minute observation period. However, if a patient experiences significant fatigue or lightheadedness (a rare side effect), they should avoid operating machinery until the symptoms resolve.

Alcohol should be avoided on the day of an allergy injection. Alcohol causes vasodilation, which may theoretically increase the rate of absorption of the allergen from the injection site, potentially increasing the risk of a systemic reaction.

Immunotherapy is typically discontinued if:

1. 1The patient experiences a severe systemic reaction.
2. 2There is no clinical improvement after 1-2 years of maintenance therapy.
3. 3The patient has completed a successful 3-5 year course and is now asymptomatic upon natural exposure.

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

• Beta-Blockers (e.g., Propranolol, Metoprolol): These medications are generally contraindicated in patients receiving immunotherapy. The reason is two-fold: first, they can increase the severity of an allergic reaction; second, and more importantly, they block the effects of epinephrine. If a patient on a beta-blocker has anaphylaxis, the standard life-saving dose of epinephrine may fail to work.

• ACE Inhibitors (e.g., Lisinopril, Enalapril): Some studies suggest that ACE inhibitors may increase the risk of systemic reactions to allergenic extracts or may worsen the severity of hypotension during anaphylaxis.
• MAO Inhibitors (e.g., Phenelzine): These can potentiate the effects of epinephrine, leading to a hypertensive crisis if epinephrine must be administered for an allergic reaction.

• Antihistamines (e.g., Cetirizine, Loratadine): While often used to manage allergy symptoms, antihistamines can suppress the 'wheal and flare' response during diagnostic skin testing. Patients must typically stop antihistamines for 3 to 7 days before skin testing to ensure accurate results. They do not, however, interfere with the efficacy of immunotherapy.
• Tricyclic Antidepressants (e.g., Amitriptyline): Similar to MAOIs, these may alter the body's response to epinephrine.

• High-Fat Meals: There is no direct interaction, but heavy meals immediately before an injection may make the patient feel nauseated if a mild systemic reaction occurs.
• Alcohol: As mentioned, alcohol should be avoided on injection days due to increased vasodilation.

• St. John's Wort: May theoretically affect the metabolism of other medications used to treat allergic reactions, though direct data with Aesculus X Carnea is lacking.
• Ginkgo Biloba: Has anti-platelet effects; while not a direct contraindication, it is worth noting for patients prone to bruising at the injection site.

• Skin Testing: The extract itself is the 'test.' However, the use of topical steroids at the site of testing can cause a false-negative result by suppressing the local inflammatory response.
• IgE Testing: Treatment with immunotherapy will eventually lead to changes in serum IgE and IgG4 levels, which is an expected pharmacological effect rather than an 'interference.'

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking.

• Severe, Unstable Asthma: Patients with an FEV1 (Forced Expiratory Volume) consistently below 70% of predicted value or those with frequent acute exacerbations should not receive Aesculus X Carnea Flower immunotherapy. The risk of a fatal bronchospasm during a systemic reaction is too high.
• Recent Myocardial Infarction (Heart Attack): Patients with unstable angina or a recent heart attack are at extreme risk if they require epinephrine for a reaction.
• Hypersensitivity to Extract Components: If a patient has a known history of anaphylaxis to even minute amounts of Aesculus proteins, the risk of testing or therapy may outweigh the benefits.

• Autoimmune Disorders: Patients with active systemic lupus erythematosus (SLE) or rheumatoid arthritis may have unpredictable immune responses to immunotherapy.
• Malignancy: Patients undergoing active chemotherapy or radiation may have a compromised immune system that cannot properly process the immunotherapy.
• Beta-Blocker Therapy: While often considered an absolute contraindication, in some life-threatening allergy cases, a doctor may perform a risk-benefit analysis (e.g., switching the patient to a different blood pressure medication).

Patients allergic to Aesculus X Carnea Flower may also react to:

• Aesculus hippocastanum (Common Horse Chestnut)
• Aesculus pavia (Red Buckeye)
• Other members of the Sapindaceae family.

> Important: Your healthcare provider will evaluate your complete medical history before prescribing Aesculus X Carnea Flower.

FDA Pregnancy Category: C

• Risk Summary: There are no adequate and well-controlled studies of Aesculus X Carnea Flower extract in pregnant women.
• Clinical Considerations: Generally, clinicians do not start immunotherapy during pregnancy because of the risk of anaphylaxis, which can cause fetal hypoxia (lack of oxygen). However, if a woman is already on a stable maintenance dose and is tolerating it well, the treatment is often continued. The dose is typically not increased during pregnancy.

It is not known whether the protein components of Aesculus X Carnea Flower extract are excreted in human milk. However, because these are large proteins that are digested in the gastrointestinal tract, they are unlikely to affect a nursing infant. The primary concern is the mother's safety; if she has a systemic reaction, the medications used to treat it (like high-dose antihistamines) might temporarily affect milk supply.

• Age Limit: Safety and efficacy are generally established for children 5 years of age and older.
• Considerations: Children may have difficulty communicating the early symptoms of a systemic reaction (like an itchy throat or 'funny feeling'). Close observation by clinical staff is even more critical in this population.

• Cardiovascular Risk: As noted, the elderly are at higher risk for complications from epinephrine.
• Polypharmacy: Older patients are more likely to be on beta-blockers or ACE inhibitors, which complicate immunotherapy safety.
• Pharmacokinetics: While the extract itself doesn't change, the aging immune system (immunosenescence) may result in a less robust response to the therapy.

No specific studies have been conducted. Given the nature of the product (biological proteins), renal impairment is not expected to significantly alter the safety profile, provided the patient is hemodynamically stable.

No dosage adjustments are required. The liver is not the primary site of action or clearance for these allergenic proteins.

> Important: Special populations require individualized medical assessment.

Aesculus X Carnea Flower extract acts as an exogenous antigen. In diagnostic use, it cross-links IgE on mast cells, causing the release of histamine. In therapeutic use, it induces 'desensitization.' This involves increasing the production of IL-10 and TGF-beta by regulatory T-cells, which suppresses the allergic Th2 response. It also induces B-cells to switch from producing IgE to producing IgG4, which acts as a 'decoy' or 'blocking' antibody, intercepting the allergen before it can reach the mast cells.

• Onset of Action (Diagnostic): 15–20 minutes for a skin test reaction.
• Onset of Action (Therapeutic): It may take 6 months to 1 year of immunotherapy before a significant reduction in symptoms is noticed.
• Duration of Effect: A successful course of immunotherapy can provide relief for 3 to 5 years (or longer) after the injections are stopped.

| Parameter | Value |

|---|---|

| Bioavailability | N/A (Subcutaneous/Local) |

| Protein Binding | Minimal in systemic circulation |

| Half-life | Variable (hours for proteins, years for immune memory) |

| Tmax | 1–2 hours (systemic absorption of proteins) |

| Metabolism | Proteolysis by tissue enzymes |

| Excretion | Renal (as small peptides/amino acids) |

• Molecular Formula: N/A (Complex mixture of proteins, glycoproteins, and polysaccharides).
• Molecular Weight: Ranges from 10 kDa to over 70 kDa for major allergens.
• Solubility: Soluble in aqueous buffers and glycerin-saline solutions.
• Description: A clear to slightly amber liquid extract derived from the flowers of Aesculus X Carnea.

Aesculus X Carnea Flower is a Non-Standardized Food Allergenic Extract [EPC]. Related medications include extracts of Aesculus hippocastanum and other tree pollens used in allergy clinics.