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Dosage for Agrimonia Eupatoria is highly individualized and must be determined by a specialist (Allergist/Immunologist) based on the patient's sensitivity levels. There is no 'standard' dose for non-standardized extracts.

Diagnostic Dosing

• Prick/Puncture Test: Usually one drop of a 1:10 or 1:20 w/v concentration applied to the skin.
• Intradermal Test: If the prick test is negative, 0.02 mL of a much more dilute solution (e.g., 1:1000 w/v) may be injected into the dermis.

Immunotherapy Dosing (SCIT)

Immunotherapy follows a two-phase schedule:

1. 1Build-up Phase: Injections are given 1–2 times per week. The starting dose is typically very low (e.g., 0.1 mL of a 1:100,000 w/v dilution). The dose is gradually increased over 3–6 months until the 'maintenance dose' is reached.
2. 2Maintenance Phase: Once the effective dose is reached, injections are given every 2–4 weeks. The maintenance dose is usually the highest dose the patient can tolerate without significant local or systemic reactions (often 0.5 mL of a 1:100 or 1:10 w/v dilution).

Agrimonia Eupatoria is generally considered safe for use in children, though immunotherapy is rarely initiated in children under the age of 5 due to the difficulty of cooperation and the risk of systemic reactions. Dosing logic for children is similar to adults but requires extreme caution and potentially slower dose escalation. Clinical studies have shown that pediatric patients may be at a higher risk for systemic reactions during the build-up phase.

Renal Impairment

No specific dosage adjustments are provided in the manufacturer labeling for renal impairment. However, patients with severely compromised renal function should be monitored closely for systemic stability.

Hepatic Impairment

No dosage adjustments are required for hepatic impairment, as the clearance of allergenic proteins does not rely on hepatic CYP450 metabolism.

Elderly Patients

Caution is advised in elderly patients, particularly those with underlying cardiovascular disease. The ability of an elderly patient to tolerate the physiological stress of a systemic reaction or the administration of epinephrine (if needed) must be assessed before starting therapy.

Agrimonia Eupatoria allergenic extract is never self-administered. It must be administered by a trained healthcare professional in a medical facility.

• Preparation: The extract is usually diluted with sterile albumin-saline or buffered saline.
• Administration: Injections are given subcutaneously (usually in the posterior aspect of the upper arm). The site should be rotated between injections.
• Observation: Patients MUST remain in the doctor's office for at least 30 minutes following any injection to monitor for signs of anaphylaxis.
• Storage: Vials should be stored in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze.

If a dose is missed during the build-up phase, the next dose may need to be reduced or the previous dose repeated, depending on the length of the delay. If a maintenance dose is missed by more than a week, the doctor may reduce the dose for the next injection to ensure safety. Consult your allergist immediately if a dose is missed.

An 'overdose' in the context of allergenic extracts refers to the administration of a dose that exceeds the patient's current tolerance level. This can occur due to a calculation error or a sudden change in the patient's sensitivity (e.g., during peak pollen season).

• Signs: Rapid onset of hives, swelling, wheezing, drop in blood pressure, or abdominal cramping.
• Emergency Measures: Administration of epinephrine (1:1000) via intramuscular injection, oxygen, intravenous fluids, and antihistamines.

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

Most patients undergoing treatment with Agrimonia Eupatoria will experience some form of local reaction. These are generally considered a normal part of the immune response to the extract.

• Local Redness (Erythema): Redness at the injection site that usually appears within minutes and resolves within a few hours.
• Swelling (Wheal): A raised, itchy bump at the injection site. If the swelling is larger than a half-dollar (approx. 3 cm), it should be reported to the doctor before the next dose.
• Pruritus (Itching): Intense itching at the site of administration.
• Tenderness: Minor soreness in the arm where the injection was given.

These reactions are slightly more significant and may require a pause or adjustment in the dosing schedule.

• Large Local Reactions: Swelling that extends across a joint or involves a large portion of the upper arm.
• Fatigue: A general feeling of tiredness or 'malaise' following the injection.
• Headache: Mild to moderate headache occurring within 24 hours of treatment.
• Mild Rhinitis: Sneezing or a runny nose shortly after the injection.

• Lymphadenopathy: Swelling of the lymph nodes near the injection site (e.g., in the armpit).
• Urticaria (Hives): Hives appearing on parts of the body other than the injection site.
• Persistent Induration: A hard lump at the injection site that lasts for several days.

> Warning: Stop taking Agrimonia Eupatoria and call your doctor immediately if you experience any of these symptoms of a systemic reaction or anaphylaxis.

• Anaphylaxis: A life-threatening allergic reaction characterized by a sudden drop in blood pressure and difficulty breathing.
• Angioedema: Severe swelling of the lips, tongue, or throat that can obstruct the airway.
• Bronchospasm: Tightness in the chest, wheezing, or a persistent cough.
• Hypotension: Feeling faint, dizzy, or losing consciousness.
• Generalized Urticaria: Rapid onset of hives over the entire body.
• Tachycardia: A racing or pounding heartbeat.

Long-term use of allergenic extracts like Agrimonia Eupatoria is generally well-tolerated over the typical 3-to-5-year course of immunotherapy. There is no evidence that long-term use leads to the development of autoimmune diseases or malignancy. However, some patients may develop a persistent sensitivity to the extract or experience 'serum sickness' (a delayed immune reaction involving joint pain and fever), though this is extremely rare with modern extracts.

WARNING: RISK OF SEVERE SYSTEMIC REACTIONS

Allergenic extracts, including Agrimonia Eupatoria, can cause severe, life-threatening systemic reactions, including anaphylaxis. Patients must be observed for at least 30 minutes in a medical facility after each injection. This product is not for use in patients with unstable or severe asthma. Patients taking beta-blockers may be resistant to the effects of epinephrine used to treat anaphylaxis. Physicians prescribing this product should be experienced in the treatment of allergic diseases and the management of emergencies.

Report any unusual symptoms to your healthcare provider.

Agrimonia Eupatoria must be used with extreme caution. The primary risk associated with this therapy is the induction of the very allergic symptoms it is intended to treat. Patients must be in stable health at the time of each injection. If you are experiencing an acute asthma flare-up or a severe respiratory infection, your doctor will likely postpone your injection.

No FDA black box warnings for Agrimonia Eupatoria are currently listed in the same format as high-risk pharmaceuticals like antidepressants; however, all allergenic extracts carry a prominent 'Warning' section in their prescribing information regarding the risk of anaphylaxis and the requirement for professional administration. This is functionally equivalent to a black box warning in the clinical setting.

• Allergic Reactions / Anaphylaxis Risk: This is the most significant risk. Reactions can occur within minutes of administration. Patients with a history of high sensitivity to Rosaceae plants are at elevated risk.
• Asthma Status: Patients with uncontrolled or severe asthma (FEV1 < 70% of predicted) are at a significantly higher risk for fatal systemic reactions. Asthma must be well-controlled before an injection is administered.
• Beta-Blocker Use: Patients taking beta-blockers (e.g., metoprolol, propranolol) are at increased risk because these drugs can interfere with the action of epinephrine, the primary treatment for anaphylaxis.
• Cardiovascular Disease: Patients with pre-existing heart conditions may not tolerate the physiological stress of a systemic reaction or the administration of epinephrine.

Patients undergoing immunotherapy with Agrimonia Eupatoria require consistent monitoring:

• Pre-Injection Assessment: The doctor will check for current symptoms (asthma, hay fever) and the size of the reaction from the previous injection.
• Post-Injection Observation: A mandatory 30-minute wait time in the clinic.
• Lung Function: Periodic peak flow or spirometry tests may be performed for patients with a history of asthma.
• Skin Testing: Periodic re-evaluation of skin sensitivity may be used to track progress.

While Agrimonia Eupatoria does not directly cause sedation, a systemic reaction or the administration of emergency medications (like antihistamines or epinephrine) can cause dizziness, drowsiness, or impaired coordination. It is recommended that patients do not engage in strenuous exercise for several hours after an injection, as this can increase the rate of drug absorption and the risk of a reaction.

There is no direct chemical interaction between alcohol and Agrimonia Eupatoria. However, alcohol consumption can cause vasodilation (widening of blood vessels), which may theoretically increase the speed of allergen absorption or mask the early signs of an allergic reaction. It is best to avoid alcohol on the day of your injection.

Immunotherapy is typically discontinued if the patient experiences a life-threatening systemic reaction or if no clinical improvement is seen after 12–24 months of maintenance therapy. There is no 'withdrawal' syndrome associated with stopping Agrimonia Eupatoria, but allergic symptoms may return if the course of treatment was not completed (usually 3–5 years).

> Important: Discuss all your medical conditions with your healthcare provider before starting Agrimonia Eupatoria.

• Beta-Adrenergic Blockers (Beta-Blockers): While not an absolute contraindication in all cases, the use of beta-blockers (e.g., atenolol, timolol eye drops) is generally avoided. The clinical consequence is that if the patient has an anaphylactic reaction to the Agrimonia extract, epinephrine may be ineffective, leading to refractory (untreatable) bronchospasm and hypotension.

• ACE Inhibitors: Drugs used for blood pressure (e.g., lisinopril) may increase the risk of severe systemic reactions and hypotension during immunotherapy.
• MAO Inhibitors (MAOIs): Medications like phenelzine may potentiate the effects of epinephrine, leading to a hypertensive crisis if emergency treatment is needed.
• Tricyclic Antidepressants: Similar to MAOIs, these can increase the cardiovascular risks associated with epinephrine administration.

• Antihistamines: Drugs like cetirizine, loratadine, or diphenhydramine will suppress the skin's response to Agrimonia Eupatoria. Patients must stop taking antihistamines for 3–7 days before diagnostic skin testing to ensure accurate results.
• Topical Corticosteroids: If applied to the skin test site, these can reduce the wheal and flare response, leading to a false-negative result.

• High-Tannin Foods: Since the Agrimonia plant is naturally high in tannins, there is a theoretical (though clinically unproven) risk of increased sensitivity if the patient consumes high amounts of other tannin-rich foods (like tea or red wine) immediately before an injection.
• Cross-Reactive Foods: Some patients sensitive to Agrimonia (Rosaceae family) may experience oral allergy syndrome when eating related fruits like apples, peaches, or strawberries. Discuss these symptoms with your doctor.

• St. John's Wort: May increase skin sensitivity to light, but no direct interaction with allergenic extracts is documented.
• Herbal Astringents: Using other herbal products containing Agrimony while undergoing immunotherapy should be discussed with a provider to avoid over-sensitization.

• Skin Prick Tests: As mentioned, antihistamines and certain antidepressants can interfere with skin test results.
• Total IgE: Immunotherapy may cause a transient increase in total IgE levels early in treatment, which does not necessarily reflect clinical worsening.

For each major interaction, the mechanism involves either the suppression of the diagnostic signal (pharmacodynamic) or the interference with emergency rescue protocols (pharmacodynamic). Management strategies always involve a thorough medication review by the allergist before every injection.

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

• Severe, Uncontrolled Asthma: Patients with an FEV1 persistently below 70% of predicted values should not receive Agrimonia Eupatoria injections. The risk of a fatal bronchospasm during a systemic reaction is unacceptably high.
• Previous Severe Systemic Reaction: If a patient has experienced life-threatening anaphylaxis to Agrimonia Eupatoria in the past, further immunotherapy is usually strictly contraindicated.
• Acute Infection or Fever: Injections should not be given during an active infection, as the immune system is already stressed, increasing the risk of an adverse reaction.
• Recent Myocardial Infarction: Patients who have had a heart attack within the last 3–6 months should avoid this therapy due to the risk associated with potential epinephrine use.

• Pregnancy (Initiation): Immunotherapy is generally not started during pregnancy. However, if a patient is already on a stable maintenance dose and becomes pregnant, the therapy may be continued under close supervision.
• Autoimmune Disorders: Patients with active systemic lupus erythematosus (SLE) or rheumatoid arthritis may have unpredictable responses to immunotherapy.
• Malignancy: Patients undergoing active chemotherapy or radiation are generally not candidates for allergen immunotherapy.
• Beta-Blocker Therapy: As noted, this requires a careful risk-benefit analysis by the physician.

Patients allergic to Agrimonia Eupatoria may show cross-sensitivity to other members of the Rosaceae family, which includes:

• Roses
• Strawberries, Raspberries, and Blackberries
• Apples, Pears, and Plums
• Hawthorn (Crataegus)

If you have had a severe reaction to any of these plants or fruits, inform your allergist before testing with Agrimonia Eupatoria.

> Important: Your healthcare provider will evaluate your complete medical history before prescribing Agrimonia Eupatoria.

Agrimonia Eupatoria is classified as FDA Pregnancy Category C. This means that animal reproduction studies have not been conducted, and it is not known whether the extract can cause fetal harm. The primary risk during pregnancy is maternal anaphylaxis, which can lead to uterine contractions, placental hypoperfusion (reduced blood flow), and fetal hypoxia (lack of oxygen). Initiation of immunotherapy is generally postponed until after delivery. If a patient is already on maintenance therapy and becomes pregnant, the dose is usually not increased to minimize the risk of a reaction.

It is not known whether the allergenic components of Agrimonia Eupatoria are excreted in human milk. However, since these are large proteins that are processed locally and systemically by the mother's immune system, it is unlikely that significant amounts reach the infant. Breastfeeding is generally considered safe during immunotherapy, but the mother should be monitored for any unusual reactions.

Allergen immunotherapy is generally indicated for children aged 5 years and older. The safety and efficacy in children under 5 have not been established. Pediatric patients require careful monitoring because they may be less able to communicate the early symptoms of a systemic reaction (e.g., an 'itchy throat' or 'funny feeling' in the chest).

Clinical studies of allergenic extracts often do not include sufficient numbers of subjects aged 65 and over. In geriatric patients, the decision to use Agrimonia Eupatoria must account for the higher prevalence of cardiovascular disease and the potential for polypharmacy (taking multiple medications), which increases the risk of drug interactions.

There are no specific guidelines for Agrimonia Eupatoria use in patients with renal impairment. Because the antigens are proteins that are enzymatically degraded rather than filtered directly by the kidneys in their active form, standard renal impairment is not usually a barrier to therapy. However, patients on dialysis should be treated with extreme caution.

No dosage adjustment is required for patients with hepatic impairment. The processing of allergenic extracts occurs via the immune system and proteolysis, not through the liver's cytochrome P450 enzyme system.

> Important: Special populations require individualized medical assessment.

Agrimonia Eupatoria allergenic extract acts as an immunomodulator. At the molecular level, the extract contains various proteins and glycoproteins that serve as epitopes (binding sites) for IgE antibodies. In diagnostic use, these epitopes trigger the cross-linking of FceRI receptors on mast cells. In therapeutic use, the repeated exposure to these epitopes induces T-cell anergy (unresponsiveness) or the development of T-regulatory cells that secrete IL-10 and TGF-beta. These cytokines suppress the allergic inflammation and promote the production of IgG4 blocking antibodies.

• Dose-Response: There is a clear dose-response relationship in skin testing; higher concentrations produce larger wheals. In immunotherapy, higher maintenance doses are generally associated with better long-term efficacy, provided they are tolerated.
• Time to Onset: Diagnostic reactions occur within 15–20 minutes. The therapeutic effect of immunotherapy usually takes 6–12 months to become noticeable.
• Duration of Effect: A completed 3-to-5-year course of immunotherapy can provide relief for several years after discontinuation.

| Parameter | Value |

|---|---|

| Bioavailability | N/A (Subcutaneous/Intradermal only) |

| Protein Binding | Primarily binds to IgE and IgG4 antibodies |

| Half-life | Varies by protein component (hours to days) |

| Tmax | 15–30 minutes for local immunological peak |

| Metabolism | Proteolysis by endogenous enzymes |

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

• Composition: A complex aqueous extract containing nitrogenous compounds, carbohydrates, and plant secondary metabolites (tannins, flavonoids).
• Molecular Weight: Ranges from 10 kDa to over 70 kDa for the primary allergenic proteins.
• Solubility: Highly soluble in water and buffered saline solutions.

Agrimonia Eupatoria belongs to the Non-Standardized Plant Allergenic Extract [EPC] class. It is grouped with other Rosaceae extracts and various weed, grass, and tree pollens used in clinical allergy practice.