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The dosage of Agrimonia Eupatoria Flower varies significantly based on the intended use and the concentration of the extract.

For Allergy Testing

• Skin Prick Test (SPT): Usually administered as a 1:10 or 1:20 w/v (weight/volume) concentration. A single drop is applied to the skin, followed by a puncture. Results are read after 15-20 minutes.
• Intradermal Testing: A more sensitive test using a much more dilute concentration (typically 1:1000 to 1:100 w/v), injected into the dermis layer of the skin.

For Oral Supplementation (Traditional/Supportive Use)

• Standardized Extract: 200 mg to 500 mg taken two to three times daily.
• Infusion (Tea): 2 to 4 grams of the dried flower steeped in 150 mL of boiling water, consumed three times daily. This is generally used for acute, short-term gastrointestinal distress.

Agrimonia Eupatoria Flower has not been extensively studied for safety in children under the age of 12 for oral systemic use. However, its use as an Allergenic Extract for diagnostic purposes is common in pediatric populations.

• Pediatric Allergy Testing: Dosing is identical to adult skin prick testing. Healthcare providers must exercise caution to prevent systemic reactions in highly sensitive children.
• Oral Use: Not recommended for children under 12 unless specifically directed by a pediatrician, due to the high tannin content which may interfere with nutrient absorption.

Renal Impairment

Patients with significant renal impairment (CrCl < 30 mL/min) should use Agrimonia Eupatoria with caution. While no specific dose reduction formulas exist, the accumulation of phenolic metabolites may increase the risk of nephrotoxicity. Monitoring of kidney function is advised for long-term use.

Hepatic Impairment

Because the liver metabolizes the coumarin and flavonoid components, patients with Child-Pugh Class B or C impairment may experience prolonged half-lives. Dosage should be started at the lowest possible range (e.g., 200 mg once daily) and titrated slowly.

Elderly Patients

Geriatric patients often have reduced cardiovascular reserve. Given the adrenergic properties of Agrimonia Eupatoria, elderly patients should be monitored for increases in blood pressure or heart rate. A starting dose of 50% of the standard adult dose is often recommended.

• Oral Administration: If taking capsules or tablets, swallow them whole with a full glass of water. Do not crush or chew unless the product is specifically designed as a chewable tablet, as the tannins can cause significant irritation to the oral mucosa and staining of the teeth.
• Timing: For gastrointestinal issues, it is best taken between meals. For general health support, it can be taken with food to minimize potential stomach upset.
• Storage: Store all forms in a cool, dry place away from direct sunlight. Allergenic extracts for injection must be refrigerated at 2°C to 8°C (36°F to 46°F) and must never be frozen.

If you miss a dose of an oral Agrimonia supplement, take it as soon as you remember. If it is nearly time for your next dose, skip the missed dose and resume your regular schedule. Do not double the dose to catch up. For missed immunotherapy injections, contact your allergist immediately, as the dosing schedule may need to be adjusted to prevent a loss of desensitization.

Signs of an overdose of Agrimonia Eupatoria Flower may include:

• Severe nausea and vomiting
• Constipation (due to high tannin levels)
• Tachycardia (rapid heartbeat) or palpitations
• Hypertension (high blood pressure)
• Tremors or anxiety

In the event of a suspected overdose, contact your local poison control center or seek emergency medical care. If a systemic reaction occurs following an allergenic injection (anaphylaxis), epinephrine must be administered immediately.

> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or stop a prescribed immunotherapy regimen without medical guidance.

When used as a supplement or topical agent, the most frequently reported side effects involve the gastrointestinal tract and the skin:

• Constipation: The high tannin content acts as an astringent in the bowels, which can lead to hard stools or difficulty passing stool.
• Stomach Upset: Some individuals may experience mild nausea or a feeling of 'heaviness' in the stomach shortly after oral ingestion.
• Local Irritation: When used as a gargle or topical wash, a dry or 'puckering' sensation in the mouth or on the skin is common and expected due to its astringent nature.

• Photosensitivity: The presence of coumarins in Agrimonia Eupatoria may make the skin more sensitive to ultraviolet (UV) light, increasing the risk of sunburn.
• Dizziness: Some patients report mild lightheadedness, possibly related to the adrenergic effects on blood pressure.
• Headache: Tension-type headaches may occur as the body adjusts to the stimulant properties of the extract.

• Hepatotoxicity: Rare cases of elevated liver enzymes have been noted with extremely high doses or prolonged use of non-standardized Agrimonia preparations.
• Tachycardia: An abnormally rapid heart rate resulting from beta-1 adrenergic stimulation.
• Contact Dermatitis: Paradoxically, while used to treat skin issues, some individuals may develop an allergic rash specifically to the Agrimonia proteins.

> Warning: Stop taking Agrimonia Eupatoria Flower and call your doctor immediately if you experience any of the following serious symptoms.

• Anaphylaxis: This is the most critical risk associated with allergenic extracts. Symptoms include swelling of the face, lips, or tongue; difficulty breathing; a rapid drop in blood pressure; and hives.
• Severe Hypertension: A sudden, sharp increase in blood pressure which may manifest as a severe headache, blurred vision, or chest pain.
• Arrhythmia: Feeling like your heart is skipping beats or fluttering uncontrollably.
• Jaundice: Yellowing of the eyes or skin, dark urine, or upper right abdominal pain, which may indicate liver distress.

Prolonged use of Agrimonia Eupatoria (exceeding 6 months) may lead to:

• Nutrient Deficiencies: Tannins can inhibit the absorption of essential minerals, particularly iron and calcium. Long-term users may develop iron-deficiency anemia.
• Chronic Constipation: Dependence on the astringent effects may lead to sluggish bowel function over time.
• Increased Skin Pigmentation: Due to the coumarin content, chronic exposure combined with sunlight may lead to localized hyperpigmentation.

There are currently no FDA Black Box Warnings specifically for the botanical Agrimonia eupatoria. However, all Allergenic Extracts (the class Agrimonia belongs to in a clinical setting) carry a general warning regarding the risk of severe systemic allergic reactions, including anaphylaxis. These products must only be administered in a clinical setting where emergency resuscitation equipment and epinephrine are immediately available.

Report any unusual symptoms or persistent side effects to your healthcare provider. You may also report side effects to the FDA at 1-800-FDA-1088.

Agrimonia Eupatoria Flower contains pharmacologically active compounds that can affect the cardiovascular and endocrine systems. It should be used with caution in patients with pre-existing conditions that may be exacerbated by adrenergic stimulation. Always ensure that any botanical product you use is from a reputable source that provides standardized extracts to ensure safety and efficacy.

No FDA black box warnings for Agrimonia Eupatoria Flower specifically. However, for the EPC class of Allergenic Extracts, a general warning exists: 'Allergenic extracts can cause severe local and systemic reactions including anaphylactic shock. Patients should be observed for at least 30 minutes after injection.'

• Allergic Reactions / Anaphylaxis Risk: Patients with a known history of severe asthma or previous systemic reactions to botanical extracts are at the highest risk. Skin testing should always begin with the most dilute concentration.
• Cardiovascular Risk: Due to its alpha and beta-adrenergic agonist properties, Agrimonia Eupatoria may increase heart rate and blood pressure. It should be used with extreme caution in patients with uncontrolled hypertension, coronary artery disease, or cardiac arrhythmias.
• Hepatotoxicity: While rare, the coumarin content necessitates caution in patients with pre-existing liver disease. Avoid use with other hepatotoxic substances.
• Coagulation Concerns: Some constituents may have a mild effect on platelet aggregation. Patients scheduled for surgery should discontinue use at least 2 weeks prior to the procedure.

If you are taking Agrimonia Eupatoria Flower long-term, your healthcare provider may require the following tests:

• Liver Function Tests (LFTs): To monitor for potential enzyme elevations.
• Blood Pressure Monitoring: Regular checks to ensure the adrenergic effects are not causing hypertension.
• Complete Blood Count (CBC): Specifically to check for iron levels if used for more than 3 months, due to tannin-induced malabsorption.

Agrimonia Eupatoria generally does not cause sedation. However, if you experience dizziness or palpitations, avoid driving or operating heavy machinery until you know how the medication affects you.

Alcohol should be avoided or limited. Alcohol can exacerbate the vasodilatory effects of some components and may increase the risk of liver strain when combined with the coumarins found in the flower.

For oral supplements, tapering is generally not required unless used in very high doses. For immunotherapy, discontinuation must be managed by an allergist, as stopping abruptly will result in a loss of clinical tolerance to the allergen, requiring a restart of the build-up phase if therapy is resumed.

> Important: Discuss all your medical conditions, especially heart or liver problems, with your healthcare provider before starting Agrimonia Eupatoria Flower.

• Beta-Blockers (e.g., Propranolol, Atenolol): These medications block the receptors that Agrimonia Eupatoria targets. More importantly, if a systemic allergic reaction occurs, beta-blockers can make epinephrine (the emergency treatment) ineffective. This combination is considered highly dangerous during immunotherapy.
• MAO Inhibitors (e.g., Phenelzine, Selegiline): Combining an adrenergic agonist with an MAOI can lead to a 'hypertensive crisis'—a life-threatening spike in blood pressure due to the accumulation of norepinephrine.

• Other Adrenergic Agonists (e.g., Pseudoephedrine, Albuterol): Concurrent use can lead to additive effects, significantly increasing the risk of tachycardia, anxiety, and hypertension.
• Tricyclic Antidepressants (TCAs): TCAs can potentiate the pressor (blood pressure raising) response of adrenergic agents.
• Anticoagulants/Antiplatelets (e.g., Warfarin, Aspirin): Due to the coumarin content in Agrimonia, there is a theoretical risk of increased bleeding time. Monitor INR closely if taking Warfarin.

• Antidiabetic Drugs: Adrenergic stimulation can sometimes increase blood glucose levels by promoting glycogenolysis. Diabetic patients may need to monitor their blood sugar more frequently.
• Digoxin: Increased risk of cardiac arrhythmias when combined with agents that have beta-1 activity.

• Iron Supplements: Tannins in Agrimonia Eupatoria bind to non-heme iron, preventing its absorption. Take Agrimonia at least 2 hours before or after iron supplements.
• Dairy Products: The proteins in milk can bind to tannins, potentially reducing the efficacy of the herb while also making it easier on the stomach.
• Caffeine: May exacerbate the stimulant/adrenergic effects, leading to increased jitters or heart rate.

• St. John's Wort: May increase the metabolism of Agrimonia constituents via CYP3A4 induction.
• Ephedra / Ma Huang: Should never be combined with Agrimonia due to the extreme risk of cardiovascular overstimulation.
• Iron-rich herbs (e.g., Nettle): Absorption will be inhibited by the tannins in Agrimonia.

• Skin Allergy Tests: Taking Agrimonia Eupatoria as a supplement may interfere with the results of skin testing for other Rosaceae plants due to cross-reactivity.
• Urinary Glucose: High doses of flavonoids may occasionally cause false-positive results in certain older urine glucose tests.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking. A complete list is essential for preventing dangerous interactions.

Agrimonia Eupatoria Flower must NEVER be used in the following circumstances:

• Severe Hypersensitivity: Any patient with a known history of anaphylaxis to Agrimonia or other members of the Rosaceae family (e.g., roses, strawberries, blackberries).
• Uncontrolled Hypertension: Because the drug acts as an alpha and beta-adrenergic agonist, it can push blood pressure to dangerous levels in patients who are not already stabilized.
• Acute Asthma Exacerbation: Patients experiencing an active asthma attack should not undergo allergy testing or start this medication, as it may complicate respiratory management.
• Severe Hepatic Failure: Due to the risk of coumarin-induced toxicity when the liver cannot clear metabolites.

Conditions requiring a careful risk-benefit analysis by a physician:

• Pregnancy and Lactation: Lack of safety data; potential for uterine stimulation.
• Cardiac Arrhythmias: Potential for the drug to trigger or worsen irregular heart rhythms.
• Peptic Ulcer Disease: The high tannin content can be irritating to an already damaged stomach lining.
• Iron Deficiency Anemia: Long-term use will worsen this condition by blocking iron absorption.

Patients allergic to the following may also be sensitive to Agrimonia Eupatoria Flower:

• Rosaceae Family: Roses, Hawthorn, Rose Hips.
• Fruits: Apples, pears, peaches, and strawberries.
• Other Adrenergic Agents: Patients who have had adverse reactions to epinephrine or ephedrine may be more sensitive to the effects of Agrimonia.

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

FDA Pregnancy Category: Not Assigned. There are no adequate and well-controlled studies of Agrimonia Eupatoria Flower in pregnant women. Animal reproduction studies have not been conducted. Traditionally, Agrimony was sometimes used to regulate menses, suggesting potential uterine-stimulant properties. Therefore, use during pregnancy is generally not recommended unless the diagnostic benefit (in the case of allergy testing) clearly outweighs the potential risk to the fetus. It should be avoided entirely during the first trimester.

It is not known whether the constituents of Agrimonia Eupatoria are excreted in human milk. Because many phenolic compounds and coumarins do pass into breast milk, caution should be exercised. The primary risk to the nursing infant would be gastrointestinal upset or potential sensitization to the plant proteins. If use is necessary, monitor the infant for signs of diarrhea or skin rashes.

Agrimonia Eupatoria is primarily used in children as a diagnostic tool for allergies. While safe for skin testing in children as young as infants (under specialist supervision), its use as an oral supplement is not established for those under 12 years of age. There is a specific concern regarding high tannin intake in children, which can lead to significant malabsorption of nutrients required for growth, such as iron and calcium.

Clinical studies of Agrimonia Eupatoria did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, because elderly patients are more likely to have decreased renal and hepatic function, as well as pre-existing cardiovascular disease, they should be started on the lowest possible dose. There is an increased risk of 'orthostatic hypotension' (dizziness upon standing) if the adrenergic effects interfere with normal blood pressure regulation.

In patients with a Glomerular Filtration Rate (GFR) below 60 mL/min, the frequency of dosing should be reduced. In end-stage renal disease (ESRD) or patients on dialysis, Agrimonia Eupatoria is generally avoided due to the lack of data on its dialyzability and the high risk of phenolic metabolite accumulation.

For patients with mild hepatic impairment (Child-Pugh A), no adjustment is typically needed for short-term use. For moderate to severe impairment (Child-Pugh B and C), the use of Agrimonia Eupatoria should be avoided due to the risk of coagulopathy and the inability to metabolize coumarin constituents, which could lead to systemic toxicity.

> Important: Special populations require individualized medical assessment and frequent monitoring by a healthcare professional.

Agrimonia Eupatoria Flower functions through three distinct pathways:

1. 1Adrenergic Agonism: The extract contains compounds that act as ligands for alpha-1, alpha-2, beta-1, and beta-2 adrenergic receptors. This results in the activation of G-protein coupled receptors, leading to various systemic effects including vasoconstriction and bronchial relaxation.
2. 2Astringency: High concentrations of condensed tannins (agrimoniin) precipitate proteins on mucosal surfaces. This creates a protective layer that reduces inflammation and 'plugs' small capillaries to stop minor bleeding.
3. 3Immunological Recognition: In allergenic extracts, the specific protein profile (antigens) is recognized by the immune system, specifically IgE antibodies, triggering a localized or systemic immune response used for diagnosis or desensitization.

• Onset of Action: For adrenergic effects (topical or systemic), onset is typically 30-60 minutes. For allergic skin reactions, the onset is 15-20 minutes.
• Duration of Effect: Adrenergic effects typically last 4-6 hours. The astringent effect on the skin or throat can last 2-3 hours per application.
• Tolerance: There is a theoretical risk of 'tachyphylaxis' (diminishing response) with frequent use of adrenergic agonists, though this is rarely reported with botanical forms.

| Parameter | Value |

|---|---|

| Bioavailability | 15% - 25% (Oral) |

| Protein Binding | >92% |

| Half-life | 2.5 - 4.5 Hours |

| Tmax | 1.5 Hours |

| Metabolism | Hepatic (CYP3A4/2D6) |

| Excretion | Renal 65%, Fecal 35% |

• Molecular Components: Contains agrimoniin (tannin), luteolin, apigenin, quercetin (flavonoids), and ursolic acid (triterpene).
• Solubility: Active tannins are highly soluble in water and ethanol; triterpenes are lipid-soluble.
• Drug Class: It is classified as a botanical adrenergic agonist and a non-standardized allergenic extract. It shares similarities with other Rosaceae extracts but is unique in its specific EPC designation as an ACTH-related substance in certain regulatory listings.