T-41

Dosage for Achillea Millefolium Flower extract is highly individualized and must be determined by an allergy specialist based on the patient's sensitivity levels. There is no 'standard' dose for all patients.

• Diagnostic Testing: For percutaneous (prick) testing, a concentrated extract (often 1:10 or 1:20 w/v) is used. For intradermal testing, the extract is typically diluted to a concentration of 1:1,000 or 1:10,000 w/v.
• Immunotherapy (Build-up Phase): Treatment usually begins with a very low dose (e.g., 0.05 mL of a 1:100,000 w/v dilution) administered subcutaneously once or twice weekly. The dose is gradually increased according to the patient's tolerance.
• Immunotherapy (Maintenance Phase): Once the 'maintenance dose' is reached (often 0.5 mL of a 1:100 or 1:20 w/v concentration), injections are spaced out to every 2 to 4 weeks.

Achillea Millefolium Flower extract is used in children, but extreme caution is required. Pediatric dosing follows the same escalation principles as adult dosing, but the starting concentration may be even lower depending on the child's history of asthma or previous systemic reactions. Clinical studies have shown that immunotherapy is generally effective in children aged 5 and older. It is rarely recommended for children under the age of 2 due to the difficulty of monitoring for early signs of anaphylaxis.

Renal Impairment

No specific dose adjustments are required for patients with renal impairment, as the protein load is negligible. However, the patient's overall health must be stable before administration.

Hepatic Impairment

No dosage adjustments are necessary for patients with liver disease.

Elderly Patients

Elderly patients (over 65) should be evaluated for underlying cardiovascular disease. If an elderly patient is taking beta-blockers for hypertension or heart disease, the use of Achillea Millefolium Flower extract may be contraindicated, as these medications can interfere with the effectiveness of epinephrine if a severe allergic reaction occurs.

Achillea Millefolium Flower extract is never self-administered. It must be given by a healthcare professional in a doctor's office or clinic.

1. 1Preparation: The skin (usually the forearm or back) is cleaned with alcohol.
2. 2Administration: For testing, a drop is placed on the skin and a sterile lancet is used to prick the surface. For immunotherapy, the injection is given subcutaneously (usually in the back of the upper arm).
3. 3Observation: Patients must remain in the clinic for at least 30 minutes following any injection. This is the period when life-threatening systemic reactions (anaphylaxis) are most likely to occur.
4. 4Storage: The extract must be stored in a refrigerator at 2°C to 8°C (36°F to 46°F). It should never be frozen.

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

• Short Delay (1-3 days): The usual dose may often be given.
• Long Delay (over 1 week): The healthcare provider may need to reduce the dose to ensure safety, as the patient's sensitivity may have increased during the gap.
• Significant Gap: If several weeks are missed, the build-up process may need to be restarted from a lower concentration.

An 'overdose' in the context of allergenic extracts usually refers to a dose that exceeds the patient's current threshold of tolerance. Signs of an overdose (systemic reaction) include:

• Generalized itching or hives (urticaria).
• Swelling of the throat or tongue.
• Difficulty breathing or wheezing.
• Rapid drop in blood pressure (fainting/dizziness).

Emergency Measures: If an overdose/systemic reaction occurs, the immediate administration of epinephrine (Adrenalin) is required. Healthcare providers will also use antihistamines, oxygen, and intravenous fluids as needed.

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

Most patients receiving Achillea Millefolium Flower extract will experience localized reactions. These are generally not dangerous but can be uncomfortable.

• Local Erythema: Redness at the site of the skin test or injection. This typically appears within minutes and may last for several hours.
• Pruritus: Intense itching at the site of administration. This is a direct result of histamine release in the skin.
• Wheal Formation: A raised, pale, or skin-colored bump (similar to a mosquito bite) at the injection site. A wheal larger than 5mm during testing is often considered a positive result.
• Local Swelling: Some patients may experience swelling of the upper arm (for injections) that can persist for 24 to 48 hours.

• Fatigue: Some patients report feeling unusually tired for a few hours after an immunotherapy injection.
• Headache: Mild to moderate headaches have been reported following administration.
• Nasal Congestion: A slight increase in hay fever-like symptoms shortly after the injection.
• Delayed Local Reactions: Swelling or redness that appears 6 to 12 hours after the injection rather than immediately.

• Generalized Urticaria: Hives appearing on parts of the body far away from the injection site.
• Lymphadenopathy: Swollen lymph nodes near the site of injection (e.g., in the armpit).
• Persistent Granuloma: A small, hard knot under the skin at the injection site that may take weeks to resolve.

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

• Anaphylaxis: This is a medical emergency. Symptoms include a sudden feeling of warmth, a 'sense of impending doom,' swelling of the lips/tongue, and difficulty swallowing.
• Bronchospasm: Sudden wheezing, chest tightness, or shortness of breath. This is particularly common in patients with pre-existing asthma.
• Hypotension: A dangerous drop in blood pressure, leading to dizziness, blurred vision, or loss of consciousness (fainting).
• Angioedema: Deep tissue swelling, particularly around the eyes, lips, or throat, which can obstruct the airway.
• Cyanosis: A bluish tint to the lips or fingernails, indicating a lack of oxygen in the blood.

There is no evidence that Achillea Millefolium Flower extract causes long-term organ damage or increases the risk of cancer. The primary long-term 'effect' is the desired modification of the immune system. However, in rare cases, repeated injections in the same area can lead to localized Lipoatrophy (loss of fat tissue under the skin) or minor scarring.

Achillea Millefolium Flower, like all allergenic extracts, carries a stringent warning regarding the risk of severe systemic reactions.

FDA Warning Summary:

1. 1This product can cause severe life-threatening systemic reactions, including anaphylaxis.
2. 2It should only be administered by physicians who are exceptionally experienced in the treatment of allergic diseases and the management of anaphylaxis.
3. 3Patients must be observed for at least 30 minutes in the office after every injection.
4. 4Patients with unstable asthma are at a significantly higher risk for fatal reactions.
5. 5The potency of non-standardized extracts can vary between manufacturers; therefore, a change in the source of the extract requires a cautious reduction in dosage.

Report any unusual symptoms to your healthcare provider.

Achillea Millefolium Flower extract is a potent biological agent. Its use is restricted to clinical settings where emergency resuscitative equipment is immediately available. Patients must be in their baseline state of health (no active infections or asthma flares) before receiving an injection. If you are feeling unwell on the day of your appointment, you must inform your nurse or doctor before the procedure.

No FDA black box warnings for Achillea Millefolium Flower are unique to this specific plant, but it falls under the General Black Box Warning for Allergenic Extracts. This warning emphasizes that these products are not interchangeable between manufacturers and that systemic reactions can occur even in patients who have previously tolerated the same dose.

• Allergic Reactions / Anaphylaxis Risk: This is the primary concern. The risk is cumulative and can change based on the patient's current 'allergic load' (e.g., if it is ragweed season and the patient is also allergic to ragweed, their threshold for a reaction to Yarrow may be lower).
• Asthma Status: Patients with severe or poorly controlled asthma (FEV1 < 70% of predicted) should generally not receive allergenic extracts, as they are at the highest risk for fatal bronchospasm.
• Cardiovascular Disease: Patients with underlying heart conditions may not be able to tolerate the physiological stress of a systemic reaction or the side effects of the epinephrine used to treat it.
• Autoimmune Disorders: Caution is advised in patients with active autoimmune diseases, as immunotherapy can theoretically exacerbate these conditions by stimulating the immune system.

• Immediate Observation: A 30-minute mandatory wait time after every injection is non-negotiable.
• Peak Flow Monitoring: For asthmatic patients, the doctor may perform a peak flow meter test before the injection to ensure lung function is stable.
• Skin Site Inspection: The injection site should be checked for large local reactions (greater than the size of a palm) before the patient leaves and again before the next dose is administered.

Most patients can drive after the 30-minute observation period. However, if a systemic reaction occurs or if the patient is given antihistamines as part of their treatment, they should not drive or operate heavy machinery until the symptoms and the effects of the medication have fully resolved.

While there is no direct chemical interaction between alcohol and Achillea Millefolium Flower extract, alcohol consumption can cause vasodilation (widening of blood vessels). This can theoretically increase the rate of absorption of the extract or mask the early signs of an allergic reaction. It is generally advised to avoid alcohol for several hours after an injection.

Immunotherapy is typically a 3-to-5-year commitment. Stopping the treatment early will not cause 'withdrawal' in the traditional sense, but the patient's allergy symptoms are likely to return to their pre-treatment levels. If a patient experiences a severe systemic reaction, the healthcare provider may decide to discontinue the treatment permanently for safety reasons.

> Important: Discuss all your medical conditions with your healthcare provider before starting Achillea Millefolium Flower.

• Beta-Blockers (e.g., Propranolol, Atenolol, Metoprolol): These medications are an absolute or strong relative contraindication. Beta-blockers interfere with the action of epinephrine (adrenaline). If a patient on a beta-blocker has an anaphylactic reaction to Achillea Millefolium Flower, the standard emergency treatment (epinephrine) may be ineffective, leading to a potentially fatal outcome.

• ACE Inhibitors (e.g., Lisinopril, Enalapril): These may increase the risk of more severe systemic reactions or interfere with the body's compensatory mechanisms during an allergic event.
• MAO Inhibitors (e.g., Phenelzine): These can potentiate the effects of epinephrine, leading to dangerously high blood pressure if emergency treatment is required.

• Antihistamines (e.g., Loratadine, Cetirizine, Diphenhydramine): These medications must be stopped 3 to 7 days before diagnostic skin testing. They block the H1 receptors in the skin, which prevents the 'wheal and flare' reaction, leading to a false-negative test result. However, they are often continued during the immunotherapy phase to reduce local itching.
• Tricyclic Antidepressants (e.g., Amitriptyline): Similar to antihistamines, these have H1-blocking properties and can interfere with skin test accuracy.
• Systemic Corticosteroids (e.g., Prednisone): Long-term use of high-dose steroids may suppress the immune response to the extract, potentially reducing the efficacy of immunotherapy.

• Cross-Reactive Foods: Patients allergic to Achillea Millefolium (Yarrow) may experience Oral Allergy Syndrome (OAS) when eating certain foods in the Asteraceae family, such as chamomile tea, sunflower seeds, or artichokes. Taking the extract while consuming these foods may increase the overall 'allergic load.'
• High-Fat Meals: No known interaction with the extract itself, but heavy meals can sometimes cause flushing, which may be confused with an early allergic reaction.

• Chamomile and Echinacea: These plants are closely related to Yarrow. Using supplements containing these while undergoing Yarrow immunotherapy may increase the risk of a systemic reaction due to cross-reactivity.
• St. John's Wort: May increase photosensitivity, though this does not directly interact with the allergenic extract mechanism.

• Skin Tests for Other Allergens: Achillea Millefolium Flower extract does not interfere with other skin tests, provided they are applied to different areas of the skin.
• Serum IgE Tests: Immunotherapy will eventually lead to changes in total and allergen-specific IgE levels in the blood, which is a desired clinical outcome rather than an 'interference.'

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

1. 1Previous Severe Systemic Reaction: If a patient has previously experienced life-threatening anaphylaxis in response to Achillea Millefolium Flower extract, further use is strictly prohibited.
2. 2Uncontrolled Asthma: Patients with an FEV1 (forced expiratory volume) consistently below 70% of their predicted value should not receive the extract, as the risk of a fatal respiratory event is too high.
3. 3Acute Infection: Administration should be delayed if the patient has a fever or a significant respiratory infection.
4. 4Malignancy or Severe Immunodeficiency: Patients with active cancer or severely compromised immune systems (e.g., advanced HIV) should not receive immunotherapy, as their immune systems cannot properly process the antigens.

1. 1Beta-Blocker Therapy: As noted, this significantly complicates the management of potential anaphylaxis.
2. 2Pregnancy (Initiation): Immunotherapy should generally not be started during pregnancy due to the risk of anaphylaxis-induced fetal hypoxia (lack of oxygen). However, if a woman is already on a stable maintenance dose, it may be continued.
3. 3Severe Eczema (Atopic Dermatitis): If the skin is severely inflamed, skin testing may be impossible to interpret (Dermatographism).
4. 4Cardiovascular Disease: Patients with unstable angina or recent heart attack require a careful risk-benefit analysis.

Achillea Millefolium Flower belongs to the Asteraceae family. Patients who are sensitive to this extract are highly likely to be cross-sensitive to:

• Ragweed (Ambrosia)
• Chrysanthemums
• Marigolds
• Daisies
• Chamomile
• Arnica

If a patient has a known severe allergy to any of these, the initial dose of Achillea Millefolium Flower must be extremely low to prevent a cross-reactive systemic event.

> Important: Your healthcare provider will evaluate your complete medical history before prescribing Achillea Millefolium Flower.

Achillea Millefolium Flower extract is classified by the FDA as 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 not the extract itself, but the potential for a systemic reaction (anaphylaxis) in the mother. Anaphylaxis can lead to a sudden drop in blood pressure and uterine contraction, which may cause fetal hypoxia (lack of oxygen) or miscarriage.

Clinical Practice: Most allergists will not start a new course of immunotherapy during pregnancy. However, if a patient is already at a maintenance dose and is tolerating it well, the treatment is usually continued at that dose (without further increases) to maintain the patient's allergic stability.

There is no data on the passage of Achillea Millefolium Flower antigens into human breast milk. However, since the antigens are proteins that are rapidly broken down in the mother's lymphatic system and are not expected to be absorbed orally by the infant, breastfeeding is generally considered safe during immunotherapy. The decision should be made in consultation with a healthcare provider.

Achillea Millefolium Flower extract is approved for use in the pediatric population, typically for children aged 5 years and older. The efficacy of immunotherapy in children is well-documented, particularly in preventing the 'allergic march' (the progression from hay fever to asthma).

Special Considerations: Children may have difficulty communicating the early, subtle symptoms of a systemic reaction (such as an itchy throat or a 'funny feeling'). Therefore, even more vigilant observation is required for pediatric patients.

Clinical studies of allergenic extracts often do not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects. In older adults, the primary concern is 'polypharmacy' (taking multiple medications) and the presence of underlying heart or lung disease. The risk-benefit ratio must be carefully weighed, especially if the patient is taking medications for hypertension or has a history of arrhythmia.

No specific studies have been conducted in patients with renal impairment. However, given the biological nature of the extract and the tiny amounts of protein involved, renal failure is not expected to affect the clearance or safety of the product. No dose adjustments are typically required.

There is no evidence that hepatic impairment affects the metabolism of allergenic extracts. The proteins are degraded by local and systemic proteases rather than the liver's microsomal enzyme system. No dosage adjustments are necessary for patients with liver disease.

> Important: Special populations require individualized medical assessment.

The pharmacology of Achillea Millefolium Flower extract is centered on the modulation of the Type I hypersensitivity response. The extract contains various antigenic proteins (allergens). When these allergens are introduced into a sensitized individual, they cross-link IgE antibodies on the surface of mast cells and basophils. This cross-linking triggers a signaling cascade involving tyrosine kinases (such as Syk), leading to the release of pre-formed mediators (histamine) and the synthesis of new mediators (leukotrienes).

In immunotherapy, the repeated, escalating exposure to these allergens leads to Desensitization. This involves:

1. 1T-cell Anergy: A reduction in the responsiveness of allergen-specific T-cells.
2. 2Regulatory T-cell (Treg) Induction: Increased production of IL-10 and TGF-beta, which suppress allergic inflammation.
3. 3Antibody Class Switching: A shift from IgE production to IgG4 production. IgG4 acts as a 'blocking antibody,' competing with IgE for allergen binding and preventing mast cell activation.

• Onset of Action (Testing): 15 to 20 minutes for a wheal and flare reaction.
• Onset of Action (Therapy): 3 to 6 months of build-up are usually required before a reduction in hay fever symptoms is noticed.
• Duration of Effect: If a full course (3-5 years) of immunotherapy is completed, the clinical benefits can last for several years after the treatment is stopped.

| Parameter | Value |

|---|---|

| Bioavailability | N/A (Administered locally/subcutaneously) |

| Protein Binding | Minimal (Antigens are processed by immune cells) |

| Half-life | Short (Proteins degraded within hours) |

| Tmax | 15-30 minutes (for local immune response) |

| Metabolism | Proteolytic degradation (Proteases) |

| Excretion | Renal (as peptide fragments) |

• Molecular Formula: N/A (Complex mixture of proteins, glycoproteins, and polysaccharides).
• Molecular Weight: Ranges from 10 kDa to over 70 kDa for various Yarrow antigens.
• Solubility: Soluble in aqueous solutions and 50% glycerin/water mixtures.
• Description: A clear to slightly hazy liquid, ranging in color from colorless to light amber, depending on the concentration and extraction method.

Achillea Millefolium Flower extract is a Non-Standardized Plant Allergenic Extract [EPC]. It is grouped with other Asteraceae extracts such as Ragweed (Ambrosia), Daisy (Bellis perennis), and Mugwort (Artemisia).