Allergena Zone 2

Dosage for Acacia Pollen immunotherapy is highly individualized and must be determined by an allergist based on the patient's sensitivity level (determined via skin testing). There is no 'standard' dose for all patients. The treatment is divided into two distinct phases:

Build-up Phase (Escalation)

During this phase, the patient receives increasing concentrations of the extract. Typically, injections are given 1 to 3 times per week. The starting dose is usually a very dilute solution (e.g., 0.05 mL of a 1:100,000 w/v dilution). The volume and concentration are gradually increased over 3 to 6 months until the 'Maintenance Dose' is reached.

Maintenance Phase

Once the target dose is achieved, the frequency of injections decreases. The maintenance dose is usually the highest dose tolerated by the patient without significant local or systemic reactions (often 0.2 mL to 0.5 mL of a 1:20 or 1:10 w/v solution). Maintenance injections are typically administered every 2 to 4 weeks for a period of 3 to 5 years.

Acacia Pollen extracts are generally approved for use in children, typically starting at age 5. Dosing principles for children are similar to those for adults, though some clinicians may use a more cautious (slower) build-up schedule. Immunotherapy is rarely started in children under the age of 5 due to the difficulty of communicating systemic symptoms and the potential risks of anaphylaxis in very young patients.

Renal Impairment

No specific dosage adjustments are required for patients with renal impairment, as the extract is not cleared via the kidneys in a manner that would lead to toxicity. However, the patient's overall health should be considered.

Hepatic Impairment

No dosage adjustments are necessary for hepatic impairment.

Elderly Patients

Caution is advised in elderly patients (over 65). While there is no specific age-based dose reduction, elderly patients are more likely to have underlying cardiovascular disease, which could make an accidental systemic reaction (anaphylaxis) more dangerous or harder to treat with epinephrine.

Acacia Pollen extracts are administered via subcutaneous injection (usually in the posterior aspect of the upper arm). They must NEVER be injected intravenously.

• Administration: Must be performed in a clinical setting by a healthcare professional.
• Observation: Patients MUST remain in the doctor's office for at least 30 minutes after every injection to monitor for signs of a systemic allergic reaction.
• Storage: Vials must be stored in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze. Potency can be lost if the extract is left at room temperature for extended periods.
• Site Rotation: It is recommended to rotate injection sites (e.g., alternating arms) to minimize local tissue irritation.

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 how much time has passed. If a dose is missed during the maintenance phase:

• 1-2 weeks late: Usually, the same dose can be given.
• 3-4 weeks late: The dose may need to be reduced by 25-50%.
• Over 4 weeks late: The physician may need to restart the build-up from a much lower concentration.

An 'overdose' in the context of immunotherapy occurs when a patient receives a dose higher than their current tolerance level. This can lead to severe local swelling or a systemic reaction (anaphylaxis). Signs include hives, itching, swelling of the throat, wheezing, or a drop in blood pressure. Emergency measures include the immediate administration of epinephrine, antihistamines, and potentially corticosteroids or oxygen.

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

Most patients undergoing Acacia Pollen immunotherapy will experience some form of local reaction at the site of the injection. These are generally considered a normal part of the body's response to the treatment.

• Local Redness (Erythema): The area around the injection site may turn red. This usually appears within minutes and resolves within a few hours.
• Swelling (Edema): A small bump or 'wheal' at the injection site. If the swelling is smaller than the size of a half-dollar (approx. 3 cm), it is generally not a cause for concern.
• Itching (Pruritus): Localized itching at the site of the needle entry.
• Tenderness: The arm may feel slightly sore or heavy for 24 hours following the injection.

• Large Local Reactions: Swelling that exceeds 5-10 cm in diameter. These may require a dose adjustment for the next scheduled injection.
• Fatigue: Some patients report feeling unusually tired for several hours after their 'allergy shots.'
• Mild Nasal Congestion: A slight 'flare' of allergy symptoms shortly after administration.

• Generalized Hives (Urticaria): Itchy red welts appearing on parts of the body far from the injection site.
• Angioedema: Deep tissue swelling, often occurring around the eyes, lips, or extremities.
• Persistent Cough: A dry, irritating cough that may signal the beginning of a systemic respiratory reaction.

> Warning: Stop taking Acacia Pollen and call your doctor immediately or seek emergency care if you experience any of these symptoms of anaphylaxis.

• Difficulty Breathing or Wheezing: Indicates constriction of the airways (bronchospasm).
• Throat Tightness: A feeling that the throat is closing or difficulty swallowing.
• Rapid or Weak Pulse: Signs of cardiovascular distress or an impending drop in blood pressure.
• Dizziness or Fainting: May indicate 'anaphylactic shock.'
• Nausea, Vomiting, or Abdominal Cramps: Systemic allergic reactions can sometimes manifest in the gastrointestinal tract.
• Cyanosis: A bluish tint to the skin or lips, indicating a lack of oxygen.

There are no known long-term 'toxic' effects of Acacia Pollen extracts on organs like the liver or kidneys. The primary long-term consideration is the development of persistent 'late-phase' local reactions, which are inflammatory swellings that appear 6 to 12 hours after the injection. In rare cases, repeated injections in the same area can lead to localized changes in skin texture (subcutaneous atrophy), though this is minimized by rotating injection sites.

Acacia Pollen allergenic extracts carry a Class-Wide Black Box Warning regarding the risk of severe anaphylaxis.

Summary of Warning:

1. 1Anaphylaxis Risk: This product can cause severe, life-threatening systemic allergic reactions, including anaphylaxis.
2. 2Supervision: It must only be administered in a setting where personnel are trained and equipment is available to treat anaphylaxis (including epinephrine).
3. 3Observation: Patients must be observed for at least 30 minutes after administration.
4. 4Pre-existing Asthma: Patients with unstable or severe asthma are at a higher risk for fatal reactions and should be evaluated carefully before each dose.
5. 5Beta-Blockers: Patients taking beta-blockers may be resistant to the effects of epinephrine used to treat a reaction.

Report any unusual symptoms to your healthcare provider.

Acacia Pollen immunotherapy is a high-potency biological treatment that requires strict adherence to safety protocols. It is not a 'cure' in the traditional sense but a long-term disease-modifying therapy. Patients must be committed to the schedule and must be honest with their provider about their current health status before every single injection.

No FDA black box warnings for Acacia Pollen specifically exist as a unique entity, but it falls under the General Black Box Warning for Allergic Extracts. This warning emphasizes that these extracts can cause severe, life-threatening anaphylaxis. It mandates that the drug be administered only by physicians who are exceptionally experienced in the treatment of systemic allergic reactions and that patients be monitored for a minimum of 30 minutes post-injection.

• Anaphylaxis Risk: This is the primary concern. Reactions can occur even in patients who have previously tolerated the same dose.
• Asthma Status: If a patient is experiencing an asthma flare or has a significantly reduced Peak Flow reading on the day of the injection, the dose should be withheld. Uncontrolled asthma is a major risk factor for a fatal reaction to immunotherapy.
• Acute Illness: Injections should be deferred if the patient has a fever or a significant respiratory infection.
• Exercise: Patients should avoid vigorous exercise for 2 hours before and 2 hours after their injection, as increased circulation can speed up the absorption of the allergen and increase the risk of a systemic reaction.

While routine blood work (like CBC or Liver Function Tests) is not required for Acacia Pollen extract, the following monitoring is essential:

• Symptom Review: Before each dose, the provider must ask about the reaction to the previous dose.
• Vital Signs: In some cases, blood pressure and heart rate may be checked.
• Lung Function: For asthmatic patients, a quick Peak Flow meter check is often performed before the injection.
• Skin Inspection: The injection site from the previous visit should be checked for lingering swelling.

Acacia Pollen itself does not cause sedation. However, if a patient experiences a systemic reaction or is given an antihistamine (like diphenhydramine) to treat a local reaction, their ability to drive or operate machinery may be impaired. Generally, if no reaction occurs during the 30-minute wait, driving is considered safe.

There is no direct chemical interaction between alcohol and Acacia Pollen extract. However, alcohol consumption can cause vasodilation (widening of blood vessels), which may theoretically increase the rate of allergen absorption or mask the early signs of an allergic reaction (such as flushing). It is best to avoid alcohol on the day of the injection.

Immunotherapy is typically discontinued after 3 to 5 years of successful maintenance. There is no 'withdrawal syndrome' associated with stopping Acacia Pollen extracts. However, if treatment is stopped prematurely, the patient's allergy symptoms are likely to return to their original severity.

> Important: Discuss all your medical conditions with your healthcare provider before starting Acacia Pollen.

There are no absolute drug-drug 'contraindications' in the way there are for chemical drugs, but certain combinations are extremely high-risk:

• Beta-Blockers (e.g., Propranolol, Atenolol, Metoprolol): These are often considered a relative contraindication. If a patient on a beta-blocker has an anaphylactic reaction to Acacia Pollen, the beta-blocker will prevent epinephrine (adrenaline) from working effectively. This can lead to an 'irreversible' or fatal reaction.

• ACE Inhibitors (e.g., Lisinopril, Enalapril): Some studies suggest that patients taking ACE inhibitors may be at an increased risk for more severe systemic reactions during immunotherapy, possibly due to the interference with the degradation of bradykinin.
• MAO Inhibitors (e.g., Phenelzine): These can potentiate the effects of sympathomimetic amines (like epinephrine) used to treat a reaction, leading to a hypertensive crisis.
• Other Immunotherapy: If a patient is receiving multiple types of allergy shots (e.g., Acacia plus Venoms or Molds), the risk of a systemic reaction is cumulatively higher.

• Antihistamines: While many patients take antihistamines to manage symptoms, regular use can 'mask' the early warning signs of a systemic reaction (like mild itching or hives), potentially allowing a more severe reaction to develop unnoticed.
• Systemic Corticosteroids: Long-term use of steroids may suppress the immune response, potentially making the immunotherapy less effective, though this is rarely a reason to stop treatment.

There are no known direct food interactions with Acacia Pollen extracts. However, patients with 'Oral Allergy Syndrome' (cross-reactivity between pollens and raw fruits/vegetables) should be aware that their sensitivity to certain foods might fluctuate during the build-up phase of immunotherapy.

• St. John’s Wort: No known interaction.
• Immunostimulants (e.g., Echinacea): Theoretically, substances that stimulate the immune system could interfere with the goal of inducing tolerance, though clinical data on this is lacking.

• Skin Tests: Taking Acacia Pollen immunotherapy will eventually cause a 'false negative' or reduced reaction on future skin prick tests for Acacia, as the body becomes desensitized.
• Serum IgE: Total and specific IgE levels may initially rise during the build-up phase before eventually falling during maintenance.

For each major interaction, the management strategy involves a careful risk-benefit analysis by the allergist. If a patient must remain on a beta-blocker for a life-threatening cardiac condition, the allergist may choose to use a more conservative immunotherapy schedule or opt for alternative treatments.

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

Acacia Pollen extracts must NEVER be used in the following circumstances:

1. 1Severe, Uncontrolled Asthma: Patients with an FEV1 (Forced Expiratory Volume) consistently below 70% of predicted values are at an unacceptably high risk for fatal bronchospasm during a systemic reaction.
2. 2Recent Myocardial Infarction or Unstable Angina: The heart must be able to withstand the stress of a potential anaphylactic reaction and the high doses of epinephrine required to treat it.
3. 3History of Severe Reaction to This Specific Extract: If a patient has previously experienced near-fatal anaphylaxis from Acacia extract despite dose adjustments, the treatment should be permanently discontinued.
4. 4Inability to Communicate: Patients who cannot report symptoms (e.g., very young children or those with severe cognitive impairment) are not candidates for SCIT (Subcutaneous Immunotherapy).

• Beta-Blocker Therapy: As noted, this increases the danger of the treatment. Some allergists will perform immunotherapy on beta-blockers if no other options exist, but it requires extreme caution.
• Autoimmune Diseases: There is a theoretical risk that stimulating the immune system could worsen conditions like Lupus or Rheumatoid Arthritis, though evidence for this is weak.
• Malignancy: Patients with active cancer are generally not started on immunotherapy, as their immune systems are often compromised or focused on the malignancy.
• Pregnancy (Starting Treatment): Immunotherapy should NOT be initiated during pregnancy due to the risk of anaphylaxis-induced fetal hypoxia (lack of oxygen).

Patients allergic to Acacia Pollen may show cross-sensitivity to other members of the Fabaceae (legume) family. This includes other tree species like Mimosa or even certain food legumes, though the clinical significance of 'pollen-food' cross-reactivity with Acacia is less common than with Birch or Ragweed.

> Important: Your healthcare provider will evaluate your complete medical history before prescribing Acacia Pollen.

Pregnancy Category C (Traditional): There are no adequate and well-controlled studies in pregnant women.

• Risk Summary: The primary risk to the fetus is not the extract itself, but the potential for maternal anaphylaxis, which can cause uterine contractions and fetal hypoxia.
• Clinical Management: If a woman is already on a stable 'Maintenance Dose' and becomes pregnant, the treatment is usually continued (as the risk of reaction is low). However, the dose is typically NOT increased during pregnancy, and the treatment is NEVER started for the first time in a pregnant patient.

It is generally considered safe to continue Acacia Pollen immunotherapy while breastfeeding. The allergenic proteins and the resulting IgG4 antibodies are not known to pass into breast milk in amounts that would harm the infant. In fact, some research suggests that maternal antibodies in breast milk might have a protective effect, though this is not proven.

• Approved Age: Generally safe for children 5 years of age and older.
• Growth Effects: There is no evidence that allergenic extracts interfere with growth or development.
• Special Considerations: Children often have higher rates of local reactions. The decision to start a child on shots must consider their ability to tolerate the pain of frequent injections and the 30-minute wait time.

In patients over 65, the risk-benefit ratio must be carefully weighed.

• Pharmacokinetic Changes: While the 'metabolism' of the extract doesn't change, the elderly have less 'physiological reserve' to survive a systemic reaction.
• Polypharmacy: Older adults are more likely to be on medications (like beta-blockers or ACE inhibitors) that complicate the management of anaphylaxis.

No specific studies have been conducted in renal impairment. However, since the proteins are processed by the immune system and not excreted as intact active drugs by the kidneys, no dose adjustment is expected to be necessary.

There is no known impact of liver disease on the safety or efficacy of Acacia Pollen extracts. The liver is not involved in the primary immunological processing of these allergens.

> Important: Special populations require individualized medical assessment.

Acacia Pollen extract acts as a biological response modifier. Its primary molecular target is the T-cell receptor (TCR) on naive T-cells. By presenting Acacia allergens (such as the proteins Aca f 1) in a controlled, escalating fashion, the extract induces a state of 'Peripheral Tolerance.'

1. 1T-Reg Induction: It stimulates the differentiation of CD4+ CD25+ Foxp3+ regulatory T cells.
2. 2Cytokine Switch: It reduces the production of Th2 cytokines (IL-4, IL-5, IL-13) which are responsible for IgE production and eosinophil recruitment, and increases Th1 cytokines (IFN-gamma) and IL-10.
3. 3B-Cell Modification: It induces B-cells to switch from IgE production to IgG4 production. IgG4 acts as a 'blocking antibody' that prevents the allergen from binding to IgE on mast cells.

• Onset of Effect: Clinical improvement is rarely immediate. It typically takes 3 to 6 months (reaching the maintenance phase) before patients notice a reduction in symptoms.
• Duration of Effect: The goal of a 3-5 year course is to provide long-lasting relief for years after the treatment is stopped.
• Tolerance: Unlike many drugs where tolerance means 'reduced effect,' in immunotherapy, 'tolerance' refers to the desired immunological state where the patient no longer reacts to the pollen.

| Parameter | Value |

|---|---|

| Bioavailability | N/A (Subcutaneous) |

| Protein Binding | N/A (Processed by APCs) |

| Half-life | Days (Immunological effect lasts years) |

| Tmax | 1-2 hours (Peak systemic absorption) |

| Metabolism | Proteolysis by immune cells |

| Excretion | Cellular catabolism |

• Molecular Formula: Complex mixture of proteins, glycoproteins, and polysaccharides.
• Molecular Weight: Ranges from 10 kDa to over 70 kDa for major allergens.
• Solubility: Highly soluble in aqueous buffered solutions or 50% glycerin.
• Description: A clear to slightly turbid liquid, ranging from colorless to light amber depending on the concentration and PNU content.

Acacia Pollen is classified as a Non-Standardized Allergenic Extract. It is part of the broader category of 'Biologicals' and 'Immunotherapeutic Agents.' It is related to other tree pollen extracts like Oak, Maple, and Juniper, but is distinguished by its specific botanical origin in the Acacia genus.