Angelica Acutiloba Root

Dosage for Angelica Acutiloba Root extract is not standardized and must be individualized based on the patient's sensitivity level, which is determined by their medical history and the results of skin testing.

Diagnostic Testing Dosage

• Prick Testing: A single drop of the extract (concentrated, often 1:10 or 1:20 w/v) is applied to the skin, and the skin is pricked through the drop.
• Intradermal Testing: If the prick test is negative, a dose of 0.02 mL to 0.05 mL of a highly diluted extract (e.g., 1:1000 w/v) may be injected into the dermis.

Immunotherapy Dosage

• Build-up Phase: Treatment typically begins with a very low dose (e.g., 0.05 mL of a 1:100,000 w/v dilution). Doses are increased weekly or bi-weekly by 50% to 100% until the 'maintenance dose' is reached.
• Maintenance Phase: The highest dose tolerated by the patient without significant systemic reactions. This is often 0.5 mL of a 1:100 or 1:10 w/v solution, administered every 2 to 4 weeks.

Angelica Acutiloba Root extract is generally considered safe for use in children, provided the child is old enough to cooperate with the testing or injection procedure.

• Dosing: Pediatric dosing follows the same escalation logic as adult dosing, though some clinicians may start at even lower concentrations for highly sensitive children.
• Safety: Children under the age of 5 may be at a higher risk of systemic reactions because they may not be able to communicate early symptoms of anaphylaxis clearly.

Renal Impairment

No specific dosage adjustments are required for patients with renal impairment, as the systemic load of the extract is extremely low. However, the patient's overall health should be considered if they are at risk for cardiovascular complications during a potential systemic reaction.

Hepatic Impairment

No dosage adjustments are formally established for hepatic impairment. The clearance of allergenic proteins is primarily through local and systemic proteolysis rather than hepatic CYP450 metabolism.

Elderly Patients

Caution should be exercised in elderly patients, particularly those with underlying cardiovascular disease. The use of epinephrine (the treatment for a severe reaction) may be more risky in this population. The dose should be increased more cautiously during the build-up phase.

This medication is NEVER for self-administration at home. It must be administered by a healthcare professional in a clinical setting.

• Administration Site: For immunotherapy, injections are given subcutaneously in the posterior aspect of the upper arm.
• Observation: Patients MUST remain in the doctor's office for at least 30 minutes following any injection or skin test to monitor for signs of a systemic reaction.
• 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 allergenic proteins, making the extract ineffective or unpredictable.

In immunotherapy, if a dose is missed:

• Less than 1 week late: Continue with the planned dose increase.
• 1-2 weeks late: Repeat the previous dose.
• More than 3 weeks late: The dose may need to be reduced significantly to avoid a 're-priming' effect that could lead to a reaction.

An 'overdose' in this context usually refers to an injection of too much extract or an injection given too soon after the previous one.

• Signs: Severe local swelling (larger than a golf ball), hives, wheezing, throat tightness, or a drop in blood pressure.
• Emergency Measures: Immediate administration of epinephrine, followed by antihistamines, corticosteroids, and emergency transport to a hospital if systemic symptoms persist.

> Important: Follow your healthcare provider's dosing instructions exactly. Do not attempt to use these extracts outside of a clinical environment.

Most patients undergoing testing or treatment with Angelica Acutiloba Root extract will experience local reactions. These are generally considered part of the drug's expected action rather than a complication.

• Local Wheal and Flare: A raised, white or flesh-colored bump surrounded by a ring of redness at the site of the skin test. This usually peaks within 15-20 minutes and resolves within an hour.
• Injection Site Swelling: During immunotherapy, redness and swelling (up to 2-3 cm) are common. This may feel like a mosquito bite or a firm 'knot' under the skin.
• Pruritus (Itching): Intense itching at the site of administration is very common and can be managed with topical cool compresses.

• Large Local Reactions (LLR): Swelling that exceeds 5-10 cm in diameter. This may be accompanied by warmth and tenderness that lasts for 24 to 48 hours.
• Fatigue: Some patients report feeling unusually tired for a few hours following an immunotherapy injection.
• Headache: Mild, transient headaches have been reported following systemic absorption of the extract.

• Generalized Urticaria: Hives appearing on parts of the body far away from the injection site.
• Angioedema: Swelling of the deeper layers of the skin, often around the eyes or lips.
• Rhinitis: Sneezing, runny nose, or nasal congestion triggered by the systemic immune response to the injection.

> Warning: Stop the procedure and call for emergency help immediately if you experience any of the following symptoms of anaphylaxis:

• Respiratory Distress: Wheezing, chest tightness, or difficulty breathing.
• Laryngeal Edema: A feeling of a 'lump in the throat,' hoarseness, or difficulty swallowing.
• Hypotension (Shock): Dizziness, fainting, rapid or weak pulse, and a sudden drop in blood pressure.
• Gastrointestinal Distress: Severe abdominal cramping, vomiting, or diarrhea occurring immediately after an injection.
• Cyanosis: Bluish tint to the lips or fingernails, indicating lack of oxygen.

Long-term use of Angelica Acutiloba Root extract in immunotherapy is generally well-tolerated. However, there is a theoretical risk of:

• Persistent Subcutaneous Nodules: Small, firm lumps at the injection site that may take months to resolve.
• Changes in Sensitivity: While the goal is desensitization, in rare cases, a patient's sensitivity to other related plants (cross-reactivity) could theoretically be altered.

Allergenic extracts, including Angelica Acutiloba Root, carry a significant FDA-mandated warning regarding the risk of severe systemic reactions.

• Anaphylaxis Risk: This extract can cause severe, life-threatening systemic reactions, including anaphylaxis and death.
• Supervision: It must only be administered by physicians who are exceptionally experienced in the treatment of anaphylaxis and have immediate access to emergency equipment (oxygen, IV fluids, epinephrine, and airway management tools).
• Patient Stability: Patients with unstable or severe asthma are at a significantly higher risk for fatal reactions and must be evaluated with extreme caution before administration.

Report any unusual symptoms, especially those occurring 30 minutes to 6 hours after an injection, to your healthcare provider immediately.

Angelica Acutiloba Root extract is a potent biological agent. Its use is restricted to diagnostic and therapeutic protocols under the guidance of an allergy specialist. It is not a supplement and should not be confused with over-the-counter 'Angelica' herbal products.

No FDA black box warnings for Angelica Acutiloba Root specifically exist as a unique entity, but it falls under the General Boxed Warning for Allergenic Extracts. This warning emphasizes that extracts may cause severe systemic reactions. Patients must be observed for at least 30 minutes. If a patient has a history of severe reactions to skin testing or previous immunotherapy, the starting dose must be extremely conservative.

• Allergic Reactions / Anaphylaxis Risk: The primary risk is an over-response of the immune system. Patients must be screened for recent illness, as a viral infection can lower the threshold for a systemic reaction.
• Asthma Status: If a patient's asthma is flaring (e.g., peak flow is down or they are using their rescue inhaler more often), the injection MUST be withheld. Uncontrolled asthma is the single greatest risk factor for a fatal reaction to allergenic extracts.
• Cardiovascular Health: Patients with significant heart disease may not be able to tolerate the physiological stress of anaphylaxis or the side effects of the epinephrine used to treat it.
• Beta-Blocker Use: Patients taking beta-blockers (e.g., metoprolol, propranolol) may be resistant to the effects of epinephrine, making a systemic reaction much harder to treat.

• Observation Period: A strict 30-minute wait time after every injection.
• Lung Function: For asthmatic patients, a peak flow meter or spirometry may be used before the injection to ensure the patient is at their baseline.
• Skin Assessment: The injection site should be checked for large local reactions 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 patient feels dizzy, fatigued, or 'off' after an injection, they should avoid driving until symptoms fully resolve.

Alcohol consumption should be avoided for several hours before and after an injection. Alcohol causes vasodilation, which can increase the rate of extract absorption and potentially increase the risk or severity of a systemic reaction.

If immunotherapy is discontinued, the patient's sensitivity to Angelica Acutiloba Root may eventually return to its baseline level. There is no 'withdrawal' syndrome, but the protective benefits of the treatment will gradually wane over several months to years.

> Important: Discuss all your medical conditions, especially respiratory or heart issues, with your healthcare provider before starting this extract.

While there are few absolute 'drug-drug' contraindications, certain combinations create unacceptable risks:

• Beta-Blockers (Systemic and Ophthalmic): Drugs like propranolol or timolol eye drops can block the effects of epinephrine. If a patient on these drugs has anaphylaxis from Angelica Acutiloba Root, standard emergency treatments may fail. This is often considered a relative or absolute contraindication depending on the clinical setting.

• ACE Inhibitors: Some studies suggest that patients taking ACE inhibitors (e.g., lisinopril) may be at a higher risk for more severe or frequent systemic reactions to allergenic extracts.
• MAO Inhibitors: These can potentiate the effects of epinephrine, leading to a hypertensive crisis if epinephrine must be administered to treat a reaction.
• Tricyclic Antidepressants: Similar to MAOIs, these can increase the cardiovascular sensitivity to epinephrine.

• Antihistamines: Drugs like cetirizine (Zyrtec) or diphenhydramine (Benadryl) will suppress the 'wheal and flare' response. These MUST be discontinued 3 to 7 days before skin testing to ensure accurate results. However, they are often continued during the immunotherapy phase to reduce local itching.
• H2 Blockers: Famotidine or ranitidine may also slightly interfere with skin test results and should be paused before diagnostic testing.
• Systemic Corticosteroids: Long-term use of high-dose steroids can suppress the immune response, potentially making skin tests less reliable or masking the early signs of a reaction.

• Cross-Reactive Foods: Patients sensitive to Angelica Acutiloba Root may also react to other members of the Apiaceae family, such as celery, carrots, parsley, or fennel. Consuming these foods immediately before or after an injection may increase the total 'allergen load' on the immune system.
• High-Fat Meals: No direct interaction, but heavy meals may complicate the management of gastrointestinal symptoms during anaphylaxis.

• St. John's Wort: May increase photosensitivity, which is relevant if the patient is also undergoing phototherapy, though not directly related to the extract's mechanism.
• Herbal Antihistamines: Supplements like Butterbur or Quercetin may interfere with skin testing in the same way as pharmaceutical antihistamines.

• Skin Prick Tests: The extract itself is the tool for this 'lab test.'
• Serum IgE Tests (ImmunoCAP): The presence of the extract in the body does not interfere with the measurement of IgE in the blood, but the treatment (immunotherapy) will eventually cause a rise in IgG4 levels and a gradual decline in specific IgE.

> Important: Tell your doctor about ALL medications, including eye drops and herbal supplements, before undergoing testing or treatment.

Angelica Acutiloba Root extract must NEVER be used in the following circumstances:

• Severe, Uncontrolled Asthma: Patients with a FEV1 (Forced Expiratory Volume) consistently below 70% of predicted values are at an extreme risk of death from an allergen-induced bronchospasm.
• Recent Myocardial Infarction (Heart Attack): Within the last 3-6 months. The heart cannot tolerate the stress of a potential systemic reaction or the epinephrine needed to treat it.
• History of Severe Anaphylaxis to this Specific Extract: If a patient has previously had a near-fatal reaction to Angelica Acutiloba Root, the risks of further treatment usually outweigh any potential benefits.

Conditions requiring careful risk-benefit analysis include:

• Beta-Blocker Therapy: Due to the interference with epinephrine mentioned previously.
• Pregnancy: While not a direct contraindication for continuing a stable maintenance dose, it is generally contraindicated to start immunotherapy during pregnancy due to the risk of fetal hypoxia during a systemic reaction.
• Autoimmune Diseases: In some cases, stimulating the immune system with extracts could theoretically exacerbate an underlying autoimmune condition.
• Malignancy: Patients with active cancer may have altered immune responses.

Patients should be aware of potential cross-reactivity with:

• Other Angelica Species: Angelica archangelica or Angelica sinensis (Dong Quai).
• Apiaceae Family: Celery, cumin, anise, and coriander. A patient with a severe allergy to celery may have a more vigorous reaction to Angelica Acutiloba Root.

> Important: Your healthcare provider will perform a comprehensive evaluation of your cardiovascular and respiratory health before prescribing this extract.

• Risk Summary: Angelica Acutiloba Root extract is classified as Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women.
• Clinical Considerations: The primary danger is not the extract itself but the potential for anaphylaxis. Anaphylaxis in the mother can lead to uterine contractions, placental abruption, and fetal hypoxia (lack of oxygen to the baby).
• Recommendation: Most allergists will NOT start a new build-up phase of immunotherapy during pregnancy. If a woman is already on a stable maintenance dose and is tolerating it well, the treatment may be continued, but the dose is typically not increased until after delivery.

• Passage into Milk: It is highly unlikely that the allergenic proteins in the extract pass into breast milk in any significant or active form.
• Safety: Immunotherapy is generally considered safe for breastfeeding mothers. There is no evidence of harm to the nursing infant.

• Approved Age: There is no specific lower age limit, but testing is rarely performed on infants under 6 months of age.
• Growth Effects: Long-term immunotherapy has not been shown to affect growth or development in children.
• Special Considerations: Because young children cannot always describe symptoms like 'throat itchiness' or 'chest tightness,' they must be monitored even more closely than adults.

• Cardiovascular Reserve: Older adults are more likely to have underlying heart disease, which increases the risk of complications from a systemic reaction.
• Renal Function: While renal clearance is not the primary pathway for the extract, age-related decline in organ function should be considered in the context of overall health.
• Polypharmacy: The higher likelihood of being on beta-blockers or ACE inhibitors makes this population higher risk.

• Dosing: No specific adjustments are required for patients with chronic kidney disease (CKD).
• Dialysis: The extract is not known to be dialyzable, but the timing of injections should not interfere with dialysis schedules.

• Dosing: No adjustments are necessary. The allergenic proteins are primarily processed by local tissue macrophages and systemic proteases rather than the liver's cytochrome P450 system.

> Important: Special populations require a highly individualized medical assessment by an allergy specialist.

Angelica Acutiloba Root extract functions as an exogenous antigen. In diagnostic testing, it cross-links IgE antibodies on the surface of mast cells and basophils. This cross-linking triggers a signal transduction cascade involving tyrosine kinases (such as Syk and Lyn), leading to the influx of calcium and the release of pre-formed mediators (histamine) and newly synthesized mediators (leukotrienes).

In immunotherapy, the mechanism is 'immune deviation.' The repeated exposure to the antigen leads to the induction of T-regulatory (Treg) cells that produce IL-10 and TGF-beta. These cytokines inhibit Th2 cells and promote the production of IgG4. IgG4 acts as a 'blocking antibody,' binding to the Angelica allergens before they can reach the IgE on the mast cells, thereby preventing the allergic reaction.

• Onset of Action: For skin testing, the onset is 15-20 minutes (immediate hypersensitivity). For immunotherapy, clinical improvement in symptoms typically takes 3 to 6 months of treatment.
• Duration of Effect: A single skin test reaction lasts 1-2 hours. The desensitization effect of immunotherapy can last for years after a 3-to-5-year course of treatment is completed.

| Parameter | Value |

|---|---|

| Bioavailability | Low (localized to skin/subcutaneous tissue) |

| Protein Binding | High (binds to specific IgE and IgG antibodies) |

| Half-life | Proteins cleared within 24-48 hours |

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

| Metabolism | Proteolysis by tissue and plasma enzymes |

| Excretion | Renal (metabolites) |

• Molecular Formula: Complex mixture of proteins, glycoproteins, and polysaccharides.
• Solubility: Soluble in aqueous buffers and glycerin-saline solutions.
• Description: A clear to slightly turbid liquid, ranging in color from straw to light brown, depending on the concentration of the root extract.

Angelica Acutiloba Root belongs to the therapeutic class of Allergenic Extracts. It is specifically grouped with non-standardized plant extracts. Related medications include extracts for Ragweed, Timothy Grass, and various tree pollens, though those are often available in standardized forms.