Large Intestine Formula

Dosage for Angelica Gigas Root extract is highly individualized and is never a 'one-size-fits-all' regimen. For diagnostic purposes, the dosage is expressed as the concentration of the extract used.

• Skin Prick Testing (SPT): Typically, a concentrated extract (e.g., 1:10 or 1:20 w/v) is applied to the skin, followed by a puncture. A positive control (histamine) and a negative control (saline/glycerin) are used simultaneously for comparison.
• Intradermal Testing: If SPT is negative, an intradermal injection of 0.02 mL to 0.05 mL of a much more dilute solution (e.g., 1:1000 or 1:500 w/v) may be administered.
• Immunotherapy (SCIT): The dosage follows a 'Build-up Phase' and a 'Maintenance Phase.'
• Build-up Phase: Starts with a very low dose (e.g., 0.05 mL of a 1:100,000 w/v dilution) once or twice weekly. The dose is incrementally increased by 20% to 50% at each visit, provided no significant local or systemic reactions occur.
• Maintenance Phase: Once the 'Top Dose' or 'Maintenance Dose' is reached (typically 0.5 mL of a 1:100 or 1:20 w/v concentration), the interval between injections is increased to every 2 to 4 weeks.

Angelica Gigas Root extract can be used in children, but extreme caution is required. There is no specific age-based dosage table; rather, the dosage is determined by the child's sensitivity level, similar to adults. However, children under the age of 5 may be less able to communicate the early symptoms of a systemic reaction (anaphylaxis), making them higher-risk candidates for immunotherapy. Pediatric dosing must be carefully monitored by a specialist in pediatric allergy.

Renal Impairment

No specific dosage adjustments are required for patients with renal impairment, as the protein load in allergenic extracts is minimal and does not place a significant burden on the kidneys. However, the patient's overall health should be stable before administration.

Hepatic Impairment

No dosage adjustments are necessary for hepatic impairment. The metabolism of allergenic proteins occurs via general proteolytic pathways rather than hepatic enzyme systems.

Elderly Patients

Elderly patients may have a diminished skin response to testing due to changes in skin elasticity and mast cell density. Furthermore, the risk of systemic reactions must be weighed against the presence of cardiovascular disease. If an elderly patient is taking beta-blockers or ACE inhibitors, immunotherapy may be contraindicated or require extreme caution.

Angelica Gigas Root extracts are strictly for professional use and are never self-administered by the patient at home.

1. 1Preparation: The healthcare provider will clean the skin (usually the forearm or back) with alcohol.
2. 2Administration: For testing, the extract is applied topically or injected intradermally. For immunotherapy, it is injected subcutaneously in the outer aspect of the upper arm.
3. 3Observation: The patient MUST remain in the medical office for at least 30 minutes following any injection or skin test to monitor for signs of anaphylaxis.
4. 4Storage: Extracts must be stored in a refrigerator at 2°C to 8°C (36°F to 46°F). They should never be frozen, as freezing can denature the allergenic proteins.

In the context of immunotherapy, a missed dose can lead to a loss of tolerance.

• If a dose is missed by only a few days, the previous dose may be repeated.
• If several weeks are missed, the dose may need to be reduced significantly to avoid a systemic reaction when restarting. Your allergist will follow a specific 'gap protocol' to safely resume treatment.

An 'overdose' in the context of allergenic extracts refers to the administration of a dose that exceeds the patient's current tolerance level, potentially leading to a systemic allergic reaction or anaphylaxis.

• Signs: Hives, itching, swelling of the throat, wheezing, shortness of breath, or a drop in blood pressure.
• Emergency Measures: Immediate administration of epinephrine (EpiPen), followed by antihistamines, corticosteroids, and emergency transport to a hospital if symptoms do not resolve rapidly.

> Important: Follow your healthcare provider's dosing instructions exactly. Do not attempt to alter the schedule or dose yourself, as this increases the risk of life-threatening reactions.

Side effects are categorized as local or systemic. Local reactions are extremely common and are often expected during the diagnostic process.

• Local Wheal and Flare: During skin testing, a raised, itchy bump (wheal) surrounded by redness (flare) is the expected positive result. This usually resolves within 1-2 hours.
• Injection Site Swelling: In immunotherapy, swelling at the site of the injection (up to the size of a half-dollar) is common. It may feel warm, itchy, or slightly painful. This typically peaks at 6-12 hours and subsides within 24-48 hours.
• Pruritus (Itching): Localized itching at the site of administration is the most frequently reported complaint.

• Large Local Reactions (LLR): Swelling that exceeds 5-10 cm in diameter at the injection site. While not dangerous, it often necessitates a dosage adjustment for the next visit.
• Fatigue: Some patients report feeling unusually tired for several hours after receiving an allergy injection.
• Headache: Mild tension-type headaches may occur following the administration of the extract.

• Systemic 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.
• Persistent Lymphadenopathy: Swelling of the lymph nodes near the injection site (e.g., in the axilla/armpit).

> Warning: Stop taking Angelica Gigas Root and call your doctor immediately or seek emergency care if you experience any of the following symptoms of anaphylaxis:

• Respiratory Distress: Wheezing, chest tightness, or difficulty breathing. This indicates bronchospasm, a serious allergic manifestation.
• Laryngeal Edema: A feeling of a 'lump in the throat,' hoarseness, or difficulty swallowing, indicating airway swelling.
• Hypotension (Shock): Dizziness, fainting, or a rapid, weak pulse. This can lead to cardiovascular collapse.
• Generalized Anaphylaxis: A combination of skin symptoms (hives), respiratory issues, and gastrointestinal distress (nausea, vomiting, cramping) occurring rapidly after administration.

There are no known 'toxic' long-term side effects of Angelica Gigas Root extract, as it is a biological protein. However, long-term immunotherapy can occasionally lead to 'serum sickness-like' reactions in very rare cases, characterized by joint pain, fever, and rash, though this is more common with heterologous sera than with plant extracts. The primary long-term 'effect' is the desired modification of the immune system.

WARNING: RISK OF SEVERE ALLERGIC REACTIONS

Angelica Gigas Root allergenic extract, like all allergenic extracts, can cause severe, life-threatening systemic reactions, including anaphylaxis.

• Extracts should only be administered by healthcare professionals prepared to manage anaphylaxis.
• Patients must be observed for at least 30 minutes after administration.
• Patients with unstable asthma are at a higher risk for fatal reactions.
• Immunotherapy may not be suitable for patients taking medications that could mask or complicate the treatment of anaphylaxis, such as beta-blockers.

Report any unusual symptoms, especially those occurring within the first hour of injection, to your healthcare provider immediately.

Angelica Gigas Root allergenic extract must only be used for the specific purpose of diagnosing or treating allergies to Angelica gigas. It is not a general-purpose supplement and should never be ingested or used in any manner other than directed by an immunology specialist. The most critical safety consideration is the potential for a rapid-onset systemic allergic reaction. Patients must be in a stable state of health before receiving an injection; for example, if you are currently suffering from an upper respiratory infection or an asthma flare-up, your injection should be postponed.

No FDA black box warnings for Angelica Gigas Root specifically exist as a standalone drug, but it falls under the General Class Warning for Allergenic Extracts. This warning emphasizes that these products can cause anaphylaxis, must be administered in a clinical setting equipped with emergency resuscitative equipment (including epinephrine), and require a mandatory 30-minute post-administration observation period.

• Allergic Reactions / Anaphylaxis Risk: This is the primary risk. The risk is higher during the build-up phase of immunotherapy and in patients with high levels of sensitivity.
• Asthma Status: Patients with severe or poorly controlled asthma are at significantly increased risk for a fatal systemic reaction. Asthma must be stable (FEV1 > 80% of predicted) before administration.
• Cardiovascular Disease: Patients with pre-existing heart conditions may be less able to tolerate the physiological stress of a systemic reaction or the effects of epinephrine if it must be administered.
• Autoimmune Disorders: Use with caution in patients with active autoimmune diseases, as immunotherapy theoretically could exacerbate these conditions, although data is limited.

• Peak Flow/Spirometry: For asthmatic patients, lung function should be checked before each injection.
• Skin Site Inspection: The injection site from the previous visit must be inspected for any delayed large local reactions before the next dose is given.
• Vitals: Blood pressure and heart rate may be monitored if a reaction is suspected.
• Observation: A strict 30-minute wait time in the clinic is the most important 'monitoring' requirement.

In most cases, Angelica Gigas Root does not affect the ability to drive. However, if a patient experiences a systemic reaction or receives epinephrine, they should not drive until cleared by a physician. Some patients may feel mild fatigue after an injection and should use caution.

Alcohol should be avoided for several hours before and after receiving an allergenic extract injection. Alcohol causes vasodilation (widening of blood vessels), which can increase the rate of allergen absorption from the injection site and potentially increase the risk or severity of a systemic reaction.

Immunotherapy is typically a 3-to-5-year commitment. If treatment is stopped prematurely, the allergic symptoms are likely to return. There is no 'withdrawal syndrome' associated with stopping allergenic extracts, but the clinical benefits will gradually diminish over time.

> Important: Discuss all your medical conditions, especially respiratory or heart problems, with your healthcare provider before starting Angelica Gigas Root.

• Beta-Blockers (e.g., Propranolol, Atenolol): These are generally contraindicated in patients receiving allergenic extracts. Beta-blockers can increase the severity of anaphylaxis and, more importantly, can make the reaction 'refractory' (resistant) to the standard treatment, which is epinephrine. If a patient must be on a beta-blocker, the risks of immunotherapy often outweigh the benefits.

• ACE Inhibitors (e.g., Lisinopril, Enalapril): These medications may increase the risk of systemic reactions or interfere with the body's natural compensatory mechanisms during an allergic event. While not strictly contraindicated, they require a careful risk-benefit analysis.
• MAO Inhibitors (e.g., Phenelzine): These can interfere with the metabolism of epinephrine, potentially leading to an exaggerated hypertensive response if emergency treatment is needed.

• Antihistamines (e.g., Cetirizine, Loratadine): These must be discontinued 3 to 7 days before skin testing, as they will suppress the wheal and flare response, leading to a false-negative result. However, they are often continued during the immunotherapy phase to reduce local itching.
• Tricyclic Antidepressants (e.g., Amitriptyline): Similar to MAOIs, these can potentiate the effects of epinephrine, requiring caution during emergency management.

• Alcohol: As mentioned, alcohol increases vasodilation and may accelerate the systemic absorption of the allergen, increasing the risk of a reaction.
• Spicy Foods: In some individuals, very spicy foods can cause flushing and may complicate the assessment of a mild allergic reaction.

• St. John's Wort: May theoretically affect the threshold for systemic reactions, though clinical data is lacking.
• Ginkgo Biloba: Known for its anti-platelet effects, it does not directly interact with the extract but could theoretically complicate the management of a severe systemic event.
• Oral Angelica Supplements: Taking oral 'Dang Gui' or Angelica supplements while undergoing immunotherapy with the root extract may lead to an 'additive' allergen load, potentially triggering a reaction. Patients should disclose all herbal use.

• Skin Tests: As noted, antihistamines and certain antidepressants (like doxepin) will interfere with the results of skin prick tests.
• Serum IgE: The administration of the extract will eventually lead to changes in serum IgE and IgG4 levels, which is a desired therapeutic outcome rather than a 'test interference.'

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, especially those for blood pressure, heart rhythm, or depression.

1. 1Severe or Uncontrolled Asthma: Patients with an FEV1 persistently below 70% of predicted or those with recent life-threatening asthma exacerbations should not receive Angelica Gigas Root extract. The risk of a fatal bronchospasm during a systemic reaction is unacceptably high.
2. 2Recent Myocardial Infarction (Heart Attack): Within the last 3-6 months. The cardiovascular stress of a potential anaphylactic reaction or the administration of epinephrine is a strict contraindication.
3. 3Hypersensitivity to Preservatives: If a patient has a known, severe allergy to phenol or glycerin (the inactive ingredients in the extract), the product must not be used.
4. 4Beta-Blocker Therapy: Due to the inability to effectively treat anaphylaxis with epinephrine.

1. 1Pregnancy: While not strictly contraindicated if a patient is already on a stable maintenance dose, starting new immunotherapy during pregnancy is generally avoided due to the risk of fetal hypoxia during a maternal systemic reaction.
2. 2Autoimmune Disease: Patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis require careful evaluation, as immune stimulation could theoretically trigger a flare.
3. 3Malignancy: Patients undergoing active chemotherapy or with certain cancers may have altered immune responses.
4. 4Severe Atopic Dermatitis: May make the interpretation of skin tests difficult or impossible.

Patients allergic to Angelica Gigas Root may show cross-reactivity with other members of the Apiaceae (Umbelliferae) family. This includes:

• Celery
• Carrots
• Fennel
• Anise
• Coriander/Cilantro
• Dill

If you have had a severe reaction to any of these foods, you must inform your allergist, as you may be at a higher risk of reacting to the Angelica Gigas Root extract.

> Important: Your healthcare provider will evaluate your complete medical history and current health status before prescribing or administering Angelica Gigas Root extract.

Angelica Gigas Root extract 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.

• Risk Summary: The primary concern during pregnancy is not the extract itself, but the risk of maternal anaphylaxis. Anaphylaxis can lead to maternal hypotension and uterine contraction, resulting in fetal hypoxia (lack of oxygen) and potential fetal death.
• Clinical Practice: Most allergists will NOT start a new course of immunotherapy during pregnancy. If a patient is already on a maintenance dose and is tolerating it well, the dose is typically maintained or slightly reduced, but not increased, until after delivery.

It is not known whether the components of Angelica Gigas Root extract are excreted in human milk. However, because the allergens are large proteins that are degraded into peptides, it is highly unlikely that they would be absorbed intact by the nursing infant. Immunotherapy is generally considered safe during breastfeeding, provided the mother is monitored for systemic reactions.

• Approved Use: There is no lower age limit for skin testing. For immunotherapy, it is rarely started in children under age 5 because of the difficulty in monitoring for early signs of anaphylaxis and the psychological stress of frequent injections.
• Growth Effects: There is no evidence that allergenic extracts affect growth or development in children.
• Special Considerations: Children with comorbid asthma must be monitored with particular care.

• Pharmacokinetic Changes: While PK is not significantly different, the physiological 'reserve' is lower.
• Comorbidities: The prevalence of cardiovascular disease and the use of medications like beta-blockers or ACE inhibitors are higher in this population, often making immunotherapy a higher-risk intervention.
• Skin Reactivity: Reduced skin turgor and mast cell reactivity may lead to smaller wheal-and-flare responses, potentially leading to under-diagnosis.

Renal impairment does not significantly alter the clearance of the small amounts of protein found in allergenic extracts. However, patients with end-stage renal disease (ESRD) may have altered immune function and should be treated with caution.

There are no specific precautions or dose adjustments required for patients with liver disease, as the liver is not the primary site of allergen degradation.

> Important: Special populations, particularly pregnant women and the elderly, require a highly individualized medical assessment before proceeding with allergenic extract therapy.

Angelica Gigas Root extract acts as a source of exogenous allergens. Its molecular mechanism involves the cross-linking of allergen-specific IgE antibodies bound to the FcεRI receptors on mast cells and basophils. This cross-linking triggers the release of pre-formed mediators (histamine, tryptase) and the de novo synthesis of lipid mediators (leukotrienes, prostaglandins). In immunotherapy, it induces 'immune deviation' by promoting the expansion of T-regulatory cells (CD4+CD25+Foxp3+) and the production of Interleukin-10 (IL-10) and Transforming Growth Factor-beta (TGF-β), which suppress the allergic Th2 response.

• Dose-Response: There is a clear dose-response relationship in skin testing; higher concentrations produce larger wheals until a plateau is reached. In immunotherapy, higher maintenance doses are generally more effective but carry a higher risk of systemic reactions.
• Onset of Effect: Skin test reactions occur within 15-20 minutes. The therapeutic effect of immunotherapy takes 6-12 months to become clinically significant.
• Duration: The diagnostic effect is transient. The therapeutic effect of a full 3-5 year course of immunotherapy can last for years after discontinuation.

| Parameter | Value |

|---|---|

| Bioavailability | Low (Subcutaneous), Negligible (Epicutaneous) |

| Protein Binding | Primarily to IgE and IgG4 antibodies |

| Half-life | Proteins degraded within hours; Immunologic effect lasts months |

| Tmax | 15-30 minutes for local reaction |

| Metabolism | Local and systemic proteolytic degradation |

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

• Molecular Components: Contains various proteins (acidic and basic), polysaccharides, and coumarins (such as decursin and decursinol). However, for the allergenic extract, the protein fraction is the primary active component.
• Solubility: Soluble in aqueous buffers and saline-glycerin mixtures.
• Storage: Must be kept at 2-8°C to prevent protein denaturation.

Angelica Gigas Root belongs to the class of Non-Standardized Plant Allergenic Extracts. It is grouped with other Umbelliferae extracts and is distinct from 'Standardized Extracts' (like Grass or Dust Mite) which have federally defined potency units.