Grain And Seed Antigens

Dosage for Amaranth allergenic extract is highly individualized and must be determined by an allergy specialist based on the patient's sensitivity levels.

Diagnostic Dosing

For skin prick testing, a single drop of the extract (typically at a concentration of 1:10 or 1:20 w/v) is applied to the skin. For intradermal testing, which is more sensitive, a much more dilute solution (ranging from 100 PNU/mL to 1000 PNU/mL) is injected into the dermis.

Immunotherapy Dosing

Immunotherapy follows a two-phase schedule:

1. 1Build-up Phase: Patients receive weekly or bi-weekly injections. The starting dose is usually very low (e.g., 0.05 mL of a 1:100,000 dilution). The dose is gradually increased over 3 to 6 months until the 'maintenance dose' is reached.
2. 2Maintenance Phase: Once the target dose is achieved (e.g., 0.5 mL of a 1:100 or 1:10 dilution), the frequency of injections is reduced to once every 2 to 4 weeks. This phase typically lasts 3 to 5 years to ensure long-term desensitization.

Amaranth allergenic extracts are generally considered safe for use in children, provided the child is old enough to undergo the testing and treatment (usually 5 years or older). The dosing logic for children is similar to adults, as it is based on immunological sensitivity rather than body weight. However, healthcare providers often use more conservative 'build-up' schedules for pediatric patients to minimize the risk of systemic reactions. Children must be monitored even more closely during the 30-minute post-injection period.

Renal Impairment

No specific dose adjustments are required for patients with renal impairment, as the proteins are naturally degraded by proteases. However, the patient's overall health status should be evaluated to ensure they can tolerate a potential systemic reaction.

Hepatic Impairment

No dose adjustments are necessary for patients with liver disease, as the metabolism of allergenic proteins does not rely on hepatic enzyme pathways.

Elderly Patients

Elderly patients may have a reduced skin response to diagnostic testing (false negatives). For immunotherapy, clinicians must carefully evaluate the patient's cardiovascular health, as the use of epinephrine (the primary treatment for a severe reaction) may be riskier in patients with underlying heart disease.

Amaranth allergenic extract is never self-administered by the patient at home. It must be administered in a clinical setting equipped with emergency resuscitation equipment.

• Skin Testing: The skin (usually the forearm or back) is cleaned with alcohol. The extract is applied, and a small prick is made through the drop. The results are read after 15 to 20 minutes.
• Immunotherapy Injections: These are given subcutaneously (just under the skin) in the outer aspect of the upper arm. The site should not be massaged after the injection.
• Storage: Extracts must be kept refrigerated at 2°C to 8°C (36°F to 46°F). Freezing the extract can denature the proteins and render them ineffective.

In immunotherapy, consistency is critical. If a dose is missed during the build-up phase, the next dose may need to be reduced or the previous dose repeated to maintain safety. If a dose is missed during the maintenance phase by more than 1-2 weeks, the healthcare provider will typically reduce the dose for the next injection and then gradually build back up to the maintenance level.

An 'overdose' in the context of allergenic extracts refers to receiving a dose higher than the patient's current tolerance level. This most commonly occurs due to a dosing error or a 'vial change' where the new extract is more potent than the old one.

• Signs: Rapid onset of hives, swelling of the throat, wheezing, drop in blood pressure, or abdominal cramping.
• Emergency Measures: Immediate administration of intramuscular epinephrine (0.3 mg for adults) and transfer to an emergency department. Patients must stay in the clinic for at least 30 minutes after every injection to monitor for these signs.

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

The most frequent side effects associated with Amaranth allergenic extracts are localized to the site of administration.

• Local Wheal and Flare: During diagnostic testing, a red, itchy bump is expected if the patient is allergic. This typically resolves within 1 to 2 hours.
• Injection Site Swelling: In immunotherapy, it is common to experience swelling and redness at the injection site (up to the size of a half-dollar). This may feel warm to the touch and be mildly painful. This 'local reaction' usually peaks at 6 to 12 hours and disappears within 24 to 48 hours.
• Pruritus (Itching): General itching at the site or a mild 'scratchy' throat may occur shortly after administration.

• Large Local Reactions: Swelling that exceeds 5-10 cm in diameter at the injection site. While not dangerous, these reactions often require a dose adjustment for the next injection.
• Fatigue: Some patients report feeling unusually tired or 'flu-like' for a few hours following an immunotherapy session.
• Headache: Mild to moderate tension-type headaches have been reported.

• Generalized Urticaria: Hives appearing on parts of the body far from the injection site.
• Angioedema: Swelling of the deeper layers of the skin, often around the eyes or lips.
• Persistent Granuloma: A small, hard knot under the skin at the injection site that may last for several weeks.

> Warning: Stop taking Amaranth and call your doctor immediately if you experience any of these symptoms of anaphylaxis.

• Respiratory Distress: Sudden wheezing, shortness of breath, or a feeling of tightness in the chest. This indicates bronchospasm (narrowing of the airways).
• Laryngeal Edema: A 'lump in the throat,' difficulty swallowing, or a hoarse voice, suggesting the airway is beginning to swell.
• Hypotension (Low Blood Pressure): Feeling dizzy, lightheaded, or fainting. This can be a sign of circulatory collapse.
• Tachycardia: A rapid or pounding heartbeat.
• Gastrointestinal Distress: Sudden, severe nausea, vomiting, or uterine cramping in women.

There are no known long-term 'toxic' effects of Amaranth allergenic extracts. Because they are natural proteins, they do not accumulate in the body like certain synthetic chemicals. The primary long-term 'effect' is the desired modification of the immune system. However, patients who undergo immunotherapy for many years should have their skin sensitivity re-evaluated periodically, as the goal is to eventually discontinue the treatment once tolerance is achieved.

While Amaranth extracts themselves may not always carry a specific boxed warning on every manufacturer's label, the entire class of allergenic extracts carries a general warning regarding Anaphylaxis.

• Summary: Allergenic extracts can cause severe, life-threatening systemic reactions, including anaphylaxis. Patients with unstable asthma are at a higher risk. Injections must be administered in a medical facility by trained personnel. Patients must be observed for at least 30 minutes. Epinephrine must be immediately available.

Report any unusual symptoms to your healthcare provider.

Amaranth allergenic extract is a potent biological product. Its use requires a careful balance between the benefit of desensitization and the risk of a systemic allergic reaction. It is not a 'vaccine' in the traditional sense and does not provide immediate relief from allergy symptoms; rather, it is a long-term disease-modifying therapy.

No FDA black box warnings for Amaranth specifically exist as a unique entity, but it is subject to the universal class warning for all Allergenic Extracts. This warning emphasizes that these products can cause severe, fatal anaphylaxis. It mandates that the product only be used by physicians experienced in the treatment of allergic diseases and that patients must be monitored for a minimum of 30 minutes following administration.

• Anaphylaxis Risk: The most significant risk is a systemic allergic reaction. This risk is higher during the 'build-up' phase of immunotherapy or when starting a new vial of extract.
• Asthma Stability: Patients with poorly controlled or unstable asthma should not receive Amaranth injections. If a patient is experiencing an asthma flare-up on the day of their injection, the dose should be withheld. Severe, even fatal, reactions to immunotherapy are significantly more common in patients with underlying asthma.
• Cardiovascular Disease: Patients with significant heart disease may be less able to tolerate the physiological stress of a systemic reaction or the effects of epinephrine used to treat such a reaction.
• Beta-Blocker Use: Patients taking beta-blockers (for blood pressure or heart issues) may be resistant to the effects of epinephrine, making a systemic reaction much harder to treat.

• Observation Period: Every patient must wait in the clinic for 30 minutes after an injection. Most fatal reactions occur within this window.
• Peak Flow Meter: For asthmatic patients, a healthcare provider may check peak expiratory flow (PEF) before the injection to ensure the lungs are functioning well.
• Skin Test Monitoring: During diagnostic testing, the patient must be observed for signs of a systemic reaction, even though the amount of allergen used is very small.

Generally, Amaranth extracts do not cause sedation or cognitive impairment. However, if a patient experiences a large local reaction or feels lightheaded after an injection, they should wait until they feel fully recovered before driving or operating heavy machinery.

There is no direct chemical interaction between alcohol and Amaranth extract. However, alcohol consumption can cause vasodilation (widening of blood vessels), which may theoretically increase the rate of absorption of the allergen or exacerbate the symptoms of an allergic reaction. It is generally advised to avoid heavy alcohol use on the day of an immunotherapy injection.

If a patient consistently experiences systemic reactions despite dose adjustments, the healthcare provider may decide to discontinue Amaranth immunotherapy. There is no 'withdrawal syndrome' associated with stopping allergenic extracts, but the patient's allergy symptoms will likely return to their baseline levels over time.

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

• Beta-Adrenergic Blockers (Beta-Blockers): These include medications like propranolol, atenolol, and metoprolol. They are contraindicated in patients receiving immunotherapy because they block the action of epinephrine. If a patient on beta-blockers has an anaphylactic reaction to Amaranth, the standard emergency treatment (epinephrine) may fail to work, leading to a potentially fatal outcome.

• ACE Inhibitors: Medications like lisinopril or enalapril, used for hypertension, have been associated with a higher risk of more severe systemic reactions during immunotherapy. While not strictly contraindicated, they require a careful risk-benefit analysis.
• MAO Inhibitors (MAOIs): These antidepressants can potentiate the effects of epinephrine, which could lead to a hypertensive crisis if epinephrine is needed to treat an allergic reaction.
• Tricyclic Antidepressants: Similar to MAOIs, these can interfere with the body's response to emergency medications.

• Antihistamines: Drugs like cetirizine (Zyrtec), loratadine (Claritin), and diphenhydramine (Benadryl) will suppress the skin's reaction to Amaranth. This leads to 'false negative' results during diagnostic testing. Patients must typically stop taking antihistamines for 3 to 7 days before a skin test.
• H2 Blockers: Medications like famotidine (Pepcid) can also mildly suppress skin test reactivity and should be discontinued before testing.
• Systemic Corticosteroids: Long-term use of oral steroids (like prednisone) can suppress the immune response, potentially making diagnostic testing less accurate and immunotherapy less effective.

There are no known direct food interactions with Amaranth allergenic extract. However, patients with a 'pollen-food allergy syndrome' (Oral Allergy Syndrome) may find that eating certain raw fruits or vegetables (like melons or bananas) can worsen their overall allergic burden, potentially making them more sensitive to Amaranth injections during peak pollen seasons.

While not extensively studied, herbal supplements that have 'immunomodulatory' properties (such as Echinacea or Astragalus) could theoretically interfere with the desensitization process of immunotherapy. Patients should inform their allergist of all supplements they are taking.

Amaranth extract administration does not typically interfere with standard blood chemistry or hematology tests. However, it will significantly affect:

• Total IgE Levels: These may temporarily rise during the build-up phase of immunotherapy.
• Specific IgE (RAST/ImmunoCAP): These tests for Amaranth sensitivity may remain positive for years, even if the patient has achieved clinical tolerance.

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

• Severe, Uncontrolled Asthma: Patients whose asthma is not well-managed with standard medications are at an unacceptably high risk of fatal bronchospasm during Amaranth immunotherapy. This is the most common factor in immunotherapy-related deaths.
• Recent Myocardial Infarction (Heart Attack): Patients who have had a recent heart attack (typically within the last 3-6 months) or have unstable angina should not start immunotherapy, as their heart cannot tolerate the stress of a potential anaphylactic reaction.
• Hypersensitivity to Excipients: Amaranth extracts contain inactive ingredients like glycerin and phenol (a preservative). Patients with a known, documented allergy to phenol must not use these products.
• Beta-Blocker Therapy: As detailed in the interactions section, the inability to respond to epinephrine makes immunotherapy too dangerous for these patients.

• Autoimmune Diseases: Conditions like systemic lupus erythematosus (SLE) or rheumatoid arthritis require careful consideration. There is a theoretical risk that stimulating the immune system with allergenic extracts could worsen an autoimmune flare.
• Malignancy: Patients currently undergoing treatment for cancer are generally advised to postpone immunotherapy until their condition is stable.
• Severe Atopic Dermatitis: If the skin is severely inflamed or damaged, diagnostic skin testing may be impossible to interpret accurately (the 'Red Dermographism' effect).

Patients who are allergic to Amaranth often show cross-sensitivity to other members of the Amaranthaceae and Chenopodiaceae families. This includes:

• Pigweed (Amaranthus retroflexus)
• Lamb's Quarters (Chenopodium album)
• Russian Thistle (Salsola kali)
• Kochia (Kochia scoparia)

If a patient has had a severe reaction to any of these 'weed' extracts, the healthcare provider will use extreme caution when initiating Amaranth testing or treatment.

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

Amaranth allergenic extracts are classified as FDA Pregnancy Category C. This means there are no adequate, well-controlled studies in pregnant women.

• Risk of Anaphylaxis: The primary concern during pregnancy is not the extract itself, but the risk of a systemic reaction. Anaphylaxis in a pregnant woman can cause sudden maternal hypotension, leading to fetal hypoxia (lack of oxygen to the baby), which can result in permanent brain damage or fetal death.
• Clinical Guidance: Most allergists will NOT start a new course of Amaranth immunotherapy during pregnancy. However, if a woman is already on a stable maintenance dose and is tolerating it well, the treatment may be continued, though the dose is usually not increased until after delivery.

It is not known whether the protein components of Amaranth extract pass into human breast milk. However, because these are large proteins that are digested in the gastrointestinal tract, it is highly unlikely they would pose a risk to a nursing infant. The benefits of continuing immunotherapy for the mother's health usually outweigh the theoretical risks to the infant.

As previously noted, Amaranth extract is frequently used in children.

• Approved Age: While there is no strict lower age limit, it is rarely started in children under age 5 because they may have difficulty communicating the early symptoms of a systemic reaction.
• Growth Effects: There is no evidence that allergenic extracts affect growth or development in children.
• Benefits: Early intervention with immunotherapy in children with allergic rhinitis has been shown in some studies to reduce the risk of developing asthma later in life (the 'Allergic March').

In patients over 65, the use of Amaranth extract requires extra caution.

• Cardiovascular Reserve: Older adults are more likely to have underlying heart disease, making them more vulnerable to the effects of a systemic reaction.
• Polypharmacy: The higher likelihood of being on beta-blockers or ACE inhibitors increases the risk profile.
• Skin Reactivity: Skin prick tests may be less reactive in the elderly, potentially leading to under-diagnosis.

There are no specific guidelines for Amaranth use in renal impairment. Since the proteins are not cleared primarily by the kidneys in their active form, no dose adjustment is typically needed. However, patients with end-stage renal disease (ESRD) should be monitored for overall fluid balance and stability.

No adjustments are required. The liver does not play a primary role in the clearance of the allergenic proteins found in Amaranth extracts.

> Important: Special populations require individualized medical assessment.

Amaranth allergenic extract functions as an immunomodulator. Its primary molecular target is the interaction between allergens and the IgE-FcεRI complex on mast cells and basophils.

• Diagnostic Phase: The extract's proteins (antigens) bind to IgE antibodies. This triggers the release of histamine, leukotrienes, and prostaglandins, creating the wheal-and-flare response.
• Therapeutic Phase: Repeated exposure to the extract induces 'immune deviation.' It stimulates the production of Interleukin-10 (IL-10) and Transforming Growth Factor-beta (TGF-β) from regulatory T-cells. This environment promotes the class-switching of B-cells from producing IgE (allergic) to producing IgG4 (protective). IgG4 acts as a 'decoy' or 'blocking' antibody, intercepting the Amaranth allergens before they can reach the IgE on mast cells.

• Dose-Response: There is a clear dose-response relationship in skin testing; higher concentrations produce larger wheals. In immunotherapy, higher maintenance doses are generally more effective but carry a higher risk of systemic reactions.
• Onset of Effect: Diagnostic results are seen in 15-20 minutes. The therapeutic benefits of immunotherapy usually take 6 to 12 months to become noticeable.
• Duration: The diagnostic effect lasts only a few hours. The therapeutic effect of a completed 3-5 year course of immunotherapy can last for many years, sometimes providing a lifetime of reduced sensitivity.

| Parameter | Value |

|---|---|

| Bioavailability | N/A (Subcutaneous/Intradermal) |

| Protein Binding | Minimal (primarily IgE/IgG4 interaction) |

| Half-life | Hours (proteins); Years (immunological memory) |

| Tmax | 1-2 hours (systemic absorption of proteins) |

| Metabolism | Proteolysis (Protease enzymes) |

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

• Molecular Formula: Complex mixture of proteins (e.g., Amr a 1, Amr a 2).
• Molecular Weight: Ranges from 10 kDa to over 70 kDa for various protein fractions.
• Solubility: Highly soluble in aqueous buffers and saline.
• Description: A clear to slightly yellowish liquid, often containing 50% glycerin as a stabilizer and 0.4% phenol as a preservative.

Amaranth is categorized as a Non-Standardized Plant Allergenic Extract. It is related to other weed extracts like Ragweed, Sagebrush, and Mugwort. Within the EPC (Electronic Product Code) system, it is also associated with Non-Standardized Food Allergenic Extracts and Adrenocorticotropic Hormone [EPC] for historical regulatory reasons.