A-17

Dosage for Barley allergenic extract is highly individualized and is not measured in standard milligrams, but rather in Protein Nitrogen Units (PNU) or dilution ratios (e.g., 1:10 w/v).

Diagnostic Testing

• Skin Prick Test (SPT): A single drop of the 1:10 or 1:20 w/v glycerinated extract is applied to the skin (usually the forearm or back). The skin is then pricked with a sterile lancet. A positive control (histamine) and negative control (saline/glycerin) are used for comparison.
• Intradermal Test: If the SPT is negative but clinical suspicion remains high, a 0.02 mL to 0.05 mL dose of a much more dilute aqueous extract (e.g., 1:1000 or 1:100 w/v) may be injected into the dermis.

Immunotherapy (SCIT)

• Build-up Phase: Treatment typically starts 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 based on patient tolerance.
• Maintenance Phase: Once the target dose is reached (the 'maintenance dose'), the interval between injections is increased to every 2 to 4 weeks. The maintenance dose is usually the highest dose the patient can tolerate without a significant systemic or local reaction.

Barley allergenic extract is used in children; however, the procedure must be performed with extreme caution by a pediatric allergist.

• Diagnostic Testing: The procedure for skin prick testing in children is identical to adults, though fewer sites may be tested at once to minimize discomfort. Intradermal testing is often avoided in very young children due to the increased risk of systemic reactions.
• Immunotherapy: Dosing follows the same escalation logic as adults but may start at even more conservative dilutions depending on the child's level of sensitivity and the presence of comorbid conditions like asthma.

Renal Impairment

No specific dosage adjustments are required for patients with renal impairment, as the extract is not systemically cleared in a way that would lead to accumulation or toxicity. However, patients with end-stage renal disease should be monitored closely for overall physiological stability during testing.

Hepatic Impairment

No dosage adjustments are necessary for patients with hepatic impairment. The metabolism of allergenic proteins does not rely on the liver's Cytochrome P450 system.

Elderly Patients

Elderly patients may have reduced skin reactivity, leading to potential false-negative results in diagnostic testing. Furthermore, the risk of cardiovascular complications during a systemic allergic reaction (anaphylaxis) is higher in this population. Healthcare providers may use more conservative dosing and extended observation periods for geriatric patients.

Barley allergenic extract is never for self-administration. It must be administered by a trained healthcare professional (usually an allergist or immunology nurse) in a medical facility.

• Preparation: The skin site is cleaned with alcohol. For immunotherapy, the injection is given subcutaneously, usually in the posterior aspect of the upper arm.
• Observation: Patients MUST remain in the medical office for at least 30 minutes following any administration of the extract to monitor for signs of anaphylaxis.
• Storage: Vials 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 proteins and render the extract ineffective or dangerous.

In the context of immunotherapy, a missed dose can disrupt the desensitization process.

• If a dose is missed by a few days, the same dose may often be given.
• If a dose is missed by more than one week, the healthcare provider may need to reduce the dose for the next injection to ensure safety and prevent a systemic reaction.
• Never attempt to 'double up' on doses to make up for a missed appointment.

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

• Signs of Overdose: Rapid onset of hives (urticaria), swelling of the throat (angioedema), wheezing, shortness of breath, drop in blood pressure, and rapid heart rate.
• Emergency Measures: Immediate administration of epinephrine (0.3 mg for adults, 0.15 mg for children) intramuscularly, followed by supplemental oxygen, IV fluids, and antihistamines. Emergency medical services must be contacted immediately.

> 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 Barley allergenic extract will experience some form of local reaction. These are generally expected and indicate that the extract is biologically active.

• Local Wheal and Flare: This is the intended result of a diagnostic skin test. It feels like a small, itchy mosquito bite. It typically appears within 15-20 minutes and resolves within 1-2 hours.
• Injection Site Redness: Following immunotherapy, the area around the injection may become red and warm. This can last for 24 to 48 hours.
• Pruritus (Itching): Intense itching at the site of administration is very common. Patients are advised not to scratch the area to avoid skin breakdown or infection.

• Large Local Reactions (LLR): Swelling at the injection site that exceeds 5-10 cm in diameter. This may be accompanied by significant discomfort and stiffness in the arm.
• Fatigue: Some patients report feeling unusually tired for several hours after receiving an immunotherapy injection.
• Headache: A mild, transient headache may occur following the administration of allergenic extracts.

• Generalized Urticaria: Hives appearing on parts of the body far from the injection or test site.
• Rhinitis: Sneezing, nasal congestion, or a runny nose triggered by the systemic immune response to the extract.
• Mild Wheezing: Patients with a history of asthma may experience a slight tightening of the chest.

> Warning: Stop taking Barley and call your doctor immediately if you experience any of these symptoms of a systemic allergic reaction (anaphylaxis).

• Angioedema: Significant swelling of the lips, tongue, or throat that can obstruct the airway.
• Bronchospasm: Severe wheezing or difficulty breathing, often associated with a feeling of 'air hunger.'
• Hypotension: A sudden drop in blood pressure, which may cause dizziness, fainting, or 'seeing spots.'
• Tachycardia: A rapid or pounding heartbeat as the body attempts to compensate for circulatory changes.
• Gastrointestinal Distress: Sudden onset of severe abdominal cramping, vomiting, or diarrhea, which can be a sign of systemic mast cell activation.
• Sense of Impending Doom: A psychological symptom often reported by patients at the onset of a life-threatening anaphylactic event.

In the majority of patients, there are no negative long-term side effects associated with Barley allergenic extract. The goal of long-term use (immunotherapy) is to induce immunological tolerance. However, in rare cases, prolonged immunotherapy has been theoretically linked to the development of other autoimmune markers, though clinical evidence for this is sparse. The most significant 'long-term' effect is the intended reduction in allergic sensitivity.

Barley allergenic extract, like most allergenic extracts, carries a significant warning regarding the risk of anaphylaxis.

Summary of FDA Warning: This product can cause severe, life-threatening systemic reactions, including anaphylaxis. It must only be administered in a setting where trained personnel and emergency equipment (including epinephrine) are immediately available. Patients with unstable asthma are at a significantly higher risk for fatal reactions. Patients must be observed for at least 30 minutes after each injection. Certain medications, such as beta-blockers, may make the patient's reaction more severe or harder to treat.

Report any unusual symptoms or delayed reactions (occurring hours after the appointment) to your healthcare provider immediately.

Barley allergenic extract is a potent biological substance that requires careful handling and administration. It is intended only for use by physicians who are experienced in the diagnosis and treatment of allergic diseases. Patients must be informed of the risks and benefits before beginning testing or therapy.

No FDA black box warnings for Barley. (Note: While allergenic extracts as a class often carry boxed warnings in their package inserts regarding anaphylaxis, specific "Non-Standardized" extracts may list these as 'Severe Warnings' rather than a formal Black Box. However, the clinical standard is to treat them with the same level of caution as boxed-warning drugs.)

• Anaphylaxis Risk: This is the primary concern. Reactions can occur even in patients who have previously tolerated the extract. The risk is highest during the build-up phase of immunotherapy.
• Asthma Status: Patients with symptomatic or poorly controlled asthma should not undergo skin testing or receive immunotherapy injections until their asthma is stabilized. A decrease in lung function (FEV1) significantly increases the risk of a fatal reaction.
• Injection Technique: For immunotherapy, the extract must be given subcutaneously. Accidental intravenous injection can lead to immediate, severe systemic toxicity.
• Infection/Illness: Injections should be withheld if the patient is experiencing an acute febrile illness or a respiratory infection, as this can lower the threshold for a systemic allergic reaction.

• Baseline Assessment: Before each injection, the provider must assess the patient for any new symptoms, changes in asthma control, or large local reactions from the previous dose.
• Post-Administration Observation: A minimum 30-minute wait time in the clinic is mandatory.
• Lung Function: For asthmatic patients, peak flow or spirometry may be performed before administration to ensure the patient is at their baseline.
• Skin Site Monitoring: The size of the wheal (for testing) or the local swelling (for therapy) must be measured and recorded in the patient's permanent medical record.

Most patients can drive or operate machinery after the 30-minute observation period, provided they feel well. However, if a patient experiences a systemic reaction or receives epinephrine, they should not drive and must be monitored in an emergency setting.

There is no direct interaction between alcohol and Barley extract. However, alcohol consumption can cause vasodilation and may theoretically increase the rate of absorption of the extract or mask early signs of an allergic reaction. It is generally advised to avoid alcohol for several hours before and after administration.

• Testing: Discontinuation occurs once the diagnostic procedure is complete.
• Immunotherapy: If a patient experiences a severe systemic reaction, the healthcare provider may decide to discontinue therapy or significantly reduce the dose. There is no 'withdrawal syndrome' associated with stopping Barley extract, but the patient's allergic sensitivity will likely return to its baseline level over time.

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

There are no drugs that are absolutely contraindicated in a 'never use' sense, but certain combinations create such high risk that they are avoided in clinical practice:

• Beta-Blockers (e.g., Propranolol, Metoprolol): Patients taking beta-blockers may be resistant to the effects of epinephrine, which is the primary treatment for anaphylaxis. If a patient on a beta-blocker has a severe reaction to Barley extract, it may be life-threatening and difficult to reverse.
• Unstable Asthma Medications: Using Barley extract while a patient is requiring frequent 'rescue' inhaler use is contraindicated due to the risk of fatal bronchospasm.

• ACE Inhibitors (e.g., Lisinopril): Some studies suggest that patients on ACE inhibitors may be at an increased risk for more severe systemic reactions to allergenic extracts.
• MAOIs and TCAs: These medications can potentiate the effects of epinephrine (if it needs to be administered), leading to dangerous increases in blood pressure or heart rate.

• Antihistamines (e.g., Loratadine, Cetirizine, Diphenhydramine): These drugs are 'moderate' interactions because they interfere with the accuracy of the test rather than the safety. Antihistamines suppress the wheal-and-flare response, leading to false-negative results. They must be stopped 3 to 7 days prior to testing.
• H2 Blockers (e.g., Famotidine): Similar to H1 antihistamines, these can partially suppress skin reactivity and should be discontinued before diagnostic testing.
• Topical Steroids: If applied to the test site, topical steroids can reduce the local inflammatory response and invalidate the test.

• Barley-Containing Foods: For patients undergoing diagnostic testing for a food allergy, consuming barley shortly before the test may theoretically prime the immune system and increase the risk of a reaction.
• High-Fat Meals: No known interaction with the extract's efficacy, though general malaise from a heavy meal might be confused with a systemic reaction.

• St. John's Wort: No direct interaction with the extract, but could affect the metabolism of other medications used to treat allergic reactions.
• Supplements with Antihistamine Properties (e.g., Quercetin, Butterbur): These may slightly suppress skin test results and should be disclosed to the allergist.

• Skin Testing: Barley extract is itself a 'test.' Its presence in the skin will interfere with any other skin tests being performed in the same area.
• Serum IgE: Administration of Barley extract for immunotherapy will eventually lead to changes in serum-specific IgE and IgG4 levels, which is the intended therapeutic effect.

For each interaction, the primary strategy is management through timing (stopping antihistamines) or risk assessment (evaluating the necessity of beta-blockers).

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

Barley allergenic extract must NEVER be used in the following circumstances:

1. 1Severe, Unstable Asthma: Patients with an FEV1 consistently below 70% of predicted or those with recent hospitalizations for asthma are at an unacceptably high risk of fatal bronchospasm during testing or therapy.
2. 2Previous Near-Fatal Reaction: If a patient has previously had a life-threatening reaction to Barley extract or a very similar grain extract, the risk of re-administration usually outweighs any diagnostic or therapeutic benefit.
3. 3Acute Infection: Injections should not be given during an active febrile illness, as the immune system is already in a heightened state of activation.
4. 4Recent Myocardial Infarction (Heart Attack): The physiological stress of a potential anaphylactic reaction could trigger another cardiac event.

These conditions require a careful risk-benefit analysis by the specialist:

• Pregnancy: While not strictly contraindicated for those already on a stable maintenance dose, starting new immunotherapy or performing skin testing during pregnancy is generally avoided due to the risk of fetal hypoxia if the mother has a systemic reaction.
• Autoimmune Disorders: Patients with active systemic lupus erythematosus (SLE) or rheumatoid arthritis may have unpredictable immune responses to allergenic extracts.
• Beta-Blocker Therapy: As mentioned, this makes treating a reaction difficult. The physician must decide if the patient can be switched to an alternative blood pressure medication.
• Young Children: Children under the age of 5 may be difficult to test and monitor effectively, and they may not be able to communicate early symptoms of a reaction.

Patients allergic to barley often show cross-sensitivity to other members of the Poaceae (grass) family. This includes:

• Wheat
• Rye
• Oats
• Timothy Grass or Bermuda Grass Pollen

A patient who has had a severe reaction to wheat extract should be approached with extreme caution when using Barley extract, as the proteins (hordeins in barley and gliadins in wheat) are structurally similar.

> Important: Your healthcare provider will evaluate your complete medical history, including all allergies and current medications, before prescribing or administering Barley extract.

Barley allergenic 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 when administered to a pregnant woman.

• Risk Summary: The primary risk during pregnancy is not the extract itself, but the potential for maternal anaphylaxis. Anaphylaxis can lead to maternal hypotension, which causes uterine hypoperfusion and fetal hypoxia (lack of oxygen to the baby).
• Clinical Practice: Allergists typically do not initiate new immunotherapy or perform diagnostic skin testing during pregnancy. However, if a woman is already on a stable maintenance dose of Barley immunotherapy and is tolerating it well, the treatment is often continued, as the risk of a reaction is low and the benefit of preventing allergic symptoms is high.

It is not known whether barley proteins from the extract are excreted in human milk. However, because these are naturally occurring proteins and the amount administered is very small, it is considered unlikely to affect a nursing infant. The decision to continue immunotherapy while breastfeeding should be made in consultation with a healthcare provider, weighing the mother's need for treatment against any theoretical risks.

Barley extract is used in the pediatric population for the diagnosis of food allergies and baker's asthma.

• Safety: The safety profile in children is generally similar to that in adults. However, children must be monitored even more closely as they may not be able to articulate symptoms like 'throat tightness' or 'dizziness.'
• Growth Effects: There is no evidence that allergenic extracts affect growth or development in children.
• Dosing: Dosing is based on immunological sensitivity rather than body weight.

In patients over 65, several factors must be considered:

• Reduced Reactivity: The skin's histamine response decreases with age, which can lead to smaller wheals and potentially false-negative results.
• Cardiovascular Health: Older adults are more likely to have underlying heart disease, making them more vulnerable to the effects of a systemic reaction or the epinephrine used to treat it.
• Polypharmacy: The higher likelihood of being on beta-blockers or ACE inhibitors increases the complexity of using allergenic extracts safely.

There are no specific studies on Barley extract in patients with renal impairment. Because the proteins are degraded by proteases and not primarily cleared by the kidneys in an active form, no dose adjustments are typically required. However, the patient's overall health status should be stable.

No dosage adjustments are required for patients with liver disease. The liver does not play a primary role in the immunological processing or clearance of the small amounts of protein found in allergenic extracts.

> Important: Special populations require individualized medical assessment and a personalized approach to allergy testing and treatment.

Barley allergenic extract functions as an immunomodulator. In diagnostic use, it acts as an antigen that cross-links IgE on mast cells, triggering a localized Type I hypersensitivity reaction. In therapeutic use (immunotherapy), it works through several mechanisms:

1. 1Induction of T-regulatory (Treg) cells: These cells produce IL-10 and TGF-beta, which suppress allergic inflammation.
2. 2Antibody Class Switching: It promotes the production of IgG4, which acts as a 'blocking antibody' to prevent IgE from binding to the barley allergens.
3. 3Reduction in Effector Cells: Over time, immunotherapy reduces the number of mast cells and eosinophils in the tissues.

• Onset of Action (Testing): 15 to 20 minutes for a wheal-and-flare response.
• Onset of Action (Therapy): Several months of build-up are usually required before a significant reduction in allergic symptoms is noted.
• Duration of Effect: Diagnostic results are transient. Therapeutic effects can last for years after a 3-to-5-year course of immunotherapy is completed.

| Parameter | Value |

|---|---|

| Bioavailability | Localized (Skin) / Low (Subcutaneous) |

| Protein Binding | Primarily to IgE and IgG antibodies |

| Half-life | Minutes (Proteins) / Weeks (Immunological memory) |

| Tmax | 15-20 minutes (Local skin reaction) |

| Metabolism | Proteolytic degradation (Non-CYP) |

| Excretion | Renal (as peptide fragments) |

• Composition: A sterile solution of proteins, glycoproteins, and polysaccharides extracted from the grain of Hordeum vulgare.
• Molecular Weight: Varies widely (10 kDa to 70 kDa for major allergens like hordeins).
• Solubility: Soluble in aqueous buffers and glycerin-saline solutions.
• Structure: Complex mixture; not a single molecular entity.

Barley extract is a Non-Standardized Food Allergenic Extract. It is grouped with other cereal grain extracts (Wheat, Rye, Oat) and is used specifically for IgE-mediated hypersensitivity conditions. It is distinct from standardized extracts (like Ragweed or Honeybee venom), which have federally mandated potency requirements.