Cerebellutem

Dosage for Amber extracts is highly individualized and must be determined by an allergist based on the patient's sensitivity, clinical history, and response to initial testing. There is no 'one-size-fits-all' dose.

Skin Testing Dosage

• Skin Prick Test (SPT): Usually performed using a concentrated extract (e.g., 1:10 or 1:20 w/v). A single drop is applied to the skin, and the skin is pricked through the drop.
• Intradermal Test: If SPT is negative, a more dilute solution (e.g., 1:100 to 1:1000) may be injected into the dermis (0.02 mL).

Immunotherapy Dosage (Allergy Shots)

• Build-up Phase: Starts with a very low dose (e.g., 0.05 mL of a 1:10,000 dilution). Injections are given 1–3 times per week, with the dose increasing incrementally.
• Maintenance Phase: Once the 'top dose' is reached (typically 0.5 mL of a 1:10 or 1:20 dilution), injections are spaced out to every 2–4 weeks for a period of 3–5 years.

Amber extracts are generally considered safe for use in children; however, the decision to start immunotherapy in children under age 5 is made with caution due to the difficulty of communicating systemic symptoms. Pediatric dosing follows the same incremental build-up principles as adult dosing, though the starting concentration may be more conservative in highly sensitive children.

Renal Impairment

No specific dosage adjustments are required for patients with kidney disease, as the proteins are not cleared by the kidneys in a manner that affects toxicity.

Hepatic Impairment

No dosage adjustments are necessary for patients with liver disease.

Elderly Patients

Caution is advised in elderly patients with underlying cardiovascular disease. If an elderly patient experiences a systemic reaction, their heart may be less able to tolerate the stress of anaphylaxis or the administration of epinephrine.

Amber allergenic extracts are never self-administered by the patient at home. They must be administered in a clinical setting by a healthcare professional.

• Administration Route: Subcutaneous injection (usually in the posterior aspect of the upper arm).
• Observation Period: Patients must remain in the doctor's office for at least 30 minutes after every injection to monitor for signs of a systemic reaction.
• Storage: Extracts must be stored in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze.

If a dose of immunotherapy is missed, the next dose may need to be reduced depending on how much time has passed.

• 1 week late: Usually the same dose.
• 2-4 weeks late: The dose may be held or reduced to the previous level.
• Over 4 weeks late: The build-up may need to be restarted from a much lower concentration to ensure safety.

An 'overdose' in the context of Amber typically refers to an injection given at too high a concentration or too large a volume, or an accidental intravenous injection.

• Signs: Rapid onset of hives, swelling, wheezing, drop in blood pressure, or loss of consciousness.
• Emergency Measures: Immediate administration of epinephrine (0.3 mg for adults), oxygen, IV fluids, and potentially antihistamines or corticosteroids. The patient must be transported to an emergency department if a systemic reaction occurs.

> Important: Follow your healthcare provider's dosing instructions exactly. Do not attempt to alter the schedule or dose without medical guidance.

Most patients receiving Amber extracts, especially during the build-up phase of immunotherapy, will experience local reactions. These are typically mild and self-limiting.

• Local Swelling and Redness: A 'wheal and flare' reaction at the site of injection. This may feel like a mosquito bite or a firm lump under the skin. It usually peaks within 20–30 minutes but can persist for several hours.
• Pruritus (Itching): Intense itching at the injection site or on the palms and soles.
• Fatigue: Some patients report feeling tired for a few hours following an injection, likely due to the immune system's activation.

• Large Local Reactions (LLR): Swelling that exceeds 5–10 cm in diameter. While not dangerous, an LLR may indicate that the next dose should not be increased.
• Nasal Congestion: Mild flare-up of hay fever symptoms shortly after administration.
• Headache: Mild, transient tension-type headaches.

• Generalized Urticaria (Hives): Hives appearing on parts of the body away from the injection site.
• Angioedema: Swelling of the deeper layers of the skin, often around the eyes or lips.
• Vasovagal Syncope: Fainting due to needle anxiety or the body's reaction to the injection, rather than an allergic response.

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

1. 1Respiratory Distress: Wheezing, chest tightness, shortness of breath, or a persistent cough.
2. 2Upper Airway Obstruction: Feeling of a 'lump in the throat,' hoarseness, or difficulty swallowing.
3. 3Cardiovascular Collapse: Rapid or weak pulse, dizziness, lightheadedness, or sudden drop in blood pressure.
4. 4Gastrointestinal Distress: Severe abdominal cramping, vomiting, or diarrhea occurring shortly after the injection.
5. 5Cyanosis: Bluish tint to the lips or fingernails, indicating low oxygen levels.

There are no known long-term 'toxic' side effects of Amber extracts, as they are natural proteins. However, prolonged immunotherapy can lead to:

• Persistent Subcutaneous Nodules: Small, painless bumps under the skin at frequent injection sites.
• Immunological Shift: While intended, the long-term shift in the immune system is the primary 'effect' of the drug.

Amber allergenic extracts carry a prominent Boxed Warning regarding the risk of severe non-fatal and fatal systemic allergic reactions (anaphylaxis).

• Summary: Extracts should only be used by physicians experienced in providing allergenic extract therapy. Patients with unstable asthma are at a higher risk for fatal reactions. Patients taking beta-blockers may be resistant to the effects of epinephrine, the primary treatment for anaphylaxis. All patients must be observed for at least 30 minutes post-injection.

Report any unusual symptoms or delayed reactions (occurring 6–24 hours later) to your healthcare provider immediately.

Amber extracts are potent biological agents that can cause life-threatening reactions if not used correctly. The primary safety concern is systemic anaphylaxis. Because these are non-standardized extracts, the concentration of specific proteins can vary between batches, requiring clinicians to exercise caution when starting a new vial of the same extract.

WARNING: RISK OF SEVERE SYSTEMIC REACTIONS

• Amber allergenic extracts can cause severe, life-threatening systemic reactions, including anaphylaxis and death.
• Administration must occur in a facility equipped with emergency supplies, including epinephrine, oxygen, and airway management tools.
• Patients must be monitored for at least 30 minutes by a healthcare professional after each injection.
• Patients with severe or unstable asthma are at increased risk for fatal systemic reactions.
• Some medications, such as beta-blockers, may interfere with the treatment of anaphylaxis.

• Asthma Status: Immunotherapy should be withheld if a patient is experiencing an acute asthma flare or if their Peak Expiratory Flow (PEF) is significantly below their personal best. Uncontrolled asthma is the single greatest risk factor for a fatal reaction to Amber.
• Allergic Reactions / Anaphylaxis Risk: Patients must be educated on the signs of anaphylaxis and how to use an epinephrine auto-injector if a delayed reaction occurs after leaving the clinic.
• Infection/Illness: Injections should be postponed if the patient has a fever or a significant respiratory infection, as this may lower the threshold for a systemic reaction.
• Exercise: Patients should avoid vigorous exercise for 2 hours before and after an injection, as increased blood flow can accelerate the absorption of the allergen.

While routine blood work (like liver or kidney tests) is not required for Amber therapy, the following monitoring is essential:

• Symptom Review: Before each injection, the provider must ask about reactions to the previous dose.
• Lung Function: For asthmatic patients, a quick peak flow meter check or auscultation (listening to the lungs) is recommended before administration.
• Vital Signs: Monitoring blood pressure and heart rate if the patient feels unwell after the dose.

Amber does not typically cause sedation. However, if a patient experiences a systemic reaction or receives epinephrine, they should not drive or operate machinery until they are fully recovered and cleared by a physician.

Alcohol should be avoided on the day of an injection. Alcohol causes vasodilation (widening of blood vessels), which can potentially increase the rate of allergen absorption and increase the risk of a systemic reaction.

Stopping Amber immunotherapy does not require a tapering schedule. However, if therapy is stopped prematurely (before 3 years), the allergic symptoms are likely to return. If a patient experiences a life-threatening reaction, the physician may decide to discontinue the therapy permanently.

> Important: Discuss all your medical conditions, especially heart or lung problems, with your healthcare provider before starting Amber.

There are no absolute drug-drug contraindications that prevent the use of Amber, but certain combinations are considered extremely high-risk:

• Beta-Blockers (e.g., Propranolol, Metoprolol): These are often considered a relative contraindication. If a patient on a beta-blocker has anaphylaxis from Amber, the beta-blocker prevents epinephrine from working effectively. This can lead to 'refractory anaphylaxis,' which is difficult to treat and potentially fatal.

• ACE Inhibitors (e.g., Lisinopril, Enalapril): Some studies suggest that patients taking ACE inhibitors may be at a higher risk for more severe systemic reactions to allergenic extracts, particularly insect venoms, as these drugs interfere with the body's ability to degrade kinins (inflammatory substances).
• MAO Inhibitors (e.g., Phenelzine): These can potentiate the effects of epinephrine if it needs to be administered, leading to a dangerous spike in blood pressure.

• Antihistamines (e.g., Loratadine, Cetirizine): While not dangerous, antihistamines can mask the early warning signs of a systemic reaction (like itching or hives) and can interfere with the accuracy of diagnostic skin testing. Patients must stop antihistamines 3–7 days before skin testing.
• H2 Blockers (e.g., Famotidine): Similar to antihistamines, these can suppress skin test reactivity.
• Tricyclic Antidepressants (TCAs): Like MAOIs, TCAs can interfere with the body's response to epinephrine.

• Alcohol: As mentioned, alcohol increases vasodilation and may increase the risk of a systemic reaction.
• Specific Food Allergens: If a patient is receiving Amber Food Allergenic Extract, they must strictly avoid eating that specific food during the build-up phase, as the combination of the injection and oral ingestion can trigger a severe reaction.

There are no well-documented interactions with herbal supplements like St. John's Wort or Ginkgo, but patients should always inform their allergist of all supplements, as some may affect heart rate or blood pressure.

• Skin Prick Tests: Amber will obviously cause a positive result on a skin test for that specific allergen.
• Serum IgE/IgG4: Immunotherapy will cause changes in these lab values (initially an increase in IgE, followed by a long-term increase in IgG4). These are expected therapeutic markers rather than 'interferences.'

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

Amber extracts must NEVER be used in the following circumstances:

1. 1Severe, Uncontrolled Asthma: Patients with a FEV1 consistently below 70% of predicted or those with frequent acute exacerbations are at an unacceptable risk for a fatal reaction.
2. 2Recent Myocardial Infarction or Unstable Angina: The heart must be healthy enough to withstand the stress of a potential anaphylactic reaction and the subsequent administration of epinephrine (which increases heart rate and oxygen demand).
3. 3Hypersensitivity to Excipients: Some Amber extracts contain phenol (as a preservative) or glycerin. Patients with a known severe allergy to these components should not receive the extract.

Conditions requiring careful risk-benefit analysis include:

• Beta-Blocker Therapy: As discussed, this makes anaphylaxis harder to treat.
• Autoimmune Diseases: There is a theoretical risk that stimulating the immune system with Amber could worsen certain autoimmune conditions (e.g., Lupus, Rheumatoid Arthritis), though evidence is limited.
• Malignancy: Patients with active cancer are generally not started on immunotherapy, though they may continue maintenance therapy if already stable.
• Pregnancy (Initiation): Immunotherapy should not be started during pregnancy due to the risk of anaphylaxis-induced fetal hypoxia (lack of oxygen to the baby).

Patients sensitive to one fungal extract (e.g., Alternaria) may show cross-reactivity to other fungi in the Amber Fungal class. Similarly, cross-reactivity is common between different types of grass pollens or tree pollens. Your allergist will use this information to design a safe and effective extract mix.

> Important: Your healthcare provider will evaluate your complete medical history, including heart and lung health, before prescribing Amber.

Amber allergenic extracts are classified as Pregnancy Category C.

• Risk Summary: There are no adequate and well-controlled studies in pregnant women. The primary risk is not the extract itself, but the risk of maternal anaphylaxis, which can cause uterine contractions, placental abruption, and fetal distress or death.
• Clinical Practice: It is standard practice not to initiate Amber immunotherapy during pregnancy. However, if a woman is already on a stable maintenance dose and is tolerating it well, the therapy may be continued throughout pregnancy, as the risk of a reaction is much lower during the maintenance phase.

It is generally considered safe to continue Amber immunotherapy while breastfeeding. The large protein molecules in the extract are unlikely to pass into breast milk in any significant quantity, and if they did, they would be digested in the infant's stomach. No adverse effects on nursing infants have been reported.

• Safety: Effective for children with allergic rhinitis and asthma.
• Age Considerations: Most allergists wait until a child is at least 5 years old to start immunotherapy. This is primarily because younger children may not be able to articulate the early symptoms of a systemic reaction (e.g., 'my throat feels funny'), making it harder to catch anaphylaxis early.
• Growth: There is no evidence that Amber extracts affect growth or development in children.

Patients over age 65 may be at higher risk for complications from Amber therapy due to a higher prevalence of cardiovascular disease.

• Assessment: A thorough cardiac evaluation is often recommended before starting an elderly patient on immunotherapy.
• Polypharmacy: Older adults are more likely to be taking beta-blockers or ACE inhibitors, which complicates the safety profile.

No dosage adjustments are required. The proteins in Amber extracts are metabolized by proteases and do not rely on renal clearance for their therapeutic effect or elimination.

No dosage adjustments are required for patients with liver disease. The liver is not the primary site of metabolism for these allergenic proteins.

> Important: Special populations require individualized medical assessment and frequent monitoring by an allergy specialist.

Amber extracts function as immunomodulators. The primary molecular mechanism is the induction of 'immune deviation.' In allergic individuals, the immune system responds to allergens via the Th2 pathway, producing IgE. Amber immunotherapy forces the immune system to recognize the allergen in a different context (subcutaneous injection without the usual mucosal inflammation). This leads to:

1. 1T-Reg Induction: The expansion of CD4+CD25+ Foxp3+ regulatory T-cells.
2. 2Cytokine Switch: A decrease in Th2 cytokines (IL-4, IL-5, IL-13) and an increase in Th1/T-reg cytokines (IFN-gamma, IL-10).
3. 3B-Cell Class Switching: B-cells stop producing IgE and start producing IgG4, which acts as a 'decoy' or 'blocking' antibody.

• Onset of Effect: Diagnostic skin testing results are visible within 15–20 minutes. For immunotherapy, clinical improvement typically takes 6–12 months of consistent treatment.
• Duration of Effect: The goal of a 3–5 year course of Amber is to provide long-lasting relief (years to decades) even after the treatment is stopped.
• Tolerance: Unlike many drugs, patients do not develop 'tolerance' in a negative sense (requiring more drug for the same effect). Instead, they develop 'immunological tolerance,' meaning they no longer react to the allergen.

| Parameter | Value |

|---|---|

| Bioavailability | N/A (Biological Protein) |

| Protein Binding | N/A |

| Half-life | Minutes to Hours (Proteins); Years (Immunological effect) |

| Tmax | 20–30 minutes (Localized peak) |

| Metabolism | Proteolysis by endogenous enzymes |

| Excretion | Minimal renal excretion of fragments |

Amber extracts are complex mixtures of proteins, glycoproteins, and polysaccharides.

• Molecular Weight: Ranges from 10 kDa to over 70 kDa for major allergens.
• Solubility: Soluble in aqueous buffers and glycerinated saline.
• Composition: Contains both 'major allergens' (those to which >50% of patients react) and 'minor allergens.'

Amber belongs to the therapeutic class of Allergenic Extracts. It is further sub-classified by the source material (Fungal, Food, Plant, or Insect). It is distinct from 'Allergen Patches' or 'Sublingual Tablets' (SLIT), as Amber extracts are primarily designed for subcutaneous injection or diagnostic testing.