Histapoll Hp

For the treatment of ragweed-induced allergic rhinitis using sublingual tablets (e.g., Ragwitek), the standard adult dosage is one tablet (12 Amb a 1-Unit) daily.

• Timing: Treatment must be initiated at least 12 weeks prior to the expected onset of the ragweed pollen season and continued throughout the entire season.
• Duration: Clinical studies suggest that for long-term disease modification, the therapy may need to be continued for 3 consecutive years, though the daily dose remains the same.

For subcutaneous immunotherapy (allergy shots), the dosage is highly individualized. It typically involves a 'build-up phase' where doses increase weekly, followed by a 'maintenance phase' where a consistent dose is given every 2 to 4 weeks.

Ambrosia Artemisiifolia sublingual tablets are typically FDA-approved for use in adults aged 18 through 65 years.

• Children and Adolescents: Some specific formulations or subcutaneous extracts may be used in children as young as 5 years old, depending on the specific product license and the clinician's assessment. However, the standardized sublingual tablet is generally not indicated for pediatric use under age 18 in many jurisdictions. Always check the specific product insert for age-related approvals.

Renal Impairment

No dosage adjustments are required for patients with renal impairment. Because the allergenic proteins are degraded locally and do not rely on renal clearance, kidney function does not significantly impact the safety or efficacy of the sublingual extract.

Hepatic Impairment

No dosage adjustments are required for patients with hepatic impairment. The extract does not undergo hepatic metabolism via the CYP450 system.

Elderly Patients

Clinical data for patients over the age of 65 is limited. While no specific dosage adjustment is recommended, healthcare providers should use caution, as elderly patients may have co-morbidities (like heart disease) that could make the management of a rare systemic allergic reaction more difficult.

1. 1First Dose Observation: The very first dose of the sublingual tablet must be taken in a healthcare provider's office. The patient must be observed for at least 30 minutes to monitor for signs of a severe systemic allergic reaction (anaphylaxis).
2. 2Administration: Place the tablet under the tongue immediately after taking it out of the blister pack.
3. 3Dissolution: Allow the tablet to remain under the tongue until it is completely dissolved. Do not swallow for at least one minute.
4. 4Food and Drink: Do not eat or drink anything for at least five minutes after the tablet has dissolved to ensure maximum local uptake by the oral mucosa.
5. 5Hand Hygiene: Wash your hands after handling the tablet to avoid accidental transfer of the allergen to the eyes or nose.
6. 6

If a dose is missed, take the next dose at the regularly scheduled time the following day. Do not take a double dose to make up for a missed one. If more than one dose is missed, or if you stop treatment for several days, contact your healthcare provider before restarting, as a dose adjustment or re-observation may be necessary.

Taking more than the prescribed dose increases the risk of local and systemic allergic reactions. Symptoms of overdose may include severe swelling of the tongue or throat, difficulty breathing, or abdominal pain. In the event of an accidental overdose, seek immediate medical attention or contact a poison control center.

> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or stop treatment early without medical guidance, as this may reduce the effectiveness of the desensitization process.

Because Ambrosia Artemisiifolia extract is an allergen, local reactions in the mouth and throat are extremely common, especially during the first week of treatment. These are generally mild to moderate and include:

• Oral Pruritus (Itching of the mouth): A tingling or itchy sensation on the tongue, roof of the mouth, or gums. This typically occurs within minutes of administration.
• Throat Irritation: A 'scratchy' or sore feeling in the back of the throat.
• Ear Pruritus: Itching deep inside the ear canal, which is a referred sensation from the oral cavity.
• Oral Edema: Mild swelling of the lips or tongue.

Most of these local symptoms resolve within 30 to 60 minutes and tend to diminish in frequency and intensity as the body becomes accustomed to the extract over the first 7-14 days of therapy.

• Nausea and Abdominal Pain: Some patients may experience mild stomach upset if they swallow the saliva containing the extract too quickly.
• Paraesthesia Oral: A 'pins and needles' sensation in the mouth.
• Stomatitis: Inflammation of the lining of the mouth.
• Urticaria (Hives): Small, itchy bumps on the skin, not necessarily at the site of administration.
• Dyspnea: A mild feeling of shortness of breath or chest tightness.

• Eosinophilic Esophagitis (EoE): A rare chronic immune system disease where white blood cells (eosinophils) build up in the lining of the esophagus. Symptoms include difficulty swallowing (dysphagia) or food getting stuck.
• Severe Glossitis: Significant inflammation and swelling of the tongue.
• Laryngeal Edema: Swelling of the larynx (voice box) which can obstruct the airway.

> Warning: Stop taking Ambrosia Artemisiifolia and call your doctor or emergency services immediately if you experience any of these signs of a systemic allergic reaction (anaphylaxis):

• Angioedema: Rapid and significant swelling of the face, lips, tongue, or throat that makes breathing or swallowing difficult.
• Wheezing or Stridor: High-pitched breathing sounds or significant chest tightness.
• Dizziness or Syncope: A sudden drop in blood pressure leading to lightheadedness or fainting.
• Rapid or Weak Pulse: Signs of cardiovascular distress during an allergic reaction.
• Severe Diarrhea or Vomiting: Systemic GI symptoms that occur rapidly after a dose.

The most significant long-term concern is the development of Eosinophilic Esophagitis (EoE). Patients who develop persistent heartburn, difficulty swallowing, or chest pain that does not go away should be evaluated for EoE. If confirmed, the immunotherapy must be permanently discontinued. Most other side effects are transient and do not result in long-term organ damage.

Ambrosia Artemisiifolia sublingual tablets carry an FDA Black Box Warning regarding the risk of severe allergic reactions.

Summary of Black Box Warning:

• This medication can cause life-threatening allergic reactions such as anaphylaxis and severe laryngopharyngeal edema.
• Do not use in patients with severe, unstable, or uncontrolled asthma.
• The first dose must be administered in a healthcare setting under supervision.
• Patients must be prescribed and trained to use an auto-injectable epinephrine (e.g., EpiPen) while taking this medication.
• Some patients may not be suitable candidates if they have medical conditions that would make them unable to survive a serious allergic reaction or if they take medications (like beta-blockers) that interfere with the treatment of anaphylaxis.

Report any unusual or persistent symptoms to your healthcare provider immediately. Maintaining a symptom diary during the first two weeks of treatment can be helpful for your doctor to assess your tolerance.

Ambrosia Artemisiifolia allergenic extract is a potent biological product. It is intended only for use by patients who have a clinically confirmed allergy to Short Ragweed pollen. It is not a treatment for acute allergy symptoms; rather, it is a long-term preventative therapy. Patients must be committed to daily administration for several months before the ragweed season begins.

No FDA black box warnings for Ambrosia Artemisiifolia? No, this is incorrect. As noted in the side effects section, Ambrosia Artemisiifolia (specifically standardized sublingual tablets like Ragwitek) DOES carry a Black Box Warning. It emphasizes the risk of anaphylaxis, the requirement for the first dose to be supervised, and the necessity for patients to have access to auto-injectable epinephrine at all times during treatment.

• Allergic Reactions / Anaphylaxis Risk: The risk is highest during the initiation of therapy but can occur at any time. Patients must be educated on how to recognize the early signs of a systemic reaction.
• Asthma: Patients with uncontrolled or severe asthma are at a much higher risk for severe respiratory complications if they have an allergic reaction to the extract. Asthma must be well-controlled before starting therapy. If a patient experiences an asthma flare-up, they should consult their doctor before taking their next dose.
• Oral Inflammation and Surgery: Treatment should be paused if the patient has oral inflammation (such as canker sores or gum disease) or following oral surgery/tooth extraction. Open wounds in the mouth can increase the systemic absorption of the allergen, raising the risk of a severe reaction.
• Eosinophilic Esophagitis (EoE): Discontinue use if the patient develops persistent gastrointestinal symptoms, including dysphagia (difficulty swallowing) or gastroesophageal reflux symptoms.

There are no specific laboratory tests (like blood counts or liver enzymes) required for monitoring Ambrosia Artemisiifolia. However, clinical monitoring is essential:

• Clinical Assessment: Regular follow-ups with an allergist to evaluate the reduction in hay fever symptoms and the need for rescue medications.
• Adherence Monitoring: Checking that the patient is taking the medication daily and starting it at the correct time (12 weeks pre-season).
• Epinephrine Proficiency: The healthcare provider must periodically verify that the patient knows how to use their epinephrine auto-injector correctly.

Ambrosia Artemisiifolia does not typically cause drowsiness or impairment. However, if a patient experiences a systemic allergic reaction, they may become dizzy or lose consciousness. Patients should not drive if they feel unwell after taking a dose.

There is no direct chemical interaction between alcohol and Ambrosia Artemisiifolia extract. However, alcohol consumption can cause vasodilation and may theoretically increase the rate of allergen absorption through the oral mucosa. It is generally advised to avoid consuming alcohol immediately before or after taking the dose.

Unlike many medications, there is no 'withdrawal syndrome' associated with stopping Ambrosia Artemisiifolia. However, stopping the medication before the end of the ragweed season or before completing the recommended 3-year course will likely result in the return of allergy symptoms. If treatment is stopped for more than a few days, the desensitization effect may wane, and the patient may need to be re-evaluated before restarting.

> Important: Discuss all your medical conditions, especially asthma or previous severe allergic reactions, with your healthcare provider before starting Ambrosia Artemisiifolia.

While there are few absolute drug-drug contraindications, the following combinations are generally avoided due to safety concerns:

• Other Allergen Immunotherapy: Taking multiple different sublingual immunotherapy (SLIT) tablets at the exact same time is generally not recommended unless specifically directed by an allergist, as it increases the total allergen load and the risk of local and systemic reactions.

• Beta-Blockers (e.g., Metoprolol, Propranolol): These medications are a major concern. If a patient on beta-blockers has a severe allergic reaction (anaphylaxis), the beta-blocker can block the effects of epinephrine (adrenaline), making the reaction much harder to treat and potentially fatal.
• Alpha-Blockers and ACE Inhibitors: Similar to beta-blockers, these medications can interfere with the body's compensatory mechanisms during an allergic reaction or complicate the treatment of hypotension (low blood pressure) associated with anaphylaxis.
• Tricyclic Antidepressants and MAOIs: These can't necessarily be used safely with epinephrine, which might be needed to treat a reaction to the ragweed extract. They may potentiate the pressor effects of epinephrine, leading to severe hypertension.

• Antihistamines and Corticosteroids: While these are often used to treat allergy symptoms, they can mask the early 'warning signs' of a local reaction to the immunotherapy. This isn't necessarily a reason to avoid them, but patients should be aware that their local mouth symptoms might be suppressed.
• Immunosuppressants: Medications that suppress the immune system (like chemotherapy or high-dose systemic steroids) may reduce the effectiveness of the immunotherapy, as the body's ability to create IgG4 and regulatory T-cells is impaired.

• High-Acid Foods/Drinks: Consuming highly acidic foods (like citrus or vinegar) or very hot beverages immediately before or after the dose may irritate the oral mucosa and potentially alter the absorption of the allergenic proteins. It is best to wait at least 5 minutes after the tablet has dissolved before eating or drinking anything.

There are no well-documented interactions between Ambrosia Artemisiifolia and common herbal supplements like St. John's Wort or Ginkgo. However, patients should avoid any herbal products known to have potent immunomodulatory effects (like high-dose Echinacea) without consulting their allergist, as these could theoretically interfere with the desensitization process.

Ambrosia Artemisiifolia will directly affect the results of Allergy Skin Testing and In Vitro IgE Testing (e.g., RAST or ImmunoCAP). Over time, the goal of therapy is to reduce IgE sensitivity. If a patient is undergoing new allergy testing, the clinician must be informed that the patient is currently receiving immunotherapy, as this will significantly alter the interpretation of the results.

For each major interaction, the mechanism is usually pharmacodynamic (how the drugs affect the body's response) rather than pharmacokinetic (how the body processes the drug). The management strategy usually involves a careful risk-benefit analysis by the physician, particularly regarding the use of beta-blockers.

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

Ambrosia Artemisiifolia must NEVER be used in the following circumstances:

1. 1Severe, Unstable, or Uncontrolled Asthma: Immunotherapy can trigger bronchospasm. In patients whose asthma is not well-managed, this can lead to fatal respiratory failure.
2. 2History of Severe Systemic Allergic Reaction: If a patient has previously had a life-threatening reaction to any component of the extract or a previous attempt at ragweed immunotherapy, the risk of recurrence is too high.
3. 3History of Eosinophilic Esophagitis (EoE): Because the extract is known to potentially cause or worsen EoE, patients with a pre-existing diagnosis of this condition should not use sublingual immunotherapy.
4. 4Hypersensitivity to Excipients: Patients with a known allergy to any of the inactive ingredients in the tablet (such as gelatin or mannitol) must avoid the product.

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

• Concurrent Beta-Blocker Therapy: As mentioned, beta-blockers make anaphylaxis more difficult to treat. Some doctors may require a switch to a different class of blood pressure medication before starting immunotherapy.
• Active Oral Lesions: Treatment should be delayed until oral ulcers, gum disease, or surgical wounds have fully healed.
• Pregnancy (Initiation): While not strictly contraindicated for women already on a stable maintenance dose, healthcare providers generally do not recommend starting Ambrosia Artemisiifolia immunotherapy during pregnancy due to the risk of anaphylaxis-induced fetal distress.

Patients allergic to Short Ragweed (Ambrosia artemisiifolia) often show cross-reactivity with other members of the Asteraceae family, such as:

• Giant Ragweed (Ambrosia trifida)
• Chamomile
• Echinacea
• Sunflowers
• Dandelions

While the extract is specific to Short Ragweed, patients with extreme sensitivities to these related plants should be monitored closely for unexpected reactions.

> Important: Your healthcare provider will evaluate your complete medical history, including your asthma control and current medications, before prescribing Ambrosia Artemisiifolia.

Ambrosia Artemisiifolia is generally classified as Pregnancy Category B (or equivalent under newer labeling rules). This means that animal reproduction studies have failed to demonstrate a risk to the fetus, but there are no adequate and well-controlled studies in pregnant women.

• Risk Summary: The primary risk during pregnancy is not the drug itself, but the potential for a severe systemic allergic reaction (anaphylaxis) in the mother. Anaphylaxis can cause a sudden drop in maternal blood pressure, leading to uterine hypoperfusion and fetal hypoxia (lack of oxygen).
• Clinical Recommendation: Most allergists recommend that immunotherapy should not be initiated during pregnancy. However, if a woman is already on a well-tolerated maintenance dose and becomes pregnant, the treatment may be continued if the benefit of controlling allergy symptoms outweighs the small risk of a reaction.

It is not known whether Ambrosia Artemisiifolia allergenic proteins are excreted in human milk. However, because these are large proteins that are degraded in the mother's digestive tract or oral mucosa and have very low systemic bioavailability, it is highly unlikely that significant amounts would reach the breast milk or be absorbed by the nursing infant. The risk to the infant is considered minimal, but the decision should be discussed with a healthcare provider.

• Approved Age: The sublingual tablet form (Ragwitek) is FDA-approved for adults aged 18 through 65. It is not currently approved for use in children under 18 in the United States, although other ragweed extracts (injections) have been used in children as young as 5.
• Growth Effects: There is no evidence that allergenic extracts affect growth or development in children.
• Special Considerations: Children are more likely to have co-morbid asthma, which must be strictly evaluated before considering any form of immunotherapy.

Clinical trials of Ambrosia Artemisiifolia sublingual tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects.

• Pharmacokinetics: No age-related changes are expected since the drug is not hepatically or renally cleared.
• Safety: The main concern in the elderly is the presence of underlying cardiovascular disease, which could make them less able to tolerate the physiological stress of a systemic allergic reaction or the effects of epinephrine.

No dose adjustment is necessary. The allergenic proteins are not cleared by the kidneys. Patients on dialysis can safely use the sublingual form, provided they are otherwise good candidates for immunotherapy.

No dose adjustment is necessary. The allergenic proteins do not undergo hepatic metabolism. Even patients with severe cirrhosis (Child-Pugh Class C) do not require a change in dosing, although their overall medical stability should be considered.

> Important: Special populations, particularly pregnant women and those with co-existing medical conditions, require individualized medical assessment by an allergy specialist.

Ambrosia Artemisiifolia allergenic extract functions as an immunomodulator. The primary active components are the pollen proteins, most notably Amb a 1 (a 38 kDa glycoprotein).

At the molecular level, the extract targets the Adaptive Immune System. Upon sublingual administration, the allergens are captured by Oral Langerhans Cells (dendritic cells). these cells process the allergens and migrate to local lymph nodes. Here, they present the allergen fragments to Naiive T-cells. In an allergic individual, this usually results in Th2 cell activation. However, the controlled, repeated exposure provided by immunotherapy induces the expansion of T-regulatory (Treg) cells. These Tregs produce IL-10, which signals B-cells to switch production from IgE to IgG4. IgG4 acts as a 'decoy' or 'blocking' antibody, binding to ragweed pollen before it can reach the IgE bound to mast cells, thus preventing the release of histamine.

• Dose-Response: There is a clear dose-response relationship; higher doses of Amb a 1 are more effective at inducing IgG4 but carry a higher risk of local side effects.
• Time to Onset: The immunological changes begin within weeks, but the clinical reduction in symptoms typically requires at least 12 weeks of pre-seasonal treatment.
• Duration of Effect: If the full 3-year course is completed, the desensitization effect can last for several years after the medication is discontinued.
• Tolerance: Unlike many drugs, the body develops 'beneficial tolerance' to the allergen, allowing the patient to eventually be exposed to ragweed pollen in the environment without significant symptoms.

| Parameter | Value |

|---|---|

| Bioavailability | Negligible (Systemic) |

| Protein Binding | N/A (Local action) |

| Half-life | N/A (Proteolytic degradation) |

| Tmax | 1-2 hours (Local tissue peak) |

| Metabolism | Local Proteolysis |

| Excretion | Not renally excreted as intact protein |

• Molecular Formula: Complex mixture of proteins (e.g., Amb a 1: C1658H2544N440O514S12 - approximate for the major allergen).
• Molecular Weight: Amb a 1 is approximately 38,000 Daltons.
• Solubility: Highly soluble in aqueous solutions and saliva.
• Description: A purified extract containing both major and minor allergens from the pollen of Ambrosia artemisiifolia.

Ambrosia Artemisiifolia belongs to the therapeutic class of Allergenic Extracts. Specifically, it is a Standardized Plant Allergenic Extract. It is grouped with other sublingual immunotherapy (SLIT) agents like Timothy Grass extract and House Dust Mite extract.