PALFORZIA: Uses, Dosage & Side Effects

What Is PALFORZIA and What Is It Used For?

PALFORZIA is a biological allergen product whose active substance is defatted peanut powder (defatted powder of Arachis hypogaea L., semen). The powder is rigorously characterised so that each dose level contains a known and reproducible amount of peanut protein, which is the part of the peanut that triggers IgE-mediated allergic reactions in patients with peanut allergy. PALFORZIA differs fundamentally from food-grade peanut flour or home-made peanut OIT preparations, which can vary substantially in protein content from batch to batch and therefore make safe up-dosing difficult.

The treatment principle behind PALFORZIA is allergen-specific immunotherapy delivered by the oral route. By introducing very small amounts of peanut protein and increasing the daily dose stepwise over several months, the immune system is gradually retrained to tolerate progressively larger quantities of allergen. The full mechanism is not completely understood, but research suggests that successful oral immunotherapy is associated with a shift in the allergen-specific T-cell response away from a Th2 (allergy-promoting) profile and towards a regulatory T-cell (Treg) profile, an early rise followed by a slow decline in peanut-specific IgE antibodies, an increase in protective peanut-specific IgG4 (blocking) antibodies, and reduced reactivity of mast cells and basophils on allergen exposure. The clinical result is that more peanut protein is needed before symptoms appear – a state known as desensitisation.

It is essential to understand what desensitisation is and what it is not. Desensitisation increases the protective threshold while treatment is being taken. It does not eliminate the allergy, and it is not the same as sustained unresponsiveness (often called “tolerance”), in which protection persists even if therapy is stopped. With PALFORZIA, the protective effect depends on continued daily dosing. If treatment is interrupted for more than a short period, the threshold falls again and full peanut sensitivity returns, often within weeks to months. For this reason, PALFORZIA is best understood as a long-term – possibly lifelong – daily treatment, in much the same way that an inhaled corticosteroid is taken daily for asthma.

PALFORZIA is approved for the treatment of patients with a confirmed diagnosis of peanut allergy. Initiation is typically permitted in children and adolescents aged 4 to 17 years; in some regions the lower age limit has been extended to include children from 1 year of age, based on data showing that earlier intervention may improve outcomes. Once Maintenance has been reached, treatment may be continued in patients aged 4 years and older to preserve desensitisation. The diagnosis of peanut allergy must be established by an allergy specialist on the basis of a convincing clinical history, supportive specific IgE measurement (skin prick test and/or peanut-specific serum IgE), and, where appropriate, a supervised oral food challenge.

Approved indications and clinical positioning for PALFORZIA include:

• Mitigation of allergic reactions, including anaphylaxis, after accidental peanut exposure in patients with a confirmed diagnosis of peanut allergy. The aim is to raise the reactive threshold so that everyday accidental ingestion (for example, food prepared in shared facilities) is less likely to trigger a serious reaction.
• Adjunct to a strict peanut-avoidant diet, not a replacement for it. Patients and caregivers must continue to read labels, avoid foods that may contain peanut, and carry an adrenaline (epinephrine) auto-injector at all times.
• Initial Dose Escalation and the first dose of each Up-Dosing level are administered under the direct supervision of a healthcare professional in a setting able to manage anaphylaxis. Subsequent home dosing within a level is performed once the initial supervised dose has been tolerated.

Peanut allergy is one of the most common and most dangerous IgE-mediated food allergies. It affects roughly 1–2% of children in many high-income countries, often persists into adulthood, and is a leading cause of fatal and near-fatal food-induced anaphylaxis. Before PALFORZIA, the only management options were strict dietary avoidance and the use of adrenaline auto-injectors for accidental exposure. PALFORZIA represents the first pharmacological treatment specifically licensed to alter the natural course of peanut allergy.

What Should You Know Before Taking PALFORZIA?

Contraindications

PALFORZIA must not be used in certain situations because the risk of severe reactions outweighs the potential benefit. Treatment is contraindicated in the following circumstances:

• Uncontrolled or severe asthma: Active asthma is the single most important risk factor for severe and fatal food-induced anaphylaxis. PALFORZIA must not be initiated if asthma is poorly controlled, and treatment is interrupted if asthma control deteriorates during therapy.
• History of eosinophilic oesophagitis (EoE) or other eosinophilic gastrointestinal disease: Oral immunotherapy can both unmask and provoke EoE, an inflammatory condition of the food pipe characterised by infiltration of eosinophils.
• Severe or life-threatening anaphylaxis within the previous 60 days: Recent severe reactions indicate a particularly reactive immune state and significantly increase the risk of further serious reactions during dose escalation.
• Severe or uncontrolled mast cell disorders, including mastocytosis and idiopathic mast cell activation syndrome, due to an unpredictable risk of severe degranulation reactions.
• Hypersensitivity to any of the inactive ingredients of the product (e.g., the excipient blend used in the powder).

Warnings and Precautions

Before and during PALFORZIA treatment, several practical precautions must be observed to minimise the risk of severe reactions:

• Adrenaline (epinephrine) auto-injector: Patients must be prescribed an auto-injector and trained in its use. The auto-injector must be available during every dose, including at home, and accompany the patient at all times.
• Asthma assessment and ongoing monitoring: Asthma must be evaluated before starting and reviewed regularly during treatment. PALFORZIA should not be initiated, and may need to be interrupted, if asthma is uncontrolled.
• Cofactors that lower the reaction threshold: Exercise, hot showers or baths, hot weather, intercurrent illness or fever, menstruation, fasting, sleep deprivation, and use of nonsteroidal anti-inflammatory drugs (NSAIDs) or alcohol can all increase the risk of allergic reactions. Strenuous physical activity and very hot showers or baths should be avoided for at least 3 hours after each dose.
• Each dose must be taken with food at approximately the same time of day. Taking PALFORZIA on an empty stomach increases the rate of absorption and the risk of systemic reactions.
• Eosinophilic oesophagitis (EoE): Persistent abdominal pain, vomiting, dysphagia (difficulty swallowing), food sticking in the throat, regurgitation, or unexplained weight loss may indicate EoE and require evaluation by a gastroenterologist, including upper endoscopy with oesophageal biopsies. PALFORZIA must be discontinued if EoE is confirmed.
• Vasovagal episodes: Some patients experience faintness, pallor, sweating or transient hypotension during or shortly after dosing, particularly during Initial Dose Escalation. These can be confused with the early symptoms of anaphylaxis and require careful evaluation by the supervising clinician.
• Chronic medical conditions: Cardiovascular disease, severe atopic dermatitis, chronic urticaria, severe seasonal allergic rhinitis or other conditions that complicate the recognition or treatment of anaphylaxis warrant additional caution and an individualised risk-benefit assessment.
• Missed doses or treatment interruptions: Specific protocols are required when doses are missed. After short interruptions the previous dose may be resumed under supervision; longer interruptions require restart at a lower level. Patients must never increase their own dose at home or attempt to make up missed doses by doubling.
• Children: PALFORZIA is administered by caregivers in young children. Caregivers must be trained to recognise and treat anaphylaxis, avoid co-factors, and follow the dosing schedule precisely.

Routine follow-up appointments with the prescribing allergy specialist are essential. These appointments allow the team to review tolerability, asthma control, adherence, and any reactions, and to coordinate the next supervised up-dosing visit.

Other Medications

Tell your doctor about all medicines you are taking before starting PALFORZIA, including prescription drugs, over-the-counter medicines, herbal remedies, and supplements. Some medications can either increase the risk of severe allergic reactions or interfere with the recognition and emergency treatment of anaphylaxis. These interactions are reviewed in detail in the next section.

Pregnancy and Breastfeeding

There are limited or no clinical data on the use of PALFORZIA during pregnancy. Initiation of PALFORZIA during pregnancy is not recommended because of the risk of systemic allergic reactions, which can compromise both maternal health and the pregnancy. In patients who become pregnant while already established on Maintenance therapy, the decision to continue PALFORZIA should be individualised in consultation with an allergy specialist and obstetrician, weighing the established benefit of maintained desensitisation against the theoretical risks. Up-Dosing should not be performed during pregnancy.

It is not known whether peanut proteins from PALFORZIA are excreted in human breast milk in clinically relevant amounts. Trace exposure of the breastfed infant to allergen-derived molecules is theoretically possible. The benefit of breastfeeding for the infant and the benefit of treatment for the mother must be considered when deciding whether to interrupt or continue PALFORZIA during breastfeeding. There are no data suggesting an effect of PALFORZIA on female or male fertility.

Driving and Operating Machinery

PALFORZIA itself does not directly impair the ability to drive or operate machinery. However, allergic reactions during treatment, the symptoms of anaphylaxis, and the use of antihistamines or adrenaline as treatment for reactions can all temporarily affect alertness, coordination and reaction time. After any clinically significant reaction, patients should not drive or operate machinery until they have fully recovered and have been cleared by their healthcare team.

Important Information About Ingredients

PALFORZIA contains peanut protein as the active substance. Patients with concomitant tree nut allergies should be aware that PALFORZIA does not protect against tree nut allergic reactions and must continue to avoid tree nuts as advised by their allergist. The product is manufactured to standardised specifications with respect to other potential allergens, but patients with multiple food allergies should discuss the safety profile with their specialist before initiation.

How Does PALFORZIA Interact with Other Drugs?

Because PALFORZIA exerts its effect by inducing immune changes rather than by reaching systemic circulation as a small-molecule drug, traditional cytochrome P450-mediated interactions are not a concern. Instead, the most relevant interactions are pharmacodynamic: medicines that change the body’s response to allergens, lower the threshold for systemic reactions, or interfere with the ability to recognise and treat anaphylaxis. Always tell your prescribing allergist about every medicine and supplement you take, including those started by other doctors.

Major Interactions

Minor Interactions and Cofactor Considerations

If PALFORZIA is started in a patient already on chronic medication for another condition, the allergist will review the regimen and coordinate with the prescribing physician. Existing medications are not typically stopped solely because of PALFORZIA, but their potential effect on allergic reactivity and emergency treatment is taken into account in the overall plan.

What Is the Correct Dosage of PALFORZIA?

The PALFORZIA dosing schedule is highly structured and must not be modified by the patient. The total course typically takes around six months to reach the daily Maintenance dose of 300 mg, after which long-term daily dosing continues. The product is supplied in two presentations: capsules of 0.5, 1, 10, 20 and 100 mg of peanut protein (which are opened and the powder mixed with food – the capsule shell is not swallowed) and a 300 mg sachet used during Maintenance.

Phase 1: Initial Dose Escalation

Phase 2: Up-Dosing

Phase 3: Maintenance

How to Take PALFORZIA

Each dose is prepared and administered as follows:

1. Wash hands before handling the product. Open the capsule(s) of the appropriate strength over a small amount (one or two teaspoons) of cold or room-temperature semi-solid food such as applesauce, yoghurt or pudding. Do not heat the food. The 300 mg Maintenance dose is supplied as a sachet, the entire contents of which are emptied onto the food.
2. Mix the powder thoroughly into the food until uniformly distributed.
3. The whole portion of food must be eaten promptly – do not save partial doses for later.
4. Take the dose at approximately the same time each day, with a meal. Avoid an empty stomach.
5. For at least 3 hours after the dose, avoid strenuous physical activity, hot showers or baths, and unusual exposure to heat.
6. Wash hands after preparing and administering each dose to avoid skin contact with peanut protein.

Missed Doses

What to do if a dose is missed depends on how many doses are missed and on the current treatment phase:

• One or two consecutive doses missed during Maintenance: Resume the usual 300 mg dose the next day. Do not double up.
• Three or four consecutive doses missed: Contact the allergy team. The next dose may need to be taken under supervision, and the dose level may be temporarily reduced.
• Five or more consecutive doses missed, or any extended interruption during Up-Dosing: Treatment must be re-initiated under specialist supervision, often at a lower level than where it was paused.

Overdose

An overdose of PALFORZIA – for example, accidentally taking more than one dose in a 24-hour period – substantially increases the risk of an allergic reaction, including anaphylaxis. If overdose is suspected, monitor closely for symptoms, administer adrenaline immediately if signs of anaphylaxis develop, and contact emergency services. Even when no immediate symptoms appear, the prescribing allergy team should be informed so that the next scheduled dose can be safely planned.

Dose Adjustments and Special Populations

• Adults (18 years and older): Initiation of PALFORZIA in adults is not part of the original approved indication in many regions, although adults already on Maintenance after initiation in adolescence may continue treatment. Specialist evaluation is required.
• Children (4–17 years): The standard schedule applies, with caregiver supervision for all aspects of dosing, cofactor avoidance and emergency response.
• Children below 4 years of age: In some regions PALFORZIA is approved for children from 1 year of age based on data from younger paediatric populations. Where approved, dosing follows the same three-phase principle, performed by an allergy specialist with paediatric experience.
• Elderly patients: No specific dose adjustment is required, but the very limited experience in elderly patients and increased frequency of cardiovascular comorbidity make initiation in this group an individualised specialist decision.
• Renal or hepatic impairment: No dose adjustment is required because PALFORZIA is not absorbed and metabolised in the conventional pharmacokinetic sense.

What Are the Side Effects of PALFORZIA?

Like all medicines, PALFORZIA can cause side effects, although not everyone experiences them. Because the active substance is the same allergen the patient is sensitised to, allergic and gastrointestinal symptoms are by far the most common adverse events. Symptoms tend to be most frequent during Initial Dose Escalation and Up-Dosing and to decrease in frequency and severity once a stable Maintenance dose has been reached.

Side Effects Overview

Eosinophilic Oesophagitis (EoE)

EoE is the most distinctive non-IgE-mediated risk associated with oral immunotherapy. It is a chronic, allergen-driven inflammatory condition of the oesophagus characterised by infiltration of eosinophils into the oesophageal mucosa. In PALFORZIA pivotal trials and post-marketing experience, EoE has been reported in approximately 1–5% of treated patients. Symptoms can include persistent abdominal pain, vomiting, regurgitation, difficulty swallowing, food sticking in the throat, and unexplained weight loss. Suspected EoE requires referral for upper gastrointestinal endoscopy with oesophageal biopsies. If EoE is confirmed, PALFORZIA must be permanently discontinued. EoE often improves but does not always resolve completely after stopping therapy.

Patterns Over Time

Adverse events follow a predictable pattern. The frequency of allergic and gastrointestinal symptoms is highest during Initial Dose Escalation and the early Up-Dosing levels and gradually decreases as the immune system adapts. Most reactions are mild to moderate, but a small proportion of patients experience severe reactions or anaphylaxis at any phase, including during long-term Maintenance. Cofactors such as exercise, hot showers, intercurrent illness, fever, menstruation and fasting can precipitate reactions even on a previously well-tolerated dose.

How Should PALFORZIA Be Stored?

Correct storage of PALFORZIA is important to maintain the consistency of the dose and the safety of treatment. Follow these recommendations carefully and refer to the patient information leaflet supplied with your specific pack for region-specific details:

• Temperature: Store at controlled room temperature, typically between 20 °C and 25 °C (68–77 °F). Brief excursions to 15–30 °C are usually permitted. Do not refrigerate and do not freeze.
• Original packaging: Keep capsules in the blister and the sachets in the carton until use to protect from light and moisture.
• Children: Keep out of the sight and reach of children. Accidental ingestion by an unintended person could trigger a peanut allergic reaction in someone with peanut allergy.
• Expiry date: Do not use after the expiry date printed on the packaging. Expired product may have reduced or unpredictable allergen content.
• Damaged packaging: Do not use a capsule or sachet that appears damaged, opened, or tampered with.
• Travel: When travelling, keep the medicine in carry-on luggage to avoid temperature extremes; never leave PALFORZIA in a hot car.
• Disposal: Do not dispose of unused medicine via wastewater or household waste. Return any unused or expired product to a pharmacy for safe disposal.

Capsules are intended to be opened and the powder mixed with food at the time of dosing – the capsule shell itself is never swallowed. Once the powder has been mixed with food, the prepared dose should be eaten immediately and not stored.

What Does PALFORZIA Contain?

Active Substance

The active substance is defatted powder of Arachis hypogaea L., semen – that is, defatted ground peanut seed. It is standardised so that each capsule or sachet contains a precisely defined amount of total peanut protein, the major triggers of which include the well-characterised peanut allergens Ara h 1, Ara h 2, Ara h 3 and Ara h 6.

The available presentations contain the following amounts of peanut protein per unit:

• 0.5 mg capsule (used during Initial Dose Escalation)
• 1 mg capsule (used during Initial Dose Escalation)
• 10 mg capsule (used during Up-Dosing)
• 20 mg capsule (used during Up-Dosing)
• 100 mg capsule (used during Up-Dosing and to assemble Maintenance-equivalent doses)
• 300 mg sachet (used for daily Maintenance therapy)

Inactive Ingredients (Excipients)

The exact list of excipients varies slightly between presentations and may include cornstarch, microcrystalline cellulose, magnesium stearate, colloidal silicon dioxide and the capsule shell components (gelatin or hypromellose with pharmaceutical colourants). Patients with hypersensitivity to any of these excipients should not use PALFORZIA. The complete excipient list for each strength is provided in the patient information leaflet supplied with the medicine.

Appearance

PALFORZIA is supplied as off-white to pale tan powder contained in coloured capsules (for the lower strengths) or in a sachet (for the 300 mg Maintenance dose). The capsules are colour-coded by strength to support correct selection during dose preparation. Capsules are not swallowed; the contents are emptied over food and consumed.

Manufacturer and Marketing Authorisation

PALFORZIA was originally developed by Aimmune Therapeutics and is currently marketed internationally by Stallergenes Greer (under licence from the marketing authorisation holder). Manufacturing and quality control are performed at facilities approved by the relevant regulatory authorities. The product is supplied under controlled distribution conditions to ensure that prescribers and patients receive appropriate training and that anaphylaxis emergency planning is in place.