Applies to pegvaliase: subcutaneous solution.

Serious side effects of Pegvaliase

Along with its needed effects, pegvaliase may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking pegvaliase:

More common

• Cough
• diarrhea
• difficulty swallowing
• dizziness
• fast heartbeat
• fever
• hives, itching, skin rash
• joint or muscle pain
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or genitals
• nausea
• numbness or tingling of the face, hands, or feet
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• redness and soreness of the eyes
• sores in the mouth
• stomach pain
• swelling of the feet or lower legs
• tightness in the chest
• trouble breathing
• unusual tiredness or weakness
• vomiting

Rare

• Feeling of discomfort
• joint swelling
• swollen lymph glands

Other side effects of Pegvaliase

Some side effects of pegvaliase may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Anxiety
• bleeding, blistering, burning, coldness, discoloration of skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
• difficulty in moving
• headache
• loss or thinning of hair
• muscle stiffness
• pain in the mouth and throat
• stuffy nose

For Healthcare Professionals

Applies to pegvaliase: subcutaneous solution.

General

The most commonly reported adverse reactions have included injection site reactions, arthralgia, hypersensitivity reactions, headache, generalized skin reactions lasting at least 14 days, pruritus, nausea, abdominal pain, oropharyngeal pain, vomiting, cough, diarrhea, and fatigue.^[Ref]

Hypersensitivity

Very common (10% or more): Hypersensitivity reactions (up to 65%)

Common (1% to 10%): Anaphylaxis, acute systemic hypersensitivity reaction, serum sickness^[Ref]

During clinical trials, a total of 42 anaphylactic episodes were reported in 29 patients (n=285). The rate of anaphylaxis was highest during induction and titration phase. Signs and symptoms of anaphylaxis included syncope, hypotension, hypoxia, dyspnea, wheezing, chest discomfort/chest tightness, tachycardia, angioedema (swelling of face, lips, eyes, tongue), throat tightness, skin flushing, rash, urticaria, pruritus, and gastrointestinal symptoms (vomiting, nausea, diarrhea). Anaphylaxis occurred within 1 hour in 81% (34/42) of the reported anaphylaxis episodes. Most episodes occurred within the first year of dosing (69%, 29/42 episodes), however, cases also occurred after one year of dosing and up to 1604 days (4.4 years) into treatment. Twenty one out of the 29 (72%) patients who experienced anaphylaxis were rechallenged and 6 out of the 21 (29%) had recurrence of anaphylaxis. All anaphylaxis episodes resolved without sequelae.

Hypersensitivity reactions other than anaphylaxis have been reported in 72% of patients (204/285). Hypersensitivity reactions have included rash, urticaria, anaphylaxis, rash generalized, hypersensitivity, rash erythematous, rash maculo-papular, rash pruritic, serum sickness, swelling face, dermatitis contact, swollen tongue, lip swelling, rash macular, pharyngeal edema, injection site hypersensitivity, eczema, drug eruption, dermatitis allergic, dermatitis, tongue edema, palatal edema, edema mouth, multiple allergies, lip edema, eye edema, exfoliative rash, drug hypersensitivity, dermatitis atopic, dermatitis acneiform, pruritus allergic, mouth swelling, implant site rash, gingival swelling, face edema, eyelid edema, eye swelling, dermatitis psoriasiform, dermatitis infected, conjunctivitis allergic, bronchospasm, angioedema, allergic sinusitis, allergic cough, eczema nummular, and rhinitis allergic.^[Ref]

Immunologic

Very common (10% or more): Anti-phenylalanine ammonia lyase (PAL) immunoglobulin G (IgG) antibodies (up to 99.6%), anti-PAL IgM antibodies (up to 98%), anti-drug IgE antibodies (up to 96%), sustained total anti-drug antibody response (up to 91%), neutralizing antibodies (up to 89%), complement factor C3 decreased (up to 84%), complement factor C4 decreased (up to 64%)^[Ref]

Local

Injection site reactions have included: Erythema, pruritus, pain, bruising, rash, swelling, urticaria, induration, hemorrhage, edema, mass, inflammation, nodule, discoloration, warmth, hematoma, irritation, vesicles, hypersensitivity, papule, discomfort, scar, paresthesia, hypertrophy, extravasation, scab, and dryness^[Ref]

Very common (10% or more): Injection site reactions (up to 93%)^[Ref]

Musculoskeletal

Very common (10% or more): Arthralgia (up to 86%), blood creatinine phosphokinase above upper limit of normal (up to 48%), myalgia (up to 12%)

Common (1% to 10%): Joint swelling, musculoskeletal stiffness, joint stiffness^[Ref]

Arthralgia included: Pain in extremity, back pain, musculoskeletal pain, and neck pain^[Ref]

Other

Very common (10% or more): C-reactive protein (CRP) above upper limit of normal (up to 71%), fatigue (up to 24%), high sensitivity CRP levels increased (up to 17%)^[Ref]

Metabolic

Very common (10% or more): Hypophenylalaninemia (up to 65%)^[Ref]

Hypophenylalaninemia (blood phenylalanine level below 30 micromol/L) on a single measurement was reported in up to 65% of patients; hypophenylalaninemia on at least 2 consecutive measurements was reported in up to 49% of patients.^[Ref]

Nervous system

Very common (10% or more): Headache (up to 56%), dizziness (up to 21%)^[Ref]

Headache included migraine and sinus headache.^[Ref]

Dermatologic

Very common (10% or more): Generalized skin reaction lasting at least 14 days (up to 47%), rash (up to 33%), pruritus (up to 27%), urticaria (up to 25%), alopecia (up to 21%), erythema (up to 11%)

Common (1% to 10%): Skin exfoliation, maculopapular rash, angioedema^[Ref]

Generalized skin reactions included pruritus, rash, urticaria, dry skin, rash erythematous, erythema, cellulitis, rash macular, pruritus generalized, petechiae, dermatitis allergic, skin infection, skin induration, rash maculopapular, rash generalized, pharyngeal edema, macule, granulomatous dermatitis, exfoliative rash, drug eruption, dermatitis atopic, dermatitis, xanthogranuloma, skin plaque, skin mass, skin lesion, skin hypopigmentation, skin hyperpigmentation, skin exfoliation, septal panniculitis, scar, rash pruritic, rash papular, psoriatic arthropathy, pruritus allergic, papule, necrobiosis lipoidica diabeticorum, furuncle, eczema, ecchymosis, dermatitis psoriasiform, dermatitis infected, blister, eczema nummular, granuloma, infected dermal cyst, lipohypertrophy, psoriasis, and skin irritation.^[Ref]

Gastrointestinal

Abdominal pain included upper abdominal pain and abdominal discomfort.^[Ref]

Very common (10% or more): Nausea (up to 31%), abdominal pain (up to 30%), oropharyngeal pain (up to 29%), vomiting (up to 30%), diarrhea (up to 27%)^[Ref]

Respiratory

Very common (10% or more): Cough (up to 30%), nasal congestion (up to 27%)^[Ref]

Psychiatric

Very common (10% or more): Anxiety (up to 21%)^[Ref]

Hematologic

Very common (10% or more): Lymphadenopathy (up to 16%)^[Ref]