PROCYSBI SIDE EFFECTS

SIDE EFFECTS

The following adverse reactions are also discussed in other sections of the labeling:

• Ehlers-Danlos-like Syndrome
• Skin Rash
• Gastrointestinal (GI) Ulcers and Bleeding
• Central Nervous System Symptoms
• Leukopenia and/or Elevated Phosphatase Levels
• Benign Intracranial Hypertension

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The data described below reflect exposure to cysteamine in 345 patients with nephropathic cystinosis (246 patients receiving immediate-release cysteamine as cysteamine hydrochloride or phosphocysteamine, and 80 patients receiving PROCYSBI) in open-label clinical trials.

Clinical Trials Experience With PROCYSBI In Patients Switched From Immediate-Release Cysteamine Bitartrate

Sixty-two patients with nephropathic cystinosis (38 males and 24 females) received PROCYSBI in two clinical trials at doses ranging from 0.29 grams/m² per day to 2.19 grams/m² per day. All patients were switched from immediate-release cysteamine to PROCYSBI. Forty-three patients, ages 6 to 26 years old, received PROCYSBI in an 8-week, open-label, randomized, cross-over trial comparing PROCYSBI to immediate-release cysteamine bitartrate. Forty of 43 patients continued PROCYSBI treatment in an open-label extension trial (36 patients were treated with PROCYSBI for longer than 2 years, and 20 patients were treated for longer than 5 years). An additional 19 patients (6 renal transplanted patients and 13 patients aged 2 to 6 years) were enrolled directly into this trial (12 patients were treated with PROCYSBI for longer than 2 years, and 9 patients were treated for longer than 5 years).

In the open-label, randomized, cross-over trial, a higher incidence of adverse reactions was reported in patients during the PROCYSBI treatment period compared with the immediate-release cysteamine bitartrate treatment period (see Table 1). Other significant adverse reactions reported during clinical trials included hypersensitivity reactions, including anaphylaxis.

Table 1: Adverse Reactions in ≥5% of Patients with Nephropathic Cystinosis in a Randomized, Cross-Over Trial

In the open-label extension trial (N=59), the most commonly reported adverse reactions (>15%) were vomitin g, headache, diarrhea, nausea, conjunctivitis, influenza, gastroenteritis, nasopharyngitis, abdominal pain, dehydration, ear infection, upper respiratory tract infection, fatigue, arthralgia, cough, and pain in extremity.

Clinical Trials Experience With PROCYSBI In Cysteamine-Naïve Patients

Seventeen cysteamine-naïve patients (fifteen patients between the ages of 1 and 5 years, one 9-year old and one 22-year old) received PROCYSBI in an open-label clinical trial. Serious adverse reactions occurring in at least 2 patients (>10%) were: gastroenteritis/viral gastroenteritis (n=6), vomiting (n=4), and electrolyte imbalance (n=2). Three patients with serious adverse reactions of gastroenteritis also had dehydration. Common adverse reactions reported at a frequency of >10% (occurring in at least 2 patients) are shown in Table 2.

Table 2: Adverse Reactions in >10% of Patients with Nephropathic Cystinosis Naïve to Cysteamine Treatment in an Open-Label Trial

Clinical Trials Experience With Immediate-Release Cysteamine

The most frequent adverse reactions involved the gastrointestinal and central nervous systems and were especially prominent at the initiation of cysteamine therapy. Most patients were able to resume therapy at lower doses. The most common reactions (>5%) were vomiting, anorexia, fever, diarrhea, lethargy, and rash. Other adverse reactions included nausea, bad breath, abdominal pain, headache, dizziness, and urticaria.

Withdrawals due to intolerance, vomiting, anorexia, lethargy, and fever occurred more frequently in those patients receiving 1.95 grams/m² per day as compared with 1.3 grams/m² per day of immediate-release cysteamine bitartrate.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of immediate-release cysteamine bitartrate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• Musculoskeletal: Joint hyperextension, leg pain, osteopenia, compression fracture, scoliosis, genu valgum.
• Skin: Erythema multiforme bullosa, toxic epidermal necrolysis, Ehlers-Danlos-like syndrome, molluscoid pseudotumors, skin striae, skin fragility.
• Central Nervous System: seizures, lethargy, somnolence, depression and encephalopathy, benign intracranial hypertension (or PTC) and/or papilledema.