warnings and cautions
5 WARNINGS AND PRECAUTIONS Ehlers-Danlos-like Syndrome: Reduce dosage if skin and bone lesions occur. ( 5.1 ) Skin Rash: Discontinue if severe skin rash such as erythema multiforme bullosa or toxic epidermal necrolysis occurs. ( 5.2 ) Gastrointestinal (GI) Ulcers and Bleeding: Monitor for GI symptoms and consider decreasing the dose if severe symptoms occur. ( 5.3 ) Central Nervous System (CNS) Symptoms: Monitor for CNS symptoms; interrupt or reduce the dose for severe symptoms or those that persist or progress ( 5.4 ). Leukopenia and/or Elevated Alkaline Phosphatase Levels: Monitor white blood cell count and alkaline phosphatase levels; decrease or discontinue the dose until values revert to normal. ( 5.5 ) Benign Intracranial Hypertension: Monitor for signs and symptoms; interrupt or reduce the dose for signs/symptoms that persist, or discontinue if diagnosis is confirmed. ( 5.6 ) 5.1 Ehlers-Danlos-like Syndrome Skin and bone lesions that resemble clinical findings for Ehlers-Danlos-like syndrome have been reported in patients treated with high doses of immediate-release cysteamine bitartrate or other cysteamine salts. These include molluscoid pseudotumors (purplish hemorrhagic lesions), skin striae, bone lesions (including osteopenia, compression fractures, scoliosis and genu valgum), leg pain, and joint hyperextension. One patient on immediate-release cysteamine bitartrate with serious skin lesions subsequently died of acute cerebral ischemia with marked vasculopathy. Monitor patients for development of skin or bone lesions and interrupt PROCYSBI dosing if patients develop these lesions. PROCYSBI may be restarted at a lower dose under close supervision, then slowly increase to the appropriate therapeutic dose [see Dosage and Administration ( 2.2 )] . 5.2 Skin Rash Severe skin rashes such as erythema multiforme bullosa or toxic epidermal necrolysis have been reported in patients receiving immediate-release cysteamine bitartrate. If severe skin rashes develop, permanently discontinue use of PROCYSBI [see Contraindications ( 4 )] . 5.3 Gastrointestinal Ulcers and Bleeding Gastrointestinal (GI) ulceration and bleeding have been reported in patients receiving immediate-release cysteamine bitartrate. GI tract symptoms including nausea, vomiting, anorexia and abdominal pain, sometimes severe, have been associated with cysteamine. If severe GI tract symptoms develop, consider decreasing the dose of PROCYSBI [see Dosage and Administration ( 2.2 )] . 5.4 Central Nervous System Symptoms Central Nervous System (CNS) symptoms such as seizures, lethargy, somnolence, depression, and encephalopathy have been associated with immediate-release cysteamine. Neurological complications have also been described in some patients with cystinosis who have not been treated with cysteamine. Carefully evaluate and monitor patients who develop CNS symptoms. Interrupt medication or adjust the dose as necessary for patients with severe symptoms or with symptoms that persist or progress. Inform patients that PROCYSBI may impair their ability to perform tasks such as driving or operating machinery. 5.5 Leukopenia and/or Elevated Alkaline Phosphatase Levels Cysteamine has been associated with reversible leukopenia and elevated alkaline phosphatase levels. Monitor white blood cell counts and alkaline phosphatase levels. If tests values remain elevated, consider decreasing the dose or discontinuing the drug until values revert to normal. 5.6 Benign Intracranial Hypertension Benign intracranial hypertension (pseudotumor cerebri; PTC) and/or papilledema have been reported in patients receiving immediate-release cysteamine bitartrate treatment. Monitor patients for signs and symptoms of PTC, including headache, tinnitus, dizziness, nausea, diplopia, blurry vision, loss of vision, pain behind the eye or pain with eye movement. If signs/symptoms persist, interrupt dosing or decrease the dose and refer the patient to an ophthalmologist. If the diagnosis is confirmed, permanently discontinue use of PROCYSBI.