CYSTEAMINE Drug Interactions: What You Need to Know

INTERACTIONS

7.1 Drugs that Increase Gastric pH Drugs that increase the gastric pH (e.g., medications containing bicarbonate or carbonate) may alter the pharmacokinetics of cysteamine due to the premature release of cysteamine from PROCYSBI and increase WBC cystine concentration. Concomitant administration of 20 mg omeprazole did not affect the pharmacokinetics of cysteamine when PROCYSBI was administered with 240 mL of orange juice or with 240 mL of water <span class="opacity-50 text-xs">[see Clinical Pharmacology (12.3) ]</span>. Monitor WBC cystine concentration when drugs that increase the gastric pH are concomitantly used <span class="opacity-50 text-xs">[see Dosage and Administration (2.5) ]</span>.

7.2 Use with Alcohol Consumption of alcohol with PROCYSBI may increase the rate of cysteamine release and/or adversely alter the pharmacokinetic properties, as well as the effectiveness and safety of PROCYSBI. Therefore, do not consume alcoholic beverages during treatment with PROCYSBI <span class="opacity-50 text-xs">[see Dosage and Administration (2.6) ]</span>.

7.3 Other Medications Used for the Management of Fanconi Syndrome PROCYSBI can be administered with other electrolyte and mineral replacements necessary for management of Fanconi syndrome, as well as vitamin D and thyroid hormone.

The use of PROCYSBI is contraindicated in patients with a serious hypersensitivity reaction, including anaphylaxis, to penicillamine or cysteamine. Hypersensitivity to penicillamine or cysteamine ( 4 )

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 )

Fibrosing

Colonopathy: Evaluate patients with severe, persistent, and/or worsening abdominal symptoms for fibrosing colonopathy. If the diagnosis is confirmed, permanently discontinue PROCYSBI and switch to immediate-release cysteamine bitartrate capsules ( 5.4 )

Central Nervous

System (CNS) Symptoms: Monitor for CNS symptoms; interrupt or reduce the dose for severe symptoms or those that persist or progress ( 5.5 ). 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. ( 5.6 )

Benign Intracranial

Hypertension: Monitor for signs and symptoms; interrupt or reduce the dose for signs/symptoms that persist, or discontinue if diagnosis is confirmed. ( 5.7 )

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 <span class="opacity-50 text-xs">[see Dosage and Administration (2.1 , 2.4) ]</span> .

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 <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> .

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 <span class="opacity-50 text-xs">[see Dosage and Administration (2.1 , 2.4) ]</span> .

5.4 Fibrosing Colonopathy Fibrosing colonopathy, including colonic stricture formation, has been reported with postmarketing use of PROCYSBI in pediatric and young adult patients with nephropathic cystinosis. Some of these patients had been treated with PROCYSBI for prolonged periods of time. Reported symptoms include: abdominal pain, vomiting, bloody or persistent diarrhea, and fecal incontinence. Evaluate patients with severe, persistent, and/or worsening abdominal symptoms for fibrosing colonopathy. If the diagnosis is confirmed, permanently discontinue PROCYSBI and switch to immediate-release cysteamine bitartrate capsules. An association between methacrylic acid-ethyl acrylate copolymer (an inactive ingredient in PROCYSBI) and fibrosing colonopathy cannot be ruled out.

5.5 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.

5.6 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.

5.7 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.