About PROCYSBI

PROCYSBI® (cysteamine bitartrate) delayed-release capsules is the first FDA-approved cystine-depleting medication dosed every 12 hours1-3

PROCYSBI is a delayed-release form of cysteamine bitartrate that works by continuously reducing the toxic concentration of cystine in cells.PROCYSBI provides continuous cystine control when taken every 12 hours.1

In a multicenter, open-label, randomized clinical trial,PROCYSBI given every 12 hours was proven noninferior to cysteamine bitartrate dosed every 6 hours.1

Why PROCYSBI?

Continuous cystine control with twice-daily dosing, given every  12-hours1

Proprietary delayed-release technology releases cysteamine into the bloodstream gradually, allowing full 12-hour cystine control.4

  • PROCYSBI capsules contain cysteamine bitartrate formulated into microspheronized, individually enteric-coated beads.2
  • Enteric coating makes PROCYSBI pH-sensitive, allowing the microbeads to bypass the stomach and be absorbed in the more alkaline environment of the proximal small intestine. Delayed time to peak concentration and half-life (Tmax [188 ± 88 min] and T1/2 [253 ± 403 min]) of PROCYSBI reflect delayed and gradual absorption.1,2
  • 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.1
    • 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. Monitor WBC cystine concentration when drugs that increase the gastric pH are concomitantly used.1

PROCYSBI given every 12 hours maintains continuous cystine control, offering patients improved dosing flexibility1,2

Because PROCYSBI works to control cystine concentration continuously over 12 hours,4 patients and caregivers can choose a schedule that fits their unique needs.

  • Peak plasma cysteamine concentration with PROCYSBI occurs later than with immediate-release (IR) cysteamine.1,2
  • The gradual decrease of plasma cysteamine with PROCYSBI allows cystine concentration to remain within therapeutic range for a full 12 hours, enabling twice-daily dosing.2
  • In a multicenter, open-label, randomized clinical trial, PROCYSBI dosed every 12 hours was proven non-inferior to cysteamine bitartrate dosed every 6 hours.1
  • Thirty-four patients have continued for at least 22 months in the extension trial and maintained their mean white blood cell (WBC) cystine concentrations below the target concentration of 1 nmol ½ cystine/mg protein over this time period.1
  • During extended treatment with PROCYSBI, mean estimates of renal function were maintained, as measured by the estimated glomerular filtration rate (eGFR).1

Adverse Events

Most common adverse reactions observed in clinical trials of PROCYSBI1:

  • Patients 6 years of age and older previously treated with cysteamine (≥5% of patients): vomiting, nausea, abdominal pain, breath odor, diarrhea, skin odor, fatigue, rash, and headache.
  • Patients 1 year to less than 6 years naïve to cysteamine treatment (>10% of patients): vomiting, gastroenteritis/viral gastroenteritis, diarrhea, breath odor, nausea, electrolyte imbalance, and headache.
  • Safety data suggest that patients taking immediate-release (IR) cystea mine can safely be switched to PROCYSBl.1

All patients but one (40 out of 41 patients) who completed the phase 3 trial chose to continue with PROCYSBI in a single-arm, open-label extension trial. These patients were treated with PROCYSBI for longer than 2 years.1

  • The most frequent adverse reactions involved the gastrointestinal and central nervous systems and were prominent at the start of therapy.1
  • Most patients were able to resume therapy at lower doses.1
  • 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.1

References

1. PROCYSBI [package insert]. Lake Forest, IL: Horizon Pharma USA, Inc; 2017.

2. Langman CB, Greenbaum LA, Sarwal M, et al. A randomized controlled crossover trial with delayed-release cysteamine bitartrate in nephropathic cystinosis: Effectiveness on white blood cell cystine levels and comparison of safety. Clin J Am Soc Nephrol. 2012;7:1112-1120.

3. CYSTAGON [package insert]. Morgantown, WV: Mylan Pharmaceuticals Inc.; 2007.

4. Gahl WA, Balog JZ, Kleta R. Nephropathic cystinosis in adults: Natural history and effects of oral cysteamine therapy. Ann Intern Med. 2007;147:242-250.

IMPORTANT SAFETY INFORMATION

INDICATIONS AND USAGE: PROCYSBI® (cysteamine bitartrate) delayed-release capsules is a cystine depleting agent indicated for the treatment of nephropathic cystinosis in adult and pediatric patients 1 year of age and older.

CONTRAINDICATIONS:

  • Serious hypersensitivity reaction, including anaphylaxis to penicillamine or cysteamine.

WARNINGS AND PRECAUTIONS:

  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Benign Intracranial Hypertension: Benign intracranial hypertension (pseudotumor cerebri; PTC) and/or papilledema has 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.

ADVERSE REACTIONS:

The most common adverse reactions (≥5%) in patients treated in clinical trials are vomiting, nausea, gastroenteritis / viral gastroenteritis, abdominal pain, breath odor, diarrhea, skin odor, fatigue, rash, headache, and electrolyte imbalance.

To report SUSPECTED ADVERSE REACTIONS, contact Horizon Pharma USA, Inc. at 1-855-888-4004 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

 

DRUG INTERACTIONS:

  • Drugs that Increase Gastric pH: Administer PROCYSBI at least 1 hour before or 1 hour after medications containing bicarbonate or carbonate.
  • 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.
  • PROCYSBI can be administered with electrolyte (except bicarbonate) and mineral replacements necessary for management of Fanconi Syndrome as well as vitamin D and thyroid hormone.

USE IN SPECIFIC POPULATIONS

Lactation:

  • Breastfeeding is not recommended while taking PROCYSBI.

Part No.: P-PYB-00033                     Derived from Full Prescribing Information December 2017