September 1, 2015
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Procysbi

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Procysbi

Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

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 [see DOSAGE AND ADMINISTRATION].

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].

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].

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 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.

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (PATIENT INFORMATION and Instructions for Use)

Ehlers-Danlos-like Syndrome

Advise patients and caregivers that PROCYSBI may cause abnormalities of the skin, bones, and joints. Advise patients to report any skin changes or problems with their bones or joints to their physician [see WARNINGS AND PRECAUTIONS].

Skin Rash

Advise patients and caregivers to contact their physician immediately if they experience a skin rash [see WARNINGS AND PRECAUTIONS].

Gastrointestinal Ulcers and Bleeding

Advise patients and caregivers that PROCYSBI may cause ulcers and bleeding. Advise patients to contact their physician immediately if they experience stomach pain, nausea, vomiting, loss of appetite, or are vomiting blood [see WARNINGS AND PRECAUTIONS].

Central Nervous System Symptoms

Advise patients and caregivers that PROCYSBI may impair their ability to perform tasks such as driving or operating machinery. Advise patients to contact their physician immediately if they experience seizures, lethargy, somnolence, depression, and encephalopathy [see WARNINGS AND PRECAUTIONS].

Benign Intracranial Hypertension

Advise patients and caregivers that PROCYSBI may cause benign intracranial hypertension. Advise patients to contact their physician immediately if they experience headache, tinnitus, dizziness, nausea, double vision, blurry vision, loss of vision, or eye pain [see WARNINGS AND PRECAUTIONS].

Use by Pregnant Women

Advise patients and to contact their physician immediately if they suspect they may be pregnant. Discuss with the patient the individual risks and benefits of continuing PROCYSBI during pregnancy [see Use in Specific Populations].

Breastfeeding

Advise patients that breastfeeding is not recommended while taking PROCYSBI [see Use In Specific Populations].

Administration
  • Advise patients and caregivers to follow the instruction below for taking PROCYSBI capsules whole.
    • Swallow PROCYSBI capsules whole. Do not crush or chew capsules or capsule contents
    • Take PROCYSBI capsules with fruit juice (except grapefruit juice)
  • For patients who have difficulty swallowing capsules or those with a Gastrostomy (G) tube, follow the instructions in the Instructions for Use for opening the capsule and administering with food or liquid.
  • Do not eat for at least 2 hours before and for at least 30 minutes after taking PROCYSBI. If unable to take PROCYSBI without eating, take with food but limit the amount of food to approximately 4 ounces (½ cup) 1 hour before through 1 hour after administration. Avoid high fat food close to dosing of PROCYSBI
  • Avoid drinking alcohol while taking PROCYSBI
  • Administer PROCYSBI at least 1 hour before or 1 hour after medications containing bicarbonate or carbonate
  • Take PROCYSBI consistently and to not miss doses. If a dose is missed, take the dose as soon as possible up to 8 hours after the scheduled time. However, if a dose is missed and the next scheduled dose is due in less than 4 hours, do not take the missed dose, and to take the next dose at the usual scheduled time. Do not take 2 doses at one time to make up for a missed dose [see DOSAGE AND ADMINISTRATION].
Laboratory Monitoring

Discuss with the patient and caregivers the importance of required laboratory testing to determine the correct dose of PROCYSBI [see DOSAGE AND ADMINISTRATION].

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Cysteamine has not been tested for its carcinogenic potential in long-term animal studies.

PROCYSBI was not mutagenic in the Ames test. It produced a negative response in an in-vitro sister chromatid exchange assay in human lymphocytes, but a positive response in a similar assay in hamster ovarian cells.

Repeat breeding reproduction studies were conducted in male and female rats. Cysteamine was found to have no effect on fertility and reproductive performance at an oral dose of 75 mg/kg per day (450 mg/m² per day, 0.4 times the recommended human dose based on body surface area). At an oral dose of 375 mg/kg per day (2250 mg/m² per day, 1.7 times the recommended human maintenance dose based on body surface area), it reduced the fertility of the adult rats and the survival of their offspring.

Use In Specific Populations

Pregnancy

Risk Summary

There are no available data on PROCYSBI use in pregnant women to inform any drug-associated risks for birth defects or miscarriage [see Data]. Cysteamine (administered as cysteamine bitartrate) was teratogenic and fetotoxic in rats at doses less than the recommended human maintenance dose.

The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Advise pregnant women of the potential risk to a fetus.

Data

Animal Data

Embryo-fetal development studies were conducted in rats using oral administration of cysteamine bitartrate, with a dose range of 37.5 to 150 mg/kg per day of cysteamine equivalent (about 0.2 to 0.7 times the recommended human maintenance dose based on body surface area). Cysteamine bitartrate was fetotoxic and produced adverse developmental effects. Observed teratogenic findings were cleft palate, kyphosis, heart ventricular septal defects, microcephaly and exencephaly.

Lactation

Risk Summary

There is no information on the presence of cysteamine in human milk, the effects on the breast-fed infant, or the effects on milk production. Cysteamine is present in the milk of lactating rats [see Data]. Because of the potential for serious adverse reactions in breastfed infants from cysteamine, breastfeeding is not recommended.

Data

A decrease in survival occurred in neonatal rats nursed by mothers receiving cysteamine [see Nonclinical Toxicology].

Pediatric Use

The safety and effectiveness of PROCYSBI have been established in pediatric patients aged 2 years and older for the treatment of nephropathic cystinosis. Use of PROCYSBI is supported by evidence from an open-label, randomized, cross-over trial in adult and pediatric patients aged 6 years and older, and an open-label extension trial which included patients aged 2 years and older [see Clinical Trials].

The safety and effectiveness of PROCYSBI in pediatric patients under 2 years of age have not been established.

Geriatric Use

No studies with PROCYSBI have been conducted in geriatric patients.

Last reviewed on RxList: 8/28/2015
This monograph has been modified to include the generic and brand name in many instances.

Warnings
Precautions

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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