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Procysbi

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Procysbi

Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Ehler-Danlos like Syndrome

Skin and bone lesions that resemble clinical findings for Ehler-Danlos 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 increased 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, discontinue use of any cysteamine product permanently. [see DOSAGE AND ADMINISTRATION]

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 or adjust the dose as necessary for patients with severe symptoms or with symptoms that persist or progress. Patients should exercise caution when driving or engaging in other hazardous activities when taking cysteamine.

Leukopenia and Elevated Alkaline Phosphatase Levels

Cysteamine has been associated with reversible leukopenia and elevated alkaline phosphatase levels. Therefore, blood counts and alkaline phosphatase levels should be monitored.

Benign Intracranial Hypertension

Benign intracranial hypertension (pseudotumor cerebri; PTC) and/or papilledema has been reported in patients receiving immediate-release cysteamine bitartrate treatment. A causal relationship between PTC and cysteamine has not been established. Physicians should 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.

Patient Counseling Information

See FDA-approved patient labeling (PATIENT INFORMATION) Instruct patients and caregivers that the constraints/risks associated with PROCYSBI include:

Laboratory Monitoring

Discuss with the patient and caregivers the requirement to do laboratory testing to determine the correct dose of PROCYSBI. WBC cystine levels (or plasma cysteamine concentration if adequate WBC cystine testing is not available) should be measured as follows:

  • Monthly for 3 months, then quarterly for one year, then twice yearly at a minimum for patients never treated with immediate release cysteamine before.
  • Two weeks, then quarterly for 6 months then twice yearly at a minimum for patients switching from immediate-release to PROCYSBI.

Measurement Timing: WBC cystine and/or plasma cysteamine measurements must be obtained 12.5 hours after the evening dose the day before, and therefore 30 minutes after the following morning dose is given.

Measurement Interpretation: In well-controlled and adherent patients with nephropathic cystinosis, the plasma cysteamine is > 0.1 mg/L, and the WBC cystine is < 1.0 nmol ½ cystine/mg protein. If the plasma cysteamine is > 0.1 mg/L, but the WBC cystine is > 1.0 nmol ½ cystine/mg protein, ask the patient about the following: adherence to dosing interval, adherence to medication, or the relationship between administration of PROCYSBI and fasted/fed state.

Dosing and Administration

Instruct patients and caregivers to take PROCYSBI consistently and to not miss doses. Advise patients to take a missed dose as soon as possible. If it is within four hours of the next dose, patients should skip the missed dose and take the next regularly scheduled dose. Patients should not double the dose.

Instruct patients and caregivers that taking PROCYSBI with meals may affect the absorption of PROCYSBI. Patients may take PROCYSBI at least 2 hours after and at least 30 minutes before eating. For patients who tolerate PROCYSBI better with food, it is permissible to eat approximately 4 ounces (½ cup) of food within one hour before and one hour after taking PROCYSBI. Instruct patients to take PROCYSBI consistently in relation to food (i.e., do not change between taking PROCYSBI while fasting and taking PROCYSBI with food) from one day to another. Avoid high fat food close to dosing of PROCYSBI.

Use by Pregnant Women

Patients should be instructed to immediately contact their physician if they suspect they may be pregnant. Discuss the individual risks and benefits of continuing PROCYSBI during pregnancy.

Breastfeeding

Breastfeeding is not recommended while taking PROCYSBI.

CNS Symptoms

Advise patients and caregivers that cysteamine may cause central nervous symptoms including seizures, lethargy, somnolence, depression, and encephalopathy that may require interrupting or decreasing the dose of PROCYSBI. Because somnolence may occur, patients should exercise caution in driving a car or engaging in other hazardous activities after taking PROCYSBI.

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.

Skin rash

Advise patients and caregivers to contact their physician immediately if they experience a skin rash.

Neutropenia and Elevated Alkaline Phosphatase Levels

Advise patients that they should have laboratory testing to monitor for a low white blood count and elevated alkaline phosphatase while taking PROCYSBI.

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.

Ehler-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 to their physician.

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/day (450 mg/m²/day, 0.4 times the recommended human dose based on body surface area). At an oral dose of 375 mg/kg/day (2,250 mg/m²/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

Pregnancy Category C

Risk Summary

There are no adequate and well-controlled studies in pregnant women. Cysteamine (administered as cysteamine bitartrate) was teratogenic and fetotoxic in rats at doses less than the recommended human maintenance dose. PROCYSBI should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

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/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.

Nursing Mothers

It is not known whether cysteamine is present in human milk. A decrease in survival occurred in neonatal rats nursed by mothers receiving cysteamine. [see Nonclinical Toxicology] Because many drugs are present in human milk and because of the potential for serious adverse reactions in nursing infants from cysteamine, nursing is not recommended.

Pediatric Use

PROCYSBI therapy should be initiated as soon as the diagnosis of nephropathic cystinosis has been confirmed in children greater than 6 years and adults. The risks and benefits of treatment with PROCYSBI in children under 6 years old are not yet established.

Last reviewed on RxList: 5/13/2013
This monograph has been modified to include the generic and brand name in many instances.

Warnings
Precautions
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