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Cystagon

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Cystagon

Warnings
Precautions

WARNINGS

If a skin rash develops, CYSTAGON® (cysteamine bitartrate) should be withheld until the rash clears. CYSTAGON® (cysteamine bitartrate) may be restarted at a lower dose under close supervision, then slowly titrated to the therapeutic dose. If a severe skin rash develops such as erythema multiforme bullosa or toxic epidermal necrolysis, CYSTAGON® (cysteamine bitartrate) should not be readministered.

CNS symptoms such as seizures, lethargy, somnolence, depression, and encephalopathy have been associated with cysteamine. If CNS symptoms develop, the patient should be carefully evaluated and the dose adjusted as necessary. Neurological complications have been described in some cystinotic patients not on cysteamine treatment. This may be a manifestation of the primary disorder. Patients should not engage in hazardous activities until the effects of CYSTAGON® (cysteamine bitartrate) on mental performance are known.

Gastrointestinal ulceration and bleeding have been reported in patients receiving cysteamine bitartrate. Physicians should remain alert for signs of ulceration and bleeding and should inform patients and/or guardians about the signs and symptoms of serious G.I. toxicity and what steps to take if they occur.

Post marketing reports include one report of interstitial nephritis with early renal failure. A causal relationship between this event and cysteamine bitartrate therapy has not been established.

PRECAUTIONS

General

Gastrointestinal tract symptoms including nausea, vomiting, anorexia and abdominal pain have been associated with cysteamine, sometimes severe. In addition, gastrointestinal ulceration and bleeding have been reported in patients on cysteamine therapy. If these develop, therapy may have to be interrupted and the dose adjusted. A cysteamine dose of 1.95 grams/m2/day (approximately 80 to 90 mg/kg/day) was associated with an increased number of withdrawals from treatment due to intolerance and an increased incidence of adverse events.

Cysteamine has occasionally been associated with reversible leukopenia and abnormal liver function studies. Therefore, blood counts and liver function studies should be monitored.

There have been reports of benign intracranial hypertension (or pseudotumor cerebri; PTC) and/or papilledema associated with CYSTAGON® (cysteamine bitartrate) treatment that has resolved with the addition of diuretic therapy. PTC may be more common in cystinotic patients because of concurrent medication and renal transplantation. Although a causal relationship of PTC to CYSTAGON® (cysteamine bitartrate) has not been established, physicians should monitor patients receiving CYSTAGON® (cysteamine bitartrate) for this condition. Physicians should instruct patients to report any of the following symptoms: headache, tinnitus, dizziness, nausea, diplopia, blurry vision, loss of vision, pain behind the eye or pain with eye movement. A periodic eye examination is needed to identify this condition early and timely treatment should be provided when it occurs to prevent vision loss.

There have been reports of serious skin lesions in patients treated with high doses of CYSTAGON® (cysteamine bitartrate) or other cysteamine salts that have responded to cysteamine dose reduction. These skin lesions are purplish hemorrhagic lesions over the elbow area on both arms and have been described as molluscoid pseudotumors. Skin striae, bone lesions (that have been described as osteopenia, compression fractures, scoliosis and genu valgum) along with leg pain and joint hyperextension may also be present. One patient with serious skin lesions subsequently died of acute cerebral ischemia with marked vasculopathy. Physicians should routinely monitor the skin and bones of patients receiving CYSTAGON (cysteamine bitartrate) . If similar skin or bone abnormalities appear, the dose of CYSTAGON (cysteamine bitartrate) should be reduced.

Information for Patients and Parents and/or Guardians

See attached information for patients and parents and/or guardians.

Laboratory Tests

Leukocyte cystine measurements are useful to determine adequate dosage and compliance. When measured 5 to 6 hours after CYSTAGON® (cysteamine bitartrate) administration, the goal should be a level < 1 nmol/½ cystine/mg protein. In some patients with poorer tolerability for CYSTAGON® (cysteamine bitartrate) , patients may still receive benefit with a white cell cystine level of less than 2 nmol/½ cystine/mg protein. Measurements should be done every three months, more frequently when patients are transferred from cysteamine hydrochloride or phosphocysteamine solutions to CYSTAGON® (cysteamine bitartrate) .

Physicians should follow patients for signs and symptoms of gastrointestinal ulceration and bleeding, and should inform patients and/or guardians of the importance of this follow-up.

Carcinogenesis, Mutagenesis, Impairment of Fertility

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

Cysteamine 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 dose based on body surface area), it reduced the fertility of the adult rats and the survival of their offspring.

Pregnancy

Teratogenic Effects. Pregnancy Category C

Teratology studies have been performed in rats at oral doses in a range of 37.5 to 150 mg/kg/day (about 0.2 to 0.7 times the recommended human maintenance dose on a body surface basis) and have revealed cysteamine bitartrate to be teratogenic and fetotoxic. Observed teratogenic findings were cleft palate, Kyphosis, heart ventricular septal defects, microcephaly and exencephaly. There are no adequate and well-controlled studies in pregnant women. CYSTAGON® (cysteamine bitartrate) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether cysteamine is excreted in human milk. Because many drugs are excreted in human milk and because of the manifested potential of cysteamine for developmental toxicity in suckling rat pups when it was administered to their lactating mothers at an oral dose of 375 mg/kg/day (2,250 mg/m2/day, 1.7 times the recommended human dose based on body surface area), a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

The safety and effectiveness of CYSTAGON® (cysteamine bitartrate) for cystinotic children have been established. Cysteamine therapy should be initiated as soon as the diagnosis of nephropathic cystinosis has been confirmed.

Last reviewed on RxList: 6/26/2007
This monograph has been modified to include the generic and brand name in many instances.

Warnings
Precautions
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