Cysteamine (Systemic)
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VA CLASSIFICATION
Primary: XX000{13}
Commonly used brand name(s): Cystagon.
† Not commercially available in Canada; however, it is available by emergency drug release from the Health Protection Branch {02}
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).
†Not commercially available in Canada.
Category:
Nephropathic cystinosis therapy—
Indications
Accepted
Cystinosis, nephropathic (prophylaxis)—Cysteamine is indicated for the management of nephropathic cystinosis in children and adults. {01} {03} {04} {05} {06} {07} {08}
Pharmacology/Pharmacokinetics
Physicochemical characteristics:
Molecular weight—
227 {01}
Mechanism of action/Effect:
Cysteamine is an aminothiol that converts cystine to cysteine and cysteine-cysteamine mixed disulfide, both of which can pass through the lysosomal membrane of patients with cystinosis. In the nephropathic form of cystinosis, the accumulation of cystine and the formation of crystals damage various organs, especially the kidney. {01} Cysteamine improves glomerular function without affecting tubular function. {03} {04} {15}
Other actions/effects:
There is some evidence that cysteamine therapy prevents accumulation of cystine in skeletal muscle. {09}
Protein binding:
Poorly bound to plasma proteins. {01}
Precautions to Consider
Cross-sensitivity and/or related problems
Patients sensitive to penicillamine may be sensitive to this medication also. {01}
Carcinogenicity
Long-term carcinogenicity studies in animals have not been performed. {01}
Mutagenicity
No evidence of mutagenicity was found in the Ames test. Cysteamine produced a negative response in the in vitro sister chromatid exchange assay in human lymphocytes, but a positive response in a similar assay in hamster ovarian cells. {01}
Pregnancy/Reproduction
Fertility—
Studies in male and female rats given oral cysteamine doses of 75 mg per kg of body weight (mg/kg) per day (450 mg per square meter of body surface area [mg/m 2] per day [0.4 times the recommended human dose based on body surface area]) found no evidence of impairment of fertility or reproductive performance. However, another study in male and female rats given 375 mg/kg per day (2250 mg/m 2 per day [1.7 times the recommended human dose based on body surface area]) revealed reduced fertility. {01}
Pregnancy—
Adequate and well-controlled studies in humans have not been done.
A study in male and female rats given 375 mg/kg per day (2250 mg/m 2 per day [1.7 times the recommended human dose based on body surface area]) revealed a reduction in survival of the offspring. {01}
FDA Pregnancy Category C. {01}
Breast-feeding
It is not known whether cysteamine is distributed into breast milk. Because of the potential of cysteamine for causing developmental toxicity in suckling rat pups when administered to their lactating mothers at an oral dose of 375 mg/kg per day (2250 mg/m 2 per day [1.7 times the recommended human dose based on body surface area]), a decision should be made whether to discontinue nursing or discontinue the drug. {01}
Pediatrics
Appropriate studies performed to date have not demonstrated pediatrics-specific problems that would limit the usefulness of cysteamine in children. Cysteamine therapy is most effective when begun early in life, before organ damage has developed. {01} {05} {06}
Geriatrics
No information is available on the relationship of age to the effects of cysteamine in geriatric patients.
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).
Risk-benefit should be considered when the following medical problems exist
Blood disorders (or history of) or {01}
Hepatic function impairment or {01} {10}
» Seizures (or history of) {01} {11} (cysteamine may exacerbate these conditions)
Sensitivity to cysteamine or penicillamine {01}
Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):
Body height and {01} {03}
Body weight and {01} {03} {05}
Creatinine clearance and {03} {05}
Creatinine, serum {01} (determinations recommended every 3 to 4 months to measure effectiveness of cysteamine therapy; creatinine clearance and serum creatinine should stabilize with therapy {01})
Complete blood count and {01} {04}
Hepatic function {01} {10} (determinations recommended every 3 to 4 months because cysteamine has been associated with anemia, leukopenia, and abnormal liver function tests {01})
» Leukocyte cystine concentrations {04} {05} (determinations recommended 5 to 6 hours after a dose, 2 weeks after initiation of therapy, and every 3 months to determine effectiveness of therapy; concentrations should be less than 1 nanomole per one-half-cystine per mg protein; however, patients unable to tolerate doses required to achieve this level may benefit from leukocyte cystine concentrations below 2 nanomole per one-half-cystine per mg protein {01})
Side/Adverse Effects
Note: The incidence of side/adverse effects increases with increasing doses. {01}
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Those indicating need for medical attention
Incidence more frequent {01}
Abdominal pain
anorexia (loss of appetite)
diarrhea
fever
lethargy (drowsiness)
nausea or vomiting {04}
skin rash{12}
Note: If skin rash develops, cysteamine therapy may need to be withheld, restarted at a lower dose, and slowly titrated to the therapeutic dose. If severe skin rash develops (e.g., erythema multiforme bullosa, toxic epidermal necrolysis), cysteamine therapy should not be readministered. {01} If abdominal pain, anorexia, or nausea or vomiting develops, therapy should be interrupted and the dose adjusted. {01}
Incidence less frequent {01}
Confusion
dizziness
headache
mental depression
sore throat
trembling
Note: If confusion, dizziness, headache, or mental depression develops, therapy should be interrupted and the dose adjusted. {01}
Incidence rare
Anemia (unusual tiredness or weakness)
dehydration (increased thirst)
leukopenia (sore throat and fever)
seizures {01}{11}(convulsions)
Note: Development of seizures may indicate need to discontinue the drug temporarily and resume at a lower dose. {01}
Those not indicating need for medical attention
Incidence less frequent
Breath odor
constipation
Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Cysteamine (Systemic).
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):
Before using this medication
» Conditions affecting use, especially:
Sensitivity to cysteamine or penicillamine
Pregnancy—Studies in animals have shown a decrease in fertility and survival of offspring
Breast-feeding—May be necessary to discontinue medication because of problems in nursing animals
Other medical problems, especially seizures
Proper use of this medication
Repeating dose once if vomited within 20 minutes; not repeating if vomiting occurs after 20 minutes
Possible need for dietary supplements
Capsule may be opened and contents sprinkled on food or mixed with formula
» Proper dosing
Missed dose: Taking as soon as possible; not taking if almost time for next dose; not doubling dose
» Proper storage
Precautions while using this medication
Regular visits to physician to check progress during therapy
May cause dizziness or drowsiness
Side/adverse effects
Signs of potential side effects, especially abdominal pain, anorexia, diarrhea, fever, lethargy, nausea or vomiting, skin rash, confusion, dizziness, headache, mental depression, sore throat, trembling, anemia, dehydration, leukopenia, and seizures
General Dosing Information
If a dose is vomited within 20 minutes after administration, the dose should be repeated once. If vomiting occurs more than 20 minutes after administration, the dose should be considered absorbed. {14}
Diet/Nutrition
Because nephropathic cystinosis may cause the loss of electrolytes from the kidney, the health care professional may recommend that dietary supplements be taken. {01}
For children six years of age and under, the capsule may be opened and the contents of the capsule sprinkled on food or mixed in formula. {01}
Oral Dosage Forms
CYSTEAMINE BITARTRATE CAPSULES
Usual adult and adolescent dose
Nephropathic cystinosis therapy
Initially, patients should be started on one-quarter to one-sixth of the maintenance dose; the dose should be raised gradually over four to six weeks. The maintenance dose for patients over 12 years of age and weighing more than 110 pounds (50 kg) is 2 grams a day in four divided doses. {01}
Usual pediatric dose
Nephropathic cystinosis therapy
Initially, patients should be started on one-quarter to one-sixth of the maintenance dose; the dose should be raised gradually over four to six weeks. The maintenance dose of 1.3 grams per square meter of body surface area per day in four divided doses can be approximated using the following table: {01} {07}
Cysteamine Maintenance Dose
| Weight (pounds) |
Weight (kg) |
Cysteamine free base every 6 hours (mg) |
|---|---|---|
| 0–10 |
0–4.5 |
100 |
| 11–20 |
5–9 |
150 |
| 21–30 |
9.5–13.6 |
200 |
| 31–40 |
14–18 |
250 |
| 41–50 |
18.6–22.7 |
300 |
| 51–70 |
23.2–31.8 |
350 |
| 71–90 |
32.3–40.9 |
400 |
| 91–110 |
41.4–50 |
450 |
| >110 |
>50 |
500 |
Strength(s) usually available
U.S.—
50 mg (Rx) [Cystagon]
150 mg (Rx) [Cystagon]
Canada—
Not commercially available; however, it is available by emergency drug release from the Health Protection Branch. {02}
Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.
Preparation of dosage form:
For patients who cannot take oral solids—Capsules may be opened and the contents sprinkled on food or mixed in formula.
Developed: 01/31/1996
References
- Cystagon product information (Mylan Pharm—US), Rev 8/94, Rec 2/95.
- Personal communication, 7/20/95.
- Yudkoff M, Foreman J, Segal S. Effects of cysteamine therapy in nephropathic cystinosis. N Engl J Med 1981; 304: 141-5.
- Gahl W, Reed G, Thoene J, et al. Cysteamine therapy for children with nephropathic cystinosis. N Engl J Med 1987; 316: 971-7.
- Markello T, Bernardini I, Gahl W. Improved renal function in children with cystinosis treated with cysteamine. N Engl J Med 1993; 328: 1157-62.
- da Silva V, Zurbrugg A, Suter H, et al. Long-term treatment of infantile nephropathic cystinosis with cysteamine. N Engl J Med 1985; 313: 1460-3.
- Reznik V, Adamson M, Adelman R, et al. Treatment of cystinosis with cysteamine from early infancy. J Pediatr 1991; 119 (3): 491-3.
- Theodoropoulos D, Krasnewich D, Kaiser-Kupfer M, et al. Classic nephropathic cystinosis as an adult disease. JAMA 1993; 270: 2200-4.
- Gahl W, Charnas L, Markello T, et al. Parenchymal organ cystine depletion with long-term cysteamine therapy. Biochem Med Metab Biol 1992; 48: 275-85.
- Avner E, Ellis D, Jaffe R. Veno-occlusive disease of the liver associated with cysteamine treatment of nephropathic cystinosis. J Pediatr 1983; 102(5): 793-6.
- Thoene J, Oshima R, Crawhali J, et al. Intracellular cystine depletion by aminothiols in vitro and in vivo. J Clin Invest 1976; 58: 180-8.
- Corden B, Schulman J, Schneider J, et al. Adverse reactions to oral cysteamine use in nephropathic cystinosis. Dev Pharmacol Ther 1981; 3: 25-30.
- Personal communication, 8/7/95.
- Reviewer comment, 1995.
- Reviewer consensus, 1995.
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