- Author: Ewa Elenberg, MD, MEd; Chief Editor: Craig B Langman, MD more...
Cysteamine, introduced in the 1980s, blunts the decline in renal function and improves the linear growth of these children, despite the fact that it does not ameliorate the defect in renal tubule transport. Oral therapy should be initiated as soon as the diagnosis is made. The delayed-release capsule (Procysbi) allows twice daily dosing (ie, q12h), whereas the immediate-release capsule (Cystagon) has to be administered every 6 hours, including throughout the night, to prevent nocturnal accumulation of cystine.
Although anecdotal in nature, a European study showed that cystinosis patients treated with cysteamine can develop skin, vascular, neurologic, muscular, and bone lesions. While underdosing is not recommended, these lesions were improved after dose reduction.
Cysteamine ophthalmic solution 0.44% (Cystaran) must be administered to each eye every hour while awake.
Cysteamine is an aminothiol compound used to treat cystinosis. Various cysteamine salts are used. Cysteamine HCl has an unpleasant taste and odor, and, therefore, other forms have been developed. Cysteamine bitartrate (Cystagon) is available in the United States. Another form, phosphocysteamine, is the phosphorothioester of cysteamine and is rapidly converted to cysteamine in the gut. Phosphocysteamine is designated as an orphan drug in the United States. Much of the clinical data refers to cysteamine HCl or phosphocysteamine.
In addition to the oral product that is available, an ophthalmic product was approved by the FDA in October 2012 to decrease corneal cystine crystals, which develop with nephropathic cystinosis.
Used as a cystine-depleting agent in cystinosis. It is a weak base that enters the cystinotic lysosome and reacts with cystine, forming a mixed disulfide of half-cystine and cysteamine. This mixed disulfide rapidly exits the lysosome via the transport system for cationic amino acids, which is normal in cystinosis. Cysteamine and its prodrug analog, phosphocysteamine, are very beneficial to patients with cystinosis, especially when started early in life. Therapy does not prevent or affect Fanconi syndrome. Diagnosis of cystinosis as early as possible is important because efficacy of cysteamine or phosphocysteamine treatment clearly relates to age at which the drugs are started.
Goal of therapy is to keep leukocyte cystine levels < 1 nmol/half-cystine/mg protein measured 5-6 h following administration of cysteamine. Check cystine levels after maintenance dose is achieved; then check every 3 mo; if cysteamine is poorly tolerated initially because of GI tract symptoms or transient rashes, temporarily stop therapy; restart at lower dose and gradually increase to proper dose. Dose is expressed as free base of drug. Cystagon (immediate-release) was approved by the FDA in August 1994. The sole distributor of this drug in the United States is CVS Procare (888-700-0024). Procysbi (delayed-release) was approved in April 2013 and will also be distributed by a specialty pharmacy service (Raptor Cares).
Cysteamine ophthalmic is a cystine-depleting agent indicated for corneal cystine crystal accumulation in patients with cystinosis. It converts cystine to cysteine-cysteamine mixed disulfides and reduces corneal cystine crystal accumulation.
Nesterova G, Gahl W. Nephropathic cystinosis: late complications of a multisystemic disease. Pediatr Nephrol. 2008 Jun. 23(6):863-78. [Medline].
[Guideline] Scottish Intercollegiate Guidelines Network (SIGN). Diagnosis and management of chronic kidney disease. A national clinical guideline. Edinburgh (Scotland): Scottish Intercollegiate Guidelines Network (SIGN); 2008. [Full Text].
Procysbi (cysteamine bitartrate) [package insert]. Novato, California: Raptor Pharmaceuticals Inc. August 2015. Available at [Full Text].
Chevalier RL, Forbes MS. Generation and evolution of atubular glomeruli in the progression of renal disorders. J Am Soc Nephrol. 2008 Feb. 19(2):197-206. [Medline].
Besouw MT, Bowker R, Dutertre JP, et al. Cysteamine toxicity in patients with cystinosis. J Pediatr. 2011 Dec. 159(6):1004-11. [Medline].
Van Stralen KJ, Emma F, Jager KJ, et al. Improvement in the renal prognosis in nephropathic cystinosis. Clin J Am Soc Nephrol. 2011 Oct. 6(10):2485-91. [Medline].
Andrews PA, Sacks SH, van't Hoff W. Successful pregnancy in cystinosis. JAMA. 1994 Nov 2. 272(17):1327-8. [Medline].
Almond PS, Matas AJ, Nakhleh RE. Renal transplantation for infantile cystinosis: long-term follow-up. J Pediatr Surg. 1993 Feb. 28(2):232-8. [Medline].
Baum M. The Fanconi syndrome of cystinosis: insights into the pathophysiology. Pediatr Nephrol. 1998 Aug. 12(6):492-7. [Medline].
Bendavid C, Kleta R, Long R, et al. FISH diagnosis of the common 57-kb deletion in CTNS causing cystinosis. Hum Genet. 2004 Nov. 115(6):510-4. [Medline].
Cystaran (cysteamine ophthalmic solution) [package insert]. Gaithersburg, MD: Sigma-tau Pharmaceuticals, Inc. October, 2012. Available at [Full Text].
Dohil R, Newbury RO, Sellers ZM, et al. The evaluation and treatment of gastrointestinal disease in children with cystinosis receiving cysteamine. J Pediatr. 2003 Aug. 143(2):224-30. [Medline].
Elenberg E, Norling LL, Kleinman RE, Ingelfinger JR. Feeding problems in cystinosis. Pediatr Nephrol. 1998 Jun. 12(5):365-70. [Medline].
Facts and Comparisons. Cysteamine bitartrate. Drug Facts and Comparisons. 5th ed. St. Louis, MO: Facts and Comparisons; 2000. 590-1.
Foreman JW. Metabolic disorders. Pediatric Nephrology. Baltimore, MD: Lippincott Williams & Wilkins; 1994. 537- 57.
Gahl WA. Cystinosis coming of age. Adv Pediatr. 1986. 33:95-126. [Medline].
Gahl WA, Reed GF, Thoene JG. Cysteamine therapy for children with nephropathic cystinosis. N Engl J Med. 1987 Apr 16. 316(16):971-7. [Medline].
Gahl WA, Thoene JG, Schneider JA. Cystinosis. N Engl J Med. 2002 Jul 11. 347(2):111-21. [Medline].
Jonas AJ, Schulman JD, Matalon R, et al. Cystinosis in non-caucasian children. Johns Hopkins Med J. 1982 Sep. 151(3):117-21. [Medline].
Kleta R, Kaskel F, Dohil R, et al. First NIH/Office of Rare Diseases Conference on Cystinosis: past, present, and future. Pediatr Nephrol. 2005 Apr. 20(4):452-4. [Medline].
Levtchenko EN, van Dael CM, de Graaf-Hess AC, Wilmer MJ, van den Heuvel LP, Monnens LA. Strict cysteamine dose regimen is required to prevent nocturnal cystine accumulation in cystinosis. Pediatr Nephrol. 2006 Jan. 21(1):110-3. [Medline].
Markello TC, Bernardini IM, Gahl WA. Improved renal function in children with cystinosis treated with cysteamine. N Engl J Med. 1993 Apr 22. 328(16):1157-62. [Medline].
Saleem MA, Milford DV, Alton H, et al. Hypercalciuria and ultrasound abnormalities in children with cystinosis. Pediatr Nephrol. 1995 Feb. 9(1):45-7. [Medline].
Schneider JA, Katz B, Melles RB. Update on nephropathic cystinosis. Pediatr Nephrol. 1990 Nov. 4(6):645-53. [Medline].
Sonies BC, Almajid P, Kleta R, Bernardini I, Gahl WA. Swallowing dysfunction in 101 patients with nephropathic cystinosis: benefit of long-term cysteamine therapy. Medicine (Baltimore). 2005 May. 84(3):137-46. [Medline].
Swinford RD, Elenberg E, Ingelfinger JR. Persistent renal disease. Nutritrition in Pediatrics: Basic Science and Clinical Applications. Hamilton, Ontario: BC Decker; 1996. 493-515.
The Cystinosis Collaborative Research Group. Linkage of the gene for cystinosis to markers on the short arm of chromosome 17. Nat Genet. 1995 Jun. 10(2):246-8. [Medline].
Theodoropoulos DS, Krasnewich D, Kaiser-Kupfer MI, Gahl WA. Classic nephropathic cystinosis as an adult disease. JAMA. 1993 Nov 10. 270(18):2200-4. [Medline].
Wuhl E, Haffner D, Gretz N, et al. Treatment with recombinant human growth hormone in short children with nephropathic cystinosis: no evidence for increased deterioration rate of renal function. The European Study Group on Growth Hormone Treatment in Short Children with Nephropathic Cy. Pediatr Res. 1998 Apr. 43(4 Pt 1):484-8. [Medline].
Wuhl E, Haffner D, Offner G, et al. Long-term treatment with growth hormone in short children with nephropathic cystinosis. J Pediatr. 2001 Jun. 138(6):880-7. [Medline].