Mercaptamine Hydrochloride

(BANM, rINNM)
Synonyms: CI-9148; Cysteamine Hydrochloride (USAN); Hidrocloruro de mercaptamina; Mercaptamine, Chlorhydrate de; Mercaptamini Hydrochloridum.
Cyrillic synonym: Меркаптамина Гидрохлорид.

💊 Chemical information

Chemical formula: C2H7NS,HCl = 113.6.
CAS — 156-57-0.
ATC — A16AA04.
ATC Vet — QA16AA04.

💊 Adverse Effects and Precautions

Mercaptamine can be unpalatable and may cause breath and body odour. It may cause gastrointestinal disturbances including anorexia, nausea, vomiting, diarrhoea, and abdominal pain, and occasionally, gastrointestinal ulceration. Other adverse effects may include drowsiness, lethargy, headache, rashes, fever, and encephalopathy. Mercaptamine may cause increases in liver en zyme values, and there have been some reports of nephrotic syndrome. Nervousness and, sometimes, hallucinations, have also been reported.

Intolerance.

Three patients with nephropathic cystinosis developed fever, maculopapular eruption, leucopenia, or headache within 2 weeks of starting mercaptamine at doses of 53, 67, and 75 mg/kg daily by mouth, respectively.1 These adverse effects resolved within 48 hours of drug withdrawal and all 3 patients were able to tolerate mercaptamine when restarted at a dose of 10 mg/kg daily, slowly increased to therapeutic levels over 2 to 3 months. Higher doses of mercaptamine had been associated with lethargy and seizures.
1. Schneider JA, et al. Cysteamine therapy in nephropathic cystinosis. N Engl J Med 1981; 304: 1172.

💊 Pharmacokinetics

1. Belldina EB, et al. Steady-state pharmacokinetics and pharmacodynamics of cysteamine bitartrate in paediatric nephropathic cystinosis patients. Br J Clin Pharmacol 2003; 56: 520–5.

💊 Uses and Administration

Mercaptamine reduces intracellular cystine levels and is given orally as the bitartrate in the treatment of cystinosis (see below); it has also been given as the hydrochloride. Doses are expressed in terms of the base; 2.94 g of the bitartrate or 1.47 g of the hydrochloride are each equivalent to 1 g of mercaptamine. Mercaptamine bitartrate is given in an initial dose that is one-sixth to one-quarter of the expected maintenance dose, and is then increased gradually over 4 to 6 weeks. The usual maintenance dose in adults weighing over 50 kg is 2 g daily in 4 divided doses with or after food. Children up to 12 years of age are given 1.3 g/m2(approximately 50 mg/kg) daily in 4 divided doses. Doses are given in conjunction with monitoring of leucocyte-cystine levels which should be kept below 1 nanomol of hemicystine per mg of protein. Phosphocysteamine, a phosphorothioester of mercaptamine, has been said to be more palatable, and is used similarly. Mercaptamine facilitates glutathione synthesis and was formerly used intravenously in the treatment of severe paracetamol poisoning to prevent hepatic damage, but other forms of treatment are now preferred.

Cystinosis.

Mercaptamine and phosphocysteamine (which appears to be rapidly hydrolysed to mercaptamine after ingestion) have been reported to be of benefit in children with cystinosis, a rare autosomal recessive metabolic disorder characterised by the intracellular accumulation of cystine. Cystinosis is marked by growth retardation, rickets, Fanconi syndrome, and renal failure; acute episodes of acidosis and dehydration may develop, and there may be photophobia associated with deposition of cystine in the eye.1 Use of mercaptamine, which results in a reduction in the concentrations of cystine in leucocytes, has been shown to be effective in controlling many of the symptoms,2-5 especially if begun early, although it has not been clear from contradictory results4,6 how much benefit would be seen on renal function. Excellent clinical outcomes were reported7 on long-term follow-up of 2 siblings with severe nephropathic cystinosis, reinforcing the need for early and diligent treatment in order to avoid progressive renal disease. Compliance may be a problem, because of the taste and odour of mercaptamine, and the more palatable prodrug phosphocysteamine has been developed as an alternative;8,9more palatable formulations of mercaptamine are also being investigated. Mercaptamine eye drops are reportedly of benefit in reversing or preventing deposition of corneal cystine crystals.10A strength of 0.11% has been used. Renal transplantation may be necessary if renal failure develops.
1. Gahl WA, et al. Cystinosis. N Engl J Med 2002; 347: 111–21
2. Yudkoff M, et al. Effects of cysteamine therapy in nephropathic cystinosis. N Engl J Med 1981; 304: 141–5
3. Gahl WA, et al. Cysteamine therapy for children with nephropathic cystinosis. N Engl J Med 1987; 316: 971–7
4. Reznik VM, et al. Treatment of cystinosis with cysteamine from early infancy. J Pediatr 1991; 119: 491–3
5. Gahl WA, et al. Nephropathic cystinosis in adults: natural history and effects of oral cysteamine therapy. Ann Intern Med 2007; 147: 242–50
6. Markello TC, et al. Improved renal function in children with cystinosis treated with cysteamine. N Engl J Med 1993; 328: 1157–62
7. Kleta R, et al. Long-term follow-up of well-treated nephropathic cystinosis patients. J Pediatr 2004; 145: 555–60
8. Gahl WA, et al. Cystinosis: progress in a prototypic disease. Ann Intern Med 1988; 109: 557–69
9. van’t Hoff WG, et al. Effects of oral phosphocysteamine and rectal cysteamine in cystinosis. Arch Dis Child 1991; 66: 1434–7
10. Kaiser-Kupfer MI, et al. A randomized placebo-controlled trial of cysteamine eye drops in nephropathic cystinosis. Arch Ophthalmol 1990; 108; 689–93.

💊 Preparations

Proprietary Preparations

Austral.: Cystagon; Belg.: Cystagon; Cz.: Cystagon; Denm.: Cystagon; Fin.: Cystagon; Fr.: Cystagon; Ger.: Cystagon; Ital.: Cystagon; Neth.: Cystagon; Pol.: Cystagon; Port.: Cystagon; Spain: Cystagon; Swed.: Cystagon; UK: Cystagon.
Published May 08, 2019.