Cysteamine bitartrate (Capsules) Instructions for Use

Marketing Authorization Holder

LIFE SCIENCES OHFK, LLC (Russia)

Manufactured By

OHFK, JSC (Russia)

ATC Code

A16AA04 (Mercaptamine)

Active Substance

Mercaptamine (Rec.INN registered by WHO)

Dosage Forms

	Cysteamine bitartrate	Capsules 50 mg
		Capsules 150 mg

Dosage Form, Packaging, and Composition

Capsules

100 pcs. – jars – cardboard packs (100 pcs.) – By prescription
50 pcs. – jars – cardboard packs (50 pcs.) – By prescription

Capsules

100 pcs. – jars – cardboard packs (100 pcs.) – By prescription
50 pcs. – jars – cardboard packs (50 pcs.) – By prescription

Pharmacotherapeutic Group

Other agents for the treatment of gastrointestinal diseases and metabolic disorders; amino acids and their derivatives

Pharmacological Action

Healthy individuals and those heterozygous for cystinosis have leukocyte cystine levels of 0.2 and typically below 1 nmol half-cystine/mg protein, respectively. In individuals with nephropathic cystinosis, the leukocyte cystine level exceeds 2 nmol half-cystine/mg protein.

Mercaptamine reacts with cystine to form a mixed mercaptamine disulfide and cysteine. The mixed disulfide is then transported out of the lysosomes via the intact lysine transport system. The reduction in leukocyte cystine levels correlates with the plasma concentration of mercaptamine for up to 6 hours after administration.

The leukocyte cystine level reaches its nadir (mean ± standard deviation (SD): 1.8 ± 0.8 hours) slightly later than the peak plasma concentration of mercaptamine (mean ± SD: 1.4 ± 0.4 hours) and returns to baseline as the plasma cystine level decreases. The concentration of mercaptamine decreases 6 hours after dose administration.

Pharmacokinetics

After a single oral dose of mercaptamine bitartrate, equivalent to 1.05 g of free mercaptamine base, in healthy volunteers, the mean (±SD) values for the time to reach C_max and its peak plasma concentration are 1.4 (±0.5) hours and 4 (±1) µg/ml, respectively.

In patients at steady state, these values are 1.4 (±0.4) hours and 2.6 (±0.9) µg/ml, respectively, after a dose ranging from 225 to 550 mg. Mercaptamine bitartrate is bioequivalent to mercaptamine hydrochloride and phosphocysteamine.

The binding of mercaptamine to plasma proteins in vitro, which is primarily to albumin, is independent of the plasma concentration of the active substance within the therapeutic range, with a mean (±SD) of 54.1% (±1.5). Protein binding in patients at steady state is similar: 53.1% (± 3.6) and 51.1% (± 4.5) at 1.5 and 6 hours after dose administration, respectively.

The terminal T_1/2 was 4.8 (±1.8) hours. The excretion of unchanged mercaptamine in urine accounts for 0.3-1.7% of the total daily dose in four patients; the major portion of mercaptamine is excreted as sulfate.

Indications

Treatment of nephropathic cystinosis.

Dosage Regimen

Orally.

For patients with a body weight over 50 kg, the maintenance dose is usually 2 g/day in 4 divided doses. The use of a dose exceeding 1.95 g/m²/day is not recommended.

For children under 12 years of age, the maintenance dose is 1.3 g/m²/day of mercaptamine in 4 divided doses.

The initial dose should be 15-25% of the recommended maintenance dose, with a gradual increase over 4-6 weeks. The dose should be increased if there is adequate tolerance and the leukocyte cystine level remains >1 nmol half-cystine/mg protein.

Adverse Reactions

Blood and lymphatic system disorders frequent – changes in liver enzyme activity in the blood; infrequent – leukopenia.

Immune system disorders infrequent – anaphylactic reaction.

Metabolism and nutrition disorders very frequent – anorexia.

Psychiatric disorders infrequent – nervousness, hallucinations.

Nervous system disorders frequent – headache, encephalopathy; infrequent – drowsiness, seizures.

Gastrointestinal disorders very frequent – vomiting, nausea, diarrhea; frequent – abdominal pain, unpleasant breath odor, dyspepsia, gastroenteritis; infrequent – ulcerative gastrointestinal lesion.

Skin and subcutaneous tissue disorders frequent – abnormal skin odor, rash; infrequent – hair color changes, skin striae, skin fragility, molluscoid pseudotumor on the elbows.

Musculoskeletal and connective tissue disorders infrequent – joint hypermobility, leg pain, valgus deformity, osteopenia, compression fracture, scoliosis.

Renal and urinary disorders infrequent – nephrotic syndrome.

General disorders and administration site conditions very frequent – lethargy, pyrexia.

Contraindications

Hypersensitivity to mercaptamine, history of hypersensitivity to penicillamine; pregnancy (except in special cases of extreme necessity), breastfeeding period.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

Dosage adjustment is usually not required; however, leukocyte cystine levels should be monitored.

Use in Renal Impairment

In patients undergoing hemodialysis, Mercaptamine may lead to a more frequent occurrence of adverse reactions. Careful monitoring of leukocyte cystine levels is recommended for such patients.

Pediatric Use

Used in children according to the indications.

Special Precautions

To achieve maximum benefit, therapy with mercaptamine should be initiated as soon as possible, immediately after confirmation of the diagnosis of nephropathic cystinosis.

Nephropathic cystinosis must be diagnosed based on both clinical signs and biochemical studies (measurement of leukocyte cystine levels).

Cases of Ehlers-Danlos syndrome and vascular disorders on the elbows have been reported in children receiving high doses of various mercaptamine preparations (mercaptamine chlorhydrate or mercaptamine bitartrate), predominantly above the maximum dose of 1.95 g/m²/day.

These skin lesions were accompanied by vascular proliferation, skin striae, and bone lesions. During mercaptamine administration, it is recommended to monitor the skin condition and, if necessary, perform X-ray examination of the bones. Patients and their parents should also be advised to perform self-examination of the skin. If such skin or bone changes appear, it is recommended to reduce the dose of mercaptamine.

Regular monitoring of blood cell count is recommended.

Oral administration of mercaptamine has not been proven to prevent the deposition of cystine crystals in the eyes. Therefore, if an ophthalmic solution of mercaptamine is used for this purpose, its use should be continued.

Unlike phosphocysteamine, Mercaptamine does not contain phosphates. Patients typically receive phosphate supplements, and when switching from phosphocysteamine to Mercaptamine, the doses of phosphate supplements for patients should be reviewed.

Effect on ability to drive and operate machinery

Mercaptamine has a minor or moderate influence on the ability to drive and operate machinery. Mercaptamine may cause drowsiness. Patients should refrain from driving vehicles and operating machinery at the beginning of therapy, as it is impossible to predict the effect of mercaptamine on the patient’s body.

Drug Interactions

Mercaptamine can be prescribed together with electrolyte and mineral replacements necessary for the treatment of Fanconi syndrome, as well as with vitamin D and thyroid hormones.

In some patients, indomethacin and Mercaptamine were used concurrently.

Patients with a kidney transplant concurrently took Mercaptamine and prescribed therapy to prevent transplant rejection.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.