Tiopronin

Tiopronin is an Orphan drug belonging to Drug for nephrolithiasis.

Tiopronin is a thiol agent indicated for the prevention of kidney stone formation in patients with severe homozygous cystinuria.

Tiopronin is absorbed from the gastrointestinal tract, reaching peak plasma concentration 3-6 hours after ingestion. In healthy subjects, the bioavailability of total and unbound tiopronin was found to be 63% and 40%, respectively. The volume of distribution of tiopronin is high at 455 L, indicating that a large portion of the drug is bound to tissues outside plasma. The principal metabolite of tiopronin is 2-mercaptopropionic acid (2-MPA). Between 10-15% of the drug is metabolized to 2-MPA via hydrolysis. Excreted mainly via urine approximately 48% within 4 hours, approximately within 72 hours.

Tiopronin shows side effects like Itching, changes in taste, skin wrinkling, nausea, vomiting, diarrhea, loss of appetite, abdominal pain, bloating, gas, sore throat, mouth sores, shortness of breath, chills, weakness, fatigue, muscle pain, high levels of protein in the urine, and anemia.

Tiopronin is available in the form of Oral Tablet.

Tiopronin is available in India, US, Canada, UK, Indonesia, Italy, Spain, Singapore, Malaysia, France, and Australia.

Tiopronin belongs to the Drug for nephrolithiasis acts as an Orphan drug.

Kidney stones form when the solubility limit is exceeded, and urine becomes supersaturated with endogenous cystine. Tiopronin is an active reducing agent which undergoes a thiol-disulfide exchange with cystine to form a water-soluble mixed disulfide complex. Thus, the amount of sparingly soluble cystine is reduced. By reducing urinary cystine concentrations below the solubility limit, tiopronin helps reduce cystine stone formation.

The Data of Onset and duration of action of Tiopronin is not clinically established.

Tiopronin is available in the form of Oral Tablet.

Tiopronin tablet is taken orally, usually in divided dose.

Tiopronin is an Orphan drug belonging to Drug for nephrolithiasis.

As an active reducing agent, tiopronin undergoes thiol-disulfide exchange with cystine to form tiopronin-cystine disulfide, which is more water soluble than cystine. As a result, the amount of sparingly soluble cystine in the urine is decreased and the formation of cystine calculi is reduced.

Tiopronin is approved for use in the following clinical indications

• Prevention of nephrolithiasis (cystine)

Tiopronin is a thiol agent indicated for the prevention of kidney stone formation in patients with severe homozygous cystinuria.

• Prevention of nephrolithiasis (cystine) Oral:

Adult Dose:

Initial: 800 mg/day in 3 divided doses; average dose: 1,000 mg/day. Consider a lower initial dose in patients with history of severe toxicity to d-penicillamine.

Maintenance: Adjust dose to reduce urinary cystine level to <250 mg/L.

Pediatric Dose:

Children ≥2 years and Adolescents

Initial: 15 mg/kg/day in 3 divided doses; titrate dose to reduce urinary cysteine level to <250 mg/L.

Maximum daily dose: 50 mg/kg/day.

Tiopronin is available in the form of Oral tablet.

• Goodpasture syndrome

Tiopronin is structurally similar to penicillamine. Penicillamine has rarely been associated with fatalities due to Goodpasture syndrome; therefore, the potential of Goodpasture syndrome in tiopronin-treated patients is possible; discontinue therapy if signs or symptoms occur.

• Hematologic effects

Tiopronin is structurally similar to penicillamine. Penicillamine has been associated with hematologic toxicities. Signs of toxicity include leukopenia without eosinophilia and thrombocytopenia. Advise patients to report early signs and symptoms including fever, sore throat, mouth ulcers, infections, easy bruising, or petechial or purpuric hemorrhage. Therapy should be discontinued if platelet count falls to <100,000/mm³ or WBC <3,500/mm³.

• Hypersensitivity

Hypersensitivity reactions (drug fever, rash, fever, arthralgia, and lymphadenopathy) have been reported.

• Myasthenia gravis

Tiopronin is structurally similar to penicillamine. Penicillamine has rarely been associated with fatalities due to myasthenia gravis; therefore, the potential of myasthenia gravis in tiopronin-treated patients is possible; discontinue therapy if signs or symptoms occur.

• Pemphigus

Tiopronin is structurally similar to penicillamine. Penicillamine has been associated with pemphigus. Discontinue treatment if pemphigus-type reactions occur; additional therapy may be needed.

• Proteinuria

Proteinuria, including nephrotic syndrome and membranous nephropathy, have been reported. Risk may be increased in pediatric patients receiving >50 mg/kg/day. Monitor for the development of proteinuria; interrupt therapy in patients who develop proteinuria.

Consumption of alcohol should be avoided 2 hours before and 3 hours after taking tiopronin.

There are no data on the presence of tiopronin in either human or animal milk or on the effects of the breastfed child. A published study suggests that tiopronin may suppress milk production. Because of the potential for serious adverse reactions, including nephrotic syndrome, advise patients that breastfeeding is not recommended during treatment with tiopronin.

Tiopronin have not identified a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. Renal stones in pregnancy may result in adverse pregnancy outcomes. In animal reproduction studies, there were no adverse developmental outcomes with oral administration of tiopronin to pregnant mice and rats during organogenesis at doses up to 2 times a 2 grams/day human dose (based on mg/m²). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively.

Common

• Fatigue, Skin rash, Nausea, oral mucosa ulcer, diarrhea, Arthralgia, asthenia, Chest pain, peripheral edema, Urticaria, ecchymoses, wrinkling of skin, pruritus, Vomiting, anorexia, abdominal pain, Proteinuria, impotence, Anemia, Cough, Fever.

Rare

• Abdominal distension, abdominal distress, ageusia, back pain, burning sensation, cardiac failure, cheilosis, decreased appetite, decreased estimated GFR (eGFR), dehydration, dermatologic disorders (abnormal skin texture), dizziness, dysgeusia, dyspepsia, eructation, flank pain, flatulence, gastroesophageal reflux disease, gastrointestinal disease, headache, hyperhidrosis, hypersensitivity reaction, hypoesthesia, increased serum transaminases, jaundice, joint swelling, limb pain, malaise, membranous glomerulonephritis, musculoskeletal pain, myalgia, neck pain, nephrotic syndrome, pain, pemphigus foliaceous, renal failure syndrome, skin irritation, swelling, vertigo, weight gain, xeroderma, xerostomia.

The common side effects of Tiopronin include the following

Common side effects

• Itching, changes in taste, skin wrinkling, nausea, vomiting, diarrhea, loss of appetite, abdominal pain, bloating, gas, sore throat, mouth sores, shortness of breath, chills, weakness, fatigue, muscle pain, high levels of protein in the urine, and anemia.

Rare side effects

• Hives, difficulty breathing, swelling of your face, lips, tongue, or throat, dizziness, rash, fever, swollen glands, and joint pain.

• Pregnancy

Pregnancy Category C

Tiopronin have not identified a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. Renal stones in pregnancy may result in adverse pregnancy outcomes. In animal reproduction studies, there were no adverse developmental outcomes with oral administration of tiopronin to pregnant mice and rats during organogenesis at doses up to 2 times a 2 grams/day human dose (based on mg/m²). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively.

• Nursing Mothers

There are no data on the presence of tiopronin in either human or animal milk or on the effects of the breastfed child. A published study suggests that tiopronin may suppress milk production. Because of the potential for serious adverse reactions, including nephrotic syndrome, advise patients that breastfeeding is not recommended during treatment with tiopronin.

• Pediatric Use

Tiopronin is indicated in pediatric patients weighing 20 kg or more with severe homozygous cystinuria, in combination with high fluid intake, alkali, and diet modification, for the prevention of cystine stone formation who are not responsive to these measures alone. This indication is based on safety and efficacy data from a trial in patients 9 years to 68 years of age and clinical experience. Proteinuria, including nephrotic syndrome, has been reported in pediatric patients. Pediatric patients receiving greater than 50 mg/kg tiopronin per day may be at greater risk. tiopronin tablets are not approved for use in pediatric patients weighing less than 20 kg.

• Geriatric Use

This drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Pharmacodynamic

Information not available.

Pharmacokinetics

• Absorption

Tiopronin is absorbed from the gastrointestinal tract, reaching peak plasma concentration 3-6 hours after ingestion. In healthy subjects, the bioavailability of total and unbound tiopronin was found to be 63% and 40%, respectively.

• Distribution

The volume of distribution of tiopronin is high at 455 L, indicating that a large portion of the drug is bound to tissues outside plasma.

• Metabolism and Excretion

The principal metabolite of tiopronin is 2-mercaptopropionic acid (2-MPA). Between 10-15% of the drug is metabolized to 2-MPA via hydrolysis. Excreted mainly via urine approximately 48% within 4 hours, approximately within 72 hours.

• https://www.uptodate.com/contents/tiopronin-drug-information?search=Tiopronin&source=panel_search_result&selectedTitle=1~6&usage_type=panel&kp_tab=drug_general&display_rank=1
• https://www.mims.com/india/drug/info/tiopronin?type=full
• https://www.drugs.com/mtm/tiopronin.html
• https://go.drugbank.com/drugs/DB06823
• https://www.rxlist.com/thiola-ec-drug.htm#clinpharm
• https://www.drugs.com/mtm/tiopronin.html