Goals of treatment Goals of treatment

Help patients achieve the goal of stone prevention with THIOLA1,2

Adherence to therapeutic lifestyle changes (consisting of daily fluid intake of 3 to 4 liters, maintaining urinary pH to an optimal level, and limiting sodium and protein intake) has been proven to be ineffective at preventing cystine stones approximately 45% of the time. If your patients are still experiencing stones even with these modifications, THIOLA can help.1-3

Adding THIOLA to a treatment regimen consisting of therapeutic lifestyle changes can help your patients achieve the goals of treatment, which include:

Stone prevention by lowering urinary cystine concentration generally to <250 mg/L.1,2

Avoiding and/or minimizing invasive procedures2,4

Keeping kidneys working normally to prevent long-term damage5

American Urological Association report

The American Urological Association (AUA) recommends using cystine-binding thiol drugs such as THIOLA as the next line of therapy when therapeutic lifestyle changes fail to prevent stones from forming.6

Get THIOLA

Indications Indications

Is your patient still forming cystine stones? Consider THIOLA.

If your patient is still experiencing recurring stones under his or her current treatment plan, THIOLA can help. 

Consider THIOLA

INDICATIONS: THIOLA® (tiopronin) tablets are indicated for the prevention of cystine (kidney) stone formation in patients with severe homozygous cystinuria with urinary cystine >500 mg/day, who are resistant to treatment with conservative measures of high fluid intake, alkali and diet modification, or who have adverse reactions to d‑penicillamine.

Efficacy Efficacy

Efficacy results in patients with cystinuria7

 

Group 1

Previously treated with d‑penicillamine (n=43)

Group 2

Naïve to d‑penicillamine (n=14)

Stone reduction7

(reduced rate of new stone formation)

81.4%

94.1%

Stone remission7

(cessation of stone formation)

62.8%

71.4%

In a multicenter clinical trial of patients with cystinuria (urinary cystine excretion of >400 mg/day), THIOLA stopped stones from forming completely, as well as reduced the rate of stone formation, regardless of whether or not participants had previously been treated with d‑penicillamine.7

The study included 66 cystine stone formers at 12 study sites (mean age 32.0 ± 13.3 years), with 1 or more stone episodes (spontaneous passage, surgical removal, or appearance on X-ray) in the prior 2 years.7

Of those 66 people, 49 patients had been previously treated with d‑penicillamine (at a mean dosage of 1125 ± 640 mg/day for a mean of 2.81 ± 3.94 years), and 17 had no prior d‑penicillamine therapy. All patients maintained ongoing dietary and fluid regimens, and 45/66 patients continued ongoing alkali therapy. Patients received THIOLA for between 4 months and 4 years at a mean dosage of 1193 ± 450 mg/day, in 3 to 4 divided doses ≥1 hour before or 2 hours after meals.7

Mechanism of action Mechanism of action

Learn how THIOLA keeps cystine levels below the line of solubility to prevent stones from forming1,2

Accumulation of excess cystine means increased risk of stone formation. Fortunately for your patients living with cystinuria, THIOLA targets the excess cystine.1,2

See how it happens

Watch Play Video

Safety Safety

THIOLA is associated with fewer or less severe reactions than d‑penicillamine7

Adverse events are more likely to occur in people with cystinuria who had previously had adverse reactions while taking d‑penicillamine.7

Group 1

Previously treated with d‑penicillamine

69% of patients discontinued d‑penicillamine due to side effects vs 31% of patients who discontinued THIOLA due to side effects.7

Of the 34 patients who had to stop taking d‑penicillamine, 22 were able to continue with THIOLA.7

Group 2

Naïve to d‑penicillamine

65% of these patients experienced adverse reactions; however, many of these side effects were minor or nonspecific.7

Only 1 patient had to stop taking THIOLA due to adverse reactions.7

Adverse reactions (≥5%) occurring in a multiclinic trial of 66 cystine stone-formers treated with THIOLA7:

Adverse reaction

Group 1 (n=49)

Group 2 (n=17)

Nausea

12 (24.5%)

2 (11.8%)

Emesis

5 (10.2%)a

-

Diarrhea/soft stools

9 (18.4%)

1 (5.9%)

Anorexia

4 (8.2%)

-

Abdominal pain

0 (0%)

1 (5.9%)

Oral ulcers

6 (12.2%)

3 (17.6%)

Rash

7 (14.3%)a

2 (11.8%)

Ecchymosis

3 (6.1%)

-

Pruritus

2 (4.1%)

1 (5.9%)

Urticaria

4 (8.2%)

-

Skin wrinkling

3 (6.1%)

1 (5.9%)

Fever

4 (8.2%)

2 (11.8%)

Arthralgia

0 (0%)

2 (11.8%)

Weakness

2 (4.1%)

1 (5.9%)

Anemia

1 (2.0%)

-

Fatigue

7 (14.3%)

1 (5.9%)

Proteinuria

5 (10.2%)

1 (5.9%)

Peripheral edema

3 (6.1%)

1 (5.9%)

Impotence

-

1 (5.9%)

Chest pain

-

1 (5.9%)

Cough

-

1 (5.9%)

aSignificant decrease vs dpenicillamine (P<.05) by chi-square test.

THIOLA dosing

Routinely monitor cystine levels with 24-hour urine tests to find the right dosage for your patients.1,3

THIOLA dosing

References:  1. THIOLA [package insert]. San Antonio, TX: Mission Pharmacal Company.  2. Pareek G, Steele TH, Nakada SY. Urological intervention in patients with cystinuria is decreased with medical compliance. J Urol. 2005;174(6):2250-2252.  3. Knoll T, Zöllner A, Wendt-Nordahl G, Michel MS, Alken P. Cystinuria in childhood and adolescence: recommendations for diagnosis, treatment, and follow-up. Pediatr Nephrol. 2005;20(1):19-24. doi:10.1007/s00467-004-1663-1.  4. Claes DJ, Jackson E. Cystinuria: mechanisms and management. Pediatr Nephrol. 2012;27(11):2031-2038. doi:10.1007/s00467-011-2092-6.  5. Biyani CS, Cartledge JJ. Cystinuria: diagnosis and management. EAU-EBU Update Series. 2006;4(5):175-183. doi:10.1016/j.eeus.2006.06.001.  6. Pearle MS, Goldfarb DS, Assimos DG, et al. Medical management of kidney stones: AUA guideline. J Urol. 2014;192(2):316-324. doi:10.1016/j.juro.2014.05.006.  7. Pak CYC, Fuller C, Sakhaee K, et al. Management of cystine nephrolithiasis with alpha-mercaptopropionylglycine. J Urol. 1986;136(5):1003-1008.

INDICATIONS: THIOLA® (tiopronin) tablets are indicated for the prevention of cystine (kidney) stone formation in patients with severe homozygous cystinuria with urinary cystine  >500 mg/day, who are resistant to treatment with conservative measures of high fluid intake, alkali and diet modification, or who have adverse reactions to d-penicillamine.

Important Safety Information 

CONTRAINDICATIONS: THIOLA is contraindicated during pregnancy (except where the benefits clearly outweigh the risks), in nursing mothers, and in patients who have previously developed agranulocytosis, aplastic anemia or thrombocytopenia while on this medication.

WARNINGS AND PRECAUTIONS:

  • While no deaths have been reported with THIOLA treatment, THIOLA can potentially cause all the serious adverse reactions reported for d-penicillamine, including death. 
  • Hematologic abnormalities requiring drug discontinuation may occur: inform patients to report promptly signs or symptoms of hematologic abnormalities.
  • Proteinuria, sometimes severe enough to cause nephrotic syndrome: monitor affected patients closely.
  • Discontinue THIOLA therapy if there are findings suggestive of Goodpasture’s syndrome, myasthenic syndrome, or myasthenia gravis. If pemphigus-type reactions occur, discontinue therapy and consider steroid treatment.
  • Inform patients about potential complications; advise them to promptly report any treatment-emergent signs or symptoms.
  • To reduce the risk of serious complications, the following tests should be conducted: 
    • Peripheral blood counts, direct platelet counts, hemoglobin, serum albumin, liver function tests, 24-hour urinary protein, routine urinalysis: 3-6 month intervals
    • Urinary cystine analysis: frequently during dose optimization, and at 6 month intervals thereafter
    • Abdominal roentgenogram: annually
  • In animal studies, THIOLA has been shown to cause fetal harm. THIOLA should only be used during pregnancy if the potential benefit justifies potential risk to the fetus.
  • THIOLA should not be used in nursing mothers.
  • The safety and efficacy of THIOLA in children under 9 years of age have not been established.

ADVERSE REACTIONS:

Adverse reactions associated with THIOLA include the following:

  • Drug fever during the first month
  • Generalized rash with pruritus
  • Lupus erythematous-like drug reaction (e.g., fever, arthralgia, lymphadenopathy, positive antinuclear antibody test)
  • Hypogeusia
  • Vitamin B6 deficiency (uncommon)
  • Wrinkling and friability of skin
  • Jaundice and abnormal liver function tests (in non-cystinuric conditions)

THIOLA is associated with fewer or less severe reactions than d-penicillamine, however the following adverse reactions may occur:  

  • Gastrointestinal (nausea, emesis, diarrhea, anorexia, abdominal pain, bloating, flatus)
  • Impairment in taste or smell
  • Dermatologic (pharyngitis, oral ulcers, rash, ecchymosis, pruritus, urticaria, warts, skin wrinkling, pemphigus, elastosis perforans serpiginosa)
  • Hypersensitivity reactions (laryngeal edema, dyspnea, respiratory distress, fever, chills, arthralgia, weakness, fatigue, myalgia, adenopathy)
  • Hematologic (increased bleeding, anemia, leukopenia, thrombocytopenia, eosinophilia)
  • Renal (proteinuria, nephrotic syndrome, hematuria)
  • Pulmonary (bronchiolitis, hemoptysis, pulmonary infiltrates, dyspnea)
  • Neurologic (myasthenic syndrome)

These reactions are more likely to occur during THIOLA therapy for patients who had previously shown toxicity to d-penicillamine.

Please see full Prescribing Information.