Propylthiouracil Tablets Product Monograph

RECENT MAJOR LABEL CHANGES

TABLE OF CONTENTS

Sections or subsections that are not applicable at the time of authorization are not listed.

RECENT MAJOR LABEL CHANGES............................................................................................ 2

TABLE OF CONTENTS .............................................................................................................. 2

PART I: HEALTH PROFESSIONAL INFORMATION ..................................................................... 4

1 INDICATIONS .............................................................................................................. 4

1.1 Pediatrics .............................................................................................................. 4

1.2 Geriatrics............................................................................................................... 4

2 CONTRAINDICATIONS ................................................................................................. 4

3 SERIOUS WARNINGS AND PRECAUTIONS BOX ............................................................ 4

4 DOSAGE AND ADMINISTRATION................................................................................. 5

4.1 Dosing Considerations ....................................................................................... 5

4.2 Recommended Dose and Dosage Adjustment..................................................... 5

4.4 Administration................................................................................................... 6

4.5 Missed Dose ...................................................................................................... 6

5 OVERDOSAGE ............................................................................................................. 6

6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ................................. 7

7 WARNINGS AND PRECAUTIONS .................................................................................. 7

7.1 Warnings and Precautions Synopsis ................................................................... 7

7.2 Special Populations ............................................................................................ 9

7.2.1 Pregnant Women ............................................................................................. 9

7.2.2 Breast-feeding................................................................................................ 10

7.2.3 Pediatrics ....................................................................................................... 10

7.2.4 Geriatrics ....................................................................................................... 10

8 ADVERSE REACTIONS ................................................................................................ 10

8.1 Adverse Reaction Overview.............................................................................. 10

8.4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data Clinical Trial Findings ............................................................ 11

8.5 Post-Market Adverse Reactions........................................................................ 11

9 DRUG INTERACTIONS................................................................................................ 11

9.1 Serious Drug Interactions ................................................................................. 11

9.2 Drug Interactions Overview.............................................................................. 11

9.4 Drug-Drug Interactions .................................................................................... 11

9.5 Drug-Food Interactions .................................................................................... 12

9.6 Drug-Herb Interactions .................................................................................... 12

9.7 Drug-Laboratory Test Interactions .................................................................... 12

10 CLINICAL PHARMACOLOGY ....................................................................................... 12

10.1 Mechanism of Action.................................................................................. 12

10.2 Pharmacodynamics .................................................................................... 12

10.3 Pharmacokinetics ....................................................................................... 13

11 STORAGE, STABILITY AND DISPOSAL ......................................................................... 13

PART II: SCIENTIFIC INFORMATION ...................................................................................... 14

13 PHARMACEUTICAL INFORMATION............................................................................ 14

14 CLINICAL TRIALS........................................................................................................ 14

15 MICROBIOLOGY ........................................................................................................ 15

16 NON-CLINICAL TOXICOLOGY ..................................................................................... 15

17 SUPPORTING PRODUCT MONOGRAPHS.................................................................... 15

PATIENT MEDICATION INFORMATION ................................................................................. 16

PART I: HEALTH PROFESSIONAL INFORMATION

1 INDICATIONS

PROPYLTHIOURACIL TABLETS (propylthiouracil tablets) is indicated:

• For the medical management of hyperthyroidism.
• In conjunction with radioiodine to hasten recovery while awaiting the effects of radiation.
• For the control of thyrotoxicosis prior to surgery.
• In the management of a thyroid storm in addition to other therapeutic measures.

1.1 Pediatrics

Pediatrics (<18 years): No data are available to Health Canada; therefore, Health Canada has not authorized an indication for pediatric use.

1.2 Geriatrics

Geriatrics (>65 years): Information specific to the geriatric population is not available for this drug product.

2 CONTRAINDICATIONS

• PROPYLTHIOURACIL TABLETS is contraindicated in patients who are hypersensitive to this drug, related thioamide derivatives or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.
• PROPYLTHIOURACIL TABLETS is contraindicated in breast-feeding women.

3 SERIOUS WARNINGS AND PRECAUTIONS BOX

Serious Warnings and Precautions

4 DOSAGE AND ADMINISTRATION

4.1 Dosing Considerations

• Treatment with PROPYLTHIOURACIL TABLETS should be individualized, according to the severity of symptoms and signs of hyperthyroidism and response to therapy.
• Usually after one or 2 weeks, but certainly after 3 weeks of therapy, objective signs of clinical improvement should be seen.
• Delayed responses are sometimes noted when the thyroid is unusually large and when iodine in any form has previously been given.
• The course of therapy may last from 6 months to 3 years. Usually within 1 to 2 years, a prolonged remission in 50% of the cases can be expected.
• When remission is observed, PROPYLTHIOURACIL TABLETS should be withdrawn over a period of 1-2 months under close supervision.

4.2 Recommended Dose and Dosage Adjustment

Adults (≥18 years of age): The recommended initial dose is 50-100 mg (1 to 2 tablets of PROPYLTHIOURACIL TABLETS) every 8 hours, with increases as necessary up to a maximum of 500 mg/day. In some cases, initial doses as high as 900 mg/day may be required.

When doses larger than 300 mg/day of PROPYLTHIOURACIL TABLETS are needed, the drug should be administered every 4 to 6 hours.

The patient should be examined regularly by the physician and the dose of PROPYLTHIOURACIL TABLETS adjusted until the patient is euthyroid (usually after 6-8 weeks). At this stage, the dose should be reduced by 1/3 every 4-6 weeks to a maintenance dosage of one tablet of PROPYLTHIOURACIL TABLETS 2 or 3 times daily, administered at regular intervals.

Geriatric (>65 years of age): No data are available to determine whether subjects aged 65 or over respond differently from younger subjects. Dose selection for an elderly patient should be cautious reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Pediatric (<18 years of age): Health Canada has not authorized an indication for pediatric use.

Hepatic impairment: No clinical studies have been performed with PROPYLTHIOURACIL TABLETS in patients with hepatic insufficiency. Since liver toxicity is associated with the use of PROPYLTHIOURACIL TABLETS, caution is warranted in patients with hepatic impairment.

Renal impairment: No clinical studies have been performed with PROPYLTHIOURACIL TABLETS in patients with renal impairment.

The following schedule is recommended by W.M. Bennett et al¹:

1. 1. Bennett WM et al. Guidelines for drug therapy in renal failure. Ann Intern Med 1977; 86:754-83.

4.4 Administration

PROPYLTHIOURACIL TABLETS can be taken with or without food. Patients should be instructed to swallow tablets whole and not to chew, split, or crush tablets. Patients should not ingest if tablets are broken, cracked, or otherwise not intact. PROPYLTHIOURACIL TABLETS should be taken at the same time each day.

4.5 Missed Dose

Advise patients to not double a dose to make up for a missed dose.

Twice-daily dose: If it is less than 6 hours before the patient’s next dose, skip the dose they missed and take their next dose when they are meant to. If the patient remembers with 6 or more hours before the next dose, they should take the missed dose as soon as they remember, then take the next dose at the scheduled time.

QID (4 times a day) dose: If it is less than 3 hours before the patient’s next dose, skip the dose they missed and take their next dose when they are meant to. If the patient remembers to take PROPYLTHIOURACIL TABLETS with 3 or more hours before the next dose, they should take the missed dose as soon as they remember, then take the next dose at the scheduled time.

5 OVERDOSAGE

Agranulocytosis is the most serious adverse effect resulting from overdose and/or prolonged administration.

There has been one reported case of overdose with PROPYLTHIOURACIL TABLETS in the literature where the patient developed Henoch-Schonlein purpura (HSP) for which causal relationship with the drug could not be confirmed.

Overdosage can result in enlargement of the thyroid gland, with signs and symptoms of hypothyroidism. This can be readily reversed by reducing or even temporarily withdrawing medication. Thyroxine replacement therapy, until the patient becomes euthyroid, may be indicated.

Overdosage in pregnant women may result in congenital goiter and hypothyroidism in the fetus. The newborn child should be examined carefully for signs of hypothyroidism and immediate thyroid therapy should be instituted if hypothyroidism is confirmed.

Haemorrhage may be controlled by the administration of vitamin K1 and the dosage of PROPYLTHIOURACIL TABLETS should be reduced.

6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING

Table 1– Dosage Forms, Strengths, Composition and Packaging

Description

Propylthiouracil is a thioamide derivative which occurs as a white crystalline powder, odourless with a bitter taste, very slightly soluble in water, sparingly soluble in ethanol and soluble in solutions of alkali hydroxides or ammonia.

50 mg tablets: white, round, biconvex and uncoated; one side is debossed 'PRESTAB' and other side is plain.

PROPYLTHIOURACIL TABLETS are supplied in bottles containing 100 tablets.

7 WARNINGS AND PRECAUTIONS

Please see 3 SERIOUS WARNINGS AND PRECAUTIONS BOX

7.1 Warnings and Precautions Synopsis

PROPYLTHIOURACIL TABLETS should be reserved for patients who cannot tolerate methimazole and in whom radioactive iodine therapy or surgery are not appropriate treatments for the management of hyperthyroidism.

The vascularity and size of the thyroid gland may increase during treatment with PROPYLTHIOURACIL TABLETS. This suggests over treatment and indicates the need for reduced dosage.

Cardiovascular

Vasculitis: Cases of vasculitis resulting in severe complications and death have been reported rarely in patients receiving therapy with PROPYLTHIOURACIL TABLETS.

The cases of vasculitis include: glomerulonephritis, leukocytoclastic cutaneous vasculitis, alveolar/pulmonary hemorrhage, cerebral angiitis, and ischemic colitis. Most cases were associated with anti-neutrophilic cytoplasmic antibodies (ANCA)-positive vasculitis. Early recognition of vasculitis is important to prevent long term organ damage and/or death. Inform patients to promptly report symptoms that may be associated with vasculitis including new rash, hematuria or decreased urine output, dyspnea or hemoptysis.

If vasculitis is suspected, discontinue PROPYLTHIOURACIL TABLETS therapy and initiate appropriate intervention.

Endocrine and Metabolism

Hypothyroidism: Propylthiouracil can cause hypothyroidism necessitating routine monitoring of serum thyrotropin (TSH) and free T4 levels with adjustments in dosing to maintain a euthyroid state. The dose

of PROPYLTHIOURACIL TABLETS should be reduced or temporarily discontinued if signs of hypothyroidism occur during treatment.

Lactose: PROPYLTHIOURACIL TABLETS contains lactose monohydrate. Patients with hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this product.

Hematologic

Agranulocytosis: Agranulocytosis occurs in approximately 0.2% to 0.5% of patients and is a potentially life-threatening side effect of propylthiouracil therapy. Agranulocytosis typically occurs within the first 3 months of therapy. Patients should be instructed to immediately report to their physicians any symptoms suggestive of agranulocytosis, such as sore throat, fever, mouth ulcers, bruising, malaise, non-specific illness or other symptoms of infection. Leukopenia, thrombocytopenia, and aplastic anemia (pancytopenia) may also occur. PROPYLTHIOURACIL TABLETS should be discontinued if agranulocytosis, aplastic anemia (pancytopenia) is suspected, and the patient’s bone marrow function should be monitored. A full blood count should be performed and treatment should be discontinued immediately if there is clinical or laboratory evidence of neutropenia. Particular care should be exercised with patients who are receiving concomitant drugs known to be associated with agranulocytosis.

Anticoagulant therapy: Propylthiouracil has occasionally been reported to cause hypoprothrombinemia which would increase the effect of anticoagulants. Doses of oral anticoagulants, administered concurrently, should be adjusted accordingly. See 9.4 Drug-Drug Interactions

Hepatic/Biliary/Pancreatic

Liver injury resulting in liver failure, liver transplantation, or death, has been reported with propylthiouracil therapy in adult and pediatric patients. Propylthiouracil-induced hepatotoxicity is not dose-related and is thought to be idiosyncratic with an autoimmune component.

Hepatocellular necrosis and fulminant hepatic failure have been reported in patients treated with propylthiouracil. Typically these reactions occur within the first two months of propylthiouracil treatment. Injury is reversible upon discontinuation of propylthiouracil although encephalopathy and/or substantial hepatic necrosis have been reported. Routine monitoring of serum transaminases is not required but may be recommended for patients with a history of liver disease or for those who have other risk factors for hepatitis, e.g. alcohol use.

Discontinue PROPYLTHIOURACIL TABLETS when signs and symptoms of hepatic injury are present (anorexia, pruritus, jaundice, light colored stools, dark urine, right upper quadrant pain, etc.). When these symptoms occur, measurement should be made of liver function (bilirubin, alkaline phosphatase) and hepatocellular integrity (ALT/AST levels). Further thionamide therapy is contraindicated as death has resulted upon rechallenge.

Monitoring and Laboratory Tests

The patient’s liver function, hepatic transaminase levels, and the complete blood count should be closely monitored. Blood formula should be determined prior to institution of treatment. Liver Function Tests are also recommended at periodic intervals during therapy. Serum Alkaline Phosphatase, Serum Glutamic Oxaloacetic Transaminase (SGOT) and Serum Glutamic Pyruvic Transaminase (SGPT) levels may be increased.

Thyroid function tests should be monitored periodically during therapy (recommended prior to initiation of therapy, at monthly intervals during stabilization, then every 2 to 3 months) via Free (unbound) Serum Thyroxine (T4) levels, Total Serum T4 levels, Serum Thyrotropin (TSH), Total Serum

Triiodothyronine (T3). Once clinical evidence of hyperthyroidism has resolved, the finding of an elevated serum TSH indicates that a lower maintenance dose of PROPYLTHIOURACIL TABLETS should be employed.

Monitoring of prothrombin time should be considered during therapy with the drug, especially before surgical procedures because PROPYLTHIOURACIL TABLETS may cause hypoprothrombinemia and bleeding. See 8 ADVERSE REACTIONS

Peri-Operative Considerations

When PROPYLTHIOURACIL TABLETS is administered pre-operatively, iodine, in the form of a strong iodine solution (Lugol’s solution or potassium iodide solution) should be given concomitantly for 7-10 days prior to surgery. The rationale for this is to reduce the vascularity and fragility of the thyroid gland.

Renal

PROPYLTHIOURACIL TABLETS should be used with caution in patients with renal impairment.

Respiratory

In view of the fact that hypothyroid patients seem to have poor adrenergic nervous function, PROPYLTHIOURACIL TABLETS should be used with caution in patients with asthma.

Skin

PROPYLTHIOURACIL TABLETS should be discontinued immediately at the appearance of a skin rash, as the rash may be, in some instances, followed by dermatological reactions/hypersensitivity syndrome (including Stevens Johnson Syndrome or, toxic epidermal necrolysis). See 8 ADVERSE REACTIONS

7.2 Special Populations

7.2.1 Pregnant Women

Hyperthyroidism in pregnant women should be adequately treated to prevent serious maternal and fetal complications.

Individual benefit/risk assessment is necessary before treatment with PROPYLTHIOURACIL TABLETS during pregnancy. If PROPYLTHIOURACIL TABLETS is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be warned of the potential hazard of the rare potential hazard to the mother and fetus of liver damage.

PROPYLTHIOURACIL TABLETS is suggested for use prior to conception and in the first trimester of pregnancy where clinically appropriate due to the higher risk of congenital abnormalities with methimazole during fetal organogenesis in the first trimester. After the first trimester of pregnancy, the use of an alternative antithyroid medication may be advisable given the potential for maternal hepatotoxicity from PROPYLTHIOURACIL TABLETS.

PROPYLTHIOURACIL TABLETS should be administered during pregnancy at the lowest effective dose, without additional administration of thyroid hormones. Close maternal, fetal and neonatal monitoring of thyroid function is recommended, with adjustment of PROPYLTHIOURACIL TABLETS as necessary.

PROPYLTHIOURACIL TABLETS, used judiciously, is an effective drug for the treatment of hyperthyroidism in pregnant women. However, the drug readily crosses the placental barrier where it can induce goiter and hypothyroidism in the developing fetus. Rare cases of congenital anomalies have been observed post-marketing. See 8.5 Post-Market Adverse Reactions

Epidemiological studies provide conflicting results regarding the risk of congenital malformations.

7.2.2 Breast-feeding

Propylthiouracil is excreted in breast milk and is contraindicated in nursing mothers. See 2 CONTRAINDICATIONS

7.2.3 Pediatrics

Pediatrics (<18 years of age): No data are available to Health Canada; therefore, Health Canada has not authorized an indication for pediatric use.

7.2.4 Geriatrics

Geriatrics (>65 years of age): Clinical studies of propylthiouracil did not include sufficient numbers of subjects aged 65 or over to determine whether they respond differently from younger subjects.

8 ADVERSE REACTIONS

8.1 Adverse Reaction Overview

The most serious adverse reactions associated with PROPYLTHIOURACIL TABLETS are agranulocytosis, hepatotoxicity and rarely, systemic vasculitis. Recovery is often possible following immediate cessation of the drug.

Inhibition of hemopoiesis (agranulocytosis, granulocytopenia, leucopenia, thrombocytopenia) is the most serious side effect. The incidence of agranulocytosis is less than 0.5%. It usually develops in the first few months of therapy, is dose-related and is reversible on rapid withdrawal of the drug.

Leukopenia with granulocytopenia, hemolytic anemia, thrombocytopenia, hypoprothrombinemia with hemorrhagic manifestations, aplastic anemia, myeloblastic leukemia and hyperglobulinemia have been reported.

Severe adverse reactions include liver injury presenting as hepatitis, liver failure necessitating liver transplantation or resulting in death. See 7 WARNINGS AND PRECAUTIONS

Hepatocellular necrosis and fulminant hepatic failure have been reported in patients treated with PROPYLTHIOURACIL TABLETS. Typically these reactions occur within the first two months of PROPYLTHIOURACIL TABLETS treatment. Injury is reversible upon discontinuation of PROPYLTHIOURACIL TABLETS although encephalopathy and/or substantial hepatic necrosis have been reported. See 7 WARNINGS AND PRECAUTIONS

Hepatotoxicity has an estimated frequency of 0.1-0.2% in patients treated with PROPYLTHIOURACIL TABLETS. Propylthiouracil-induced hepatotoxicity is not dose-related and is thought to be idiosyncratic with an autoimmune component.

There are reports of a vasculitis associated with the presence of anti-neutrophilic cytoplasmic antibodies (ANCA), resulting in severe complications and death. See 7 WARNINGS AND PRECAUTIONS

There have been rare reports of serious hypersensitivity reactions (e.g., Stevens Johnson syndrome and toxic epidermal necrolysis) in patients treated with PROPYLTHIOURACIL TABLETS. See 7 WARNINGS AND PRECAUTIONS

Itching, urticaria, pruritus and a mild papular rash which may be accompanied by purpura are the most common skin reactions; (incidence approximately 3%). Loss or depigmentation of the hair are less frequent. Two cases of vesicular eruption in the newborn have been reported, secondary to maternal PROPYLTHIOURACIL TABLETS therapy.

Other adverse reactions include nausea, vomiting, ageusia, abdominal discomfort, drowsiness, headache, dizziness, arthralgia and paresthesia occur occasionally. Drug fever, lymphadenopathy, splenomegaly, hepatitis, cholestatic jaundice, neuritis, nephritis, unusual increase or decrease in urination, backache, sialadenopathy, recurrent keratitis, conjunctival disorders, connective tissue disorders resembling polyarteritis, arthritis, lupus erythematosus and an ototoxic reaction presenting as unilateral sensorineural hearing impairment.

8.4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data Clinical Trial Findings

It should be noted that about 10% of patients with untreated hyperthyroidism have leucopenia (white blood cell count of less than 4,000/mm³), often with relative granulocytopenia.

8.5 Post-Market Adverse Reactions

• Cases of congenital anomalies have been rarely reported in neonates whose mothers were treated with PROPYLTHIOURACIL TABLETS and other drugs during pregnancy. The pattern of congenital anomalies associated with PROPYLTHIOURACIL TABLETS is unclear, but may include anal atresia, accessory auricle, intestinal malrotation, gastrointestinal malformation and ventricular septal defect. See 7.2.1 Pregnant Women

9 DRUG INTERACTIONS

9.1 Serious Drug Interactions

9.2 Drug Interactions Overview

Pre-treatment with PROPYLTHIOURACIL TABLETS may reduce the effectiveness of radio-iodine (¹³¹I) therapy for hyperthyroidism.

9.4 Drug-Drug Interactions

Anticoagulants (oral): Due to the potential inhibition of vitamin K activity by propylthiouracil, the activity of oral anticoagulants (e.g. warfarin) may be increased; additional monitoring of PT/INR should be considered, especially before surgical procedures.

Beta-adrenergic blocking agents: Hyperthyroidism may cause an increased clearance of beta blockers with a high extraction ratio. A reduced dose of beta-adrenergic blockers may be needed when a hyperthyroid patient becomes euthyroid.

Digitalis glycosides: Serum digitalis levels may be increased when hyperthyroid patients on a stable digitalis glycoside regimen become euthyroid; a reduced dose of digitalis glycosides may be needed.

Theophylline: Theophylline clearance may decrease when hyperthyroid patients on a stable theophylline regimen become euthyroid; a reduced dose of theophylline may be needed.

9.5 Drug-Food Interactions

Interactions with food have not been established.

9.6 Drug-Herb Interactions

Interactions with herbal products have not been established.

9.7 Drug-Laboratory Test Interactions

Interactions with laboratory tests have not been established.

10 CLINICAL PHARMACOLOGY

10.1 Mechanism of Action

Propylthiouracil affects the synthesis of thyroid hormones by inhibiting the incorporation of iodide into thyroglobulin. This is probably done by interfering with the mechanism of oxidation of the iodide ion through thyroid peroxidase activities. It does not inactivate thyroid hormones previously formed or interfere with their release from the gland. The observation that ¹³¹iodine uptake remains elevated in hyperthyroid patients even when the euthyroid state is approached suggests that its action may be more complex, involving effects on organic binding and coupling.

Propylthiouracil may also decrease the rate of conversion of T4(1-thyroxine) to T3(triiodothyronine) in peripheral tissues. Iodide uptake is not decreased by propylthiouracil.

Depending on the activity of the disease and on whether or not the patient has previously received iodide, the clinical effects will not appear until the stored supply of thyroid hormones has been utilized. Clinical response may be delayed for up to two weeks.

In responsive patients, prolonged remission may be obtained only after several months of treatment and may take up to several years. The average duration of treatment is usually one year.

Data suggest that stopping therapy as soon as the euthyroid state is attained is as effective in some patients as continuing therapy for a year or longer.

10.2 Pharmacodynamics

The rapidity of the therapeutic response will depend largely on the completeness of blockade of thyroid hormones synthesis, the amount of stored hormones and the peripheral rate of turnover of these hormones.

The effect of a dose of 100 mg of propylthiouracil begins to wear off in 2 to 3 hours; a dose of 500 mg completely inhibits thyroid function for 6 to 8 hours.

10.3 Pharmacokinetics

Absorption: Absorption of effective amounts occurs within 20 to 30 minutes after oral administration.

Distribution: Propylthiouracil labelled with ³⁵S has been found to accumulate in the thyroid gland. Protein binding is about 40%. It crosses the placental barrier and is found in the milk of nursing mothers. The serum or plasma half-life ranges between 1-1.6 hours after a single oral dose.

Metabolism: The metabolites of propylthiouracil have not yet been satisfactorily identified.

Elimination: Propylthiouracil, to the extent of 50% of the dose, is conjugated to glucuronic acid and is mainly excreted via the kidneys within 24 hours. Only a small amount (1-3%) of the drug is found free in the urine.

11 STORAGE, STABILITY AND DISPOSAL

Store at room temperature (15°C to 30°C). Keep this medicine out of the sight and reach of children.

12 SPECIAL HANDLING INSTRUCTIONS

None required.

PART II: SCIENTIFIC INFORMATION

13 PHARMACEUTICAL INFORMATION

Drug Substance

Proper name: Propylthiouracil

Chemical name: 2,3-Dihydro-6-propyl-2-thioxo-4(1H)-pyrimidinone;

4-hydroxy-2-mercapto-6-propylpyrimidine;

6-n-propyl-2-thiouracil;

6-propyl-2-thiopyrimidine-2,4(1H,3H)-dione;

6-propylthiouracil;

2-mercapto-6-propylpyrimid-4-one;

6-Propyl-2-thiouracil.

Molecular formula and molecular mass:

C₇H₁₀N₂OS

170.23 g/mol

Structural formula:

Physicochemical properties:

Description: White or almost white, crystalline powder or crystals.

Melting range: 217 – 221 °C

Solubility: Very slightly soluble in water, sparingly soluble in alcohol. Easily soluble in aqueous ammonia solution and solutions of alkali hydroxides. Practically insoluble in ether, chloroform, benzene.

14 CLINICAL TRIALS

The clinical trial data on which the original indication was authorized is not available.

15 MICROBIOLOGY

No data available.

16 NON-CLINICAL TOXICOLOGY

No data available.

17 SUPPORTING PRODUCT MONOGRAPHS

1. 1. PROPYL-THYRACIL® (50 mg tablets), Control No.: 233767, Prescribing Information, Paladin Labs Inc. (Apr. 06, 2020)
2. 2. PTU^TM (50 mg tablets), N/A, Australian Product Information, Phebra Pty Ltd (Feb. 24, 2020)