Propylthiouracil Tablets Instructions

Date of approval.
Date of revision.
 Propylthiouracil Tablets Instructions
Please read the instructions carefully and use under the guidance of a physician.
Warnings
 Drug Name]
Generic name: Propylthiouracil Tablets
English name: Propylthiouracil Tablets
Hanyu Pinyin：Bingliuyang Miding Pian
Ingredients
The main ingredient of this product is: propylthiouracil, whose chemical name is: 6-propyl-2-thio-2,3-dihydro-4(1H)pyrimidinone.
Chemical structure formula.
 
 Molecular formula: C7H10N2OS
Molecular weight: 170.24
Properties
This product is a white tablet.
Indications]
For patients with various types of hyperthyroidism who are intolerant to methimazole; especially for: 1. patients with mild to moderate enlargement of the thyroid gland; 2. patients with recurrence after thyroid surgery who are not suitable for radioactive 131I treatment; 3. preparation for surgery; 4. as adjuvant therapy to 131I radiotherapy.
Specification
50mg
Dosage and Administration
For the treatment of adult hyperthyroidism, the starting dose is generally 300mg (6 tablets) per day, depending on the severity of the disease, between 150-400mg (3-8 tablets), divided into oral doses, the maximum amount of 600mg (12 tablets) per day. The maintenance dose is 50-150mg (1 to 3 tablets) per day, adjusted according to the condition.
The starting dose for pediatric patients is 4mg/kg per day by weight, divided into oral doses, and the maintenance dose is reduced as appropriate.
A detailed examination of liver and kidney function should be performed before starting treatment with this product.
Because the elimination half-life of propylthiouracil can increase hepatic and renal injury, dose changes are necessary in cases of decreased hepatic and renal function, renal insufficiency, and the need for dialysis. For mild to moderate renal injury, the dose should be reduced to 25%. In severe renal injury, the dose should be reduced by 50%. Patients with hepatic impairment should also reduce the dose accordingly, and relevant contraindications must be considered.
Adverse reactions]
According to the literature
The following adverse reactions have been reported with propylthiouracil treatment. Because these events are generally reported voluntarily by an indeterminate number of people, it is not possible to reliably estimate the incidence or establish a causal relationship related to drug exposure.
Blood and lymphatic system disorders
Neutropenia usually has no clinically significant symptoms. Occasional serious adverse reactions are granulocytic leukocyte deficiency, granulocytopenia, aplastic anemia, and thrombocytopenia. Granulocytic deficiency occurs in up to 0.6% of patients on propylthiouracil and may also occur weeks to months after the start of therapy; patients are advised to discontinue the drug immediately and in most cases it may recede on its own (see Contraindications). Lymphadenopathy and thrombocytopenia occur rarely. In isolated cases, impaired erythropoiesis (aplastic anemia), hemolysis (hemolytic anemia) and a positive Coombs test have been observed.
Endocrine disorders
Sometimes stromal formation occurs in neonates and existing goiter may be enlarged.
Gastrointestinal disorders
Gastric intolerance and, in isolated cases, gastrointestinal discomfort (nausea, vomiting) may sometimes occur.
Skin and subcutaneous tissue disorders
Occasional itchy rash or urticaria, other occasional exfoliative dermatitis, erythema nodosum, skin hyperpigmentation, pruritus have been reported.
Skeletal muscle and connective tissue disorders
Occasionally, arthralgia is observed, usually progressive after several months of treatment, without objective signs of inflammation. In isolated cases, neuromuscular disease and polyarthritis have been observed. If there are signs of myalgia, creatine phosphokinase levels should be checked.
Rarely occurring adverse reactions, especially at high doses, are
Immune system disorders
including allergic reactions and drug fever. Severe hypersensitivity reactions (e.g., Stevens-Johnson syndrome and toxic epidermolysis bullosa) have been reported rarely in patients treated with propylthiouracil.
Effects of immune system disorders on other organ systems (skeletal muscle, blood vessels, kidneys, respiratory tract)
Patients with Graves’ disease treated with propylthiouracil may develop anti-neutrophil cytoplasmic antibodies against myeloperoxidase (MPO-ANCA), associated with rheumatic diseases (myalgia, arthralgia) and, in isolated cases, with vasculitis (see Precautions), nephritis, glomerulonephritis, or alveolar hemorrhage.
Lupus-like syndrome (including splenomegaly and vasculitis), periarteritis, and hypoprothrombinemia have also been reported.
Hepatobiliary disease
Rarely, liver damage (hepatic reaction with hepatocyte necrosis, transient cholestasis) occurs, manifesting as hepatitis (toxic hepatitis), liver failure resulting in the need for liver transplantation or death (see precautions), jaundice.
Neurological disorders
In isolated cases, the following have been observed: taste and smell disturbances, sensory abnormalities, neuritis and polyneuropathy.
In other individual case reports, acute salivary gland swelling, dizziness, headache, somnolence, interstitial pneumonia, epigastric distress, peripheral edema, nodular arteritis, lymph node enlargement, alopecia and insulin autoimmune syndrome (dramatic drop in blood glucose levels) have been observed.
In addition, reducing the pathologically increased energy expenditure in hyperthyroidism can lead to weight gain (which is usually expected). Patients should be informed that energy expenditure will normalize as clinical symptoms improve.
Contraindications
Propylthiouracil is contraindicated in patients with known hypersensitivity reactions to propylthiouracil or any other component of this product.
It is contraindicated in patients with severe hepatic impairment, severe leukocyte deficiency, or hypersensitivity to thioureas.
Precautions]
Warning
1. Hepatotoxicity: Hepatic failure, liver transplantation or death due to liver injury has been reported in adult and pediatric patients treated with propylthiouracil. No cases of hepatic failure have been reported in pediatric patients treated with methimazole. Therefore, propylthiouracil is not recommended for pediatric patients unless methimazole is not tolerated and surgery or radioiodine therapy is not indicated.
Because of the rapid and unpredictable onset of severe liver injury, biochemical monitoring of liver function (bilirubin, alkaline phosphatase) and hepatocyte integrity (ALT, AST) cannot reduce the risk of developing severe liver injury. Patients should be informed of the risk of liver failure. Patients should be instructed to report any symptoms of abnormal liver function (anorexia, pruritus, right upper abdominal pain, etc.), especially during the first six months of treatment. When these symptoms occur, propylthiouracil should be discontinued immediately and liver function, ALT and AST levels should be checked.
Use with caution in patients with abnormal liver function.
2. Use in pregnant women: Cases of liver injury, including liver failure and death, have been reported in women treated with propylthiouracil during pregnancy. Two cases of intrauterine exposure with hepatic failure and neonatal death have been reported. If propylthiouracil is administered during pregnancy or if pregnancy occurs while propylthiouracil is administered, patients should be warned of the potential hazard of causing liver injury to the mother and fetus, although it is rare.
When administered to pregnant women, propylthiouracil can cross the placenta and can cause fetal goiter and cretinism.
After early pregnancy, replacement with other antithyroid drugs is recommended.
In pregnant women with untreated or inadequately treated Graves’ disease, there is an increased risk of maternal heart failure, spontaneous abortion, preterm delivery, stillbirth, and adverse events of fetal or neonatal hyperthyroidism.
If propylthiouracil is used during pregnancy, or if pregnancy occurs while propylthiouracil is being used, patients should be warned of the potential, albeit rare, hazard of propylthiouracil causing liver damage to the mother and fetus.
Because propylthiouracil can cross the placental membrane and induce goiter and ketosis in the developing fetus, it is important that adequate therapeutic doses but not excessive doses be given during pregnancy. In many pregnant women, thyroid dysfunction decreases as pregnancy continues; therefore, the dose can be reduced. In some cases, antithyroid therapy may be discontinued weeks or months before delivery.
Because methimazole may be associated with rare fetal malformations, propylthiouracil may be the drug of choice in early pregnancy. Considering that propylthiouracil may be hepatotoxic to the mother, it is advisable to consider switching from propylthiouracil to methimazole therapy in the middle and late stages of pregnancy.
3. Granulocytic leukocyte deficiency: The incidence of granulocytic leukocyte deficiency/reduction is about 0.2% to 0.5%, which is a potentially life-threatening adverse effect of propylthiouracil treatment, so the blood picture should be checked regularly during the drug administration. Use with caution if peripheral blood leukocytes are low. When the leukocyte count is lower than 4×109/L or neutrophils are lower than 1.5×109/L, the drug should be discontinued or adjusted according to medical advice. Granulocytic leukocyte deficiency usually occurs within the first 3 months of treatment. Patients should be instructed to immediately report any symptoms suggestive of granulocytic leukocyte deficiency, such as fever or sore throat. Leukopenia, thrombocytopenia, and aplastic anemia (holocytopenia) are also possible. In case of suspected granulocytic leukopenia, aplastic anemia (holocytopenia), propylthiouracil should be discontinued and the patient’s bone marrow indicators should be monitored.
4. Vasculitis: Cases of serious complications and death due to vasculitis have been reported in patients treated with propylthiouracil. Cases of vasculitis include: glomerulonephritis, leukocyte fragmentation cutaneous vasculitis, alveolar/pulmonary hemorrhage, cerebral vasculitis and ischemic colitis. Most cases are associated with anti-neutrophil cytoplasmic antibody (ANCA)-positive vasculitis. In some cases, vasculitis resolves/improves with drug discontinuation; however, more severe cases require additional therapeutic measures, including corticosteroids, immunosuppressive therapy, and plasmapheresis. If vasculitis is suspected, treatment should be discontinued and appropriate interventions should be initiated.
5. Hypothyroidism: Propylthiouracil can cause hypothyroidism and requires regular monitoring of TSH and free T4 levels and dose adjustment to maintain normal thyroid function. The use of propylthiouracil in pregnant women can cause fetal goiter and cretinism because the drug easily crosses the placental membrane (see Precautions, Use in Pregnancy).
General matters
1. Monitoring and reporting: Patients should be instructed to report any symptoms of abnormal liver function (anorexia, pruritus, jaundice, light-colored stools, dark urine, right upper abdominal pain, etc.), especially during the first six months of treatment. When these symptoms occur, liver function (bilirubin, alkaline phosphatase) and hepatocyte integrity (ALT/AST levels) should be monitored.
Patients treated with propylthiouracil should be closely supervised and should be informed of the need to report immediately any signs of illness, especially sore throat, rash, fever, headache or general malaise. In such cases, white blood cell counts and sorting counts should be checked to confirm the diagnosis of granulocytic leukocyte deficiency that has occurred. Special care should be taken if the patient is co-administering medications that have a clear association with granulocytic leukocyte deficiency.
2. Patient instructions: Patients should be informed that if they become pregnant or plan to become pregnant while on antithyroid medication, they should immediately report their therapy to their physician.
Patients should be informed that serious complications and deaths due to vasculitis have occurred during the propylthiouracil treatment period. Advise patients to promptly report symptoms that may be associated with vasculitis, including new-onset rash, hematuria or decreased urine output, dyspnea, or hemoptysis (see Warnings and Adverse Reactions).
3. Laboratory tests: Because propylthiouracil can cause hypoprothrombinemia and bleeding, monitoring of prothrombin time should be considered during drug therapy, especially prior to surgical procedures.
Thyroid function should be checked periodically during the treatment period. Once clinical evidence of hyperthyroidism has resolved, detection of elevated serum TSH levels indicates that a lower maintenance dose of propylthiouracil should be administered.
Interference with diagnosis: prolongs prothrombin time and increases AST, ALT, ALP, Bil.
4. Carcinogenicity, mutagenicity, fertility impairment: Experimental animals administered with propylthiouracil for more than 1 year have shown thyroid hyperplasia and cancer formation. Such animal test results can be observed when adequate doses of various antithyroid drugs are administered, as well as under conditions such as iodine-deficient diet, major thyroidectomy, and implantation of autonomic thyrotropin-secreting pituitary tumors, with persistent suppression of thyroid function. Pituitary adenomas have also been documented.
5. Lactating women: The infant may be affected by the use of the drug during lactation and requires special observation. During lactation, if anti-thyroid medication is necessary, this product may be used as an optional treatment. Propylthiouracil tablets may be administered during lactation because the concentration of the drug in breast milk is at most 1/10 of the serum drug concentration in the mother, but the infant should be specially monitored because individual cases of hypothyroidism have been reported.
6. Pediatric Use: In the pediatric population, cases of serious liver injury, including reports of liver failure requiring liver transplantation or resulting in death, have been reported post-marketing (see WARNINGS). No such reports have been observed with methimazole treatment. Therefore, propylthiouracil is not recommended for use in pediatric patients unless methimazole is not tolerated and surgical or radioiodine therapy is not indicated.
When used in children, parents and patients should be informed of the risk of liver failure. Patients taking propylthiouracil who develop fatigue, nausea, anorexia, fever, pharyngitis, or discomfort should discontinue propylthiouracil immediately and contact their physician to have their white blood cell count, liver function, and transaminase levels checked.
[For pregnant and lactating women].
Use in Pregnant Women
In pregnant women with untreated or inadequately treated Graves’ disease, there is an increased risk of maternal heart failure, spontaneous abortion, preterm delivery, stillbirth, and fetal or neonatal hyperthyroidism as adverse events.
Cases of liver injury, including liver failure and death, have been reported in women treated with propylthiouracil during pregnancy. Two cases of intrauterine exposure with liver failure and neonatal death have been reported.
If propylthiouracil is used during pregnancy, or if pregnancy occurs while propylthiouracil is being used, patients should be warned of the potential, albeit rare, hazard of liver injury to the mother and fetus from propylthiouracil.
Because propylthiouracil can cross the placental membrane and induce goiter and ketosis in the developing fetus, it is important that adequate therapeutic doses but not excessive doses be given during pregnancy. In many pregnant women, thyroid dysfunction decreases as pregnancy continues; therefore, the dose can be reduced. In some cases, antithyroid therapy may be discontinued weeks or months before delivery.
Because methimazole may be associated with rare fetal malformations, propylthiouracil may be the drug of choice in early pregnancy. Considering the possible maternal hepatotoxicity of propylthiouracil, conversion of propylthiouracil to methimazole therapy may be considered in mid- and late pregnancy.
Dosage for nursing women.
The infant may be affected by the use of the drug during lactation and will require special observation. During lactation, if antithyroid drugs are necessary, treatment with this product may be applied as an option. Propylthiouracil tablets may be administered during lactation because the concentration of the drug in breast milk is at most 1/10 of the serum drug concentration in the mother, but the infant should be specially monitored because hypothyroidism has been reported in isolated cases.
[Children’s medication].
Propylthiouracil is not recommended for pediatric patient groups except in rare cases where no other suitable alternative therapy is available. Doses as low as 50 mg/day have been reported in the foreign literature, although cases of severe liver injury have occurred, most cases have occurred at doses above 300 mg/day. See [Precautions] for details.
Geriatric Use]
Clinical studies of propylthiouracil did not enroll sufficient numbers of older adults over 65 years of age to determine whether their response differed from that of younger subjects. In other reported clinical trials, no response differences were observed between older and younger patients.
In general, dosing in older patients should be chosen with caution, taking into account the greater chance of decreased hepatic, renal, and cardiac function in the elderly and the greater chance of comorbid diseases or other medications. The dose of medication should be reduced in the elderly, especially in those with reduced renal function. If hypothyroidism is found, thyroid tablets should be added.
[Drug Interactions].
Anticoagulants (oral): The activity of oral anticoagulants (e.g. warfarin) may be enhanced because propylthiouracil inhibits the activity of vitamin K; additional monitoring of PT/INR should be considered, especially prior to surgical procedures.
Beta-adrenergic blockers: hyperthyroidism may lead to increased clearance of beta-blockers with high extraction rates. The dose of beta-adrenergic blockers may need to be reduced in patients with hyperthyroidism who transition to normal thyroid function.
Sulfasalazine, para-aminosalicylic acid, paterazone, barbiturates, phentolamine, tolazoline, vitamin B12, and sulfonylureas have thyroid suppressing and goitre causing effects, so care should be taken when combining this product.
Digitalis glycosides: Serum digitalis levels may increase when patients with hyperthyroidism on a stable digitalis glycoside regimen transition to normal thyroid function; dose reduction of digitalis glycosides may be required.
Theophylline: Theophylline clearance may decrease when patients with hyperthyroidism on a stable theophylline regimen transition to normal thyroid function; a reduction in the dose of theophylline may be required.
Iodine: Intake of foods or medications high in iodine can worsen hyperthyroidism and increase the need for or duration of antithyroid medication; therefore, iodine should be avoided prior to taking this product.
This product may change the effective amount of the derivatives of the psilocybin and coumarin in the blood.
Drug overdose]
Signs and symptoms
Nausea, vomiting, epigastric discomfort, headache, fever, arthralgia, pruritus, edema and pancytopenia. Granulocytic leukopenia is the most serious drug effect. Rarely, exfoliative dermatitis, hepatitis, neuropathy or central nervous system irritation or depression may occur.
Information is not available on the LD50; the concentration of propylthiouracil in biological fluids associated with toxicity and/or death; the amount of a single dose of drug usually associated with overdose symptoms; or the amount of a single dose of propylthiouracil that may be life-threatening.
Treatment
The potential for multiple drug overdoses, drug-drug interactions, and abnormal pharmacokinetic profiles in patients should be considered when managing drug overdoses.
If an overdose occurs, appropriate supportive therapy should be initiated as directed by the patient’s medical condition. Chronic overdose can lead to goiter and hypothyroidism and concomitant symptoms, in which case the medication should be discontinued. If the degree of hypothyroidism is severe or the goiter is significant, thyroxine supplementation is necessary. Generally, thyroid function will recover on its own after discontinuation of medication.
Pharmacology and Toxicology
Pharmacological effects
Propylthioxypyrimethamine inhibits peroxidase in the thyroid gland, thereby preventing the iodination of tyrosine and the condensation of iodinated tyrosine in the thyroid gland, thereby inhibiting the synthesis of thyroxine. Also, it inhibits the change of T4 to T3 in peripheral tissues, resulting in a relatively rapid decrease in the level of the more active T3 in serum.
Toxicological studies
Thyroid hyperplasia and tumor formation were seen in animals given propylthiouracil for more than 1 year. Such animal findings were seen when adequate doses of various antithyroid drugs, iodine-deficient diets, major thyroidectomy and implantation of autonomic thyrotropin-secreting pituitary tumors were administered, accompanied by persistent suppression of thyroid function.
Pharmacokinetics]
It is readily absorbed orally and distributed throughout the body, reaching the thyroid gland 20-30 minutes after administration. 60% is metabolized in the liver; T1/2 is 2 hours. The product can be excreted through placenta and milk.
Storage】Store under light and seal.
Package】High density polyethylene bottle for oral solid medicine, 100 tablets/bottle/box.
Expiration date】24 months
Execution Standard
Approval Number】State Drug Administration H31021082
Drug marketing license holder
Name: Shanghai Chaohui Pharmaceutical Co.
Registered Address: No. 2151 Fuyuan Road, Baoshan District, Shanghai
Postal Code: 201908
Contact: 021-66866679
Fax: 021-66866679
Web address: http://www.zhpharma.com
Manufacturer
Company name: Shanghai Chaohui Pharmaceutical Co.
Address: No. 2151, Fuyuan Road, Baoshan District, Shanghai
Postal Code：201908
Contact：021-66866679
Fax: 021-66866679
Web address: http://www.zhpharma.com