Propylthiouracil (PTU) is an oral antithyroid agent. Propylthiouracil, a thio-urea derivative, differs both chemically and structurally from methimazole, another antithyroid agent. Antithyroid agents are indicated for various hyperthyroid conditions including maintenance of a euthyroid state in patients with Graves' disease or toxic multinodular goiter. Due to a risk for hepatotoxicity, PTU should be reserved for patients who can not tolerate methimazole and in whom radioiodine therapy or surgery are not appropriate treatments for the management of hyperthyroidism. An exception to this restriction is that PTU is generally the preferred agent in the first trimester of pregnancy, due to the known teratogenic effects of methimazole. Propylthiouracil was approved by the FDA in 1947.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Hazardous Drugs Classification
-NIOSH 2016 List: Group 2
-NIOSH (Draft) 2020 List: Table 2
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure and require additional protective equipment. Oral liquid drugs require double chemotherapy gloves and protective gown; may require eye/face protection.
Route-Specific Administration
Oral Administration
-Propylthiouracil, PTU is administered orally. The daily dose is generally divided into 3 equal parts and administered at regular intervals (generally every 8 hours).
Rectal Administration
NOTE: Rectal administration is usually reserved for thyrotoxic emergencies in patients unable to tolerate oral therapy.
Rectal Enema*:
-Dissolve eight 50-mg propylthiouracil tablets in 60 ml aqueous sodium phosphates solution (e.g., Fleet's Phospho-Soda).
Rectal Suppository*:
-Using eight 50-mg propylthiouracil tablets and sufficient hardfat (Withepsol H15), compound 4 suppositories containing 100 mg of propylthiouracil each.
-Moisten the suppository with water prior to insertion. If suppository is too soft because of storage in a warm place, chill in the refrigerator for 30 minutes or run cold water over it before removing the wrapper.
Leukopenia occurs in up to 15% of adults and 25% of children taking propylthiouracil. Patients are usually asymptomatic but may have persistent or severe fever or chills, throat infection, cough, or mouth sores. Lymphadenopathy and sialadenopathy have also been reported. Instruct patients to immediately report any evidence of illness, particularly sore throat, fever, or general malaise. Obtain white blood cell and differential counts if symptoms of an infection are present. Of note, approximately 10% of patients with untreated hyperthyroidism have leukopenia (white blood cell count < 4000/mm3) often with relative granulopenia. Therapy usually can be continued, but WBC counts should be monitored.
Agranulocytosis, pancytopenia, and/or aplastic anemia can occur with propylthiouracil, PTU. Agranulocytosis occurs in approximately 0.2-0.5% of patients and can be life-threatening. Discontinue propylthiouracil if agranulocytosis, aplastic anemia, pancytopenia, or fever is suspected, and obtain the patient's bone marrow indices. Instruct patients to immediately report any symptoms suggestive of agranulocytosis such as fever or sore throat. Most cases of agranulocytosis occur during the first 3 months of therapy and diminish significantly by 4 months of treatment. The risk for agranulocytosis increases substantially in patients older than 40 years of age and is not dose-related.
Hepatotoxicity, usually in the form of hepatitis, cholestatic jaundice, and/or hepatic necrosis, has occurred with propylthiouracil (PTU). Serious hepatic injury, including hepatic failure and fatalities, has also been reported in adults and children; liver transplantation has been required in some cases. PTU is associated with an unacceptable risk of hepatotoxicity in pediatric patients, with a risk of liver failure of 1 in 2,000 to 4,000 children and adolescents taking the medication. FDA Medwatch data indicate that pediatric patients are more susceptible to hepatotoxic reactions from PTU than are adults, and PTU is not recommended for treatment of pediatric patients unless no other treatments are acceptable. In patients experiencing hepatic toxicity, elevated hepatic enzymes may be present, and symptoms may include anorexia, nausea, vomiting, pruritus, jaundice, light colored stools, dark urine, right upper quadrant pain, etc. Immediately discontinue PTU and obtain bilirubin, alkaline phosphatase, ALT, and AST concentrations in the presence of hepatic dysfunction symptoms. Unfortunately, periodic laboratory monitoring of liver function and hepatocellular integrity is not expected to attenuate the risk of severe liver injury due to its rapid and unpredictable onset. Tell patients about the risk of hepatic failure, and instruct them to immediately report any symptoms of hepatic dysfunction, particularly in the first 6 months of therapy.
Adverse dermatologic reactions including rare reports of serious hypersensitivity reactions (e.g., Stevens-Johnson syndrome and toxic epidermal necrolysis) have been reported in patients receiving propylthiouracil, PTU. Rash (unspecified), alopecia, skin hyperpigmentation, urticaria, and pruritus occurred in < 1% of patients receiving propylthiouracil, PTU. Rarely, exfoliative dermatitis or erythema nodosum have been reported. Of note, pruritus may be a symptom of hepatic dysfunction. Rashes are often self-limiting and may be symptomatically managed. If exfoliative dermatitis or other serious skin reaction is suspected, discontinue propylthiouracil.
Arthralgia can occur in up to 5% of patients who receive propylthiouracil, PTU and can occur more frequently when higher doses are used. Myalgia may also occur. Children may have a higher incidence of these adverse reactions.
Hypothyroidism can occur with prolonged use of propylthiouracil, PTU although the incidence appears to be low. Periodically monitor thyroid function tests. The incidence of this adverse reaction can be minimized by using the smallest dose that controls thyrotoxicosis once euthyroidism is achieved. Some clinicians continue with the initial dosage and supplement propylthiouracil therapy with levothyroxine.
Propylthiouracil, PTU has led to the development of hypoprothrombinemia and bleeding episodes. Also, thrombocytopenia has been reported. Consider monitoring the prothrombin time during treatment with PTU, especially before surgical procedures.
Teratogenesis is less of a concern with propylthiouracil, PTU than with methimazole; PTU has been used for the management of hyperthyroidism during pregnancy since the 1940s. PTU is transferred across the placenta. Antithyroid drugs, including PTU, have been shown to cause goiter and hypothyroidism in the developing fetus, so maternal thyroid status requires close monitoring to avoid excessive dosage. There is also a risk for hepatotoxicity from PTU to the mother or the fetus. Hepatic injury, including hepatic failure and death, have been reported in women treated with PTU during pregnancy, and cases of in utero exposure with liver failure and death of a newborn have been reported. PTU is considered to have less risk of birth defects than methimazole, a drug for which teratogenic effects are well documented. Population studies note an increase in the rate of birth defects (2.3% above the background rate) observed after PTU exposure in early pregnancy, but these defects tended to be less severe than with methimazole. Because of the risk of fetal abnormalities associated with methimazole, propylthiouracil (PTU) is considered the treatment of choice when an antithyroid drug is indicated during or just prior to the first trimester of pregnancy. Methimazole should be used when antithyroid drug therapy is started after the first trimester, unless the patient is allergic or intolerant.
Peripheral neuropathy, paresthesias, headache, neuritis, vertigo, dysgeusia, taste loss, and drowsiness (CNS depression) have all been reported with propylthiouracil, PTU. CNS stimulation may also occur.
Interstitial nephritis, edema, glomerulonephritis, interstitial pneumonitis, periarteritis, and lupus-like symptoms including splenomegaly and vasculitis have been reported with propylthiouracil, PTU. Renal involvement may very rarely result in acute renal failure (unspecified). The cases of vasculitis include interstitial nephritis or glomerulonephritis, leukocytoclastic cutaneous vasculitis, pulmonary infiltrates or alveolar hemorrhage, cerebral angiitis, and ischemic colitis. Most cases were associated with anti-neutrophilic cytoplasmic antibodies (ANCA)-positive vasculitis. In milder cases, vasculitis resolved and/or improved with drug discontinuation; however, more severe cases required treatment with additional measures including corticosteroids, immunosuppressant therapy, and plasmapheresis. Discontinue PTU if vasculitis is suspected and initiate appropriate intervention.
Antithyroid agents, such as PTU, should be discontinued at least 3 to 4 days prior to treatment with radioiodine (sodium iodide, I-131). Typically, antithyroid agents are not reintroduced until 1 week after the radioiodine treatment.
Propylthiouracil (PTU) is contraindicated in patients with a history of hypersensitivity to the drug. Cross-hypersensitivity occurs in roughly 50% of patients who have previously exhibited a significant hypersensitivity to an antithyroid thioimidazole medication (i.e., methimazole). PTU has been associated with severe side effects. Agranulocytosis (severe neutropenia) occurs in approximately 0.2% to 0.5% of patients and is a potentially life-threatening side effect of PTU therapy. Agranulocytosis typically occurs within the first 3 months of therapy. Leukopenia, thrombocytopenia, and aplastic anemia (pancytopenia) may also occur. PTU should be discontinued if agranulocytosis, aplastic anemia (pancytopenia) is suspected, and the patient's bone marrow indices should be obtained. Use the drug with caution in patients with risk factors for bone marrow suppression and with extreme caution in combination with other drugs known to cause agranulocytosis. Baseline leukopenia occurs in 10% of untreated hyperthyroid patients and is not a contraindication for the use of PTU; however, a CBC and differential should be monitored periodically during PTU treatment. Propylthiouracil (PTU)-associated vasculitis may be severe and is normally associated with fever, sore throat, arthralgia, and skin lesions but may also involve multiple organ systems. Some cases have resulted in nephritis, interstitial pneumonitis, cerebral angiitis, other serious conditions, or death. Drug discontinuation may improve or resolve some cases of vasculitis; however, more severe cases require treatment with corticosteroids, immunosuppressant therapy, and plasmapheresis. If vasculitis is suspected, discontinue therapy and initiate appropriate intervention. Instruct patients taking PTU to immediately report any symptoms suggestive of hypersensitivity, vasculitis, or agranulocytosis, including fever or a sore throat, headache, skin eruptions, hematuria, decreased urine output, dyspnea, or hemoptysis to their prescriber.
Hepatotoxicity is a potential complication of propylthiouracil, PTU. Propylthiouracil can cause hepatic complications such as jaundice, fatal hepatic necrosis, and death. Severe hepatic injury and acute hepatic failure, in some cases fatal, have been reported; these events include cases requiring liver transplantation. Pediatric patients appear especially at risk. Patients with preexisting hepatic disease should receive propylthiouracil with caution, although there is no evidence that pre-existing hepatic disease increases the risk for severe hepatic reactions to PTU. When compared to methimazole, PTU has an increased risk of hepatotoxicity; however, the decision to initiate either therapy in patients with liver dysfunction with a new diagnosis of Grave's disease should be carefully considered. Experts do suggest that prescribers to reconsider whether to initiate PTU therapy in patients with baseline liver transaminase levels more than 5 times the upper level of normal (ULN). Biochemical routine monitoring of hepatocellular integrity/liver function tests (LFTs such as bilirubin, alkaline phosphatase, ALT, AST) is not expected to attenuate the risk of severe liver injury due to its rapid and unpredictable onset. Inform patients of the risk of liver failure. Patients on PTU therapy should be monitored for signs and symptoms of hepatic injury, especially during the first 6 months after drug initiation; discontinue PTU if clinical evidence of hepatic dysfunction (e.g., abdominal pain, anorexia, pruritus, light-colored stools, or LFT elevation, hepatitis) occurs. When these symptoms occur, discontinue PTU immediately and monitor LFTs.
Propylthiouracil (PTU) is associated with an unacceptable risk of hepatotoxicity in pediatric patients, with a risk of liver failure of 1 in 2,000 to 4,000 children and adolescents taking the medication. FDA Medwatch data indicate that pediatric patients are more susceptible to hepatotoxic reactions from PTU than are adults. For this reason, PTU propylthiouracil is not recommended for use in the pediatric population except in rare instances in which methimazole is not well-tolerated and surgery or radioactive iodine therapy are not appropriate. In children, there have been postmarketing reports of severe hepatic injury with doses as low as 50 mg/day; most cases, however, were associated with doses of 300 mg/day and higher. Reports include hepatic failure requiring liver transplantation or resulting in death in pediatric patients taking PTU. If PTU is used in children or adolescents, warn the patients and caregivers of the hepatic risk, and monitor for signs and symptoms of liver failure, including tiredness, nausea, anorexia, fever, pharyngitis, or malaise. Tell patients to contact their health care prescriber immediately. Discontinue PTU immediately if symptoms suggestive of liver injury develop, and obtain a white blood cell count, liver function tests, and transaminase levels. The safety and effectiveness of propylthiouracil, PTU in infants have not been established.
Female patients of childbearing potential should contact their physician immediately if pregnancy occurs or is desired; close monitoring of the thyroid condition and fetal health is needed. Because of the risk of fetal abnormalities associated with methimazole, propylthiouracil (PTU) may be the treatment of choice when an antithyroid drug is indicated during or just prior to the first trimester of pregnancy. Methimazole should be used when antithyroid drug therapy is started after the first trimester unless the patient is allergic or intolerant, as PTU does present health risks to the mother and the exposed fetus. PTU is transferred across the placenta. Antithyroid drugs, including PTU, have been shown to cause goiter and hypothyroidism in the developing fetus. There is also a risk for maternal or fetal hepatotoxicity from PTU. Hepatic injury, including hepatic failure and death, has been reported in women treated with PTU during pregnancy, and cases of in utero exposure with liver failure and death have been reported in neonates. PTU is considered to have less risk of birth defects than methimazole, a drug for which teratogenic effects are well documented. Population studies note an increase in the rate of birth defects (2.3% above the background rate) observed after PTU exposure in early pregnancy, but these defects tended to be less severe than with methimazole. The dosage of any antithyroid drug used during pregnancy should be closely monitored so that sufficient, but not excessive, the dosage is used to produce the desired clinical results. Because thyroid dysfunction may improve as pregnancy proceeds in some patients, it may be possible to discontinue PTU in the 2 to 3 months prior to delivery after careful clinical evaluation of thyroid function; hyperthyroidism may recur following delivery.
According to the American Thyroid Association (ATA) guidelines, propylthiouracil (PTU) may be used in breast-feeding individuals when necessary; low to moderate doses are recommended (up to 450 mg/day). A small, but detectable amount of PTU is transferred into breast milk and therefore the lowest effective dose should always be administered. The high protein binding and significant ionization at physiologic pH limits PTU distribution into breast milk versus other antithyroid agents (e.g., methimazole). In 1 study, lactating women (n = 9) were administered 400 mg PTU orally; the mean amount of PTU excreted into the breast milk during the 4 hours after drug administration was 0.025% of the administered dose. The ATA recommends that breastfed children of individuals who are treated with PTU be monitored for appropriate growth and development during routine pediatric health and wellness evaluations. Routine assessment of serum thyroid function in the child is not recommended.
Counsel patients about stopping biotin and biotin-containing supplements for at least 2 days prior to thyroid testing. Biotin in blood or other samples taken from patients who are ingesting higher biotin dosages (i.e., doses of 10 to 300 mg biotin/day) in dietary supplements, including multivitamins, prenatal vitamins, and supplements for hair, skin, and nail growth, can cause clinically significant laboratory test interference in assays that use biotin-streptavidin technology. One patient reportedly had abnormal thyroid function tests (TFTs) that did not match the clinical context after starting biotin. Within 3 days of stopping supplementation with biotin, repeated TFTs were normal. Then, biotin was reintroduced to the same patient, and TFTs taken 16 hours after the last dose and after an overnight fast showed further evidence of biotin immunoassay interference. Discuss dietary supplement intake, particularly those that may contain biotin, with patients and communicate to the lab conducting testing if the patient reports taking biotin-containing supplements. Consider laboratory test interference from biotin as a possible source of error if the lab test result does not match the clinical presentation of the patient and report any adverse events thought to be due to biotin interference to the lab test manufacturer and the FDA.
For the treatment of thyrotoxicosis, including hyperthyroidism, Graves' disease, toxic multinodular goiter, and thyroid storm*:
-for the treatment of thyrotoxicosis, including hyperthyroidism, Graves' disease, and toxic multinodular goiter:
Oral dosage:
Adults: 50 to 150 mg PO every 8 hours, initially. Initial doses of 600 to 900 mg/day are sometimes needed. Reduce dose as the patient becomes euthyroid. Usual maintenance dose: 50 mg PO 2 to 3 times daily. PTU is indicated as an alternative for persons who are intolerant of or allergic to methimazole or other therapies.
Children and Adolescents 6 to 17 years: 50 mg/day PO divided every 8 hours or 5 to 7 mg/kg/day PO divided every 8 hours, initially. Reduce dose as the patient becomes euthyroid. Usual maintenance dose: one-third to two-thirds of initial dose PO divided every 8 hours. Severe liver injury in children is usually associated with doses of 300 mg/day or more; however, cases have been reported with doses as low as 50 mg/day. Guidelines recommend methimazole in pediatric patients with thyrotoxicosis due to an unacceptable risk of hepatotoxicity associated with PTU in this population.
Infants* and Children* 1 to 5 years: 5 to 7 mg/kg/day PO divided every 8 hours, initially. Reduce dose as the patient becomes euthyroid. Usual maintenance dose: one-third to two-thirds of initial dose PO divided every 8 hours. Guidelines recommend methimazole in pediatric patients with thyrotoxicosis due to an unacceptable risk of hepatotoxicity associated with PTU in this population.
Neonates: 5 to 10 mg/kg/day PO divided every 8 hours. Guidelines recommend methimazole in pediatric patients with thyrotoxicosis due to an unacceptable risk of hepatotoxicity associated with PTU in this population.
-for the treatment of thyroid storm*:
Oral dosage:
Adults: 500 to 1,000 mg PO loading dose, then 250 mg PO every 4 hours.
Maximum Dosage Limits:
PTU has a narrow therapeutic window; individualize dosage. General max. doses for routine treatment of hyperthyroidism are listed. Higher doses in the treatment of thyrotoxicosis are typically necessary.
-Adults
900 mg/day PO; 1.2 grams/day PO in severe disease.
-Geriatric
900 mg/day PO; 1.2 grams/day PO in severe disease.
-Adolescents
300 mg/day PO or maximum based on weight: 7 mg/kg/day PO. If growth is complete, doses used may be similar to adult dosing.
-Children
11 years and older: 300 mg/day PO. Usual weight based maximum: 7 mg/kg/day PO.
6 to 10 years: 150 mg/day PO. Usual weight based maximum: 7 mg/kg/day PO.
Less than 6 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
10 mg/kg/day PO has been used off-label for neonatal Graves' disease.
Patients with Hepatic Impairment Dosing
While there is no evidence that pre-existing hepatic disease increases the risk of complications from propylthiouracil, PTU, experts suggest that a prescriber reconsider the use of PTU in a patient with liver transaminase (AST and/or ALT) levels more than 5-fold above the upper limit of normal (ULN). Discontinue PTU and evaluate the patient if evidence of hepatic dysfunction occurs during PTU use.
Patients with Renal Impairment Dosing
No dosage adjustment is needed; less than 10% of PTU is excreted unchanged in the urine.
*non-FDA-approved indication
Acebutolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Atenolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Atenolol; Chlorthalidone: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Beta-blockers: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Betaxolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Bisoprolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Brimonidine; Timolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Carteolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Carvedilol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Deferiprone: (Major) Avoid concomitant use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis, such as propylthiouracil, PTU; however, if this is not possible, closely monitor the absolute neutrophil count and interrupt deferiprone therapy if neutropenia develops.
Digoxin: (Minor) Serum concentrations of digoxin can increase as hyperthyroidism is corrected. In patients receiving antithyroid therapy, the dosage of digoxin may need to be reduced as the patient becomes euthyroid.
Dorzolamide; Timolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Esmolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Iodine; Potassium Iodide, KI: (Contraindicated) Potassium iodide should not be used concurrently with other antithyroid agents. Agents such as methimazole and propylthiouracil, PTU can increase the likelihood of hypothyroidism when used in combination with potassium iodide.
Iodoquinol: (Moderate) Iodoquinol should be used with caution in patients treated with thyroid agents. Iodine-containing compounds like iodoquinol may result in overt thyroid disease.
Labetalol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Levobunolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Levothyroxine: (Major) Antithyroid agents should generally not be administered with the thyroid hormones due to their opposing effects. However, in selected cases some clinicians co-administer T4 (e.g., levothyroxine) to circumvent drug-induced hypothyroidism when large suppressive doses of antithyroid agents are administered for long periods of time. However, clinical and biochemical euthyroid status may usually be maintained with careful titration of the antithyroid agent dosage alone.
Levothyroxine; Liothyronine (Porcine): (Major) Antithyroid agents should generally not be administered with the thyroid hormones due to their opposing effects. However, in selected cases some clinicians co-administer T4 (e.g., levothyroxine) to circumvent drug-induced hypothyroidism when large suppressive doses of antithyroid agents are administered for long periods of time. However, clinical and biochemical euthyroid status may usually be maintained with careful titration of the antithyroid agent dosage alone.
Levothyroxine; Liothyronine (Synthetic): (Major) Antithyroid agents should generally not be administered with the thyroid hormones due to their opposing effects. However, in selected cases some clinicians co-administer T4 (e.g., levothyroxine) to circumvent drug-induced hypothyroidism when large suppressive doses of antithyroid agents are administered for long periods of time. However, clinical and biochemical euthyroid status may usually be maintained with careful titration of the antithyroid agent dosage alone.
Liothyronine: (Major) Antithyroid agents should generally not be administered with the thyroid hormones due to their opposing effects. However, in selected cases some clinicians co-administer T4 (e.g., levothyroxine) to circumvent drug-induced hypothyroidism when large suppressive doses of antithyroid agents are administered for long periods of time. However, clinical and biochemical euthyroid status may usually be maintained with careful titration of the antithyroid agent dosage alone.
Macimorelin: (Major) Avoid use of macimorelin with drugs that may blunt the growth hormone response to macimorelin, such as antithyroid agents. Healthcare providers are advised to discontinue antithyroid therapy at least 1 week before administering macimorelin. Use of these medications together may impact the accuracy of the macimorelin growth hormone test.
Methylprednisolone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
Metoprolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Metoprolol; Hydrochlorothiazide, HCTZ: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Nadolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Nebivolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Nebivolol; Valsartan: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Pexidartinib: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with propylthiouracil. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
Pindolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Potassium Iodide, KI: (Contraindicated) Potassium iodide should not be used concurrently with other antithyroid agents. Agents such as methimazole and propylthiouracil, PTU can increase the likelihood of hypothyroidism when used in combination with potassium iodide.
Prednisone: (Moderate) The metabolism of corticosteroids is increased in hyperthyroidism and decreased in hypothyroidism. Dosage adjustments may be necessary when initiating, changing or discontinuing thyroid hormones or antithyroid agents.
Pretomanid: (Major) Avoid coadministration of pretomanid with propylthiouracil, especially in patients with impaired hepatic function, due to increased risk for hepatotoxicity. Monitor for evidence of hepatotoxicity if coadministration is necessary. If new or worsening hepatic dysfunction occurs, discontinue hepatotoxic medications.
Propranolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Riluzole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and propylthiouracil. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Sodium Iodide: (Contraindicated) The recent intake of antithyroid agents will affect the uptake of radioiodide from sodium iodide, I-131; patients must discontinue all medications and supplements that may interfere with iodide uptake into thyroid tissue prior to therapy with sodium iodide I-131. Various protocols are used. Many manufacturers state that concurrent antithyroid agents should be discontinued at least 3 to 4 days before administration of radioiodide. The following withdrawal timing recommendations were set forth in a procedure guideline published by the Society of Nuclear Medicine in February 2002. Antithyroid agents may affect iodide protein binding for an average of 5 days after administration; allow a 3 day wash out period for the antithyroid agent (e.g., PTU, methimazole) prior to sodium iodide I-131 administration. The antithyroid agent may be resumed 2 to 3 days after treatment.
Sotalol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Theophylline, Aminophylline: (Minor) Patients with hyperthyroidism may exhibit accelerated clearance of theophylline. Correction of hyperthyroidism can lead to a decrease in theophylline clearance. Theophylline serum concentrations should be monitored closely during the initial stages of treatment for hyperthyroidism.
Thyroid hormones: (Major) Antithyroid agents should generally not be administered with the thyroid hormones due to their opposing effects. However, in selected cases some clinicians co-administer T4 (e.g., levothyroxine) to circumvent drug-induced hypothyroidism when large suppressive doses of antithyroid agents are administered for long periods of time. However, clinical and biochemical euthyroid status may usually be maintained with careful titration of the antithyroid agent dosage alone.
Timolol: (Minor) Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid.
Warfarin: (Moderate) The interaction between thioamine antithyroid agents and warfarin is variable. Administration of propylthiouracil, PTU can reduce the effectiveness of warfarin. Conversely, the effects of warfarin can be enhanced due to the anti-vitamin K properties of propylthiouracil, PTU. Prothrombin times should be monitored closely. Warfarin dosage should be adjusted accordingly based on the INR and the clinical goals for the patient.
Propylthiouracil (PTU) directly interferes with the first step in thyroid hormone biosynthesis in the thyroid gland. By acting as a substrate for the catalyst thyroid peroxidase, propylthiouracil inhibits the incorporation of iodide into the thyroid hormone precursor, thyroglobulin. Consequently, the drug is iodinated and degraded within the thyroid gland. Oxidized iodine is diverted away from thyroglobulin, which effectively diminishes the biosynthesis of thyroid hormone. An additional mechanism is the inhibition of iodotyrosyl residues coupling to form thyroglobulin. Propylthiouracil may interfere with the oxidation of the iodide ion and iodotyrosyl groups. Eventually, thyroglobulin is depleted and circulating thyroid hormone levels diminish. Unlike methimazole, propylthiouracil inhibits the conversion of peripheral thyroxine (T4) to triiodothyronine (3). This action may be an advantage in the treatment of severe hyperthyroidism. Propylthiouracil does not, however, alter the action of existing thyroxine (T4) and triiodothyronine (T3) in the circulation or in the thyroid gland. Similarly, no alterations in the effectiveness of exogenously administered thyroid hormones have been observed.
Propylthiouracil (PTU) is administered orally. Propylthiouracil is actively concentrated by the thyroid gland following absorption. The drug is 60-80% protein-bound and is significantly ionized at physiologic pH. Because of higher protein binding and ionization, propylthiouracil has less placental transfer and distribution into breast milk than methimazole, and is often preferred over methimazole when treatment is needed in pregnant or lactating females.
The metabolism of PTU is complex due to the concentration of the drug in the thyroid gland. Extensive hepatic metabolism occurs via glucuronidation. The plasma elimination half-life of propylthiouracil is approximately 1 hour and is not appreciably altered by the patient's thyroid status. The drug persists in the thyroid gland despite the short plasma half life, thereby allowing an 8-hour or longer dosing interval. The drug and its metabolites are excreted partially via the kidney (35%); but only 10% or less of PTU is excreted as unchanged drug.
-Route-Specific Pharmacokinetics
Oral Route
Following administration, propylthiouracil is rapidly absorbed from the gastrointestinal tract with peak serum concentrations occurring in 1 hour. However, it usually takes 2-4 months of treatment to achieve initial euthyroid status; response rates are dependent on several pharmacodynamic and patient variables.
-Special Populations
Hepatic Impairment
Propylthiouracil (PTU) is metabolized extensively by the liver; use cautiously in hepatic disease as these patients may exhibit reduced drug clearance.
Renal Impairment
While clearance may be somewhat prolonged in patients with renal impairment, specific dosage adjustment of propylthiouracil in renal impairment is not recommended.