Drug class: Antithyroid Agents
ATC class: H03BA02
VA class: HS852
CAS number: 51-52-5

Medically reviewed by Drugs.com on Nov 17, 2023. Written by ASHP.

Introduction

Antithyroid agent;¹⁰⁹ thiourea-derivative.^b

Uses for Propylthiouracil

Hyperthyroidism

Used in patients with Graves’ disease with hyperthyroidism or toxic multinodular goiter who are intolerant of methimazole and for whom surgery or radioactive iodine therapy is not an appropriate treatment option.¹⁰⁹

Amelioration of symptoms of hyperthyroidism in preparation for thyroidectomy or radioactive iodine therapy in patients who are intolerant of methimazole.¹⁰⁹

Propylthiouracil is associated with a higher risk for clinically serious or fatal liver injury compared with methimazole in adult and pediatric patients; therefore, when initiating hyperthyroid treatment, reserve propylthiouracil for patients who cannot tolerate methimazole and for whom radioactive iodine therapy or surgery are not appropriate for the management of hyperthyroidism.^{100 112 100 103 107 109 112 118} (See Boxed Warning and also see Hepatotoxicity under Cautions.)

Not recommended for use in pediatric patients except in rare instances in which methimazole is not well tolerated and surgery or radioactive iodine therapy are not appropriate therapies.^{100 103 106 109 112} (See Pediatric Use under Cautions.)

Preferred agent when an antithyroid drug is indicated during or just prior to the first trimester of pregnancy because of the risk of fetal abnormalities associated with methimazole.^{100 103 107 108 109 112 118 119} For second and third trimesters (i.e., after first trimester), may be preferable to switch from propylthiouracil to methimazole because of the risk of adverse maternal effects associated with propylthiouracil (e.g., hepatotoxicity).^{108 109 118 119} (See Fetal/Neonatal Morbidity and also see Pregnancy under Cautions.)

Therapy with thioamide antithyroid agents (e.g., propylthiouracil, methimazole) maintains patients with Graves’ disease in euthyroid state for a period of several (generally 1–2) years until spontaneous remission occurs;^{118 b} however, spontaneous remission does not occur in all patients, and most eventually require ablative therapy (i.e., surgery, radioactive iodine).^b Thioamide antithyroid agents do not affect underlying cause of hyperthyroidism. Minimum duration of therapy necessary before assessing whether spontaneous remission has occurred not clearly established;^b however, some clinicians consider a treatment duration of 12–18 months to be optimal.^{122 123 124 125}

Therapy with propylthiouracil returns hyperthyroid patient to a normal metabolic state prior to thyroidectomy and controls the thyrotoxic crisis that may accompany thyroidectomy.^b

Therapy with propylthiouracil controls the symptoms of hyperthyroidism before and after radioactive iodine therapy until the ablative effects of iodine occur.^{123 129 130 131 b} However, beneficial and detrimental effects and optimal sequencing of antithyroid drugs before or after radioactive iodine therapy not clearly established.¹²⁹ Pretreatment with propylthiouracil may increase radioresistance of thyroid and risk of radioactive iodine treatment failure.^{118 123 129 130}

Does not induce remission in patients with nodular thyroid disease (i.e., toxic adenoma^{† [off-label]}, toxic multinodular goiter); discontinuance of therapy results in relapse.¹¹⁸ Therefore, some clinicians suggest that adults with overt toxic adenoma or toxic multinodular goiter be treated with either radioactive iodine therapy or thyroidectomy.¹¹⁸

Thyrotoxic Crisis

May be used for management of thyrotoxic crisis;^{103 109 118 b} preferred over methimazole because of its ability to inhibit peripheral conversion of thyroxine [T₄] to triiodothyronine [T₃].^{103 118} Usually initiated before iodide (e.g., potassium iodide, strong iodine solution) therapy.^b

Alcoholic Liver Disease

Has been studied in patients with alcoholic liver disease^{† [off-label]}.¹¹⁶

No substantial benefit has been demonstrated on any clinically important outcomes of alcoholic liver disease (e.g., all-cause mortality, liver-related mortality, complications associated with the liver disease, liver histology); currently available evidence does not support its use outside of randomized clinical studies.¹¹⁶

Propylthiouracil Dosage and Administration

General

Concomitant Therapy

• May use a β-adrenergic blocking agent (e.g., propranolol) concomitantly to manage peripheral signs and symptoms of hyperthyroidism, particularly cardiovascular effects (e.g., tachycardia).^b

Administration

Administer orally.¹⁰⁹

Oral Administration

Manufacturer recommends administering total daily dosage in 3 equally divided doses at approximately 8-hour intervals.¹⁰⁹ More frequent administration (e.g., at 4- or 6-hour intervals) may be necessary in some cases.^b

Dosage

Pediatric Patients

Hyperthyroidism

Oral

Generally not recommended for use in pediatric patients except in rare instances in which alternative therapies are not appropriate options.¹⁰⁹ (See Pediatric Use under Cautions.) Although studies evaluating appropriate dosage regimens not conducted in pediatric population, manufacturer states that general practice would suggest initiation of therapy in children ≥6 years of age at 50 mg daily with careful upward titration based on clinical response and evaluation of TSH and free T4 concentrations.¹⁰⁹

Severe liver injury reported with dosages as low as 50 mg daily, but most cases were associated with dosages of ≥300 mg daily.¹⁰⁹ (See Hepatotoxicity under Cautions.)

Adults

Hyperthyroidism

Graves’ Disease with Hyperthyroidism or Toxic Multinodular Goiter

Oral

Initially, 300 mg daily, usually given in 3 equally divided doses at approximately 8-hour intervals.¹⁰⁹ For patients with severe hyperthyroidism and/or very large goiters, initial dosage may be increased to 400 mg daily;¹⁰⁹ occasionally, an initial dosage of 600–900 mg daily may be required.¹⁰⁹ Alternatively, for treatment of Graves’ disease, some clinicians recommend an initial dosage of 50–150 mg 3 times daily, depending on severity of hyperthyroidism.¹¹⁸

Considerable improvement or normal thyroid function generally achieved following 4–12 weeks of therapy, after which dosage may be decreased while maintaining normal thyroid function.^{118 122 123 124} Carefully adjust subsequent dosage according to patient’s tolerance and therapeutic response.^b (See Laboratory Monitoring under Cautions.)

Usual maintenance dosage: Manufacturer recommends 100–150 mg daily, usually given in 3 equally divided doses at approximately 8-hour intervals.¹⁰⁹ Alternatively, as clinical findings and thyroid function tests return to normal, some clinicians suggest a maintenance dosage of 50 mg 2 or 3 times daily.¹¹⁸

Optimum duration of antithyroid therapy not clearly established.^b However, some clinicians consider a treatment duration 12–18 months to be optimal in patients with Graves’ disease.^{122 123 124 125}

Preparation for Thyroidectomy

Oral

Initially, 300 mg daily, usually given in 3 equally divided doses at approximately 8-hour intervals.¹⁰⁹ For patients with severe hyperthyroidism and/or very large goiters, initial dosage may be increased to 400 mg daily;¹⁰⁹ occasionally, an initial dosage of 600–900 mg daily may be required.¹⁰⁹

Discontinue propylthiouracil at time of procedure.¹¹⁸

Preparation for Radioactive Iodine Therapy

Oral

Initially, 300 mg daily, usually given in 3 equally divided doses at approximately 8-hour intervals.¹⁰⁹ For patients with severe hyperthyroidism and/or very large goiters, usual initial dosage may be increased to 400 mg daily;¹⁰⁹ occasionally, an initial dosage of 600–900 mg daily may be required.¹⁰⁹

Some clinicians recommend discontinuing propylthiouracil 2–7 days before administration of radioactive iodine; may restart propylthiouracil 3–7 days after radioactive iodine therapy, then discontinue propylthiouracil once thyroid function normalizes.^{122 123 130}

Thyrotoxic Crisis

Oral

Some clinicians recommend a loading dose of 500 mg to 1 g, followed by 250 mg every 4 hours.¹¹⁸

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.¹⁰⁹

Renal Impairment

No specific dosage recommendations at this time.¹⁰⁹

Geriatric Patients

Select dosage with caution because of the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy.¹⁰⁹ (See Geriatric Use under Cautions.)

Pregnancy

If used during pregnancy for management of hyperthyroidism, a sufficient, but not excessive, dosage is necessary.¹⁰⁹ Thyroid dysfunction diminishes in many women as pregnancy proceeds; reduction in dosage may be possible, and, in some patients, propylthiouracil can be discontinued several weeks or months before delivery.¹⁰⁹ (See Pregnancy under Cautions and also see Hepatotoxicity under Cautions.)

Cautions for Propylthiouracil

Contraindications

• Known hypersensitivity to propylthiouracil or any ingredient in the formulation.¹⁰⁹

Warnings/Precautions

Warnings

Hepatotoxicity

Liver injury (including severe liver injury) resulting in hepatitis, liver failure (including acute liver failure), liver transplantation, or death reported in adult and pediatric patients.^{100 101 102 103 104 106 107 109 112} (See Boxed Warning.) FDA has concluded that use of propylthiouracil is associated with a higher risk for clinically serious or fatal liver injury compared with methimazole in both adult and pediatric patients.¹¹²

No cases of liver failure reported with use of methimazole in pediatric patients; therefore, propylthiouracil not recommended for use in pediatric patients except in rare instances in which methimazole is not well tolerated and surgery or radioactive iodine therapy are not appropriate therapies.¹⁰⁹ (See Pediatric Use under Cautions.)

Cases of liver injury, including liver failure and death, reported in women receiving propylthiouracil during pregnancy.¹⁰⁹ Two cases of in utero exposure with liver failure and death of a newborn also reported.¹⁰⁹ Use of an alternative antithyroid drug (e.g., methimazole) may be advisable after the first trimester of pregnancy.¹⁰⁹ (See Fetal/Neonatal Morbidity and also see Pregnancy under Cautions.)

Extent of propylthiouracil-induced hepatitis and true incidence of severe liver injury not known.^{104 107}

Propylthiouracil-induced liver failure may occur at any time during therapy with a sudden onset, rapid progression, and a low chance of reversibility;^{103 104} liver failure has been observed after 6–450 days of propylthiouracil therapy (median: 120 days).¹⁰⁷

Effect of dosage on risk of hepatotoxicity not clearly elucidated;¹⁰⁴ however, reported average daily dosage associated with liver failure was approximately 300 mg in both children and adults.¹⁰⁷

Perform liver function tests (e.g., alkaline phosphatase, aminotransferase, bilirubin) prior to initiating therapy in patients with Graves’ disease.¹¹⁸

Routine biochemical monitoring of liver function (bilirubin, alkaline phosphatase) and hepatocellular integrity (ALT, AST) may not be effective in identifying patients at risk of liver failure and is not expected to attenuate risk of severe liver injury due to its rapid and unpredictable onset; however, should be performed in symptomatic patients.^{103 104 107 109 118}

Closely monitor patients for signs and symptoms of liver injury (e.g., fatigue, weakness, vague abdominal pain, right upper quadrant pain, anorexia, pruritus, easy bruising, jaundice, pruritic rash, light-colored stool, dark urine, joint pain, bloating, nausea), particularly during the first 6 months following initiation of therapy.^{100 109 112 118} If such symptoms occur, immediately discontinue the drug, evaluate the patient for evidence of liver injury (including evaluation of liver function [bilirubin, alkaline phosphatase] and hepatocellular integrity [ALT, AST]), and provide supportive care.^{100 109 118}

Some clinicians recommend discontinuing propylthiouracil if aminotransferase concentrations (whether elevated at initiation of therapy, found incidentally, or measured as clinically indicated) increase to 2–3 times the ULN and fail to improve within 1 week with repeat testing.¹¹⁸ After discontinuing the drug, monitor liver function (i.e., alkaline phosphatase, bilirubin, transaminases) weekly until there is evidence of resolution.¹¹⁸ If resolution is not evident, promptly refer patient to a gastroenterologist or hepatologist.¹¹⁸

Hematologic Effects

Risk of agranulocytosis;¹⁰⁹ usually occurs within first 3 months of therapy,¹⁰⁹ but rarely may occur after 4 months of therapy.^b May occur irrespective of dosage, length of treatment, or previous exposure to antithyroid drug, and may occur more frequently in geriatric patients.^{122 123}

Leukopenia, thrombocytopenia, and aplastic anemia (pancytopenia) may occur.¹⁰⁹ Hypoprothrombinemia and bleeding also may occur.¹⁰⁹ (See Laboratory Monitoring under Cautions.)

Perform baseline CBC, including white count with differential, prior to initiating therapy in patients with Graves’ disease.¹¹⁸

Monitor patient carefully for signs or symptoms of illness (e.g., sore throat, skin eruptions, fever, chills, headache, general malaise), particularly during the early stages of therapy.^b If fever, sore throat, or other signs or symptoms of illness occur, determine leukocyte and differential counts to assess whether agranulocytosis has developed.^{109 b} When evaluating myelopoietic response to propylthiouracil, consider that leukopenia (i.e., WBC <4000/mm³) occurs in 10% of untreated hyperthyroid patients and is often associated with relative granulocytopenia.^{109 b}

If agranulocytosis, aplastic anemia (pancytopenia), or fever is suspected, discontinue propylthiouracil and obtain bone marrow indices.¹⁰⁹ In patients who develop agranulocytosis or other serious adverse effects while receiving propylthiouracil or methimazole, use of the other drug is contraindicated because of risk of cross-sensitivity between the two drugs.¹¹⁸

Hypothyroidism

May cause hypothyroidism necessitating routine monitoring of TSH and free T₄ concentrations with dosage adjustments to maintain a euthyroid state.¹⁰⁹

May cause fetal goiter and cretinism when administered to a pregnant woman, because the drug readily crosses the placenta.¹⁰⁹ (See Fetal/Neonatal Morbidity and also see Pregnancy under Cautions.)

Fetal/Neonatal Morbidity

May cause fetal harm (i.e., induction of goiter, hypothyroidism, or cretinism).^{109 113}

Congenital malformations reported approximately 3 times more often with prenatal exposure to methimazole compared with propylthiouracil.¹¹² Distinct and consistent pattern of congenital malformations associated with the use of methimazole, but not with propylthiouracil, particularly craniofacial malformations (e.g., scalp epidermal aplasia [aplasia cutis], facial dysmorphism, choanal atresia).¹¹² Specific birth defects were associated with use of methimazole during the first trimester of pregnancy and not found when the drug was administered later in pregnancy.¹¹² FDA has not found a consistent pattern of birth defects associated with use of propylthiouracil and has concluded there is no convincing evidence of an association between propylthiouracil use and congenital malformations, even with use during the first trimester.¹¹² (See Pregnancy under Cautions and also see Distribution under Pharmacokinetics.)

If used during pregnancy or if pregnancy occurs during therapy, apprise of rare potential hazard to the mother and fetus of liver damage; inform the patient of these potential risks and risks of methimazole-associated fetal malformations when considering antithyroid drug use during pregnancy.^{104 106 109} (See Hepatotoxicity under Cautions.)

Sensitivity Reactions

Cross-Sensitivity

Cross-sensitivity between thioamides may occur^{118 121} (i.e., in approximately 50% of patients switched from one thioamide agent to the other).¹²²

In patients who develop serious adverse effects (e.g., agranulocytosis) while receiving either propylthiouracil or methimazole, use of other drug also is contraindicated, because of risk of cross-sensitivity between the two drugs.¹¹⁸ In patients experiencing serious allergic reactions to propylthiouracil, use of the alternative antithyroid drug (i.e., methimazole) not recommended.¹¹⁸

General Precautions

Laboratory Monitoring

Before initiating thioamide therapy in patients with Graves’ disease, some clinicians recommend obtaining baseline free T₄ and TSH concentrations; CBC, including white count and differential; and liver function tests (e.g., alkaline phosphatase, aminotransferase, bilirubin).¹¹⁸ Routine biochemical monitoring of liver function (bilirubin, alkaline phosphatase) and hepatocellular integrity (ALT, AST) not expected to attenuate risk of severe liver injury, but should be performed in symptomatic patients.^{103 104 107 109 118} (See Hepatotoxicity under Cautions.)

Monitor thyroid function (e.g., serum free T₄, serum free or total T₃, TSH) periodically (e.g., every 4–8 weeks [with subsequent dosage adjustments as needed] until thyroid function is stable or patient is euthyroid); once euthyroidism is achieved, monitor thyroid function every 2–3 months.^{109 118 122 123 124} Serum TSH not a reliable parameter to monitor early in therapy because it may remain suppressed for several months after initiation of therapy despite normalization of free T₄ concentrations.^{118 122 123 124} A suppressed TSH concentration during this period does not indicate a need for dosage increase.¹²³ However, once hyperthyroidism resolves, decrease maintenance dosage if serum TSH is elevated.^{109 123} Monitoring serum T₃ concentrations may sometimes be useful for dosage adjustment; if total or free T₃ concentrations remain elevated despite low, normal, or reduced free T₄ concentrations, may need to increase antithyroid dosage.^{122 123 124}

Determine leukocyte and differential counts in patients who develop any signs or symptoms of illness (e.g., fever, sore throat) during therapy.^{109 b}

Consider monitoring PT during therapy, particularly before surgical procedures, because of possible risk of hypoprothrombinemia and bleeding.¹⁰⁹

Dermatologic Effects

Exfoliative dermatitis reported.¹⁰⁹ If exfoliative dermatitis is suspected, discontinue propylthiouracil.¹⁰⁹

Immunologic Effects

Vasculitic syndrome associated with the presence of antineutrophil cytoplasmic antibody (ANCA) reported.¹⁰⁹ Manifestations of ANCA-positive vasculitis may include rapidly progressive glomerulonephritis (crescentic and pauci-immune necrotizing glomerulonephritis) sometimes leading to acute renal failure, pulmonary infiltrates or alveolar hemorrhage, skin ulcers, and leukocytoclastic vasculitis.¹⁰⁹ If ANCA-positive vasculitis is suspected, discontinue propylthiouracil.¹⁰⁹

Pulmonary Effects

Interstitial pneumonitis reported.¹⁰⁹ If interstitial pneumonitis is suspected, discontinue propylthiouracil.¹⁰⁹

Specific Populations

Pregnancy

Category D.¹⁰⁹ (See Fetal/Neonatal Morbidity under Cautions and also see Distribution under Pharmacokinetics.)

Despite potential fetal hazard, antithyroid agents still considered therapy of choice for management of hyperthyroidism during pregnancy.^{108 118 119 122} Since methimazole may be associated with the rare development of fetal abnormalities (e.g., aplasia cutis, choanal atresia), propylthiouracil is preferred when an antithyroid drug is indicated during organogenesis, in the first trimester of pregnancy, or just prior to the first trimester of pregnancy.^{100 103 106 107 108 109 118 119} (See Boxed Warning and also see Fetal/Neonatal Morbidity under Cautions.) Switch patients receiving methimazole to propylthiouracil if pregnancy is confirmed in first trimester.¹¹⁹ May be preferable to switch from propylthiouracil to methimazole for the second and third trimesters (i.e., after the first trimester), because of potential adverse maternal effects of propylthiouracil (e.g., hepatotoxicity).^{108 109 118 119} (See Hepatotoxicity under Cautions.) If switching from propylthiouracil to methimazole, assess thyroid function after 2 weeks and then every 2–4 weeks thereafter.¹⁰⁸ Not known if risk of methimazole-induced aplasia cutis or embryopathy outweighs risk of propylthiouracil-induced hepatotoxicity.¹⁰⁴

If used during pregnancy, a sufficient, but not excessive, dosage is necessary.¹⁰⁹ Initiate or adjust antithyroid drug therapy to maintain maternal free T₄ concentrations at or just above the ULN of nonpregnant reference range, or to maintain total T₄ concentrations at 1.5 times the ULN or the free T₄ index in the ULN, while using lowest possible dosage.^{108 119} As thyroid dysfunction diminishes in many women as pregnancy proceeds, may be possible to reduce propylthiouracil dosage; in some patients, may discontinue propylthiouracil several weeks or months before delivery.¹⁰⁹

If used during pregnancy or if patient becomes pregnant while receiving the drug, apprise of rare potential hazard to the mother and fetus of liver damage; inform the patient of these potential risks and risks of methimazole-associated fetal malformations when considering antithyroid drug use during pregnancy.^{104 106 109} Although liver toxicity may appear abruptly, it is reasonable to monitor liver function every 3–4 weeks in pregnant women receiving propylthiouracil and to encourage patients to promptly report any new symptoms.¹⁰⁸

Lactation

Distributed into milk to a small extent and, therefore, likely does not result in clinically important doses to the nursing infant.^{109 110} Mean amount of propylthiouracil distributed into milk during 4 hours following single oral 400-mg dose in 9 lactating women was 0.025% (range: 0.007–0.077%) of the administered dose.^{109 110}

Generally compatible with breast-feeding; moderate dosages (i.e., <300 mg daily) appear to be safe.^{119 120 121 122} However, considered by some clinicians to be a second-line agent in nursing women because of concerns regarding severe hepatotoxicity (i.e., hepatic necrosis in either woman or child); methimazole is the preferred antithyroid drug in nursing women.^{118 119} If antithyroid drug is used in nursing women, some clinicians recommend administering drug after a feeding and in divided doses, and monitoring thyroid function of nursing infants.¹¹⁹

Pediatric Use

Postmarketing cases of severe liver injury, including hepatic failure requiring liver transplantation or resulting in death, reported in pediatric patients; however, no such reports observed with methimazole.^{109 117} Propylthiouracil not recommended for use in pediatric patients except in rare instances in which methimazole is not well tolerated and surgery or radioactive iodine therapy are not appropriate therapies.^{100 103 106 109} In addition, some experts state that alternative therapy should be considered for children who are currently receiving propylthiouracil and that it is reasonable and prudent to discontinue propylthiouracil use in children receiving this drug for the treatment of Graves’ disease.^{105 106}

When propylthiouracil is used in children, inform parents and patients of risk of liver failure.¹⁰⁹ If patients develop tiredness, nausea, anorexia, fever, pharyngitis, or malaise, immediately discontinue the drug, contact a clinician, and obtain WBC count, liver function tests, and transaminase concentrations.¹⁰⁹ (See Hepatotoxicity under Cautions.)

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.¹⁰⁹ Select dosage with caution due to greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy.¹⁰⁹

Common Adverse Effects

Rash,¹⁰⁹ urticaria,¹⁰⁹ pruritus,¹⁰⁹ abnormal hair loss,¹⁰⁹ skin pigmentation,¹⁰⁹ edema,¹⁰⁹ nausea,¹⁰⁹ vomiting,¹⁰⁹ epigastric distress,¹⁰⁹ loss of taste,¹⁰⁹ taste perversion,¹⁰⁹ arthralgia,¹⁰⁹ myalgia,¹⁰⁹ paresthesia,¹⁰⁹ headache,¹⁰⁹ drowsiness,¹⁰⁹ neuritis,¹⁰⁹ vertigo,¹⁰⁹ jaundice,¹⁰⁹ sialadenopathy,¹⁰⁹ lymphadenopathy.¹⁰⁹

Drug Interactions

Drugs Known to be Associated with Agranulocytosis

Use concomitantly with extreme caution.¹⁰⁹ (See Hematologic Effects under Cautions.)

Specific Drugs

Propylthiouracil Pharmacokinetics

Absorption

Bioavailability

Rapidly and readily absorbed from the GI tract following oral administration.^{109 b} Peak plasma concentrations attained within 1–1.5 hours;^b however, plasma concentrations do not appear to correlate with therapeutic effects.^b

Bioavailability is approximately 75%.^b

Distribution

Extent

Distribution into human body tissues and fluids not fully characterized; however, drug appears to be concentrated in the thyroid gland.^b

Readily crosses the placenta.^{109 b} (See Fetal/Neonatal Morbidity and also Pregnancy under Cautions.)

Distributed into milk to a small extent; extent of distribution is about 0.007–0.077% of a single orally administered dose.^{109 110 111} (See Lactation under Cautions.)

Elimination

Metabolism

Extensively metabolized to its glucuronide conjugate and other minor metabolites.^{109 b}

Elimination Route

35% of dose excreted in urine as unchanged drug and metabolites within 24 hours.^{109 b}

Half-life

Approximately 1–2 hours.^b

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).¹⁰⁹

Actions

• Inhibits the synthesis of thyroid hormones¹⁰⁹ by interfering with the incorporation of iodine into tyrosyl residues of thyroglobulin;^b also inhibits the coupling of these iodotyrosyl residues to form iodothyronine. ^b

  Exact mechanism(s) not fully elucidated; however, propylthiouracil may interfere with the oxidation of iodide ion and iodotyrosyl groups.^b

• Limited evidence suggests that coupling reaction is more sensitive to antithyroid agents than the iodination reaction.^b

• Does not inhibit the action of thyroid hormones already formed and present in the thyroid gland or circulation; also does not interfere with the effectiveness of exogenously administered thyroid hormones.^{109 b} Patients whose thyroid gland contains relatively high concentration of iodine (e.g., from prior ingestion or from administration during diagnostic radiologic procedures) may respond relatively slowly to antithyroid agents.^b

• Inhibits peripheral deiodination of T₄ to T₃.^{109 b}

Advice to Patients

• Importance of patient reading the manufacturer’s medication guide prior to initiating therapy with the drug and each time the prescription is refilled.^{112 113}

• Risk of liver failure.^{100 103 109 112} Importance of immediately discontinuing the drug and promptly contacting clinicians if signs and symptoms of liver injury or hepatic dysfunction (e.g., fatigue, weakness, vague abdominal pain, right upper quadrant pain, loss of appetite, itching, easy bruising, yellowing of the eyes or skin, pruritic rash, light-colored stool, dark urine, joint pain, bloating, nausea) occur, particularly in the first 6 months of therapy.^{100 103 109 112 118} (See Hepatotoxicity under Cautions.)

• Importance of informing clinicians immediately if signs or symptoms of illness (e.g., sore throat, skin eruptions, fever, chills, headache, general malaise) occur.^{109 b} Importance of immediately discontinuing the drug and contacting clinicians if signs or symptoms suggestive of agranulocytosis (e.g., fever, sore throat) occur.^{109 118} (See Hematologic Effects under Cautions.)

• Importance of patient not discontinuing propylthiouracil therapy unless instructed by their clinician.¹¹²

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹⁰⁹

• Importance of women immediately informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{109 112} Necessity for clinicians to advise women of rare potential hazard to the mother and fetus of propylthiouracil-associated liver toxicity, as well as risks of methimazole-associated fetal malformations when considering antithyroid drug use during pregnancy.^{104 106 109} (See Fetal/Neonatal Morbidity and also see Hepatotoxicity under Cautions.)

• Importance of informing patients of other important precautionary information.¹⁰⁹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Frequently asked questions

• How does propylthiouracil work?

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