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Propylthiouracil: Drug information

Propylthiouracil: Drug information
(For additional information see "Propylthiouracil: Patient drug information" and see "Propylthiouracil: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Hepatotoxicity:

Severe liver injury and acute liver failure, in some cases fatal, have been reported in patients treated with propylthiouracil. These reports of hepatic reactions include cases requiring liver transplantation in adults and pediatric patients.

Reserve propylthiouracil for patients who cannot tolerate methimazole and in whom radioactive iodine therapy or surgery are not appropriate treatments for the management of hyperthyroidism.

Pregnancy:

Because of the risk of fetal abnormalities associated with methimazole, propylthiouracil may be the treatment of choice when an antithyroid drug is indicated during or just prior to the first trimester of pregnancy.

Brand Names: Canada
  • Halycil;
  • Propyl-Thyracil [DSC]
Pharmacologic Category
  • Antithyroid Agent;
  • Thioamide
Dosing: Adult
Hyperthyroidism associated with Graves disease

Hyperthyroidism associated with Graves disease:

Note: Preferred over methimazole during the first trimester of pregnancy; may also be used as chronic low-dose treatment in patients who have minor skin reactions to methimazole (eg, rash, hives) and do not wish to undergo definitive therapy (ie, radioactive iodine therapy or surgery) (ATA [Ross 2016]).

Use during pregnancy:

Oral: Initial: 50 mg 2 to 3 times daily; doses up to 300 mg/day may be required in patients with severe hyperthyroidism (ATA [Alexander 2017]; Ross 2022a).

Patients switching from methimazole therapy: 5 mg of methimazole is equivalent to ~100 mg of propylthiouracil (ATA [Alexander 2017]; ATA [Ross 2016]).

Dosage adjustment:

Note: Adjust dose based on thyroid function tests obtained every 4 weeks to maintain serum free T4 concentration at or just above the ULN (using a trimester-specific reference range) and serum TSH concentrations below the reference range for pregnancy (ATA [Alexander 2017]).

Usual maintenance dose: Oral: ≤50 mg twice daily (Ross 2022a).

Duration of therapy: After 16 weeks’ gestation, may switch to methimazole or continue propylthiouracil based on shared decision-making with the patient; may consider discontinuation of antithyroid drug therapy during the third trimester of pregnancy based on thyroid function tests and TSH-receptor antibody levels. Continue to monitor TSH and free or total T4 throughout pregnancy and in the postpartum period; Graves disease often worsens postpartum (ATA [Alexander 2017]; ATA [Ross 2016]).

Use in nonpregnant patients (eg, patients who have minor skin reactions to methimazole):

Initial dosage: Oral: 50 to 150 mg 3 times daily; doses up to 800 mg/day may be required in patients with severe hyperthyroidism (eg, free T4 ≥2 times ULN) (ATA [Ross 2016]; Burch 2018).

Patients switching from methimazole therapy: 5 mg of methimazole is equivalent to ~100 mg of propylthiouracil (ATA [Ross 2016]).

Dosage adjustment: Oral: Usual maintenance dose: 50 mg 2 to 3 times daily (ATA [Ross 2016]). Assess free T4 and total T3 at 4- to 6-week intervals; gradually adjust dose to achieve euthyroidism (Ross 2022b).

Duration of therapy:

Patients undergoing definitive therapy: Prior to definitive therapy, continue until euthyroid (typically 4 to 6 weeks); discontinue 2 to 3 days before radioactive iodine therapy or on the day of thyroidectomy (ATA [Ross 2016]).

Patients not undergoing definitive therapy: Continue therapy for a total of ~12 to 18 months, then assess for remission (ATA [Ross 2016]).

Hyperthyroidism

Hyperthyroidism: Oral: Initial: 300 mg daily in 3 equally divided doses (~8-hour intervals); 400 mg daily in patients with severe hyperthyroidism and/or very large goiters; an occasional patient will require 600 to 900 mg daily; usual maintenance: 100 to 150 mg daily in 3 equally divided doses.

Adjust dosage as required to achieve and maintain serum T3, T4, and TSH levels in the normal range. An elevated T3 may be the sole indicator of inadequate treatment. An elevated TSH indicates excessive antithyroid treatment.

Internal contamination with radioactive iodine

Internal contamination with radioactive iodine (I-131) (off-label use): Use may be considered if potassium iodide is unavailable, contraindicated, or unlikely to be effective (eg, too late for potassium iodide to be effective). In patients >40 years of age, treatment for inhalational exposure to radioactive iodine is not recommended unless the projected thyroid dose is >5 sievert (Sv) (REMM 2022b).

Oral: 100 mg 3 times daily for 8 days (REMM 2022a).

Thyroid storm

Thyroid storm (off-label use): Note: Use in combination with other appropriate agents; if iodine is administered, delay iodine administration by ≥1 hour after propylthiouracil (ATA [Ross 2016]).

Oral: 500 mg to 1 g loading dose, followed by 200 to 250 mg every 4 hours (ATA [Ross 2016]; Ross 2022c); some experts do not administer a loading dose (Ross 2022c). Once clinically stable, switch to methimazole; in patients with minor skin reactions to methimazole (eg, rash, hives), may gradually reduce propylthiouracil dose (eg, to 100 to 600 mg/day) (ATA [Ross 2016]; Goldberg 2003). In patients who cannot take propylthiouracil by mouth, alternative administration routes (eg, nasogastric, rectal) may be considered (Jongjaroenprasert 2002; Nayak 2006; Yeung 1995).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Pediatric

(For additional information see "Propylthiouracil: Pediatric drug information")

Note: Due to reports of severe liver toxicity, propylthiouracil is not recommended for use in pediatric patients; use should be limited to patients who have developed minor toxic reactions to methimazole and who are not candidates for surgery or radioactive iodine treatment. If use deemed necessary, patients and parents should be informed of risks and propylthiouracil therapy limited to a short course with close patient monitoring (eg, baseline CBC, liver profile including LFTs, bilirubin, and alkaline phosphatase recommended). Discontinue therapy at first sign of hepatotoxicity and initiate hepatic assessment (see "Dosing: Hepatic Impairment: Pediatric") (ATA [Ross 2016]).

Hyperthyroidism, alternate therapy

Hyperthyroidism, alternate therapy: Note: Adjust dosage to maintain T3, T4, and thyroid stimulating hormone (TSH) in normal range; elevated T3 may be sole indicator of inadequate treatment. Elevated TSH indicates excessive antithyroid treatment.

Children: ≥6 years and Adolescents: Limited data available (Propyl-Thyracil Canadian product monograph):

Initial:

BSA-directed dosing: Oral: 150 mg/m2/day in divided doses every 8 hours.

Age-directed fixed dosing:

6 to 10 years: Oral: 50 to 150 mg/day divided every 8 hours.

≥10 years: Oral: 150 to 300 mg/day divided every 8 hours.

Maintenance (once euthyroid): Dose should be individualized based on patient response: Oral: Usual dose: 50 mg twice daily.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosage adjustment for toxicity: Discontinue use for signs of infection (fever, arthralgias, mouth sores, pharyngitis, or malaise); assess WBC count (ATA [Ross 2016]).

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Pediatric

Due to reports of severe liver toxicity, propylthiouracil is not recommended for use in pediatric patients. If used, limit duration to short course of therapy.

Baseline hepatic impairment: ALT or AST >5 x ULN: Reconsider initiation of therapy (ATA [Ross 2016]).

Hepatotoxicity during treatment: Discontinue therapy at first sign of liver injury (eg, anorexia, pruritus, rash, jaundice, light stool, dark urine, joint pain, right upper quadrant pain, abdominal bloating, nausea, malaise) and assess LFTs. Permanently discontinue if AST or ALT 2 to 3 times ULN fails to resolve within a week of repeat testing (ATA [Ross 2016]).

Dosing: Older Adult

Refer to adult dosing; use with caution.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Generic: 50 mg

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Halycil: 50 mg

Propyl-Thyracil: 50 mg [DSC], 100 mg [DSC]

Generic: 50 mg

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/006188s026lbl.pdf#page=7, must be dispensed with this medication.

Administration: Adult

Nasogastric: In thyroid storm, nasogastric administration has been described (Nayak 2006).

Oral: Administer in 3 equally divided doses at approximately 8-hour intervals.

Rectal: In thyroid storm, rectal administration has been described (Jongjaroenprasert 2002; Yeung 1995).

Administration: Pediatric

Oral: Administer in 3 equally divided doses at approximately 8-hour intervals.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 2]).

Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage.

NIOSH recommends single gloving for administration of intact tablets or capsules. If manipulating tablets/capsules (eg, to prepare an oral suspension), NIOSH recommends double gloving, a protective gown, and preparation in a controlled device; if not prepared in a controlled device, respiratory and eye/face protection as well as ventilated engineering controls are recommended. NIOSH recommends double gloving, a protective gown, and (if there is a potential for vomit or spit up) eye/face protection for administration of an oral liquid/feeding tube administration (NIOSH 2016). Assess risk to determine appropriate containment strategy (USP-NF 2017).

Use: Labeled Indications

Hyperthyroidism: Treatment of hyperthyroidism in patients with Graves disease or toxic multinodular goiter who are intolerant of methimazole and for whom surgery or radioactive iodine therapy is not an appropriate treatment regimen; amelioration of hyperthyroid symptoms in preparation for thyroidectomy or radioactive iodine therapy (in patients who are intolerant of methimazole).

Note: Current guidelines suggest that propylthiouracil may be preferred over methimazole during the first trimester of pregnancy (ATA [Alexander 2017]; ATA [Ross 2016]).

Use: Off-Label: Adult

Internal contamination with radioactive iodine (I-131); Thyroid storm

Medication Safety Issues
Sound-alike/look-alike issues:

Propylthiouracil may be confused with Purinethol [DSC]

PTU is an error-prone abbreviation (mistaken as mercaptopurine [Purinethol; 6-MP])

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

<1%: Hematologic: Agranulocytosis

Frequency not defined:

Cardiovascular: Edema

Dermatologic: Alopecia, pruritus, skin pigmentation, skin rash, urticaria

Gastrointestinal: Ageusia, dysgeusia, epigastric discomfort, nausea, salivary gland disease, vomiting

Hematologic & oncologic: Leukopenia, lymphadenopathy

Hepatic: Jaundice

Nervous system: Drowsiness, headache, neuritis, paresthesia, vertigo

Neuromuscular & skeletal: Arthralgia, myalgia

Postmarketing:

Cardiovascular: Hypersensitivity angiitis, periarteritis, vasculitis (ANCA-positive and cerebral)

Dermatologic: Erythema nodosum, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis

Gastrointestinal: Ischemic colitis

Hematologic & oncologic: Aplastic anemia, granulocytopenia, hemorrhage, hypoprothrombinemia, splenomegaly, thrombocytopenia

Hepatic: Hepatic failure (including acute hepatic failure), hepatic injury (severe), hepatitis, hepatotoxicity (idiosyncratic) (Chalasani 2014)

Hypersensitivity: Hypersensitivity reaction

Nervous system: Drug fever

Neuromuscular & skeletal: Lupus-like syndrome

Renal: Glomerulonephritis, nephritis

Respiratory: Interstitial pneumonitis, pulmonary alveolar hemorrhage

Contraindications

Hypersensitivity to propylthiouracil or any component of the formulation

Canadian labeling: Additional contraindications (not in US labeling): Breastfeeding

Warnings/Precautions

Concerns related to adverse effects:

• Bleeding: May cause hypoprothrombinemia and bleeding. Monitoring is recommended, especially before surgical procedures.

• Bone marrow suppression: May cause significant bone marrow depression; the most severe manifestation is agranulocytosis (usually occurs within first 3 months of therapy). Aplastic anemia (Shaikh 2019), thrombocytopenia, and leukopenia may also occur. Use with caution in patients receiving other drugs known to cause myelosuppression (particularly agranulocytosis); discontinue if significant bone marrow suppression occurs, particularly agranulocytosis or aplastic anemia.

• Dermatologic toxicity: May occur; discontinue in the presence of exfoliative dermatitis.

• Fever: Discontinue in the presence of unexplained fever.

• Hepatotoxicity: [US Boxed Warning]: Severe liver injury and acute liver failure (some fatal) have been reported and have included cases requiring liver transplantation in adult and pediatric patients, including pregnant women. Reserve propylthiouracil for patients who cannot tolerate methimazole and in whom radioactive iodine therapy or surgery are not appropriate treatments for the management of hyperthyroidism. Current guidelines suggest that propylthiouracil may be preferred over methimazole during the first trimester of pregnancy (ATA [Alexander 2017]; ATA [Ross 2016]). Routine LFT monitoring may not reduce risk due to unpredictable and rapid onset. Patients should be counseled to recognize and report symptoms suggestive of hepatic dysfunction (eg, anorexia, pruritus, right upper quadrant pain), especially in first 6 months of treatment, which should prompt immediate discontinuation. Discontinue therapy if transaminases are >3 times the ULN or if levels elevated at the onset of therapy increase further (ATA [Ross 2016]).

• Hypothyroidism: May cause hypothyroidism; routinely monitor TSH and free T4 levels, adjust dose to maintain euthyroid state.

• Lupus-like syndrome: A lupus-like syndrome (including splenomegaly and vasculitis) may occur.

• Nephritis: Has been associated with nephritis and glomerulonephritis, sometimes leading to acute renal failure.

• Pneumonitis: Interstitial pneumonitis has been reported; discontinue if this reaction occurs.

• Vasculitis: Cases of vasculitis resulting in severe complications and death have been reported. Most cases were ANCA-positive and included alveolar/pulmonary hemorrhage, cerebral angiitis, glomerulonephritis, ischemic colitis, and leukocytoclastic cutaneous vasculitis. Discontinue use for confirmed or suspected vasculitis. Some cases resolve/improve with drug discontinuation; severe cases may require further treatment (eg, corticosteroids, immunosuppressant therapy, plasmapheresis).

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP 1997; CDC 1982); some data suggest that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.

Warnings: Additional Pediatric Considerations

In pediatric patients, severe liver injury including hepatic failure requiring transplantation or resulting in death have been reported with propylthiouracil (most cases with doses ≥300 mg, but has also been reported with the lower 50 mg dose). Routine liver function test monitoring may not reduce risk due to unpredictable and rapid onset. Use is not recommended and should be limited to patients who have developed minor toxic reactions to methimazole and who are not candidates for surgery or radioactive iodine treatment. If use necessary, patients and parents should be informed of risks and propylthiouracil therapy limited to a short course with close patient monitoring (baseline CBC, liver profile including LFTs, bilirubin, and alkaline phosphatase recommended). Discontinue use, contact prescriber, and obtain CBC (WBC) and LFTs (transaminases) if any of the following occur: Tiredness, nausea, anorexia, fever, pharyngitis, malaise, pruritus, rash, jaundice, light-colored stool or dark urine, joint pain, right upper quadrant pain, abdominal bloating (ATA [Ross 2016]).

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

Cardiac Glycosides: Antithyroid Agents may increase the serum concentration of Cardiac Glycosides. Risk C: Monitor therapy

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Macimorelin: Propylthiouracil may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination

MetyraPONE: Antithyroid Agents may diminish the diagnostic effect of MetyraPONE. Management: Consider alternatives to the use of the metyrapone test in patients taking antithyroid agents. Risk D: Consider therapy modification

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification

Sodium Iodide I131: Antithyroid Agents may diminish the therapeutic effect of Sodium Iodide I131. Management: Discontinue antithyroid medications at least 3 days before sodium iodide I-131 administration, and avoid concurrent use. Risk X: Avoid combination

Theophylline Derivatives: Antithyroid Agents may increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Antithyroid Agents may diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Reproductive Considerations

Patients taking propylthiouracil should use effective contraception and postpone becoming pregnant until a stable euthyroid state is achieved. Unless otherwise contraindicated, propylthiouracil may be the preferred treatment when an antithyroid drug is indicated just prior to the first trimester of pregnancy. Patients taking propylthiouracil should notify their health care provider immediately once pregnancy is suspected. The decision to continue antithyroid medications during pregnancy should be individualized (ATA [Alexander 2017]).

Pregnancy Considerations

Propylthiouracil crosses the placenta.

Adverse events associated with propylthiouracil use during pregnancy include liver damage in the mother and fetus and hypothyroidism in the fetus/neonate. Face and neck cysts and urinary tract abnormalities in male offspring have also been reported (ATA [Alexander 2017]).

Uncontrolled maternal hyperthyroidism may result in adverse neonatal and maternal outcomes. Adverse outcomes associated with poorly controlled thyrotoxicosis include pregnancy loss, pregnancy-induced hypertension, maternal congestive heart failure, and thyroid storm, as well as prematurity, low birth weight, intrauterine growth restriction, and stillbirth (ATA [Alexander 2017]).

The pharmacokinetic properties of propylthiouracil are not significantly changed by pregnancy; however, the severity of hyperthyroidism may fluctuate throughout pregnancy (Clark 2006; Sitar 1979; Sitar 1982). If a euthyroid state is maintained, doses of propylthiouracil may be decreased as pregnancy progresses and discontinued weeks to months prior to delivery.

To avoid potential adverse effects, antithyroid drugs may be discontinued as soon as pregnancy is detected in select patients with well-controlled Graves disease at low risk for relapse; close monitoring of maternal and fetal thyroid function is recommended (ATA [Alexander 2017]). When treatment is necessary, antithyroid drugs are the treatment of choice for the control of hyperthyroidism during pregnancy (ACOG 2020; ATA [Alexander 2017]). Propylthiouracil may be the treatment of choice when an antithyroid drug is indicated during the first 16 weeks of pregnancy. Due to the potential for hepatic toxicity, other antithyroid medications could be considered after 16 weeks' gestation (ATA [Alexander 2017]). To prevent adverse outcomes, the lowest effective dose should be used to keep the maternal TT4/FT4 at or just above the pregnancy-specific ULN. Propylthiouracil may be used for the treatment of thyroid storm in pregnant patients (ACOG 2020; ATA [Alexander 2017]).

Breastfeeding Considerations

Propylthiouracil is present in breast milk.

Information related to the presence of propylthiouracil in breast milk is available from 9 euthyroid breastfeeding women (2 with Graves disease) at 1 to 8 months postpartum. Propylthiouracil 400 mg was administered as a single dose and drug concentrations in maternal serum and breast milk were measured every 30 minutes for 4 hours. The mean maternal serum concentration at 90 minutes was 7.7 ± 1 mcg/mL and decreased to 3.9 ± 0.5 mcg/mL after 4 hours. The mean propylthiouracil concentration in milk at 90 minutes was 0.7 ± 0.2 mcg/mL and decreased to 0.5 ± 0.1 mcg/mL after 4 hours. The mean volume of milk collected in 4 hours contained propylthiouracil equivalent to 0.025% of the ingested dose. The authors calculated that a 3.5 kg infant would receive a dose equivalent to 3 mg (range: 0.8 to 9.2 mg) for a 70 kg adult and it is unlikely to affect infant thyroid hormone metabolism (Kampmann 1980). Using a mean milk concentration of 0.7 mcg/mL, the estimated exposure to the breastfeeding infant would be 0.11 mg/kg/day (relative infant dose [RID] <2% based on a weight adjusted maternal dose of 400 mg/day). In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).

Based on available data, thyroid function is normal in infants exposed to propylthiouracil via breast milk. The treatment of hyperthyroidism in breastfeeding patients is the same as non-breastfeeding patients. Maternal use of propylthiouracil is considered acceptable while breastfeeding (ATA [Alexander 2017]; WHO 2002) although it may not be preferred due to the potential risk of maternal hepatic toxicity (Amino 2020). The lowest effective dose should be used; maternal doses of propylthiouracil ≤450 mg/day are advised in breastfeeding patients. Infants exposed to antithyroid medications via breast milk should be monitored for adequate growth and development; routine tests of thyroid function are not recommended (ATA [Alexander 2017]). Taking the dose of propylthiouracil after breastfeeding may help decrease potential infant exposure by providing a 3- to 4-hour interval before the next feed (Amino 2020).

Monitoring Parameters

Signs and symptoms of illness (ie fever, sore throat, skin eruptions, general malaise) or vasculitis.

CBC with differential (baseline and if development of febrile illness or pharyngitis occurs); prothrombin time (especially before surgical procedures), LFTs (bilirubin, alkaline phosphatase, ALT, AST at baseline and if symptoms of liver injury occur) (ATA [Ross 2016]; manufacturer's labeling).

Thyroid function tests:

Serum free T4 and total T3 at 4- to 6-week intervals during dose titration, then every 2 to 3 months once euthyroid levels are achieved; with long-term therapy (ie, >18 months) may extend interval to every 4 to 6 months. In patients with Graves disease, if thyrotropin receptor autoantibodies (TRAbs) are negative, thyroid function tests should be monitored every 2 to 3 months for the first 6 months after discontinuing therapy, then at 4- to 6-month intervals for the next 6 months, then every 6 to 12 months thereafter (ATA [Ross 2016]).

Thyroid stimulating hormone (TSH) periodically throughout treatment; TSH is not an adequate parameter to assess initial response as levels may remain suppressed for several months after starting therapy (ATA [Ross 2016]).

TRAb in patients with Graves disease prior to stopping medication, elevation at the end of therapy decreases likelihood of remission (ATA [Ross 2016]).

Pregnant patients: Free T4 and total T3 every 2 to 4 weeks until stabilized (ACOG 2020). Free T4, total T4, and TSH approximately every 4 weeks throughout pregnancy. TRAb once pregnancy is confirmed, at 18 to 22 weeks' gestation, and 30 to 34 weeks' gestation (ATA [Alexander 2017]).

Reference Range

Normal laboratory values:

Total T4: 5 to 12 mcg/dL

Serum T3: 90 to 185 ng/dL

Free thyroxine index (FT4 I): 6 to 10.5

TSH: 0.5 to 4.0 microunits/mL

TRAb: <1.75 int. units/L

Mechanism of Action

Inhibits the synthesis of thyroid hormones by interfering with thyroid peroxidase (TPO) which oxidizes iodide, subsequently catalyzes formation of mono- and di-iodotyrosines (MIT and DIT) on thyroglobulin, and catalyzes coupling reactions between MIT and DIT to form thyroxine (T4) and triiodothyronine (T3) (Burch 2015); also blocks conversion of T4 to T3 in peripheral tissues (does not inactivate existing T4 and T3 stores in circulating blood and the thyroid and does not interfere with replacement thyroid hormones). Propylthiouracil also acts as a thyroid blocker to decrease the retention of radioactive iodine (I-131) into the thyroid (REMM 2022b).

Pharmacokinetics

Onset of action: For significant therapeutic effects 24 to 36 hours are required; remission of hyperthyroidism usually does not occur before 4 months of continued therapy

Duration: 12 to 24 hours (Clark 2006)

Distribution: Concentrated in the thyroid gland (Clark 2006)

Protein binding: 80% to 85% (Clark 2006)

Metabolism: Hepatic

Bioavailability: 53% to 88% (Clark 2006)

Half-life elimination: ~1 hour (Clark 2006)

Time to peak, serum: 1 to 2 hours (Clark 2006)

Excretion: Urine (35%; primarily as metabolites)

Pricing: US

Tablets (Propylthiouracil Oral)

50 mg (per each): $0.90

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Antiroid (KR);
  • Bingsaiyou (CN);
  • CP-PTU (HK);
  • Lothisil (VN);
  • Peteyu (TH);
  • Polupi (TW);
  • Procarbizol (PK);
  • Procil (TW);
  • Propil (BR);
  • Propilracil (BR);
  • Propycil (CH, CZ, DE, HN, HU, PT, SK, TR);
  • Propyl (SG, TH);
  • Propylex (FR);
  • Propylthiocil (IL);
  • Propylthiouracil ”Dak” (DK);
  • Propylthiouracile (BE);
  • Propyltiouracil ”Medic” (DK);
  • Prothiucil (AT);
  • Prothuril (GR);
  • PTU (AU, IN, LK, TH, UY, VN);
  • Pyroid (HK);
  • Thyrocil (EG);
  • Thyrosan (PL);
  • Tiotil (EE, SE);
  • Tirostat (CO, EC);
  • Uracil (TH)


For country code abbreviations (show table)
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  4. Aloush V, Litinsky I, Caspi D, et al. Propylthiouracil-Induced Autoimmune Syndromes: Two Distinct Clinical Presentations With Different Course and Management. Semin Arthritis Rheum. 2006;36(1):4-9. [PubMed 16887463]
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  7. Amino N, Arata N. Thyroid dysfunction following pregnancy and implications for breastfeeding. Best Pract Res Clin Endocrinol Metab. 2020;34(4):101438. doi:10.1016/j.beem.2020.101438 [PubMed 32651061]
  8. Anderson PO, Sauberan JB. Modeling drug passage into human milk. Clin Pharmacol Ther. 2016;100(1):42-52. doi:10.1002/cpt.377 [PubMed 27060684]
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