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PROPYLTHIOURACIL

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Propylthiouracil is an antithyroid medication; a thioamide derivative.

Specific Substances

    1) 2,3-Dihydro-6-propyl-2-thioxopyrimidin-4 (1H)-one
    2) 2-Mercapto-6-propyl-pyrimidin-4-ol
    3) 2-Thio-4-oxo-6-propyl-1,3-pyrimidine
    4) 2-Thio-6-propyl-1,3-pyrimidin-4-one
    5) 6-Propyl-2-thiouracil
    6) Propylthiouracilum
    7) PTU
    8) CAS 51-52-5
    1.2.1) MOLECULAR FORMULA
    1) C7H10N2OS

Available Forms Sources

    A) FORMS
    1) Propylthiouracil is available in 50 mg tablets (Prod Info propylthiouracil oral tablets, 2011).
    B) USES
    1) Propylthiouracil blocks the production of thyroid hormones and is considered second-line drug therapy in adults for hyperthyroidism due to Graves disease or toxic multinodular goiter except in patients who are intolerant of methimazole or surgery, or if radioactive iodine therapy is not appropriate (Prod Info propylthiouracil oral tablets, 2011).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Propylthiouracil is indicated for treatment of Grave disease with hyperthyroidism or toxic multinodular goiter in patients who are intolerant to methimazole and are not candidates for surgery or radioactive iodine therapy. It may be used to lessen symptoms of hyperthyroidism in preparation for surgery or radioactive iodine therapy in patients intolerant of methimazole.
    B) PHARMACOLOGY: Propylthiouracil is a thiocarbamide compound that inhibits the synthesis of thyroid hormones as an effective therapy for hyperthyroidism. However, it neither affects the stored thyroxine and triiodothyronine in the thyroid or bloodstream, nor interferes with the thyroid hormone activity when administered orally or parenterally.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) Adverse effects following the therapeutic use of propylthiouracil include rash, urticaria, nausea, vomiting, epigastric distress, arthralgia, paresthesias, loss of taste, taste perversion, abnormal loss of hair, myalgia, headache, pruritus, drowsiness, neuritis, edema, vertigo, skin pigmentation, jaundice, sialadenopathy, and lymphadenopathy. Serious adverse effects include liver injury, hepatitis, liver failure, agranulocytosis, granulopenia, thrombocytopenia, aplastic anemia, drug fever, a lupus-like syndrome (including splenomegaly and vasculitis), hepatitis, periarteritis, hypoprothrombinemia, nephritis, glomerulonephritis, interstitial pneumonitis, exfoliative dermatitis, erythema nodosum, and vasculitis syndrome. Vasculitis syndrome associated with the presence of anti-neutrophilic cytoplasmic antibodies (ANCA) is manifested as rapidly progressive glomerulonephritis (crescentic and pauci-immune necrotizing glomerulonephritis), and may cause acute renal failure, pulmonary infiltrates or alveolar hemorrhage, skin ulcers, and leukocytoclastic vasculitis.
    E) WITH POISONING/EXPOSURE
    1) Very little data are available on the effects of acute overdose. Nausea, vomiting, epigastric distress, headache, fever, arthralgia, pruritus, edema, pancytopenia, and agranulocytosis may occur with overdose. Other rare effects include exfoliative dermatitis, hepatitis, neuropathies, or CNS simulation or depression. Chronic overdose may result in clinical hypothyroidism. Decreased T3 and elevated alkaline phosphatase levels were the only effects seen after a massive overdose in a 12-year-old girl.

Laboratory Monitoring

    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor vital signs and thyroid function. Measurement of T3 (triiodothyronine) and reverse T3 (a major metabolite of T4 with no metabolic activity) levels may confirm a history of ingestion, but the clinical significance is unknown.
    C) Monitor CBC with differential and platelet count, renal function, liver enzymes, and serum electrolytes in symptomatic patients.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO SEVERE TOXICITY
    1) Treatment is symptomatic and supportive.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Myelosuppression has been reported. Monitor serial CBC with differential. For severe neutropenia, administer colony stimulating factor (eg, filgrastim, sargramostim). Transfusions as needed for severe thrombocytopenia, bleeding.
    C) DECONTAMINATION
    1) PREHOSPITAL: Consider activated charcoal if the overdose is recent, the patient is not vomiting, and is able to maintain airway.
    2) HOSPITAL: Consider activated charcoal if the overdose is recent, the patient is not vomiting, and is able to maintain airway.
    D) AIRWAY MANAGEMENT
    1) Ensure adequate ventilation and perform endotracheal intubation early in patients with severe respiratory distress.
    E) ANTIDOTE
    1) None.
    F) MYELOSUPPRESSION
    1) Severe neutropenia: filgrastim 5 mcg/kg/day IV or SubQ or sargramostim 250 mcg/m(2)/day IV infused over 4 hours. Monitor serial CBC with differential. Transfusions may be required for severe thrombocytopenia or bleeding.
    G) ENHANCED ELIMINATION
    1) It is unknown if hemodialysis would be effective in overdose.
    H) PATIENT DISPOSITION
    1) HOME CRITERIA: A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    2) OBSERVATION CRITERIA: Patients with a deliberate overdose, and those who are symptomatic, need to be monitored until they are clearly improving and clinically stable.
    3) ADMISSION CRITERIA: Patients with severe symptoms despite treatment should be admitted.
    4) CONSULT CRITERIA: Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    I) PITFALLS
    1) When managing a suspected overdose, the possibility of multidrug involvement should be considered.
    J) PHARMACOKINETICS
    1) Bioavailability: About 77% in euthyroid and hyperthyroid individuals. Tmax: 1 to 2 hours. Protein binding: 75% to 80%. Vd: 0.3 to 0.4 L/kg. Excretion: 61% of the dose was excreted in the urine as the glucuronic acid conjugate, 8% to 9% as inorganic sulfate, 8% to 10% as unknown metabolites, and a small amount as unchanged drug. Elimination half-life: About 1 to 2 hours.
    K) DIFFERENTIAL DIAGNOSIS
    1) Includes other agents that may cause myelosuppression or hepatotoxicity.

Range Of Toxicity

    A) TOXICITY: Limited data are available. In one overdose, ingestion of 5 to 13 grams resulted in an uneventful outcome.
    B) THERAPEUTIC DOSES: ADULT: Initial: 300 mg orally per day in 3 evenly divided doses at 8-hour intervals; patients with severe hyperthyroidism may require 400 mg daily and in rare cases 600 to 900 mg/day. Maintenance: 100 to 150 mg/day. PEDIATRIC: Usually not recommended except in rare cases. Initial, 6 years or older: 50 mg orally daily in 3 evenly divided doses at 8-hour intervals.

Clinical Effects

Summary Of Exposure

    A) USES: Propylthiouracil is indicated for treatment of Grave disease with hyperthyroidism or toxic multinodular goiter in patients who are intolerant to methimazole and are not candidates for surgery or radioactive iodine therapy. It may be used to lessen symptoms of hyperthyroidism in preparation for surgery or radioactive iodine therapy in patients intolerant of methimazole.
    B) PHARMACOLOGY: Propylthiouracil is a thiocarbamide compound that inhibits the synthesis of thyroid hormones as an effective therapy for hyperthyroidism. However, it neither affects the stored thyroxine and triiodothyronine in the thyroid or bloodstream, nor interferes with the thyroid hormone activity when administered orally or parenterally.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) Adverse effects following the therapeutic use of propylthiouracil include rash, urticaria, nausea, vomiting, epigastric distress, arthralgia, paresthesias, loss of taste, taste perversion, abnormal loss of hair, myalgia, headache, pruritus, drowsiness, neuritis, edema, vertigo, skin pigmentation, jaundice, sialadenopathy, and lymphadenopathy. Serious adverse effects include liver injury, hepatitis, liver failure, agranulocytosis, granulopenia, thrombocytopenia, aplastic anemia, drug fever, a lupus-like syndrome (including splenomegaly and vasculitis), hepatitis, periarteritis, hypoprothrombinemia, nephritis, glomerulonephritis, interstitial pneumonitis, exfoliative dermatitis, erythema nodosum, and vasculitis syndrome. Vasculitis syndrome associated with the presence of anti-neutrophilic cytoplasmic antibodies (ANCA) is manifested as rapidly progressive glomerulonephritis (crescentic and pauci-immune necrotizing glomerulonephritis), and may cause acute renal failure, pulmonary infiltrates or alveolar hemorrhage, skin ulcers, and leukocytoclastic vasculitis.
    E) WITH POISONING/EXPOSURE
    1) Very little data are available on the effects of acute overdose. Nausea, vomiting, epigastric distress, headache, fever, arthralgia, pruritus, edema, pancytopenia, and agranulocytosis may occur with overdose. Other rare effects include exfoliative dermatitis, hepatitis, neuropathies, or CNS simulation or depression. Chronic overdose may result in clinical hypothyroidism. Decreased T3 and elevated alkaline phosphatase levels were the only effects seen after a massive overdose in a 12-year-old girl.

Vital Signs

    3.3.3) TEMPERATURE
    A) WITH POISONING/EXPOSURE
    1) FEVER may occur with overdose (Prod Info propylthiouracil oral tablets, 2012).

Heent

    3.4.4) EARS
    A) WITH THERAPEUTIC USE
    1) CASE REPORT: SENSORINEURAL HEARING LOSS was reported following chronic propylthiouracil therapy in a 12-year-old girl. Systemic lupus erythematosus was also present. Hearing normalized within 3 weeks of discontinuation of propylthiouracil (Smith & Spaulding, 1972).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) HEMOPTYSIS
    1) WITH THERAPEUTIC USE
    a) Hemoptysis and pulmonary cavitary lesions have been reported with chronic use (Cassorla et al, 1983; Houston et al, 1979).
    B) ACUTE LUNG INJURY
    1) WITH THERAPEUTIC USE
    a) Adult respiratory distress-like syndrome has been associated with propylthiouracil therapy (Chevrolet et al, 1991).
    C) DYSPNEA
    1) WITH THERAPEUTIC USE
    a) Exertional dyspnea, hypoxemia, cough, and productive sputum have been noted with therapeutic use (Miyazono et al, 1984).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) HEADACHE
    1) WITH POISONING/EXPOSURE
    a) Headache may occur with overdose (Prod Info propylthiouracil oral tablets, 2012).
    B) CENTRAL NERVOUS SYSTEM FINDING
    1) WITH POISONING/EXPOSURE
    a) CNS stimulation or depression may rarely occur with overdose (Prod Info propylthiouracil oral tablets, 2012).
    C) NEUROPATHY
    1) WITH POISONING/EXPOSURE
    a) Neuropathies may rarely occur with overdose (Prod Info propylthiouracil oral tablets, 2012).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH POISONING/EXPOSURE
    a) Nausea and vomiting may occur with overdose (Prod Info propylthiouracil oral tablets, 2012).
    B) ABDOMINAL PAIN
    1) WITH POISONING/EXPOSURE
    a) Epigastric distress may occur with overdose (Prod Info propylthiouracil oral tablets, 2012).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) TOXIC LIVER DISEASE
    1) WITH THERAPEUTIC USE
    a) Chronic ingestion of propylthiouracil produces a characteristic hepatocellular or mixed cytotoxic-cholestatic hepatitis, believed to be a hypersensitivity reaction. Transaminase levels are typically elevated, with or without elevated bilirubin and alkaline phosphatase. The onset of symptoms is 2 weeks to 5 months after initiation of therapy (Vitug & Goldman, 1985).
    b) Liver injury resulting in hepatitis, liver failure, a need for liver transplantation or death have been reported in patients receiving propylthiouracil (Prod Info propylthiouracil oral tablets, 2012).
    c) Thirty-four cases of severe liver injury have been reported in both adult and pediatric patients. Some cases were fatal and many required liver transplantation (U.S. Food and Drug Administration (FDA), 2010).
    d) Hepatotoxicity was reported in patients treated for Graves disease (N=449). Patients were randomized to either methimazole 15 mg/day, methimazole 30 mg/day in 2 divided doses, or propylthiouracil 300 mg/day in 2 or 3 divided doses. Hepatoxicity developed at significantly higher rates with propylthiouracil (25.8%) compared with 8.7% and 9% in the methimazole 15-mg and 30-mg groups, respectively. On average, hepatotoxicity was reported 28 days after initiation of therapy. In 4 of 11 patients with hepatoxicity after methimazole treatment, the same side effect occurred with administration of propylthiouracil (Otsuka et al, 2012).
    B) CHOLESTATIC HEPATITIS
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: A 33-year-old woman receiving propylthiouracil 300 mg/day for 2 weeks developed cholestatic hepatitis, demonstrated by biopsy and migration inhibition factor test. Transaminase levels were normal, while alkaline phosphatase and bilirubin were elevated (Seidman et al, 1986).
    b) CASE REPORT: A 13-year-old girl diagnosed with hyperthyroidism was started on propylthiouracil (250 mg/day), and four months later jaundice, fatigue, fever and diarrhea developed. Hyperbilirubinemia and elevated liver enzymes were present on admission, and the patient then developed an elevated ammonia level accompanied by deterioration in mental status. Although the patient underwent successful orthotopic liver transplantation, metabolic encephalopathy progressed and the patient died on the third postoperative day (pupils were fixed and dilated and a nuclear scan indicated no cerebral blood flow) when life support measures were removed (Deidiker & deMello, 1996).
    2) WITH POISONING/EXPOSURE
    a) Hepatitis may rarely occur with overdose (Prod Info propylthiouracil oral tablets, 2012).
    C) LIVER ENZYMES ABNORMAL
    1) WITH POISONING/EXPOSURE
    a) In the only reported case of propylthiouracil overdose, the serum alkaline phosphatase level was elevated, with no clinical evidence of liver toxicity (Jackson et al, 1979).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) PRECOCIOUS SEXUAL DEVELOPMENT
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: Menstruation and breast enlargement were seen in a 2-1/2-year-old girl taking propylthiouracil 25 mg three times a day for ten months. Resolution of symptoms occurred when therapy was reinstituted at a lower dose (Sadeghi-Nejad & Senior, 1971).
    B) NEPHRITIS
    1) WITH THERAPEUTIC USE
    a) Nephritis and glomerulonephritis have been associated with therapeutic use (Prod Info propylthiouracil oral tablets, 2012; Cassorla et al, 1983).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) AGRANULOCYTOSIS
    1) WITH THERAPEUTIC USE
    a) Chronic ingestion of therapeutic doses of propylthiouracil has been associated with agranulocytosis and leukopenia. It is potentially the most serious effect reported with therapy (Prod Info propylthiouracil oral tablets, 2012; Valenta et al, 1981; Fibbe et al, 1986; Guffy et al, 1984; Ostlere & Apthorp, 1988; Toth et al, 1988).
    1) This is most likely immunologically mediated (Guffy et al, 1984; Toth et al, 1988), but direct bone marrow toxicity cannot be excluded. It does not appear to be a dose-related reaction.
    b) Patients over 40 years of age are at a greater risk. Symptoms of malaise, fever, chills, and pharyngitis may indicate the need for hematologic evaluation. Fatalities were reported in 10% of those affected (Cooper et al, 1983).
    2) WITH POISONING/EXPOSURE
    a) Agranulocytosis may occur with overdose (Prod Info propylthiouracil oral tablets, 2012).
    B) PANCYTOPENIA
    1) WITH POISONING/EXPOSURE
    a) Pancytopenia may occur with overdose (Prod Info propylthiouracil oral tablets, 2012).
    C) BLOOD COAGULATION PATHWAY FINDING
    1) WITH THERAPEUTIC USE
    a) HYPOPROTHROMBINEMIA: A prothrombin time of 200 seconds (control 12 sec) was reported in a 52-year-old woman undergoing subtotal thyroidectomy. She had been pretreated with propylthiouracil 200 mg every 6 hours until 5 days before the surgery. The PTT was also prolonged (Gotta et al, 1972).
    D) APLASTIC ANEMIA
    1) WITH THERAPEUTIC USE
    a) Aplastic anemia may develop with therapeutic use (Prod Info propylthiouracil oral tablets, 2012).
    E) DISSEMINATED INTRAVASCULAR COAGULATION
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: Disseminated intravascular coagulation was reported in a 16-year-old girl receiving propylthiouracil 75 to 150 mg/day for 2 years (Sammon et al, 1971).
    F) EOSINOPHIL COUNT RAISED
    1) WITH THERAPEUTIC USE
    a) Eosinophilia has been reported with therapeutic use (Pacini et al, 1982).
    G) ACUTE LEUKEMIA
    1) WITH THERAPEUTIC USE
    a) Acute myeloblastic leukemia has been associated with propylthiouracil in 2 cases (Aksoy et al, 1974; Azizerli et al, 1988).
    H) THROMBOCYTOPENIC DISORDER
    1) WITH THERAPEUTIC USE
    a) Thrombocytopenia may occur with therapeutic use (Prod Info propylthiouracil oral tablets, 2012; Berkman et al, 1983).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) ERUPTION
    1) WITH THERAPEUTIC USE
    a) Skin rashes and urticaria may develop during therapeutic use (Prod Info propylthiouracil oral tablets, 2012).
    B) ITCHING OF SKIN
    1) WITH POISONING/EXPOSURE
    a) Pruritus may occur with overdose (Prod Info propylthiouracil oral tablets, 2012).
    C) DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) Exfoliative dermatitis may rarely occur with overdose (Prod Info propylthiouracil oral tablets, 2012).
    D) EDEMA
    1) WITH POISONING/EXPOSURE
    a) Edema may occur with overdose (Prod Info propylthiouracil oral tablets, 2012).
    E) VASCULITIS
    1) WITH THERAPEUTIC USE
    a) Cutaneous hypersensitivity vasculitis is an immune-mediated adverse reaction to propylthiouracil. The duration of therapy has ranged from 6 weeks to 48 months (Reidy et al, 1982; Vasily & Tyler, 1980).
    b) Vasculitis syndrome associated with the presence of anti-neutrophilic cytoplasmic antibodies (ANCA) is manifested as rapidly progressive glomerulonephritis (crescentic and pauci-immune necrotizing glomerulonephritis ), and may cause acute renal failure, pulmonary infiltrates or alveolar hemorrhage, skin ulcers, and leukocytoclastic vasculitis (Prod Info propylthiouracil oral tablets, 2012).
    c) CASE REPORT: A 25-year-old woman developed antineutrophil cytoplasmic antibody-positive (ANCA-positive) vasculitis after treatment with propylthiouracil and the symptoms recurred after methimazole treatment. The patient presented with worsening fatigue, weight loss, generalized myalgia, and joint pain. She had a history of hyperthyroidism and delivered a baby 4 months prior. She was treated with propylthiouracil 50 mg 2 times daily after the hyperthyroidism diagnosis 15 months prior and the dosage was recently increased to 50 mg 3 times daily. After physical and laboratory examination, Graves disease and propylthiouracil associated ANCA-positive vasculitis were diagnosed. When propylthiouracil was discontinued and beta-adrenergic blocker treatment was started, the patient reported improvement of her symptoms. The woman was started on methimazole 10 mg daily; however, her vasculitis symptoms recurred and treatment was discontinued and prednisone initiated. Signs of vasculitis were still absent 3 months after stopping methimazole treatment. Crossreactivity between propylthiouracil and methimazole should be considered when prescribing alternative therapies (Ahmed et al, 2010).
    d) CASE REPORT: A 43-year-old woman with a history of Graves' disease and receiving propylthiouracil 50 mg daily for 9 years, developed a palpable, purpuric rash. Laboratory studies revealed an elevated erythrocyte sedimentation rate and ANCA titers consistent with necrotizing vasculitis. Despite prednisone therapy, symptoms did not improve until propylthiouracil was discontinued. The patient gradually improved; rechallenge with propylthiouracil was not done (Stein et al, 2008).
    F) DRUG-INDUCED LUPUS ERYTHEMATOSUS
    1) WITH THERAPEUTIC USE
    a) Lupus-like dermatologic symptoms may be seen (Berkman et al, 1983; Horton et al, 1989).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) ARTHRITIS
    1) WITH THERAPEUTIC USE
    a) Arthritis as well as polymyositis, synovitis, arthralgias, and an SLE-like syndrome may be seen with therapeutic use (Oh et al, 1983; Horton et al, 1989; Berkman et al, 1983; Werner et al, 1989).
    B) JOINT PAIN
    1) WITH POISONING/EXPOSURE
    a) Arthralgia may occur with overdose (Prod Info propylthiouracil oral tablets, 2012).
    C) OSTEOMYELITIS
    1) WITH THERAPEUTIC USE
    a) Osteomyelitis occurred in one case, probably secondary to propylthiouracil-induced immunosuppression (Kornberg et al, 1985).

Endocrine

    3.16.2) CLINICAL EFFECTS
    A) FINDING OF THYROID FUNCTION
    1) WITH THERAPEUTIC USE
    a) Ingestions of 200 to 800 mg of propylthiouracil have produced an increase in reverse T3 and a decrease in T3 levels lasting 4 and 9 hours, respectively (Laurberg & Weeke, 1981).
    2) WITH POISONING/EXPOSURE
    a) Chronic overdose may result in clinical hypothyroidism.

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) LEUKOPENIA
    1) WITH THERAPEUTIC USE
    a) Blood dyscrasias are thought to result from production of drug-dependent, granulocytotoxic antibodies, possibly IgM (Guffy et al, 1984; Toth et al, 1988).
    B) DRUG-INDUCED LUPUS ERYTHEMATOSUS
    1) WITH THERAPEUTIC USE
    a) A lupus-like syndrome may occur with therapeutic use; drug-dependent autoantibodies have been implicated (Berkman et al, 1983; Horton et al, 1989).
    b) CASE REPORT: A case of propylthiouracil-induced lupus, antiphospholipid syndrome, and acute ischemic stroke is described in a 27-year-old man with Graves disease receiving propylthiouracil 150 mg 3 times daily and metoprolol 25 mg/day for approximately 2 weeks. The patient presented to the emergency room with double vision and numbness in the face and right arm. Physical examination revealed vital signs within normal range, no apparent distress, no exophthalmos, and an enlarged thyroid without nodules. The patient had normal language function, gait, and coordination. A brain MRI revealed acute ischemic stroke in the left thalamus, left occipital lobe, and right cerebellum. Laboratory testing results showed suppressed thyrotropin levels and high levels of free thyroxine and triiodothyronine, prolonged partial thromboplastin time, positive lupus anticoagulant, Sjogren antibodies, and antinuclear antibodies, elevated anticardiolipin IgA and anti-double-stranded DNA antibodies. Propylthiouracil therapy was discontinued and treatment with radioactive iodine was implemented. The patient's neurological deficits improved and the patient was discharged. The patient's laboratory values stabilized over the next 12 months and at a one year follow up the patient had no further evidence of thromboembolic events or connective tissue disorders (Ortiz et al, 2011).
    C) DISORDER OF IMMUNE FUNCTION
    1) WITH THERAPEUTIC USE
    a) Immunosuppression may occur secondary to neutropenia (Kornberg et al, 1985).

Reproductive

    3.20.2) TERATOGENICITY
    A) HUMANS
    1) Propylthiouracil is transferred across the placenta and can induce goiter and hypothyroidism in the unborn (Burrow et al, 1978; Solomon, 1981). Hyperthyroidism may also occur as a compensatory mechanism. Infants of women with Graves' disease who were treated with propylthiouracil may be either hypothyroid or hyperthyroid (Hayek & Brooks, 1975; Burrow, 1985).
    2) The effects on the fetal thyroid gland are usually mild, but can occasionally be severe enough to cause suffocation (Seligman & Pescovitz, 1950). Fetal goiter and hyperthyroidism can be diagnosed prenatally with ultrasonography (Belfar et al, 1991; Soliman et al, 1994). Propylthiouracil-induced fetal goiter has been reviewed (Klevit, 1969).
    3) The estimated incidence of neonatal hypothyroidism in children of mothers taking propylthiouracil is 1 to 5% (Davis et al, 1989; Becks & Burrow, 1991). Subclinical hypothyroxinemia may be much more common (Cheron et al, 1981).
    4) While these are not strictly congenital malformations (because they are reversible after cessation of exposure), there may be a risk of secondary effects on the developing fetal nervous system. The administration of propylthiouracil to the mother from the 14th week of pregnancy or later has been of concern because of the possible development of goiter and mental retardation in the infant (Aaron et al, 1955; Burrow, 1965; Worley & Crosby, 1974) Mujtaba & Burrow, 1976).
    5) Limited studies suggest that secondary effects of fetal propylthiouracil-induced hypothyroidism are not common. No differences in intelligence, motor skills, or growth were seen in children exposed prenatally to propylthiouracil and their unexposed siblings (Burrow et al, 1978; Eisenstein et al, 1992) Burrow, 1968; (Messer et al, 1990). Other investigators have noted abnormal skull growth and intellectual impairment (Daneman & Howard, 1980). The risk for subsequent intellectual or developmental impairment might be related to the severity of the neonatal hypothyroidism in individual cases.
    6) Incidence of birth defects was not significantly higher in children of women who had been treated with propylthiouracil during pregnancy (Momotani & Ito, 1991; Burrow, 1965; Talbert et al, 1970; Goluboff et al, 1974). In one retrospective study of 99 women receiving propylthiouracil monotherapy, the incidence of birth defects was 3%, comparable to that in the general population (Wing et al, 1994).
    7) One case each of hypospadias, aortic atresia, and developmental retardation has been reported following maternal use of propylthiouracil during pregnancy (Schardein, 1993; (Mujtaba & Burrow, 1975). These isolated cases are not sufficient to allow propylthiouracil to be classified as a human teratogen.
    8) An infant with aplasia cutis congenita was born to a woman who had received propylthiouracil at a dose of 50 mg/day during the last two trimesters and methimazole at 10 mg/day during the first trimester. This effect was attributed to methimazole (Kalb & Grossman, 1986). Because of the mixed exposure, it cannot be attributed to propylthiouracil alone. This defect was not seen in two series of infants born to mothers who had received propylthiouracil alone (Mujtaba & Burrow, 1975; Wing et al, 1994).
    9) Propylthiouracil has been used via maternal administration to treat fetal hyperthyroidism (Petersen & Serup, 1977; Petersen & Serup, 1977; Serup, 1978; Bruinse et al, 1988; Hatjis, 1993).
    10) Fourteen cases of birth defects in the face and neck region and in the urinary system were identified after exposure to propylthiouracil (PTU) during early pregnancy. In 11 of these cases, the children were exposed to PTU only. The remaining infants were exposed to methimazole and switched to PTU during early pregnancy. Of the children with birth defects in the face/neck region, 3 were diagnosed with preauricular sinus/cysts and required surgery. In addition, 1 child was diagnosed with sinus/cyst/fistula of the branchial cleft also requiring surgery. The remaining 3 children with face/neck birth defects had an unspecified diagnosis. Birth defects of the urinary system were predominately congenital hydronephrosis and were reported only in male children. Surgical procedures were required in some cases (Andersen et al, 2014).
    11) CASE REPORT: A 31-year-old woman treated with methimazole 10 mg/day during the first trimester and propylthiouracil 50 mg/day during the remainder of her pregnancy delivered an infant with aplasia cutis congenita of the scalp. The defect was attributed to methimazole (Kalb & Grossman, 1986).
    B) LACK OF EFFECT
    1) A Food and Drug Administration alert suggests propylthiouracil may be more appropriate than methimazole in pregnant patients (during the first trimester) with Graves' disease. Embryopathy and aplasia cutis have rarely been reported with the use of methimazole during pregnancy; however, no such cases have been reported with propylthiouracil (US Food and Drug Administration, 2009).
    C) ANIMAL STUDIES
    1) Similar effects (enlarged thyroids but no malformations) have been seen in rabbits exposed to propylthiouracil during gestation (Krementz et al, 1957). Propylthiouracil was teratogenic in mice, but not in guinea pigs, rats, or rabbits (Schardein, 1993). Functional brain development was retarded in rats exposed to propylthiouracil prenatally (Walker et al, 1989). Delayed behavioral changes were seen in rats exposed to propylthiouracil during lactation, and fewer synaptic contacts were seen in the cerebellar cortex (Schalock et al, 1979).
    2) Male rats previously made hypothyroid with propylthiouracil prenatally or through suckling develop increased testicular size and sperm production after sexual maturity (Mendis-Handagama & Sharma, 1994; Cooke et al, 1993; Hardy et al, 1993; Hess et al, 1993; Cooke et al, 1992; Joyce et al, 1993; Van Haaster et al, 1992).
    3.20.3) EFFECTS IN PREGNANCY
    A) PREGNANCY CATEGORY
    1) Propylthiouracil is US FDA Pregnancy Category D for all trimesters (Prod Info propylthiouracil oral tablet, usp, 2002).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) The American Academy of Pediatrics has concluded that use of propylthiouracil is usually compatible with breast-feeding (AAP, 1994).
    2) Propylthiouracil is transferred to breast milk, but in minimal concentrations. Concentrations have been reported to be approximately 10% of those in maternal serum, or 0.025% of the administered dose. From a total maternal dose of 600 mg/day, a nursing infant would receive approximately 40 to 460 mcg/day. This dose is unlikely to interfere with infantile thyroid hormone metabolism (Momotani, 1989).
    3) Concentrations in breast milk were about 10% of that in the serum, with a mean amount of 0.025% of the dose excreted in 4 hours. With a maternal dose of 200 mg three times a day, an infant would receive about 150 mcg per day, an amount unlikely to interfere with thyroid hormone metabolism (Kampmann et al, 1980).

Carcinogenicity

    3.21.1) IARC CATEGORY
    A) IARC Carcinogenicity Ratings for CAS51-52-5 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
    1) IARC Classification
    a) Listed as: Propylthiouracil
    b) Carcinogen Rating: 2B
    1) The agent (mixture) is possibly carcinogenic to humans. The exposure circumstance entails exposures that are possibly carcinogenic to humans. This category is used for agents, mixtures and exposure circumstances for which there is limited evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals. It may also be used when there is inadequate evidence of carcinogenicity in humans but there is sufficient evidence of carcinogenicity in experimental animals. In some instances, an agent, mixture or exposure circumstance for which there is inadequate evidence of carcinogenicity in humans but limited evidence of carcinogenicity in experimental animals together with supporting evidence from other relevant data may be placed in this group.
    3.21.3) HUMAN STUDIES
    A) HUMANS
    1) Chronic propylthiouracil use has been linked with acute myeloblastic leukemia in isolated cases (Aksoy et al, 1974) Azizerli et al, 1983). No large epidemiological studies were found on the possible carcinogenic effects of propylthiouracil in humans.
    3.21.4) ANIMAL STUDIES
    A) ANIMAL STUDIES
    1) Propylthiouracil is an animal carcinogen. Adenomas of the pituitary and carcinomas of the thyroid were seen in male A strain mice given dietary exposure for 77 weeks (HSDB , 1996). Pituitary adenomas also developed in C57BL mice given 10 and 12 g/kg in the diet (HSDB , 1996).
    2) Thyroid adenomas developed in Wistar rats given 0.02% propylthiouracil in the diet (HSDB , 1996). Rats given propylthiouracil developed benign thyroid tumors (HSDB , 1996). Wistar rats given propylthiouracil in the drinking water at an initial concentration of 7 mg/kg/day and declining to 1 mg/kg/day over 3 months developed adenomas or carcinomas of the thyroid (HSDB , 1996). Thyroid adenomas were seen in Long-Evans rats given 0.1% propylthiouracil in the diet for 1 year (HSDB , 1996).
    3) Thyroid tumors were also produced in Syrian hamsters given 0.2% propylthiouracil in the drinking water for 100 weeks, and in guinea pigs at a concentration of 0.03% in drinking water for 104 weeks (HSDB , 1996).

Genotoxicity

    A) As an RNA antimetabolite, propylthiouracil would be expected to have a broad range of genetic activity. However, few genetic studies were found at this review.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor vital signs and thyroid function. Measurement of T3 (triiodothyronine) and reverse T3 (a major metabolite of T4 with no metabolic activity) levels may confirm a history of ingestion, but the clinical significance is unknown.
    C) Monitor CBC with differential and platelet count, renal function, liver enzymes, and serum electrolytes in symptomatic patients.
    4.1.2) SERUM/BLOOD
    A) ENDOCRINE
    1) Plasma concentrations are not readily available or clinically useful in the management of overdose. Measurement of T3 (triiodothyronine) and reverse T3 (a major metabolite of T4 with no metabolic activity) levels may confirm a history of ingestion, but the clinical significance is unknown.
    2) Acute ingestion of 200 to 800 mg of propylthiouracil produces an increase in reverse T3 and a decrease in T3 levels lasting 4 and 9 hours, respectively (Laurberg & Weeke, 1981).
    a) Normal values of T3 range from 60 to 160 ng/dL (0.92 to 2.46 nmol/L). Normal values of reverse T3 (rT3) range from 10 to 50 ng/dL (0.15 to 0.77 nmol/L) (Henry, 1984).
    B) HEMATOLOGIC
    1) Agranulocytosis is an immunologic effect of chronic therapy. Total and differential leukocyte counts may aid in diagnosis.
    C) BLOOD/SERUM CHEMISTRY
    1) Alkaline phosphatase levels have been elevated in overdose cases. Isoenzyme determination is recommended. Elevations in alkaline phosphatase do not necessarily reflect liver toxicity and may be related to increased bone or bile isoenzyme (Kolenda & Hosenfeld, 1978).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with severe symptoms despite treatment should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with a deliberate overdose, and those who are symptomatic, need to be monitored until they are clearly improving and clinically stable.

Monitoring

    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor vital signs and thyroid function. Measurement of T3 (triiodothyronine) and reverse T3 (a major metabolite of T4 with no metabolic activity) levels may confirm a history of ingestion, but the clinical significance is unknown.
    C) Monitor CBC with differential and platelet count, renal function, liver enzymes, and serum electrolytes in symptomatic patients.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) MANAGEMENT OF MILD TO SEVERE TOXICITY
    a) Treatment is symptomatic and supportive.
    2) MANAGEMENT OF SEVERE TOXICITY
    a) Treatment is symptomatic and supportive. Myelosuppression has been reported. Monitor serial CBC with differential. For severe neutropenia, administer colony stimulating factor (eg, filgrastim, sargramostim). Transfusions as needed for severe thrombocytopenia, bleeding.
    B) MONITORING OF PATIENT
    1) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    2) Monitor vital signs and thyroid function. Measurement of T3 (triiodothyronine) and reverse T3 (a major metabolite of T4 with no metabolic activity) levels may confirm a history of ingestion, but the clinical significance is unknown.
    3) Monitor CBC with differential and platelet count, renal function, liver enzymes, and serum electrolytes in symptomatic patients.
    C) MYELOSUPPRESSION
    1) There is little data on the use of hematopoietic colony stimulating factors to treat neutropenia after drug overdose or idiosyncratic reactions. These agents have been shown to shorten the duration of severe neutropenia in patients receiving cancer chemotherapy (Hartman et al, 1997; Stull et al, 2005). They have also been used to treat agranulocytosis induced by nonchemotherapy drugs (Beauchesne & Shalansky, 1999). They may be considered in patients with severe neutropenia who have or are at significant risk for developing febrile neutropenia.
    a) Filgrastim: The usual starting dose in adults is 5 micrograms/kilogram/day by intravenous infusion or subcutaneous injection (Prod Info NEUPOGEN(R) injection, 2006).
    b) Sargramostim: Usual dose is 250 micrograms/square meter/day infused IV over 4 hours (Prod Info LEUKINE(R) injection, 2006).
    c) Monitor CBC with differential.
    2) Transfusion of platelets and/or packed red cells may be needed in patients with severe thrombocytopenia or hemorrhage.

Enhanced Elimination

    A) HEMODIALYSIS
    1) It is unknown if hemodialysis would be effective in overdose.

Abstracts

Case Reports

    A) ADULT
    1) A 42-year-old woman developed hepatitis progressing to fatal hepatic necrosis after being treated with propylthiouracil 300 mg/day for one year. All other potential causes were ruled out (Limaye & Ruffolo, 1987).
    B) PEDIATRIC
    1) Jackson et al (1979) reported a 12-year-old hyperthyroid girl ingested 100 to 260 tablets containing 50 mg of propylthiouracil (5,000 to 13,000 mg). All laboratory values were normal except an alkaline phosphatase level of 7350 mU/mL. T3 decreased by a greater amount than T4, both remaining in the normal range. Blood samples of propylthiouracil 17 hours postingestion contained no detectable amounts of propylthiouracil. The patient was discharged after 4 days without difficulty. The benign outcome in this case may be related to prior thyroidectomy in this patient, and enhanced elimination of propylthiouracil (Jackson et al, 1979)

Range Of Toxicity

Summary

    A) TOXICITY: Limited data are available. In one overdose, ingestion of 5 to 13 grams resulted in an uneventful outcome.
    B) THERAPEUTIC DOSES: ADULT: Initial: 300 mg orally per day in 3 evenly divided doses at 8-hour intervals; patients with severe hyperthyroidism may require 400 mg daily and in rare cases 600 to 900 mg/day. Maintenance: 100 to 150 mg/day. PEDIATRIC: Usually not recommended except in rare cases. Initial, 6 years or older: 50 mg orally daily in 3 evenly divided doses at 8-hour intervals.

Therapeutic Dose

    7.2.1) ADULT
    A) ORAL
    1) INITIAL DOSE: 300 mg orally daily in 3 evenly divided doses at 8-hour intervals; may increase to 400 mg/day for severe hyperthyroidism, very large goiters, or both; occasionally 600 to 900 mg/day may be required (Prod Info propylthiouracil oral tablets, 2012).
    2) MAINTENANCE DOSE: 100 to 150 mg/day orally daily in 3 divided doses every 8 hours (Prod Info propylthiouracil oral tablets, 2012).
    7.2.2) PEDIATRIC
    A) ORAL
    1) CHILDREN AGED 6 YEARS AND OLDER
    a) INITIAL DOSE: 50 mg/day orally in 3 evenly divided doses at 8-hour intervals (Prod Info propylthiouracil oral tablets, 2012).
    b) MAINTENANCE DOSE: Variable and dependent on individual response. Toxicity has occurred with doses ranging from 50 mg to 300 mg/day or more (Prod Info propylthiouracil oral tablets, 2012).

Maximum Tolerated Exposure

    A) CASE REPORTS
    1) Acute ingestion of 5 to 13 grams resulted in an uneventful outcome in a 12-year-old (Jackson et al, 1979).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) Peak serum levels of 10 mcg/mL were found after oral ingestion of 400 mg (Kampmann & Hansen, 1981).
    2) No data on toxic serum levels exist. In one patient who overdosed on 5,000 to 13,000 mg, serum levels were undetectable 17 hours postingestion. Urine levels were 90 mg/dL (900 mcg/mL) twelve hours postingestion (Jackson et al, 1979).

Workplace Standards

    A) ACGIH TLV Values for CAS51-52-5 (American Conference of Governmental Industrial Hygienists, 2010):
    1) Not Listed

    B) NIOSH REL and IDLH Values for CAS51-52-5 (National Institute for Occupational Safety and Health, 2007):
    1) Not Listed

    C) Carcinogenicity Ratings for CAS51-52-5 :
    1) ACGIH (American Conference of Governmental Industrial Hygienists, 2010): Not Listed
    2) EPA (U.S. Environmental Protection Agency, 2011): Not Listed
    3) IARC (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004): 2B ; Listed as: Propylthiouracil
    a) 2B : The agent (mixture) is possibly carcinogenic to humans. The exposure circumstance entails exposures that are possibly carcinogenic to humans. This category is used for agents, mixtures and exposure circumstances for which there is limited evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals. It may also be used when there is inadequate evidence of carcinogenicity in humans but there is sufficient evidence of carcinogenicity in experimental animals. In some instances, an agent, mixture or exposure circumstance for which there is inadequate evidence of carcinogenicity in humans but limited evidence of carcinogenicity in experimental animals together with supporting evidence from other relevant data may be placed in this group.
    4) NIOSH (National Institute for Occupational Safety and Health, 2007): Not Listed
    5) MAK (DFG, 2002): Not Listed
    6) NTP (U.S. Department of Health and Human Services, Public Health Service, National Toxicology Project ): Not Listed

    D) OSHA PEL Values for CAS51-52-5 (U.S. Occupational Safety, and Health Administration (OSHA), 2010):
    1) Not Listed

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) ANIMAL DATA
    1) LD50- (ORAL)RAT:
    a) 1250 mg/kg ((RTECS, 2000))

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Propylthiouracil is a thiocarbamide compound that inhibits the synthesis of thyroid hormones as an effective therapy for hyperthyroidism. However, it neither affects the stored thyroxine and triiodothyronine in the thyroid or bloodstream, nor interferes with the thyroid hormone activity when administered orally or parenterally (Prod Info propylthiouracil oral tablets, 2012).

Toxicologic Mechanism

    A) Elevations in alkaline phosphatase do not necessarily reflect liver toxicity and may be related to increased bone or bile isoenzyme (Kolenda & Hosenfeld, 1978).
    B) In rats, propylthiouracil blocked the pyrimidine pathway, resulting in mitotic inhibition and agranulocytosis. Leukocyte and erythrocyte counts were markedly reduced following 1.0 to 1.5 mmol/kg IP for 14 days. This was a dose-related effect (Kariya et al, 1983).

Physicochemical

Physical Characteristics

    A) This compound exists as a white, bitter, crystalline powder, with a starch-like appearance (HSDB , 2000) that is very slightly soluble in water (Prod Info propylthiouracil oral tablets, 2002).

Molecular Weight

    A) 170.23 (Prod Info propylthiouracil oral tablets, 2002)

References

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