PROPYLTHIOURACIL (propylthiouracil)

There are 3 contraindications. Absolute contraindication.

Contraindication List
Acute hepatic failure
Drug-induced hepatitis
Pancytopenia

There are 5 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Bone marrow depression
Hyperbilirubinemia
Leukopenia
Pregnancy
Thrombocytopenic disorder

There are 1 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Hypothyroidism

There are 34 severe adverse reactions.

More Frequent	Less Frequent
Pruritus of skin Skin rash	Acute abdominal pain Arthralgia Lupus-like syndrome Vasculitis

Rare/Very Rare

Agranulocytosis Alveolar hemorrhage Aplastic anemia Cerebral vasculitis Erythema nodosum Exfoliative dermatitis Fever Glomerulonephritis Hepatic failure Hepatic necrosis Hepatitis Hypersensitivity angiitis Hypoprothrombinemia Interstitial pneumonitis Ischemic colitis Jaundice Leukopenia Lymphadenopathy Nephritis Peripheral neuropathy Polyarteritis nodosa Pulmonary infiltrates Renal vasculitis Skin ulcer Stevens-johnson syndrome Thrombocytopenic disorder Toxic epidermal necrolysis Urticaria

There are 14 less severe adverse reactions.

More Frequent	Less Frequent
None.	Nausea Vomiting

Rare/Very Rare
Alopecia Drowsy Dysgeusia Edema Headache disorder Hypothyroidism Loss of taste Myalgia Paresthesia Salivary secretion disorder Skin pigmentation enhancement Vertigo

Propylthiouracil crosses the placenta and may cause fetal harm when administered to pregnant women; the drug can induce goiter and hypothyroidism (cretinism) in the developing fetus. In April 2010, FDA reported a review of postmarketing data analyzing the potential for birth defects associated with use of propylthiouracil or methimazole during pregnancy. FDA found that congenital malformations were reported approximately 3 times more often with prenatal exposure to methimazole compared with propylthiouracil (29 cases with methimazole; 9 cases with propylthiouracil).

In addition, there was a distinct and consistent pattern of congenital malformations associated with the use of methimazole that was not found with propylthiouracil. Approximately 90% of the congenital malformations with methimazole were craniofacial malformations (e.g., scalp epidermal aplasia (aplasia cutis), facial dysmorphism, choanal atresia). In most of the cases, there were multiple malformations that frequently included a combination of craniofacial defects and GI atresia or aplasia.

These specific birth defects were associated with the use of methimazole during the first trimester of pregnancy but were not found when the drug was administered later in pregnancy. In contrast, FDA did not find a consistent pattern of birth defects associated with the use of propylthiouracil and concluded that there is no convincing evidence of an association between propylthiouracil use and congenital malformations, even with use during the first trimester. Despite the potential fetal hazard, antithyroid agents are still considered the therapy of choice for the management of hyperthyroidism during pregnancy.

Since methimazole may be associated with the rare development of fetal abnormalities, such as aplasia cutis and choanal atresia, propylthiouracil is the preferred agent when an antithyroid drug is indicated during organogenesis in the first trimester of pregnancy or just prior to the first trimester of pregnancy. Patients receiving methimazole should be switched to propylthiouracil if pregnancy is confirmed in the first trimester. Because of the potential adverse maternal effects of propylthiouracil (e.g., hepatotoxicity), however, it may be preferable to switch from propylthiouracil to methimazole for the second and third trimesters (i.e., after the first trimester).

If the patient is switching from propylthiouracil to methimazole, thyroid function should be assessed after 2 weeks and then every 2-4 weeks thereafter. It is not known if the risk of methimazole-induced aplasia cutis or embryopathy outweighs the risk of propylthiouracil-induced hepatotoxicity. If propylthiouracil is used during pregnancy for the management of hyperthyroidism, the manufacturer states that a sufficient, but not excessive, dosage of propylthiouracil is necessary.

Some clinicians state that antithyroid drug therapy should be initiated or adjusted to maintain maternal free thyroxine (T4) concentrations at or just above the upper limit of normal (ULN) of the 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 the lowest possible dosage of antithyroid drugs. In women receiving antithyroid drugs during pregnancy, free T4 and TSH concentrations should be monitored approximately every 2-6 weeks.

The manufacturer states that because thyroid dysfunction diminishes in many women as pregnancy proceeds, a reduction in dosage may be possible, and, in some patients, propylthiouracil can be discontinued several weeks or months before delivery. Patients should be advised to contact their clinician immediately about their therapy if they are or plan to become pregnant while receiving an antithyroid drug. If propylthiouracil is used during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be advised of the rare potential hazard of liver damage in the mother and fetus; in addition, when considering antithyroid drug use during pregnancy, the patient should be informed of this potential risk, as well as the risks of methimazole-associated fetal malformations.

Although liver toxicity may appear abruptly, some clinicians state that 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. (See Cautions: Hepatic Effects and also see Cautions: Precautions and Contraindications.)

The manufacturer and some clinicians state that propylthiouracil is distributed into milk to a small extent and, therefore, is unlikely to result in clinically important doses in the nursing infant. In one study in 9 lactating women who received a single 400-mg dose of propylthiouracil orally, the mean amount of propylthiouracil distributed into milk during 4 hours following drug administration was 0.025% (range: 0.007-0.077%) of the administered dose.

Propylthiouracil generally is compatible with breast-feeding, and moderate dosages of the drug (i.e., less than 300 mg daily) appear to be safe during breast-feeding. However, some clinicians consider propylthiouracil to be a second-line agent in nursing women because of concerns regarding severe hepatotoxicity (i.e., hepatic necrosis in either woman or child) following maternal use of the drug; these clinicians state that methimazole is the preferred antithyroid drug in nursing women. If an antithyroid drug is used in nursing women, some clinicians recommend that the drug be administered after a feeding and in divided doses, and that thyroid function be monitored in nursing infants.

No enhanced Geriatric Use information available for this drug.