Propylthiouracil

Today's med: Propylthiouracil (proe pil thye oh YOOR a sil) 

(index name: PTU (error-prone abbreviation)

Drug Class:  Thyroid Hormone Synthesis Inhibitor, Antithyroid Agent, Thioamide

Other Drugs in this class: Methimazole (Tapazole)

Action: Inhibits the synthesis of thyroid hormones by blocking the oxidation of iodine in the thyroid gland; blocks synthesis of thyroxine and triiodothyronine

Indications: Adjunctive therapy in patients intolerant of methimazole to ameliorate hyperthyroidism symptoms in preparation for surgical treatment or radioactive iodine therapy; treatment of hyperthyroidism in patients intolerant of methimazole and not candidates for surgical/radiotherapy

Use: Unlabeled

Management of Graves' disease, thyrotoxic crisis, or thyroid storm

Contraindications: Hypersensitivity to propylthiouracil or any component of the formulation

Adverse Effects: Frequency not defined.

Cardiovascular: Periarteritis, vasculitis (ANCA-positive, cutaneous, leukocytoclastic)

Central nervous system: Drowsiness, drug fever, fever, headache, neuritis, vertigo

Dermatologic: Alopecia, erythema nodosum, exfoliative dermatitis, pruritus, skin pigmentation, skin rash, skin ulcers, urticaria

Endocrine & metabolic: Goiter, weight gain

Gastrointestinal: Constipation, loss of taste, nausea, sialoadenopathy, splenomegaly, stomach pain, taste perversion, vomiting

Hematologic: Agranulocytosis, aplastic anemia, bleeding, granulopenia, hypoprothrombinemia, leukopenia, thrombocytopenia

Hepatic: Acute liver failure, cholestatic jaundice, hepatitis

Neuromuscular & skeletal: Arthralgia, myalgia, paresthesia

Renal: Acute renal failure, glomerulonephritis, nephritis

Respiratory: Alveolar hemorrhage, interstitial pneumonitis

Miscellaneous: Lymphadenopathy, SLE-like syndrome

Concerns related to adverse effects:

• Bleeding: May cause hypoprothrombinemia and bleeding

• Bone marrow suppression: May cause significant bone marrow depression; the most severe manifestation is agranulocytosis (commonly within first 3 months of therapy). Aplastic anemia, 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.

• Dermatitis: Has been associated with rare but severe dermatologic reactions; discontinue in the presence of exfoliative dermatitis.

• Fever: Discontinue in the presence of unexplained fever.

• Hepatic reactions: [U.S. Boxed Warning]: Severe liver injury (some fatal) and acute liver failure (some cases requiring transplantation) have been reported. Patients should be counseled to recognize and report symptoms suggestive of hepatic dysfunction (especially in first 6 months of treatment), which should prompt immediate discontinuation. Routine liver function test monitoring may not reduce risk due to unpredictable and rapid onset.

• Lupus-like syndrome: Has been associated with a variety of autoimmune reactions, including a lupus-like syndrome; discontinuation may be warranted.

• Nephritis: Has been associated with glomerulonephritis and interstitial nephritis with acute renal failure; discontinuation of therapy may be warranted.

• Pneumonitis: Has been associated with rare reports of interstitial pneumonitis. Prompt evaluation is warranted in patients reporting respiratory signs/symptoms consistent with this reaction; discontinuation is warranted in cases or interstitial pneumonitis.

• Vasculitis: Has been associated (rarely) with the development of ANCA-positive vasculitis or leukocytoclastic vasculitis; prompt discontinuation is warranted in patients who develop vasculitis during therapy.

Other warnings/precautions:

• Appropriate use: Propylthiouracil should be reserved for adults or children unable to tolerate methimazole or in whom surgery or radioactive iodine treatment are not appropriate.

Monitoring Parameters

CBC with differential, prothrombin time, liver function tests (bilirubin, alkaline phosphatase, transaminases), and thyroid function tests (TSH, T₃, T₄) every 4-6 weeks until euthyroid; periodic blood counts are recommended for chronic therapy

Standard Dosing: Oral: Administer in equally divided doses every 8 hours. Adjust dosage to maintain T₃, T₄, and TSH levels in normal range; elevated T₃ may be sole indicator of inadequate treatment. Elevated TSH indicates excessive antithyroid treatment.

Children: Initial: 5-7 mg/kg/day or 150-200 mg/m²/day in divided doses every 8 hours

or

Manufacturer's recommendations:

6-10 years: 50-150 mg/day

>10 years: 150-300 mg/day

Adults:

Hyperthyroidism: Initial: 300 mg/day in 3 divided doses; 400 mg/day in patients with severe hyperthyroidism and/or very large goiters; an occasional patient will require 600-900 mg/day; usual maintenance: 100-150 mg/day

Graves’ disease (unlabeled use): Initial: 50-150 mg (depending on severity) 3 times daily to restore euthyroidism; maintenance: 50 mg 2-3 times daily for a total of 12-18 months, then tapered or discontinued if TSH is normal at that time (Bahn, 2011)

Thyrotoxic crisis/thyroid storm (unlabeled use): Note: Recommendations vary widely and have not been evaluated in comparative trials. Typical dosing is 800-1200 mg/day given as 200-300 mg every 4-6 hours; some clinicians advocate an initial loading dose of 600-1000 mg. After initial response, dose may be reduced gradually to a maintenance dosage (100-600 mg/day in divided doses) (Goldberg, 2003; Nayak, 2006). The American Thyroid Association and the American Association of Clinical Endocrinologists recommend 500-1000 mg loading dose followed by 250 mg every 4 hours (Bahn, 2011).

Duration of therapy: Clinical improvement generally occurs in 1-3 months, after which dosage reduction may be employed (to prevent hypothyroidism), with discontinuation considered after 12-18 months of therapy. Thyroid function should be monitored every 2 months thereafter for 6 months until remission is confirmed, followed by annual evaluations (Cooper, 2005).

Drug interactions: http://www.drugs.com/drug-interactions/propylthiouracil.html

A total of 54 drugs (224 brand and generic names) are known to interact with propylthiouracil.

• 6 major drug interactions (15 brand and generic names)
• 48 moderate drug interactions (209 brand and generic names)

Show all medications in the database that may interact with propylthiouracil.

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

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for agranulocytosis may be increased. Avoid combination

Sodium Iodide I131: Antithyroid Agents may diminish the therapeutic effect of Sodium Iodide I131. Management: Discontinue antithyroid therapy 3-4 days prior to sodium iodide I-131 administration. Avoid combination

Theophylline Derivatives: Antithyroid Agents may increase the serum concentration of Theophylline Derivatives.Exceptions: Dyphylline. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Antithyroid Agents may diminish the anticoagulant effect of Vitamin K Antagonists.Consider therapy modification

Propylthiouracil and Methimazole: Graves-ly Propyl-pared with the best Meth-id to stop the thyroxine. (Methimazole is the preferred Tx).