PROPYLTHIOURACIL (PTU)

(proe-pill-thye-oh-yoor'a-sill)

Propyl-Thyracil

Classifications: hormone; antithyroid agent;
Therapeutic: antithyroid
Pregnancy Category: D

Availability

50 mg tablets

Action

Interferes with use of iodine and blocks synthesis of thyroxine (T₄) and triiodothyronine (T₃). Does not interfere with release and utilization of stored thyroid hormone; thus antithyroid action is delayed days and weeks until preformed T₃ and T₄ are degraded.

Therapeutic Effect

Drug-induced hormone reduction results in compensatory release of thyrotropin (TSH), which causes marked hyperplasia and vascularization of thyroid gland.

Uses

Hyperthyroidism, iodine-induced thyrotoxicosis, and hyperthyroidism associated with thyroiditis; to establish euthyroidism prior to surgery or radioactive iodine treatment; palliative control of toxic nodular goiter.

Contraindications

Hypersensitivity to propylthiouracil; concurrent administration of sulfonamides or coal tar derivatives such as aminopyrine or antipyrine; pregnancy (category D).

Cautious Use

Infection; concomitant administration of anticoagulants or other drugs known to cause agranulocytosis; bone marrow depression; impaired liver function.

Route & Dosage

Hyperthyroidism
Adult: PO 300–450 mg/d divided q8h, may need 600–1200 mg/d initially
Geriatric: PO 150–300 mg/d divided q8h
Child: PO 6–10 y, 50–150 mg/d; >10 y, 150–300 mg/d or 150 mg/m²/d
Neonates: PO 5–10 mg/kg/d

Thyrotoxic Crisis
Adult: PO 200 mg q4–6h until full control achieved

Administration

Give at the same time each day with relation to meals. Food may alter drug response by changing absorption rate.
If drug is being used to improve thyroid state before radioactive iodine (RAI) treatment, discontinued 3 or 4 d before treatment to prevent uptake interference. PTU therapy may be resumed if necessary 3–5 d after the RAI administration.
Store drug at 15°–30° C (59°–86° F) in light-resistant container.

Adverse Effects (≥1%)

CNS: Paresthesias, headache, vertigo, drowsiness, neuritis. GI: Nausea, vomiting, diarrhea, dyspepsia, loss of taste, sialoadenitis, hepatitis. Hematologic: Myelosuppression, lymphadenopathy, periarteritis, hypoprothrombinemia, thrombocytopenia, leukopenia, agranulocytosis. Metabolic: Hypothyroidism (goitrogenic): Enlarged thyroid, reduced GI motility, periorbital edema, puffy hands and feet, bradycardia, cool and pale skin, worsening of ophthalmopathy, sleepiness, fatigue, mental depression, dizziness, vertigo, sensitivity to cold, paresthesias, nocturnal muscle cramps, changes in menstrual periods, unusual weight gain. Skin: Skin rash, urticaria, pruritus, hyperpigmentation, lightening of hair color, abnormal hair loss. Body as a Whole: Drug fever, lupus-like syndrome, arthralgia, myalgia, hypersensitivity vasculitis.

Diagnostic Test Interference

Propylthiouracil may elevate prothrombin time and serum alkaline phosphatase, AST, ALT levels.

Interactions

Drug: Amiodarone, potassium iodide, sodium iodide, thyroid hormones can reverse efficacy.

Pharmacokinetics

Absorption: Rapidly from GI tract. Peak: 1–1.5 h. Distribution: Appears to concentrate in thyroid gland; crosses placenta; some distribution into breast milk. Metabolism: Rapidly to inactive metabolites. Elimination: 35% in urine within 24 h. Half-Life: 1–2 h.

Nursing Implications

Assessment & Drug Effects

Be aware that about 10% of patients with hyperthyroidism have leukopenia <4000 cells/mm³ and relative granulopenia.
Observe for signs of clinical response to PTU (usually within 2 or 3 wk): Significant weight gain, reduced pulse rate, reduced serum T₄.
Lab tests: Baseline and periodic T₃ and T₄; periodic CBC with differential and platelet count.
Satisfactory euthyroid state may be delayed for several months when thyroid gland is greatly enlarged.
Be alert to signs of hypoprothrombinemia: Ecchymoses, purpura, petechiae, unexplained bleeding. Warn ambulatory patients to report these signs promptly.
Be alert for important diagnostic signs of excess dosage: Contraction of a muscle bundle when pricked, mental depression, hard and nonpitting edema, and need for high thermostat setting and extra blankets in winter (cold intolerance).
Monitor for urticaria (occurs in 3–7% of patients during weeks 2–8 of treatment). Report severe rash.

Patient & Family Education

Note that PTU treatment may be reinstituted if surgery fails to produce normal thyroid gland function.
Be aware that thyroid hormone may be given concomitantly with PTU throughout pregnancy to prevent hypothyroidism in mother with little effect on fetus.
Report severe skin rash or swelling of cervical lymph nodes. Therapy may be discontinued.
Report to physician sore throat, fever, and rash immediately (most apt to occur in first few months of treatment). Drug will be discontinued and hematologic studies initiated.
Avoid use of OTC drugs for asthma, or cough treatment without checking with the physician. Iodides sometimes included in such preparations are contraindicated.
Learn how to take pulse accurately and check daily. Report to physician continued tachycardia.
Report diarrhea, fever, irritability, listlessness, vomiting, weakness; these are signs of inadequate therapy or thyrotoxicosis.
Chart weight 2 or 3 times weekly; clinical response is monitored through changes in weight and pulse.
Continue monitoring and recording weight and pulse rate while in remission. Report onset of tremor, anxiety state, gradual ascending pulse rate, and loss of weight to physician (signs of hormone deficiency).
Do not alter drug regimen (e.g., increase, decrease, omit doses, change dosage intervals).
Check with physician about use of iodized salt and inclusion of seafood in the diet.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

(154)