Dosing and uses of PropylThyracil, PTU (propylthiouracil)
Adult dosage forms and strengths
tablet
- 50mg
Hyperthyroidism
300-450 mg/day PO divided q8hr initially (may require up to 600-900 mg/day)
Maintenance: 100-150 mg/day divided q8hr
Thyrotoxic Crisis (Unlabeled)
Initial 200-300 mg PO q4-6hr initially on Day 1 (may require 800-1200 mg/day), then reduce gradually; some practitioners propose an initial dose of 600-1000 mg with gradual dose reduction after initial response
Maintenance: 100-150 mg/day PO divided q8-12hr
Graves Disease
50-150 mg PO q8hr initially
Maintenance: 50 mg PO q8-12hr for up to 12-18 months; then taper and discotinue if euthyroidism restored (TSH) is normaL
Renal Impairment
Dose adjustment not necessary
Other Indications & Uses
Off-label: alcoholic liver disease
Pediatric dosage forms and strengths
tablet
- 50mg
Hyperthyroidism
Neonates (<28 days old): 5-10 mg/kg/day PO divided q8hr initially
<6 years: 5-7 mg/kg/day PO divided q8hr initially Or
6-10 years: 50-150 mg/day PO divided q8hr
>10 years: 150-300 mg/day
Maintenance: Usually 1/3-2/3 of intial dose based on response divided q8-12hr
PropylThyracil, PTU (propylthiouracil) adverse (side) effects
Frequency not defined
Agranulocytosis
Aplastic anemia
Dermatologic reactions
Hepatitis
Polyarthritis
Drowsiness
Fever
Headache
Vertigo
Alopecia
Erythema nodosum
Exfoliative dermatitis
Skin rash
Skin ulcers
Goiter
Weight gain
Constipation
Loss of taste
Granulopenia
Leukopenia
Thrombocytopenia
Postmarketing Reports
Inhibition of myelopoiesis (agranulocytosis, granulopenia, aplastic anemia, and thrombocytopenia)
Drug fever, a lupus-like syndrome (including splenomegaly and vasculitis)
Periarteritis
Hypoprothrombinemia
Bleeding
Nephritis
Glomerulonephritis
Interstitial pneumonitis
Exfoliative dermatitis
Erythema nodosum
Vasculitis syndrome associated with the presence of antineutrophilic cytoplasmic antibodies (ANCA) Skin rash
Uticaria
Nausea
Vomiting
Epigastric distress
Arthralgia
Paresthesias
Loss of taste
Taste perversion
Warnings
Black box warnings
Severe liver injury and acute liver failure, some of which have been fatal, have been reported in adult and pediatric patients taking propylthiouraciL
Closely monitor for symptoms and signs of liver injury (eg, , anorexia, nausea, vomiting, fatigue, pruritus, dark colored urine, or jaundice), especially during first 6 months after initiating therapy
Reserve propylthiouracil use for those unable to tolerate other treatments (eg, methimazole, radioactive iodine, surgery)
Propylthiouracil may be the treatment of choice during and just before the first trimester of pregnancy (strong association of methimazole with congenital malformation during first trimester)
Contraindications
Hypersensitivity
Cautions
Liver disease, bleeding disorder, pregnancy, concurrency with other agranulocytosis-causing drugs
Risk of severe liver injury and rare immunoallergenic hepatitis
Discontinue immediately if abnormal LFTs (transmainase >3 times ULN)
Risk of rare but serious agranulocytosis may occur
Bone marrow suppression reported
Severe dermatologic reactions reported
Discontinue in the presence of unexplained fever
Lupus-like syndrome reported (may need to discontinue)
Glomerulonephritis and interstitial nephritis with acute renal failure reported
Interstitial pneumonitis and different forms of vasculitis may occur
High relapse rate (more likely in smokers)
May cause hypoprothrombinemia
Propylthiouracil can cause hypothyroidism necessitating routine monitoring of TSH and free T4 levels with adjustments in dosing to maintain a euthyroid state; because drug readily crosses placental membranes, propylthiouracil can cause fetal goiter and cretinism when administered to a pregnant woman
Patients should be instructed to report any symptoms of hepatic dysfunction (anorexia, pruritus, jaundice, light colored stools, dark urine, right upper quadrant pain, etc.), particularly in the first six months of therapy; when symptoms occur, measurement should be made of liver function (bilirubin, alkaline phosphatase) and hepatocellular integrity (ALT/AST levels)
Pregnancy and lactation
Pregnancy category: d
Lactation: distributed in breast milk, contraindicated by some sources (AAP Committee states compatible w/ nursing ; AAFP states safe for nursing)
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of PropylThyracil, PTU (propylthiouracil)
Mechanism of action
Inhibits synthesis of thyroid hormone by blocking oxidation of iodine in thyroid gland; blocks synthesis of T4 and T3
Pharmacokinetics
Absorption: 75%
Duration: 12-24 hr
Half-life elimination: 1-2 hr, increase in ESRd
Vd: 0.4 L/kg
Protein Bound: 80-85%
Concentration (200-400 mg single dose): 6-9 mcg/mL
Peak plasma time: 1-2 hr
Peak plasma concentration: (200-400 mg single dose): 6-9 mcg/mL
Metabolism: liver, to glucuronide conjugates, inorganic sulfates, sulfur metabolites
Total body clearance: 7 L/hr
Excretion: Urine (35%)
