Propylthiouracil

=Propylthiouracil=

How it works
//Block thyroid hormone synthesis; propylthiouracil also inhibits peripheral conversion (deiodination) of T4 to T3.//

Questions to Ask
What medications? - medical conditions? - allergies?

- PTU crosses the placenta, primary effect on the foetus is the production of a mild hypothyroidism when the drug is used close to term (resolves within a few days without treatment) - the hypothyroid state may be observed as a goitre in the newborn, a result of the increased levels of foetal pituitary thyrotropin - use of PTU in early pregnancy does not produce foetal goitre because the foetal thyroid does not begin hormone production until approximately the 11th or 12th week of gestation - Maternal hyperthyroidism itself has been shown to be a cause of malformations - the risk of congenital defects with PTU is not increased over that of nontreated controls (but PTU is more likely than methimazole to cause suppression of foetal thyroid production) - combination therapy (thyroid and anti-thyroid drugs) are now considered inappropriate as use of thyroid hormones may require higher doses of PTU to be used and placental transfer of T4 and T3 is minimal and not sufficient to reverse foetal hypothyroidism Use the lowest effective dosage (especially during the 3rd trimester); propylthiouracil preferred; do not use block-replace regimen; ADEC category C. Check TSH and free thyroid hormone every 6 weeks.
 * Pregnancy**

Propylthiouracil preferred because of lower secretion in breast milk; use the lowest effective dosage with appropriate monitoring of infant. - one mother took 200-300 mg daily while breastfeeding, with no changes in any of the infant's thyroid parameters observed - PTU does not seem to pose a significant risk to the breast-fed infant, but periodic evaluation of the infant's thyroid function would be prudent - PTU is the drug of choice because it is ionised at physiologic pH and protein bound (80%)
 * Breastfeeding**

How to take
//Initially//, 200–400 mg daily in 2–4 divided doses for 3–4 weeks. //Adjusted regimen//, maintenance dose 25–300 mg daily in divided doses, according to response. //Block-replace regimen//, continue initial dosage and add 100–150 micrograms thyroxine when T4 in normal range.
 * Hyperthyroidism**

//Adult//, 600–800 mg daily, in divided doses, gradually reduced
 * Thyroid storm**

Side effects
//Occur most often during the first 8 weeks of treatment. Itching and mild rashes may respond to antihistamines while continuing treatment; if a change in treatment is needed, the 2 drugs can often be interchanged without recurrence of adverse effects (unless agranulocytosis occurred, in which case seek specialist advice for future management).//
 * Common:** itching, rash, mild leucopenia, nausea, vomiting, gastric discomfort, headache, arthralgia
 * Rare:** agranulocytosis (below), hypoprothrombinaemia and bleeding, myositis, hepatotoxicity (below), vasculitis, lupus-like syndrome

Most likely in first 3 months of treatment; its rapid onset means regular monitoring is of questionable use.
 * Agranulocytosis**

Asymptomatic increases in serum transaminases may occur commonly during the first 2 months of propylthiouracil treatment, but resolve with continued treatment. Serious hepatotoxic reactions (usually hepatocellular hepatitis) occur rarely with propylthiouracil and may be immune-based. Cholestatic jaundice has rarely been associated with carbimazole. As the mechanisms of hepatic damage with the 2 drugs are thought to be different, the other drug may be tried cautiously in cases of drug-induced hepatic adverse effects.
 * Hepatotoxicity**

Other advice?
Tell your doctor immediately if you develop a fever, mouth ulcers, sore throat, rash, severe fatigue, nausea, abdominal pain or jaundice.

CMI
[|AMH]