Drugs for hypothyroidism

Levothyroxine is a synthetic form of the thyroid hormone thyroxine (T4). Levothyroxine is commonly used for oral replacement therapy in the treatment of hypothyroidism. It has poor and variable oral bioavailability (40% to 80%) that can be decreased by age, foods, and certain drugs. Typically it should be taken with water only on an empty stomach 30 minutes to one hour before food, one hour before taking food, soya milk, coffee or bulk-forming laxatives (dietary fibre), and four hours before iron or calcium supplements or antacids. Levothryoxine is converted to the more potent triiodothyronine (T3) by deiodinases in the liver, kidney, and various target tissues and organs. It has a long half-life of 6 to 8 days, so it takes several weeks to reach steady-state plasma concentration. When administered orally, it has an onset of action in 3 to 5 days and must be taken consistently for 3 to 4 weeks before the peak clinical effect is achieved. The major adverse effects are due to the risk of hyperthyroidism on overdose. Risks include cardiac arrest,  hypertension, palpitations, tachycardia, anxiety, heat intolerance, hyperactivity, insomnia, irritability, and weight loss. Long-term use of high doses has been associated with increased bone resorption and reduced bone mineral density, especially in post-menopausal women.

Liothyronine is a synthetic form of the thyroid hormone triiodothyronine (T3). Liothyronine is administered intravenously and orally for the treatment of myxoedema. Compared to levothyroxine, it has better oral bioavailability (approximately 95%), which is less strongly impacted by food and drugs, and a much faster onset of clinical action (2 to 4 hours) and time to peak therapeutic effect (typically 2 to 3 days). The faster onset of action is an advantage over levothyroxine in treating myxoedema. However, liothyronine is less desirable for chronic replacement therapy than levothyroxine as it is more potent and therefore has a greater risk of the cardiovascular adverse effects associated with thyroid hormone excess. Oral liothyronine is also sometimes used in combination with levothyroxine for chronic replacement therapy in patients with persistent complaints impacting their quality of life after levothyroxine alone. However, the benefits and long-term safety of combination replacement therapy remain inconclusive.