Pasireotide is a synthetic somatostatin analog. This compound mimics the actions of somatostatin, a naturally occurring hormone in the body that helps regulate various bodily functions, including the secretion of other hormones. Pasireotide is utilized in managing rare and complex endocrine disorders, particularly when other treatment approaches have not been effective or are not suitable.
Conditions Pasireotide Treats
Pasireotide is primarily used in the treatment of Cushing’s disease and acromegaly, two distinct endocrine disorders resulting from hormonal imbalances.
Cushing’s disease occurs when the body produces too much cortisol, often due to a noncancerous tumor in the pituitary gland that overproduces adrenocorticotropic hormone (ACTH). This excess cortisol can lead to symptoms such as weight gain, particularly in the trunk and face, thinning skin, easy bruising, and high blood pressure.
Acromegaly involves an excess of growth hormone (GH) in adults, typically caused by a benign tumor in the pituitary gland. This overproduction of GH stimulates the liver to produce insulin-like growth factor 1 (IGF-1), which causes abnormal growth of bones, cartilage, and other tissues. Symptoms can include enlarged hands and feet, changes in facial features, joint pain, and increased sweating.
How Pasireotide Works
Pasireotide functions by acting as a somatostatin analog, binding to specific somatostatin receptors (SSTRs) found on various cells throughout the body. Unlike older somatostatin analogs, pasireotide has a broader binding profile, showing high affinity for multiple SSTR subtypes, including SSTR1, SSTR2, SSTR3, and SSTR5. Its highest affinity is for SSTR5, which is particularly relevant for its therapeutic effects.
In Cushing’s disease, pasireotide binds to SSTR5 on pituitary tumors, which then inhibits the secretion of ACTH. This reduction in ACTH subsequently lowers the production of cortisol from the adrenal glands, helping to alleviate the disease’s symptoms. For acromegaly, pasireotide’s action on SSTR5 and other somatostatin receptors on pituitary adenomas reduces the secretion of GH and, consequently, IGF-1 levels. This targeted action helps manage the symptoms associated with excessive growth hormone.
Administering Pasireotide
Pasireotide is administered through injections, with two main formulations available: subcutaneous and intramuscular. The subcutaneous form is typically given twice daily.
The intramuscular formulation, known as pasireotide long-acting release (LAR), is administered once every four weeks. This long-acting version helps maintain stable drug levels over an extended period. The choice of administration route and specific dosage depends on the individual’s condition, response to treatment, and tolerability, and is determined by a healthcare professional.
Potential Side Effects and Important Considerations
Pasireotide treatment can lead to various side effects, with elevated blood sugar, or hyperglycemia, being a common concern. This occurs because pasireotide can suppress insulin secretion. Patients may experience increased thirst, frequent urination, fatigue, and weight loss, even with increased appetite. Regular monitoring of blood sugar levels, including fasting plasma glucose and HbA1c, is recommended before starting therapy, weekly for the first three months, and periodically thereafter, especially for those with pre-existing diabetes.
Cardiac issues, including QT prolongation and bradycardia, are potential side effects. QT prolongation, a delay in the heart’s electrical recharging process, can increase the risk of irregular heart rhythms, while bradycardia is a slower-than-normal heart rate. Patients should have baseline and periodic electrocardiograms (ECGs) to monitor heart rhythm, and serum potassium and magnesium levels should be checked and corrected if needed, as imbalances can affect heart function.
Gastrointestinal disturbances include diarrhea, nausea, abdominal pain, and gallstones. Gallstone formation can occur due to pasireotide’s effect on gallbladder contractility and bile production. Pasireotide may suppress other pituitary hormones, which can cause adrenal insufficiency with symptoms such as confusion, weakness, and appetite changes. Patients should inform their healthcare provider about all medications they are taking, as pasireotide can interact with other drugs, especially those affecting heart rhythm or blood glucose levels.