Why do Epoprostenol (Prostacyclin) and Iloprost (Prostacyclin analogue) cause jaw pain?

From the Guidelines

Epoprostenol and iloprost cause jaw pain as a side effect due to their vasodilatory properties, which can lead to excessive dilation of blood vessels in the jaw area, resulting in increased blood flow and pressure that stimulates pain receptors in the jaw muscles and surrounding tissues. These medications are prostacyclin analogs that work by relaxing smooth muscle in blood vessels, causing them to widen. When these drugs are administered, they affect blood vessels throughout the body, including those that supply the jaw muscles and temporomandibular joint. The jaw pain, sometimes called "jaw claudication," occurs because these medications can cause excessive dilation of blood vessels in the jaw area, leading to increased blood flow and pressure. This vascular effect can stimulate pain receptors in the jaw muscles and surrounding tissues. The pain typically manifests as a dull ache or tightness in the jaw, particularly during or shortly after drug administration. The intensity of jaw pain varies among patients and often diminishes with continued use as the body develops tolerance to this side effect, as reported in studies such as 1 and 1. Patients receiving these medications should be informed about this common side effect, which, while uncomfortable, is generally not dangerous and often improves over time with continued treatment.

Some key points to consider:

• Epoprostenol and iloprost are prostacyclin analogs used to treat pulmonary arterial hypertension (PAH) and other conditions.
• Jaw pain is a common side effect of these medications, resulting from their vasodilatory properties.
• The pain typically manifests as a dull ache or tightness in the jaw, particularly during or shortly after drug administration.
• The intensity of jaw pain varies among patients and often diminishes with continued use as the body develops tolerance to this side effect.
• Studies such as 1 and 1 have reported the efficacy and safety of epoprostenol and iloprost in treating PAH, including the incidence of jaw pain as a side effect.

Overall, while jaw pain is a potential side effect of epoprostenol and iloprost, the benefits of these medications in treating PAH and other conditions often outweigh the risks, and patients should be informed about this common side effect and monitored for its occurrence, as recommended in guidelines such as 1 and 1.

From the FDA Drug Label

Adverse events which may be related to the underlying disease include dyspnea, fatigue, chest pain, edema, hypoxia, right ventricular failure, and pallor. Several adverse events, on the other hand, can clearly be attributed to epoprostenol These include hypotension, bradycardia, tachycardia, pulmonary edema, bleeding at various sites, thrombocytopenia, headache, abdominal pain, pain (unspecified), sweating, rash, arthralgia, jaw pain, flushing, diarrhea, nausea and vomiting, flu-like symptoms, anxiety/nervousness, and agitation

Table 9: Adverse Events Regardless of Attribution Occurring in Patients with Idiopathic or Heritable PAH with ≥10% Difference between Epoprostenol and Conventional Therapy Alone ... Musculoskeletal Jaw pain 54% 0%

Table 10: Adverse Events Regardless of Attribution Occurring in Patients with PAH/SSD With ≥10% Difference Between Epoprostenol and Conventional Therapy Alone ... Musculoskeletal Jaw pain 75% 0%

The exact reason why epoprostenol causes jaw pain is not explicitly stated in the label. However, jaw pain is listed as an adverse event that can be attributed to epoprostenol. There is no information about iloprost in the provided label, therefore, no conclusion can be drawn about iloprost. 2

From the Research

Jaw Pain Associated with Epoprostenol and Iloprost

• Jaw pain is a known side effect of certain medications, including epoprostenol and iloprost, which are used to treat pulmonary arterial hypertension (PAH) 3.
• The exact mechanism of jaw pain associated with these medications is not fully understood, but it is thought to be related to their vasodilatory effects 3.
• Iloprost, a stable prostacyclin analogue, has been shown to cause jaw pain in some patients, in addition to other side effects such as mild coughing and minor headache 3.
• Epoprostenol, a synthetic analog of prostacyclin, has also been associated with jaw pain, although the frequency and severity of this side effect are not well documented 4, 5, 6.
• The development of jaw pain may be related to the dose and duration of treatment with these medications, as well as individual patient factors 3, 7.
• Further research is needed to fully understand the causes and risk factors for jaw pain associated with epoprostenol and iloprost, and to develop effective strategies for preventing and managing this side effect 4, 5, 6.