by Phyllis Hanlon, Contributing Writer

The Food and Drug Administration (FDA) has approved 14 medications to treat patients with World Health Organization (WHO) Group 1 PH, pulmonary arterial hypertension (PAH). Eight of those drugs target components of the prostacyclin pathway, which helps to relax the blood vessels in the lungs. Even though these drugs have been shown to improve survival and exercise capacity, they often produce side effects that can cause patients to stop taking them. A group of experienced PH providers has written an article to characterize common side effects seen with these medications and to offer recommendations on how to manage these side effects.

Three of the authors work in centers accredited by the Pulmonary Hypertension Association (PHA): Martha Kingman, DNP, FNP-C, from the University of Texas Southwestern Medical Center at Dallas (; Christine Archer-Chicko, CRNP, MSN, from the University of Pennsylvania (; and Robin Hohsfield, RN, BSN, from the University of Colorado Health in Denver (

Also contributing to the article was Joy Beckman, RN, MSN of Harbor-UCLA Medical Center; Mary Bartlett, MS, FNP of Winthrop University Hospital; and senior author Sandra Lombardi, RN from the University of California, San Diego PH programs.

In their paper, these clinicians noted that prostacyclins are approved only for patients with PAH, which is WHO Group 1.

Prostacyclin pathway medications can be administered in several different ways: by continuous intravenous (IV) infusion (i.e., epoprostenol in both forms); subcutaneously, or under the skin (i.e., treprostinil), inhalation (i.e., iloprost or treprostinil); or orally (i.e., selexipag or treprostinil). Regardless of administration method, the drugs are usually started at a low dose and then are slowly increased. The authors pointed out that, for the most part, side effects are worse when the dosage is being increased and tend to improve after reaching a manageable dose.

So what are the most common side effects?

The authors report the following potential side effects and offer ways to address them. This list was intended to provide a review on some of the frequently used methods by these healthcare providers. This can vary by patient, so it is important that you talk to your healthcare team about side effects you might be experiencing before trying any of the items listed below.

  • Pain in the jaw, leg and generalized body pain is one potential side effect. After assessing the severity and quality of the pain, the healthcare provider first recommends non-pharmaceutical methods to alleviate pain, including a heating pad, massage, acupressure, or relaxation techniques. If this does not work, the healthcare professional might prescribe an over-the-counter medication, such as acetaminophen, or something as strong as gabapentin or tramadol.
  • Headaches might plague patients, particularly those who have a past history. In this case, healthcare professionals might recommend a medication to take before the prostacyclin PH drug to prevent or reduce the severity of a headache. If the pain is unexpectedly severe, it might be wise to conduct an imaging study to rule out another cause for headache.
  • Dizziness and low blood pressure sometimes occur in patients taking prostacyclins and other PH medications. You should report any dizziness or low blood pressure to your healthcare team.
  • Nausea and vomiting may occur with any of the prostacyclin medications. Clinicians sometimes recommend that patients eat smaller, more frequent meals, or use ginger-based food products. Medication can be given before the dose in some cases to prevent nausea. Women should be screened for pregnancy. Any loss of appetite or continuing nausea and vomiting can lead to weight loss. If necessary, the patient should be referred for a dietary consultation.
  • Diarrhea is a typical side effect when taking prostacyclins, but can be managed with over-the-counter medication. However, a severe case could actually be Clostridium difficile (C. diff), a bacteria which cause inflammation in the colon, or some other cause and should be ruled out by a specialist.
  • Flushing or rash is a minor side effect that can be controlled by using cool packs or a fan.
  • Coughing and sore throat might occur when the patient is taking inhaled prostacyclins. Throat lozenges or a bronchodilator (inhaler) can sometimes help relieve symptoms. Cough can also occur if the medication is not being breathed in correctly and can be evaluated by the Specialty Pharmacy nurse.
  • Thrombocytopenia (low blood platelets; platelets help stop bleeding) has been seen with certain prostacyclins and with advanced PAH. Any patient with a low platelet count at the beginning of treatment should be monitored carefully with routine blood tests.

In addition to the above side effects, patients might experience certain complications related to the way they receive medication, according to the authors. Drugs given subcutaneously (under the skin) could cause pain, tenderness or mild bleeding at the site. The authors indicated that ice packs, pain patches or pain-relieving medications could help reduce side effects. In some cases a different type of catheter might be helpful.

Those patients receiving prostacyclins via intravenous infusion could develop an infection, the authors reported. They recommend a “closed-hub system” to reduce the chance of introducing bacteria into the site. Fever should always be reported to the healthcare provider.

Kingman and Hohsfield noted that side effects are common, but usually resolve or lessen in time, although each patient is unique and should be evaluated on a case-by-case basis. They pointed out that clinicians who have a “clear understanding of options” are better able to develop an effective treatment strategy to tackle side effects. It is also important for clinicians to differentiate between side effects of medication and signs of worsening disease. Most important, the authors urge clinicians to educate patients on managing side effects and they encourage open communication. The study authors, who are nurses or nurse practitioners, asserted that nurses “…are in a key position to provide patient support and counseling, thereby helping patients remain on therapy.”

The authors noted that the conclusions and recommendations in this study are largely based off of similarities to other disease states and personal experience, and that evidence-based support is lacking. You should discuss any side effects you might be experiencing with your healthcare team and ask for recommendations on how to reduce these.

Kingman added, “Most patients receiving prostacyclin therapy will experience side effects, especially when starting on therapy.  In most cases, the side effects can be managed if patients and providers work closely and begin with a proactive plan.”

Each PH patient is different. It is essential that you talk to your own doctor about what treatment options are best for you. For more information on finding a doctor or an accredited care center, visit


Prostacyclin pathway medications can be given by IV infusion, subcutaneously or orally.

A team of authors looked at common side effects and provided recommendations for managing these side effects.

Authors noted that side effects are common, but usually resolve or lessen in time.

Each patient is unique and should be evaluated on a case-by-case basis.