Side Effects of treprostinil oral inhalation: A Synthesis of Findings from 6 Studies

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Original Abstract of the Article

Major Research Findings

Treprostinil (TRE) is a pulmonary vasodilator drug used to treat pulmonary arterial hypertension (PAH). 2 However, due to its short half-life, TRE requires frequent administration, leading to increased side effects. 2 To address this issue, researchers have developed a long-acting inhaled prodrug formulation of treprostinil called treprostinil palmitil (TP). 2 TP is formulated in lipid nanoparticles (LNPs) and administered as a nebulized inhaled suspension (TPIS). 2

Preclinical studies have shown that TPIS maintains high concentrations of TP in the lungs while minimizing systemic exposure to TRE, suggesting reduced systemic side effects. 2 TPIS demonstrated efficacy in animal models by inhibiting pulmonary vasoconstriction and remodeling. 2 Notably, TPIS did not cause cough in animal models at doses that induced cough with inhaled TRE. 2 Additionally, TPIS exhibited anti-fibrotic and anti-inflammatory effects in animal models of pulmonary fibrosis and asthma. 2

Reasons for side effects

Treprostinil is a prostanoid analog, and its vasodilator effects can lead to systemic side effects, such as headache and nausea. 1 Inhaled treprostinil, due to its local concentration in the lungs, can cause respiratory side effects like cough and throat irritation. 1

Common Side Effects

Headache

Treprostinil can cause headache due to its vasodilator effects. 1

Nausea

Treprostinil can cause nausea and other gastrointestinal symptoms due to its vasodilator effects. 1

Cough

Inhaled treprostinil can cause cough due to its local concentration in the lungs. 1

Throat Irritation

Inhaled treprostinil can cause throat irritation due to its local concentration in the lungs. 1

Side effects management

Headache

If headache is severe, consult your doctor. 1 Pain relievers may be prescribed. 1

Nausea

If nausea is severe, consult your doctor. 1 Anti-nausea medication may be prescribed. 1

Cough

If cough is severe, consult your doctor. 1 Cough suppressants may be prescribed. 1

Throat Irritation

If throat irritation is severe, consult your doctor. 1 Gargling with saline water may provide relief. 1

Comparison between Studies

Commonalities in Studies

Multiple studies have consistently acknowledged the short half-life of treprostinil. 2

Differences in Studies

Treprostinil side effect research may exhibit variability in results due to differences in study design and participant populations. 1 For example, the side effects of inhaled treprostinil formulations may vary based on the type of formulation and dosage administered. 1

Considerations for Real-World Application

While treprostinil is an effective treatment for PAH, it is essential to be aware of potential side effects. 1 Consulting a physician before starting treatment and adhering to prescribed dosage instructions are crucial. 1

Limitations of Current Research

Research on treprostinil side effects remains insufficient. 1 Further investigation is warranted. 1

Future Research Directions

Research aimed at mitigating treprostinil side effects is crucial. 1 This could include developing novel treprostinil formulations or discovering medications to suppress treprostinil side effects. 1

Conclusion

Treprostinil is an effective PAH treatment, but it's important to be aware of potential side effects. 1 While research on treprostinil side effects is ongoing, further research is needed to minimize side effects. 1

Literature analysis of 6 papers
Positive Content
6
Neutral Content
0
Negative Content
0
Article Type
1
0
0
2
6
2.

An overview of the biology of a long-acting inhaled treprostinil prodrug.

Author: ChapmanRichard W, CorbozMichel R, MalininVladimir S, PlauntAdam J, KonicekDonna M, LiZhili, PerkinsWalter R

PAH treatment
Respiratory side effects

This report describes the discovery and preclinical development of treprostinil palmitil (TP), a long-acting prodrug of treprostinil (TRE), for the treatment of pulmonary arterial hypertension (PAH). TP, formulated as a nebulized inhaled suspension (TPIS), was shown to have a slower conversion rate to TRE than short-alkyl chain TRE prodrugs, providing a longer duration of action.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

3.

Acute effects of the combination of sildenafil and inhaled treprostinil on haemodynamics and gas exchange in pulmonary hypertension.

Author: VoswinckelRobert, ReichenbergerFrank, EnkeBeate, KreckelAndre, KrickStefanie, GallHenning, SchermulyRalph Theo, GrimmingerFriedrich, RubinLewis J, OlschewskiHorst, SeegerWerner, GhofraniHossein A

Increased CO
Reduced PVR
Reduced mPAP

The combination of oral sildenafil and inhaled treprostinil was well tolerated and induced additive pulmonary selective vasodilatation in pulmonary hypertension patients.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

4.

Safety and efficacy of transition from inhaled treprostinil to parenteral treprostinil in selected patients with pulmonary arterial hypertension.

Author: PrestonIoana R, FeldmanJeremy, WhiteJames, FrancoVeronica, IshizawarDavid, BurgerCharles, WaxmanAaron B, HillNicholas S

PAH treatment
Prostacyclin overdose

This study characterized PAH patients transitioned from inhaled treprostinil to parenteral treprostinil, finding it to be safe with the potential for clinical improvement.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

5.

[Emerging therapies for the treatment of pulmonary arterial hypertension].

Author: GhofraniHossein Ardeschir, VoswinckelRobert, ReichenbergerFrank, GrimmingerFriedrich, SeegerWerner

Excellent tolerability
Improved exercise tolerance
Improved prognosis
Improved quality of life
Strong efficacy
Elaborate application techniques
Side effects

Pulmonary arterial hypertension is a serious and potentially fatal condition. Several new medications, including oral endothelin receptor antagonists, inhaled prostanoids, and the phosphodiesterase-5 inhibitor sildenafil, have improved the treatment of this disease. Combination therapies are considered the most promising approach for the future.

English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : German

6.

Oral treprostinil for the treatment of pulmonary arterial hypertension in patients receiving background endothelin receptor antagonist and phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C2 study): a randomized controlled trial.

Author: TapsonVictor F, JingZhi-Cheng, XuKai-Feng, PanLei, FeldmanJeremy, KielyDavid G, KotlyarEugene, McSwainC Shane, LaliberteKevin, ArnesonCarl, RubinLewis J,

PAH treatment

This study evaluated the efficacy and safety of oral treprostinil, a sustained-release formulation of treprostinil, in patients with pulmonary arterial hypertension (PAH). Oral treprostinil was found to be effective and safe in patients with PAH who were already receiving stable background therapy with endothelin receptor antagonists and/or phosphodiesterase type 5 inhibitors.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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