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Iloprost

Medically reviewed on August 12, 2018

Pronunciation

(EYE loe prost)

Index Terms

  • Iloprost Tromethamine
  • Prostacyclin PGI2

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Inhalation [preservative free]:

Ventavis: 10 mcg/mL (1 mL); 20 mcg/mL (1 mL) [contains alcohol, usp, tromethamine]

Brand Names: U.S.

  • Ventavis

Pharmacologic Category

  • Prostacyclin
  • Prostaglandin
  • Vasodilator

Pharmacology

Acutely, iloprost dilates systemic and pulmonary arterial vascular beds. With longer-term use, alters pulmonary vascular resistance and suppresses vascular smooth muscle proliferation. In addition, it is a mild endogenous inhibitor of platelet aggregation when aerosolized (Beghetti 2002).

Distribution

Vd: 0.7 to 0.8 L/kg

Metabolism

Hepatic via beta oxidation of the carboxyl side chain; main metabolite, tetranor-iloprost (inactive in animal studies)

Excretion

Urine (68% as metabolite); feces (12%)

Time to Peak

Serum: Within 5 minutes after inhalation

Duration of Action

30 to 60 minutes

Half-Life Elimination

20 to 30 minutes (effect), 7 to 9 minutes (elimination)

Protein Binding

~60%, primarily to albumin

Special Populations: Renal Function Impairment

Inhaled iloprost has not been evaluated in subjects with impaired renal function. In a study with IV infusion of iloprost in patients with ESRD requiring intermittent dialysis treatment, the mean AUC0-4h was 230 pg•h/mL compared with 54 pg•h/mL in patients with renal failure not requiring intermittent dialysis, and 48 pg•h/mL in healthy patients. The half-life was similar in both groups.

Special Populations: Hepatic Function Impairment

Inhaled iloprost has not been evaluated in subjects with impaired hepatic function. In an IV iloprost study in patients with liver cirrhosis, the mean Cl in Child-Pugh class B subjects was approximately 10 mL/min/kg (half that of healthy patients). Following oral administration, the mean AUC0-8h in Child-Pugh class B patients was 1,725 pg•h/mL compared with 117 pg•h/mL in healthy subjects receiving the same oral iloprost dose. In Child-Pugh class A subjects, the mean AUC0-8h was 639 pg•h/mL. Although exposure increased with hepatic impairment, there was no effect on half-life.

Use: Labeled Indications

Pulmonary arterial hypertension: Treatment of pulmonary arterial hypertension (PAH) (World Health Organization [WHO] group I) in patients with New York Heart Association (NYHA) functional class (FC) III or IV symptoms to improve exercise tolerance, symptoms, and diminish clinical deterioration.

Guideline recommendations: Note: The following are derived from the treatment guidelines from the Fifth World Symposium on Pulmonary Hypertension (WSPH) and the American College of Chest Physicians (ACCP) (ACCP [Taichman 2014]; WSPH [Gailè 2013]):

In patients with PAH who remain symptomatic on an endothelin receptor antagonist (ERA), phosphodiesterase-5 inhibitor (PDE-5i), soluble guanylate cyclase (sGC) stimulator, or a combination of therapies, inhaled iloprost may be considered.

In treatment-naive PAH patients in WHO FC IV who are unable or do not desire parenteral prostanoid therapy, inhaled iloprost in combination with oral PAH therapies may be considered.

In patients with PAH who remain symptomatic on stable doses of an ERA, a PDE-5i or a sGC stimulator, addition of inhaled iloprost may be considered.

Off Label Uses

Acute vasodilator testing in pulmonary arterial hypertension

Data from a limited number of patients from a crossover study suggest that iloprost may be beneficial for acute vasodilator testing in pulmonary arterial hypertension (PAH) patients [Jing 2009]. Additional data may be necessary to further define the role of iloprost in this condition.

Based on the American College of Cardiology Foundation and American Heart Association (ACCF/AHA) 2009 Expert Consensus Document on Pulmonary Hypertension and the Fifth World Symposium on Pulmonary Hypertension (WSPH) updated treatment algorithm of PAH, inhaled iloprost is an alternative agent (inhaled nitric oxide is preferred) for acute vasodilator testing to identify patients with PAH who are likely to have a favorable response to oral calcium channel blockers (eg, high-dose extended-release nifedipine), which have been shown to improve survival. Response to acute vasodilator testing is currently defined as a reduction in mean pulmonary artery pressure (mPAP) of ≥10 mm Hg, to an absolute mPAP <40 mm Hg, with an unchanged or increased cardiac output. Of note, acute vasodilator testing is not recommended and may be harmful in patients with significantly elevated left heart filling pressures.

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Dosing: Adult

Acute vasodilator testing in patients with PAH (off-label use): Note: Acute vasodilator testing should only be done in patients who might be considered candidates for calcium channel blocker therapy. Inhalation: Initial: 5 mcg delivered over 15 minutes (Jing 2009)

Pulmonary arterial hypertension (PAH): Inhalation: Initial: 2.5 mcg/dose; if tolerated, increase to 5 mcg/dose. Administer 6 to 9 times daily (dosing at intervals ≥2 hours while awake according to individual need and tolerability). Maintenance dose: 2.5 to 5 mcg/dose; maximum daily dose: 45 mcg (ie, 5 mcg/dose 9 times daily)

Dosing: Geriatric

Refer to adult dosing.

Administration

Inhalation: Immediate access to medication and a back-up inhalation device is essential to prevent treatment interruptions. Do not mix with other medications. For inhalation only via the I-neb AAD System. Refer to the I-neb AAD System instructions for adding ampul contents to the medication chamber. The 20 mcg/mL concentration is intended for patients who are maintained at the 5 mcg dose and who have repeatedly experienced extended treatment times. After use, discard remainder of the medicine; not for reuse.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (58°F to 86°F).

Drug Interactions

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): Prostacyclin Analogues may enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification

Anticoagulants: Prostacyclin Analogues may enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination. Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Blood Pressure Lowering Agents: Prostacyclin Analogues may enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Avoid combination

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy

Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Thrombolytic Agents: May enhance the adverse/toxic effect of Prostacyclin Analogues. Specifically, the antiplatelet effects of prostacyclin analogues may lead to an increased risk of bleeding when combined with thrombolytic agents. Monitor therapy

Adverse Reactions

>10%:

Cardiovascular: Flushing (27%), hypotension (11%)

Central nervous system: Headache (30%), trismus (12%)

Gastrointestinal: Nausea (13%)

Neuromuscular & skeletal: Jaw pain (12%)

Respiratory: Cough (39%), flu-like symptoms (14%)

1% to 10%:

Cardiovascular: Syncope (8%), palpitations (7%)

Central nervous system: Insomnia (8%)

Endocrine & metabolic: Increased gamma-glutamyl transferase (6%)

Gastrointestinal: Vomiting (7%), glossalgia (4%)

Hepatic: Increased serum alkaline phosphatase (6%)

Neuromuscular & skeletal: Back pain (7%), muscle cramps (6%)

Respiratory: Hemoptysis (5%), pneumonia (4%)

<1%, postmarketing, and/or case reports: Bronchospasm, cardiac failure, chest pain, dizziness, dyspnea, dysgeusia, epistaxis, hypersensitivity reaction, mouth irritation, paradoxical reaction (increased post-void residual urine volume), renal failure, skin rash, supraventricular tachycardia, thrombocytopenia, tongue irritation, wheezing

Warnings/Precautions

Concerns related to adverse effects:

• Pulmonary edema: If pulmonary edema occurs during administration, discontinue therapy immediately; may be a sign of pulmonary venous hypertension.

• Rebound pulmonary hypertension: Abrupt withdrawal/large dosage reductions may worsen symptoms of PAH. Immediate access to medication and back-up inhalation device is essential to prevent treatment interruptions.

• Syncope: Hypotension leading to syncope has been observed. Dosage or therapy adjustment may be required if exertional syncope occurs. Use caution with concurrent conditions or medications that may increase risk of syncope.

Disease-related concerns:

• Bleeding disorders: Use with caution in patients with active bleeding or at increased risk of bleeding (eg, concomitant anticoagulation); mild inhibitor of platelet aggregation when administered as an aerosol.

• Hypotension: Do not use in patients with hypotension (systolic BP <85 mm Hg).

• Respiratory disease: Safety and efficacy have not been established in patients with other concurrent pulmonary diseases (eg, COPD, severe asthma, or acute pulmonary infections); may induce bronchospasm in patients with hyper-reactive airways.

Other warnings/precautions:

• Administration: Intended for inhalation administration using only the I-neb AAD System. Solution should not come in contact with skin or eyes. Monitor vital signs during initiation.

Monitoring Parameters

Heart rate, blood pressure, and respiratory rate at baseline and with dosage adjustment. Monitor for improvements in pulmonary function, decreased exertional dyspnea, fatigue, syncope and chest pain, blood pressure, pulmonary vascular resistance, pulmonary arterial pressure and quality of life.

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events were observed in some animal reproduction studies. Information related to the use of iloprost in pregnancy is limited (Horng 2016). Women with pulmonary arterial hypertension (PAH) are encouraged to avoid pregnancy (McLaughlin 2009; Taichman 2014).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience back pain, mouth pain, cough, headache, jaw tightness, flushing, muscle cramps, nausea, vomiting, insomnia, or flu-like symptoms. Have patient report immediately to prescriber severe dizziness, passing out, bruising, bleeding, angina, tachycardia, difficulty breathing, coughing up blood, urinary retention, change in amount of urine passed, abnormal heartbeat, shortness of breath, excessive weight gain, swelling in arms or legs, or difficulty opening mouth (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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