|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
Pronunciation
(EYE loe prost)
Generic Available (U.S.)
No
Index Terms
Brand Names: U.S.
Pharmacologic Category
Use: Labeled Indications
Treatment of pulmonary arterial hypertension (PAH) (WHO Group I) in patients with NYHA Class III or IV symptoms to improve exercise tolerance, symptoms, and diminish clinical deterioration
Use: Unlabeled/Investigational
WHO group III and IV pulmonary arterial hypertension (PAH)
Pregnancy Risk Factor
C
Pregnancy Considerations
Iloprost was shown to be embryolethal or teratogenic in some, but not all, animal studies. There are no adequate or well-controlled studies in pregnant women; use only if clearly needed. Women with pulmonary hypertension are urged to avoid pregnancy.
Lactation
Excretion in breast milk unknown/ not recommended
Contraindications
There are no contraindications listed within the FDA-approved labeling.
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: 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.
• Hepatic impairment: Use with caution in patients with Child-Pugh classes B and C hepatic impairment; inhaled iloprost has not been evaluated in this population. Studies of I.V. (not an FDA-approved route) administered iloprost in Child-Pugh class B patients have demonstrated an approximate 50% reduction in iloprost clearance.
• Hypotension: Do not use in patients with hypotension (systolic BP <85 mm Hg).
• Renal impairment: Inhaled iloprost has not been evaluated in this population; use with caution. Studies of I.V. (not an FDA-approved route) administered iloprost in patients on dialysis demonstrated an approximate fivefold increase in iloprost AUC when compared to healthy individuals.
• 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 or Prodose® AAD® System. Solution should not come in contact with skin or eyes. Monitor vital signs during initiation.
Adverse Reactions
>10%:
Cardiovascular: Flushing (27%), hypotension (11%)
Central nervous system: Headache (30%)
Gastrointestinal: Nausea (13%)
Neuromuscular & skeletal: Trismus (12%), jaw pain (12%)
Respiratory: Cough increased (39%)
Miscellaneous: Flu-like syndrome (14%)
≥3% to 10%:
Cardiovascular: Syncope (8%), palpitation (7%)
Central nervous system: Insomnia (8%)
Gastrointestinal: Vomiting (7%), tongue pain (4%)
Hepatic: Alkaline phosphatase increased (6%), GGT increased (6%)
Neuromuscular & skeletal: Back pain (7%), muscle cramps (6%)
Respiratory: Hemoptysis (5%), pneumonia (4%)
<3%: Chest pain, CHF, dizziness, dyspnea, kidney failure, peripheral edema, supraventricular tachycardia
Postmarketing and/or case reports: Abnormal taste, bronchospasm, diarrhea, epistaxis, gingival bleeding, hypersensitivity, mouth irritation, paradoxical reaction (increased PVR), rash, tongue irritation, wheezing
Metabolism/Transport Effects
None known.
Drug Interactions
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. Risk C: Monitor therapy
Antihypertensives: Prostacyclin Analogues may enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Antiplatelet Agents: Prostacyclin Analogues may enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
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).
Mechanism of Action
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).
Pharmacodynamics/Kinetics
Duration: 30-60 minutes
Distribution: Vd: 0.7-0.8 L/kg
Protein binding: ~60%, primarily to albumin
Metabolism: Hepatic via beta oxidation of the carboxyl side chain; main metabolite, tetranor-iloprost (inactive in animal studies)
Half-life elimination: 20-30 minutes (effect), 7-9 minutes (elimination)
Time to peak, serum: Within 5 minutes after inhalation
Excretion: Urine (68% as metabolite); feces (12%)
Dosage
Inhalation: Adults: Pulmonary arterial hypertension (PAH): Initial: 2.5 mcg/dose; if tolerated, increase to 5 mcg/dose; administer 6-9 times daily (dosing at intervals ≥2 hours while awake according to individual need and tolerability); maintenance dose: 2.5-5 mcg/dose; maximum daily dose: 45 mcg (ie, 5 mcg/dose 9 times daily)
Dosage adjustment in renal impairment: Inhaled iloprost has not been studied in renal impairment; however, according to the manufacturer, no adjustment is required in patients with renal impairment who are not on dialysis (the effect of dialysis on iloprost is unknown).
Dosage adjustment in hepatic impairment: Child-Pugh class B or C: Consider increasing dosing interval (eg, every 3-4 hours) based on response at the end of the dose interval
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 or Prodose® AAD® System. Refer to the I-neb® AAD® System or Prodose® AAD® System instructions for adding ampul contents to the medication chamber. After use, discard remainder of the medicine; not for reuse.
Monitoring Parameters
With initiation and dosage adjustments, monitor heart rate, blood pressure, and respiratory rate at baseline. Monitor for improvements in pulmonary function, improved exercise tolerance, and NYHA Class improvement.
Patient Education
Instruct patient to notify prescriber if he/she experiences trouble breathing; changes in CNS status, such as severe headache, severe dizziness, or loss of consciousness; severe nausea or vomiting; severe diarrhea; or any abnormal bruising or bleeding.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Jaw pain (reported in >10% of patients).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause insomnia
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Monitor vital signs for decrease in blood pressure, especially if on antihypertensives; monitor for signs of abnormal bleeding/clotting, especially if on anticoagulants. Assess for improvement in pulmonary function.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, for oral inhalation [preservative free]:
Ventavis®: 10 mcg/mL (1 mL, 2 mL [DSC]); 20 mcg/mL (1 mL)
References
Badesch DB, Abman SH, Simonneau G, et al, “Medical Therapy for Pulmonary Arterial Hypertension: Updated ACCP Evidence-Based Clinical Practice Guidelines,” Chest, 2007, 131(6):1917-28.
Baghetti M, Reber G, de Moerloose P, et al, “Aerosolized Iloprost Induces a Mild but Sustained Inhibition of Platelet Aggregation,” Eur Respir J, 2002, 19(3):518-24.
Emmel M, Keuth B, and Schickendantz S, “Paradoxical Increase of Pulmonary Vascular Resistance During Testing of Inhaled Iloprost,” Heart, 2004, 90(1):e2.
Humbert M, Sitbon O, and Simmoneau G, “Treatment of Pulmonary Arterial Hypertension,” N Engl J Med, 2004, 351(14):1425-36.
McLaughlin VV, Archer SL, Badesch DB, et al, “ACCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension: A Report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: Developed in Collaboration with the American College of Chest Physicians, American Thoracic Society, Inc, and the Pulmonary Hypertension Association,” J Am Coll Cardiol, 2009, 53(11):1573-619.
Olschewski H, Hoeper MM, Behr J, et al, "Long-Term Therapy With Inhaled Iloprost in Patients With Pulmonary Hypertension," Respir Med, 2010, 104(5):731-40.
Olschewski H, Rohde B, Behr J, et al, “Pharmacodynamics and Pharmacokinetics of Inhaled Iloprost, Aerosolized by Three Different Devices, in Severe Pulmonary Hypertension,” Chest, 2003, 124(4):1294-304.
Olschewski H, Simonneau G, Galie N, et al, “Inhaled Iloprost for Severe Pulmonary Hypertension,” N Engl J Med, 2002, 347(5):322-9.
International Brand Names
Lexi-Comp.com
Last full review/revision December 2011
|
