Class: Prostacyclin analog
- Solution, inhalation 10 mcg/mL
- Solution, inhalation 20 mcg/mL
Dilates systemic and pulmonary arterial vascular beds. It also affects platelet aggregation.
Absolute bioavailability of inhaled iloprost has not been determined. Following a 5 mcg inhalation, the C max is approximately 150 pg/mL.
Vd after IV infusion is 0.7 to 0.8 L/kg. Protein binding is approximately 60%, primarily to albumin.
Metabolized primarily by beta-oxidation of the carboxyl side chain to tetranor-iloprost (metabolite). CYP-450 plays a minor role in iloprost metabolism.
The half-life is 20 to 30 min. Elimination is 68% in urine and 12% in feces.
30 to 60 min.
Special PopulationsRenal 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 AUC 0-4h 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.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 AUC 0-8h 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 AUC 0-8h was 639 pg•h/mL. Although exposure increased with hepatic impairment, there was no effect on half-life.
Indications and Usage
Treatment of pulmonary arterial hypertension (WHO group I) in patients with New York Heart Association (NYHA) class III or IV symptoms.
IV administration for treatment of severe Raynaud phenomenon associated with systemic sclerosis.
None well documented.
Dosage and AdministrationPulmonary arterial hypertension
Oral inhalation Start with 2.5 mcg (as delivered at the mouthpiece). If this dose is tolerated, increase dosing to 5 mcg and maintain that dose; otherwise maintain the dose at 2.5 mcg. Should be taken 6 to 9 times/day but not more often than every 2 h during waking hours (max, 45 mcg/day).Hepatic function impairment
Oral inhalation Consider increasing the dosing interval (eg, 3 to 4 h between doses depending on the patient's response at the end of the dosing interval) in patients with Child-Pugh class B or C hepatic impairment.
- For aerosol administration only. Not for parenteral or oral administration.
- Do not allow iloprost solution to come into contact with the skin or eyes. If accidental skin or eye contact occurs, flush the exposed areas with water.
- Administer only with the I-neb Adaptive Aerosol Delivery ( AAD ) or Prodose AAD system. To avoid potential interruptions in drug delivery caused by equipment malfunctions, the patient should have easy access to a backup I-neb AAD or Prodose AAD system.
- For patients using the I-neb AAD system, the entire contents of 1 ampule containing 10 mcg/mL of iloprost or 1 ampule containing 20 mcg/mL of iloprost should be transferred to the drug chamber of the nebulizer immediately before each inhalation session. The 10 mcg/mL ampule delivers a dose of either 2.5 or 5 mcg of the drug to the mouthpiece. The 20 mcg/mL ampule delivers a dose of 5 mcg of the drug to the mouthpiece. One single-use ampule is required for each inhalation session.
- For patients using the Prodose AAD system, the entire contents of 2 ampules containing 10 mcg/mL of iloprost should be transferred to the drug chamber of the nebulizer immediately before each inhalation session. The two 10 mcg/mL ampules deliver a dose of either 2.5 or 5 mcg of the drug to the mouthpiece. The 20 mcg/mL ampule should not be used with the Prodose AAD system. Two single-use ampules are required for each inhalation session.
- 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 that could result in incomplete dosing. Transitioning patients to the 20 mcg/mL concentration using the I-neb AAD system will decrease treatment times to help maintain patient compliance.
- Administer iloprost according to instructions provided by the manufacturer for use with the I-neb AAD or Prodose AAD system.
- Direct mixing of iloprost with other medications in the I-neb AAD or Prodose AAD system has not been evaluated; do not mix with other medications.
- Discard any remaining solution in the medication chamber following each inhalation session. Use of remaining solution for next inhalation session will result in unpredictable dosing.
- Follow manufacturer instructions for cleaning the I-neb AAD or Prodose AAD system components after each inhalation session.
Store between 59° and 86°F.
Drug InteractionsAnticoagulants, platelet inhibitors
Because iloprost inhibits platelet function, the risk of bleeding may be increased. Clinical and laboratory monitoring is warranted.Antihypertensive agents, vasodilators
The hypotensive effects of these agents may be increased by iloprost. Monitor BP.Disulfiram, metronidazole
Because iloprost contains alcohol, there is a risk that an alcohol intolerance reaction may occur. Avoid coadministration with disulfiram or metronidazole.
Vasodilation/flushing (27%); hypotension (11%); syncope (8%); palpitations (7%); chest pain/discomfort/tightness, CHF, supraventricular tachycardia.
Headache (30%); insomnia (8%); dizziness.
Nausea (13%); vomiting (7%); diarrhea, dysgeusia (postmarketing).
Epistaxis, gingival bleeding (postmarketing).
Increased alkaline phosphatase, increased GGT (6%).
Trismus (12%); back pain (7%); muscle cramps (6%).
Increased cough (39%); hemoptysis (5%); pneumonia (4%); dyspnea; bronchospasm, wheezing (postmarketing).
Flu syndrome (14%); tongue pain (4%); kidney failure; peripheral edema; hypersensitivity, mouth and tongue irritation, rash (postmarketing).
Monitor vital signs while initiating iloprost.
Category C .
Safety and efficacy not established.
Use with caution, usually starting at the low end of the dose range, because of the greater frequency of decreased cardiac, hepatic, or renal function, and of concomitant diseases or other drug therapy.
Use with caution in patients on dialysis.
Use with caution in patients with Child-Pugh class B or higher hepatic impairment.
Special Risk Patients
Use has not been evaluated in patients with pulmonary hypertension, COPD, severe asthma, or acute pulmonary infections.
Stop treatment immediately if pulmonary edema occurs when administered to patients with pulmonary hypertension; this may be a sign of pulmonary venous hypotension.
Syncope may occur. Do not initiate in patients with systemic BP less than 85 mm Hg.
Extension of the pharmacologic effects, including diarrhea, flushing, headache, hypotension, nausea, and vomiting.
- Advise patient or caregiver to use iloprost only as prescribed with the pulmonary drug delivery devices, I-neb AAD or Prodose AAD system, following the manufacturer instructions.
- Ensure patient or caregiver has been trained in proper administration techniques, including dosing frequency, opening ampules, transferring solution, disposal of empty ampule, I-neb AAD or Prodose AAD system operation, and equipment cleaning and maintenance.
- To avoid interruptions in therapy caused by equipment malfunction, ensure patient or caregiver has easy access to a backup I-neb AAD or Prodose AAD system.
- Caution patient or caregiver to avoid oral ingestion or skin or eye contact with iloprost. Advise patient if accidental skin or eye contact occurs to flush the exposed area with water.
- Caution patient or caregiver not to put any other medications in the I-neb AAD or Prodose AAD system while using iloprost.
- Advise patient or caregiver that iloprost should be inhaled at intervals of no less than 2 h and that the beneficial effects of iloprost may not last 2 h. Caution patient or caregiver against increasing the frequency of administration if beneficial effects do not last the entire time between treatments.
- Caution patient or caregiver that BP may fall during or shortly after iloprost administration and that dizziness or fainting can occur. Advise patient to stand up slowly when getting out of a chair or bed. Advise patient or caregiver to notify health care provider if dizziness gets worse or if fainting occurs.
- Advise patient or caregiver that the most common adverse effects of iloprost therapy (aside from low BP and fainting) include reddening of the face caused by widening of blood vessels (flushing), increased cough, headache, nausea, spasms of the jaw muscles that cause trouble opening the mouth, and syncope. Advise patient or caregiver to notify health care provider if any of these develop and are intolerable.
Copyright © 2009 Wolters Kluwer Health.