Pronunciation
(EYE loe
prost)
Index Terms
Iloprost TromethamineProstacyclin 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
ProstacyclinProstaglandinVasodilator
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:
0.7-0.8 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
30-60
minutes
Half-Life Elimination
20-30
minutes (effect), 7-9 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 AUC0-4hwas 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 (World Health Organization [WHO] group I) in
patients with New York Heart Association (NYHA) class III or IV symptoms to
improve exercise tolerance, symptoms, and diminish clinical deterioration.
Contraindications
There are
no contraindications listed in the manufacturer's labeling.
Dosing: Adult
Pulmonary
arterial hypertension (PAH): Inhalation:
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)
Dosing: Geriatric
Refer to
adult dosing.
Dosing: 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).
Dosing: 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
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
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%
(Limited to important or life-threatening): Bronchospasm, cardiac failure,
dyspnea, epistaxis, hypersensitivity reaction, paradoxical reaction (increased
post-void residual urine volume), renal failure, supraventricular tachycardia,
thrombocytopenia
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
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.
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.
