Iloprost

B01A - Antithrombotic agents ATC B01AC11 Small molecule approved 2003 Parenteral Topical Natural product

JFDA label: Lilopost 0.05mg/0.5ml

Mechanism of Action

Agonist of Prostacyclin receptor — Prostanoid IP receptor agonist

Target	Action	Gene / class
Prostacyclin receptor efficacy	AGONIST	PTGIR

Indications

Approved

Pulmonary arterial hypertension

Contraindications

Source: Lexicomp

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

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (4)

Very Common Flushing · hypotension

Common palpitations · Syncope

Nervous system disorders (3)

Very Common Headache · trismus

Common Insomnia

Hepatobiliary disorders (1)

Common Increased serum alkaline phosphatase

Metabolism and nutrition disorders (1)

Common Increased gamma-glutamyl transferase

Gastrointestinal disorders (3)

Very Common Nausea

Common glossalgia · Vomiting

Musculoskeletal and connective tissue disorders (3)

Very Common Jaw pain

Common Back pain · muscle cramps

Respiratory, thoracic and mediastinal disorders (4)

Very Common Cough · flu-like symptoms

Common Hemoptysis · pneumonia

Dosing

Source: Lexicomp

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)

Refer to adult dosing.

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).

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.

Warnings & Precautions

Source: Lexicomp

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 • 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.

Pregnancy & Lactation

Pregnancy

FDA category C

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).

Lactation

It is not known if iloprost is excreted in breast milk. Due to the potential for serious adverse reactions in the nursing infant, the manufacturer recommends a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother.

Monitoring

Clinical pearl	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.

Chemistry & Properties

Formula	C22H32O4
Molecular weight	360.49 g/mol
IUPAC name	(5E)-5-[(3aS,4R,5R,6aS)-5-hydroxy-4-[(E,3S)-3-hydroxy-4-methyloct-1-en-6-ynyl]-3,3a,4,5,6,6a-hexahydro-1H-pentalen-2-ylidene]pentanoic acid
CAS	78919-13-8
PubChem CID	5311181
InChIKey	`HIFJCPQKFCZDDL-ACWOEMLNSA-N`
logP	3.54 (XLogP 2.8)
Polar surface area	77.76 Å²
H-bond acceptors / donors	3 / 3
Drug-likeness (QED)	0.35
Lipinski violations	0

SMILES

CC#CCC(C)[C@H](O)/C=C/[C@@H]1[C@H]2C/C(=C/CCCC(=O)O)C[C@H]2C[C@H]1O

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	1.341 h
Volume of distribution	0.391 L/kg
Protein binding	58.1%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2C9	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)OATP2B1 (Substrate)OATP3A1 (Substrate)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Acalabrutinib	major
Apixaban	major
Ardeparin	major
Avapritinib	major
Betrixaban	major
Cabozantinib	major
Dalteparin	major
Danaparoid	major
Dasatinib	major
Deferasirox	major
Drotrecogin alfa	major
Edoxaban	major
Enoxaparin	major
Fondaparinux	major
Ibritumomab tiuxetan	major
Ibrutinib	major
Inotersen	major
Omacetaxine mepesuccinate	major
Panobinostat	major
Ponatinib	major
Ramucirumab	major
Regorafenib	major
Rivaroxaban	major
Tinzaparin	major
Tipranavir	major
Tizanidine	major
Tositumomab	major
Tositumomab (I-131)	major
Zanubrutinib	major
Abciximab	moderate
Acebutolol	moderate
Acetazolamide	moderate
Acetylsalicylic acid	moderate
Aldesleukin	moderate
Alfuzosin	moderate
Aliskiren	moderate
Alprostadil	moderate
Alteplase	moderate
Amifostine	moderate
Amiloride	moderate

Showing 40 of 100+.

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Lilopost 0.05mg/0.5ml	Vial 0.05 mg/0.5 ml	5 vial	MS PHARMA/JORDAN	—