iloprost (Rx)

>10%

Flushing (18%)

Cough (39%)

Hypotension (11%)

Nausea (13%)

Headache (30%)

Jaw pain (12%)

Trismus (12%)

1-10%

Palpitations (7%)

Syncope (8%)

Insomnia (8%)

Vomiting (7%)

Tongue pain (4%)

Back pain (7%)

Muscle cramps (6%)

GGT elevated (6%)

Hemoptysis (5%)

Pneumonia (4%)

<1%

Kidney failure

Bronchospasm

Hypersensitivity

Supraventricular tachycardia

Contraindications

None well documented

Cautions

Iloprost has been listed by the FDA as one of the drugs to monitor after having identified potential signs of serious risks or new safety information in the agency's Adverse Event Reporting System (AERS) database during the last 3 months of 2011. Hemoptysis has been reported with iloprost use. The FDA said that it is not suggesting that clinicians should stop prescribing any drugs on the watch list, or that patients should stop taking them. It advises patients with questions about watch-list drugs to discuss them with their clinician.

Use caution in patients experiencing other types of pulmonary diseases (i.e. COPD)

Syncope may occur with pulmonary arterial hypertension, particularly with physical exertion (adjust dose and reassess efficacy)

Risk of syncope - monitor vital signs when initiating

Use cautioin in patients with bleeding disorders

Rebound hypertension may occur with dose reductions or withdrawals

Administered only via the Prodose® AAD® System

Not for use in patients with hypotension (systolic BP <85 mm Hg)

Discontinue immediately if signs of pulmonary edema

Bleeding events are most commonly reported as epistaxis or hemoptysis

Pregnancy

Limited published data from case series and case reports in pregnant women have not identified drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes; there are risks to mother and fetus associated with pulmonary arterial hypertension

Pulmonary arterial hypertension in pregnancy increases risk for maternal heart failure, stroke and death, miscarriage, preterm delivery, low birthweight infants, and stillbirth

Animal data

• In animal reproductive studies, administration of continuous intravenous therapy to pregnant Han-Wistar rats during organogenesis at doses 2-times recommended human dose on a mg/m² basis resulted in adverse developmental outcomes
• However, there were no adverse developmental outcomes with intravenous administration of iloprost to pregnant Sprague- Dawley rats, rabbits and monkeys at doses 1200-, 180-, and 14-times, respectively, the recommended human dose on a mg/m² basis

Lactation

There are no data on presence of iloprost in human milk, effects on breastfed infant, or on milk production; drug is present in rat milk; when drug present in animal milk, it is likely drug will be present in human milk

Because of potential for serious adverse reactions, advise women not to breastfeed during treatment

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Synthetic analog of prostagladin PGI2, dilates systemic & pulmonary arterial beds; suppresses vascular smooth muscle proliferation and alters pulmonary vascular resistance when used long term

Pharmacokinetics

Vd: 0.7-0.8 L/kg

Protein Bound: 60%

Duration: 30-60 min

Metabolism: Principally via beta-oxidation of carboxyl side-chain

Metabolite: Tetranor-iloprost (inactive)

Half-life: 20-30 min

Peak serum time: Within 5 min (following inhalation)

Excretion: Urine (68%); feces (12%)