Iloprost (Ventavis), a synthetic analogue of prostacyclin or PGI-2, promotes pulmonary and systemic circulation vascular dilatation. In order to treat pulmonary arterial hypertension, it is employed.

Uses:

• Pulmonary arterial hypertension:

  • It is recommended for individuals with pulmonary arterial hypertension (World Health Organization group I) and New York Heart Association (NYHA) functional class III or IV symptoms in order to reduce symptoms, increase exercise tolerance, and slow the course of the condition.

• Guideline recommendations:

  • Note:
    • The following treatment guidelines are derived from the Fifth World Symposium on Pulmonary Hypertension and the American College of Chest Physicians:
      • Patients with PAH who are using an endothelin receptor antagonist like bosentan, a phosphodiesterase-5 inhibitor like sildenafil and vardenafil, a soluble guanylate cyclase stimulator, or a combination of treatments but are still experiencing symptoms may want to think about trying inhaled iloprost.
      • The inclusion of inhaled iloprost may be considered for patients who continue to experience symptoms while taking stable doses of an endothelin receptor antagonist, a phosphodiesterase-5 inhibitor, and a soluble guanylate cyclase stimulator.
    • In treatment-naive patients with pulmonary arterial hypertension with WHO functional class IV who do not desire or are unable to use parenteral prostanoid therapy, inhaled iloprost in combination with oral therapies may be considered.

• Off Label Use of Iloprost in Adults:

  • It is used as an off-label drug for acute vasodilator testing in pulmonary arterial hypertension.

Iloprost (Ventavis) Dose in Adults:

Iloprost (Ventavis) Dose in the treatment of Acute vasodilator testing in patients with PAH (off-label):

Note:

• Only those patients who might be candidates for calcium channel blocker medication should undergo acute vasodilator testing.
• Initial Inhalational dose:
  • 5 mcg delivered over fifteen minutes.

Iloprost (Ventavis) Dose in the treatment of pulmonary arterial hypertension (PAH):

• Initial Inhalational dose:
  • 2.5 mcg/dose.
• If the initial dose is tolerated, it is increased to 5 mcg/dose.
• The drug is administered 6 - 9 times a day according to the patient's need and tolerability.
• The maintenance dose:
  • 2.5 to 5 mcg/dose
• The maximum daily dose:
  • 45 mcg (i.e. 5 mcg/dose nine times a day.

Iloprost (Ventavis) Dose in Children:

Note:

• To prevent rebound pulmonary hypertension when discontinuing the dose, abrupt withdrawal or sudden large reductions in the dose should be avoided.

Iloprost (Ventavis) Dose in the treatment of pulmonary arterial hypertension (PAH):

• Infants, Children, and Adolescents:

  • Initial Inhalational dose:
    • 2.5 mcg/dose;
  • If the initial dose is tolerated, titrate up to 5 mcg/dose
  • For infants and low-weight children some experts recommend initiating treatment at a lower initial dose (ie, 1.25 mcg/dose).
  • Administer 6 to 9 times a day with dosing intervals of every 2 to 3 hours while awake.
  • The highest reported daily dose is 100 mcg/day.
  • The usual adult maximum dose is 45 mcg/day.

Iloprost (Ventavis) Dose in the treatment of postoperative pulmonary hypertensive crisis:

Note:

• The efficacy may be impacted by the drug delivery system and depends on the type of nebulizer, the placement in the ventilator circuit, and the mode of ventilation).

• Infants, Children, and Adolescents:

  • Initial Inhalational dose:
    • 0.5 mcg/kg over ten minutes;
  • The dose may be increased to 1 mcg/kg over 10 minutes and then to a maximum dose of 2 mcg/kg over 10 minutes if no clinically meaningful response is achieved.
  • Up to 5 doses may be administered every thirty minutes.

Iloprost (Ventavis) Pregnancy Risk Category: C

• Its use in pregnancy is not known.
• Effective contraception should be used for female patients with pulmonary hypertension and reproductive potential.
• Moderate to severe pulmonary hypertension should not be treated with pregnancy.

Iloprost use during breastfeeding:

• It is unknown if the drug will be excreted into breastmilk.
• The manufacturer suggests that you stop breastfeeding your baby because of the risk of serious adverse drug reactions.

Iloprost (Ventavis) Dose in Kidney Disease:

Adjustment in the dose is not necessary.

• Dialysis:
  • In the manufacturer's labeling, adjustments in the dose have not been provided.

Iloprost (Ventavis) Dose in Liver disease:

• Mild impairment (Child-Pugh class A):
  • In the manufacturer's labeling, adjustments in the dose have not been provided.
• Moderate to severe impairment (Child-Pugh class B or C):
  • Based ion the clinical response at the end of the dose intervals, the interval of dosing should be increased every 3 to 4 hours.

Common Side Effects of Iloprost (Ventavis):

• Cardiovascular:

  • Flushing
  • Hypotension

• Central Nervous System:

  • Headache
  • Trismus

• Gastrointestinal:

  • Nausea

• Neuromuscular & Skeletal:

  • Jaw Pain

• Respiratory:

  • Cough
  • Flu-Like Symptoms

Less Common Side Effects of Iloprost (Ventavis):

• Cardiovascular:

  • Syncope
  • Palpitations

• Central Nervous System:

  • Insomnia

• Endocrine & Metabolic:

  • Increased Gamma-Glutamyl Transferase

• Gastrointestinal:

  • Vomiting
  • Glossalgia

• Hepatic:

  • Increased Serum Alkaline Phosphatase

• Neuromuscular & Skeletal:

  • Back Pain
  • Muscle Cramps

• Respiratory:

  • Hemoptysis
  • Pneumonia

Contraindications to Iloprost (Ventavis):

• The manufacturer's labeling does not contain any contraindications.

Warnings and precautions

• Pulmonary edema

  • If there is pulmonary edoema, treatment ought to stop right away. It's possible that this represents pulmonary vein hypertension.

• Rebound pulmonary hypertension

  • Patients who suddenly stop taking large amounts of the drug abruptly have experienced worsening symptoms of pulmonary hypertension.
  • To avoid interruptions in treatment, patients should be able to immediately access the medicine and backup inhalation device.

• Syncope

  • It can cause hypotension, which may lead to syncope.
  • Patients taking syncope-inducing medications should be cautious.

• Bleeding disorders:

  • Aerosols can be used to administer it. It has mild antiplatelet properties and inhibits platelet accumulation.
  • Patients who are at high risk of bleeding, such as those taking concomitant anticoagulants like Warfarin or Rivaroxaban, should be cautious when using the drug.

• Hypotension

  • Patients with symptomatic hypotension or a systolic BP less than 85 mm Hg should not use it.

• Respiratory disease

  • Patients with other pulmonary conditions (such as Severe Asthma or Bronchiectasis and COPD) have not been able to establish the safety and efficacy.
  • It can worsen or cause bronchospasm in patients with hyper-reactive lungs.

Iloprost: Drug Interaction

Monitoring parameters:

• Heart rate
• BP
• Respiratory rate 
• Monitor for improvements in the following clinical and laboratory parameters:
  • Pulmonary function tests,
  • Decreased exertional dyspnea,
  • Fatigue,
  • Syncope and chest pain,
  • Blood pressure,
  • Pulmonary vascular resistance,
  • Pulmonary arterial pressure and
  • Quality of life.

How to administer Iloprost (Ventavis)?

Inhalation:

• The medicine should not be mixed with other medications. To prevent treatment interruptions, access to the drug, and a back-up inhalation device is essential.
• It should be used for inhalation only via the I-neb AAD System. To add the contents of the ampoule to the medication chamber, refer to the I-neb AAD System instructions.
• The 20 mcg/ml concentration is intended for those patients who have experienced extended intervals of the treatment repeatedly and those who are maintained at the 5 mcg dose.
• The remainder medicine should be discarded after use (It should not be reused).

Mechanism of action of Iloprost (Ventavis):

• It immediately dilates the systemic as well as pulmonary arterial vessels. 
• It can be used for a longer time to alter the pulmonary resistance and inhibit the proliferation of the smooth muscles.
• Aerosolized, it inhibits platelet aggregation.

Duration:

• 30 to 60 minutes

Protein binding:

• The majority of the medication—60%—is bonded to albumin and other plasma proteins.

Metabolism:

• It is converted to the primary metabolite, tetranoriloprost, in the liver through beta-oxidation of the carboxyl side chain (inactive in animal studies)

Half-life elimination:

• 20 to 30 minutes (effect),
• 7 to 9 minutes (elimination)

Time to peak serum concentration:

• Within five minutes after it is inhaled.

Excretion:

• 68% as metabolites in urine
• 12% in feces.

International Brands of Iloprost:

• Ventavis
• Homedin
• Ilomedin
• Ilomedine
• Ventavis RES

Iloprost Brand Names in Pakistan:

No Brands Available in Pakistan.