Iloprost
Encyclopedia
Iloprost is a drug used to treat pulmonary arterial hypertension
(PAH), scleroderma
, Raynaud's phenomenon
and ischemia
. It was developed by the pharmaceutical company
Schering AG and is marketed by Bayer Schering Pharma AG
in Europe and Actelion Pharmaceuticals in the USA.
PGI2. Iloprost dilates systemic and pulmonary arterial vascular
beds. It also affects platelet
aggregation but the relevance of this effect to the treatment of pulmonary hypertension is unknown. The two diastereoisomers
of iloprost differ in their potency in dilating blood vessels, with the 4S isomer substantially more potent than the 4R isomer.
Ventavis is supplied in 1 mL single-use glass ampules containing either 10 mcg/mL or 20 mcg/mL. 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 which 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.
The approved dosing regimen for iloprost is 6 to 9 times daily (no more than every 2 hours) during waking hours, according to individual need and tolerability. The significant clinical effects observed in the pivotal study of patients with PAH were achieved with a median dose of 30 mcg per day (range: 12.5 to 45 mcg delivered at the mouthpiece), corresponding to 6 daily inhalations of 5 mcg. The majority of patients (> 80%) in the pivotal study used this median dose or a higher dose with an excellent treatment compliance after 12 weeks.
The first inhaled dose of iloprost should be 2.5 mcg (as delivered at the mouthpiece). If this dose is well tolerated, dosing should be increased to 5 mcg and maintained at that dose. Any patient who cannot tolerate the 5 mcg dose should be maintained at 2.5 mcg.
Each inhalation treatment requires one entire single-use ampule. Each single-use ampule delivers a concentration of 10 mcg/mL to the medication chamber of either the I-Neb AAD or Prodose AAD System, and delivers a nominal dose of either 2.5 mcg or 5.0 mcg to the mouthpiece. After each inhalation session, any solution remaining in the medication chamber should be discarded. Use of the remaining solution, even if the reservoir is “topped off” with fresh medication, will result in unpredictable dosing. Patients should follow the manufacturer’s instructions for cleaning the I-Neb AAD or Prodose AAD System components after each dose administration.
Complete information regarding use of iloprost in specific populations (e.g. nursing mothers, pediatrics, patients with hepatic or renal impairment), drug interactions, and overdosage can be found in full prescribing information.
Iloprost is also available in an intravenous form, developed and marketed by Schering AG under the trade name Ilomedine.
IV Iloprost is usually administered, diluted, via a peripheral vein or central venous catheter. The diluted Iloprost should be delivered by an accurate rate delivery system such as a syringe driver. Doses vary with individuals as side effects are better tolerated by some patients than others. The duration of the treatment is typically 3 days. This is usually repeated every 8 to 12 weeks
Common side effects:
Serious adverse events reported with the use of inhaled iloprost include congestive heart failure
, chest pain, supraventricular tachycardia
, shortness of breath
, peripheral edema
, and kidney failure.
Warnings:
Pulmonary hypertension
In medicine, pulmonary hypertension is an increase in blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion...
(PAH), scleroderma
Scleroderma
Systemic sclerosis or systemic scleroderma is a systemic autoimmune disease or systemic connective tissue disease that is a subtype of scleroderma.-Skin symptoms:...
, Raynaud's phenomenon
Raynaud's phenomenon
In medicine, Raynaud's phenomenon is a vasospastic disorder causing discoloration of the fingers, toes, and occasionally other areas. This condition can also cause nails to become brittle with longitudinal ridges. Named for French physician Maurice Raynaud , the phenomenon is believed to be the...
and ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
. It was developed by the pharmaceutical company
Pharmaceutical company
The pharmaceutical industry develops, produces, and markets drugs licensed for use as medications. Pharmaceutical companies are allowed to deal in generic and/or brand medications and medical devices...
Schering AG and is marketed by Bayer Schering Pharma AG
Bayer Schering Pharma AG
Bayer Schering Pharma AG is a research-centered pharmaceutical company that was formed by the merger of Schering with Bayer on 29 December 2006. The company was originally founded in 1851 by Ernst Christian Friedrich Schering . The company employs more than 26,000 people in 140 subsidiaries all...
in Europe and Actelion Pharmaceuticals in the USA.
Clinical pharmacology
Iloprost is a synthetic analogue of prostacyclinProstacyclin
Prostacyclin is a member of the family of lipid molecules known as eicosanoids.As a drug, it is also known as "epoprostenol". The terms are sometimes used interchangeably.-History:...
PGI2. Iloprost dilates systemic and pulmonary arterial vascular
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
beds. It also affects platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
aggregation but the relevance of this effect to the treatment of pulmonary hypertension is unknown. The two diastereoisomers
Isomer
In chemistry, isomers are compounds with the same molecular formula but different structural formulas. Isomers do not necessarily share similar properties, unless they also have the same functional groups. There are many different classes of isomers, like stereoisomers, enantiomers, geometrical...
of iloprost differ in their potency in dilating blood vessels, with the 4S isomer substantially more potent than the 4R isomer.
Inhaled Iloprost
In the U.S., iloprost is inhaled specifically using the I-Neb AAD or Prodose AAD delivery systems. In Europe Iloprost has been approved for use with two compressed air nebulizers with AAD delivery systems (Halolite and Prodose) as well as with two ultrasonic nebulizers Ventaneb and I-Neb.Ventavis is supplied in 1 mL single-use glass ampules containing either 10 mcg/mL or 20 mcg/mL. 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 which 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.
The approved dosing regimen for iloprost is 6 to 9 times daily (no more than every 2 hours) during waking hours, according to individual need and tolerability. The significant clinical effects observed in the pivotal study of patients with PAH were achieved with a median dose of 30 mcg per day (range: 12.5 to 45 mcg delivered at the mouthpiece), corresponding to 6 daily inhalations of 5 mcg. The majority of patients (> 80%) in the pivotal study used this median dose or a higher dose with an excellent treatment compliance after 12 weeks.
The first inhaled dose of iloprost should be 2.5 mcg (as delivered at the mouthpiece). If this dose is well tolerated, dosing should be increased to 5 mcg and maintained at that dose. Any patient who cannot tolerate the 5 mcg dose should be maintained at 2.5 mcg.
Each inhalation treatment requires one entire single-use ampule. Each single-use ampule delivers a concentration of 10 mcg/mL to the medication chamber of either the I-Neb AAD or Prodose AAD System, and delivers a nominal dose of either 2.5 mcg or 5.0 mcg to the mouthpiece. After each inhalation session, any solution remaining in the medication chamber should be discarded. Use of the remaining solution, even if the reservoir is “topped off” with fresh medication, will result in unpredictable dosing. Patients should follow the manufacturer’s instructions for cleaning the I-Neb AAD or Prodose AAD System components after each dose administration.
Complete information regarding use of iloprost in specific populations (e.g. nursing mothers, pediatrics, patients with hepatic or renal impairment), drug interactions, and overdosage can be found in full prescribing information.
Intravenous Iloprost
IV Iloprost is usually administered, diluted, via a peripheral vein or central venous catheter. The diluted Iloprost should be delivered by an accurate rate delivery system such as a syringe driver. Doses vary with individuals as side effects are better tolerated by some patients than others. The duration of the treatment is typically 3 days. This is usually repeated every 8 to 12 weeks
Important safety information
Contraindications:- There are no known contraindications.
Common side effects:
- In clinical studies, common adverse reactions due to inhaled iloprost included: vasodilationVasodilationVasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When...
(flushing, 27%), cough (39%), headache (30%), flu syndrome (14%), nausea (13%), neck spasmsTrismus-Common causes:*Pericoronitis is the most common cause of trismus.*Inflammation of muscles of mastication. It is a frequent sequel to surgical removal of mandibular third molars . The condition is usually resolved on its own in 10–14 days, during which time eating and oral hygiene are compromised...
(12%), hypotensionHypotensionIn physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
(11%), insomnia (8%), and fainting (syncope) (8%); other serious adverse events reported with the use of Ventavis included congestive heart failureCongestive heart failureHeart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...
, chest pain, supraventricular tachycardiaTachycardiaTachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
, dyspneaDyspneaDyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...
, swelling of the limbs (especially around the ankles and feet)Peripheral edemaPeripheral edema is the swelling of tissues, usually in the lower limbs, due to the accumulation of fluids.The condition is commonly associated with aging, but can be caused by many other conditions, including congestive heart failure, trauma, alcoholism, altitude sickness, pregnancy,...
, and kidney failureRenal failureRenal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
.
Serious adverse events reported with the use of inhaled iloprost include congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...
, chest pain, supraventricular tachycardia
Supraventricular tachycardia
Supraventricular tachycardia is a general term that refers to any rapid heart rhythm originating above the ventricular tissue. Supraventricular tachycardias can be contrasted to the potentially more dangerous ventricular tachycardias - rapid rhythms that originate within the ventricular...
, shortness of breath
Dyspnea
Dyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...
, peripheral edema
Peripheral edema
Peripheral edema is the swelling of tissues, usually in the lower limbs, due to the accumulation of fluids.The condition is commonly associated with aging, but can be caused by many other conditions, including congestive heart failure, trauma, alcoholism, altitude sickness, pregnancy,...
, and kidney failure.
Warnings:
- Iloprost as Ventavis is intended for inhalation administration only via the I-Neb AAD or Prodose AAD Systems, pulmonary drug delivery devices. It has not been studied with any other nebulizers.
- Vital signs should be monitored while initiating inhaled iloprost therapy. Dose adjustments or a change in therapy should be considered if exertional syncope occurs. Inhaled Iloprost should not be initiated in patients with systolic blood pressure lower than 85 mm Hg. Iloprost should be stopped immediately if signs of pulmonary edema occur. This may be a sign of pulmonary venous hypertension. Iloprost has not been evaluated in patients with chronic obstructive pulmonary diseaseChronic obstructive pulmonary diseaseChronic obstructive pulmonary disease , also known as chronic obstructive lung disease , chronic obstructive airway disease , chronic airflow limitation and chronic obstructive respiratory disease , is the co-occurrence of chronic bronchitis and emphysema, a pair of commonly co-existing diseases...
(COPD), severe asthmaAsthmaAsthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
, or with acute pulmonary infections. - Should signs of pulmonary edema occur when inhaled iloprost is administered in patients with pulmonary hypertension, the treatment should be stopped immediately. This may be a sign of pulmonary venous hypertension.
See also
- pulmonary arterial hypertensionPulmonary hypertensionIn medicine, pulmonary hypertension is an increase in blood pressure in the pulmonary artery, pulmonary vein, or pulmonary capillaries, together known as the lung vasculature, leading to shortness of breath, dizziness, fainting, and other symptoms, all of which are exacerbated by exertion...
(PAH) - Raynaud's
- SclerodermaSclerodermaSystemic sclerosis or systemic scleroderma is a systemic autoimmune disease or systemic connective tissue disease that is a subtype of scleroderma.-Skin symptoms:...