Drugs Details

Drugs Info of Ventavis
Drugs Details
  • Drugs Type  : Multum
  • Date : 26th Jun 2015 03:30 am
  • Brand Name : Ventavis
  • Generic Name : iloprost inhalation (Pronunciation: ill O prost)
Descriptions

Ventavis (iloprost) Inhalation Solution is a clear, colorless, sterile solution containing iloprost formulated for inhalation via the I-neb® AAD® (Adaptive Aerosol Delivery) System. Ventavis is supplied in 1 mL single-use glass ampules containing either 10 mcg/mL or 20 mcg/mL.

For the 10 mcg/mL solution, one mL of the solution contains 0.01 mg iloprost, 0.81 mg ethanol, 0.121 mg tromethamine, 9.0 mg sodium chloride, and approximately 0.51 mg hydrochloric acid (for pH adjustment to 8.1) in water for injection.

For the 20 mcg/mL solution, one mL of the solution contains 0.02 mg iloprost, 1.62 mg ethanol, 0.242 mg tromethamine, 9.0 mg sodium chloride, and approximately 0.76 mg hydrochloric acid (for pH adjustment to 8.4) in water for injection.

The solution contains no preservatives.

The chemical name for iloprost is (E)-(3aS, 4R, 5R, 6aS)-hexahydro-5-hydroxy-4-[(E)(3S,4RS)-3-hydroxy-4-methyl-1-octen-6-ynyl]-Δ2(1H), Δ -pentalenevaleric acid. Iloprost consists of a mixture of the 4R and 4S diastereoisomers at a ratio of approximately 53:47. Iloprost is an oily substance, which is soluble in methanol, ethanol, ethyl acetate, acetone, and pH 7 buffer, sparingly soluble in buffer pH 9, and very slightly soluble in distilled water, buffer pH 3, and buffer pH 5. The molecular formula of iloprost is C22H32O4. Its relative molecular weight is 360.49. The structural formula is shown below:

 

VENTAVIS® (iloprost) Structural Formula Illustration

What are the possible side effects of iloprost inhalation (Ventavis)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • feeling like you might pass out;
  • pounding heartbeats or fluttering in your chest;
  • coughing up blood;
  • unusual bleeding (nosebleeds, bleeding gums);
  • fever, chills, cough with yellow or green mucus;
  • chest tightness, stabbing chest pain, wheezing, feeling short of breath; or
  • anxiety, sweating,...

Read All Potential Side Effects and See Pictures of Ventavis »

What are the precautions when taking iloprost (Ventavis)?

Before using iloprost, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: low blood pressure, liver problems, kidney problems, bleeding problems, other breathing problems (such as asthma).

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your...

Read All Potential Precautions of Ventavis »


This monograph has been modified to include the generic and brand name in many instances.

Indications

Pulmonary Arterial Hypertension

Ventavis® is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve a composite endpoint consisting of exercise tolerance, symptoms (NYHA Class), and lack of deterioration. Studies establishing effectiveness included predominately patients with NYHA Functional Class III-IV symptoms and etiologies of idiopathic or heritable PAH (65%) or PAH associated with connective tissue diseases (23%) [see Clinical Studies].

Dosage Administration

Recommended Dosing

Ventavis is intended to be inhaled using the I-neb® AAD® System. The first inhaled dose should be 2.5 mcg (as delivered at the mouthpiece). If this dose is well tolerated, dosing should be increased to 5.0 mcg and maintained at that dose; otherwise maintain the dose at 2.5 mcg. Ventavis should be taken 6 to 9 times per day (no more than once every 2 hours) during waking hours, according to individual need and tolerability. The maximum daily dose evaluated in clinical studies was 45 mcg (5 mcg 9 times per day).

Direct mixing of Ventavis with other medications in the I-neb® AAD® System has not been evaluated; do not mix with other medications. To avoid potential interruptions in drug delivery due to equipment malfunctions, the patient should have easy access to a back-up I-neb® AAD® System.

Ventavis is supplied in 1 mL ampules in two concentrations: 10 mcg/mL and 20 mcg/mL.

 

Nebulizer Delivered dose from ampule of :
10 mcg/mL 20 mcg/mL
I-neb® AAD® 2.5 or 5 mcg from one ampule 5 mcg from one ampule

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 Ineb®AAD® System will decrease treatment times to help maintain patient compliance.

For each inhalation session, the entire contents of each opened ampule of Ventavis should be transferred into the I-neb® AAD® System medication chamber immediately before use [see PATIENT INFORMATION]. After each inhalation session, any solution remaining in the medication chamber should be discarded. Use of the remaining solution will result in unpredictable dosing. Patients should follow the manufacturer's instructions for cleaning the I-neb® AAD® System components after each dose administration.

Monitoring

Vital signs should be monitored while initiating Ventavis. [see WARNINGS AND PRECAUTIONS].

Use In Patients With Pre-existing Hepatic Impairment

Because iloprost elimination is reduced in patients with impaired liver function [see Special Populations], consider increasing the dosing interval (e.g., 3-4 hours between doses depending on the patient's response at the end of the dose interval) in patients with Child-Pugh Class B or C hepatic impairment.

Use In Patients With Pre-existing Renal Impairment

Dose adjustment is not required in patients who are not on dialysis. The effect of dialysis on iloprost is unknown [see Special Populations].

How Supplied

Dosage Forms And Strengths

1 mL ampules in two concentrations: 10 mcg/mL and 20 mcg/mL.

Storage And Handling

Ventavis (iloprost) Inhalation Solution is supplied in cartons of 30 x 1 mL clear glass single-use ampules as follows:

1 mL ampule containing iloprost 10 mcg per mL, carton of 30 (NDC 66215-302-30)
1 mL ampule containing iloprost 20 mcg per mL, carton of 30 (NDC 66215-303-30)

Storage

Store at 20 – 25°C (68 – 77°F)

Excursions permitted to 15 – 30°C (59 – 86°F)

[See USP Controlled Room Temperature]

Issued November 2013. Manufactured for: Actelion Pharmaceuticals US, Inc. 5000 Shoreline Court, Ste. 200 South San Francisco, CA 94080 ©2013 Actelion Pharmaceuticals US, Inc.


This monograph has been modified to include the generic and brand name in many instances.

Side Effects

Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Pre-marketing safety data on Ventavis were obtained from 215 patients with pulmonary arterial hypertension receiving iloprost in two 12-week clinical trials and two long-term extensions. Patients received inhaled Ventavis for periods of from 1 day to more than 3 years. The median number of weeks of exposure was 15. Forty patients completed 12 months of open-label treatment with iloprost.

The following table shows adverse events reported by at least 4 Ventavis patients and reported at least 3% more frequently for Ventavis patients than placebo patients in the 12week placebo-controlled study.

Table 1: Adverse Events in Phase 3 Clinical Trial

Adverse Event Ventavis
n = 101
Placebo
n = 102
Placebo subtracted %
Vasodilation (flushing) 27 9 18
Cough increased 39 26 13
Headache 30 20 10
Trismus 12 3 9
Insomnia 8 2 6
Nausea 13 8 5
Hypotension 11 6 5
Vomiting 7 2 5
Alk phos increased 6 1 5
Flu syndrome 14 10 4
Back pain 7 3 4
Tongue pain 4 0 4
Palpitations 7 4 3
Syncope 8 5 3
GGT increased 6 3 3
Muscle cramps 6 3 3
Hemoptysis 5 2 3
Pneumonia 4 1 3

Pre-marketing serious adverse events reported with the use of inhaled Ventavis and not shown in Table 1 include congestive heart failure, chest pain, supraventricular tachycardia, dyspnea, peripheral edema, and kidney failure.

In a small clinical trial (the STEP trial) [see Clinical Studies], safety trends in patients receiving concomitant bosentan and Ventavis were consistent with those observed in the larger experience of the Phase 3 study in patients receiving only Ventavis or bosentan.

Adverse events with higher doses

In a study in healthy subjects (n=160), inhaled doses of iloprost solution were given every 2 hours, beginning with 5 mcg and increasing up to 20 mcg for a total of 6 dose inhalations (total cumulative dose of 70 mcg) or up to the highest dose tolerated in a subgroup of 40 subjects. There were 13 subjects (32%) who failed to reach the highest scheduled dose (20 mcg). Five were unable to increase the dose because of (mild to moderate) transient chest pain/discomfort/tightness, usually accompanied by headache, nausea, and dizziness. The remaining 8 subjects discontinued for other reasons.

Postmarketing Experience

The following adverse reactions have been identified during the postapproval use of Ventavis. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cases of bronchospasm and wheezing have been reported, particularly in patients with a history of hyperreactive airways [see WARNINGS AND PRECAUTIONS]. Bleeding events most commonly reported as epistaxis and hemoptysis were observed on Ventavis treatment [see DRUG INTERACTIONS]. Cases of thrombocytopenia, dizziness, diarrhea, mouth and tongue irritation, nasal congestion, dysgeusia, hypersensitivity, and rash have also been reported with the use of Ventavis.

Read the Ventavis (iloprost) Side Effects Center for a complete guide to possible side effects

Interactions

During clinical trials, iloprost was used concurrently with anticoagulants, diuretics, cardiac glycosides, calcium channel blockers, analgesics, antipyretics, nonsteroidal anti-inflammatory drugs, corticosteroids, and other medications. Intravenous infusion of iloprost had no effect on the pharmacokinetics of digoxin. Acetylsalicylic acid did not alter the clearance (pharmacokinetics) of iloprost.

Cytochrome P450

Although clinical studies have not been conducted with Ventavis (inhaled iloprost), in vitro studies of iloprost indicate that no relevant inhibition of cytochrome P450 drug metabolism would be expected.

Antihypertensives and Vasodilators

In studies in normal subjects, there was no pharmacodynamic interaction between intravenous iloprost and either nifedipine, diltiazem, or captopril. However, Ventavis has the potential to increase the hypotensive effect of vasodilators and antihypertensive agents.

Anticoagulants and Platelet Inhibitors

Since Ventavis inhibits platelet function, there is a potential for increased risk of bleeding, particularly in patients maintained on anticoagulants or platelet inhibitors.

Read the Ventavis Drug Interactions Center for a complete guide to possible interactions


This monograph has been modified to include the generic and brand name in many instances.

Warnings

Included as part of the PRECAUTIONS section.

Precautions

Ventavis solution should not be allowed to come into contact with the skin or eyes; oral ingestion of Ventavis solution should be avoided.

Risk of Syncope

Monitor vital signs while initiating Ventavis. Do not initiate Ventavis in patients with systolic blood pressure below 85 mmHg. Syncope can also occur in association with pulmonary arterial hypertension, particularly in association with physical exertion. The occurrence of exertional syncope may reflect a therapeutic gap or insufficient efficacy, and the need to adjust dose or change therapy should be considered.

Pulmonary Venous Hypertension

Should signs of pulmonary edema occur when inhaled Ventavis is administered in patients with pulmonary hypertension, stop treatment immediately, as this may be a sign of pulmonary venous hypertension.

Bronchospasm

Ventavis inhalation can induce bronchospasm. Bronchospasm may be more severe or frequent in patients with a history of hyperreactive airways. Ventavis has not been evaluated in patients with chronic obstructive pulmonary disease (COPD), severe asthma, or with acute pulmonary infections.

Patient Counseling Information

Patients receiving Ventavis should be advised to use the drug only as prescribed with the I-neb® AAD® System, following the manufacturer's instructions. Patients should be trained in proper administration techniques including dosing frequency, ampule dispensing, I-neb® AAD® System operation, and equipment cleaning.

Advise patients that they may have a fall in blood pressure with Ventavis, so they may become dizzy or even faint. They should stand up slowly when they get out of a chair or bed. If fainting gets worse, patients should consult their physicians about dose adjustment.

Advise patients that Ventavis should be inhaled at intervals of not less than 2 hours and that the acute benefits of Ventavis may not last 2 hours. Thus patients may want to adjust times of administration to cover planned activities.

See FDA-approved patient labeling.

Preparation Instructions

Ventavis ampules may be opened with a rubber pad or with an ampule breaker.

When using a rubber pad:

1. With one hand, hold the bottom of the ampule with the blue dot facing away from your body.

 

Hold the bottom of the ampule - Illustration

2. With the other hand, wrap the included rubber pad around the entire ampule.

 

Wrap the included rubber pad around the entire ampule - Illustration

3. Using your thumbs, break open the neck of the ampule by snapping the top towards you and then carefully dispose of the top of the ampule into a sharps bin.

 

Break open the neck of the ampule - Illustration

When using an ampule breaker:

1. Align the blue dot on the Ventavis ampule with the dot on the ampule breaker, if available, and then insert the top of the ampule into the ampule breaker.

 

Align the blue dot - Illustration

2. Gently break open the neck of the ampule by levering away from the dot on the Ventavis ampule to snap off the ampule lid.

 

Gently break open the neck of the ampule - Illustration

3. Carefully dispose of the top of the ampule into a sharps bin or appropriate storage container.

 

Carefully dispose of the top of the ampule - Illustration

For either:

4. After opening the ampule, use the small tube (pipette) supplied with Ventavis, draw-up the entire amount of one ampule of Ventavis and transfer the entire contents of the ampule into the medication chamber of the I-neb® AAD® System.

 

draw-up the entire amount of one ampule of Ventavis - Illustration

5. Safely dispose of the open ampule and pipette as instructed by your healthcare practitioner. Keep ampules and pipettes out of the reach of children.

 

Safely dispose of the open ampule - Illustration

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Iloprost was not mutagenic in bacterial and mammalian cells in the presence or absence of extrinsic metabolic activation. Iloprost did not cause chromosomal aberrations in vitro in human lymphocytes and was not clastogenic in vivo in NMRI/SPF mice. There was no evidence of a tumorigenic effect of iloprost clathrate (13% iloprost by weight) in Sprague-Dawley rats dosed orally for up to 8 months at doses of up to 125 mg/kg/day (Cmax of 45 ng/mL serum), followed by 16 months at 100 mg/kg/day, or in Crl:CD1® (ICR)BR albino mice dosed orally for up to 24 months at doses of up to 125 mg/kg/day (Cmax of 156 ng/mL serum). The recommended clinical dosage regimen for iloprost (5 mcg) affords a serum Cmax of 0.16 ng/mL. Fertility of males or females was not impaired in Han-Wistar rats at intravenous doses up to 1 mg/kg/day.

Use In Specific Populations

Pregnancy

Pregnancy Category C

Ventavis has been shown to be teratogenic in rats as described below. There are no adequate and well controlled studies in pregnant women. Ventavis should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

In developmental toxicity studies in pregnant Han-Wistar rats, continuous intravenous administration of iloprost at a dosage of 0.01 mg/kg daily (serum levels not available) led to shortened digits of the thoracic extremity in fetuses and pups. In comparable studies in pregnant Sprague-Dawley rats which received iloprost clathrate (13% iloprost by weight) orally at dosages of up to 50 mg/kg/day (Cmax of 90 ng/mL), in pregnant rabbits at intravenous dosages of up to 0.5 mg/kg/day (Cmax of 86 ng/mL), and in pregnant monkeys at dosages of up to 0.04 mg/kg/day (serum levels of 1 ng/mL), no such digital anomalies or other gross-structural abnormalities were observed in the fetuses/pups. However, in gravid Sprague-Dawley rats, iloprost clathrate (13% iloprost) significantly increased the number of non-viable fetuses at a maternally toxic oral dosage of 250 mg/kg/day and in Han-Wistar rats was found to be embryolethal in 15 of 44 litters at an intravenous dosage of 1 mg/kg/day.

Nursing Mothers

It is not known whether Ventavis is excreted in human milk. In studies with Han-Wistar rats, higher mortality was observed in pups of lactating dams receiving iloprost intravenously at 1 mg/kg daily. In Sprague-Dawley rats, higher mortality was also observed in nursing pups at a maternally toxic oral dose of 250 mg/kg/day of iloprost clathrate (13% iloprost by weight). In rats a passage of low levels of iloprost or metabolites in to the milk was observed (less than 1% of iloprost dose given intravenously). No disturbance of post-natal development and reproductive performance was seen in animals exposed during lactation. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Ventavis, a decision to discontinue nursing should be made, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and efficacy in pediatric patients have not been established.

Geriatric Use

Clinical studies of Ventavis did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently than younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

Hepatic Impairment

Ventavis has not been evaluated in subjects with impaired hepatic function. However, in an intravenous iloprost study in patients with liver cirrhosis, the mean clearance in Child- Pugh Class B subjects (n=5) was approximately 10 mL/min/kg (half that of healthy subjects). Following oral administration, the mean AUC0-8h in Child-Pugh Class B subjects (n=3) was 1725 pg*h/mL compared to 117 pg*h/mL in normal subjects (n=4) receiving the same oral iloprost dose. In Child-Pugh Class A subjects (n=5), the mean AUC0-8h was 639 pg*h/mL. Although exposure increased with hepatic impairment, there was no effect on half-life.

Renal Impairment

Ventavis has not been evaluated in subjects with impaired renal function. However, in a study with intravenous infusion of iloprost in patients with end-stage renal failure requiring intermittent dialysis treatment (n=7), the mean AUC0-4h was 230 pg*h/mL compared to 54 pg*h/mL in patients with renal failure (n=8) not requiring intermittent dialysis and 48 pg*h/mL in normals. The half-life was similar in both groups. The effect of dialysis on iloprost exposure has not been evaluated.


This monograph has been modified to include the generic and brand name in many instances.

OverDose

In clinical trials of Ventavis, no case of overdose was reported. Signs and symptoms to be anticipated are extensions of the dose-limiting pharmacological effects, including hypotension, headache, flushing, nausea, vomiting, and diarrhea. A specific antidote is not known. Interruption of the inhalation session, monitoring, and symptomatic measures are recommended.

ContrainDications

None


This monograph has been modified to include the generic and brand name in many instances.

Clinical Pharamacology

Mechanism of Action

Iloprost is a synthetic analog of prostacyclin 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.

Pharmacokinetics

General

In pharmacokinetic studies in animals, there was no evidence of interconversion of the two diastereoisomers of iloprost. In human pharmacokinetic studies, the two diastereoisomers were not individually assayed.

Iloprost administered intravenously has linear pharmacokinetics over the dose range of 1 to 3 ng/kg/min. The half-life of iloprost is 20 to 30 minutes. Following inhalation of iloprost (5 mcg) patients with pulmonary hypertension have iloprost peak plasma levels of approximately 150 pg/mL. Iloprost was generally not detectable in plasma 30 minutes to 1 hour after inhalation.

Absorption and Distribution

The absolute bioavailability of inhaled iloprost has not been determined. Following intravenous infusion, the apparent steady-state volume of distribution was 0.7 to 0.8 L/kg in healthy subjects. Iloprost is approximately 60% protein-bound, mainly to albumin, and this ratio is concentration-independent in the range of 30 to 3000 pg/mL.

Metabolism and Excretion

In vitro studies reveal that cytochrome P450-dependent metabolism plays only a minor role in the biotransformation of iloprost. Iloprost is metabolized principally via β-oxidation of the carboxyl side chain. The main metabolite is tetranor-iloprost, which is found in the urine in free and conjugated form. In animal experiments, tetranor-iloprost was pharmacologically inactive.

Clearance in normal subjects was approximately 20 mL/min/kg.

A mass-balance study using intravenously and orally administered [3H]-iloprost in healthy subjects (n=8) showed recovery of 81% of total radioactivity over 14 hours post-dose, with 68% and 12% recoveries in urine and feces, respectively.

Clinical Studies

A randomized, double-blind, multi-center, placebo-controlled trial was conducted in 203 adult patients (inhaled iloprost: n=101; placebo: n=102) with NYHA Class III or IV pulmonary arterial hypertension (PAH, WHO Group 1; idiopathic in 53%, associated with connective tissue disease, including CREST and scleroderma, in 17%, or associated with anorexigen use in 2%) or PAH related to chronic thromboembolic disease (WHO Group 4; 28%). Inhaled iloprost (or placebo) was added to patients' current therapy, which could have included anticoagulants, vasodilators (e.g., calcium channel blockers), diuretics, oxygen, and digoxin, but not PGI2 (prostacyclin or its analogs) or endothelin receptor antagonists. Patients received 2.5 or 5.0 mcg of iloprost by repeated inhalations 6 to 9 times per day during waking hours. The mean age of the entire study population was 52 years and 68% of the patients were female. The majority of patients (59%) were NYHA Class III. The baseline 6-minute walk test values reflected a moderate exercise limitation (the mean was 332 meters for the iloprost group and 315 meters for the placebo group). In the iloprost group, the median daily inhaled dose was 30 mcg (range of 12.5 to 45 mcg/day). The mean number of inhalations per day was 7.3. Ninety percent of patients in the iloprost group never inhaled study medication during the nighttime.

The primary efficacy endpoint was clinical response at 12 weeks, a composite endpoint defined by: a) improvement in exercise ability (6-minute walk test) by at least 10% versus baseline evaluated 30 minutes after dosing, b) improvement by at least one NYHA class versus baseline, and c) no death or deterioration of pulmonary hypertension. Deterioration required two or more of the following criteria: 1) refractory systolic blood pressure < 85 mmHg, 2) worsening of right heart failure with cardiac edema, ascites, or pleural effusion despite adequate background therapy, 3) rapidly progressive cardiogenic hepatic failure (e.g., leading to an increase of GOT or GPT to > 100 U/L, or total bilirubin ≥ 5 mg/dL), 4) rapidly progressive cardiogenic renal failure (e.g., decrease of estimated creatinine clearance to ≤ 50% of baseline), 5) decrease in 6-minute walking distance by ≥ 30% of baseline value, 6) new long-term need for i.v. catecholamines or diuretics, 7) cardiac index ≤ 1.3 L/min/m², 8) CVP ≥ 22 mmHg despite adequate diuretic therapy, and 9) SVO2 ≤ 45% despite nasal O2 therapy.

Although effectiveness was seen in the full population (response rates for the primary composite endpoint of 17% and 5%; p=0.007), there was inadequate evidence of benefit in patients with pulmonary hypertension associated with chronic thromboembolic disease (WHO Group 4); the results presented are therefore those related to patients with PAH (WHO Group 1). The response rate for the primary efficacy endpoint among PAH patients was 19% for the iloprost group, compared with 4% for the placebo group(p=0.0033). All three components of the composite endpoint favored iloprost (Figure 1)

Figure 1: Composite Primary Endpoint for PAH Patients (WHO Group I)

Composite Primary Endpoint for PAH Patients - Illustration

The absolute change in 6-minute walk distance (Figure 2) measured (using all available data and no imputation) 30 minutes after inhalation among patients with PAH was greater in the iloprost group compared to the placebo group at all time points. At Week 12, the placebo-corrected difference was 40 meters (p < 0.01). When walk distance was measured immediately prior to inhalation, the improvement compared to placebo was approximately 60% of the effect seen at 30 minutes after inhalation.

Figure 2: Change (Mean ± SEM) in 6-Minute Walk Distance 30 Minutes Post-inhalation in PAH Patients (WHO Group 1).

Change (Mean ± SEM) in 6-Minute Walk Distance 30 Minutes - Illustration

The effect of Ventavis in various subgroups is shown in Table 2.

Table 2: Treatment Effects by Subgroup among PAH Patients (WHO Group 1)

View Enlarged Table

Hemodynamic assessments obtained at week 12 before inhalation in both groups (at least 2 hours after a previous dose, trough) and after inhalation in the iloprost group (approximately 15 minutes after a dose, peak), are shown in Table 3. The relationship between hemodynamic changes and clinical effects is unknown.

Table 3 : Hemodynamic Parameters Before and After Iloprost Inhalation: Change from Baseline to Week 12*

Parameter Baseline Mean (± SD) change from baseline at Week 12
Iloprost Placebo Iloprost Placebo
Before Inhalation After Inhalation
PVR (dyn•s•cm–5) 1029 ± 390 1041 ± 493 -9 ± 275 (n=76) -239 ± 279 (n=70) +96 ± 323 (n=77)
mPAP (mmHg) 53 ± 12 54 ± 14 -0.2 ± 7.3 (n=93) -4.6 ± 9.3 (n=90) -0.1 ± 6.9 (n=82)
CO (L/min) 3.8 ± 1.1 3.8 ± 0.9 +0.1 ± 0.9 (n=91) +0.5 ± 1.1 (n=89) -0.2 ± 0.8 (n=80)
SVO2 (%) 60 ± 8 60±8 -1.1 ± 7.6 (n=72) +1.8 ± 8.3 (n=70) -3.2 ± 6.7 (n=63)
*Patients of all etiologies of PAH, including CTEPH.

In a small, randomized, double-blind, placebo-controlled study (the STEP trial), 34 patients treated with bosentan 125 mg bid for at least 16 weeks tolerated the addition of inhaled iloprost (up to 5 mcg 6 to 9 times per day during waking hours). The mean daily inhaled dose was 27 mcg and the mean number of inhalations per day was 5.6.


This monograph has been modified to include the generic and brand name in many instances.

Patient Information

Ventavis®
(ven TAY vis)
(iloprost) Inhalation Solution

Read the Patient Information that comes with Ventavis before you start using it and each time you get a refill. There may be new information. The leaflet does not take the place of talking with your doctor about your medical condition or your treatment.

What is Ventavis?

Ventavis is a prescription medicine used to treat adults with certain kinds of severe pulmonary arterial hypertension (PAH), a condition in which blood pressure is too high in the blood vessels between the heart and the lungs. Ventavis may improve your ability to exercise and your symptoms for a short time by lowering your blood pressure and opening up the blood vessels in your lungs.

Ventavis has not been studied in children younger than 18 years old.

What should I tell my doctor before taking Ventavis?

Ventavis may not be right for you. Before taking Ventavis, tell your doctor about all of your medical conditions, including if you:

  • have liver or kidney problems. Your doctor may need to give you a lower dose of Ventavis.
  • are pregnant, or plan to become pregnant. It is not known if Ventavis can harm your unborn baby. Ventavis should only be used during pregnancy if the benefit to you is worth the possible risk to your baby.
  • are breast-feeding. It is not known if Ventavis passes into your breast milk. You and your doctor should decide if you will take Ventavis or breast feed.

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements.

Ventavis and other medicines may affect each other causing side effects. Ventavis may affect the way other medicines work, and other medicines may affect how Ventavis works.

Especially tell your doctor if you take:

  • medicines used to treat high blood pressure or heart problems
  • medicines that lessen blood clotting (warfarin, Coumadin, Jantoven)

Know the medicines you take. Keep a list of your medicines and show it to your doctor and pharmacist when you get a new medicine.

How should I take Ventavis?

See the end of this leaflet for detailed instructions for using Ventavis.

  • Take Ventavis exactly as your doctor tells you to take it. Your doctor may change your dose if needed.
  • You should not take Ventavis more than every 2 hours. The benefits of Ventavis may not last 2 hours, so you may adjust the times that you use it to cover planned activities.
  • Do not drink Ventavis.
  • Do not let Ventavis solution come into contact with your skin or eyes. If it does, rinse your skin or eyes with water right away.
  • Do not allow other people to be exposed to Ventavis while you are breathing it, especially babies and pregnant women.
  • If you take too much Ventavis, you may have a headache, red face, dizziness, nausea, vomiting and diarrhea. If this happens stop taking Ventavis. If your symptoms do not go away, call your doctor or get emergency help right away.

What are the possible side effects of Ventavis?

Ventavis may cause side effects, including feeling dizzy, lightheaded and faint. If you have any of these side effects, you should stand up slowly when you get out of chairs or bed. Tell your doctor if your fainting gets worse during treatment with Ventavis. Your doctor may need to change your dose or your treatment.

Do not drive a car or operate any tools or machines if dizziness or fainting from low blood pressure is a problem for you.

You may have trouble breathing after taking Ventavis because it may cause the muscles around your airway to tighten (bronchospasm). Get emergency help right away if you have trouble breathing.

Other important side effects of Ventavis include:

  • bleeding
  • red face (flushing)
  • increased cough
  • low blood pressure
  • headaches
  • nausea
  • spasm of your jaw muscles that makes it hard to open your mouth

Talk to your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Ventavis. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA 1088.

How should I store Ventavis?

  • Store Ventavis between 68°F to 77°F (20°C to 25°C).
  • Safely throw away Ventavis that is out of date or no longer needed.

Keep Ventavis and all medicines out of the reach of children.

General Information about Ventavis

Medicines are sometimes prescribed for conditions that are not listed in the patient leaflet. Do not use Ventavis for a condition for which it was not prescribed. Do not give Ventavis to other people, even if they have the same symptoms you have. It may harm them.

This patient information leaflet summarizes the most important information about Ventavis. If you would like more information about Ventavis talk with your doctor. You can ask your doctor or pharmacist for information about Ventavis that is written for health professionals. For more information go to www. VENTAVIS.com or call 1-866-ACTELION (1-866-228-3546).

What are the ingredients in Ventavis?

Active ingredient: iloprost

Inactive ingredients: tromethamine, ethanol, sodium chloride, hydrochloric acid for pH adjustment, and water for injection.

Ventavis is a clear, colorless solution.

Patient Instructions for Using Ventavis

To take Ventavis, you will need to use the I-neb Adaptive Aerosol Delivery (AAD) System. This system is used to give you the right dose of Ventavis. You should not use other systems to take Ventavis as other systems may not give you the amount of Ventavis you need.

Do not use Ventavis until your doctor has showed you how to use this system the right way. Make sure you understand all the instructions or ask questions until you do.

I-neb AAD System

 

I-neb AAD System - Illustration

Ventavis Ampule

 

Ventavis Ampule - Illustration

With the I-neb System, you will receive two medicine chambers (one with a red latch and one with a purple latch) and two color-matching dosing discs to use with the 10 micrograms per 1 mL of Ventavis.

I-neb System Medication Chamber

 

I-neb System Medication Chamber - Illustration

You should use the red dosing disc with the red latched medicine chamber (gives you a 2.5 microgram dose). You should use the purple dosing disc with the purple-latched medicine chamber (gives you a 5 microgram dose). Always use all of the contents of only 1 ampule when using the I-neb System.

If you are using the I-neb System and usually have long treatment times, your doctor may ask you to switch to a third medicine chamber (one with a gold latch). The medicine chamber with the gold latch and matching dosing disc are only for use with the 20 micrograms per 1 mL ampule of Ventavis. You should use the gold dosing disc with the gold latched medicine chamber (gives you a 5 microgram dose.).

Do not change the medicine chamber and dosing disc in your I-neb System without talking to your doctor.

Do not put any medicines other than Ventavis in your I-neb System.

To Use Ventavis:

Open the small glass bottle (ampule) of Ventavis by using either an ampule breaker or a rubber pad. Use either the ampule breaker or the rubber pad. You do not need to use both methods to open a Ventavis ampule.

When using an ampule breaker:

Step 1. Line up the blue dot on the Ventavis ampule with the dot on the ampule breaker, if available, and then insert the top of the ampule into the ampule breaker.

 

Line up the blue dot - Illustration

Step 2. Gently break open the neck of the ampule by pushing away from the dot on the Ventavis ampule to snap off the ampule lid.

 

Gently break open the neck - Illustration

Step 3. Carefully throw away the top of the ampule into a safe container.

 

Carefully throw away the top - Illustration

When using a rubber pad:

Step 1. Hold the ampule with the blue dot facing away from your body.

 

Hold the ampule with the blue dot facing away - Illustration

Step 2. Wrap the rubber pad around the ampule to protect yourself from getting cut.

 

Wrap the rubber pad around - Illustration

Step 3. Use your thumbs to break open the neck of the ampule by snapping the top toward you.

 

Use your thumbs to break open the neck of the ampule - Illustration

Step 4. Using the small tube (pipette ) that comes with Ventavis, draw-up the entire amount of one ampule of Ventavis and empty it into the center of the I-neb System medicine chamber. The amount of Ventavis you receive will be controlled by either the dosing disc or the medicine chamber.

I-neb System

 

I-neb System - Illustration

Step 5. Throw away in a safe container the:

  • top of the ampule (the ampule lid)
  • open ampule

Keep both the ampule and the pipette out of the reach of children.

 

Throw away in a safe container - Illustration

Step 6. To breathe in your dose of Ventavis, follow the instructions that come with your I-neb System. Each treatment session with Ventavis lasts about 4 to 10 minutes. Call your doctor if you usually have longer treatment times as your dose may need to be changed.

The I-neb System allows you to stop your treatment for up to ten minutes with no effect on the final dose you get. If your treatment is stopped for more than ten minutes, the I-neb System will reset itself. If that happens, throw away the solution in the chamber and wait at least two hours before taking your next dose. If you take a second dose right away you could get too much medicine.

Step 7. Throw away any Ventavis that is left in the medicine chamber after each treatment. Do not use the rest of the Ventavis because it will not give you the right dose.

Step 8. Clean your system after each treatment. Follow the instructions that come with your system.

Step 9. Make sure you have access to a back-up I-neb System to use for Ventavis treatments. This is important if your original system does not work for some reason.


This monograph has been modified to include the generic and brand name in many instances.

Consumer Overview Uses

MPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

 

ILOPROST SOLUTION - INHALATION

 

(EYE-loe-prost)

 

COMMON BRAND NAME(S): Ventavis

 

USES: This medication is used to treat a type of high blood pressure in the lungs (pulmonary arterial hypertension). Iloprost helps to increase your ability to exercise and improves symptoms such as shortness of breath and tiredness. It works by relaxing and widening the blood vessels (arteries) in the lungs and other parts of the body so that blood can flow more easily. This medication belongs to a class of drugs known as vasodilators.

 

HOW TO USE: Read the Patient Information Leaflet available from your pharmacist. This medication comes in a glass bottle (ampule). Follow the manufacturer's instructions on how to open the ampule and how to prepare each dose. This product is used with a special breathing device (nebulizer). Ask your doctor, pharmacist or respiratory therapist how to inhale this medication properly with this equipment. Make sure you understand how to properly clean the nebulizer to prevent infections.

Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid. Do not mix with other medications in the nebulizer.

Inhale this medication by mouth as directed by your doctor, usually 6 to 9 times daily, at least 2 hours apart. Do not drink the solution. Do not get this medication on the skin or in your eyes. If this happens, rinse the area with water. The dosage is based on your medical condition and response to treatment.

Use this medication regularly to get the most benefit from it. To help you remember, use it at the same times each day.

To avoid not being able to use your medication, be sure to have access to a back-up nebulizer in case your regular device stops working properly.

Tell your doctor if your condition does not improve or if it worsens.

Consumer Overview Side Effect

SIDE EFFECTS: Nausea, vomiting, diarrhea, headache, dizziness, jaw pain, muscle spasms of the jaw, flushing, or trouble sleeping may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: wheezing, sudden weight gain, worsening breathing, chest pain, fainting.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

 

Read the Ventavis (iloprost) Side Effects Center for a complete guide to possible side effects

Learn More »

PRECAUTIONS: Before using iloprost, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: low blood pressure, liver problems, kidney problems, bleeding problems, other breathing problems (such as asthma).

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is unknown if this drug passes into breast milk. Consult your doctor before breast-feeding.

Consumer Overview Missed Dose

DRUG INTERACTIONS: The effects of some drugs can change if you take other drugs or herbal products at the same time. This can increase your risk for serious side effects or may cause your medications not to work correctly. These drug interactions are possible, but do not always occur. Your doctor or pharmacist can often prevent or manage interactions by changing how you use your medications or by close monitoring.

To help your doctor or pharmacist give you the best care, be sure to tell your doctor or pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products) before starting treatment with this product. While using this product, do not start, stop, or change the dosage of any other medicines you are using without your doctor's approval.

Iloprost may lower your blood pressure. Your doctor may also direct you to take other medications that may also lower your blood pressure (such as "water pills"/diuretics such as furosemide, ACE inhibitors such as captopril, calcium channel blockers such as nifedipine, other vasodilators such as nitrates). Your doctor may also prescribe "blood thinners" (such as warfarin) to prevent blood clots. Iloprost may increase your risk of bleeding if you take "blood thinners." Your doctor or pharmacist will monitor you for these possible drug interactions. Tell your doctor or pharmacist immediately if you develop symptoms such as easy or unusual bleeding/bruising, severe dizziness, or fainting.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

 

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe dizziness, fainting.

 

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (such as blood pressure, liver function tests) may be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

 

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

 

STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

 

Information last revised December 2013. Copyright(c) 2013 First Databank, Inc.

Patient Detailed Side Effect

Brand Names: Ventavis

Generic Name: iloprost inhalation (Pronunciation: ill O prost)

  • What is iloprost inhalation (Ventavis)?
  • What are the possible side effects of iloprost inhalation (Ventavis)?
  • What is the most important information I should know about iloprost inhalation (Ventavis)?
  • What should I discuss with my healthcare provider before taking iloprost inhalation (Ventavis)?
  • How should I use iloprost inhalation (Ventavis)?
  • What happens if I miss a dose (Ventavis)?
  • What happens if I overdose (Ventavis)?
  • What should I avoid while using iloprost inhalation (Ventavis)?
  • What other drugs will affect iloprost inhalation (Ventavis)?
  • Where can I get more information?

What is iloprost inhalation (Ventavis)?

Iloprost inhalation is an synthetic prostacyclin. It works by opening blood vessels in the lungs.

Iloprost inhalation is used to treat pulmonary arterial hypertension (PAH). It decreases symptoms of this condition and improves your ability to exercise.

Iloprost inhalation may also be used for purposes not listed in this medication guide.

What are the possible side effects of iloprost inhalation (Ventavis)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • feeling like you might pass out;
  • pounding heartbeats or fluttering in your chest;
  • coughing up blood;
  • unusual bleeding (nosebleeds, bleeding gums);
  • fever, chills, cough with yellow or green mucus;
  • chest tightness, stabbing chest pain, wheezing, feeling short of breath; or
  • anxiety, sweating, pale skin, severe shortness of breath, wheezing, gasping for breath, cough with foamy mucus, chest pain, fast or uneven heart rate.

Less serious side effects may include:

  • flushing (warmth, redness, or tingly feeling);
  • increased cough;
  • nausea, vomiting, diarrhea;
  • headache, dizziness;
  • muscle cramps, back pain;
  • sleep problems (insomnia);
  • tongue pain, jaw tightness or pain, trouble chewing or speaking; or
  • altered sense of taste.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Ventavis (iloprost) Side Effects Center for a complete guide to possible side effects

Learn More »

What is the most important information I should know about iloprost inhalation (Ventavis)?

Before using iloprost inhalation, tell your doctor if you have liver or kidney disease, heart disease, low blood pressure, asthma or COPD, or a chest cold with cough.

Iloprost inhalation is usually given 6 to 9 times per day. Your doses should not be spaced less than 2 hours apart, even if you feel like the effects of the medicine have worn off in less than 2 hours.

Iloprost should be used only with the I-neb ADD System, or the Prodose AAD System. Do not use iloprost inhalation with any other type of nebulizers. You will be shown how to use your nebulizer at home.

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Side Effects Centers
  • Ventavis

Patient Detailed How Take

What should I discuss with my healthcare provider before taking iloprost inhalation (Ventavis)?

To make sure you can safely use iloprost, tell your doctor if you have other medical conditions, especially:

  • liver disease;
  • heart disease;
  • kidney disease;
  • low blood pressure;
  • chronic obstructive pulmonary disease (COPD);
  • asthma; or
  • a chest cold or cough.

FDA pregnancy category C. It is not known whether iloprost will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

It is not known whether iloprost passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using iloprost.

How should I use iloprost inhalation (Ventavis)?

Use exactly as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Iloprost inhalation is usually given 6 to 9 times per day. Follow the directions on your prescription label.

Your doses should not be spaced less than 2 hours apart, even if you feel like the effects of the medicine have worn off in less than 2 hours.

Your doctor may occasionally change your dose or daily dosing schedule to make sure you get the best results.

Iloprost is an inhaled medicine that should be used only with the I-neb ADD System, or the Prodose AAD System. Do not use iloprost inhalation with any other type of nebulizers.

You will be shown how to use your nebulizer at home. Your nebulizer system comes with patient instructions for safe and effective use, and for cleaning and care. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.

Each single-use ampule (bottle) of this medicine is for one use only. Throw away after one use, even if there is still some medicine left in it after empyting the entire contents into your nebulizer.

Store at room temperature away from moisture and heat.

Side Effects Centers
  • Ventavis

Patient Detailed Avoid Taking

What happens if I miss a dose (Ventavis)?

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

What happens if I overdose (Ventavis)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include severe forms of some of the side effects listed in this medication guide.

What should I avoid while using iloprost inhalation (Ventavis)?

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Avoid getting this medication in your eyes or mouth, or on your skin. If this does happen, rinse with water.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Avoid allowing anyone else to breathe in this medication while you are inhaling your dose, especially children or pregnant women.

What other drugs will affect iloprost inhalation (Ventavis)?

Tell your doctor about all other medicines you use, especially:

  • blood pressure medication;
  • a blood thinner such as warfarin (Coumadin, Jantoven); or
  • medication used to prevent blood clots, such as abciximab (ReoPro), anagrelide (Agrylin), cilostazol (Pletal), clopidogrel (Plavix), dipyridamole (Persantine, Aggrenox), eptifibatide (Integrilin), prasugrel (Effient), rivaroxaban (Xarelto), ticlopidine (Ticlid), or tirofiban (Aggrastat).

This list is not complete and other drugs may interact with iloprost inhalation. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

Your doctor or pharmacist can provide more information about iloprost inhalation.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 3.01. Revision date: 9/11/2012.

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