Remodulin 5mg/ml Inj., 20ml
It is used to treat high blood pressure in the lungs.
Drug Class
Pulmonary Hypertension Agent
Pharmacologic Class
Prostacyclin Analog; Vasodilator; Antiplatelet
Pregnancy Category
Category B
FDA Approved
May 2002
DEA Schedule
Not Controlled
Overview
What is this medicine?
Remodulin is a medicine used to treat a serious lung condition called pulmonary arterial hypertension (PAH). It works by relaxing the blood vessels in your lungs, which helps blood flow more easily and reduces the strain on your heart. It is given as a continuous infusion, either under the skin (subcutaneous) or directly into a vein (intravenous) using a small pump.
How to Use This Medicine
Proper Use of This Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. This medication is administered continuously into a vein or the fatty part of the skin. Your doctor may instruct you on how to administer it yourself. Before and after handling the medication, wash your hands thoroughly.
If you need to mix this medication with another fluid, make sure you use the correct type of fluid. If you're unsure, consult your doctor or pharmacist. Do not use the medication if the solution appears cloudy, is leaking, or contains particles. Additionally, do not use it if the solution has changed color.
Disposal and Storage
Dispose of used needles and other sharp objects in a designated needle/sharp disposal box. Do not reuse needles or other items. When the box is full, follow local regulations for proper disposal. If you have any questions, consult your doctor or pharmacist.
Storage Instructions
Store unopened vials at room temperature.
Missed Dose
If you miss a dose, contact your doctor to determine the best course of action.
To use this medication correctly, follow your doctor's instructions and read all the information provided. This medication is administered continuously into a vein or the fatty part of the skin. Your doctor may instruct you on how to administer it yourself. Before and after handling the medication, wash your hands thoroughly.
If you need to mix this medication with another fluid, make sure you use the correct type of fluid. If you're unsure, consult your doctor or pharmacist. Do not use the medication if the solution appears cloudy, is leaking, or contains particles. Additionally, do not use it if the solution has changed color.
Disposal and Storage
Dispose of used needles and other sharp objects in a designated needle/sharp disposal box. Do not reuse needles or other items. When the box is full, follow local regulations for proper disposal. If you have any questions, consult your doctor or pharmacist.
Storage Instructions
Store unopened vials at room temperature.
Missed Dose
If you miss a dose, contact your doctor to determine the best course of action.
Lifestyle & Tips
- Never stop or interrupt your infusion suddenly, as this can cause your PAH symptoms to worsen severely and rapidly.
- Learn proper sterile technique for preparing and administering your infusion to prevent serious infections, especially if using the intravenous route.
- Always have backup supplies (pump, medication, batteries) readily available.
- Avoid activities that significantly worsen your PAH symptoms.
- Report any signs of infection at the infusion site (redness, swelling, pain, pus, fever) immediately.
- Report any unusual bleeding or bruising.
Available Forms & Alternatives
Available Strengths:
Generic Alternatives:
Dosing & Administration
Adult Dosing
Standard Dose:
Initial dose 1.25 ng/kg/min (subcutaneous or intravenous continuous infusion). Titrate by 1.25 ng/kg/min increments weekly or bi-weekly based on clinical response and tolerability. Max dose can exceed 40 ng/kg/min.
Dose Range:
1.25 - 40 mg
Condition-Specific Dosing:
Pulmonary Arterial Hypertension (PAH):
Continuous subcutaneous or intravenous infusion. Dose titration is critical and individualized.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Used in pediatric PAH; initial dose typically 0.625 ng/kg/min, titrated based on clinical response and tolerability. Dosing is highly individualized and complex.
Adolescent:
Used in pediatric PAH; initial dose typically 0.625 ng/kg/min, titrated based on clinical response and tolerability. Dosing is highly individualized and complex.
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment required.
Moderate:
No specific dose adjustment required.
Severe:
No specific dose adjustment required, but caution and close monitoring are advised due to potential for increased exposure.
Dialysis:
Considerations: No specific recommendations, but monitor for adverse effects.
Hepatic Impairment:
Mild:
Initial dose 0.625 ng/kg/min (50% reduction from normal starting dose). Titrate cautiously.
Moderate:
Initial dose 0.625 ng/kg/min (50% reduction from normal starting dose). Titrate cautiously.
Severe:
Initial dose 0.625 ng/kg/min (50% reduction from normal starting dose). Titrate cautiously. Avoid if possible due to significantly increased exposure.
Pharmacology
Mechanism of Action
Treprostinil is a prostacyclin analogue. It directly dilates pulmonary and systemic arterial beds, and inhibits platelet aggregation. These actions contribute to improved hemodynamics and reduced symptoms in patients with pulmonary arterial hypertension (PAH).
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 100% (subcutaneous)
Tmax:
3-5 hours (subcutaneous)
FoodEffect:
Not applicable for parenteral administration.
Distribution:
Vd:
Approximately 14 L/70kg
ProteinBinding:
Approximately 91% (primarily to albumin)
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 4 hours (subcutaneous/intravenous)
Clearance:
Approximately 29 L/hr (total body clearance)
ExcretionRoute:
Primarily renal (79% in urine), with a smaller portion in feces (13%).
Unchanged:
<4% (in urine)
Pharmacodynamics
OnsetOfAction:
Rapid (within minutes of initiation/dose change for IV, hours for SC)
PeakEffect:
Not distinctly defined due to continuous infusion and titration; effects are sustained.
DurationOfAction:
Effects persist as long as infusion is maintained; half-life dictates offset after discontinuation.
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of bleeding, including:
+ Vomiting or coughing up blood
+ Vomit that resembles coffee grounds
+ Blood in the urine
+ Black, red, or tarry stools
+ Bleeding from the gums
+ Abnormal vaginal bleeding
+ Unexplained bruises or bruises that increase in size
+ Uncontrollable bleeding
Severe dizziness or fainting
Shortness of breath, significant weight gain, or swelling in the arms or legs
Worsening or new breathing difficulties
Abnormal burning, numbness, or tingling sensations
Anxiety or restlessness
Pain or irritation at the injection site
Arm swelling
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other symptoms that bother you or persist, contact your doctor:
Dizziness or headache
Flushing
Jaw pain
Diarrhea
Upset stomach or vomiting
* Irritation at the injection site
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of bleeding, including:
+ Vomiting or coughing up blood
+ Vomit that resembles coffee grounds
+ Blood in the urine
+ Black, red, or tarry stools
+ Bleeding from the gums
+ Abnormal vaginal bleeding
+ Unexplained bruises or bruises that increase in size
+ Uncontrollable bleeding
Severe dizziness or fainting
Shortness of breath, significant weight gain, or swelling in the arms or legs
Worsening or new breathing difficulties
Abnormal burning, numbness, or tingling sensations
Anxiety or restlessness
Pain or irritation at the injection site
Arm swelling
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other symptoms that bother you or persist, contact your doctor:
Dizziness or headache
Flushing
Jaw pain
Diarrhea
Upset stomach or vomiting
* Irritation at the injection site
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Sudden worsening of shortness of breath or chest pain (signs of rebound PAH if infusion is interrupted)
- Severe dizziness or fainting (signs of low blood pressure)
- Unusual bleeding or bruising
- Severe headache
- Signs of infection at the infusion site (redness, swelling, warmth, pain, pus, fever, chills)
- Severe nausea, vomiting, or diarrhea
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you have liver disease, as this may affect your ability to take this medication.
This list is not exhaustive, and it is crucial to discuss all your medications, health conditions, and concerns with your doctor. This includes:
All prescription and over-the-counter (OTC) medications you are taking
Any natural products or vitamins you are using
* Any health problems you have, as they may interact with this medication
To ensure your safety, always check with your doctor before starting, stopping, or changing the dose of any medication. This will help prevent potential interactions and ensure that it is safe for you to take this medication with your other drugs and health conditions.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you have liver disease, as this may affect your ability to take this medication.
This list is not exhaustive, and it is crucial to discuss all your medications, health conditions, and concerns with your doctor. This includes:
All prescription and over-the-counter (OTC) medications you are taking
Any natural products or vitamins you are using
* Any health problems you have, as they may interact with this medication
To ensure your safety, always check with your doctor before starting, stopping, or changing the dose of any medication. This will help prevent potential interactions and ensure that it is safe for you to take this medication with your other drugs and health conditions.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
When starting this medication, avoid driving and other activities that require alertness until you understand how it affects you. To minimize the risk of dizziness or fainting, get up slowly from sitting or lying down, and be cautious when climbing stairs.
Be aware that this medication may increase your risk of bleeding. Take precautions to avoid injury, and use a soft-bristled toothbrush and an electric razor for shaving.
Do not abruptly stop taking this medication without consulting your doctor, as this may worsen symptoms of high blood pressure in the lungs, such as shortness of breath, dizziness, or weakness.
If you receive this medication intravenously, you may be at a higher risk of developing a severe, potentially life-threatening infection. Discuss this risk with your doctor.
If you experience symptoms of withdrawal or suspect that the medication pump is not functioning correctly, seek immediate medical attention. Always have a backup system readily available in case of emergencies.
If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects.
If you are pregnant, planning to become pregnant, or breastfeeding, inform your doctor to discuss the potential benefits and risks to you and your baby.
When starting this medication, avoid driving and other activities that require alertness until you understand how it affects you. To minimize the risk of dizziness or fainting, get up slowly from sitting or lying down, and be cautious when climbing stairs.
Be aware that this medication may increase your risk of bleeding. Take precautions to avoid injury, and use a soft-bristled toothbrush and an electric razor for shaving.
Do not abruptly stop taking this medication without consulting your doctor, as this may worsen symptoms of high blood pressure in the lungs, such as shortness of breath, dizziness, or weakness.
If you receive this medication intravenously, you may be at a higher risk of developing a severe, potentially life-threatening infection. Discuss this risk with your doctor.
If you experience symptoms of withdrawal or suspect that the medication pump is not functioning correctly, seek immediate medical attention. Always have a backup system readily available in case of emergencies.
If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects.
If you are pregnant, planning to become pregnant, or breastfeeding, inform your doctor to discuss the potential benefits and risks to you and your baby.
Overdose Information
Overdose Symptoms:
- Severe flushing
- Headache
- Hypotension (low blood pressure)
- Nausea
- Vomiting
- Diarrhea
- Dizziness
- Syncope
What to Do:
If overdose is suspected, immediately reduce or discontinue the infusion. Provide supportive care as needed. Call 911 or your local emergency number. For poison control, call 1-800-222-1222.
Drug Interactions
Major Interactions
- Strong CYP2C8 inhibitors (e.g., gemfibrozil): May significantly increase treprostinil exposure, requiring dose reduction.
- Strong CYP2C8 inducers (e.g., rifampin): May significantly decrease treprostinil exposure, requiring dose increase.
Moderate Interactions
- Anticoagulants (e.g., warfarin): Increased risk of bleeding.
- Antiplatelet agents (e.g., aspirin, clopidogrel): Increased risk of bleeding.
- Antihypertensive agents (e.g., beta-blockers, ACE inhibitors, calcium channel blockers): Increased risk of systemic hypotension.
- Diuretics: Increased risk of systemic hypotension.
- Other vasodilators (e.g., nitrates, PDE5 inhibitors): Increased risk of systemic hypotension.
Monitoring
Baseline Monitoring
Diagnosis of PAH
Rationale: Confirm eligibility and severity of PAH.
Timing: Prior to initiation
Liver function tests (LFTs)
Rationale: Assess baseline hepatic function, as dose adjustments are needed for hepatic impairment.
Timing: Prior to initiation
Renal function tests (e.g., creatinine, eGFR)
Rationale: Assess baseline renal function.
Timing: Prior to initiation
Hemodynamic parameters (e.g., right heart catheterization)
Rationale: Establish baseline pulmonary vascular resistance, pulmonary artery pressure, cardiac output.
Timing: Prior to initiation
6-minute walk distance (6MWD)
Rationale: Assess functional capacity.
Timing: Prior to initiation
Routine Monitoring
Blood pressure and heart rate
Frequency: Regularly, especially during dose titration and with changes in concomitant medications.
Target: Maintain within patient's normal range, avoid symptomatic hypotension.
Action Threshold: Symptomatic hypotension or significant bradycardia/tachycardia.
Symptoms of PAH (e.g., dyspnea, fatigue, chest pain, syncope)
Frequency: Daily, with each patient encounter.
Target: Improvement or stabilization of symptoms.
Action Threshold: Worsening symptoms, indicating need for dose adjustment or re-evaluation.
Infusion site reactions (for SC infusion)
Frequency: Daily, with each site change.
Target: Minimal pain, erythema, induration.
Action Threshold: Severe pain, swelling, blistering, ulceration, or signs of infection.
Signs of bleeding
Frequency: Regularly, especially if on concomitant anticoagulants/antiplatelets.
Target: Absence of abnormal bleeding.
Action Threshold: Unusual bruising, petechiae, epistaxis, GI bleeding.
6-minute walk distance (6MWD)
Frequency: Every 3-6 months, or as clinically indicated.
Target: Improvement or stabilization.
Action Threshold: Significant decline.
Symptom Monitoring
- Dyspnea (shortness of breath)
- Fatigue
- Chest pain
- Syncope (fainting)
- Dizziness
- Headache
- Nausea
- Vomiting
- Diarrhea
- Jaw pain
- Flushing
- Infusion site pain, erythema, induration, swelling, rash, bruising, bleeding, infection (for SC infusion)
- Signs of catheter-related bloodstream infection (for IV infusion): fever, chills, redness/pain at catheter site.
Special Patient Groups
Pregnancy
Category B. Animal studies have shown no evidence of harm to the fetus. However, there are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if clearly needed.
Trimester-Specific Risks:
First Trimester:
No specific increased risk identified in animal studies.
Second Trimester:
No specific increased risk identified in animal studies.
Third Trimester:
No specific increased risk identified in animal studies.
Lactation
It is not known whether treprostinil is excreted in human milk. Due to the potential for serious adverse reactions in breastfed infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Infant Risk:
Unknown; caution advised.
Pediatric Use
Safety and effectiveness have been established in pediatric patients aged 1 month to 16 years with PAH. Dosing is weight-based and requires careful titration. Infusion site reactions are common.
Geriatric Use
No specific dose adjustment is required based on age. However, elderly patients may have reduced hepatic or renal function, or more comorbidities, requiring careful monitoring and individualized dosing.
Clinical Information
Clinical Pearls
- Remodulin is a life-sustaining medication for PAH; abrupt discontinuation can be fatal due to rebound pulmonary hypertension.
- Dose titration is highly individualized and requires close monitoring of patient symptoms and tolerability.
- Infusion site pain and reactions are very common with subcutaneous administration and can be a major limiting factor for patients. Rotation of infusion sites is crucial.
- Intravenous administration carries a significant risk of catheter-related bloodstream infections and sepsis, necessitating strict sterile technique and patient education.
- Patients and caregivers must be thoroughly trained on pump operation, sterile technique, and emergency procedures.
- Consider drug interactions, especially with CYP2C8 inhibitors/inducers, and other vasodilators/anticoagulants.
Alternative Therapies
- Epoprostenol (Flolan, Veletri) - another prostacyclin analog, IV only, very short half-life.
- Iloprost (Ventavis) - inhaled prostacyclin analog.
- Selexipag (Uptravi) - prostacyclin receptor agonist, oral.
- PDE5 inhibitors (e.g., sildenafil, tadalafil) - oral.
- Endothelin Receptor Antagonists (ERAs) (e.g., ambrisentan, bosentan, macitentan) - oral.
- Soluble Guanylate Cyclase (sGC) Stimulators (e.g., riociguat) - oral.
Cost & Coverage
Average Cost:
Highly variable, typically tens of thousands of USD per month. per 20ml vial (5mg/ml)
Generic Available:
Yes
Insurance Coverage:
Specialty Tier; requires prior authorization and often managed by specialty pharmacies.
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more information. If you have any questions or concerns about this medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide details about the overdose, including the medication taken, the amount, and the time it occurred.