Remodulin 10mg/ml Inj., 20ml
It is used to treat high blood pressure in the lungs.
Drug Class
Vasodilator, Antiplatelet Agent
Pharmacologic Class
Prostacyclin Analogue
Pregnancy Category
B
FDA Approved
May 2002
DEA Schedule
Not Controlled
Overview
What is this medicine?
Treprostinil is a medicine used to treat a serious lung condition called pulmonary hypertension. It works by relaxing and widening the blood vessels in your lungs, which helps your heart pump blood more easily and improves your breathing. It also helps prevent blood clots.
How to Use This Medicine
Proper Use of This Medication
To use this medication correctly, follow your doctor's instructions and read all accompanying information carefully. This medication is administered continuously into a vein or the fatty part of the skin. Your doctor may provide guidance 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, ensure you use the correct type of fluid. If you're unsure, consult your doctor or pharmacist.
Important Safety Precautions
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. Dispose of needles and other sharp objects in a designated disposal box. Never reuse needles or other items. When the disposal box is full, follow local regulations for proper disposal. If you have any questions or concerns, consult your doctor or pharmacist.
Storage and Disposal
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 accompanying information carefully. This medication is administered continuously into a vein or the fatty part of the skin. Your doctor may provide guidance 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, ensure you use the correct type of fluid. If you're unsure, consult your doctor or pharmacist.
Important Safety Precautions
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. Dispose of needles and other sharp objects in a designated disposal box. Never reuse needles or other items. When the disposal box is full, follow local regulations for proper disposal. If you have any questions or concerns, consult your doctor or pharmacist.
Storage and Disposal
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 the infusion suddenly, as this can lead to a dangerous worsening of your condition.
- Learn and practice proper infusion technique and aseptic care to prevent infections, especially for IV administration.
- Carry a backup pump and medication supply at all times.
- Avoid activities that cause excessive exertion, as advised by your doctor.
- Maintain good hygiene around the infusion site to prevent infection.
- Report any new or worsening symptoms, or signs of infection, immediately to your healthcare provider.
Available Forms & Alternatives
Available Strengths:
Generic Alternatives:
Dosing & Administration
Adult Dosing
Standard Dose:
Initial dose of 1.25 ng/kg/min administered as a continuous subcutaneous or intravenous infusion. Dose is increased gradually (e.g., by 1.25 ng/kg/min per week for SC, or 2.5 ng/kg/min every 1-2 weeks for IV) based on clinical response and tolerability.
Dose Range:
1.25 - 80 mg
Condition-Specific Dosing:
Pulmonary Arterial Hypertension (PAH):
Continuous subcutaneous or intravenous infusion. Dose titration is highly individualized based on clinical response and tolerability, aiming for the highest tolerated dose.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established (used off-label in some cases, highly individualized weight-based dosing)
Adolescent:
Not established (used off-label in some cases, highly individualized weight-based dosing)
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment recommended.
Moderate:
No specific dose adjustment recommended, monitor closely.
Severe:
Caution advised, monitor closely for adverse effects. No specific dose adjustment guidelines.
Dialysis:
Not well studied; treprostinil is extensively metabolized, so dialysis is unlikely to significantly affect clearance of the parent drug.
Hepatic Impairment:
Mild:
Reduce initial dose to 0.625 ng/kg/min and titrate cautiously.
Moderate:
Reduce initial dose to 0.625 ng/kg/min and titrate cautiously.
Severe:
Contraindicated or extreme caution; significant dose reduction required (e.g., 0.625 ng/kg/min initial dose) and very slow titration. Consider alternative therapies.
Pharmacology
Mechanism of Action
Treprostinil is a prostacyclin analogue. It directly dilates pulmonary and systemic arterial vascular beds and inhibits platelet aggregation. It reduces pulmonary vascular resistance (PVR) and improves cardiac output, stroke volume, and pulmonary artery pressure.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 100% (subcutaneous relative to intravenous)
Tmax:
3-5 hours (subcutaneous)
FoodEffect:
Not relevant for injection formulation.
Distribution:
Vd:
Approximately 14 L/70 kg
ProteinBinding:
Approximately 96% (primarily to albumin)
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 2-4 hours (terminal half-life)
Clearance:
Approximately 20-30 L/hr
ExcretionRoute:
Primarily urine (79% as metabolites, 4% unchanged), feces (13%)
Unchanged:
Approximately 4% in urine
Pharmacodynamics
OnsetOfAction:
Rapid (minutes for IV, hours for SC)
PeakEffect:
Dose-dependent, typically within hours of reaching a stable infusion rate.
DurationOfAction:
Sustained as long as continuous infusion is maintained.
Safety & Warnings
BLACK BOX WARNING
Chronic intravenous infusions of Remodulin are administered using a permanent indwelling central venous catheter and an ambulatory infusion pump. This route of administration is associated with the risk of bloodstream infections and other complications. Therefore, continuous subcutaneous infusion is the preferred route of administration.
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
While rare, some people may experience severe and potentially life-threatening side effects when 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 enlarge
+ Uncontrollable bleeding
Severe dizziness or fainting
Shortness of breath, sudden weight gain, or swelling in the arms or legs
Worsening or new breathing difficulties
Abnormal sensations, such as burning, numbness, or tingling
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. Although 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 unusual symptoms, contact your doctor for advice:
Dizziness or headache
Flushing
Jaw pain
Diarrhea
Upset stomach or vomiting
* Irritation at the injection site
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
While rare, some people may experience severe and potentially life-threatening side effects when 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 enlarge
+ Uncontrollable bleeding
Severe dizziness or fainting
Shortness of breath, sudden weight gain, or swelling in the arms or legs
Worsening or new breathing difficulties
Abnormal sensations, such as burning, numbness, or tingling
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. Although 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 unusual symptoms, contact your doctor for advice:
Dizziness or headache
Flushing
Jaw pain
Diarrhea
Upset stomach or vomiting
* Irritation at the injection site
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns, contact 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:
- Severe headache
- Sudden dizziness or fainting
- Chest pain or severe shortness of breath
- Unusual bleeding or bruising
- Signs of infection at the infusion site (e.g., severe pain, redness, swelling, warmth, 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, including prescription and over-the-counter drugs, natural products, and vitamins, with your doctor and pharmacist. They will help you determine if it is safe to take this medication in combination with your other medications and health conditions.
Remember, do not start, stop, or change the dose of any medication without first consulting your doctor to ensure your safety.
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, including prescription and over-the-counter drugs, natural products, and vitamins, with your doctor and pharmacist. They will help you determine if it is safe to take this medication in combination with your other medications and health conditions.
Remember, do not start, stop, or change the dose of any medication without first consulting your doctor to ensure your safety.
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 a sitting or lying position, 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 and 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 an emergency.
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 a sitting or lying position, 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 and 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 an emergency.
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 (fainting)
What to Do:
If overdose is suspected, reduce the dose or discontinue the infusion immediately. Provide supportive care as needed. Contact a poison control center or seek emergency medical attention. Call 1-800-222-1222 (Poison Control).
Drug Interactions
Major Interactions
- Anticoagulants (e.g., warfarin, heparin): Increased risk of bleeding due to antiplatelet effects.
- Antiplatelet agents (e.g., aspirin, clopidogrel): Increased risk of bleeding.
- Antihypertensives (e.g., diuretics, ACE inhibitors, beta-blockers, calcium channel blockers): Additive hypotensive effects.
- CYP2C8 inhibitors (e.g., gemfibrozil): May increase treprostinil exposure, requiring dose reduction.
- CYP2C8 inducers (e.g., rifampin): May decrease treprostinil exposure, requiring dose increase.
Moderate Interactions
- PDE5 inhibitors (e.g., sildenafil, tadalafil): Additive vasodilatory effects, monitor for hypotension.
- Other vasodilators: Additive hypotensive effects.
Monitoring
Baseline Monitoring
Confirmation of PAH diagnosis (e.g., right heart catheterization)
Rationale: To ensure appropriate indication for therapy.
Timing: Prior to initiation of therapy.
Liver function tests (ALT, AST, bilirubin)
Rationale: Treprostinil is metabolized hepatically; baseline assessment is crucial, especially for patients with hepatic impairment.
Timing: Prior to initiation of therapy.
Renal function tests (SCr, eGFR)
Rationale: To assess baseline kidney function.
Timing: Prior to initiation of therapy.
Blood pressure and heart rate
Rationale: To establish baseline and monitor for hypotensive effects.
Timing: Prior to initiation of therapy.
Bleeding risk assessment
Rationale: Due to antiplatelet effects and potential for increased bleeding risk.
Timing: Prior to initiation of therapy.
Routine Monitoring
Clinical symptoms (dyspnea, fatigue, syncope, chest pain)
Frequency: Regularly, especially during dose titration and long-term therapy.
Target: Improvement or stabilization of symptoms.
Action Threshold: Worsening symptoms may indicate need for dose adjustment or re-evaluation of therapy.
Blood pressure and heart rate
Frequency: Regularly, especially during dose titration and with changes in clinical status.
Target: Maintain within acceptable limits, avoid symptomatic hypotension.
Action Threshold: Symptomatic hypotension or significant bradycardia/tachycardia.
Infusion site assessment (for SC infusion)
Frequency: Daily or with each dressing change.
Target: Absence of pain, redness, swelling, induration, or infection.
Action Threshold: Signs of infection, severe pain, or skin breakdown requiring intervention.
Liver function tests
Frequency: Periodically, especially in patients with hepatic impairment or signs of liver dysfunction.
Target: Within normal limits or stable.
Action Threshold: Significant elevation of liver enzymes.
6-minute walk test (6MWT)
Frequency: Every 3-6 months or as clinically indicated.
Target: Improvement or stabilization of walk distance.
Action Threshold: Significant decline in 6MWT distance.
Symptom Monitoring
- Headache
- Nausea
- Diarrhea
- Flushing
- Jaw pain
- Hypotension
- Dizziness
- Bleeding (e.g., epistaxis, bruising)
- Infusion site pain/reaction (redness, swelling, induration, rash, infection)
- Dyspnea
- Fatigue
- Syncope
Special Patient Groups
Pregnancy
Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal studies have shown adverse effects on fetal development.
Trimester-Specific Risks:
First Trimester:
Potential for adverse developmental effects observed in animal studies.
Second Trimester:
Potential for adverse developmental effects observed in animal studies.
Third Trimester:
Potential for adverse developmental effects observed in animal studies.
Lactation
It is unknown 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:
Potential for serious adverse reactions; caution advised.
Pediatric Use
Safety and efficacy have not been established in pediatric patients. Use in children is generally off-label and requires highly individualized dosing and close monitoring by specialists.
Geriatric Use
No specific dose adjustment is recommended based on age alone. However, geriatric patients may have age-related decreases in renal or hepatic function and may be more sensitive to the hypotensive effects of treprostinil. Monitor closely for adverse effects.
Clinical Information
Clinical Pearls
- Abrupt discontinuation or sudden large dose reductions of treprostinil can lead to rebound pulmonary hypertension and potentially fatal outcomes. Doses must be tapered gradually under medical supervision.
- Infusion site pain is a very common and often dose-limiting side effect with subcutaneous administration. Strategies include rotating sites, using higher concentrations, or switching to intravenous administration if tolerated.
- Strict aseptic technique is paramount for intravenous administration to minimize the risk of catheter-related bloodstream infections, which can be life-threatening.
- Dose titration is a slow and individualized process, requiring close monitoring of patient symptoms, hemodynamics, and tolerability.
- Patients should always carry a backup infusion pump and sufficient medication supply, especially when traveling.
Alternative Therapies
- Epoprostenol (Flolan, Veletri)
- Iloprost (Ventavis)
- Selexipag (Uptravi)
- Bosentan (Tracleer)
- Ambrisentan (Letairis)
- Macitentan (Opsumit)
- Sildenafil (Revatio)
- Tadalafil (Adcirca)
- Riociguat (Adempas)
Cost & Coverage
Average Cost:
Highly variable, typically thousands of dollars per vial/month depending on concentration and volume. per vial
Generic Available:
Yes
Insurance Coverage:
Specialty Tier, typically requires prior authorization and may have strict coverage criteria.
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe and effective treatment, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea to check with your pharmacist for more information. If you have any questions or concerns about this medication, don't hesitate to discuss them with 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 medication taken, the amount, and the time it happened.