Orenitram ER 1mg Tablets
It is used to treat high blood pressure in the lungs.
Drug Class
Vasodilator; Antihypertensive, Pulmonary
Pharmacologic Class
Prostacyclin analogue
Pregnancy Category
Not available
FDA Approved
Dec 2013
DEA Schedule
Not Controlled
Overview
What is this medicine?
Orenitram is a medication 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. This can improve your ability to exercise and help you feel better.
How to Use This Medicine
Taking Your Medication Correctly
To ensure you get the most benefit from your medication, follow these steps:
Take your medication exactly as directed by your doctor.
Read all the information provided with your medication and follow the instructions carefully.
Take your medication with food to help your body absorb it properly.
Swallow the tablet whole - do not chew, break, or crush it.
Do not take any tablets that are chipped or broken.
Storing and Disposing of Your Medication
To keep your medication safe and effective:
Store it at room temperature in a dry place, away from the bathroom.
Keep all medications in a safe location, out of the reach of children and pets.
Dispose of any unused or expired medication properly. Do not flush it down the toilet or pour it down the drain unless instructed to do so by your pharmacist.
Check with your pharmacist for guidance on the best way to dispose of your medication. You may also have access to a drug take-back program in your area.
What to Do If You Miss a Dose
If you miss a dose of your medication:
Take it as soon as you remember, with food.
If it's close to the time for your next dose, skip the missed dose and resume your regular schedule.
Do not take two doses at the same time or take extra doses.
* If you miss two doses, contact your doctor for further instructions.
To ensure you get the most benefit from your medication, follow these steps:
Take your medication exactly as directed by your doctor.
Read all the information provided with your medication and follow the instructions carefully.
Take your medication with food to help your body absorb it properly.
Swallow the tablet whole - do not chew, break, or crush it.
Do not take any tablets that are chipped or broken.
Storing and Disposing of Your Medication
To keep your medication safe and effective:
Store it at room temperature in a dry place, away from the bathroom.
Keep all medications in a safe location, out of the reach of children and pets.
Dispose of any unused or expired medication properly. Do not flush it down the toilet or pour it down the drain unless instructed to do so by your pharmacist.
Check with your pharmacist for guidance on the best way to dispose of your medication. You may also have access to a drug take-back program in your area.
What to Do If You Miss a Dose
If you miss a dose of your medication:
Take it as soon as you remember, with food.
If it's close to the time for your next dose, skip the missed dose and resume your regular schedule.
Do not take two doses at the same time or take extra doses.
* If you miss two doses, contact your doctor for further instructions.
Lifestyle & Tips
- Take Orenitram exactly as prescribed, usually twice a day, with or without food. Try to take it at the same times each day.
- Do NOT crush, chew, or split the tablets. Swallow them whole.
- Do not stop taking Orenitram suddenly without talking to your doctor, as this can worsen your condition.
- Monitor your blood pressure and heart rate as advised by your doctor.
- Report any new or worsening symptoms, especially shortness of breath, chest pain, dizziness, or swelling in your legs/ankles.
- Stay hydrated, especially if experiencing diarrhea or vomiting.
- Avoid activities that may lead to excessive drops in blood pressure, such as sudden changes in position.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Initial 0.25 mg twice daily (BID), titrated by 0.25 mg or 0.5 mg BID every 3-4 days based on tolerability and clinical response.
Dose Range:
0.25 - 16 mg
Condition-Specific Dosing:
Pulmonary Arterial Hypertension (PAH):
Initial 0.25 mg BID. Titrate by 0.25 mg or 0.5 mg BID every 3-4 days. Doses typically range from 0.25 mg to 16 mg BID, but higher doses may be used based on individual patient response and tolerability. Max dose is patient-specific and limited by tolerability.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment required.
Moderate:
No specific dose adjustment required.
Severe:
Use with caution; monitor for adverse effects. No specific dose adjustment recommendations, but consider lower initial doses and slower titration.
Dialysis:
Not well studied. No specific recommendations, but monitor closely for adverse effects due to potential for altered pharmacokinetics.
Hepatic Impairment:
Mild:
Reduce initial dose to 0.125 mg BID. Titrate cautiously.
Moderate:
Reduce initial dose to 0.125 mg BID. Titrate cautiously.
Severe:
Avoid use if possible. If necessary, consider further dose reduction and extreme caution. Not recommended due to lack of data and potential for increased exposure.
Pharmacology
Mechanism of Action
Treprostinil is a prostacyclin analogue. It directly dilates pulmonary and systemic arterial beds and inhibits platelet aggregation. In patients with pulmonary arterial hypertension (PAH), it improves exercise capacity and delays clinical worsening. Its vasodilatory effects reduce pulmonary arterial pressure, pulmonary vascular resistance, and mean right atrial pressure, while increasing cardiac index.
Pharmacokinetics
Absorption:
Bioavailability:
10-15%
Tmax:
4-6 hours
FoodEffect:
A high-fat meal increases Cmax by approximately 1.5-fold and AUC by approximately 1.2-fold. Administer consistently with or without food.
Distribution:
Vd:
Approximately 14 L
ProteinBinding:
Approximately 96%
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 5-6 hours
Clearance:
Approximately 30 L/hr
ExcretionRoute:
Urine (79%), Feces (13%)
Unchanged:
<4% (in urine)
Pharmacodynamics
OnsetOfAction:
Gradual (due to extended-release formulation and titration)
PeakEffect:
Not precisely defined for therapeutic effect, but plasma concentrations peak at 4-6 hours.
DurationOfAction:
Approximately 12 hours (due to BID dosing of ER formulation)
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 experience 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, significant weight gain, or swelling in the arms or legs
New or worsening trouble breathing
Signs of low potassium levels, such as:
+ Muscle pain or weakness
+ Muscle cramps
+ An irregular heartbeat
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
Pain in the arms or legs
Stomach pain
Note: You may notice the tablet shell in your stool, but this is a normal and harmless occurrence.
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns about side effects, 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 experience 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, significant weight gain, or swelling in the arms or legs
New or worsening trouble breathing
Signs of low potassium levels, such as:
+ Muscle pain or weakness
+ Muscle cramps
+ An irregular heartbeat
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
Pain in the arms or legs
Stomach pain
Note: You may notice the tablet shell in your stool, but this is a normal and harmless occurrence.
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns about side effects, 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:
- Severe dizziness or fainting (syncope)
- Sudden or severe shortness of breath
- Chest pain or discomfort
- Unusual bleeding or bruising
- Severe headache that does not go away
- Persistent nausea, vomiting, or diarrhea leading to dehydration
- Significant swelling in the hands, ankles, or feet
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 the safety and efficacy of the medication.
This list is not exhaustive, and it is crucial to discuss all your health conditions and medications with your doctor. Please provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter (OTC) medications you are taking
Any natural products or vitamins you are using
* Your health problems, including any medical conditions or diseases
To ensure your safety, do not start, stop, or change the dose of any medication without first consulting your doctor. It is vital to verify that it is safe to take this medication with all 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 the safety and efficacy of the medication.
This list is not exhaustive, and it is crucial to discuss all your health conditions and medications with your doctor. Please provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter (OTC) medications you are taking
Any natural products or vitamins you are using
* Your health problems, including any medical conditions or diseases
To ensure your safety, do not start, stop, or change the dose of any medication without first consulting your doctor. It is vital to verify that it is safe to take this medication with all 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 a sitting or lying position, and exercise caution 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 pulmonary hypertension, such as shortness of breath, dizziness, or weakness. Discuss any concerns with your doctor.
Note that the tablet's outer shell does not dissolve and may pose a problem if you have a condition like diverticulosis. If this applies to you, consult your doctor.
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 exercise caution 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 pulmonary hypertension, such as shortness of breath, dizziness, or weakness. Discuss any concerns with your doctor.
Note that the tablet's outer shell does not dissolve and may pose a problem if you have a condition like diverticulosis. If this applies to you, consult your doctor.
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 hypotension (very low blood pressure)
- Flushing
- Headache
- Nausea
- Vomiting
- Diarrhea
- Dizziness
What to Do:
Seek immediate medical attention. Call 911 or your local emergency number. Management is supportive, focusing on symptomatic treatment of hypotension and other adverse effects. Call 1-800-222-1222 (Poison Control Center).
Drug Interactions
Major Interactions
- Gemfibrozil (strong CYP2C8 inhibitor): May significantly increase treprostinil exposure, leading to increased adverse effects (e.g., hypotension, flushing, headache). Consider dose reduction of treprostinil.
- Rifampin (strong CYP2C8 inducer): May significantly decrease treprostinil exposure, leading to reduced efficacy. Consider dose increase of treprostinil.
Moderate Interactions
- Anticoagulants/Antiplatelets (e.g., warfarin, aspirin, clopidogrel): Increased risk of bleeding due to treprostinil's antiplatelet effects. Monitor for signs of bleeding.
- Antihypertensives/Diuretics: Increased risk of systemic hypotension. Monitor blood pressure closely, especially during initiation and dose titration.
- Other vasodilators (e.g., nitrates, PDE5 inhibitors): Increased risk of systemic hypotension.
Confidence Interactions
Monitoring
Baseline Monitoring
Diagnosis of PAH
Rationale: Confirm appropriate indication for therapy.
Timing: Prior to initiation
Liver function tests (LFTs)
Rationale: Treprostinil is metabolized hepatically; baseline assessment is important, especially for patients with hepatic impairment.
Timing: Prior to initiation
Renal function tests (creatinine, eGFR)
Rationale: Assess baseline kidney function, though renal impairment generally does not require dose adjustment.
Timing: Prior to initiation
Blood pressure and heart rate
Rationale: Establish baseline and monitor for hypotensive effects.
Timing: Prior to initiation
Routine Monitoring
Blood pressure and heart rate
Frequency: Regularly, especially during dose titration and with changes in concomitant medications.
Target: Individualized, maintain normotension or acceptable range.
Action Threshold: Symptomatic hypotension or significant drop from baseline.
Symptoms of PAH (e.g., dyspnea, fatigue, chest pain, syncope)
Frequency: Ongoing, at each clinical visit.
Target: Improvement or stabilization of symptoms.
Action Threshold: Worsening symptoms, signs of right heart failure.
Adverse effects (e.g., headache, nausea, diarrhea, flushing, jaw pain, peripheral edema)
Frequency: Ongoing, at each clinical visit.
Target: Minimization of side effects to improve tolerability.
Action Threshold: Intolerable side effects requiring dose adjustment or discontinuation.
Liver function tests (LFTs)
Frequency: Periodically, or as clinically indicated, especially in patients with hepatic impairment or those on interacting medications.
Target: Within normal limits or stable.
Action Threshold: Significant elevation indicating liver injury.
Symptom Monitoring
- Worsening dyspnea
- Increased fatigue
- Chest pain
- Syncope or presyncope
- Peripheral edema
- Signs of right heart failure (e.g., ascites, jugular venous distension)
- Persistent or severe headache
- Nausea, vomiting, or diarrhea
- Flushing
- Jaw pain
- Dizziness
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 at doses higher than human therapeutic doses. There are no adequate and well-controlled studies in pregnant women.
Trimester-Specific Risks:
First Trimester:
Potential for developmental toxicity observed in animal studies.
Second Trimester:
Potential for developmental toxicity observed in animal studies.
Third Trimester:
Potential for developmental toxicity observed 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:
Moderate risk (L3) - Unknown excretion in human milk, but potential for serious adverse effects based on drug's pharmacology.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established. Use is not recommended.
Geriatric Use
No specific dose adjustment is required based on age alone. However, elderly patients may have decreased renal or hepatic function, which could affect drug clearance. Monitor closely for adverse effects and consider starting at the lower end of the dosing range.
Clinical Information
Clinical Pearls
- Orenitram ER is an extended-release formulation; it must be swallowed whole and not crushed, chewed, or split to avoid rapid absorption and potential overdose.
- Dose titration is crucial and should be done slowly (every 3-4 days) to optimize efficacy and minimize dose-limiting side effects (e.g., headache, nausea, diarrhea, jaw pain, flushing).
- Patients should be educated on the importance of consistent dosing and not missing doses, as abrupt discontinuation can lead to clinical worsening of PAH.
- Manage common side effects symptomatically (e.g., antiemetics for nausea, antidiarrheals for diarrhea, analgesics for headache/jaw pain).
- Consider drug interactions, especially with strong CYP2C8 inhibitors (e.g., gemfibrozil) or inducers (e.g., rifampin), which may necessitate treprostinil dose adjustments.
Alternative Therapies
- Other prostacyclin analogues: Epoprostenol (Flolan, Veletri), Iloprost (Ventavis), Selexipag (Uptravi), Treprostinil (Remodulin - subcutaneous/intravenous, Tyvaso - inhaled)
- Endothelin Receptor Antagonists (ERAs): Ambrisentan (Letairis), Bosentan (Tracleer), Macitentan (Opsumit)
- Phosphodiesterase-5 Inhibitors (PDE5i): Sildenafil (Revatio), Tadalafil (Adcirca)
- Soluble Guanylate Cyclase (sGC) Stimulators: Riociguat (Adempas)
Cost & Coverage
Average Cost:
Extremely high (typically thousands of USD) per 30 tablets
Generic Available:
Yes
Insurance Coverage:
Specialty Tier (requires prior authorization, often subject to high co-pays or co-insurance)
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 your 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 medication taken, the amount, and the time it happened.