Treprostinil parenteral
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Parenteral formulations of treprostinil sodium.
Drugs List
Therapeutic Indications
Uses
Pulmonary arterial hypertension - grade 3 functional status
Pulmonary arterial hypertension - grade 4 functional status
Treatment of idiopathic or heritable pulmonary arterial hypertension (PAH) in patients classified as New York Heart Association (NYHA) functional class III to improve exercise tolerance and symptoms of the disease.
OR
Treatment of adult patients with WHO Functional Class III or IV in conjunction with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent CTEPH following surgical treatment to improve exercise tolerance.
Dosage
Adults
Initial infusion rate of 1.25nanograms/kg/minute. If poorly tolerated, reduce infusion rate to 0.625nanograms/kg/minute.
Infusion rate should be increased in increments of 1.25nanograms/kg/minute per week for the first four weeks of treatment, then 2.5nanograms/kg/minute per week thereafter.
Patients with Hepatic Impairment
Initial dose of treprostinil should be reduced to 0.625nanograms/kg/minute. Incremental doses thereafter should be made cautiously.
Additional Dosage Information
For obese patients weighing 30% or more than ideal body weight, initial dose and following dose increments should be based on ideal body weight.
Abrupt withdrawal or sudden reductions in dose may cause a rebound in pulmonary arterial hypertension. If an abrupt accidental dose reduction or interruption occurs, restart the infusion as soon as possible. If interrupted for a few hours, restarting treprostinil can be done using the same dose rate; interruptions for longer periods may require re-titration.
Interruptions for up to 24 hours may require a 50% reduction of the most recent dose with subsequent doses titrated to the clinically effective dose.
Some manufacturers advise that when transitioning to intravenous epoprostenol the following treatment transition should be followed:
First decrease the treprostinil infusions slowly by 2.5nanograms/kg/minute. After at least one hour at the new treprostinil dose, epoprostenol treatment can be initiated at a maximum dose of 2nanograms/kg/minute. The treprostinil dose should then be decreased at subsequent intervals of at least 2 hours, at the same time gradually increase the epoprostenol dose after the initial dose is maintained for at least one hour.
Administration
To be given by subcutaneous infusion.
Some brands may be given by intravenous infusion. In these products, subcutaneous infusion (undiluted) is the preferred method of administration. Continuous intravenous infusion should be reserved for patients stabilised with treprostinil subcutaneous infusion who became intolerant of the subcutaneous route and in patients where the risk is considered acceptable. See product literature for specific information regarding administration.
Contraindications
Children under 18 years
Predisposition to bleeding complications
Predisposition to haemorrhage
Systolic blood pressure < 85mmHg
Breastfeeding
Congestive cardiac failure with reduced left ventricular ejection fraction
Gastrointestinal ulcer
Intracranial haemorrhage
Ischaemic heart disease
Pulmonary hypertension secondary to venous occlusive disorder
Serious cardiac arrhythmias
Severe hepatic impairment
Unstable angina
Valvular defects with associated myocardial function disorder
Within 3 months of a cerebrovascular accident
Within 3 months of a transient ischaemic attack
Within 6 months of a myocardial infarction
Precautions and Warnings
Elderly
Females of childbearing potential
Obese patients with a BMI greater than 30kg/m2
Restricted sodium intake
Decompensated cardiac failure
Hepatic impairment
Pregnancy
Renal impairment
Hepatic impairment: Reduce initial dose; make further increments cautiously
Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Not all available brands are licensed for all indications
Treatment to be initiated and supervised by a specialist
Emergency equipment must be available
Monitor heart rate and blood pressure regularly
Consider veno-occlusive disease if pulmonary oedema occurs
Avoid abrupt withdrawal
Discontinue if pulmonary oedema occurs
Interrupt infusion if hypotension occurs
Interrupt treatment if systolic blood pressure falls to 85mmHg or lower
In obese patients dosing should be based on ideal weight
Advise patient not to take St John's wort concurrently
Female: Ensure adequate contraception during treatment
Flushing the infusion line whilst connected to the patient may lead to accidental overdose.
For products that are licensed for intravenous infusion, administering via peripheral intravenous infusion for more than a few hours may be associated with an increased risk of thrombophlebitis.
Patients must be fully trained to use the infusion device, with proper aseptic technique when preparing the treprostinil infusion reservoir and priming the infusion delivery tubing and connection.
Treprostinil is contraindicated in patients with decompensated cardiac failure if not under close medical supervision.
Pregnancy and Lactation
Pregnancy
Use treprostinil with caution during pregnancy.
The manufacturer does not recommend using treprostinil during pregnancy. At the time of writing there is limited published information regarding the use of treprostinil during pregnancy. Potential risks are unknown. Briggs (2015) notes that maternal hypotension, resulting in decreased placental perfusion and foetal hypoxia is a potential risk. It is recommended that treprostinil should only be used during pregnancy if the benefit to the mother outweighs the potential risk to the foetus.
Lactation
Treprostinil is contraindicated during breastfeeding.
Use of treprostinil when breastfeeding is contraindicated by the manufacturer. The presence of treprostinil in human breast milk is unknown but due to its low molecular weight (412 Da) and method of administration, transfer is expected (Briggs, 2015). Effects on exposed infants are unknown.
Side Effects
Abscess formation (injection site)
Arthralgia
Back pain
Bacteraemia
Bleeding
Bone pain
Cellulitis
Decreased appetite
Diarrhoea
Dizziness
Dyspepsia
Exanthema
Eyelid oedema
Fatigue
Flushing
Haematoma (injection site)
Haemorrhage (injection site)
Headache
High output cardiac failure
Hypotension
Infections
Injection site reactions
Jaw pain
Local pain (injection site)
Maculopapular rash
Myalgia
Nausea
Oedema
Painful extremities
Pruritus
Rash
Sepsis
Thrombocytopenia
Thrombophlebitis
Vasodilatation
Vomiting
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: January 2021.
Reference Sources
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
Summary of Product Characteristics: Treprostinil Tillomed 2.5mg/ml solution for infusion. Tillomed Laboratories Ltd. Revised July 2020.
Summary of Product Characteristics: Treprostinil Tillomed 5mg/ml solution for infusion. Tillomed Laboratories Ltd. Revised July 2020.
Summary of Product Characteristics: Treprostinil 1mg/ml solution for infusion. Dr. Reddy's Laboratories (UK) Ltd. Revised November 2020.
Summary of Product Characteristics: Treprostinil 2.5mg/ml solution for infusion. Dr. Reddy's Laboratories (UK) Ltd. Revised November 2020.
Summary of Product Characteristics: Treprostinil 5mg/ml solution for infusion. Dr. Reddy's Laboratories (UK) Ltd. Revised November 2020.
Summary of Product Characteristics: Treprostinil 10mg/ml solution for infusion. Dr. Reddy's Laboratories (UK) Ltd. Revised November 2020.
Summary of Product Characteristics: Trepulmix 1mg/ml solution for infusion. AOP Orphan Ltd. Revised February 2022.
Summary of Product Characteristics: Trepulmix 10mg/ml solution for infusion. AOP Orphan Ltd. Revised February 2022.
Summary of Product Characteristics: Trepulmix 2.5mg/ml solution for infusion. AOP Orphan Ltd. Revised February 2022.
Summary of Product Characteristics: Trepulmix 5mg/ml solution for infusion. AOP Orphan Ltd. Revised February 2022.
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