Peripheral Vasodilators-
Isoxsuprine hcl, Papaverine hcl, Hydralazine hcl, Minodoxil, Epoprostenol sodium,
Tresprostinil sodium,

Drug interactions- summary

Epoprosternol +
---------------------
Diuretics /vasodilators

coadmin. cpould cause additional reductions in blood pressure


Antiplatelet agents/Anticoagulants

coadmin. can increase the risk of bleeding


 

Pulmonary  hypertension

Peripheral Vasodilators-

Isoxsuprine hcl, Papaverine hcl, Hydralazine hcl, Minodoxil, Epoprostenol sodium, Tresprostinil sodium,

                       
 Adverse reactions-

More common Occurence with epoprosternol


CARDIOVASCULAR -                                                                                                         Tachycardia 35%, Flushing 42%

GI  -                                                                                                                                       Diarrhea 37%     Nausea/vomiting 67%

MUSCULOSKELETAL -                                                                                                    Jaw  pain  54%     Myalgia 44%     Non specific muscular pain 35%

CNS -                                                                                                                                     Anxiety  /Nervousness/Tremor  21%  Dizziness 83% Headache 83%
  Hypesthesia, Hypersthesia, Paresthesia  12%

MISCELLANEOUS -                                                                                         Chills/Fever/sepsis / Flu like symptoms 25%

 

Chronic use in patients with CHF due to severe left ventricular systolic dysfunction, hypersensitivity
 to the drug or to structurally related compounds

Special precautions:
Diagnosis- carefully establish the diagnosis of PPH by standard clinical tests to exclude secondary  causes of pulmonary hypertension

Dose ranging- during asympatomatic increases in pulmonary artery pressure coincident with increases in cardiac output occured rarely.
 In such cases consider dose reduction, but such an increase dose not imply that chronic treatment  is contra-indicated.

Chronic use- base the decison to initiate therapy with epoprostenol on the understanding that there  is a high likelihood that IV therapy will be needed for prolonged periods possibly years.

Warnings-
Reconstitution- Epoprostenol must be reconstituted only as directed using sterile diluent for epoprostenol.
Epoprostenol must not be reconstituted or mixed with any other parentral medications or solutions  prior to or during administration.

Abrupt withdrawal- abrupt withdrawal (including interruptions during drug delivery) or sudden large  reductions in dosage may result in symptoms associated with rebound pulmonary hytpertension,  including dyspnea, dizziness, and asthenia.

Pulmonary edema- some patients with pulmonary hypertension have developed pulmonary edema  during dosage ranging, which may be associated with pulmonary veno-occlusive disease.
Epoprostenol should not be used chronically in patients who develop pulmonary edema during dosing.

Elderly- In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, or cardiac function and of concomittant disease or other drug therapy

Pregnancy- No adequate and well controlled studies in pregnancy. Use during pregnancy
 only when needed.

Lactation- Not known whether this drug is excreted in breast milk. Excerciise caution when
 epiprostenol is administerd to nursing woman

Children- Safety and efficacy have not been established

Indication:
Pulmonary hypertension

Dosage:
Administer the intial chronic infusion rates of epoprostenol an acute dose ranging  procedure

Initial dosage- 2ng/kg/min IV - if the initial infusion rate is not tolerated, identify a lower dose
 which is tolerated by the patient.
Dosage titration- increase in increments of 2ng/kg/min every 15 min or longer until  dose-limiting
pharmacologic effect  are elicted or  until tolerance limit of the drug is established and
further increase in infusion rate is not warranted.

If dose- limiting phamacologic effects occur, then decrease the infusion rate whereby the
pharmacologic effects of epoprosterenol are tolerated

Overdosage-

                         Symptoms                                                        

Signs and symptoms of epoprostenol includes                     
flushing, headache, hypotension, tachycardia, nausea, vomiting and diarrhea.
One patient vomitted and became unconscious with an intially uncontrolled blood pressure.
Epoprostenol was discontinued and the patient regained consciousness within seconds.

Treatment
1. Treatment will ordinarily require dose reduction of  epoprostenol.

Missed dose-
1. If you miss a dose of this medicine, take it as soon as possible.
2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing
   schedule.
3. Do not double doses.  

 

1.Patients receiving epoprostenol should receive the following information-
   The drug is infused continously through a permanent indwelling central venous        catheter     via a small ,   portable   infusion pump.
   Thus, therapy with epoprostenol requires commitment by the patient to drug reconstitution,      drug  administration and care of the permanent central catheter.

2. Brief interuptions in the delivery of epoprostenol may result in rapid symptomatic deterioration.

3. Base the decison to receive epoprostenol for PPH on the understanding that there is a high   likelihood that the therapy with epoproetenol will be needed for prolonged periods, possibly years.

Peripheral Vasodilators-

Isoxsuprine hcl, Papaverine hcl, Hydralazine hcl, Minodoxil, Epoprostenol sodium, Tresprostinil sodium,

Pharmacology:

Epoprostenol has two major pharmacological actions-

1. Direct vasodilation of pulmonary and systemic arterial vascular beds

2. Inhibition of platelet aggregation Pharmacokinetics:

Epoprostenol is rapidly hydrolysed at neutral pH in blood and is also subject to enzymatic degradation. Epoprostenol is metabolised to two primary metabolites- 6-keto-PGF1a (formed by spontaneous degradation) and 6,1-5 diketo-13, 14-dihydro-PGF1a (enzymatically formed ) both of which have pharmacological activity orders of magnitude less than epoprostenol in animal test systems.

Not reported

Pregnancy-

No adequate and well controlled studies in pregnancy. Use during pregnancy only when needed.

Lactaiton-

Not known whether this drug is excreted in breast milk. Excerciise caution when epiprostenol is administerd to nursing woman Children- Safety and efficacy have not been established