Drugs List

Therapeutic Indications

Uses

To be used in conjunction with aspirin and unfractionated heparin for:

Prevention of early myocardial infarction in patients presenting with unstable angina or non-Q-wave myocardial infarction, with the last episode of chest pain occurring within 24 hours and with ECG changes and/or elevated cardiac enzymes.

Patients likely to benefit most from this treatment are those at high risk of developing myocardial infarction within the first 3-4 days after the onset of acute angina symptoms (e.g. those likely to undergo an early PTCA).

Administration

For intravenous administration.

Inspect vial contents before use. If particulate matter or discolouration is present, discard vial.

Compatibilities

Eptifibatide may be administered through an intravenous line with the following medicinal products:
Atropine sulfate
Dobutamine
Glyceryl trinitrate
Heparin
Lidocaine
Metoprolol
Midazolam
Morphine
Pethidine
Tissue plasminogen activator
Verapamil
0.9% sodium chloride solution for infusion
Dextrose 5% in Normasol R (with/without potassium chloride)

Incompatibilities

Eptifibatide is not compatible with furosemide.

Do not mix this product with any medicinal product other than those mentioned in the compatibilities section.

Contraindications

Abnormal bleeding within 30 days
History of haemorrhagic stroke
Stroke within 30 days
History of intracranial disease e.g. neoplasm, arteriovenous malformation or aneurysm
Major surgery or severe trauma within past 6 weeks
Bleeding diathesis
Thrombocytopenia (below 100,000 cells/cubic millimetre)
Raised prothrombin times (greater than 1.2 times control or INR greater than or equal to 2)
Severe hypertension (systolic blood pressure greater than 200mmHg or diastolic blood pressure greater than 110 mmHg on antihypertensive therapy)
Severe renal impairment (creatinine clearance below 30ml/minute)
Severe hepatic impairment
Renal dialysis
Breastfeeding (see Lactation section)
Children under 18 years

Precautions and Warnings

Treatment should be initiated and supervised in hospital by a specialist.

Hepatic impairment: see Dosage, Hepatic Impairment.

Pregnancy - see Pregnancy section.

Increased risk of bleeding. Monitor carefully, especially in the following patients:
Females
Patients with low body weight
Elderly
Moderate renal impairment (creatinine clearance 30-50ml/minute) - see Dosage Renal Impairment.
Monitor potential bleeding sites e.g. catheter insertion sites, needle puncture, cutdown sites, gastrointestinal/genitourinary tracts, central and peripheral nervous system and retroperitoneal sites.

An increased risk of bleeding may also be observed in patients who receive early administration of eptifibatide ( e.g. upon diagnosis) compared to receiving it immediately prior to PCI.

Caution when puncturing the femoral artery. Arterial sheaths may be removed when coagulation returns to normal. Careful haemostasis must be ensured under close supervision after removal of the introducer sheath.

Monitor haematological parameters (prothrombin time (PT), activated partial prothrombin time (aPTT), serum creatinine, platelet count, haemoglobin and haematocrit levels) prior to treatment. Haemoglobin, haematocrit and platelet count should then be monitored within six hours of administration and at least once daily thereafter while on therapy (or more often if there is evidence of a marked decrease).

Eptifibatide inhibits platelet aggregation, but does not appear to affect viability of the platelets. Thrombocytopenia has been observed with eptifibatide use. The mechanism, whether immune and /or non immune mediated, by which eptifibatide may induce thrombocytopenia is not fully understood. However, treatment with eptifibatide was associated with antibodies that recognise GPIIb/IIIa occupied by eptifibatide, suggesting an immune mediated mechanism. Thrombocytopenia occurring after the first exposure to a GPIIb/IIIa inhibitor may be explained by the fact that antibodies are naturally present in some normal individuals.

Since either repeat exposure with any GPIIb/IIIa ligand mimetic agent (e.g. abciximab or eptifibatide) or first time exposure to a GPIIb/IIIa inhibitor may be associated with immune mediated thrombocytopenic responses, monitoring is required, i.e. platelet counts should be monitored prior to treatment, within 6 hours of administration and at least once daily thereafter while on therapy and immediately at clinical signs of unexpected bleeding tendency.

If either a confirmed platelet decrease to below 100,000 per cubic millimetre or acute profound thrombocytopenia is observed, discontinuation of each treatment medication having known or suspected thrombocytopenic effects, including eptifibatide, heparin, clopidogrel, should be considered immediately. The decision to use platelet transfusions should be based upon clinical judgement on an individual basis.

In patients with previous immune mediated thrombocytopenia from other parenteral GPIIb/IIIa inhibitors, there are no data for the use of eptifibatide. Therefore it is not recommended to administer eptifibatide in patients who have previously experienced immune mediated thrombocytopenia with GPIIb/IIIa inhibitors including eptifibatide.

Discontinue if circumstances arise that require thrombolytic therapy, emergency CABG or intra-aortic balloon pump.

Discontinue eptifibatide and any concurrent heparin if severe haemorrhage occurs which is not controllable with pressure.

Heparin administration is recommended unless a contraindication is present (see Additional Dosage section and product information for heparin) .

Monitor activated clotting time (ACT) in percutaneous coronary intervention (PCI) to maintain a value between 300 to 350 seconds. Discontinue heparin if activated clotting time (ACT) exceeds 300 seconds. Do not administer eptifibatide until the ACT falls below 300 seconds.

Not recommended for use in acute transmural myocardial infarction with new pathological Q waves or elevated ST-segments or left bundle branch block in ECG. There is a lack of experience in these patients.

Pregnancy and Lactation

Pregnancy

There are no adequate data from the use of eptifibatide in pregnant women.

Animal studies are insufficient with respect to effects on pregnancy, embryonal or foetal development, parturition or post natal development. The primary risk appears to be from maternal haemorrhage during administration. Eptifibatide should not be used during human pregnancy unless clearly necessary.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Licensed in pregnancy? - No

Recommended for use in pregnancy? - No

Lactation

There is limited data on use during breastfeeding due to the indication for eptifibatide. It is unknown whether eptifibatide is excreted in human milk, however the molecular weight (about 832) and the potentially long intravenous infusions of the drug suggest that some eptifibatide will be excreted into the breast milk. The effect of this exposure on a nursing infant is unknown, but Briggs (2011) concludes that the risk is very low or nil because the drug should be digested in the infants gastrointestinal tract. Until more safety data is available, it is recommended that interruption of breastfeeding during treatment with eptifibatide should occur.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Considered suitable or recommended by manufacturer? - No.

Drug substance licensed in infants? - No.

Side Effects

Bleeding
Thrombocytopenia
Cerebral ischaemia
Anaphylactic reaction
Rash
Urticaria
Hypotension
Atrial fibrillation
Congestive cardiac failure
Shock
Cardiac arrest
Atrioventricular block
Phlebitis
Ventricular fibrillation
Ventricular tachycardia
Haematoma
Decrease in haemoglobin
Decrease in haematocrit

Presentation

Solution for infusion containing 75mg eptifibatide in 100ml.
Solution for injection containing 20mg eptifibatide in 10ml.

Drugs List

Therapeutic Indications

Uses

To be used in conjunction with aspirin and unfractionated heparin for:

Prevention of early myocardial infarction in patients presenting with unstable angina or non-Q-wave myocardial infarction, with the last episode of chest pain occurring within 24 hours and with ECG changes and/or elevated cardiac enzymes.

Patients likely to benefit most from this treatment are those at high risk of developing myocardial infarction within the first 3-4 days after the onset of acute angina symptoms (e.g. those likely to undergo an early PTCA).

Dosage

Treatment should be initiated in hospital by a specialist, as soon as possible after diagnosis.

Eptifibatide is intended for use with aspirin and unfractionated heparin unless contraindicated.

Eptifibatide infusion must be used in conjunction with eptifibatide injection.

Adults

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Administration

For intravenous administration.

Inspect vial contents before use. If particulate matter or discolouration is present, discard vial.

Compatibilities

Eptifibatide may be administered through an intravenous line with the following medicinal products:
Atropine sulfate
Dobutamine
Glyceryl trinitrate
Heparin
Lidocaine
Metoprolol
Midazolam
Morphine
Pethidine
Tissue plasminogen activator
Verapamil
0.9% sodium chloride solution for infusion
Dextrose 5% in Normasol R (with/without potassium chloride)

Incompatibilities

Eptifibatide is not compatible with furosemide.

Do not mix this product with any medicinal product other than those mentioned in the compatibilities section.

Contraindications

Abnormal bleeding within 30 days
History of haemorrhagic stroke
Stroke within 30 days
History of intracranial disease e.g. neoplasm, arteriovenous malformation or aneurysm
Major surgery or severe trauma within past 6 weeks
Bleeding diathesis
Thrombocytopenia (below 100,000 cells/cubic millimetre)
Raised prothrombin times (greater than 1.2 times control or INR greater than or equal to 2)
Severe hypertension (systolic blood pressure greater than 200mmHg or diastolic blood pressure greater than 110 mmHg on antihypertensive therapy)
Severe renal impairment (creatinine clearance below 30ml/minute)
Severe hepatic impairment
Renal dialysis
Breastfeeding (see Lactation section)
Children under 18 years

Precautions and Warnings

Treatment should be initiated and supervised in hospital by a specialist.

Hepatic impairment: see Dosage, Hepatic Impairment.

Pregnancy - see Pregnancy section.

Increased risk of bleeding. Monitor carefully, especially in the following patients:
Females
Patients with low body weight
Elderly
Moderate renal impairment (creatinine clearance 30-50ml/minute) - see Dosage Renal Impairment.
Monitor potential bleeding sites e.g. catheter insertion sites, needle puncture, cutdown sites, gastrointestinal/genitourinary tracts, central and peripheral nervous system and retroperitoneal sites.

An increased risk of bleeding may also be observed in patients who receive early administration of eptifibatide ( e.g. upon diagnosis) compared to receiving it immediately prior to PCI.

Caution when puncturing the femoral artery. Arterial sheaths may be removed when coagulation returns to normal. Careful haemostasis must be ensured under close supervision after removal of the introducer sheath.

Monitor haematological parameters (prothrombin time (PT), activated partial prothrombin time (aPTT), serum creatinine, platelet count, haemoglobin and haematocrit levels) prior to treatment. Haemoglobin, haematocrit and platelet count should then be monitored within six hours of administration and at least once daily thereafter while on therapy (or more often if there is evidence of a marked decrease).

Eptifibatide inhibits platelet aggregation, but does not appear to affect viability of the platelets. Thrombocytopenia has been observed with eptifibatide use. The mechanism, whether immune and /or non immune mediated, by which eptifibatide may induce thrombocytopenia is not fully understood. However, treatment with eptifibatide was associated with antibodies that recognise GPIIb/IIIa occupied by eptifibatide, suggesting an immune mediated mechanism. Thrombocytopenia occurring after the first exposure to a GPIIb/IIIa inhibitor may be explained by the fact that antibodies are naturally present in some normal individuals.

Since either repeat exposure with any GPIIb/IIIa ligand mimetic agent (e.g. abciximab or eptifibatide) or first time exposure to a GPIIb/IIIa inhibitor may be associated with immune mediated thrombocytopenic responses, monitoring is required, i.e. platelet counts should be monitored prior to treatment, within 6 hours of administration and at least once daily thereafter while on therapy and immediately at clinical signs of unexpected bleeding tendency.

If either a confirmed platelet decrease to below 100,000 per cubic millimetre or acute profound thrombocytopenia is observed, discontinuation of each treatment medication having known or suspected thrombocytopenic effects, including eptifibatide, heparin, clopidogrel, should be considered immediately. The decision to use platelet transfusions should be based upon clinical judgement on an individual basis.

In patients with previous immune mediated thrombocytopenia from other parenteral GPIIb/IIIa inhibitors, there are no data for the use of eptifibatide. Therefore it is not recommended to administer eptifibatide in patients who have previously experienced immune mediated thrombocytopenia with GPIIb/IIIa inhibitors including eptifibatide.

Discontinue if circumstances arise that require thrombolytic therapy, emergency CABG or intra-aortic balloon pump.

Discontinue eptifibatide and any concurrent heparin if severe haemorrhage occurs which is not controllable with pressure.

Heparin administration is recommended unless a contraindication is present (see Additional Dosage section and product information for heparin) .

Monitor activated clotting time (ACT) in percutaneous coronary intervention (PCI) to maintain a value between 300 to 350 seconds. Discontinue heparin if activated clotting time (ACT) exceeds 300 seconds. Do not administer eptifibatide until the ACT falls below 300 seconds.

Not recommended for use in acute transmural myocardial infarction with new pathological Q waves or elevated ST-segments or left bundle branch block in ECG. There is a lack of experience in these patients.

Pregnancy and Lactation

Pregnancy

There are no adequate data from the use of eptifibatide in pregnant women.

Animal studies are insufficient with respect to effects on pregnancy, embryonal or foetal development, parturition or post natal development. The primary risk appears to be from maternal haemorrhage during administration. Eptifibatide should not be used during human pregnancy unless clearly necessary.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Licensed in pregnancy? - No

Recommended for use in pregnancy? - No

Lactation

There is limited data on use during breastfeeding due to the indication for eptifibatide. It is unknown whether eptifibatide is excreted in human milk, however the molecular weight (about 832) and the potentially long intravenous infusions of the drug suggest that some eptifibatide will be excreted into the breast milk. The effect of this exposure on a nursing infant is unknown, but Briggs (2011) concludes that the risk is very low or nil because the drug should be digested in the infants gastrointestinal tract. Until more safety data is available, it is recommended that interruption of breastfeeding during treatment with eptifibatide should occur.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Considered suitable or recommended by manufacturer? - No.

Drug substance licensed in infants? - No.

Side Effects

Bleeding
Thrombocytopenia
Cerebral ischaemia
Anaphylactic reaction
Rash
Urticaria
Hypotension
Atrial fibrillation
Congestive cardiac failure
Shock
Cardiac arrest
Atrioventricular block
Phlebitis
Ventricular fibrillation
Ventricular tachycardia
Haematoma
Decrease in haemoglobin
Decrease in haematocrit

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 ).

Shelf Life and Storage

Store at 2 to 8 degrees C
Store in original packaging (protected from light)

Discard unused portion after opening.

Further Information

Last Full Review Date: April 2012

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Eptifibatide Accord 2 mg/ml solution for injection. Accord Healthcare Limited. Revised January 2016.
Summary of Product Characteristics: Eptifibatide Accord 0.75 mg/ml solution for infusion. Accord Healthcare Limited. Revised January 2016.
Summary of Product Characteristics: Integrilin 2mg solution for injection, 0.75mg solution for infusion. GlaxoSmithKline. Revised March 2012.

The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 29 September 2017