INVAROX FILM COATED TABLET 2.5MG [SIN16979P]

Product Info

INVAROX FILM COATED TABLET 2.5MG

[SIN16979P]

4.1 Indications
INVAROX, co-administered with acetylsalicylic acid (ASA) alone or with ASA plus clopidogrel or ticlopidine, is indicated for the prevention of cardiovascular death in adult patients after an acute coronary syndrome (ACS) with elevated cardiac biomarkers (see sections ‘Contraindications’, ‘Special warnings and precautions for use’ and ‘Pharmacodynamic properties’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

INVAROX, in combination with aspirin, is indicated to reduce the risk of major cardiovascular events (cardiovascular (CV) death, myocardial infarction (MI) and stroke) in adult patients with chronic coronary artery disease (CAD) or peripheral artery disease (PAD) at high risk of ischemic events.

4.2 Dosage and method of administration

4.2.1 Method of administration

Oral use

4.2.2 Recommended usual dose

ACS

The recommended vascular protection regimen is one tablet of 2.5 mg INVAROX twice daily. Patients should also take a daily dose of 75–100 mg ASA or a daily dose 75–100 mg ASA in addition to either a daily dose of 75 mg clopidogrel or a standard daily dose of ticlopidine.

CAD or PAD

The recommended vascular protection regimen for patients with CAD or PAD is one tablet of 2.5 mg INVAROX twice daily in combination with a daily dose of 75–100 mg ASA.

4.2.3 Duration of treatment

Treatment should be regularly evaluated in the individual patient weighing the risk for ischaemic events against the bleeding risks. In patients with ACS, extension of treatment beyond 12 months should be done on an individual patient basis as experience up to 24 months is limited (see section ‘Pharmacodynamic properties’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

In patients with an acute thrombotic event or vascular procedure and a need for dual antiplatelet therapy, the continuation of INVAROX 2.5 mg twice daily should be evaluated depending on type of event or procedure and antiplatelet regimen. Safety and efficacy of INVAROX 2.5 mg twice daily in combination with ASA plus clopidogrel/ticlopidine has only been studied in patients with recent ACS. Dual antiplatelet therapy has not been studied in combination with INVAROX 2.5 mg twice daily in patients with CAD or PAD (see section ‘Pharmacodynamic properties’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.2.4 Method and frequency of administration

Treatment with INVAROX should be started as soon as possible after stabilization of the ACS event (including revascularization procedures); at the earliest 24 hours after admission to hospital and at the time when parenteral anticoagulation therapy would normally be discontinued.

In patients diagnosed with CAD or PAD, treatment with INVAROX 2.5 mg twice daily in combination with ASA 75–100 mg once daily can be started at any time. One 2.5 mg tablet of INVAROX should be taken twice daily.

INVAROX 2.5 mg tablets may be taken with or without food.

For patients who are unable to swallow whole tablets, INVAROX tablet may be crushed and mixed with water or soft foods such as applesauce immediately prior to use and administered orally.

The crushed INVAROX tablet may be given through gastric tubes. Gastric placement of the tube should be confirmed before administering INVAROX. The crushed tablet should be administered in a small amount of water via a gastric tube after which it should be flushed with water (see section ‘Pharmacokinetic properties’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.2.5 Missed Dose

If a dose is missed the patient should continue with the regular 2.5 mg INVAROX dose as recommended at the next scheduled time. The dose should not be doubled to make up for a missed dose.

4.2.6 Additional information on special populations

4.2.6.1 Patients with hepatic impairment

INVAROX is contraindicated in patients with hepatic disease which is associated with coagulopathy and clinically relevant bleeding risk including cirrhotic patients with Child Pugh B and C (see section ‘Contraindications’ and ‘Pharmacokinetic properties’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

No dose adjustment is necessary in patients with other hepatic diseases (see section ‘Pharmacokinetic Properties’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.2.6.2 Patients with renal impairment

No dose adjustment is required if INVAROX is administered in patients with mild (Creatinine clearance (CrC): 80–50 mL/min) or moderate (CrC: <50–30 mL/min) renal impairment (see section ‘Pharmacokinetic Properties’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Limited clinical data for patients with severe renal impairment (CrC: <30–15 mL/min) indicate that rivaroxaban plasma levels are significantly increased in this patient population. Therefore INVAROX must be used with caution in these patients (see section ‘Special Warnings and Precautions for Use’, ‘Pharmacokinetic Properties’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Use of INVAROX is not recommended in patients with CrC: <15 mL/min. (see section ‘Special Warnings and Precautions for Use’, ‘Pharmacokinetic Properties’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.2.6.3 Converting from Vitamin K Antagonists (VKA) to INVAROX

When converting patients from VKAs to INVAROX, INR values will be falsely elevated after the intake of INVAROX. The INR is not valid to measure the anticoagulant activity of INVAROX, and therefore should not be used (see section ‘Interaction with other medicinal products and other forms of interaction’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.2.6.4 Converting from INVAROX to Vitamin K antagonists (VKA)

There is a potential for inadequate anticoagulation during the transition from INVAROX to VKA. Continuous adequate anticoagulation should be ensured during any transition to an alternate anticoagulant. It should be noted that INVAROX can contribute to an elevated INR.

In patients converting from INVAROX to VKA, VKA should be given concurrently until the INR is ≥2.0. For the first two days of the conversion period, standard initial VKA dosing should be used followed by VKA dosing guided by INR testing. While patients are on both INVAROX and VKA, the INR should not be tested earlier than 24 hours (after the previous dose but prior to the next dose of INVAROX. Once INVAROX is discontinued INR testing may be done reliably 24 hours after the last dose (see section ‘Interaction with other medicinal products and other forms of interaction’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.2.6.5 Converting from parenteral anti-coagulants to INVAROX

For patients currently receiving a parenteral anticoagulant, INVAROX should be started 0 to 2 hours before the time of the next scheduled administration of the parenteral medicinal drug (e.g. low molecular weight heparins) or at the time of discontinuation of a continuously administered parenteral drug (e.g. intravenous unfractionated heparin).

4.2.6.6 Converting from INVAROX to parenteral anti-coagulants

Give the first dose of parenteral anticoagulant at the time that the next INVAROX dose would be taken.

4.2.6.7 Paediatric population

The safety and efficacy of INVAROX in children aged 0 to 18 years have not been established. No data are available. Therefore, INVAROX is not recommended for use in children below 18 years of age.

4.2.6.8 Geriatric patients

No dose adjustment is required based on age. The risk of bleeding increases with increasing age (see section ‘Pharmacokinetic Properties and Special warnings and precautions for use’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.2.6.9 Gender

No dose adjustment is required based on gender (see section ‘Pharmacokinetic Properties’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.2.6.10 Body weight

No dose adjustment is required based on body weight (see section ‘Pharmacokinetic Properties and Special warnings and precautions for use’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.2.6.11 Ethnic differences

No dose adjustment is required based on ethnic differences (see section ‘Pharmacokinetic Properties’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

4.3 Contraindications

INVAROX is contraindicated in patients with hypersensitivity to rivaroxaban or any excipient of the tablet (see section ‘Pharmaceutical Particulars’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

INVAROX is contraindicated in patients with clinically significant active bleeding (e.g., intracranial bleeding, gastrointestinal bleeding).

INVAROX is contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk including cirrhotic patients with Child Pugh B and C (see section ‘Pharmacokinetic properties’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

INVAROX is contraindicated for concomitant treatment of ACS with antiplatelet therapy in patients with a prior stroke or a transient ischaemic attack (TIA) (see section ‘Special warnings and precautions for use’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Lesion or condition if considered to be a significant risk of major bleeding. This may include current or recent gastrointestinal ulceration, presence of malignant neoplasms at high risk of bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial haemorrhage, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities.

Concomitant treatment with any other anticoagulant agent e.g. unfractionated heparin (UFH), low molecular weight heparins (enoxaparin, dalteparin, etc.), heparin derivatives (fondaparinux, etc.), oral anticoagulants (warfarin, apixaban, dabigatran, etc.) except under the circumstances of switching therapy to or from rivaroxaban (see section Dosage and administration) or when UFH is given at doses necessary to maintain an open central venous or arterial catheter (see section Interaction with other medicinal products and other forms of interaction – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Safety and efficacy of INVAROX have not been established in pregnant women. Animal data show that rivaroxaban crosses the placental barrier. Therefore use of INVAROX is contraindicated throughout pregnancy (see section ‘Pregnancy and Lactation’, ‘Preclinical Safety Data’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Safety and efficacy of INVAROX have not been established in nursing mothers. Animal data indicate that rivaroxaban is secreted into breast milk. Therefore INVAROX may only be administered after breastfeeding is discontinued (see section ‘Pregnancy and Lactation’, ‘Preclinical Safety Data’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).