Source: European Medicines Agency (EU) Revision Year: 2024 Publisher: Bristol-Myers Squibb/Pfizer EEIG, Plaza 254, Blanchardstown Corporate Park 2, Dublin 15, D15 T867, Ireland
Treatment of venous thromboembolism (VTE) and prevention of recurrent VTE in paediatric patients from 28 days to less than 18 years of age.
Apixaban treatment for paediatric patients from 28 days to less than 18 years of age should be initiated following at least 5 days of initial parenteral anticoagulation therapy (see section 5.1).
The recommended dose of apixaban is based on the patient’s weight as shown in Table 1. The dose should be adjusted according to weight-tier as treatment progresses. For patients weighing ≥35 kg, Eliquis 2.5 mg and 5 mg film coated tablets can be administered twice daily, not to exceed the maximum daily dose. Refer to the Eliquis 2.5 mg and 5 mg film coated tablets Summary of Product Characteristics for dosing instructions.
For weight not listed in the dosing table, no dosing recommendation can be provided.
Table 1. Dose recommendations for treatment of VTE and prevention of recurrent VTE in paediatric patients, by weight in kg:
| Days 1-7 | Day 8 and beyond | ||||
| Pharmaceutical forms | Body weight (kg) | Dosing schedule | Maximum daily dose | Dosing schedule | Maximum daily dose |
| Granules in capsules for opening 0.15 mg | 4 to <5 | 0.6 mg twice daily | 1.2 mg | 0.3 mg twice daily | 0.6 mg |
| Coated granules in sachet 0.5 mg, 1.5 mg, 2.0 mg | 5 to <6 | 1 mg twice daily | 2 mg | 0.5 mg twice daily | 1 mg |
| 6 to <9 | 2 mg twice daily | 4 mg | 1 mg twice daily | 2 mg | |
| 9 to <12 | 3 mg twice daily | 6 mg | 1.5 mg twice daily | 3 mg | |
| 12 to <18 | 4 mg twice daily | 8 mg | 2 mg twice daily | 4 mg | |
| 18 to <25 | 6 mg twice daily | 12 mg | 3 mg twice daily | 6 mg | |
| 25 to <35 | 8 mg twice daily | 16 mg | 4 mg twice daily | 8 mg | |
| Film-coated tablets 2.5 mg and 5.0 mg | ≥35 | 10 mg twice daily | 20 mg | 5 mg twice daily | 10 mg |
Based on VTE treatment guidelines in the paediatric population, duration of overall therapy should be individualised after careful assessment of the treatment benefit and the risk for bleeding (see section 4.4).
A missed morning dose should be taken immediately when it is noticed, and it may be taken together with the evening dose. A missed evening dose can only be taken during the same evening, the patient should not take two doses the next morning. The patient should continue with the intake of the regular dose twice daily as recommended on the following day.
Switching treatment from parenteral anticoagulants to Eliquis (and vice versa) can be done at the next scheduled dose (see section 4.5). These medicinal products should not be administered simultaneously.
When converting patients from vitamin K antagonist (VKA) therapy to Eliquis, warfarin or other VKA therapy should be discontinued and Eliquis started when the international normalised ratio (INR) is <2.
No data are available for paediatric patients.
When converting patients from Eliquis to VKA therapy, administration of Eliquis should be continued for at least 2 days after beginning VKA therapy. After 2 days of coadministration of Eliquis with VKA therapy, an INR should be obtained prior to the next scheduled dose of Eliquis. Coadministration of Eliquis and VKA therapy should be continued until the INR is ≥2.
In adult patients with mild or moderate renal impairment, the following recommendations apply:
In adult patients with severe renal impairment (creatinine clearance 15-29 mL/min) the following recommendations apply (see sections 4.4 and 5.2):
In patients with creatinine clearance <15 mL/min, or in patients undergoing dialysis, there is no clinical experience therefore apixaban is not recommended (see sections 4.4 and 5.2).
Based on adult data and limited data in paediatric patients (see section 5.2), no dose adjustment is necessary in paediatric patients with mild to moderate renal impairment. Apixaban is not recommended in paediatric patients with severe renal impairment (see section 4.4).
Apixaban has not been studied in paediatric patients with hepatic impairment.
Eliquis is contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk (see section 4.3).
It is not recommended in patients with severe hepatic impairment (see sections 4.4. and 5.2).
It should be used with caution in patients with mild or moderate hepatic impairment (Child Pugh A or B). No dose adjustment is required in patients with mild or moderate hepatic impairment (see sections 4.4 and 5.2).
Patients with elevated liver enzymes alanine aminotransferase (ALT)/aspartate aminotransferase (AST) >2 x ULN or total bilirubin ≥1.5 x ULN were excluded from clinical studies. Therefore Eliquis should be used with caution in this population (see sections 4.4 and 5.2). Prior to initiating Eliquis, liver function testing should be performed.
Apixaban paediatric administration is based on a fixed-dose by weight-tier regimen (see section 4.2).
No dose adjustment required (see section 5.2).
The safety and efficacy of Eliquis in paediatric patients aged 28 days to less than 18 years have not been established in indications other than treatment of venous thromboembolism (VTE) and prevention of recurrent VTE. No data are available in neonates and for other indications (see also section 5.1). Therefore, Eliquis is not recommended for use in neonates and in paediatric patients aged 28 days to less than 18 years in indications other than treatment of VTE and prevention of recurrent VTE.
The safety and efficacy of Eliquis in children and adolescents below age 18 have not been established for the indication of thromboembolism prevention. Currently available data on thromboembolism prevention are described in section 5.1 but no recommendation on a posology can be made.
Oral use.
Each capsule for opening is for single use only.
The capsule for opening should NOT be swallowed. The capsule must be opened and the entire contents should be sprinkled in liquid and administered. Eliquis granules should be mixed with either water or baby formula as described in the instructions for use (IFU). The liquid mixture should be administered within 2 hours of preparation. Alternatively, for patients who have difficulty swallowing, the liquid mixture can be delivered through a gastrostomy tube and nasogastric tube.
Detailed instructions for the use of this medicinal product are provided in the instructions for use.
Overdose of apixaban may result in a higher risk of bleeding. In the event of haemorrhagic complications, treatment must be discontinued and the source of bleeding investigated. The initiation of appropriate treatment, e.g., surgical haemostasis, the transfusion of fresh frozen plasma or the administration of a reversal agent for factor Xa inhibitors should be considered (see section 4.4).
In controlled clinical studies, orally-administered apixaban in healthy adult subjects at doses up to 50 mg daily for 3 to 7 days (25 mg twice daily (BID) for 7 days or 50 mg once daily (od) for 3 days) had no clinically relevant adverse reactions.
In healthy adult subjects, administration of activated charcoal 2 and 6 hours after ingestion of a 20 mg dose of apixaban reduced mean apixaban AUC by 50% and 27%, respectively, and had no impact on Cmax. Mean half-life of apixaban decreased from 13.4 hours when apixaban was administered alone to 5.3 hours and 4.9 hours, respectively, when activated charcoal was administered 2 and 6 hours after apixaban. Thus, administration of activated charcoal may be useful in the management of apixaban overdose or accidental ingestion.
Haemodialysis decreased apixaban AUC by 14% in adult subjects with end-stage renal disease (ESRD), when a single dose of apixaban 5 mg was administered orally. Therefore, haemodialysis is unlikely to be an effective means of managing apixaban overdose.
For situations in which reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding, a reversal agent for factor Xa inhibitors (andexanet alfa) is available for adults (see section 4.4). Administration of prothrombin complex concentrates (PCCs) or recombinant factor VIIa may also be considered. Reversal of apixaban pharmacodynamic effects, as demonstrated by changes in the thrombin generation assay, was evident at the end of infusion and reached baseline values within 4 hours after the start of a 30 minute 4-factor PCC infusion in healthy subjects. However, there is no clinical experience with the use of 4-factor PCC products to reverse bleeding in individuals who have received apixaban. Currently there is no experience with the use of recombinant factor VIIa in individuals receiving apixaban. Re-dosing of recombinant factor VIIa could be considered and titrated depending on improvement of bleeding.
A specific reversal agent (andexanet alfa) antagonising the pharmacodynamic effect of apixaban is not established in the paediatric population (refer to the summary of product characteristics of andexanet alfa). Transfusion of fresh frozen plasma, or administration of prothrombin complex concentrates (PCCs), or recombinant factor VIIa may also be considered.
Depending on local availability, coagulation expert consultation should be considered in case of major bleeding.
3 years.
Once mixed with water or baby formula, the liquid mixture must be used within 2 hours.
This medicinal product does not require any special storage conditions.
High-density polyethylene (HDPE) bottle with a foil induction seal and a child-resistant polypropylene cap packed into a carton.
Each bottle contains 28 capsules for opening.
Detailed instructions for the preparation and administration of the dose are provided in instructions for use.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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