CELSENTRI Film-coated tablet Ref.[8785] Active ingredients: Maraviroc

Therapy should be initiated by a physician experienced in the management of HIV infection.

Posology

Before taking CELSENTRI it has to be confirmed that only CCR5-tropic HIV-1 is detectable (i.e. CXCR4 or dual/mixed tropic virus not detected) using an adequately validated and sensitive detection method on a newly drawn blood sample. The Monogram Trofile assay was used in the clinical studies of CELSENTRI (see sections 4.4 and 5.1). The viral tropism cannot be safely predicted by treatment history and assessment of stored samples.

There are currently no data regarding the reuse of CELSENTRI in patients that currently have only CCR5-tropic HIV-1 detectable, but have a history of failure on CELSENTRI (or other CCR5 antagonists) with a CXCR4 or dual/mixed tropic virus. There are no data regarding the switch from a medicinal product of a different antiretroviral class to CELSENTRI in virologically suppressed patients. Alternative treatment options should be considered.

Adults

The recommended dose of CELSENTRI is 150 mg (with potent CYP3A inhibitor with or without a potent CYP3A inducer), 300 mg (without potent CYP3A inhibitors or inducers) or 600 mg twice daily (with potent CYP3A inducer without a potent CYP3A inhibitor) depending on interactions with concomitant antiretroviral therapy and other medicinal products (see section 4.5).

Children from 2 years of age and weighing at least 10kg

The recommended dose of CELSENTRI should be based on body weight (kg) and should not exceed the recommended adult dose. If a child is unable to reliably swallow CELSENTRI tablets, the oral solution (20 mg per mL) should be prescribed (refer to Summary of Product Characteristics for CELSENTRI oral solution).

The recommended dose of CELSENTRI differs depending on interactions with concomitant antiretroviral therapy and other medicinal products. Refer to section 4.5 for corresponding adult dosage.

Many medicines have profound effects on maraviroc exposure due to drug-drug interactions. Prior to deciding the dose of CELSENTRI by weight, please refer to Table 2 in section 4.5 to carefully determine the corresponding adult dose. The corresponding paediatric dose can then be obtained from Table 1 below. If uncertainty still exists, contact a pharmacist for advice.

Table 1. Recommended dosing regimen in children aged 2 years and above and weighing at least 10 kg:

* Based on drug-drug Interactions (refer to section 4.5)

Special populations

Elderly

There is limited experience in patients >65 years of age (see section 5.2), therefore CELSENTRI should be used with caution in this population.

Renal impairment

In adult patients with a creatinine clearance of <80 mL/min, who are also receiving potent CYP3A4 inhibitors, the dose interval of maraviroc should be adjusted to 150 mg once daily (see sections 4.4 and 4.5).

Examples of agents/regimens with such potent CYP3A4-inhibiting activity are:

• ritonavir-boosted protease inhibitors (with the exception of tipranavir/ritonavir),
• cobicistat,
• itraconazole, voriconazole, clarithromycin and telithromycin,
• telaprevir and boceprevir.

CELSENTRI should be used with caution in adult patients with severe renal impairment (CLcr <30 mL/min) who are receiving potent CYP3A4 inhibitors (see sections 4.4 and 5.2).

There are no data available to recommend a specific dose in paediatric patients with renal impairment. Therefore, CELSENTRI should be used with caution in this population.

Hepatic impairment

Limited data are available in adult patients with hepatic impairment and no data are available to recommend a specific dose for paediatric patients. Therefore, CELSENTRI should be used with caution in patients with hepatic impairment (see sections 4.4 and 5.2).

Paediatric patients (children younger than 2 years of age or weighing less than 10 kg) The safety and efficacy of CELSENTRI in children younger than 2 years of age or weighing less than 10 kg has not been established (see section 5.2). No data are available.

Method of administration

Oral use.

CELSENTRI can be taken with or without food.

Symptoms

The highest dose administered in clinical studies was 1,200 mg. The dose limiting adverse reaction was postural hypotension.

Prolongation of the QT interval was seen in dogs and monkeys at plasma concentrations 6 and 12 times, respectively, those expected in humans at the maximum recommended dose of 300 mg twice daily. However, no clinically significant QT prolongation compared to placebo + OBT was seen in the Phase 3 clinical studies using the recommended dose of maraviroc or in a specific pharmacokinetic study to evaluate the potential of maraviroc to prolong the QT interval.

Management

There is no specific antidote for overdose with maraviroc. Treatment of overdose should consist of general supportive measures including keeping the patient in a supine position, careful assessment of patient vital signs, blood pressure and ECG.

If indicated, elimination of unabsorbed active maraviroc should be achieved by emesis or gastric lavage. Administration of activated charcoal may also be used to aid in removal of unabsorbed active substance. Since maraviroc is moderately protein bound, dialysis may be beneficial in removal of this medicine. Further management should be as recommended by the national poisons centre, where available.

Shelf life: 5 years.

This medicinal product does not require any special storage condition.

CELSENTRI 25 mg film-coated tablets: High density polyethylene bottles (HDPE) with polypropylene child resistant (CR) closures and an aluminium foil/polyethylene heat induction seal containing 120 film-coated tablets.

CELSENTRI 75 mg film-coated tablets: High density polyethylene bottles (HDPE) with polypropylene child resistant (CR) closures and an aluminium foil/polyethylene heat induction seal containing 120 film-coated tablets.

CELSENTRI 150 mg film-coated tablets: High density polyethylene bottles (HDPE) with polypropylene child resistant (CR) closures and an aluminium foil/polyethylene heat induction seal containing 180 film-coated tablets.

Polyvinyl chloride (PVC) blisters with child-resistant (CR) aluminium/polyethylene terephthalate (PET) lidding foil in a carton containing 30, 60, 90 film-coated tablets and multipacks containing 180 (2 packs of 90) film-coated tablets.

CELSENTRI 300 mg film-coated tablets: High density polyethylene bottles (HDPE) with polypropylene child resistant (CR) closures and an aluminium foil/polyethylene heat induction seal containing 180 film-coated tablets.

Polyvinyl chloride (PVC) blisters with child-resistant (CR) aluminium/polyethylene terephthalate (PET) lidding foil in a carton containing 30, 60, 90 film-coated tablets and multipacks containing 180 (2 packs of 90) film-coated tablets.

Not all pack sizes may be marketed.

Any unused product or waste material should be disposed of in accordance with local requirements.