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Celsentri is a brand name for Maraviroc. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: CELSENTRI film-coated tablets, in combination with other antiretroviral medicinal products, is indicated for treatment-experienced adults, adolescents and children weighing at least 30 kg infected with only CCR5-tropic HIV-1 detectable (see sections 4.2 and 5.1).
Verbatim from this product's EMA label. Tap a section to expand.
Therapy should be initiated by a physician experienced in the management of HIV infection. e. CXCR4 or dual/mixed tropic virus not detected) using an adequately validated and sensitive detection method on a newly drawn blood sample. 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 3 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. 5). Children and adolescents weighing at least 30 kg 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.
5 for corresponding adult dosage. Many medicines have profound effects on maraviroc exposure due to drug-drug interactions. 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 adolescents and children (weighing at least 30 kg) based on weight Adult dosage* Concomitant Medications Dose of CELSENTRI in adolescents and children based on weight 30 to less than 40 kg at least 40 kg 150 mg twice daily CELSENTRI with products that are potent CYP3A inhibitors (with or without a CYP3A inducer) 100 mg twice daily+ 150 mg twice daily 300 mg twice daily CELSENTRI with products that are not potent CYP3A inhibitors or potent CYP3A inducers 300 mg twice daily 300 mg twice daily 600 mg twice daily CELSENTRI with products that are CYP3A inducers (without a potent CYP3A inhibitor) Data to support these doses are lacking and CELSENTRI is not recommended in children taking concomitant interacting medicinal products that in adults would require a 600 mg twice daily dose.
1). The most frequently reported adverse reactions occurring in the Phase 2b/3 studies were nausea, diarrhoea, fatigue and headache. These adverse reactions were common (≥ 1/100 to < 1/10). Tabulated list of adverse reactions 15 The adverse reactions are listed by system organ class (SOC) and frequency.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1,000) , not known (cannot be estimated from the available data).
The adverse reactions and laboratory abnormalities presented below are not exposure adjusted. 4). Skin and liver reactions can occur as single events, or in combination. In HIV infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise.
4). Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to combination antiretroviral therapy (CART). 4). Cases of syncope caused by postural hypotension have been reported.
Laboratory abnormalities Table 4 shows the incidence ≥1% of Grade 3-4 Abnormalities (ACTG Criteria) based on the maximum shift in laboratory test values without regard to baseline values. 9 ULN: Upper Limit of Normal OBT: Optimised Background Therapy * Percentages based on total patients evaluated for each laboratory parameter The MOTIVATE studies were extended beyond 96 weeks, with an observational phase extended to 5 years in order to assess the long-term safety of maraviroc.
The Long-Term Safety/Selected Endpoints (LTS/SE) included death, AIDS-defining events, hepatic failure, Myocardial infarction/cardiac ischaemia, malignancies, rhabdomyolysis and other serious infectious events with maraviroc treatment.
Hepatic disease The safety and efficacy of maraviroc have not been specifically studied in patients with significant underlying liver disorders. 5 Cases of hepatotoxicity and hepatic failure with allergic features have been reported in association with maraviroc.
8). 8). Patients with pre-existing liver dysfunction, including chronic active hepatitis, can have an increased frequency of liver function abnormalities during combination antiretroviral therapy and should be monitored according to standard practice.
g. pruritic rash, eosinophilia or elevated IgE). 1). Caution should be exercised when treating these patients. In case of concomitant antiviral therapy for hepatitis B and/or C, please refer to the relevant product information for these medicinal products.
2). Severe skin and hypersensitivity reactions Hypersensitivity reactions including severe and potentially life-threatening events have been reported in patients taking maraviroc, in most cases concomitantly with other medicinal products associated with these reactions.
These reactions included rash, fever, and sometimes organ dysfunction and hepatic failure. Discontinue maraviroc and other suspect agents immediately if signs or symptoms of severe skin or hypersensitivity reactions develop. Clinical status and relevant blood chemistry should be monitored and appropriate symptomatic therapy initiated.
Cardiovascular safety Limited data exist with the use of maraviroc in patients with severe cardiovascular disease, therefore special caution should be exercised when treating these patients with maraviroc. In the pivotal studies of treatment-experienced patients coronary heart disease events were more common in patients treated with maraviroc than with placebo (11 during 609 PY vs 0 during 111 PY of follow-up).
In treatment-naïve patients such events occurred at a similarly low rate with maraviroc and control (efavirenz). Postural hypotension When maraviroc was administered in studies with healthy volunteers at doses higher than the recommended dose, cases of symptomatic postural hypotension were seen at a greater frequency than with placebo.
1.
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5) 4 + This dose cannot be achieved with CELSENTRI film-coated tablets. Please refer to Summary of Product Characteristics for CELSENTRI oral solution. 2), therefore CELSENTRI should be used with caution in this population. 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.
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.
2). Paediatric patients (children weighing less than 30 kg) CELSENTRI film-coated tablets are not indicated in children and adolescents weighing less than 30 kg. Please refer to the Summary of Product Characteristics for CELSENTRI oral solution for appropriate use in children from 2 years of age and weighing 10 to less than 30 kg.
2). No data are available. Method of administration Oral use. CELSENTRI can be taken with or without food.
The incidence of these selected endpoints for subjects on maraviroc in this observational phase was consistent with the incidence seen at earlier timepoints in the studies. In treatment-naïve patients, the incidence of grade 3 and 4 laboratory abnormalities using ACTG criteria was similar among the maraviroc and efavirenz treatment groups.
Paediatric population The adverse reaction profile in paediatric patients is based on 48 Week safety data from study A4001031 in which 103 HIV-1 infected, treatment-experienced patients aged 2 to <18 years received maraviroc twice-daily with optimised background therapy (OBT).
Overall, the safety profile in paediatric patients was similar to that observed in adult clinical studies. 17 Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are […]
Caution should be used when administering maraviroc in patients on concomitant medicinal products known to lower blood pressure. Maraviroc should also be used with caution in patients with severe renal insufficiency and in patients who have risk factors for, or have a history of postural hypotension.
Patients with cardiovascular co-morbidities could be at increased risk of cardiovascular adverse reactions triggered by postural hypotension. Renal impairment An increased risk of postural hypotension may occur in patients with severe renal insufficiency who are treated with potent CYP3A inhibitors or boosted protease inhibitors (PIs) and maraviroc.
6 This risk is due to potential increases in maraviroc maximum concentrations when maraviroc is co-administered with potent CYP3A inhibitors or boosted PIs in these patients. Immune reconstitution syndrome In HIV infected patients with severe immune deficiency at the time of institution of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of symptoms.
Typically, such reactions have been observed within the first few weeks or months of initiation of CART. Relevant examples are cytomegalovirus retinitis, generalised and/or focal mycobacterial infections, and pneumonia caused by Pneumocystis jiroveci (formerly known as Pneumocystis carinii).
Any inflammatory symptoms should be evaluated and treatment initiated when necessary. Autoimmune disorders (such as Graves’ disease and autoimmune hepatitis) have also been reported to occur in the setting of immune reactivation; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment.
e. 1). The Monogram Trofile assay was used in the clinical studies of maraviroc. The viral tropism cannot be predicted by treatment history or assessment of stored samples. Changes in viral tropism occur over time in HIV-1 infected patients.
Therefore, there is a need to start therapy shortly after a tropism test. Background resistance to other classes of antiretrovirals have been shown to be similar in previously undetected CXCR4-tropic virus of the minor viral population, as that found in CCR5-tropic virus.
1). Dose adjustment Physicians should ensure that appropriate dose adjustment of maraviroc is made when maraviroc is co-administered with potent CYP3A4 inhibitors and/or inducers since maraviroc concentrations and its therapeutic effects may be […]