EDURANT PACKAGE INSERT PDF

Drug information on Rilpivirine Tablet (film coated) for health care professionals. Edurant (rilpivirine) Tablets, Package Insert. EDURANT is a human immunodeficiency virus type 1 (HIV-1) specific, non-nucleoside reverse. For patients concomitantly receiving rifabutin, the EDURANT dose should be increased to 50 mg .. The interaction between rilpivirine and the medicinal product was evaluated in a clinical study. See package leaflet for further information.

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White to off-white, round, biconvex, film-coated tablet with a diameter of 6. For patients concomitantly receiving rifabutin, the EDURANT dose should be increased to 50 mg two tablets of 25 mg each taken once daily.

If the patient misses a dose of EDURANT within 12 hours of the time it is usually taken, the patient must take the medicine with a meal as soon as possible and resume the normal dosing schedule.

If a patient misses a dose of EDURANT by more than 12 hours, the packagr should not take the missed dose, but resume the usual dosing schedule. If a patient vomits more than 4 hours after taking the medicine, the patient does not need to take another dose of EDURANT until the next regularly scheduled packagge. No dose adjustment of rilpivirine is required in patients with mild or moderate renal impairment.

In patients with severe renal impairment or inserg renal disease, rilpivirine should be used with caution. In patients with severe renal impairment or end-stage renal disease, the combination of rilpivirine eduraht a strong CYP3A inhibitor e.

Treatment with rilpivirine resulted in an early small increase of mean serum creatinine levels which remained stable over time and is not considered clinically innsert see section 4. Lower exposures of rilpivirine were observed during pregnancy, therefore viral load should be monitored closely.

Alternatively, switching to another ART regimen could be considered see sections 4. It is recommended that the film-coated tablet be swallowed whole with water and not be chewed or crushed.

While effective viral suppression with antiretroviral therapy has been proven to substantially reduce the risk of sexual transmission, a residual risk cannot be excluded. Precautions to prevent transmission should be taken in accordance with national guidelines.

The list of rilpivirine resistance-associated mutations presented in section 5. The greater risk of virologic failure for patients in the rilpivirine arm was observed in the first 48 weeks of these trials see section 5.

Findings in adolescents 12 to less than 18 years of age in trial C were generally in line with these data for details see section 5. Only adolescents deemed likely to have good adherence to antiretroviral therapy should ddurant treated with rilpivirine, as suboptimal adherence can lead to development of resistance and the loss of future treatment options.

As with other antiretroviral medicinal products, resistance testing should guide the use eduran rilpivirine see section 5. At supra-therapeutic doses 75 and mg once dailyrilpivirine has been associated with prolongation of the QTc interval of the electrocardiogram Pwckage see sections 4.

In HIV infected patients with severe immune deficiency at the time of initiation of CART, an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause serious clinical conditions or aggravation of symptoms.

Edurant (rilpivirine) Tablets, Package Insert

Typically, such reactions have been observed within the first weeks or months of initiation of CART. Any inflammatory symptoms should be evaluated and treatment instituted 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 see section 4.

Edurant should be used during pregnancy only if the potential benefit justifies the potential risk. Lower exposures of rilpivirine were observed when rilpivirine 25 mg once daily was taken during pregnancy. In the phase 3 studies, lower rilpivirine exposure, similar to that seen during pregnancy, has been associated with an increased risk of virological failure, therefore viral load should be monitored closely see sections 4.

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Alternatively, switching to another ART regimen could be considered. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Medicinal products that induce or inhibit CYP3A may thus affect the clearance of rilpivirine see section 5. Co-administration of rilpivirine and medicinal products that induce CYP3A has been observed to decrease the plasma concentrations of rilpivirine, which could reduce the therapeutic effect of rilpivirine.

Co-administration of rilpivirine and medicinal products that inhibit CYP3A has been observed to increase the plasma concentrations of rilpivirine. Co-administration of rilpivirine with medicinal products that increase gastric pH may result in decreased plasma concentrations of rilpivirine which could potentially reduce the therapeutic effect of EDURANT.

Rilpivirine at a dose of 25 mg once daily is not likely to have a clinically relevant effect on the exposure of medicinal products metabolised by CYP enzymes. Rilpivirine inhibits P-glycoprotein in vitro IC 50 is 9. In a clinical study, rilpivirine did not significantly affect the pharmacokinetics of digoxin. However, it may not be completely excluded that rilpivirine can increase the exposure to other medicines transported by P-glycoprotein that are more sensitive to intestinal P-gp inhibition, e.

The clinical implications of this finding are currently unknown. Established and theoretical interactions with selected antiretrovirals and non-antiretroviral medicinal products are listed in table 1. No dose adjustment is required.

Didanosine should be administered at least two hours before or at least four hours after rilpivirine. Concomitant use of rilpivirine with ritonavir-boosted PIs causes an increase in the plasma concentrations of rilpivirine, but no dose adjustment is required.

Rilpivirine must not be used in combination with these anticonvulsants as co-administration may result in loss of therapeutic effect of rilpivirine see section 4. At the recommended dose of 25 mg once daily, no dose adjustment is required when rilpivirine is co-administered with ketoconazole. Throughout co-administration of rilpivirine with rifabutin, the rilpivirine dose should be increased from 25 mg once daily to 50 mg once daily.

When rifabutin co-administration is stopped, the rilpivirine dose should be decreased to 25 mg once daily. Rilpivirine must not be used in combination with rifampicin as co-administration is likely to result in loss of therapeutic effect of rilpivirine see section 4.

Rilpivirine must not be used in combination with rifapentine as co-administration is likely to result in loss of therapeutic effect of rilpivirine see section 4. Rilpivirine should not be used in combination with systemic dexamethasone except as a single dose as co-administration may result in loss of therapeutic effect of rilpivirine see section 4. Alternatives should be considered, particularly for long-term use.

Rilpivirine must not be used in combination with proton pump inhibitors as co-administration is likely to result in loss of therapeutic effect of rilpivirine see section 4. The combination of rilpivirine and H 2 -receptor antagonists should be used with particular caution.

Only H 2- receptor antagonists that can be dosed once daily should be used. A strict dosing schedule, with intake of H 2- receptor antagonists at least 12 hours before or at least 4 hours after rilpivirine should be used.

The combination of rilpivirine and antacids should be used with particular caution. Antacids should only be rdurant either at least 2 hours before or at least 4 hours after rilpivirine. No dose adjustments are required when initiating co-administration of methadone with rilpivirine.

However, clinical monitoring is recommended as methadone maintenance therapy may need to be adjusted in some patients. Rilpivirine must not be used in combination with products containing St John’s wort as co-administration may result in loss of therapeutic effect of rilpivirine see section 4.

All other drug-drug interactions shown are predicted. This interaction study has been performed with a dose higher than the recommended dose for rilpivirine assessing the maximal effect on the co-administered medicinal product.

The dosing recommendation is applicable to the recommended dose of rilpivirine of 25 mg once daily. There is limited information available on the potential for a pharmacodynamic interaction between rilpivirine and medicinal products that prolong the QTc interval of the ECG. In a study of healthy subjects, supratherapeutic doses of rilpivirine 75 mg once daily and mg once daily have been shown to prolong the QTc interval of the ECG see section 5.

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There are limited amount of data less than pregnancy outcomes from the use of rilpivirine in pregnant women see sections 4. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity see section 5. It is not known whether rilpivirine is excreted in human milk. Rilpivirine is excreted in the milk of rats.

Because of both the potential for HIV transmission and the potential for adverse reactions in breastfed infants, mothers should be instructed not to breast-feed if they are receiving rilpivirine. No human data on the effect of rilpivirine on fertility are available. No clinically relevant effects on fertility were seen in animal studies see section 5. However, fatigue, dizziness and somnolence have been reported in some patients taking EDURANT and should be considered when assessing a patient’s ability to drive or operate machinery.

The most frequent serious treatment-related ADRs were reported in 7 1. The median duration of exposure for patients in the rilpivirine arm and efavirenz arm was Most ADRs occurred in edrant first 48 weeks of treatment. ADRs reported in adult patients treated with rilpivirine are summarised in Table 2.

Within each frequency grouping, ADRs are presented in order of decreasing frequency. In HIV infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy CARTan inflammatory reaction to asymptomatic or residual opportunistic infections may arise.

Autoimmune disorders such as Graves’ disease and imsert hepatitis have also been reported; however, the reported time to insery is more variable and edurany events can occur many months after initiation of treatment see section 4. The median duration of exposure for patients was There were no patients who discontinued treatment due to ADRs. No new ADRs were identified compared to those seen in adults.

Edurant 25 mg tablets – Summary of Product Characteristics (SmPC) – (eMC)

Most ADRs were Grade 1 or 2. No data are available. In patients co-infected with hepatitis B or C virus receiving rilpivirine, the incidence of hepatic enzyme elevation was higher than in patients receiving rilpivirine who were not co-infected. This observation was the same in the efavirenz arm.

The pharmacokinetic exposure of rilpivirine in co-infected patients was comparable to that in patients without co-infection.

Reporting suspected adverse reactions after authorisation of pakage medicinal product is important. Healthcare professionals are asked to report any suspected adverse reactions via:. Human experience of overdose with rilpivirine is edurajt. Treatment of overdose with rilpivirine consists of general supportive measures including monitoring of vital signs and ECG QT interval as well as observation of the clinical status of the patient.

Administration of activated charcoal may be used to aid in removal of unabsorbed active substance. Since rilpivirine is highly bound to plasma protein, dialysis is unlikely to result in significant removal of the active substance. Antiviral for systemic use, non-nucleoside reverse transcriptase inhibitors, ATC code: For the resistance analysis, a broader definition of virologic pakcage was used than in the primary efficacy analysis.

In the week 48 pooled resistance analysis from the Phase III trials, 62 of a total of 72 virologic failures in the rilpivirine arm had resistance data at baseline and time of failure. In this analysis, eurant resistance-associated mutations RAMs associated with NNRTI resistance that developed in at least 2 paxkage virologic failures were: In the trials, the presence of the mutations V90I and VI, at baseline, did not affect response.

The EK substitution emerged most frequently during rilpivirine treatment, commonly in combination with the MI substitution.