Composition, form of production and packaging
Tablets covered with a film shell from white to almost white, round, biconvex, with engraving "TMC" on one side and "25" on the other side; on the fracture - from white to almost white.
1 tab.
rilpivirin hydrochloride 27.5 mg,
which corresponds to the content of rilpivirine 25 mg
Excipients: lactose monohydrate - 55.145 mg, microcrystalline cellulose - 16.605 mg, croscarmellose sodium - 6.05 mg, povidone K30 - 3.25 mg, magnesium stearate 1.1 mg, polysorbate 20 - 0.35 mg.
The composition of the membrane: hypromellose 2910 6 mPa.s - 1.76 mg, lactose monohydrate 0.968 mg, macrogol 3000 0.352 mg, triacetin 0.264 mg, titanium dioxide 1.056 mg.
30 pcs. - bottles of high-density polyethylene (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
PHARMACHOLOGIC EFFECT
Rilpivirin is a diaryl pyrimidine non-nucleoside inhibitor of HIV-1 reverse transcriptase. The activity of rilpivirin is mediated by the non-competitive inhibition of HIV-1 reverse transcriptase. Rilpivirin does not inhibit human alpha, beta, gamma-DNA polymerase.
Antiviral activity in vitro
Rilpivirin is active against laboratory wild-type HIV-1 strains in acute infected T-cell lines with an average EC 50 of HIV-1 / IIIB of 0.73 nMol (0.27 ng / ml). Rilpivirin shows limited activity against HIV-2 in vitro with EC 50 values ​​from 2510 to 10,830 nMol (920-3970 ng / ml), but in the absence of clinical trial data, it is not recommended to administer Eduardant ® for the treatment of HIV-2 infection.
Rilpivirin has antiviral activity against a wide range of representatives of the M group of HIV-1 (subtypes A, B, C, D, E, F, G, H) for which its average effective dose (EC 50 ) varies from 0.07 to 1.01 nM ( 0.03-0.37 ng / ml), and
primary isolates of group O, for which its average effective dose (EC 50 ) varies from 2.88 to 8.45 nM (1.06-3.10 ng / ml).
Rilpivirin has additive antiviral activity in combination with nucleotide / nucleoside reverse transcriptase inhibitors (abacavir, didanosine, emtricitabine, stavudine and tenofovir), with protease inhibitors (amprenavir, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, tipranavir and saquinavir), with non-nucleoside reverse transcriptase inhibitors (efavirenzem, etravirine and nevirapine), and also in combination with a fusion inhibitor-enfuvirtide and a CCR 5 antagonist, the co-receptor pa - maraviroc. Rilpivirin provides a synergistic or additive antiviral effect in combination with nucleoside reverse transcriptase inhibitors lamivudine and zidovudine, as well as an integrase inhibitor with raltegravir.
Resistance
Cell culture
When selecting wild-type HIV-1 strains of different origin and different subtypes, as well as selection of HIV-1 strains resistant to NNRTI, the following amino acid substitutions were most often encountered: L100I, K101E, V108I, E138K, V179F, Y181C, H221Y, F227C, M230I.
The biological threshold value (RPL) for rilpivirin was determined with a multiple change in EC 50 (FC) of 3.7, taking into account the sensitivity analysis of a large number of clinical isolates and recombinant wild-type HIV-1 strains.
Patients who have not previously received antiretroviral therapy
Amino acid substitutions that were associated with NNRTI resistance and were most commonly encountered in such patients were: V 901, K101E, E138K, E138Q, V179I, Y181C, V189I, H221Y and F227C. However, in the course of clinical studies, the presence of V 901 and V189I substitutions at the initial stage of treatment did not affect the response to rilpivirin therapy. The replacement of E138K appeared most often during rilpivirin therapy, usually in combination with the replacement of M184I.
In a large number of patients with virological failure of Eduardant В® therapy, resistance to lamivudine / emtricitabine was observed compared with patients who had a virological failure of efavirenz therapy.
Taking into account all available data in vivo and in vitro the following amino acid substitutions present at the initial stage of treatment affect the activity of rilpivirin: K101E, K101P, E138A, E138G, E138K, E138R, E138Q, V179L, Y181C, Y181I, Y181V, H221Y, F227C, M230I and M230L.
Cross-resistance
Mutant strains with resistance to HIV-1
Of the 67 laboratory recombinant HIV-1 strains with one amino acid substitution in the reverse transcriptase gene, with a mutation resistant to NNRTI, including frequently occurring K103N and Y181C, rilpivirin demonstrated antiviral activity against 64 (96%) of these strains. At the same time, it was shown that the presence of the mutation K103N does not in itself lead to a decrease in sensitivity, but the presence of a combination of mutations K103N and L100I results in a 7-fold decrease in sensitivity. Single amino acid substitutions associated with a loss of sensitivity to rilpivirin were K101P, Y181I and Y181V.
Isolates of recombinant strains
Rilpivirin demonstrated sensitivity (FC <BDT) for 62% of the 4,786 isolates of recombinant strains with resistance to efavirenz and / or nevirapine.
HIV-1 infected patients who had not previously received antiretroviral therapy.
According to the clinical study, 31 patients from 62 patients with virological failure, against the background of treatment with Eduardant В® and phenotypic resistance, ceased to respond to rilpivirin therapy. And 28 patients had resistance to etravirine, 27 - to efavirenz and 14 - to nevirapine.
Influence on the parameters of the electrocardiogram
The effect of Eduardant В® on the QTcF interval when taken at the recommended dose of 25 mg 1 time / day was studied in healthy volunteers. When taking Eduardant В® at a recommended dose of 25 mg 1 time / day, there was no clinically significant effect on the QTc interval.
When studying the use of Eduardant ® in doses exceeding the therapeutic dose (75 mg once a day and 300 mg 1 time / day) taken by healthy volunteers, the maximum average and time-matched (upper bound of the confidential interval 95%), the difference in the QTcF interval between the study drug and the placebo and after correction of the values ​​was 10.7 (15.3) and 23.3 (28.4) ms, respectively. Against the background of the equilibrium state, taking the drug at doses of 75 mg once a day and 300 mg once a day led to an increase in the average value of C max in the blood plasma by about 2.6 or 6.7 times, respectively, compared with the mean C max , which was noted against the background of the equilibrium state with the administration of Eduardant ® in the recommended dose of 25 mg 1 time / day.
PHARMACOKINETICS
The pharmacokinetic properties of rilpivirin have been studied in adult healthy volunteers and adult HIV-1-infected patients who have not previously received antiretroviral therapy. The effect of rilpivirin on HIV-1-infected patients was lower than on healthy volunteers.
Suction
After ingestion of C max, rilpivirin in the blood plasma was reached within 4-5 hours. Absolute bioavailability of rilpivirin is unknown.
Exposure rilpivirina was about 40% lower when taking the drug on an empty stomach than when taking with meals the usual caloric intake (533 kcal) or with food high in fat (928 kcal). When the Eduardant В® preparation was taken with a drink enriched with proteins, the exposure was 50% lower than when it was taken with food at the same time.
Distribution
In vitro, 99.7% of rilpivirin binds to plasma proteins, predominantly with albumin. Distribution rilpivirina in biological fluids (cerebrospinal fluid, secrets of the genital tract), has not been studied.
Metabolism
In vitro studies have shown that rilpivirin undergoes oxidative metabolism mediated by cytochrome P450 (CYP) 3A system.
Excretion
The final T 1/2 of rilpivirin is approximately 45 hours. After taking a single dose of 14 C-rilpivirin by mouth, about 85% and 6.1% of the dose containing the radioactive label were found in feces and urine, respectively.
The amount of rilpivirine found in the stool in unchanged form averaged 25% of the administered dose. In urine, only a small amount of unchanged rilpivirin was detected (less than 1% of the dose taken).
Pharmacokinetics in specific patient groups
The pharmacokinetics of rilpivirin in children is currently being studied. Due to the insufficient study of the drug in children, it is not possible to provide recommendations for the administration of Eduardant В® to children.
Pharmacokinetic analysis of data of HIV-1-infected patients showed that the pharmacokinetics of rilpivirin remains comparable for all age groups (18 to 78 years). Correction of the dose of the drug in elderly patients is not required.
There were no clinically significant differences in the pharmacokinetics of rilpivirin in men and women .
Pharmacokinetic analysis of HIV-1-infected patients showed that race does not affect the effectiveness of Eduardant В® .
Rilpivirin is metabolized and excreted by the liver. In a study comparing pharmacokinetic parameters in patients with mild hepatic impairment (class A on the Child-Pugh scale) and patients in the control group, as well as the pharmacokinetic parameters of patients with moderate hepatic impairment (class B on the Child-Pugh scale) and patients from the of the control group, the action of rilpivirin taken in multiple doses was 47% higher in patients with mild hepatic impairment, and 5% higher in patients with moderate impaired hepatic function. In patients with mild or moderate impairment of liver function, dose adjustment is not required. The pharmacokinetics of the Eduardant В® preparation in patients with severe impairment of liver function (class C on the Child-Pugh scale) has not been studied.
Pharmacokinetic analysis in populations of patients showed that co-infection with the hepatitis B virus and / or C did not have a clinically significant effect on the action of rilpivirin.
The pharmacokinetics of rilpivirin in patients with impaired renal function has not been studied. The kidneys show a small amount of rilpivirin. Impact of violation the kidney function for deducing rilpivirin is considered to be minimal. It is unlikely that hemodialysis or peritoneal dialysis can significantly accelerate the removal of rilpivirin from the body, since rilpivirin has a high affinity for plasma proteins.
INDICATIONS
- in combination with other antiretroviral drugs as first-line therapy for the treatment of infection caused by human immunodeficiency virus type 1 (HIV-1) in adult patients.
DOSING MODE
Treatment should be performed by a doctor who has experience of HIV therapy. The drug Edurant В® should be used only in combination with other antiretroviral agents. The recommended dose of the drug is 25 mg (1 tab.) Orally 1 time / day during meals.
If the delay in taking the drug is less than 12 hours, the patient should take a tablet of Eduardant В® as soon as possible with the food, the next tablet is taken at the usual time. If the delay in taking the drug is more than 12 hours, the missed dose should not be taken; the next tablet is taken at the usual time.
Correction of the dose of Eduardant В® in elderly patients is not required.
The effectiveness and safety of Eduardant В® in children under the age of 18 years is not established.
In patients with mild or moderate liver function disorder (class A or B on the Child-Pugh scale), dose adjustment is not required. Data on the use of the drug in patients with severe impairment of liver function (class C on the scale Child-Pugh) are absent.
In patients with impaired renal function, dose adjustment of Eduardant В® is not required.
SIDE EFFECT
AT During clinical trials, the most common adverse reactions were: depression, insomnia, headache, increased hepatic transaminase activity and rash.
Among the adverse reactions, a severe increase in the activity of transaminases (1.6%), depression (0.7%), abdominal pain (0.4%), dizziness (0.3%), rash (0.3%).
Adverse reactions of the drug are systematized relative to each of the organ systems depending on the frequency of occurrence, using the following classification: very often (? 1/10), often (? 1/100, <1/10), infrequently (? 1/1000, < 1/100), rarely (? 1/10 000, <1/1000), very rarely (<1/10 000), including isolated cases.
From the digestive system: often - decreased appetite, pain in the abdomen, vomiting, nausea; infrequently - discomfort in the abdomen.
From the side of the central nervous system: often - depression, insomnia, unusual dreams, sleep disorder, dizziness, headache; infrequent - a decrease in mood, drowsiness.
From the skin and subcutaneous tissue: often - a rash.
On the part of laboratory indicators: often - increased activity of transaminases. There were also cases of a decrease in the concentration of hemoglobin, platelets, leukocytes, increased activity of AST, ALT, pancreatic amylase, lipase, increased bilirubin, total cholesterol, LDL and triglycerides. The mean change in total cholesterol concentration (fasting) was 2 mg / dL, HDL (fasting) 4 mg / dL, LDL fast (1 mg / dL) and triglycerides (fasting) 7 mg / dl.
General: often - fatigue.
Description of individual adverse reactions
Redistribution of subcutaneous fat (FFA)
Combined antiretroviral therapy causes the redistribution of PLN (lipodystrophy) in HIV-infected patients and is manifested by loss of subcutaneous fat on the periphery (upper and lower extremities) and the facial area, increased levels of fat in the intraperitoneal and visceral regions, mammary hypertrophy and accumulation of subcutaneous fat in the dorsocervical region (the "buffalo hump").
Immunodeficiency Syndrome
In HIV-infected patients with severe form of immunodeficiency, who have just begun to receive combined antiretroviral therapy, the inflammatory response to the presence of opportunistic agents with the appearance or exacerbation of symptoms of a disease previously asymptomatic (immune reconstitution syndrome) may develop on the background of restoration of the immune system.
Patients who are co-infected with hepatitis B and / or hepatitis C virus
In patients who were co-infected with the hepatitis B or C virus that received Eduardant В® , the frequency of hepatic enzyme elevation was higher than in patients with HIV infection alone. The pharmacokinetic effect of rilpivirin in co-infected patients is comparable to that of patients without co-infection.
The level of serum creatinine
The increase in serum creatinine was observed during the first four weeks of therapy and remained stable until the 48th week. The mean change after 48 weeks of therapy was 0.09 mg / dL (range: -0.20 mg / dl to 0.62 mg / dL). In patients with mild to moderate renal insufficiency, this increase in serum creatinine levels was comparable to an increase in serum creatinine in patients with normal renal function. These changes were regarded as clinically insignificant, and no patient discontinued therapy due to an increase in serum creatinine levels.
CONTRAINDICATIONS
- Children under 18 years of age (there is currently insufficient data on the safety and efficacy of Eduardant В® in children under 18 years of age, so unless clinical data on the safety and efficacy of the drug in children are obtained, it is not recommended to use the drug in this category patients);
- Severe liver dysfunction (class C on the Child-Pugh scale (there is currently insufficient data on the safety and efficacy of Eduardant В® in patients with severe liver function disorder (Child-Pugh class C), so while clinical data on safety and efficacy of the drug in patients with severe impaired liver function (class C on the Child-Pugh scale) will not be received, it is not recommended to use the drug in this category of patients);
- simultaneous administration with drugs that significantly reduce the concentration of rilpivirin in the plasma, as this may lead to a loss of virologic response or to the development of resistance to the Edurant В® preparation or to the entire class of non-nucleoside reverse transcriptase inhibitors. A significant decrease in the concentrations of rilpivirin in plasma can occur when drugs taken simultaneously with the drug Edurant В® are metabolized through the isozyme CYP3A or increase the pH level in the stomach: anticonvulsants - carbamazepine, oxcarbazepine, phenobarbital, phenytoin; antituberculous agents - rifabutin, rifampicin, rifapentin; proton pump inhibitors - such as esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole; SCS of systemic action - dexamethasone (when taken more than 1 time); preparations based on St. John's wort (Hypericum perforatum);
- lactose intolerance, lactase deficiency, glucose-galactose malabsorption;
- Hypersensitivity to rilpivirin or any other components of the drug.
Caution should be used preparation Edurant В® in combination with drugs that can cause polymorphic ventricular tachycardia such as "pirouette". Data on the potential interaction of rilpivirin and drugs that extend the QT interval are limited. In a study involving healthy volunteers, it was found that rilpivirin in high doses (75 mg once a day and 300 mg once a day) prolongs the QT interval on the ECG.
PREGNANCY AND LACTATION
Not been adequate and well-controlled clinical and pharmacokinetic studies of the drug Edyurant В® in pregnant women. In an animal study evidence of embryo toxicity or effects on reproductive function have been identified. The drug Edyurant В® should be used during pregnancy only if the potential benefit to the mother outweighs the potential risk to the fetus.
It is not known whether rilpivirine passes into breast milk of nursing women. Due to the risk of HIV infection and the possible development of adverse events in infants are breastfed, it is not recommended to breast-feeding during treatment.
In the absence of adequate and well-controlled clinical trials of the drug Edyurant В® in pregnant women, women of childbearing age is recommended to use effective contraception during treatment.
Data on the effects of rilpivirine on reproductive function are absent.
APPLICATION FOR FUNCTIONS OF THE LIVER
Patients with impaired renal function dose correction Edyurant В® not required.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
In patients with mild or moderate hepatic impairment (Class A or B on the scale of Child-Pugh) correction dose is not required. Data on the use of the drug in patients with severe hepatic impairment (class C by Child-Pugh) are absent.
APPLICATION FOR CHILDREN
At the moment insufficient data on safety and efficacy of the drug Edyurant В® in children under 18 years. Therefore, while clinical data on the safety and efficacy of the drug in children have been received, it is not recommended to use the drug in these patients
APPLICATION IN ELDERLY PATIENTS
EdyurantВ® correct dose of the drug in elderly patients is not required.
SPECIAL INSTRUCTIONS
Patients should be informed that the current treatment using antiretroviral agents HIV infection can not be cured, but also can not prevent HIV infection through blood or by sexual contact. Necessary precautions should be taken for the prevention of HIV infection.
Before starting therapy with Edyurant В® should be taken into account: in study participants receiving Edyurant drug В® , with HIV-1 RNA above 100 000 copies / ml at the time of initiation of therapy often noted the absence of virological response, compared with patients who have at at the start of therapy, HIV-1 RNA values were less than 100 000 copies. The observed virologic failure in the treatment of drug EdyurantВ® resulted in a higher frequency of formation of drug resistance NNRTI class. In patients with observed virological failure receiving therapy with Edyurant В® , often developed resistance to lamivudine / emtricitabine, compared with patients with observed virological failure receiving drug efavirenz.
Interaction with other drugs
should be cautious when administering the drug Edyurant В® in combination with other drugs that may reduce the therapeutic effect rilpivirine.
depressive disorders
Known cases of depressive disorders (mood deterioration, depression, dysphoria, major depression, unstable behavior, negative thoughts, suicidal ideation, suicidal attempts) in patients receiving the drug Edyurant В® . Most cases have been expressed in the mild or moderate severity. In case of the patient's symptoms moderate depression patient should seek medical help in order to determine whether the occurrence of these symptoms with taking the drug due Edyurant В® . If communication with the administration of the drug proved to be to assess the risk versus the benefit of continued therapy.
Redistribution of subcutaneous fat
Combination antiretroviral therapy may cause a redistribution of subcutaneous fat (lipodystrophy) in HIV-infected patients. The exact mechanism of occurrence and long-term consequences of this phenomenon are not currently known. It is assumed that there is a link between the development of visceral lipomatosis and PIs and between lipoatrophy and nucleoside reverse transcriptase inhibitors (NRTIs). Increased risk of lipodystrophy associated with individual factors such as older age, as well as factors related to the reception of medicines, for example, a longer course of antiretroviral treatment and associated metabolic disorders. Clinical examination of the patient should include assessment of physical signs of redistribution of subcutaneous fat.
Immune reconstitution syndrome
Top of antiretroviral therapy in HIV-infected patients with severe immunodeficiency may develop an inflammatory response to the presence of asymptomatic with the advent of opportunistic agents or exacerbation of symptoms previously asymptomatic (immune reconstitution syndrome), which may require further careful observation and treatment. Typically such reactions are observed during the first weeks after beginning treatment. Similar examples include cytomegalovirus retinitis, generalized and / or focal mycobacterial infections and Pneumocystis pneumonia. Should evaluate any symptoms of inflammation and, if necessary, prescribe treatment.
Effect on driving and working mechanisms
Edyurant В® no effect or has little effect on the ability to drive vehicles and operate machinery.
OVERDOSE
Data on drug overdose in humans are few.
Symptoms of overdose may include headache, nausea, dizziness, and / or unusual dreams.
Treatment. Any specific antidote does not exist. Treatment involves the use of general measures of maintenance therapy, including monitoring of vital signs and electrocardiogram (QT interval), and monitor the patient's clinical condition. If there are indications for removal of the dose absorbed is not the active substance is possible gastric lavage. For this purpose also can receive the activated carbon. Since rilpivirine is highly Plasma protein binding, dialysis in the case of overdose ineffective.
DRUG INTERACTION
Drugs that influence the metabolism rilpivirine
rilpivirine metabolized involving isozymes of cytochrome P450 (CYP) 3A, therefore, drugs that induce or inhibit CYP3A affect the excretion rilpivirine.
Simultaneous administration of the drug Edyurant В® and drugs capable of inducing CYP3A, may reduce rilpivirine plasma concentration and therapeutic effect to reduce rilpivirine.
Simultaneous administration of the drug Edyurant В® drugs that inhibit CYP3A, may increase rilpivirine plasma concentrations.
Simultaneous reception Edyurant preparation В®and drugs that increase the pH in the stomach can result in lower plasma concentrations of rilpivirine and possible reduction rilpivirine therapeutic action.
Rilpivirine Effect on the metabolism of other drugs
is unlikely that drug Edyurant В® , received a dose of 25 mg 1 time / day clinically significant effect on the elimination of drugs metabolised by cytochrome P450 isozymes.
Drug interaction rilpivirine while receiving with drugs shown in Table 1 (increasing denoted - ^, lower - v, no changes - - not applicable - NP, CI - CI).
Table 1. Patient interaction and guidance on the selection of the dose.
Medications Effects on the pharmacokinetic parameters of drugs Least squares mean ratio (90% CI; 1.00 = no effect) Recommendations for simultaneous reception of other drugs
Antivirals
Antiretroviral agents
NRTIs / NtRTIs
Didanosine * # 400 mg / day AUC didanosine ^ 1.12 (0.99 -1.27) C min didanosine NP C max didanosine - 0.96 (0.80-1.14) AUC rilpivirine - 1.00 (0.95-1.06) C min rilpivirine -1.00 (0.92-1.09) C maxrilpivirine - 1.00 (0.90-1.10) while receiving drugs Edyurant В® ddI dose adjustment is required. Didanosine should be taken on an empty stomach, and at least 2 hours to 4 hours after receiving rilpivirine.
Tenofovir * # 300 mg / day AUC tenofovir 1.23 ^ (1.16-1.31) C min tenofovir 1.24 ^ (1.10-1.38) C max tenofovir - 1.19 (1.06-1.34) AUC rilpivirine - 1.01 (0.87-1.18) C min rilpivirine - 0.99 (0.83-1.16) C max rilpivirine - 0.96 (0.81-1.13) while receiving drugs Edyurant В® with tenofovir dose adjustment is required.
Other NRTIs (abacavir, emtricitabine, lamivudine, stavudine and zidovudine) Not studied Given various ways rilpivirine excretion and other NRTIs clinically significant drug interactions between the drugs and rilpivirine not assumed.
NNRTIs
Delavirdine, efavirenz, etravirine, nevirapine Not studied Not to take Edyurant В® concurrently with other NNRTIs.
Protease inhibitors - reinforced low dose ritonavir
darunavir / r * # 800/100 mg / day AUC darunovira - 0.89 (0.81-0.99) C min darunovira 0.89 v (0.68-1.16) C max darunovira - 0.90 (0.81-1.00) AUC ^ rilpivirine 2.30 (1.98-2.67) C minrilpivirine 2.78 * (2.39-3.24) C max rilpivirine ^ 1.79 (1.56-2.06) while receiving drugs Edyurant В® with darunavir / rilpivirine increase ritonavir plasma concentrations can be observed (inhibition isoenzyme CYP3A). When concomitantly with rilpivirine darunavir / ritonavir dose adjustment is required.
Lopinavir / ritonavir (soft gelatin capsule) * # 400/100 mg of 2 times / day AUC of lopinavir - 0.99 (0.89-1.10) C min lopinavir 0.89 v (0.73-1.08) C max lopinavir - 0.96 (0.88-1.05) AUC ^ rilpivirine 1.52 (1.36-1.70) C min rilpivirine 1.74 ^ (1.46-2.08) C maxrilpivirine ^ 1.29 (1.18-1.40) while receiving drugs Edyurant В® with lopinavir / ritonavir can increase rilpivirine observed plasma concentrations (inhibition of CYP3A enzyme). When concomitantly with rilpivirine lopinavir / ritonavir dose adjustment is required.
Other reinforced protease inhibitors (atazanavir / ritonavir, fosamprenavir / ritonavir, saquinavir / ritonavir, tipranavir / ritonavir) Not studied while receiving drugs Edyurant В® with enhanced protease inhibitors may increase rilpivirine observed plasma concentrations (inhibition of CYP3A enzyme). There is a low probability that rilpivirine will affect the concentration of concurrently administered protease inhibitors in blood plasma.
Protease inhibitors - without amplification ritonavir
Pharmacologically not reinforced protease inhibitors (atazanavir, fosamprenavir, indinavir, nelfinavir) Not studied while receiving drugs Edyurant В® with enhanced protease inhibitors may increase rilpivirine observed plasma concentrations (inhibition of CYP3A enzyme). There is a low probability that rilpivirine will affect the concentration of concomitant protease inhibitors in plasma.
CCR5 antagonist
maraviroc have not been studied clinically significant interactions are not expected at the same time taking rilpivirine and maraviroc.
HIV integrase inhibitor
raltegravir raltegravir AUC ^ 9 the C% maxraltegravir C ^ 10% min raltegravir ^ 27% - AUC rilpivirine - C max rilpivirine - C min rilpivirine dose correction is not required, while taking with raltegravir.
Other antivirals
ribavirin have not been studied clinically significant interactions are not expected at the same time taking rilpivirine and ribavirin.
Telaprevir (750 mg every 8 hours) AUC telaprevir v C 5% max telaprevir v 3 C% min telaprevir v 11% AUC rilpivirine ^ C 78% max rilpivirine C ^ 49% min rilpivirine ^ 93% Simultaneous treatment with telaprevir preparation Edyurant В®may cause an increased concentration in the blood plasma rilpivirine (by inhibiting isoenzyme CYP3A). It does not require dose adjustment of telaprevir and while taking rilpivirine.
Other drugs
of antiarrhythmic agent
digoxin (0.5 mg single dose) - AUC - C max is not required dose correction at concomitantly with digoxin.
Anticonvulsants
carbamazepine, oxcarbazepine, phenobarbital, phenytoin Not studied should not take the drug Edyurant В® in combination with the data anticonvulsants, since this can lead to a reduction in plasma concentration of rilpivirine (induction of isoenzyme CYP3A4), which may cause a decrease in the therapeutic efficacy of the drug EdyurantВ® .
Azole antifungals group
ketoconazole * # 400 mg / day of ketoconazole AUC 0.76 v (0.70-0.82) the C min of ketoconazole 0.34 v (0.25-0.46) the C max of ketoconazole - 0.85 (0.80-0.90) AUC rilpivirine ^ 1.49 (1.31-1.70) C min rilpivirine 1.76 * (1.57-1.97) C max rilpivirine ^ 1.30 (1.13-1.48) while receiving drugs Edyurant В® with ketoconazole rilpivirine increasing concentrations in plasma can be observed (inhibition of CYP3A enzyme). When concomitantly with ketoconazole rilpivirine dose adjustment is required.
Fluconazole, itraconazole, posaconazole, voriconazole Not studied while receiving drugs Edyurant В® with azole antifungals group can be observed increase rilpivirine plasma concentrations (inhibition of enzyme CYP3A). In simultaneous reception rilpivirine with drugs such dose adjustment is required.
Antituberculosis drugs
Rifabutin * # 300 mg / day of rifabutin AUC - 1.03 (0.97-1.09) C min rifabutin - 1.01 (0.94-1.09) C max rifabutin - 1.03 (0.93-1.14) AUC 25-O-dezatsetilrifabutina - 1.07 (1.02-1.11 ) C min of 25-O-dezatsetilrifabutina - 1.12 (1.03-1.22) C max25-O-dezatsetilrifabutina - 1.07 (0.98-1.17) AUC rilpivirine 0.54 * (0.50-0.58) C min rilpivirine 0.51 * (0.48-0.54) C max rilpivirine ^ 0.65 (0.58-0.74) should not use Edyurant В® in combination with rifabutin because this may lead to a decrease in rilpivirine plasma levels (induction of CYP3A4 enzyme) and, in turn, cause a loss of therapeutic effect of rilpivirine.
Rifampin * # 600 mg / day of rifampicin AUC - 0.99 (0.92-1.07) C min rifampicin NP C max rifampicin - 1.02 (0.93-1.12) AUC 25-O-dezatsetilrifampitsina 0.91 v (0.77-1.07) C min of 25-O-dezatsetilrifampitsina NP the C max25-O-dezatsetilrifampitsina - 1.00 (0.87-1.15) AUC rilpivirine 0.20 v (0.18-0.23) C min rilpivirine 0.11 v (0.10-0.13) C max rilpivirine v 0.31 (0.27-0.36) should not use Edyurant В® in combination with rifampicin because this may lead to a decrease in rilpivirine plasma levels (induction of CYP3A4 enzyme) and, in turn, cause a loss of therapeutic effect of rilpivirine.
