Tivicay pills 50mg, 30pcs

Composition

>

of 1 tab. contains:

Active ingredient: dolutegravir sodium – 52.6 mg, which corresponds to the content of dolutegravir-50 mg; Excipients: mannitol-q. s. up to 145.4 mg, microcrystalline cellulose-60 mg, povidone K 29/32-15 mg, sodium carboxymethyl starch-21 mg, sodium stearyl fumarate-6 mg; Composition of the film shell: Opadray II yellow 85 A 92461 – 9 mg (hydrolyzed polyvinyl alcohol 40%, titanium dioxide 23.45%, macrogol (polyethylene glycol) 20.2%, talc 14.8%, iron oxide yellow 1.55%).

Pharmacological action

Pharmacodynamics

Mechanism of action

Dolutegravir inhibits HIV integrase by binding to the integrase active site and blocking the chain transfer step during retroviral deoxyribonucleic acid (DNA) integration, which is essential for the HIV replication cycle.

Biochemical chain transfer analysis using purified HIV-1 integrase and pretreated DNA substrate yielded IC50 values of 2.7 nM and 12.6 nM (concentrations that inhibit replication by 50%). In vitro, dolutegravir slowly dissociates from the active site of the wild-type DNA integrase complex (t1/2 71 hours).

Pharmacodynamic effects

In a randomized trial to determine the optimal dose in HIV-1 infected patients who received dolutegravir monotherapy (ING111521), rapid and dose-dependent antiviral effects were observed, with an average decrease in HIV-1 RNA on day 11 compared to baseline levels of 1.5,2.0 and 2.5 log10 for 2 mg,10 mg and 50 mg dolutegravir taken once a day, respectively.

This antiviral response was maintained for 3-4 days after the last dose in the group of patients taking 50 mg of dolutegravir.

Antiviral activity in cell culture

In peripheral blood mononuclear cells (MCPC) infected with the Bal strain of HIV-1 or the NL432 strain of HIV-1, IC50 values of 0.51 nM and 0.53 nM were obtained for dolutegravir, respectively. In MT-4 cells infected with the 1MB HIV-1 strain and incubated with dolutegravir for 4 or 5 days, IC50 values of 0.71 and 2.1 nM were obtained.

In a viral integrase sensitivity analysis using an integrase coding region from 13 clinically distinct subtype B isolates, dolutegravir demonstrated antiviral activity similar to that against laboratory strains, with an average IC50 of 0.52 nM.

In the ICPC analysis of a panel consisting of 24 HIV-1 clinical isolates [Group M (subtypes A, B. C, D, E, F and G) and Group O], as well as 3 HIV-2 clinical isolates, the geometric mean IC50 was 0.20 nM, and the IC50 values ranged from 0.02 to 2.14 nM for HIV-1, while for HIV-2 isolates the geometric mean IC50 was 0.18 nM. and the IC50 values ranged from 0.09 to 0.61 nM.

Antiviral activity in combination with other antiviral drugs

None of the drugs with typical antiviral activity against HIV showed antagonism to dolutegravir [in vitro studies were conducted in combination with stavudine, abacavir, efavirenz, nevirapine, lopinavir, amprenavir, enfuvirtide, maravirok, adefovir and raltegravir, selected in staggered order).

In addition, antiviral drugs without typical activity against HIV (ribavirin) did not have a visible effect on the activity of dolutegravir

Effect of blood serum and human serum proteins

In vitro studies confirmed a 75-fold change (CI) in the IC50 of dolutegravir in the presence of 100% human serum (by extrapolation), and the IC90 adjusted for protein binding (PA-IC90) in MCPC was 64 ng/ml.

The minimum concentration of dolutegravir after a single dose of 50 mg in patients who had not previously taken imtegase inhibitors (InI) was 1.20 mcg / ml,9 times higher than the established PA-IC90.

In vitro resistance

Wild-type HIV-1 isolates:  during the 112-day passage of strain IIIB, no viruses with high resistance to dolutegravir were detected. The maximum 4.1-fold change was observed in the groups of resistant viruses obtained during passages with SI53Y and S153F substitutions in the conservative positions of the integrase gene.

Passage of the wild-type HIV-1 strain HL432 in the presence of dolutegravir resulted in the selection of substitutions 92Q (transplanted virus group with CI = 3.1) and G193B (transplanted virus group with CI 3.2) on day 56. Additional passage of B. subtypes. C and A / G of wild-type virus in the presence of dolutegravir resulted in selection of R263K. Gl 18R and S153T.

Antiviral activity against resistant strains:  strains resistant to reverse transcriptase inhibitors (RTI) and protease inhibitors (AI): Aolutegravir showed the same activity against 2 non-nucleoside (NN)-RTI-resistant,3 nucleoside (H)-RTI-resistant and 2 IP-resistant mutant clones of HIV-1 (1 with triple and 1 with six-fold resistance) compared to the wild strain.

HIV-1 strains resistant to InI: 60 mutant isolates of HIV-1 resistant to InI (28 with one substitution and 32 with 2 or more substitutions) were obtained from wild-type virus HL432 by site-directed mutagenesis.

Dolutegravir showed antiviral activity (sensitivity) against HIV with CI < 5 against 27 out of 8 mutant viruses resistant to InI with one substitution, including T66A/I/K. E92Q/V,43C/M/R. Q148H/K/R and N15511, while for raltegravir and elvitegravir, activity was shown against 17/28 and 11/21 tested mutant viruses with CI 

In addition, of the 32 mutant viruses resistant to InI with 2 or more substitutions,23 out of 32 showed CI < 5 for dolutegravir compared to And < 5 for 4 out of 32 for raltegravir and CI

HIV-2 strains that are resistant to InI:  The viruses were obtained by site-directed mutagenesis of HIV-2 isolates isolated from HIV-2 infected patients who received raltegravir and who had virologically ineffective treatment.

Overall, the CI of HIV-2 was similar to that of HIV-1, which was observed with a similar set of mutations. The CI of dolutegravir was < 5 against 4 HIV-2 viruses (S163D, G140A/Q148R, A153G/N155H/S163G, and I292Q/T97A/N155H/S163D); for E 92Q/N155II, the CI of dolutegravir was 8.5, and for G140S/QI48R, the CI of dolutegravir was 17.

Dolutegravir, raltegravir, and elvitegravir showed the same activity against HIV-2 with a site-directed mutation with SI63D as for the wild type, and for the remaining mutant HIV-2 viruses, the CI ranges of raltegravir were 6.4-420, and the CI ranges of elvitegravir were 22-640.

Clinical isolates in patients with virological ineffectiveness of raltegravir treatment:  30 clinical isolates with genotypic and phenotypic resistance to raltegravir (median CI >81) were tested for sensitivity to olutegravir (median CI 1.5) by Monogram Biosciences Plieno Sense analysis.

The median CI of dolutegravir for isolates with substitutions at positions 140S-I-Q148II was 3.75: G140S + Q148R-13.3: T 97A + Y143R-1.05 and 15511-1.37.705 raltegravir-resistant isolates obtained from patients treated with raltegravir were analyzed for sensitivity to dolutegravir by Monogram Biosciences Pheno Sense analysis.

Dolutegravir showed CI<10 in 93.9% of 705 clinical isolates, while 16 (9%) of 184 isolates with QI48 + 1 replacement with InI resistance and 25 (27%) of 92 clinical isolates with Q148 + > 2 replacement with InI resistance showed more than a 10-fold change.

Resistance in vivo:  patients who did not take InI

No mutations of InI resistance or treatment-related resistance to nucleoside reverse transcriptase inhibitors (NRTIs)were observed basics of therapy in previously untreated patients who took 50 mg of dolutegravir once a day ( SPRING-1, SPRING-2, SINGLE and FLAMINGO studies).

In the SAILINGy study of patients treated with dolutegravir and previously untreated with InI (n = 354 in the delutegravir group), treatment-related substitutions in integrase were observed at week 48 in 4 of 17 patients with virologic inefficiency receiving dolutegravir.

2 out of 4 patients had a unique R263K substitution in the integrase gene with a maximum K and 1.93,1 patient had a polymorphic V151V/I integrase substitution with a maximum FC of 0.92, and 1 patient had already initially had integrase mutations and was assumed to have previously received InI or been infected with an InI-resistant virus.

Sustainability in vivo:  patients with resistance to InI

The VIKING-3 study examined dolutegravir (plus optimized baseline therapy) in patients with existing resistance to InI. Prior to 24 pedels,36 out of 183 patients showed protocol-defined virological inefficiency (PDVF).

Of these,32 patients had paired data on baseline and PDVF resistance for analysis. and 17/32 (53%) had treatment-related mutations, the following treatment-related mutations or combinations of mutations were observed: L74L/M (n =1), E92Q (n = 2), T 97A (n = 9), E 138 K/A/T (n = 8), G140S (n = 2), Y143H (n = 1). S147G (n=l), Q148H/K/R (n = 4). N155II (n=1) and E157E/Q (n=1).

14 of the 17 patients with treatment-related viral mutations had a C-148 mutation at baseline or in the anamnesis. 5 other patients had PDVF between pedels 24 and 48, and 2 of these 5 patients had treatment-related mutations.Noted mutations that occurred during treatment or combinations of mutations were L74I (n = 1), M 55 H(n = 2).

The VIKING-4 study examined dolutegravir (plus optimized baseline therapy) in 30 patients with primary genotypic resistance to InI identified during screening. The mutations that occurred during treatment were consistent with those observed in the VIKING-3 study.

Influence on electrocardiogram (ECG)parameters In a randomized, cross-sectional, placebo-controlled clinical trial,42 healthy volunteers received a single dose of placebo,250 mg dolutegravir suspension (approximately 3 times the exposure to 50 mg once daily at steady state), and moxifloxacin (400 mg, active control) in random order. Dolutegravir did not cause prolongation of the corrected interval (QTc) within 24 hours after taking the drug. After correcting for baseline ECG values and taking placebo, the maximum mean change in QTc based on the Frederick formula correction (QTcF) was 1.99 msec (the upper limit of the 1-way 95% confidence interval is 4.53 msec).

Effects on kidney function

The effect of dolutegravir on serum creatinine clearance (CC), glomerular filtration rate (GFR) in the yoxxol sample, and effective renal plasma flow (EPP) in the paraaminohipiurate sample was evaluated in an open-label, randomized, placebo — controlled study in 3 groups of 37 healthy volunteers who took 50 mg of dolutegravir I once daily (n = 12),50 mg twice daily (n = 13), or placebo once a day (n=12) for 14 days.

There was a moderate decrease in creatinine clearance when dolutegravir was used during the first week of treatment, corresponding to the decrease that was observed in clinical studies.

Dolutegravir did not have a significant effect on GFR or EPP when taken at both doses. These data are supported by in vitro studies, which suggest that the small increases in creatinine levels observed in clinical studies are caused by non-pathological inhibition of the organic cation transporter (OST 2) in the proximal renal tubules, which causes tubular creatinine secretion.

Pharmacokinetics

The pharmacokinetics of dolutegravir in healthy volunteers and HIV-infected patients are the same. The pharmacokinetic variability of dolutegravir was low to moderate.

In Phase 1 studies involving healthy volunteers, the coefficient of variation (KB) among participants for the area under the pharmacokinetic curve “concentration-time” (AUC) and for the maximum concentration (With max) varied from 20 to 40%, and the concentration at the end of the dosage interval (Cmax) — from 30 to 65%. Individual variability in the pharmacokinetics of dolutegravir between participants was higher in HIV-infected patients than in healthy volunteers. Individual variability in pharmacokinetic parameters was lower than that between individuals.

Suction

Dolutegravir is rapidly absorbed after oral use, and the median time to maximum concentration (Tmax) after a tablet dose is 2-3 hours. The linearity of the pharmacokinetics of dolutegravir depends on the dose and dosage form.

After oral use, dolugegravir in tablet form generally showed non-linear pharmacokinetics, with a less than dose-dependent increase in plasma exposure from 2 to 100 mg, but the increase in dolutegravir exposure was proportional to the dose from 25 mg to 50 mg.

Dolutegravir can be taken regardless of food intake. Food increases the degree and decreases the rate of absorption of dolutegravir. The bioavailability of dolutegravir depends on the urine content: when taking food with low, moderate and high fat content, the AUQ0-∞) of dolutegravir increased by 33%,41% and 66%, Cmax increased by 46%,52% and 67%, Tmax was extended to 3,4 and 5 hours compared to 2 hours when taken on an empty stomach, respectively. These increases are not clinically relevant. The absolute bioavailability of dolutegravir has not been established.

Distribution

According to in vitro data, dolutegravir binds significantly to human plasma proteins ( 99.3% of fibroids).

The apparent volume of distribution (after oral suspension, Vd/F) is approximately 12.5 l. The binding of dolutegravir to plasma proteins was independent of concentration. The ratio of the total concentration of the radiolabeled drug in blood and plasma was 0.441-0.535, which indicates a minimal association of the radiolabeled drug with the cellular components of the blood.

The free fraction of dolutegravir in blood plasma is approximately 0.2-1.1% in healthy volunteers, approximately 0.4-0.5% in patients with moderate hepatic insufficiency,0.8-1.0% in patients with severe renal insufficiency, and 0.5% in patients infected with HIV-1.

Dolutegravir penetrates into the cerebrospinal fluid (CSF). In 12 previously untreated patients who took dolutegravir and abacavir / lamivudine II for 16 weeks, the average CSF concentration of dolutegravir was 15.4 ng / ml at week 2 and 12.6 ng / ml at week 16, with a range of 3.7 to 23.2 ng / ml (comparable to pre-bound plasma concentrations).

The ratio of dolutegravir concentration in CSF to plasma concentration ranged from 0.11 to 2.04%. Concentrations of dolugegravir in CSF exceeded IC50, which confirms a median decrease in the concentration of HIV-1 RNA in CSF compared to the initial concentration at 2.2 log tcc after 2 weeks of therapy and 3.4 log after 16 weeks of therapy (see section Pharmacodynamics”).

Delutegravir is found in the male and female genital tracts. AUC in cervical-vaginal fluid, cervical and vaginal tissues was 6-10% of that in blood plasma at steady state. AUC in seminal fluid was 7%, and in rectal tissues-17% of that in blood plasma at steady-state concentration.

Metabolism

Dolutegravir is primarily metabolized by uridine diphosphate-glucoronosyltransferase UDP-GT 1 A 1 with a minor component of the CYP3A isoenzyme (9.7% of the total dose taken in a human mass balance study).

Dolutegravir is the main compound circulating in the blood plasma, unchanged form is slightly excreted through the kidneys ( 53% of the total dose taken in hrv is excreted unchanged through the intestine.

It is not known whether this is due to incomplete absorption of the drug or excretion with bile of the glucuronide conjugate, which can then break down to form related compounds in the intestinal lumen. 31% of the total oral dose is excreted via the kidneys in the form of dolugegravir glucuronide ester (18.9% of the total dose). N-dealkylated metabolite (3.6% of the total dose) and a metabolite formed by cross-linking benzyl carbon (3.0% of the total dose).

Deduction

The final half-life of dolugegravir is approximately 14 hours, and the apparent clearance (CL/F) is 0.56 l / h.

Indications

Treatment of HIV-1 infection in adults and children aged 12 years and weighing 40 kg or more as part of combined antiretroviral therapy (APT).

Use during pregnancy and lactation

Fertility

There are no data on the effect of the drug Tivikay on the ability to conceive in men and in women. Animal studies have shown no effect of dolutegravir on the ability to conceive in males or females.

Pregnancy

Appropriate and well-controlled studies of the drug Tivicay in pregnant women have not been conducted.

The effect of Tivicay on pregnancy in women is unknown. In animal reproductive toxicity studies, dolutegravir has been shown to cross the placenta. Tivicay® can only be used during pregnancy if the expected benefit to the mother outweighs the potential risk to the fetus.

Breast-feeding period

It is recommended that HIV-infected patients refrain from breastfeeding their children in order to avoid vertical transmission of HIV infection.

Based on animal data, dolutegravir is expected to be excreted in women with breast milk, although this has not been confirmed in humans.

Contraindications

Hypersensitivity to dolutegravir or any other component introduced into the drug. Concomitant use with dofetilide or pelsicainide, children under 12 years of age and weighing less than 40 kg.

WITH CAUTION

Severe hepatic insufficiency (Child-Pugh class C);

When used concomitantly with medications (prescription and over-the-counter) that may change the effect of the drug Tivikay®, or drugs that may change the effect under the action of the drug Tivikay®.

Side effects

The adverse reactions presented below are identified by analyzing the combined data from Phase IIb and Phase III clinical trials and are listed according to organ and organ system involvement and frequency of occurrence. The frequency of occurrence is determined as follows: very common (≥ 1/10), common (≥ 1/100 and < 1/10), infrequent (≥ 1/1,000 and < 1/100), rare (≥ 1/10,000 and < 1/1,000) and very rare (

Frequency of adverse reactions

Immune system disorders

Infrequently: hypersensitivity reaction, immune recovery syndrome.

Mental disorders

Are Common: insomnia, unusual dreams, depression.

Infrequently: suicidal ideation or suicide attempt (especially in patients with a history of depression or mental illness).

Nervous system disorders

Very often: headache, often: dizziness.

Disorders of the gastrointestinal tract

Very common: nausea, diarrhea,

Often: vomiting, flatulence, upper abdominal pain, abdominal pain, abdominal discomfort.

Liver and biliary tract disorders

Infrequently: hepatitis.

Skin and subcutaneous tissue disorders

are common: rash, itching.

General disorders and disorders at the injection site

Often: fatigue.

Laboratory and instrumental data

are frequently used: increased activity of alanine aminotransferase (ALT) and / or aspartate aminotransferase (ACT), creatine phosphokinase (CPK).

The safety profile was similar in the populations of previously untreated patients, treated patients (and not treated with integrase inhibitors), and patients with resistance to integrase inhibitors.

Description of individual side effects

Changes in laboratory parameters

During the first week of treatment with Tivicay®, an increase in serum creatinine concentration was observed, which persisted for 48 weeks. The mean change in creatinine concentration at 48 weeks of therapy was 9.96 mmol/l.

The increase in creatinine concentration was comparable for different background therapy regimens. These changes are not considered clinically significant because they do not reflect changes in glomerular filtration rate.

Immune recovery syndrome

At the time of initiation of combined antiretroviral therapy (cART) HIV-infected patients with severe immunodeficiency may develop an inflammatory reaction against the background of asymptomatic opportunistic infections or their residual phenomena.

Cases of autoimmune diseases (such as Graves ‘ disease) have also been reported during immune recovery, but the time of initial manifestations varied, and the disease could occur many months after the start of therapy.

Use in children

Based on limited data on use in children and adolescents aged 12 to 18 years, it can be concluded that there are no additional types of adverse reactions, in addition to those observed in adults.

Co-infection with HIV and hepatitis B or C virus

Patients with hepatitis B and/or C virus co-infection were allowed to be included in Phase III studies, provided that the results of initial laboratory liver function indicators did not exceed the upper limit of normal (ULN) by more than 5 times.

Overall, the safety profile of patients with hepatitis B and/or C virus co-infection was the same as that of patients without hepatitis B or C virus co-infection, although the incidence of ACT and ALT activity abnormalities was higher in the subgroup of patients with hepatitis B and/or C virus co-infection in all treatment groups.

An increase in liver enzyme activity consistent with immune restoration syndrome has been observed in some patients with hepatitis B and/or C virus co-infection at the start of therapy with Tivicay®, especially in those who have withdrawn hepatitis B treatment.

Post-registration data

Musculoskeletal and connective tissue disorders

Infrequently: arthralgia, myalgia.

How to take, course of use and dosage

Therapy with Tivicay should be performed by a doctor with experience in the treatment of HIV infection

The drug Tivikay can be taken regardless of food intake.

Adults

Patients infected with HIV-1, without resistance to InI

The recommended dose of the drug Tivikay is 50 mg once a day.

When used concomitantly with efavirenz, nevirapine, rifampicin or tmpranavir in combination with ritonavir, the recommended dose of Tivicay in the DSH category of patients should be 50 mg 2 times a day.

Patients infected with HIV-1 with resistance to InI (documented or suspected clinically)

The recommended dose of the drug Tivikay* is 50 mg 2 times a day. The decision to use the drug Tivikai in such patients should be made taking into account drug resistance to InI.

Concomitant use with efavirenz, nevirapine, rifampicin or tipranavir in combination with ritonavir should be avoided in this category of patients.

Skipping medication

If a patient has missed a dose of Tivicay*, they should take the missed dose as soon as possible, if the next dose is at least 4 hours away. If there are less than 4 hours left before the next dose, the patient should not take the missed dose, and it is necessary to resume taking the drug according to the reception schedule.

Children aged 12-18 years and weighing 40 kg or more

Recommended dose of Tivicay for patients who have not previously received InI treatment (age-12-18 years, body weight 40 kg or more) it is 50 mg once a day.

There is insufficient data to recommend the dose of Tivicay to children aged 12-18 years with resistance to InI.

Special patient groups

Children under 12 years of age and weighing less than 40 kg

There are insufficient data on safety and efficacy to recommend the dose of Tivikai to children under 12 years of age or with a body weight of less than 40 kg.

Elderly patients

Data on the use of Tivicay in patients aged 65 years and older are limited. However, there are no data on the need for dose adjustment in elderly patients (see section “Pharmacokinetics” — “Special patient groups”).

Patients with impaired renal function

Patients with mild, moderate or severe renal impairment (CC No data are available for dialysis patients, but no differences in pharmacokinetics are expected in this population (see section “Pharmacokinetics — – ” Special patient groups”).

Patients with impaired liver function

Patients with mild or moderate hepatic impairment (Child-Pugh class A or B) do not require dose adjustment.

Overdose

Symptoms

Data on overdose of Tivicay are limited.

Limited experience with the use of higher single doses (up to 250 mg in healthy volunteers) did not reveal any special symptoms or signs, except for those described in the section “Side effects”.

Treatment

Further treatment should be carried out in accordance with the clinical indications or recommendations of the National toxicology Center, where applicable. There is no specific treatment for overdose with Tivicay.

In case of overdose, maintenance therapy and appropriate monitoring should be carried out. Due to the high binding of dolutegravir to plasma proteins, it is unlikely that a significant amount of it can be eliminated by dialysis.

Special instructions

Hypersensitivity reactions

Hypersensitivity reactions were reported with the use of InI, including the drug Tivikay, which were characterized by a rash, violation of systemic parameters and, sometimes, impaired organ function, including liver damage.

If signs or symptoms of hypersensitivity occur (including, but not limited to, a severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint pain).

Bullous lesions, oral mucosal lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema), the use of Tivicay and other medications that could cause such reactions should be immediately discontinued.

It is necessary to monitor the clinical condition, including indicators of hepatic aminotransferases, and conduct appropriate therapy.

A delay in discontinuing treatment with Tivicay* or other medications that could cause similar reactions, after the development of hypersensitivity reactions, can lead to life-threatening reactions.

Immune recovery syndrome

HIV-infected patients with severe immunodeficiency may experience an inflammatory response to asymptomatic or residual opportunistic infections at the time of initiation of APT, which may cause serious clinical conditions or aggravation of symptoms.

Typically, these reactions were observed within the first few weeks or months after the start of APT. Typical examples of these conditions are cytomegalovirus retinitis, generalized and / or focal mycobacterial infections, and pneumonia caused by Pneumocystis jiroveci (P. carinii).

Any inflammatory symptoms should be evaluated immediately and, if necessary, treatment should be initiated. Autoimmune diseases (such as Graves ‘ disease, polymyositis, and Guillain-Barre syndrome) were observed during immune recovery, but the time of initial manifestations varied, and the disease could occur many months after the start of therapy and have an atypical course.

At the beginning of therapy with Tivicay, some patients with coinfection with hepatitis B and or C showed increased activity of liver enzymes, reflecting the immune recovery syndrome. It is recommended to monitor the activity of liver enzymes in patients with hepatitis B and/or C coinfection.

Special monitoring should be given to the initiation or continuation of hepatitis B therapy (in accordance with current guidelines) in patients receiving treatment with dolutegravir (see section “Side effects”).

Opportunistic infections

Patients receiving Tivicay or other APT may develop opportunistic infections or other complications of HIV infection. Therefore, patients should be closely monitored by a clinician with experience in treating HIV-related diseases.

Transmission of infection

Patients should be notified that the risk of HIV transmission to others through sexual contact or blood has not been proven to be prevented by taking the currently available rattle APT. including the drug Tivicay. The necessary precautions should continue to be taken.

Interaction with other medicinal products

Caution should be exercised when using concomitantly with medications (prescription and over-the-counter) that may change the exposure of dolutegravir, or medications whose exposure may change under the influence of dolutegravir (see the section “Interaction with other medications”).

The recommended dose of Tivicay is 50 mg twice daily when used concomitantly with etravirine (without strengthening with protease inhibitors), efavirenz, nevirapine, tipranavir / ritonavir. rifampicin, carbamazepine, phenytoin, phenobarbital, and St. John’s wort (see “interaction with other medicinal products”).

The drug Tivikay should not be prescribed together with antacids containing ambivalent cations. It is recommended to use the drug Tivikay 2 hours before or 6 hours after the use of these drugs (see the section “Interaction with other drugs”).

It is recommended to take the drug Tivikai 2 hours before or 6 hours after taking calcium-containing or iron-containing dietary supplements, or, alternatively, take it with food (see the section “Interaction with other medications”).

The drug Tivicay increases the concentration of mctformin. Consideration should be given to adjusting the dose of metformin at the beginning and at the end of co-use of dolutegravir with metformin, in order to maintain glycemic control (see section “Interaction with other medicinal products”).

Resistance to integrase inhibitors of particular importance

When making a decision on the use of dolutegravir in the presence of resistance to AI, it should be taken into account that the activity of dolutegravir against viral strains carrying secondary mutations Q148 + >2 in the regions G140A/C/S, E 138 A/K/T, L74I significantly decreases.

The extent to which dolutegravir provides additional efficacy in the presence of such InI resistance remains unclear.

Osteonecrosis

Despite the fact that the etiology of this disease is multifactorial (including the use of corticosteroids, diphosphonates, alcohol consumption, severe immunosuppression, high body mass index), cases of osteonecrosis most often occurred in patients with late-stage HIV infection and / or long-term use of combined APT.

Patients should consult a doctor if they experience joint pain and stiffness or difficulty moving.

INFLUENCE ON THE ABILITY TO DRIVE VEHICLES AND MECHANISMS

No studies have been conducted on the effect of the drug Tivikay on the ability to drive TRPN vehicles and work with mechanisms. The patient’s clinical condition and adverse event profile of Tivicay® should be considered when considering the patient’s ability to drive or operate machinery.

Storage conditions

Store at a temperature not exceeding 30°C. Keep out of reach of children.

Shelf

life is 2 years.

Active ingredient

Dolutegravir

Conditions of release from pharmacies

Prescription