Emtritab pills 200mg 30pcs

Composition

Active ingredient:

Emtricitabine 200 mg

Auxiliary substances:

Core: pregelatinized starch-12.0 mg, colloidal silicon dioxide (aerosil brand A-300) – 2.0 mg, croscarmellose sodium-12.0 mg, lactose-118.0 mg, magnesium stearate-4.0 mg, microcrystalline cellulose-40.0 mg.

Film coating: hydroxypropylmethylcellulose (hypromellose) – 8.7 mg, copovidone 0.3 mg, macrogol 6000-1.74 mg, talc-0.3 mg, titanium dioxide-0.96 mg

Pharmacological action

Pharmacotherapy group: antiviral [HIV] sredstvo ATH: J. 05. A. F. 09 Emtricitabine Pharmacodynamics : Synthetic nucleoside analog of cytidine. The mechanism of action is associated with the suppression of HIV-1 reverse transcriptase activity. Emtricitabine is phosphorylated to the active metabolite emtricitabine – 5′-triphosphate inside the cell. Emtricitabine-5′ – triphosphate inhibits HIV-1 reverse transcriptase by a competitive mechanism, resulting in an interruption of DNA chain synthesis.

Emtricitabine 5′ – triphosphate is a weak inhibitor of mammalian DNA polymerases a, b, and e and mitochondrial DNA polymerase y.

Antiviral activity

The antiviral activity of emtricitabine against laboratory and clinical isolates of HIV-I strains was evaluated on lymphoblastoid cell lines (MAGI-CCR5 cell line) and peripheral blood mononuclear cells. The concentration of emtricitabine EC 50 (EC 50 is the concentration of the drug required to suppress 50% of viruses) ranged from 0.0013 to 0.64 mmol.

In cell culture, emtricitabine showed antiviral activity against HIV-1 subtypes A, B, C, D, E, and F. G (EC50 was 0.007-0.075 mmol), as well as inhibitory effect on some HIV-2 strains (ec50 was 0.007-1.5 mmol).

Resistance

Resistance to emtricitabine has been observed in vitro in some HIV-1 infected patients due to substitution of reverse transcriptase codons M184V or Ml841. No other mechanisms of emtricitabine resistance have been identified.

Cross-resistance

Emtricitabine-resistant strains with substitution at codon M184V / 1 showed cross-resistance to lamivudine, but remained sensitive to didanosine, stavudine, tenofovir, and zidovudine. Virus strains with substitutions that cause a decrease in sensitivity to stavudine, and with mutations of resistance to zidovudine analogues-thymidine (M41L, D67N, K70R, L210W, T215Y/F, K219Q/E) or didanosh Ea (L74V) remained sensitive to emtricitabine. HIV-1 strains containing a KINASE substitution or other substitutions associated with resistance to rilpivirine and other nucleoside NMR reverse transcriptase inhibitors remained sensitive to emtricitabine. Pharmacokinetics: When taken orally, emtricitabine is rapidly absorbed from the gastrointestinal tract. Food does not significantly affect the bioavailability of emtricitabine. With repeated oral use at a dose of 200 mg / day, the maximum concentration (Cmax)of emtricitabine in blood plasma is 1.8±0.7 mcg/ml, and the area under the concentration-time curve in the observation interval from 0 to 24 hours (AUC0-24) is 10.0±3.1 mcg*h/ml. The time to reach the maximum concentration in the blood (TMAX) is 1-2 hours.

The average values of the minimum plasma concentrations of emtricitabine 24 hours after use at steady state are or exceed the average value of IC90-the concentration required to suppress the replication of 90% of viruses in vitro. With repeated use in the dose range from 25 to 200 mg, the pharmacokinetic parameters of emtricitabine are proportional to the dose.

The binding of emtricitabine to plasma proteins in vitro is less than 4% and does not depend on the concentration in the range from 0.02 to 200 mcg / ml. Data from in vitro studies indicate that emtricitabine has no inhibitory effect on human cytochrome p450 isoenzymes. Emtricitabine is mainly excreted by the kidneys (approximately 86%) and through the intestines (approximately 14%).13% of the administered dose of emtricitabine was detected in the urine as three suspected metabolites. The average systemic clearance of emtricitabine is 307 ml/min.

Metabolites of emtricitabine include Z’ – sulfoxnde diastereomers (approximately 9% of the dose) and their conjugate with glucuronic acid in the form of 2-O-glucuronide (approximately 4% of the dose). After a single oral dose, the elimination half-life (T 1/2) of emtricitabine is approximately 10 hours. With subsequent dosing in the course mode, the value of the intracellular T 1/2 of emtricitabine-5′ – triphosphate (the active metabolite of emtricitabine) in peripheral blood mononuclear cells is 39 hours.

Emtricitabine is eliminated by glomerular filtration and active tubular secretion.

Special patient groups

Patients with impaired renal function

In patients with impaired renal function (creatinine clearance < 80 ml/min), the pharmacokinetics of emtricitabine are altered. Systemic exposure to emtricitabine (mean ± standard deviation) increased from 11.8 ± 2.9 mcg * h / ml in patients with normal renal function to 19.9 ± 1.1 mcg*h / ml,25.0 ± 5.7 mcg*h / ml, and 34.0 ± 2.1 mcg*h/ml in patients with creatinine clearance of 50-80 ml / min,30-49 ml / min, and

Patients with impaired liver function

The pharmacokinetics of emtricitabine have not been studied in patients with hepatic insufficiency.

Gender and race

No significant differences in pharmacokinetic parameters were observed in adult males and females and in different races.

Children

In general, the pharmacokinetics of emtricitabine in children are similar to those in adults. When taking emtricitabine at a dose of 50 mg/kg per day, the average AUC0-24 values in children are comparable to those in adults when taking the drug at a dose of 200 mg once a day.

Elderly patients

There are no data on the pharmacokinetics of emtricitabine in patients over 65 years of age.

Indications

Treatment of HIV-1 infection in combination antiretroviral therapy

Use during pregnancy and lactation

No adequate and well-controlled studies have been conducted in pregnant women. Emtricitabine should be used in pregnant women only when absolutely necessary, in cases where the expected benefit to the mother exceeds the possible risk to the fetus. Emtricitabine has been shown to be excreted in breast milk. Experts do not recommend that HIV-infected patients breastfeed to avoid transmitting HIV infection to their child. Since emtricitabine and HIV infection pass through breast milk, breast-feeding is contraindicated.

Contraindications

Hypersensitivity to emtricitabine and other components of the drug.

Children under 3 years of age and weighing less than 33 kg (for this dosage form).

Lactation period.

Concomitant use with combination drugs containing emtricitabine, as well as with lamivudine, zalcitabine.

Lactase deficiency, lactose intolerance, glucose-galactose malabsorption. since the drug contains lactose.

With caution:

Renal insufficiency, elderly age, pregnancy, liver diseases, simultaneous use with drugs that are eliminated by active tubular secretion.

Side effects

From the side of the blood system and hematopoietic organs:  often-neutropenia; infrequently-anemia.

From the immune system: often-allergic reactions.

From the digestive system: very often – diarrhea, nausea; often-increased amylase activity, including increased pancreatic amylase activity; increased serum lipase activity, vomiting, abdominal pain, dyspepsia.

From the nervous system: very often – headache, often-dizziness. Mental disorders: often – insomnia, pathological dreams.

From the side of the hepatobiliary system:  often increased activity of – aspartate aminotransferase (ACT) and / or serum alanine aminotransferase (ALT), hyperbilirubinemia.

From the side of the skin:  often-vesiculobullous rash, pustular rash, maculopapular rash, rash, pruritus, urticaria, skin discoloration (increased pigmentation); infrequently – angioedema.

Musculoskeletal and connective tissue disorders:  very often – increased creatine kinase activity.

Other services:  pain, asthenia.

Combined antiretroviral therapy was associated with metabolic disorders such as hypertriglyceridemia, hypercholesterolemia, hyperglycemia and hyperlactatemia; redistribution/accumulation of subcutaneous fat (lipodystrophy).

Lactic acidosis has been reported in HIV-infected patients treated with nucleoside analogues, which is usually accompanied by severe hepagomegaly and fatty liver disease. The frequency of development depends on many factors, including the specific combination of antiretroviral drugs.

Cases of osteonecrosis have been reported in patients with risk factors such as advanced HIV infection or long-term combination antiretroviral therapy.

Patients taking emtricitabine or other antiretroviral drugs may develop opportunistic infections or other complications of HIV infection.

Children

In clinical studies, the side effects of the drug in children and adults were similar. Most often, the development of hyperpigmentation was noted. An additional adverse reaction reported in clinical trials in children was anemia.

How to take it, course of use and dosage

Inside as part of a combination therapy, regardless of food intake.

Adults (aged 18 years and older) emtricitabine is prescribed 200 mg once a day.

Children under 18 years of age and weighing more than 33 kg: 200 mg once a day.

If the delay in taking the drug is less than 12 hours, the missed dose should be taken as soon as possible and the usual dosage regimen should be resumed. If

the delay in taking the drug is more than 12 hours, the missed dose should not be taken; the next dose of emtricitabine is taken at the usual time.

If the patient experiences vomiting within 1 hour of taking the drug, another dose of emtricitabine should be taken. If the patient vomits more than 1 hour after taking the drug, there is no need to take an additional dose of emtricitabine until the next scheduled dose of the drug is received.

Patients with impaired renal function

In patients with renal insufficiency, the following dosage regimen of emtricitabine is recommended: for creatinine clearance > 50 ml/min,200 mg every 24 hours; for creatinine clearance 30-49 ml/min,200 mg every 48 hours; for creatinine clearance 15-29 ml/min,200 mg every 72 hours. With creatinine clearance If the drug is taken on the day of dialysis, emtricitabine is taken after the hemodialysis session or dialysis is performed at least 12 hours after the last dose of emtricitabine.

In children with impaired renal function, the same dosage adjustment scheme is recommended depending on the creatinine clearance value as in adults. Patients with impaired liver function

The use of emtricitabine has not been studied in patients with hepatic impairment. The drug should be used with caution in this category of patients.

Elderly patients

The use of emtricitabine has not been studied in patients over 65 years of age. The drug should be used with caution in this category of patients due to a possible decrease in the excretory function of the kidneys.

Overdose

In case of overdose, the patient should be examined for possible signs of intoxication. If necessary, standard maintenance therapy is used.

To eliminate emtricitabine, hemodialysis is possible, and a 3-hour hemodialysis procedure removes approximately 30% of the drug dose. Interaction with other medicinal products

The probability of pharmacokinetic interaction with drugs that are metabolized with the participation of CYP450 isoenzymes is low, since emtricitacin is not an inhibitor of these isoenzymes.

Emtricitabine is mainly excreted by the kidneys. Concomitant use of emtricitabine with drugs that impair renal function or compete for active tubular secretion may lead to increased serum concentrations of emtricitabine and/or other drugs that are excreted by the kidneys. When emtricitabine was administered in combination with zidovudine, indinavir, stavudine, famciclovir and tenofovir disoproxil fumarate, there were no clinically significant pharmacokinetic interactions between these drugs and emtricitabine.

Special instructions

Emtricitabine should not be administered concomitantly with combination medications containing emtricitabine, as well as with medications that contain lamivudine (due to its similarity to emtricitabine).

Patients should be warned that treatment with antiretroviral drugs, including emtricitabine, does not prevent the risk of HIV transmission to other people through sexual contact or blood transfusions. Therefore, patients should take appropriate precautions.

Opportunistic infections

Patients receiving emtricitabine or other antiretroviral drugs may develop opportunistic infections or other complications, so they should be closely monitored by a doctor with experience in treating HIV infection.

Impaired renal function

In patients with renal insufficiency (with creatinine clearance

The pharmacokinetics of emtricitabine in patients with hepatic insufficiency have not been studied. However, since emtricitabine is only slightly metabolized in the liver, no significant effect of hepatic insufficiency on the pharmacokinetics of the drug is expected.

Lactic acidosis / severe hepatomegaly with fatty liver disease Cases of lactic acidosis have been reported in HIV-infected patients (mainly women) who took nucleoside analogues as monotherapy or in combination with other antiretroviral drugs, which was usually accompanied by severe hepatomegaly and fatty liver disease, including with a fatal outcome. Symptoms that may indicate the development of lactic acidosis include: general weakness, loss of appetite, sudden unexplained weight loss, disorders of the gastrointestinal tract and respiratory system (shortness of breath), the appearance of neurological symptoms (including movement disorders). Lactic acidosis leads to high mortality in the absence of urgent treatment and may be associated with pancreatitis, liver or kidney failure. Lactic acidosis, as a rule, manifests itself after several months of therapy. Patients with co-morbid hepatitis C receiving interferon alpha and ribavirin therapy may be particularly at risk. Such patients require careful monitoring.

Treatment with emtricitabine always requires caution, and especially if the patient has risk factors for developing liver disease. In case of clinical or laboratory signs of lactic acidosis or impaired liver function (including hepatomegaly and fatty liver dystopia, even in the absence of a significant increase in the level of hepatic transaminases), emtricitabiine should be discontinued. Redistribution/accumulation of subcutaneous fat

In some patients, combined antiretroviral therapy may be accompanied by a redistribution/accumulation of subcutaneous fat, including a decrease in the amount of peripheral fat and an increase in visceral fat, weight loss of the limbs and face, an increase in the mammary glands and fat deposition along the back of the neck and back (“buffalo hump”), as well as an increase in serum lipids and blood glucose levels. Although one or more of the above-mentioned adverse reactions associated with the common syndrome, often referred to as lipodystrophy, can be caused by all drugs from the classes of protease inhibitors and nucleoside reverse transcriptase inhibitors, accumulated data indicate that there are differences between individual representatives of these drug classes in the ability to cause these adverse reactions.

It should also be noted that lipodystrophy syndrome has a multifactorial etiology; for example, the stage of HIV infection, old age, and duration of antiretroviral therapy play an important, possibly synergistic role in the development of this complication. The long-term consequences of these adverse reactions are currently unknown. Clinical examination of patients should include assessment of physical signs of adipose tissue redistribution. Serum lipids and blood glucose concentrations should also be measured. Lipid metabolism disorders should be corrected based on their clinical manifestations.

Immune recovery syndrome

Patients who received combination antiretroviral therapy, including emtricitabine, developed immune recovery syndrome. When immune function is restored, asymptomatic or residual opportunistic infections (including those caused by Mycobacterium avium, Mycobacterium tuberculosis, Pneumocystis carinii, Cytomegalovirus) may worsen, which may require additional examination and treatment. 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.

Osteonecrosis. Despite the fact that the etiology of osteonecrosis is considered to be multifactorial (including the use of glucocorticosteroids, alcohol consumption, severe immunosuppression, high body mass index), cases of osteonecrosis have been reported in particular in patients with advanced HIV infection and/or long-term combined antiretroviral therapy. Patients should be advised to consult a doctor if they experience joint pain, stiffness in the joints, or difficulty moving.

Mitochondrial dysfunction

In vitro and in vivo studies revealed the ability of nucleotide and nucleoside analogues to cause various degrees of mitochondrial damage. Mitochondrial disorders have been reported in HIV-negative newborns exposed to intrauterine and / or postnatal exposure to nucleoside analogues. The main manifestations of mitochondrial dysfunction are hematological disorders (anemia, neutropenia) and metabolic disorders (hyperlactatemia, hyperlipazemia). These changes are often temporary.Some long-term neurological disorders (hypertension, seizures, behavioral disorders) have been reported. All children who have been exposed to nucleosides or nucleoside analogues in utero, even HIV-negative newborns, should be carefully monitored for signs or symptoms and undergo a thorough examination for possible mitochondrial disorders.

Patients who are simultaneously infected with HIV and hepatitis B virus or C

The risk of hepatotoxic effects of antiretroviral drugs in patients with co-infection with HIV and hepatitis B or C virus is higher than in the presence of HIV infection alone. Therefore, patients with chronic hepatitis B or C who are simultaneously taking antiretroviral drugs are at an increased risk of adverse effects on the liver with a possible fatal outcome. Such patients should be carefully monitored, both clinically and in the laboratory.

Discontinuation of emtricitabine therapy may cause severe exacerbation of hepatitis in patients infected with the hepatitis B virus (HBV). Therefore, before starting anti-retroviral therapy, it is recommended to examine patients for hepatitis B virus. In patients infected with HIV-1 and HBV, liver function should be carefully monitored, at least for several months after discontinuation of emtricitabine. In some cases, it may be necessary to resume therapy for viral hepatitis. In patients with severe liver disease (cirrhosis), it is not recommended to stop treatment, since the exacerbation of hepatitis that occurs after discontinuation of therapy can lead to decompensation of liver function.

Influence on the ability to drive vehicles and mechanisms:There was no specific study of the effect of emtricitabine on the ability to drive a car and work with machinery. However, when evaluating the patient’s ability to drive a car or move machinery, the patient’s general condition and the nature of emtricitabine adverse reactions should be taken into account. If dizziness occurs, you should refrain from performing these activities.

Storage conditions

Store in the original manufacturer’s packaging at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Shelf

life is 2 years. Do not use after the expiration date indicated on the package.

Active ingredient

Emtricitabine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets