Stokrin
Stokrin: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Stocrin
ATX code: J05AG03
Active ingredient: Efavirenz (Efavirenz)
Producer: Merck Sharp and Dome (Australia)
Description and photo update: 2019-07-08
Stokrin is a non-nucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase, an antiviral drug.
Release form and composition
- capsules (30 and 90 pcs. in vials or 6 pcs. in blisters, in a cardboard box 1 bottle or 7 packages);
- film-coated tablets, 200 mg: round, yellow, engraved on one side "223"; at the break - white (30, 60 and 90 pcs. in plastic bottles, 1 bottle in a cardboard box);
- film-coated tablets, 600 mg: capsule-shaped, yellow, engraved on one side "225" (30, 60 and 90 pcs. in plastic bottles, 1 bottle in a cardboard box).
The active substance is efavirenz:
- 1 capsule - 50, 100 or 200 mg;
- 1 tablet - 200 or 600 mg.
Additional components of the tablets:
- excipients: hyprolose, magnesium stearate, microcrystalline cellulose, sodium croscarmellose, lactose monohydrate, sodium lauryl sulfate;
- shell composition: Opadry yellow (Opadry ® Yellow), which includes titanium dioxide (E171), hypromellose 6cP (HPMC 2910), carnauba wax, macrogol (PEG400), iron dye yellow oxide (E172).
Pharmacological properties
Pharmacodynamics and pharmacokinetics
The antiviral effect of Stokrin is due to the ability of efavirenz to selectively inhibit HIV-1 reverse transcriptase. The dominant type is the non-competitive type of inhibition.
Efavirenz does not inhibit the synthesis of cellular DNA polymerases and HIV-2 transcriptase in humans. The adsorption and time to reach the maximum concentration of efavirenz in blood plasma in HIV-infected and healthy people are practically the same. In uninfected individuals, efavirenz at concentrations of 1.6-9.1 μM is detected in blood plasma 5 hours after administration, regardless of the dose taken (it can vary in the range of 100-1600 mg) and the duration of the course of treatment. A week later, stable concentrations of this substance are recorded in the blood plasma. In the infected, the maximum concentration and the time to reach it are determined by the value of the daily dose.
It was noted that when the tablets were taken with fatty foods, the concentration of efavirenz in the body remained constant for longer.
The degree of binding of efavirenz to plasma proteins, mainly albumin, is quite high. The concentration of the bound substance in plasma is approximately 3 times higher than the content of its free fractions. Efavirenz easily penetrates into the cerebrospinal fluid and is metabolized in the liver and blood plasma. The half-life from the blood is 52–76 hours with a single dose or 40–55 hours with regular treatment. Also, the time of elimination from the body increases with severe liver dysfunctions. Efavirenz is excreted in urine and feces.
Indications for use
Stokrin is a drug used for combination therapy of HIV infection.
Contraindications
For all forms of release:
- hepatic failure of moderate and severe degree;
- the simultaneous use of ergot alkaloids (for example, dihydroergotamine, ergotamine, ergonovine, methylergonovine), triazolam, pimozide, midazolam, bepridil, cisapride, astemizole, terfenadine;
- simultaneous use of preparations / herbal products containing St. John's wort;
- hypersensitivity to any component of the drug.
Additionally, for capsules - children under 3 years of age and body weight less than 13 kg.
Additionally for tablets:
- lactose intolerance, lactase deficiency, glucose-galactose malabsorption;
- children under 3 years old and children weighing less than 13 kg (for 200 mg tablets), children weighing less than 40 kg (for 600 mg tablets).
Carefully:
- a history of psychiatric disorders in patients at risk of developing serious adverse reactions from the psyche;
- mild to moderate liver disease;
- a history of convulsions;
- concomitant use of anticonvulsants metabolized primarily in the liver, such as phenobarbital, phenytoin, and carbamazepine.
Instructions for use of Stokrin: method and dosage
Stocrin should be taken orally, preferably at bedtime and on an empty stomach (since side effects may increase when taken with meals).
Treatment should be carried out by a physician experienced in HIV therapy.
The drug is used in combination with other antiretroviral drugs.
Adults
The drug is prescribed at 600 mg 1 time per day in combination with nucleoside reverse transcriptase inhibitors (NRTIs), without or with an HIV protease inhibitor. However, you should consider:
- if Stokrin is used in combination with rifampicin in patients weighing 50 kg or more, it may be necessary to increase the dose of efavirenz to 800 mg once a day;
- if Stokrin is used concurrently with voriconazole, the dose of the latter should be increased to 400 mg 2 times a day, and the dose of efavirenz should be reduced by 50%, i.e., to 300 mg (however, tablets with such a dose are not registered in the Russian Federation). After the end of the course of taking voriconazole, the dose of Stokrin is increased to the initial dose of 600 mg.
Children from 3 years old (or weighing more than 13 kg)
Stocrin is given in combination with an HIV protease inhibitor and / or an NRTI.
Recommended doses depending on the weight of the child:
- 13-15 kg - 200 mg;
- 15-20 kg - 250 mg;
- 20-25 kg - 300 mg;
- 25-32.5 kg - 350 mg;
- 32.5-40 kg - 400 mg;
- more than 40 kg - 600 mg.
Side effects
- disorders of the skin and subcutaneous tissues: very often (≥1 / 10) - skin rashes; often (≥1 / 100, <1/10) - itchy skin; infrequently (≥ 1/1000, <1/100) - exudative erythema multiforme, Stevens-Johnson syndrome; rarely (≥ 1/10 000, <1/1000) - photoallergic dermatitis *;
- mental disorders: often - insomnia, pathological dreams, depression, anxiety; infrequently - paranoid behavior, confusion, aggression, hallucinations, tendency to euphoria, mania, suicidal intentions and attempts, tendency to affect, psychosis *; rarely - neurosis *, delirium *, death due to suicide *;
- disorders of the nervous system: often - dizziness, headaches, attention disorder, drowsiness, impaired cerebellar coordination and balance *; infrequently - impaired coordination of movements, ataxia, convulsions, amnesia, impaired thinking, anxiety, tremor *;
- disorders of the immune system: infrequently - hypersensitivity reactions;
- disorders of the liver and biliary tract: often - increased activity of gamma-glutamyl transferase (GGT), aspartate aminotransferase (ACT) and alanine aminotransferase (ALT); infrequently - acute hepatitis; rarely - liver failure *;
- vascular disorders: infrequently - rush of blood to the skin of the face *;
- disorders of the gastrointestinal tract: often - abdominal pain, nausea, diarrhea, vomiting; infrequently - pancreatitis;
- violations of the genitals and mammary gland: infrequently - gynecomastia;
- disorders of the organ of vision, organ of hearing and labyrinth disorders: infrequently - blurred vision, vertigo, tinnitus *;
- metabolic and nutritional disorders: often - hypertriglyceridemia; infrequently - hypercholesterolemia;
- general disorders: often - increased fatigue.
* These side effects were recorded in the post-registration period of observation.
Overdose
In some patients who accidentally took efavirenz 600 mg 2 times a day, there was an increase in side effects from the central nervous system (for example, involuntary muscle contractions).
In case of an overdose of the drug, general supportive measures are carried out, including monitoring the patient's clinical condition and monitoring the basic indicators of the body's vital activity. Activated carbon is prescribed to remove unabsorbed efavirenz. There is no specific antidote for cases of Stokrin overdose. Because efavirenz is highly protein bound, dialysis is unlikely to remove large amounts of this substance from the body.
special instructions
Stokrin should not be used as the only drug for treating HIV infection, as viral resistance can quickly develop. Also, do not add efavirenz as the only agent to an ineffective regimen.
When choosing new antiretroviral drugs for use in combination with efavirenz, the likelihood of developing viral cross-resistance should be considered.
During antiretroviral therapy (ART), the risk of transmission of HIV to others through blood or sexual contact is not excluded, and therefore it is recommended that appropriate precautions are taken.
It is not recommended to prescribe Stocrin at the same time as tablet forms of drugs with fixed combinations of emtricitabine, efavirenz, tenofovir disoproxil fumarate.
When prescribing any other drug in combination, the medical instructions for their use should be considered.
If any antiretroviral agent used in combination ARVT is canceled due to suspicion of intolerance, all antiretroviral drugs should be canceled at the same time, if possible, and after the disappearance of symptoms of intolerance, resume taking. It is not recommended to administer intermittent monotherapy and consistently re-prescribe antiretroviral drugs, since the likelihood of a virus resistant to therapy is high.
According to the instructions, Stokrin can cause side effects from the central nervous system (including insomnia, impaired attention and dizziness). If they appear, it is recommended to refrain from driving and performing potentially dangerous types of work.
Application during pregnancy and lactation
During treatment with efavirenz, conception must be avoided, therefore it is recommended to use reliable methods of barrier contraception in combination with other methods (including oral or other hormonal contraceptives). Since the half-life of efavirenz from the body is long enough, reliable contraception should be used within 12 weeks after drug withdrawal. All women of reproductive age must have a pregnancy test before starting Stokrin.
The drug is not recommended for use during pregnancy, unless the likely benefit of the treatment to the mother outweighs the potential risk to the fetus, and there are no alternative treatments. If the patient is taking Stocrin during the first trimester of pregnancy, or pregnancy has occurred during therapy with efavirenz, she should be warned about the possible consequences for the health of the fetus.
Adequate and well-controlled clinical studies of the effects of efavirenz on a pregnant woman have not been conducted. In some cases of the use of efavirenz as an element of combination antiretroviral therapy (ARVT) during the first trimester of pregnancy, in most cases, there was no increase in the incidence of malformations in newborns, with the exception of isolated reports of neural tube defects (including meningomyelocele) diagnosed in infants. Such reports were retrospective, so the causal relationship was not reliably determined.
Efavirenz passes into breast milk, however, there is no clinically confirmed data on its effect on newborns and infants. Women who are prescribed the drug during lactation are advised to stop breastfeeding. HIV-infected mothers are strongly advised not to breastfeed their babies under any circumstances to avoid infecting their children with HIV.
Pediatric use
For children over 3 years of age, doses are selected in accordance with body weight. Efavirenz is prescribed only for children who can swallow tablets. The safety and effectiveness of taking the drug in children under 3 years of age or weighing less than 13 kg have not been proven.
With impaired renal function
In patients with renal failure, the pharmacokinetics of efavirenz are poorly understood. However, due to the fact that less than 1% of the accepted dose of Stokrin is excreted through the kidneys, renal dysfunction should not significantly affect the excretion of efavirenz. There is no experience in the treatment of patients with severe renal insufficiency with the drug, therefore, in this case, careful monitoring of the safety of using Stokrin is required.
For violations of liver function
The appointment of Stokrin is contraindicated in patients with hepatic insufficiency (class C on the Child-Pugh scale) and is not recommended for patients with moderate liver damage, since today there is no reliable information on the basis of which a decision on dose adjustment can be made.
Due to the intensive metabolism of efavirenz with the participation of the cytochrome P 450 system and limited experience with the use of the drug in patients with chronic liver disease, caution should be exercised during treatment with Stokrin for mild liver disease. In this case, patients are left under observation for the timely detection of dose-dependent undesirable effects, especially from the central nervous system. Also, at regular intervals, it is recommended to monitor laboratory parameters indicating the state of the liver.
The safety and effectiveness of efavirenz therapy has not been proven in patients with a history of significant liver dysfunction. Patients with chronic hepatitis B or C undergoing combined ART are at risk of developing severe liver complications that can cause death.
Patients with a history of liver dysfunctions (including those with chronic active hepatitis) have an increased incidence of liver dysfunctions during combined ARVT, so they should remain under medical supervision according to the standard regimen. If a patient has a worsening of chronic liver disease or a sustained increase in serum transaminase activity, more than 5 times the ULN, it is necessary to compare the benefits of treatment with efavirenz with the likely risk of a hepatotoxic effect. In this case, it is recommended to consider the feasibility of canceling or temporarily interrupting ART.
When efavirenz is combined with other drugs with known hepatotoxicity, liver enzyme activity should be monitored. In patients with hepatitis B or C, when prescribing combination antiviral therapy, doctors are guided by the instructions for the use of drugs prescribed for the treatment of hepatitis.
Use in the elderly
Elderly patients were included in clinical studies of the effect of efavirenz on the body. Their results showed that the effect of efavirenz on the body in patients of this category is identical to that in patients of a younger age.
Drug interactions
Stokrin should not be used concomitantly with the following drugs: terfenadine, cisapride, astemizole, midazolam, bepridil, pimozide, ergot alkaloids (eg, ergometrine, methylergometrine, ergotamine, dihydroergotamine). This is due to the fact that such combinations can lead to the development of serious and even life-threatening consequences.
You should not take drugs or products containing St. John's wort at the same time, as it can significantly reduce the plasma concentration of efavirenz. It should be borne in mind that the effect of St. John's wort can persist for at least 2 weeks after its withdrawal.
With the combined use of efavirenz can reduce the concentration in blood plasma of compounds that are substrates of isoenzymes CYP3A4, CYP2B6 and UDP-GT1A1.
It is not recommended to prescribe efavirenz in combination with ritonavir and atazanavir. If their use becomes necessary, consideration should be given to increasing the dose of ritonavir to 200 mg and atazanavir to 400 mg in combination with efavirenz. Treatment in this case should be carried out under close clinical monitoring.
Avoid using the drug in combination with fosamprenavir / saquinavir, atovachone / proguanil, posaconazole.
With simultaneous use of darunavir / ritonavir with efavirenz, the concentration of darunavir may decrease.
Efavirenz reduces the plasma concentration of indinavir, boceprevir, voriconazole.
When Stocrin is given in combination with low-dose ritonavir, there may be an increase in the incidence of EFV-related adverse events.
In the case of concomitant administration of lopinavir / ritonavir in the form of soft capsules or oral solution, there is a significant decrease in the exposure to lopinavir.
If rifabutin is planned, the dose should be increased by 50%.
If it is necessary to prescribe telaprevir, its dose should be increased to 1125 mg 3 times a day.
Efavirenz reduces the concentration of clarithromycin. Although the clinical significance of these changes has not been established, another antibiotic, such as azithromycin, is recommended.
Rifampicin decreases the concentration of efavirenz.
In the absence of recommendations on the dosing regimen of itraconazole and ketoconazole, the possibility of prescribing alternative antifungal drugs should be considered. The same goes for carbamazepine - another anticonvulsant is recommended.
With the simultaneous use of anticonvulsants that are substrates of CYP450 isoenzymes (for example, phenytoin, phenobarbital), their concentration in the blood should be monitored.
Caution should be exercised when using efavirenz with artemether and lumefantrine in combination.
The interaction of efavirenz with warfarin and acenocoumarol has not been studied. Presumably, both a decrease and an increase in their concentrations are possible, therefore, dose adjustment may be required.
In the case of the simultaneous use of valproic acid, patients should be under medical supervision to control seizures.
Stokrin reduces the effectiveness of hormonal contraceptives (oral, prolonged-release for intramuscular administration and implants).
Patients who receive atorvastatin, pravastatin or simvastatin during the period of treatment require periodic monitoring of the concentration of cholesterol in the blood.
If it is necessary to use immunosuppressants, their blood concentrations should be carefully monitored for at least 2 weeks from the start of therapy with efavirenz or its end (until stable concentrations are established). Dose adjustment of the immunosuppressant may be required.
In case of concomitant use of methadone, patients should be under close medical supervision for timely detection of withdrawal symptoms. Increasing the methadone dose may be required to reduce withdrawal symptoms.
Analogs
Stokrin's analogues are: Arverenz, Effakhon, Estiva, Efkur, Efavir, Eferven, Efamat, Efavirenz.
Terms and conditions of storage
Keep out of reach of children at temperatures up to 25 ° C.
The shelf life is 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Stokrin
Many reviews about Stokrin are favorable. Side effects are observed in a small number of patients treated with the drug. However, cases when it had to be replaced with another drug are registered. It is noted that the course of therapy makes it possible to achieve a persistent improvement in the state of health, which lasts for several years.
Price for Stokrin in pharmacies
The price for Stokrin in a dosage of 200 mg averages 1060–1200 rubles (90 pcs per pack). You can buy the drug in a dosage of 600 mg for 380–430 rubles (30 pcs per pack).
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
