Olitide, 300 mg 60 pcs.

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Indications

Active ingredient

Composition

Active ingredient:

Abacavir sulfate: 351.0 mg, which corresponds to the content of abacavir: 300.0 mg,

Excipients:

Hydroxypropyl cellulose (Hyprolose), 24.0 mg;

sodium carboxymethyl starch (primogel), 24.0 mg;

Colloidal silicon dioxide (aerosil grade A-300) – 4.0 mg;

Magnesium stearate – 5.0 mg;

Microcrystalline cellulose – 98.0 mg.

Film jacket: Ready water-soluble film jacket – 14.0 mg. (Shell composition: hydroxypropyl methylcellulose (hypromellose) – 74.2%, polyethylene glycol 6000 (Macrogol 6000) – 14.3%, titanium dioxide – 3.5%, talc – 2.3%, iron oxide red dye – 1.4%, iron oxide yellow dye – 4.3%).

How to take, the dosage

The drug Olitide is taken orally, regardless of meals.

Adults, children and adolescents weighing more than 30 kg

The recommended daily dose is 600 mg. The drug is prescribed in a dose of 300 mg twice a day or 600 mg once a day.

In children 3 years of age and older with a body weight of less than 30 kg

In children with a body weight of 14-21 kg, the recommended dose is 150 mg twice daily or 300 mg once daily.

In children with a body weight of more than 21 kg and less than 30 kg, the recommended dose is 150 mg in the morning and 300 mg in the evening, or 450 mg once daily.

Patients with impaired renal function:

In patients with impaired renal function no adjustment of the drug dose is required.

Patients with impaired liver function

The use of the drug Olitide in patients with hepatic impairment is contraindicated.

Interaction

The results of in vitro studies and analysis of the main metabolic pathways of abacavir indicate that its interaction with other drugs mediated by cytochrome P450 isoenzymes is unlikely.

Abacavir does not inhibit metabolic processes involving CYP3A4 enzyme. In in vitro studies it has been shown that abacavir does not inhibit the activity of CYP3A4, CYP2C9 or CYP2D6 isoenzymes. Clinical studies have shown no induction of hepatic metabolism of exogenous substances under the action of the drug. Thus, interaction of abacavir with HIV protease inhibitors and other drugs metabolized with participation of main isoenzymes of cytochrome P450 system is unlikely.

Clinical studies have shown no clinically significant interactions between abacavir, zidovudine and lamivudine.

The use of abacavir concomitantly with rifampicin, phenobarbital and phenytoin (UDF-glucuronyltransferase inducers) may lead to a slight decrease in plasma concentrations of abacavir.

Ethanol slows the metabolism of abacavir, resulting in a 41% increase in the AUC of abacavir. However, the clinical significance of this change is small. Abacavir has no effect on ethanol metabolism.

According to pharmacokinetic studies, use of abacavir at a dose of 600 mg twice daily in combination with methadone decreases Cmax of abacavir in serum by 35%, increases time to maximum concentration in serum by 1 hour, but does not change AUC. The clinical significance of these changes is small. In the same study, abacavir was found to increase total methadone clearance by 22%. In most cases, these changes are also considered clinically insignificant, but certain situations may require a change in methadone dose. Retinoids, such as isotretinoin, are eliminated with alcohol dehydrogenase, so they may interact with abacavir, but to date there have been no specific studies.

In concomitant administration of abacavir and ribavirin it is possible to decrease concentration of phosphorylated metabolites of ribavirin that in turn can lead to decreased efficacy of treatment in patients co-infected with HIV and hepatitis C virus receiving therapy with pegylated interferon and ribavirin. Special caution should be exercised when concomitant administration of abacavir and ribavirin.

Special Instructions

The use of abacavir is not recommended in patients with the HLA-B*5701 allele and should be considered only in exceptional cases under close medical supervision when the potential benefit exceeds the risk associated with the use of the drug.

The clinical diagnosis of a suspected hypersensitivity reaction should remain the basis for the decision to use abacavir-containing drugs in all patients. Even in the absence of the HLA-B*5701 allele, abacavir should be discontinued and not restarted in all cases where a hypersensitivity reaction cannot be excluded based on clinical data because of the potential risk of serious adverse effects or even death.

Clinical picture. Hypersensitivity to abacavir is characterized by the appearance of symptoms suggestive of multiple organ involvement. Most patients report fever and/or rash as part of the syndrome.

Other symptoms of hypersensitivity to abacavir include fatigue, malaise, gastrointestinal disturbances including vomiting, nausea, diarrhea and abdominal pain; respiratory disturbances including shortness of breath, sore throat, cough, lung involvement (mostly as localized infiltrative changes seen on chest x-ray).

Symptoms of hypersensitivity can occur at any time after starting treatment with abacavir, but most commonly within the first six weeks. If treatment with abacavir continues while symptoms of hypersensitivity occur, they become more severe and may become life-threatening. After discontinuation of the drug, the symptoms of hypersensitivity usually reverse.

Patients treated with abacavir should be closely monitored for hypersensitivity during the first two months of treatment with consultations every two weeks, although it should be remembered that such reactions can occur later, at any time.

Screening for carriage of the HLA-B*5701 allele is recommended prior to re-prescribing abacavir in patients with unknown HLA-B*5701 -status who have previously tolerated abacavir therapy well. Re-prescribing abacavir to patients with the HLA-B*5701 allele is not recommended and should only be considered in exceptional cases under close medical supervision when the potential benefit of treatment with the drug outweighs all possible risks.

Patient Information Required

The physician prescribing the drug should advise the patient of the following information about the hypersensitivity reaction:

The patient must be made aware of the possibility of life-threatening hypersensitivity symptoms and the risk of death, as well as the increased risk of hypersensitivity reaction in carriers of the HLA-B*5701 allele;

The patient must be warned that even in the absence of the HLA-B*5701 allele a hypersensitivity reaction may develop. Thus, all patients should contact their physician immediately if symptoms that may be due to a hypersensitivity reaction occur, and patients with hypersensitivity to abacavir should be warned not to resume use of Olitide or other products containing abacavir, regardless of HLA-B*5701 status. – Patients who have had hypersensitivity reactions are advised to return the remaining tablets of Olitide to their physician to avoid reuse;

Patients who have interrupted treatment with Olitide for any reason (especially for possible adverse reactions or treatment complications) should see their physician before resuming the medication.

Lactoacidosis, hepatomegaly and fatty liver dystrophy

Lactoacidosis, hepatomegaly and fatty liver dystrophy, including death, have been reported following antiretroviral therapy with nucleoside analogues, including abacavir, taken alone or in combination. Most of these complications occur in women.

Symptoms indicative of lactoacidosis include general weakness, decreased appetite, rapid weight loss of unknown etiology, GI disturbances and respiratory disturbances (dyspnea and tachypnea).

The use of abacavir-containing drugs in any patient requires caution, especially if there are risk factors for liver damage. If clinical or laboratory signs of lactoacidosis or hepatotoxicity appear (may be manifested by hepatomegaly and fatty liver dystrophy, even in the absence of a marked increase in aminotransferase activity), treatment with abacavir should be stopped.

The redistribution of subcutaneous fat

Combination antiretroviral therapy may be accompanied by the development of one or more of the following symptoms obesity, redistribution of subcutaneous fat with deposition on the trunk, neck (“buffalo hump”), significant reduction in subcutaneous fat layer on the extremities and face, gynecomastia, increased serum lipid concentration and blood glucose levels.

All of these symptoms are manifestations of lipodystrophy. One or more of these symptoms may occur with treatment with any HIV protease inhibitors and nucleoside reverse transcriptase inhibitors. However, the risk of these adverse reactions depends on the drug used

Lipodystrophy syndrome has a complex etiology and can develop from a variety of factors that may act synergistically. HIV infection itself, advanced age of the patient and duration of antiretroviral therapy play an important role in its development.

In the clinical examination of patients, attention should be paid to redistribution of subcutaneous fat. Laboratory examination should include determination of serum lipid concentration and blood glucose levels. If lipid metabolism is disturbed, appropriate treatment is prescribed.

Mitochondrial dysfunction

The ability of nucleotide and nucleoside analogs to cause mitochondrial damage of varying degrees has been shown under in vitro and in vivo conditions. There are reports of mitochondrial dysfunction in HIV-negative children exposed to nucleoside analogues in utero or immediately after birth. The main manifestations of mitochondrial dysfunction, often transient, were anemia, neutropenia, hyperlactatemia, and increased plasma lipase activity. Later manifestations of this disorder have also been noted: hypertonicity of muscles, seizures, behavioral abnormalities.

Immune reconstitution syndrome

If HIV-infected patients with severe immunodeficiency have asymptomatic or asymptomatic opportunistic infections at the time of initiation of antiretroviral therapy (APT), the use of APT may lead to increased symptoms of opportunistic infections or other serious consequences. These reactions usually occur within the first weeks or months after initiation of APT. Typical examples are cytomegalovirus retinitis, generalized or focal infection caused by mycobacteria, and pneumonia caused by Pneumocystis jiroveci (P. carinii). The appearance of any symptoms of inflammation requires immediate evaluation and, if necessary, treatment. Autoimmune diseases (such as Graves’ disease, polymyositis and Guillain-Barré syndrome) were observed against the background of immune reconstitution, but the time of the primary manifestations varied, and the disease could occur many months after the start of therapy and have an atypical course.

Opportunistic infections

The use of abacavir or other antiretrovirals does not rule out the possibility of opportunistic infections or other complications of HIV infection, so patients should remain under the care of a physician experienced in treating HIV-associated disease.

Kidney dysfunction

In patients with impaired renal function, no dose adjustment of abacavir is necessary.

Hepatic impairment

The use of Olitide in patients with hepatic impairment is contraindicated.

Patients with chronic hepatitis B or C

The risk of hepatotoxic effects of antiretroviral drugs in patients with HIV and hepatitis B or C co-infection is higher than in those with HIV alone. Therefore, patients with chronic hepatitis B or C who take antiretroviral drugs at the same time are at increased risk of adverse effects on the liver, with possible death. These patients should be closely monitored, both clinically and laboratory.

The concomitant administration of abacavir and ribavirin may decrease concentration of phosphorylated metabolites of ribavirin, which in turn may lead to decreased treatment efficacy in patients co-infected with HIV and hepatitis C virus receiving pegylated interferon and ribavirin therapy. Special caution should be exercised when concomitant administration of abacavir and ribavirin.

Transmission

The provision of antiretroviral therapy, including abacavir, does not prevent sexual transmission of HIV or exposure to infected blood, and so appropriate precautions should not be taken.

Myocardial infarction

A prospective, observational, epidemiologic study to examine the incidence of myocardial infarction in patients receiving combination antiretroviral therapy found an association of prior, 6 months of abacavir administration with an increased risk of myocardial infarction. No increased risk of myocardial infarction associated with abacavir was observed according to a pooled analysis of clinical trials. The biological mechanisms explaining the potentially increased risk are unknown. In general, the available data from observational cohorts and controlled clinical trials do not unequivocally define an association between abacavir therapy and the risk of myocardial infarction.

Contraindications

Hypersensitivity to abacavir or any other component of the drug, hepatic insufficiency, children under 3 years of age and body weight less than 14 kg (for this dosage form).

Pregnancy, patients with possible risk of coronary heart disease.

Side effects

Hypersensitivity

Skin and subcutaneous fat: ≥10% – rash (usually maculopapular or uretic).

Gastrointestinal tract: ≥10% – nausea, vomiting, diarrhea, abdominal pain; ulceration of the oral mucosa is possible.

Hepatic and pancreatic disorders: ≥10% – increased liver enzyme activity; liver failure is possible.

Respiratory system: ≥10% – shortness of breath, cough; possible – sore throat, adult respiratory distress syndrome, respiratory failure.

Nervous system disorders: ≥10% – headache; paresthesias possible.

Hematopoietic system: lymphopenia is possible.

Muscular system: ≥10% – myalgia; rarely – myolysis, arthralgia, increased creatine phosphokinase (CPK) activity.

Urinary system disorders: increased serum creatinine concentration, renal failure are possible.

Other: ≥10% – fever, fatigue, malaise; edema, lymphadenopathy, arterial hypotension, conjunctivitis, anaphylactic reactions are possible. Hypersensitivity reactions may initially be regarded as a respiratory disease (pneumonia, bronchitis, pharyngitis, respiratory viral infection), gastroenteritis or as adverse reactions associated with taking other drugs. Continued use of abacavir if a hypersensitivity reaction develops, as well as resumption of use after symptoms have subsided, is fraught with serious consequences, up to and including death. Therefore, if any of the above symptoms occur, it is necessary to thoroughly examine the patient to rule out a hypersensitivity reaction. If a hypersensitivity reaction cannot be excluded, re prescription of Olitid or other abacavir-containing drugs is strictly contraindicated.

Occasionally a hypersensitivity reaction will develop when resuming therapy with abacavir after discontinuation, caused by the appearance of only one of the main symptoms of this reaction (rash, fever, malaise, fatigue, gastrointestinal or respiratory disturbances).

In rare cases, this reaction has occurred when patients who have not experienced any symptoms of hypersensitivity before discontinuing abacavir have resumed taking the drug.

The nature of other adverse events other than hypersensitivity observed in patients receiving abacavir is not fully understood. Whether these adverse events are due to the use of abacavir or other drugs administered concomitantly with it or to the disease itself has not yet been determined.

Many of the following adverse effects associated with abacavir administration (nausea, vomiting, diarrhea, fever, fatigue, rash) may also be seen when hypersensitivity reaction develops. Therefore, if any of these symptoms occur, careful evaluation of the patient is indicated to confirm or rule out a hypersensitivity reaction. If abacavir has been discontinued due to a suspected hypersensitivity reaction, resumption of the drug is prohibited. Resumption of therapy with abacavir after interruption due to the occurrence of the above symptoms should only be done after exclusion of a hypersensitivity reaction and under direct medical supervision. Most of the adverse reactions listed below do not limit the use of abacavir. Definition of the frequency of adverse reactions: very common (> 1/10), common (1/100 to 1/10), infrequent (1/1000 to 1/100), rare ( 1/10 000 to 1/1000) and very rare (frequency below 1/10 000).

Metabolic side: frequent – hyperlactatemia; rare – lactoacidosis, fatty tissue accumulation / redistribution, hypertriglyceridemia, hypercholesterolemia, insulin resistance, hyperglycemia.

The frequency of these adverse reactions depends on many factors, including the antiretroviral drugs used in combination with abacavir.

Gastrointestinal tract: frequently – nausea, vomiting, diarrhea; rarely – pancreatitis (causal relationship with the use of abacavir is not definitely established).

Hepatobiliary system: rarely – hepatitis, hepatomegaly, fatty liver dystrophy.

Nervous system disorders: often – headache.

Skin and subcutaneous fat: often – rash (in the absence of systemic manifestations); very rarely – erythema multiforme, including Stevens-Johnson syndrome and toxic epidermal necrolysis. Other: often – fever, somnolence, fatigue, loss of appetite.

Cases of osteonecrosis have been reported in patients with risk factors such as late-stage HIV infection or long-term combination antiretroviral therapy (incidence unknown).

Patients taking abacavir or other antiretrovirals may develop opportunistic infections or other complications of HIV infection.

Overdose

Symptoms: In clinical trials, patients received single doses of abacavir up to 1200 mg and daily doses up to 1800 mg. No adverse reactions have been reported. The effects of higher doses of abacavir are unknown.

Treatment: In case of overdose it is necessary to control patient’s condition in order to detect signs of intoxication and start treatment in time. If necessary symptomatic therapy is prescribed. There are no data on the possibility of abacavir excretion with hemodialysis and peritoneal dialysis.

Pregnancy use