Ziagen^® (Solution) Instructions for Use

Marketing Authorization Holder

ViiV Healthcare UK, Limited (United Kingdom)

Manufactured By

Bora Pharmaceutical Services, Inc. (Canada)

ATC Code

J05AF06 (Abacavir)

Active Substance

Abacavir (Rec.INN registered by WHO)

Dosage Form

Ziagen®

Oral solution 20 mg/ml: bottle 240 ml in a set with an adapter, dosing syringe, and patient card

Dosage Form, Packaging, and Composition

Oral solution yellowish in color, from transparent to slightly opalescent, with a fruity odor.

Excipients : sorbitol 70% (non-crystalline) – 492 mg, sodium saccharin – 0.3 mg, strawberry flavor – 2 mg, banana flavor – 2 mg, sodium citrate – 10 mg, citric acid – 7 mg, methylparahydroxybenzoate – 1.5 mg, propylparahydroxybenzoate – 0.18 mg, propylene glycol – 50 mg, hydrochloric acid – to pH 4.1, sodium hydroxide solution – to pH 4.1, purified water – to 1 ml.

240 ml – high-density polyethylene bottles (1) in a set with an adapter, dosing syringe, and a tear-off warning card for the patient about hypersensitivity reactions – cardboard packs.

Clinical-Pharmacological Group

Antiviral drug active against HIV

Pharmacotherapeutic Group

Antiviral [HIV] agent

Pharmacological Action

Antiviral agent, a synthetic carbocyclic nucleoside analogue. Inside the cell, Abacavir is converted by cellular enzymes into the active metabolite carbovir triphosphate.

Carbovir triphosphate is an analogue of deoxyguanosine-5′-triphosphate (dGTP). Carbovir triphosphate inhibits the activity of HIV-1 reverse transcriptase, which is due to competition with the natural substrate dGTP and disruption of its incorporation into viral DNA.

The loss of the 3′-OH group in the incorporated nucleoside analogue prevents the formation of 5′- and 3′-phosphodiester bonds necessary for DNA chain elongation. As a result, the growth of viral DNA stops.

Pharmacokinetics

After oral administration, absorption is high, bioavailability is 83%. C_max – 3 µg/ml, T_max – 1-1.5 h. AUC (over 12 hours after administration) – 6 µg/ml/h.

Food slows down the absorption of abacavir and reduces C_max, but does not affect AUC. Penetrates the blood-brain barrier, the concentration of abacavir in the cerebrospinal fluid is 30-44% of that in plasma.

Plasma protein binding is low. Metabolized in the liver with the participation of acetaldehyde dehydrogenase and the formation of glucuronide conjugates (5′-carboxylic acid and 5′-glucuronide). T_1/2 – 1.5 h.

Excreted by the kidneys – 83% as metabolites and 2% unchanged; the rest is excreted through the intestines. Does not accumulate.

Indications

Treatment of HIV infection (as part of combination therapy).

ICD codes

Dosage Regimen

Administer orally in combination with other antiretroviral agents.

For adults, the dose is 300 mg twice daily.

For pediatric patients aged 3 months to 16 years, the dose is 8 mg/kg twice daily.

Do not use in children under 3 months of age or with a body weight less than 14 kg.

Calculate the dose for children using the patient’s body weight at each visit to ensure accuracy.

Use the provided dosing syringe for accurate measurement of the oral solution.

Shake the bottle well before each use.

The total daily dose for any patient must not exceed 600 mg.

This regimen applies to patients with normal renal and hepatic function.

Take with or without food.

Adverse Reactions

Skin and skin appendages: rash (usually maculopapular or urticarial); very rarely – multiform exudative erythema, including Stevens-Johnson syndrome and toxic epidermal necrolysis.

Digestive system: loss of appetite, nausea, vomiting, diarrhea, abdominal pain, ulceration of the oral mucosa, increased activity of liver enzymes, liver failure.

Respiratory system: shortness of breath, cough, sore throat, adult respiratory distress syndrome, respiratory failure.

Nervous system: headache, paresthesia, drowsiness.

Hematopoietic and lymphatic system: lymphopenia.

Urinary system: increased serum creatinine concentration, renal failure.

Musculoskeletal system: often – hyperlactatemia; rarely – lactic acidosis, accumulation/redistribution of adipose tissue, myalgia, rhabdomyolysis, arthralgia, increased CPK activity.

Other: fever, feeling of fatigue, malaise, edema, lymphadenopathy, arterial hypotension, conjunctivitis, anaphylactic reactions.

Contraindications

Moderate and severe liver dysfunction; children under 3 months of age and body weight less than 14 kg; hypersensitivity to abacavir.

Use in Pregnancy and Lactation

Adequate and well-controlled clinical studies on the safety of abacavir use during pregnancy and lactation have not been conducted.

If use during pregnancy is necessary, the expected benefit of therapy for the mother and the potential risk to the fetus should be weighed.

It is not known whether Abacavir is excreted in breast milk. If use during lactation is necessary, the issue of discontinuing breastfeeding should be decided.

Use in Hepatic Impairment

Contraindication: moderate and severe liver dysfunction.

Use of abacavir in any patient requires caution, especially in the presence of risk factors for liver damage. If clinical or laboratory signs of lactic acidosis or hepatotoxicity appear (which may manifest as hepatomegaly and fatty liver even in the absence of a marked increase in aminotransferase activity), treatment with abacavir should be discontinued.

Use in Renal Impairment

Use with caution in patients with impaired renal function.

Pediatric Use

For children aged 3 months to 16 years – 8 mg/kg 2 times/day. Contraindication: children under 3 months of age and body weight less than 14 kg.

Special Precautions

Symptoms of hypersensitivity may appear at any time after starting treatment with abacavir, but most often they occur within the first 6 weeks.

If patients continue to take Abacavir when a hypersensitivity reaction develops, the clinical manifestations become more pronounced and can become life-threatening. In most cases, symptoms disappear after discontinuation of abacavir.

There have been reports of the development of lactic acidosis, hepatomegaly and fatty liver, including fatal outcomes, due to antiretroviral therapy with nucleoside analogues, including Abacavir, lamivudine and zidovudine, taken both separately and in combination. In most cases, these complications occur in women.

Symptoms indicating lactic acidosis include general weakness, loss of appetite, rapid weight loss of unclear etiology, gastrointestinal disorders and respiratory disorders (shortness of breath and tachypnea).

Use of abacavir in any patient requires caution, especially in the presence of risk factors for liver damage. If clinical or laboratory signs of lactic acidosis or hepatotoxicity appear (which may manifest as hepatomegaly and fatty liver even in the absence of a marked increase in aminotransferase activity), treatment with abacavir should be discontinued.

Combined antiretroviral therapy may be accompanied by the development of lipodystrophy syndrome. During clinical examination of patients during treatment, attention should be paid to the redistribution of subcutaneous adipose tissue. Laboratory examination should include determination of serum lipid concentrations and blood glucose concentration. If lipid metabolism is impaired, appropriate treatment is prescribed.

If HIV-infected patients with severe immunodeficiency have asymptomatic or mild opportunistic infections at the time of initiation of antiretroviral therapy (ART), such therapy may lead to an increase in the symptoms of opportunistic infections or other serious consequences. These reactions usually occur within the first weeks or months after starting ART. Typical examples are cytomegalovirus retinitis, generalized or focal infection caused by mycobacteria, and pneumonia caused by Pneumocystis jirovecii (formerly P. carinii). The appearance of any symptoms of inflammation requires immediate examination and, if necessary, treatment.

The use of abacavir does not exclude the possibility of developing opportunistic infections or other complications of HIV infection, so patients should remain under the supervision of a physician experienced in the treatment of these diseases.

Antiretroviral therapy, including drugs containing Abacavir, should be prescribed with caution to patients with a possible risk of coronary artery disease. All measures must be taken to minimize all modifiable risk factors (such as hypertension, dyslipidemia, diabetes mellitus and smoking).

Drug Interactions

According to pharmacokinetic studies, the use of abacavir at a dose of 600 mg 2 times/day in combination with methadone reduces the C_max of abacavir in serum by 35%, increases the time to reach C_max in serum by 1 hour, but does not change AUC. The clinical significance of these changes is small. The same study found that Abacavir increases the systemic clearance of methadone by 22%. In most cases, these changes are also considered clinically insignificant, but in certain situations, a change in the methadone dose may be required.

Retinoids, such as isotretinoin, are eliminated with the participation of alcohol dehydrogenase, so they may interact with abacavir, but no specific studies have been conducted to date.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.