Trizivir

/ GSK

Recommended dosage is one tablet twice daily.
Renal impairment: Whilst no dose adjustment of abacavir is necessary in patients with renal dysfunction, lamivudine and zidovudine concentrations are increased in patients with renal impairment due to decreased clearance. Therefore, as dose adjustments of these may be necessary, it is recommended that separate preparations of abacavir, lamivudine and zidovudine be administered to patients with reduced renal function (creatinine clearance ≤ 50 ml/min). Physicians should refer to the individual prescribing information of these medicinal products. This product should not be administered to patients with end-stage renal disease.
Hepatic impairment: It is contraindicated in patients with hepatic impairment.|
Elderly: No pharmacokinetic data are currently available in patients over 65 years of age. Special care is advised in this age group due to age associated changes such as the decrease in renal function and alteration of haematological parameters.
Paediatric population: The safety and efficacy in children has not been established. No data are available.
Dose adjustments in patients with haematological adverse reactions: Dose adjustment of zidovudine may be necessary if the haemoglobin level falls below 9 g/dl or 5.59 mmol/l or the neutrophil count falls below 1.0 x 109/l. As dose adjustment is not possible, separate preparations of abacavir, lamivudine and zidovudine should be used. Physicians should refer to the individual prescribing information of these medicinal products.

The drug is indicated for the treatment of Human Immunodeficiency Virus (HIV) infection in adults.

Hypersensitivity to the active substances or to any of the excipients. Patients with end-stage renal disease. Due to the active substance zidovudine, the drug is contraindicated in patients with abnormally low neutrophil counts (< 0.75 x 10^9/l), or abnormally low haemoglobin levels (< 7.5 g/dl or 4.65 mmol/l).

Hypersensitivity Reactions: Abacavir is associated with a hypersensitivity reactions. The risk for abacavir HSR to occur is high for patients who test positive for the HLA-B*5701 allele. However, abacavir HSRs have been reported at a lower frequency in patients who do not carry this allele.
Lactic acidosis: Lactic acidosis, usually associated with hepatomegaly and hepatic steatosis, has been reported with the use of nucleoside analogues.zidovudine. Early symptoms (symptomatic hyperlactatemia) include benign digestive symptoms (nausea, vomiting and abdominal pain), non-specific malaise, loss of appetite, weight loss, respiratory symptoms (rapid and/or deep breathing) or neurological symptoms (including motor weakness). Anaemia, neutropenia and leucopenia (usually secondary to neutropenia) can be expected to occur in patients receiving zidovudine. These occurred more frequently at higher zidovudine doses (1200-1500 mg/day) and in patients with poor bone marrow reserve prior to treatment, particularly with advanced HIV disease. Haematological parameters should therefore be carefully monitored in patients receiving this drug  These  haematological effects are not usually observed before four to six week’s therapy. For patients with advanced symptomatic HIV disease, it is generally recommended that blood tests are performed at least every two weeks for the first three months of therapy and at least monthly thereafter.
Pancreatitis: Cases of pancreatitis have occurred rarely in patients treated with abacavir, lamivudine and zidovudine. However, it is not clear whether these cases were due to treatment with these medicinal  products or to the underlying HIV disease. Treatment with this product should be stopped immediately if clinical signs, symptoms or laboratory abnormalities suggestive of pancreatitis occur.
Liver disease: If lamivudine is being used concomitantly for the treatment of HIV and HBV, additional information relating to the use of lamivudine in the treatment of hepatitis B infection is available in the lamivudine physician information.
See prescribing information for full details.

Adverse reactions have been reported with abacavir, lamivudine and zidovudine used separately or in combination for therapy of HIV disease. Because this product contains abacavir, lamivudine and zidovudine, the adverse reactions associated with these compounds may be expected. Hypersensitivity to abacavir, anaemia, neutropenia and leucopenia, anorexia, headache, insomnia, dizziness, cough, nasal symptoms, nausea, vomiting, diarrhea, abdominal pain, raised blood levels of liver enzymes and bilirubin, rash, alopecia, arthralgia, muscle disorders, myalgia, fever, lethargy, fatigue, malaise, Lactic acidosis, Lipodystrophy/metabolic abnormalities,  Immune Reactivation Syndrome, Osteonecrosis.
See prescribing information for full details.

This product contains abacavir, lamivudine and zidovudine, therefore any interactions identified for these individually are relevant. Clinical studies have shown that there are no clinically significant interactions between abacavir, lamivudine and zidovudine. Abacavir is metabolised by UDP-glucuronyltransferase (UGT) enzymes and alcohol dehydrogenase; co-administration of inducers or inhibitors of UGT enzymes or with compounds eliminated through alcohol dehydrogenase could alter abacavir exposure. Zidovudine is primarily metabolised by UGT enzymes; co-administration of inducers or inhibitors of UGT enzymes could alter zidovudine exposure. Lamivudine is cleared renally. Active renal secretion of lamivudine in the urine is mediated Page 8 of 27 through organic cation transporters (OCTs); co-administration of lamivudine with OCT inhibitors may increase lamivudine exposure. Abacavir, lamivudine and zidovudine are not significantly metabolised by cytochrome P450 enzymes (such as CYP 3A4, CYP 2C9 or CYP 2D6) nor do they inhibit or induce this enzyme system. Therefore, there is little potential for interactions with antiretroviral protease inhibitors, non-nucleosides and other medicinal products metabolised by major P450 enzymes. Interaction studies have only been performed in adults.
See prescribing information for full details.

Pregnancy: As a general rule, when deciding to use antiretroviral agents for the treatment of HIV infection in pregnant women and consequently for reducing the risk of HIV vertical transmission to the newborn, the animal data as well as the clinical experience in pregnant women should be taken into account. In the present case, the use in pregnant women of zidovudine, with subsequent treatment of the newborn infants, has been shown to reduce the rate of maternal-foetal transmission of HIV. There are no data on the use of this product in pregnancy. A moderate amount of data on pregnant women taking the individual actives abacavir, lamivudine and zidovudine in combination indicates no malformative toxicity (more than 300 outcomes from first trimester exposures). A large amount of data on pregnant women taking lamivudine or zidovudine indicate no malformative toxicity (more than 3000 outcomes from first trimester exposure each, of which over 2000 outcomes involved exposure to both lamivudine and zidovudine). Moderate amount of data (more than 600 outcomes from first trimester) indicates no malformative toxicity for abacavir. The malformative risk is unlikely in humans based on the mentioned moderate amount of data.
Lactation: It is recommended that mothers infected by HIV do not breast-feed their infants under any circumstances in order to avoid transmission of HIV.
See prescribing information for full details.  

There is no experience of overdose with this product. No specific symptoms or signs have been identified following acute overdose with zidovudine or lamivudine apart from those listed as adverse reactions. No fatalities occurred, and all patients recovered. Single doses up to 1,200 mg and daily doses up to 1,800 mg of abacavir have been administered to patients in clinical studies. No unexpected adverse reactions were reported. The effects of higher doses are not known. If overdose occurs the patient should be monitored for evidence of toxicity, and standard supportive treatment applied as necessary. Since lamivudine is dialysable, continuous haemodialysis could be used in the treatment of overdose, although this has not been studied. Haemodialysis and peritoneal dialysis appear to have a limited effect on elimination of zidovudine, but enhance the elimination of the glucuronide metabolite. It is not known whether abacavir can be removed by peritoneal dialysis or haemodialysis.

The drug can be taken with or without food.