Tivizid300 mg+150 mg+300 mg

Tivizid is a fixed-dose combination of three nucleoside reverse transcriptase inhibitors (NRTIs) indicated for the treatment of HIV-1 infection.

Established / FDA-approved use

• Alone as a complete antiretroviral regimen, or in combination with other antiretroviral agents, for the treatment of HIV-1 infection in adults and adolescents weighing at least 40 kg.

Important limitations on use

• Tivizid is not recommended as initial therapy in antiretroviral-naive patients with a baseline HIV-1 RNA level greater than 100,000 copies/mL, because clinical trial data have shown a higher rate of virologic failure with this triple-NRTI regimen compared to other combination regimens at high baseline viral loads.
• This is a complete triple-NRTI regimen appropriate only for specific treatment situations as determined by current antiretroviral treatment guidelines; it is not a first-line choice for all patients with HIV-1.
• Use of Tivizid requires specialist HIV-management prescribing, baseline HLA-B*5701 testing, and ongoing clinical and laboratory monitoring.

Strict adherence to the prescribed regimen is essential to maintain viral suppression and reduce the risk of drug resistance.

Each film-coated tablet of Abacavir + Lamivudine + Zidovudine contains:

• Abacavir (as abacavir sulfate) 300 mg
• Lamivudine 150 mg
• Zidovudine 300 mg

Tivizid is an oral, fixed-dose combination antiretroviral tablet that brings together three nucleoside reverse transcriptase inhibitors (NRTIs) — abacavir, lamivudine, and zidovudine — in a single film-coated tablet.

By combining agents from within the same drug class that act at different points of the same enzymatic step, Tivizid provides a complete triple-NRTI antiretroviral regimen for selected adults and adolescents with HIV-1 infection, reducing pill burden while requiring careful specialist selection of patients (including genetic screening) before initiation.

Antiretroviral agent - Fixed-dose combination of three Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

Abacavir + Lamivudine + Zidovudine combines three synthetic nucleoside analogues, each of which is phosphorylated intracellularly by host cell enzymes to its active triphosphate form:

• Abacavir is converted to carbovir triphosphate.
• Lamivudine is converted to lamivudine triphosphate.
• Zidovudine is converted to zidovudine triphosphate.

Each active triphosphate competes with the corresponding natural deoxynucleotide for incorporation into viral DNA by HIV-1 reverse transcriptase. Once incorporated, the analogue lacks the 3'-hydroxyl group required to extend the DNA chain, causing chain termination and blocking further viral DNA synthesis, which halts HIV-1 replication. Combining three NRTIs from different chemical sub-classes is intended to maximize antiviral activity in a complete regimen, though this triple-NRTI approach has shown reduced virologic efficacy compared with other regimens at high baseline viral loads (see Indications).

Tivizid tablets should be swallowed whole with water and should not be crushed or split, as this is a fixed-dose combination tablet.

• May be taken with or without food.
• Take doses approximately 12 hours apart to maintain steady drug levels.
• Do not skip, delay, or double doses; missed doses should be taken as soon as remembered unless the next dose is nearly due.
• Continue taking Tivizid exactly as prescribed, even if feeling well, and do not stop or share the medicine without consulting the prescribing physician, as inconsistent dosing promotes drug resistance.

Tivizid contains abacavir, lamivudine, and zidovudine; clinically significant interactions relevant to its components include:

• Ribavirin: Co-administration with the zidovudine component increases the risk of lactic acidosis and hepatic decompensation, including fatal cases; this combination should be avoided.
• Methadone: Reduces zidovudine clearance, increasing zidovudine exposure; monitor for zidovudine-related toxicity (e.g., hematologic effects).
• Drugs causing myelosuppression (e.g., ganciclovir, valganciclovir, other cytotoxic or bone-marrow-suppressive agents): Additive risk of neutropenia and anemia with the zidovudine component; avoid concurrent use where possible or monitor blood counts closely.
• Interferon alfa with or without ribavirin: Increased risk of hepatic decompensation and worsened anemia in combination with the zidovudine component.
• Alcohol: Alters zidovudine metabolism and increases its plasma concentration; avoid regular alcohol use.
• Other abacavir-, lamivudine-, or zidovudine-containing products (including other combination antiretrovirals with overlapping components): Should not be co-administered, to avoid duplicate dosing and additive toxicity.

Always inform the physician of all other medicines being taken before starting Tivizid.

Side effects of Tivizid reflect its three components. Serious reactions (hypersensitivity, lactic acidosis/hepatomegaly, and hematologic toxicity) are described fully under Precautions and Warnings.

Common

• Nausea, vomiting, diarrhea, loss of appetite
• Headache
• Malaise, fatigue, generalized weakness
• Insomnia or other sleep disturbance
• Muscle aches (myalgia)

Less common / serious (see Precautions and Warnings for full detail)

• Hypersensitivity reaction (fever, rash, GI symptoms)
• Neutropenia and anemia (zidovudine-related bone marrow suppression)
• Myopathy with prolonged use
• Lactic acidosis with hepatic steatosis
• Fat redistribution/lipodystrophy with long-term antiretroviral use
• Immune reconstitution inflammatory syndrome on starting therapy

Pregnancy: Tivizid should be used during pregnancy only if the potential benefit to the mother clearly justifies the potential risk to the fetus. Antiretroviral therapy decisions in pregnancy should always be individualized by a physician experienced in HIV management, weighing maternal health and prevention of mother-to-child transmission against any theoretical risk; do not start, stop, or change this medicine during pregnancy without medical advice.

Lactation: All three components pass into breast milk. In addition to potential drug exposure to the infant, mothers with HIV-1 infection are generally advised not to breastfeed, where safe and affordable infant feeding alternatives are available, to avoid the risk of postnatal HIV transmission through breast milk. Consult a physician for individualized feeding guidance.

Boxed warnings

• Hypersensitivity reactions (abacavir component): Potentially fatal hypersensitivity reactions have occurred with abacavir, strongly associated with the HLA-B*5701 allele. Genetic screening for HLA-B*5701 is recommended before starting Tivizid. Symptoms may include fever, rash, gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain), and severe malaise, and typically occur within the first six weeks. If hypersensitivity is suspected, discontinue Tivizid immediately and permanently - it must never be restarted, even in patients who are HLA-B*5701-negative, because rechallenge can cause a more severe and potentially fatal reaction within hours.
• Lactic acidosis and severe hepatomegaly with steatosis: Reported with nucleoside analogues, including the components of Tivizid, sometimes fatal; use with caution in all patients, particularly those with risk factors for liver disease, and discontinue if clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity develop.
• Hematologic toxicity and myopathy (zidovudine component): Zidovudine has been associated with neutropenia and anemia, particularly in patients with advanced HIV disease, and with myopathy after prolonged use. Regular blood count monitoring is required during treatment.

Other precautions

• Some observational data have suggested a possible increased cardiovascular risk with abacavir-containing regimens; discuss with the prescriber if additional cardiovascular risk factors are present.
• Tivizid is a complete triple-NRTI regimen appropriate only for specific treatment situations under current antiretroviral guidelines, and is not suitable as first-line therapy for all patients; it requires specialist HIV-management prescribing and ongoing monitoring.
• Consistent adherence to the prescribed regimen is critical; missed or irregular doses increase the risk of developing drug-resistant HIV.

There is no specific antidote for overdose with Tivizid. If overdose is suspected, seek immediate medical attention or contact a poison control center / emergency services without delay. Management is supportive and should be provided under medical supervision, with monitoring of the patient's clinical status; it is not known whether the components of Tivizid are effectively removed by peritoneal dialysis or hemodialysis. Do not attempt home treatment of a suspected overdose.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Renal impairment

Tivizid is not recommended in patients with creatinine clearance below 50 mL/min, because the fixed-dose tablet does not permit the dose adjustments of the lamivudine and zidovudine components that renal impairment requires; such patients should receive the individual component drugs dosed separately.

Hepatic impairment

Contraindicated in moderate-to-severe hepatic impairment (see Contraindications). Use with caution and close monitoring in mild hepatic impairment.

Pediatric use

Tivizid is not recommended for patients weighing less than 40 kg, as the fixed tablet strength does not allow appropriate weight-based dosing of the individual components in this population; safety and efficacy of this specific fixed-dose combination tablet have not been established below 40 kg. Adolescents weighing at least 40 kg may be dosed as adults.

Elderly

Clinical experience in patients over 65 years is limited. Use with caution, with attention to concomitant illnesses, age-related decline in renal/hepatic function, and other medications.

Tivizid is used long-term as part of ongoing antiretroviral therapy for HIV-1 infection, for as long as directed by the treating physician. Treatment should not be interrupted or stopped without medical advice, as consistent, uninterrupted therapy is essential to maintain viral suppression and prevent resistance.

Nucleoside Reverse Transcriptase Inhibitor (NRTI) fixed-dose combination; Antiretroviral (ARV) agent

Abacavir + Lamivudine + Zidovudine works by combining three NRTIs that are each converted intracellularly to active triphosphate metabolites. These metabolites competitively inhibit HIV-1 reverse transcriptase and are incorporated into growing proviral DNA chains, causing premature chain termination because they lack a 3'-hydroxyl group. This blocks reverse transcription of the viral RNA genome into DNA, preventing HIV-1 from replicating in infected cells.

C

Tivizid is not recommended for use in children or adolescents weighing less than 40 kg. The fixed strengths in this combination tablet cannot be adjusted to the weight-based doses required in lower-weight pediatric patients, and safety and efficacy of this specific fixed-dose product have not been established in that population. Adolescents weighing 40 kg or more may be treated with the same adult dose under specialist supervision. Younger or lower-weight children requiring an abacavir/lamivudine/zidovudine-based regimen should instead receive the individual component medicines at doses calculated for their body weight.