Diavix150 mg+300 mg

Diavix is a fixed-dose combination of two nucleoside reverse transcriptase inhibitors (NRTIs) indicated, in combination with other antiretroviral agents, for the treatment of HIV-1 infection.

Established / Guideline-Supported Use

• Treatment of HIV-1 infection in adults and pediatric patients weighing at least 30 kg, always as part of a complete combination antiretroviral therapy (ART) regimen (typically with a third agent from another drug class, such as an integrase inhibitor, protease inhibitor, or non-nucleoside reverse transcriptase inhibitor).

Important Limitation

Diavix must never be used as complete monotherapy for HIV-1 infection. It supplies only the two-NRTI "backbone" of a regimen; an additional antiretroviral of a different class is required to form a complete, effective treatment regimen and to reduce the risk of resistance.

Adherence to the full prescribed regimen is essential; missed or inconsistent dosing increases the risk of viral resistance and treatment failure.

Each film-coated tablet of Lamivudine + Zidovudine typically contains Lamivudine 150 mg and Zidovudine 300 mg (strengths may vary slightly by manufacturer; confirm the exact strength on the product label/pack insert).

Diavix combines two synthetic nucleoside analogue reverse transcriptase inhibitors (NRTIs) — lamivudine and zidovudine — in a single tablet for the treatment of HIV-1 infection. Combining both agents into one tablet simplifies dosing of the two-drug NRTI backbone that forms part of a complete antiretroviral regimen.

Lamivudine and zidovudine were among the earliest antiretroviral agents developed and remain part of several combination regimens used worldwide, including in national HIV treatment programs.

Antiretroviral agent — fixed-dose combination of two Nucleoside Reverse Transcriptase Inhibitors (NRTIs); Diavix belongs to the broader class of antiretroviral (ARV) medicines used in combination antiretroviral therapy (cART/HAART).

Lamivudine + Zidovudine combines two NRTIs that act on the same viral enzyme through a common mechanism but at different steps of intracellular activation.

Mechanism

• Lamivudine is phosphorylated intracellularly to lamivudine triphosphate, which competitively inhibits HIV-1 reverse transcriptase and, after incorporation into viral DNA, causes chain termination due to the absence of a 3'-OH group.
• Zidovudine is similarly phosphorylated to zidovudine triphosphate, which competitively inhibits HIV-1 reverse transcriptase and is incorporated into growing viral DNA, causing premature chain termination.

Both components require intracellular phosphorylation by host cell kinases to become pharmacologically active. By blocking reverse transcription, Lamivudine + Zidovudine suppresses HIV-1 replication, which is why it must be combined with an agent acting at a different step of the viral life cycle for a complete regimen.

Pharmacokinetics

Both lamivudine and zidovudine are well absorbed orally, are widely distributed (including penetration into cerebrospinal fluid), undergo largely renal (lamivudine) and hepatic-glucuronidation plus renal (zidovudine) elimination, and have plasma half-lives of a few hours, supporting twice-daily dosing of the combination tablet.

Diavix tablets may be taken with or without food. Swallow the tablet whole with water; do not crush or split unless a healthcare provider specifically advises otherwise. Try to take doses at evenly spaced times approximately 12 hours apart to maintain consistent drug levels.

The following are well-documented, clinically significant interactions with Diavix. Report all prescription, over-the-counter, and herbal products to your physician before starting Diavix.

• Ribavirin: Concomitant use with the zidovudine component is generally avoided; ribavirin antagonizes the antiviral activity of zidovudine and increases the risk of severe anemia.
• Stavudine: Must not be co-administered; there is antagonism of intracellular phosphorylation between zidovudine and stavudine, reducing antiviral efficacy.
• Other bone-marrow-suppressive or cytotoxic drugs (e.g., ganciclovir, valganciclovir, interferon-alfa, dapsone, pyrimethamine, chemotherapeutic agents): Increased risk of additive hematologic toxicity (anemia, neutropenia) when combined with the zidovudine component; more frequent monitoring is needed.
• Trimethoprim/sulfamethoxazole (co-trimoxazole), high dose: May increase zidovudine plasma concentrations and hematologic toxicity.
• Methadone: Zidovudine plasma concentrations may increase in patients on methadone maintenance; monitor for zidovudine-related toxicity.
• Doxorubicin: In vitro antagonism with zidovudine has been reported; concurrent use should be approached cautiously under specialist supervision.
• Other lamivudine-containing products (e.g., for hepatitis B): Avoid duplicate lamivudine dosing from other combination products.

Side effects of Diavix range from common and mild to rare but serious.

Common

• Headache
• Nausea, vomiting, diarrhea
• Fatigue and general malaise
• Insomnia and dizziness
• Musculoskeletal pain / myalgia

Serious (Seek Medical Attention)

• Bone marrow suppression: anemia, neutropenia (fatigue, pallor, frequent infections, unusual bleeding/bruising)
• Lactic acidosis and severe hepatomegaly with steatosis (rare, potentially fatal — see Precautions and Warnings)
• Myopathy with prolonged use (muscle weakness, pain)
• Signs of severe allergic reaction (rash, swelling, difficulty breathing)
• Signs of liver problems (yellowing of skin/eyes, dark urine)

Pregnancy: Diavix should be used during pregnancy only if clearly needed and if the potential benefit to the mother justifies the potential risk to the fetus; use only under the supervision of a physician experienced in HIV management, following current perinatal HIV treatment guidelines. Do not stop or change antiretroviral therapy during pregnancy without consulting your physician, as untreated HIV carries significant risks to both mother and infant.

Lactation: Breastfeeding is generally not recommended for mothers with HIV where safe and adequate replacement feeding is available, to avoid the risk of postnatal HIV transmission; both components of Diavix pass into breast milk. Feeding decisions should be individualized in consultation with a physician based on local guidelines and circumstances.

Boxed Warnings

• Hematologic toxicity: The zidovudine component can cause anemia and neutropenia, particularly in patients with advanced HIV disease, low baseline bone marrow reserve, or receiving higher doses. Regular CBC monitoring is required throughout treatment; dose adjustment, temporary interruption, or transfusion may be needed for severe cytopenias.
• Myopathy: Prolonged use of the zidovudine component has been associated with myopathy and myositis, related to mitochondrial toxicity.
• Lactic acidosis and severe hepatomegaly with steatosis: A rare but potentially fatal class effect of NRTIs, including Diavix. Suspend treatment if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur.
• Exacerbation of hepatitis B: Severe acute exacerbations of hepatitis B have been reported in HBV/HIV co-infected patients who discontinue the lamivudine component. Hepatic function should be monitored closely for several months after stopping Diavix in such patients; anti-hepatitis B therapy may need to be initiated if appropriate.

Other Precautions

• Immune reconstitution inflammatory syndrome (IRIS): May occur during initial combination antiretroviral treatment, unmasking underlying opportunistic infections or triggering autoimmune conditions.
• Fat redistribution/lipodystrophy: Long-term antiretroviral therapy has been associated with redistribution of body fat.
• Antiretroviral stewardship: Always use as part of a complete combination regimen; adherence counseling is essential to prevent development of drug resistance. Do not stop, extend, skip doses, or share this medicine with others without medical advice.
• Use with caution in patients with pre-existing renal or hepatic impairment, or reduced bone marrow reserve.

Limited data exist on acute overdose of Diavix. If overdose is suspected, seek immediate medical attention or contact a poison control center / emergency services right away. Management is supportive, based on the patient's clinical status; there is no specific antidote. Hemodialysis may help remove zidovudine and its metabolites, though its clinical benefit in overdose is not well established; do not attempt home treatment.

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

Renal Impairment

The fixed-dose combination tablet is not recommended in patients with creatinine clearance below 50 mL/min; use of the individual components with adjusted dosing intervals, under physician supervision, is preferred.

Hepatic Impairment

Use with caution; zidovudine metabolism is reduced in hepatic impairment, increasing exposure and toxicity risk. Individual component dosing may allow more precise adjustment.

Elderly

Limited specific data; use with caution given the higher likelihood of decreased renal/hepatic function and concomitant medications — monitor closely.

HBV Co-infection

See Precautions and Warnings regarding hepatitis B exacerbation risk upon discontinuation of the lamivudine component.

Pediatric Use

See Pediatric Uses section.

Diavix is intended for long-term, typically lifelong, use as part of a complete antiretroviral regimen for chronic management of HIV-1 infection. Duration and any regimen changes should be determined by an HIV specialist based on virologic response, tolerability, and resistance testing; do not discontinue without medical advice.

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

Lamivudine + Zidovudine works by combining two NRTIs that both target HIV-1 reverse transcriptase but require separate intracellular activation. After phosphorylation to their active triphosphate forms, lamivudine triphosphate and zidovudine triphosphate compete with natural nucleotides for incorporation into viral DNA during reverse transcription. Once incorporated, each lacks the 3'-hydroxyl group needed to extend the DNA chain, causing premature chain termination and halting HIV-1 replication. Using two NRTIs together, plus a third agent from a different class, reduces the likelihood of the virus developing resistance compared with any single agent alone.

C

Diavix fixed-dose tablets are indicated for children and adolescents weighing at least 30 kg, dosed the same as adults (one tablet twice daily), always as part of a complete antiretroviral regimen.

For children weighing less than 30 kg, the fixed-dose combination tablet does not allow appropriate weight-based dosing; the individual components (lamivudine and zidovudine) should be dosed separately according to body weight, under the supervision of a pediatric HIV specialist. Safety and efficacy of the fixed-dose combination tablet specifically have not been established below 30 kg body weight.

Regular hematologic monitoring (CBC) is particularly important in pediatric patients due to the risk of zidovudine-associated anemia and neutropenia.