Combivir 150 mg + 300 mg Tablets

Brand name

The trade name of the drug is Combivir. This is the registered name under which the drug is known in medical practice and is available in the pharmacy network.

International Nonproprietary Name (INN)

The international nonproprietary name is lamivudine + zidovudine. These names denote the two active active ingredients in the drug and are used in pharmacology internationally.

Form of release

Combivir is available as film-coated tablets containing a fixed combination of 150 mg lamivudine and 300 mg zidovudine. Tablets have white color, oval shape and are packed in blisters of 10 pieces or vials of 60 pieces. This form provides convenience of use and accurate dosing of active components in combination therapy.

Composition

Active substance

The main active components are lamivudine (150 mg) and zidovudine (300 mg) in each tablet. These substances act synergistically, enhancing the antiviral effect of the drug.

Auxiliary components

The tablets contain such excipients as microcrystalline cellulose, sodium starch glycolate, magnesium stearate, colloidal anhydrous silicon dioxide, as well as film coating of hypromellose, titanium dioxide, polyethylene glycol and polysorbate 80. These components ensure stability and bioavailability of active substances.

Pharmacologic Properties

Pharmacodynamics

Combivir is a combination of two nucleoside analogs, lamivudine and zidovudine, which inhibit HIV reverse transcriptase. Lamivudine and zidovudine, after phosphorylation inside cells, are converted into active triphosphate forms that competitively block the reverse transcriptase enzyme needed to convert viral RNA into DNA. This interrupts the viral replication process, preventing the virus from replicating in infected cells. In addition, the incorporation of these analogs into the growing viral DNA strand causes it to break, which further suppresses viral activity.

Lamivudine is highly active against HIV-1 and to a lesser extent against hepatitis B virus, while zidovudine enhances the antiviral effect by providing a broader spectrum of action. Synergism of these components allows to reduce the viral load in the blood to an undetectable level with proper adherence to the therapy regimen. The drug does not completely destroy the virus, but significantly slows the progression of infection, improving the function of CD4-lymphocytes and preventing the development of opportunistic diseases. The effect is noticeable after 4-12 weeks of regular administration as part of ART.

Pharmacokinetics

Absorption

Lamivudine and zidovudine are well absorbed from the gastrointestinal tract after oral administration. The maximum plasma concentration of lamivudine is reached after 0.5-2 hours, and that of zidovudine after 0.5-1.5 hours. Bioavailability of lamivudine is about 86%, zidovudine - about 64%, and food intake may slightly slow absorption, but does not affect the overall efficacy.

Distribution

Lamivudine binds to plasma proteins by less than 36% and zidovudine by 34-38%. The volume of distribution of lamivudine is about 1.3 L/kg and that of zidovudine is about 1.6 L/kg, indicating their penetration into tissues, including the central nervous system and cerebrospinal fluid. Both substances cross the placental barrier.

Metabolism

Lamivudine is minimally metabolized (5-10%) and is excreted predominantly unchanged. Zidovudine undergoes more intensive metabolism in the liver with the participation of glucuronidation enzymes, forming an inactive metabolite - 5'-glucuronide zidovudine, which is about 75% of the administered dose.

Excretion

The elimination half-life of lamivudine is 5-7 hours, that of zidovudine is 0.8-1.2 hours. Lamivudine is excreted through the kidneys (about 70% unchanged), zidovudine - through the kidneys (about 14% unchanged, the rest in the form of metabolites) and partially through the intestine. Complete excretion takes about 24 hours.

Indications for Use

Combivir is indicated for the treatment of the following conditions:

• HIV-1 infection in adults and children as part of combination antiretroviral therapy;
• Prevention of HIV infection progression to AIDS;
• Reduction of viral load and maintenance of immune status in patients with confirmed HIV diagnosis.

The drug is used exclusively in combination with other antiretroviral agents to prevent resistance.

Contraindications

The use of Combivir is prohibited in:

• Hypersensitivity to lamivudine, zidovudine or auxiliary components;
• Severe neutropenia (less than 0.75 × 10⁹/L) or anemia (hemoglobin less than 7.5 g/dL);
• Severe renal impairment (creatinine clearance less than 50 mL/min);
• Children under 3 years of age or body weight less than 14 kg;
• Pregnancy (first trimester) and lactation without strict indications.

With caution administered in hepatitis B or C, obesity, bone marrow dysfunction.

Method of Administration and Dosage

How to take

Combivir tablets are taken orally, drinking water (100-150 ml), regardless of meals. Tablets are not chewed and crushed to keep the fixed combination of active substances. It is recommended to adhere to the same time of intake to maintain stable concentration.

Dosages for adults and children

Adults and children with a body weight greater than 30 kg

The standard dose is 1 tablet (150 mg lamivudine + 300 mg zidovudine) twice daily, 12 hours apart.

Children 14 to 30 kg

Dosage - half a tablet (75 mg lamivudine + 150 mg zidovudine) twice daily.

Dose adjustment for certain conditions

In renal insufficiency (creatinine clearance less than 50 ml/min) the drug is not used in a fixed combination; separate drugs with dose adjustment are used. In hepatic insufficiency correction is not required, but monitoring of the condition is necessary.

Side Effects

Possible adverse reactions include:

• Hematopoietic system: anemia, neutropenia, thrombocytopenia;
• Gastrointestinal system: nausea, vomiting, abdominal pain, diarrhea;
• Nervous system: headache, fatigue, insomnia;
• Metabolism: lactoacidosis, lipodystrophy;
• Allergic reactions: rash, itching, fever;
• Other: myalgia, elevation of liver enzymes.

Side effects are more likely to occur in the first few weeks and require monitoring.

Overdose

Symptoms of overdose

Nausea, dizziness, anemia, neutropenia, neutropenia, lactoacidosis may occur when taking doses higher than recommended (e.g., more than 4 tablets per day).

First aid measures

Stop taking, call a doctor. Gastric lavage (if less than one hour has elapsed) and give activated charcoal. Symptomatic treatment in hospital is required.

Drug Interactions

Influence on the effects of other drugs

Combivir increases the toxicity of drugs that inhibit bone marrow (hansivir). Ribavirin reduces the activity of zidovudine. CYP3A4 inhibitors (ketoconazole) may increase the concentration of the components.

Compatibility with alcohol and food

Alcohol increases the risk of lactoacidosis. Food does not affect efficacy but improves tolerability.

Special Precautions

Use in pregnancy and breastfeeding

Use in the first trimester of pregnancy is limited; in the second and third trimesters, by strict indication. Breast-feeding is prohibited due to penetration into milk.

Effect on driving and mechanisms

The drug may cause fatigue and dizziness, which requires caution when driving.

Particularities of use in the elderly and children

The elderly need monitoring of renal and blood function. In children, the dosage is adjusted for body weight.