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Combivir is a brand name for Lamivudine. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Combivir is indicated in antiretroviral combination therapy for the treatment of Human Immunodeficiency Virus (HIV) infection (see section 4.2).
Verbatim from this product's EMA label. Tap a section to expand.
Therapy should be initiated by a physician experienced in the management of HIV infection. Combivir may be administered with or without food. To ensure administration of the entire dose, the tablet(s) should ideally be swallowed without crushing.
2). Adults and adolescents weighing at least 30 kg The recommended dose of Combivir is one tablet twice daily. Children weighing between 21 kg and 30 kg The recommended oral dose of Combivir is one-half tablet taken in the morning and one whole tablet taken in the evening.
Children weighing from 14 kg to 21 kg The recommended oral dose of Combivir is one-half tablet taken twice daily. The dosing regimen for paediatric patients weighing 14-30 kg is based primarily on pharmacokinetic modelling and supported by data from clinical studies using the individual components lamivudine and zidovudine.
A pharmacokinetic overexposure of zidovudine can occur, therefore close safety monitoring is warranted in these patients. If gastrointestinal intolerance occurs in patients weighing 3 21-30 kg, an alternative dosing schedule with one-half tablet taken thrice daily can be applied in attempt to improve tolerability.
Combivir tablets should not be used for children weighing less than 14 kg, since doses cannot be appropriately adjusted for the weight of the child. In these patients, lamivudine and zidovudine should be taken as separate formulations according to the prescribed dosing recommendations for these products.
For these patients and for patients, who are unable to swallow tablets, oral solutions of lamivudine and zidovudine are available. For situations where discontinuation of therapy with one of the active substances of Combivir, or dose reduction is necessary separate preparations of lamivudine and zidovudine are available in tablets/capsules and oral solution.
4). Therefore as dosage adjustment of these may be necessary it is recommended that separate preparations of lamivudine and zidovudine be administered to patients with severe renal impairment (creatinine clearance 30 mL/min). Physicians should refer to the individual prescribing information for these medicinal products.
Hepatic impairment Limited data in patients with cirrhosis suggest that accumulation of zidovudine may occur in patients with hepatic impairment because of decreased glucuronidation. Data obtained in patients with moderate to severe hepatic impairment show that lamivudine pharmacokinetics are not significantly affected by hepatic dysfunction.
Adverse reactions have been reported during therapy for HIV disease with lamivudine and zidovudine separately or in combination. For many of these events, it is unclear whether they are related to lamivudine, zidovudine, the wide range of medicinal products used in the management of HIV disease, or as a result of the underlying disease process.
As Combivir contains lamivudine and zidovudine, the type and severity of adverse reactions associated with each of the compounds may be expected. There is no evidence of added toxicity following concurrent administration of the two compounds.
4). Treatment with zidovudine has been associated with loss of subcutaneous fat which is most evident in the face, limbs and buttocks. Patients receiving Combivir should be frequently examined and questioned for signs of lipoatrophy.
4). 4) In HIV-infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise. 4). Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to CART.
4). Lamivudine The adverse reactions considered at least possibly related to the treatment are listed below by body system, organ class and absolute frequency. Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Blood and lymphatic systems disorders Uncommon:
Neutropenia and anaemia (both occasionally severe), thrombocytopenia Very rare: Pure red cell aplasia Metabolism and nutrition disorders Very Rare: Lactic acidosis 12 Nervous system disorders Common: Headache, insomnia Very rare: Peripheral neuropathy (or paraesthesiae) Respiratory, thoracic and mediastinal disorders Common: Cough, nasal symptoms Gastrointestinal disorders Common: Nausea, vomiting, abdominal pain or cramps, diarrhoea Rare: Pancreatitis, rises in serum amylase Hepatobiliary disorders Uncommon: Transient rises in liver enzymes (AST, ALT) Rare: Hepatitis Skin and subcutaneous tissue disorders Common: Rash, alopecia Rare: Angioedema Musculoskeletal and connective tissue disorders Common : Arthralgia, muscle disorders Rare: Rhabdomyolysis General disorders and administration site conditions Common: Fatigue, malaise, fever Zidovudine The adverse reactions profile appears similar for adults and adolescents.
The special warnings and precautions relevant to both lamivudine and zidovudine are included in this section. There are no additional precautions and warnings relevant to the combination Combivir. 2). In these cases, the physician should refer to the individual prescribing information for these medicinal products.
5). Opportunistic infections Patients receiving Combivir or any other antiretroviral therapy may continue to develop opportunistic infections and other complications of HIV infection. Therefore patients should remain under close clinical observation by physicians experienced in the treatment of HIV infection.
Haematological adverse reactions Anaemia, neutropenia and leukopenia (usually secondary to neutropenia) can be expected to occur in patients receiving zidovudine. These occurred more frequently at higher zidovudine dosages (1200- 1500 mg/day) and in patients with poor bone marrow reserve prior to treatment, particularly with advanced HIV disease.
3) in patients receiving Combivir. These haematological effects are not usually observed before four to six weeks 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.
In patients with early HIV disease haematological adverse reactions are infrequent. Depending on the overall condition of the patient, blood tests may be performed less often, for example every one to three months. g. 2). As dosage adjustment of Combivir is not possible separate preparations of zidovudine and lamivudine should be used.
Physicians should refer to the individual prescribing information for these medicinal products. Pancreatitis Cases of pancreatitis have occurred rarely in patients treated with lamivudine and zidovudine. However, it is not clear whether these cases were due to the antiretroviral treatment or to the underlying HIV disease.
1. 65 mmol/L). 4).
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
Other brands of Lamivudine in European Union.
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However, as dosage adjustments for zidovudine may be necessary, it is recommended that separate preparations of lamivudine and zidovudine be administered to patients with severe hepatic impairment. Physicians should refer to the individual prescribing information for these medicinal products.
4). As dosage adjustment of Combivir is not possible, separate preparations of zidovudine and lamivudine should be used. Physicians should refer to the individual prescribing information for these medicinal products. Dosage in the elderly No specific data are available, however 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.
The most serious adverse reactions include anaemia (which may require transfusions), neutropenia and leukopenia. 4). The incidence of neutropenia was also increased in those patients whose neutrophil counts, haemoglobin levels and serum vitamin B12 levels were low at the start of zidovudine therapy.
The adverse reactions considered at least possibly related to the treatment are listed below by body system, organ class and absolute frequency. Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Blood and lymphatic system disorders Common :
Anaemia, neutropenia and leukopenia Uncommon: Thrombocytopenia and pancytopenia (with marrow hypoplasia) Rare : Pure red cell aplasia Very rare : Aplastic anaemia 13 Metabolism and nutrition disorders Rare : Lactic acidosis in the absence of hypoxaemia, anorexia Psychiatric disorders Rare: Anxiety and depression Nervous system disorders Very common : Headache Common : Dizziness Rare : Insomnia, paraesthesiae, somnolence, loss of mental acuity, convulsions Cardiac disorders Rare :Cardiomyopathy Respiratory, thoracic and mediastinal disorders Uncommon: Dyspnoea Rare : Cough Gastrointestinal disorders Very common : Nausea Common : Vomiting, abdominal pain and diarrhoea Uncommon : Flatulence Rare : Oral mucosa pigmentation, taste perversion and dyspepsia.
Pancreatitis Hepatobiliary disorders Common :
Raised blood levels of liver enzymes and bilirubin Rare : Liver disorders such as severe hepatomegaly with steatosis Skin and subcutaneous tissue disorders Uncommon : Rash and pruritus Rare : Nail and skin pigmentation, urticaria and sweating Musculoskeletal and connective tissue disorders Common : Myalgia Uncommon : Myopathy Renal and urinary disorders Rare: Urinary frequency Reproductive system and breast disorders Rare : Gynaecomastia General disorders and administration site conditions Common : Malaise Uncommon : Fever, generalised pain and asthenia 14 Rare :Chills, chest pain and influenza-like syndrome The available data from both placebo-controlled and open-label studies indicate that the incidence of nausea and other frequently reported clinical adverse events consistently decreases over time during the first few weeks of therapy with zidovudine.
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Treatment with Combivir should be stopped immediately if clinical signs, symptoms or laboratory abnormalities suggestive of pancreatitis occur. Lactic acidosis Lactic acidosis usually associated with hepatomegaly and hepatic steatosis has been reported with the use of 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).
Lactic acidosis has a high mortality and may be associated with pancreatitis, liver failure, or renal failure. Lactic acidosis generally occurred after a few or several months of treatment. Treatment with zidovudine should be discontinued if there is symptomatic hyperlactatemia and metabolic/lactic acidosis, progressive hepatomegaly, or rapidly elevating aminotransferase levels.
Caution should be exercised when administering zidovudine to any patient (particularly obese women) with hepatomegaly, hepatitis or other known risk factors for liver disease and hepatic steatosis 5 (including certain medicinal products and alcohol).
Patients co-infected with hepatitis C and treated with alpha interferon and ribavirin may constitute a special risk. Patients at increased risk should be followed closely. Mitochondrial dysfunction following exposure in utero Nucleoside and nucleotide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine.
There have been reports of mitochondrial dysfunction in HIV-negative infants exposed in utero and/or post-natally to nucleoside analogues; these have predominantly concerned treatment with regimens containing zidovudine. The main adverse reactions reported are haematological disorders (anaemia, neutropenia) and metabolic disorders (hyperlactatemia, hyperlipasemia).
These events have often been transitory. Late-onset neurological disorders have been reported rarely (hypertonia, convulsion, abnormal behaviour). Whether such neurological disorders are transient or permanent is currently unknown. These findings should be considered for any child exposed in utero to nucleoside and nucleotide analogues, who presents with severe clinical findings of unknown etiology particularly neurologic findings.
These findings do not affect current national recommendations to use antiretroviral therapy in pregnant women to prevent vertical transmission of HIV. Lipoatrophy Treatment with zidovudine has been associated with loss of subcutaneous fat, which has been linked to mitochondrial toxicity.
The incidence and severity of lipoatrophy are related to cumulative exposure. This fat loss, which is most evident in the face, limbs and buttocks, may not be reversible when switching to a zidovudine-free regimen. Patients should be regularly assessed for signs of lipoatrophy during therapy with zidovudine and zidovudine-containing products (Combivir and Trizivir).
Therapy should be switched to an alternative regimen if there is suspicion of lipoatrophy development. Weight and metabolic parameters An increase in weight and in levels of blood lipids and glucose may occur during antiretroviral therapy.
Such changes may in part be linked to disease control and life style. For lipids, there is in some cases evidence for a treatment effect, while for weight […]