Lamivudine and Zidovudine
(la mi' vyoo deen) (zye doe' vyoo deen)
P Â - Caution when used during pregnancy
L Â - Contraindicated in lactation
|Indication & Dosage||Oral
Adult:Â As a combination containing lamivudine 150 mg, zidovudine 300 mg: >30 kg: 1 tablet bid.
Child:Â As a combination containing lamivudine 150 mg, zidovudine 300 mg: <14 kg: combined formulation not recommended; 14-21 kg: Â½ tablet bid; 21-30 kg: Â½ tablet each morning, 1 tablet each night (if not tolerated: Â½ tablet bid); >30 kg: 1 tablet bid.
|Administration||Should be taken with food. Take immediately after meals.
|Overdosage||Due to zidovudine component. Symptoms: nausea, vomiting, ataxia and granulocytopenia. Treatment: symptom specific and supportive. Dialysis does not significantly remove lamivudine or zidovudine (does increase clearance of primary metabolite).|
|Contraindications||Neutrophil count <0.75 x 109/l; haemoglobin levels <7.5 g/dl or 4.65 mmol/l. Lactation.|
|Special Precautions||Renal and hepatic impairment; poor bone marrow reserve prior to treatment; risk of opportunistic infection; patients (especially obese women) with risk factors for or active liver disease. Patients with low body wt should avoid the combined formulation. Separate formulations of lamivudine or zidovudine should not be given at the same time as the combined formulation. If dose adjustment is necessary for either component, separate formulations should be used. Monitor haematological parameters (advanced disease: 2 wkly for 1st 3 mth of treatment, then monthly; early disease: 1-3 mthly), LFTs, mean cell volume, serum creatinine kinase, viral load, CD4 counts and blood lactate levels. Patient to report any sore throat, nausea, vomiting, unexplained bruising or bleeding. Maintain adequate hydration (2-3 L/day) unless fluid restricted. Withdraw treatment if symptomatic hyperlactaemia, metabolic/lactic acidosis, progressive heptomegaly or rapidly elevating aminotransferase levels occur. Cases of lactic acidosis and hepatic steatosis syndrome have been reported in pregnancy. Monitor hepatic enzymes and electrolytes regularly during 3rd trimester.|
|Adverse Drug Reactions||Headache, malaise and fatigue,
fever or chills, nausea, diarrhoea, anorexia, abdominal pain, neuropathy, insomnia and other sleep disorders, dizziness, depressive disorders, nasal signs
and symptoms, skin rashes, musculoskeletal pain, myalgia, arthralgia; anaemia, neutropenia and leucopenia (particularly at high doses of zidovudine;
1200-1500 mg/day), usually seen 4-5 wk after therapy commencing; respiratory symptoms eg rapid and/or deep breathing; if symptomatic hyperlactatemia,
metabolic/lactic acidosis, progressive hepatomegaly, or rapidly elevating aminotransferase levels occur, withdraw treatment; mitochondrial damage leading to
hyperlactatemia and hyperlipasemia; lipodystrophy; immune reactivation syndrome, osteonecrosis.
Potentially Fatal:Â Lactic acidosis associated with liver failure and pancreatitis (normally after several mth of treatment); haematological toxicity (eg neutropenia and severe anaemia).
|Drug Interactions||Zidovudine: acyclovir and valacyclovir may increase CNS depression. Increased risk of haematologic toxicity with ganciclovir, valganciclovir, dapsone, doxorubicin, vincristine and vinblastine. Doxorubicin may reduce phophorylation; fluconazole may increase levels/effects; increased risk of hepatic decompensation or haematologic toxicities with interferon-Î± and ribavirin (also increases risk of pancreatitis and lactic acidosis). Methadone may increase effects/levels. Increased risk of myalgia, malaise and/or fever, maculopapular rash and effects/levels with probenecid. Stavudine may decrease antiviral activity; valproic acid may increase plasma levels (AUC increased by 80%). Lamivudine: Increased risk of hepatic decompensation or haematologic toxicities with interferon-Î± and ribavirin (also increases risk of mitochondrial toxicity, pancreatitis and lactic acidosis). Ganciclovir and valganciclovir may increase effects and toxicity; sulfamethoxazole/trimethoprim may increase AUC and decrease clearance (increasing levels and effects).Â Please consult detailed drug interactions before prescribing.|
|Pregnancy Category (US FDA)||Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.|
|Storage||Oral:Â Store 2-30 Â°C.|
|Pharmacology||Synergistically reduce viral resistance and
inhibit reverse transcriptase via DNA chain termination.
Absorption:Â Lamivudine: oral bioavailability: 80-85% (children 66%); Cmax: 1.6 mcg/ml (32%); AUC: 6.1 mcg.h/ml (20%); Tmax: 0.75 (0.5-2.0 hr). Zidovudine: oral bioavailability: 60-70%; Cmax: 2.0 mcg/ml (40%); AUC: 2.4 mcg.h/ml; Tmax0.5 (0.25-2.0) hr.
Distribution:Â Volume of distribution: lamivudine 1.3 l/kg; zidovudine 1.6 l/kg. Protein binding: lamivudine: <36 %; zidovudine: 34-38%. Lamivudine and zidovudine enter CSF.
Metabolism:Â Lamivudine: Hepatically (small extent). Zidovudine: metabolised via glucuronidation to 3'-amino-3'-deoxythymidine (major metabolite; approx 50-80%).
Excretion:Â Elimination half-life: lamivudine: (adults) 5-7 hr, (children) 2 hr; zidovudine: 1.1 hr.
|ATC Classification||J05AF01 - zidovudine; Belongs to the class of nucleoside and
nucleotide reverse transcriptase inhibitors. Used in the systemic treatment of viral infections.Â
J05AF05 - lamivudine; Belongs to the class of nucleoside and nucleotide reverse transcriptase inhibitors. Used in the systemic treatment of viral infections.
Lamivudine and zidovudine may stop your body from making enough blood cells. Tell your doctor if you have or have ever had any blood disorders such as anemia or bone marrow problems. If you experience any of the following symptoms, call your doctor immediately: unusual bleeding or bruising; shortness of breath; pale skin; fever, sore throat, chills, and other signs of infection; or unusual tiredness or weakness.
Lamivudine and zidovudine may cause muscle disorders. Tell your doctor if you have or have ever had any disease or swelling of the muscles. If you experience muscle pain or weakness, call your doctor immediately.
When used alone or in combination with other antiretroviral medication, lamivudine and zidovudine may also cause serious damage to the liver and a condition called lactic acidosis. Tell your doctor if you drink or have ever drunk large amounts of alcohol and if you have or have ever had liver disease. Tell your doctor if you are taking acetaminophen (Tylenol) and if you have been taking medication to treat HIV infection for a long time. If you experience any of the following symptoms, call your doctor immediately: fatty and foul-smelling stools, upset stomach, extreme tiredness, unusual bleeding or bruising, lack of energy, loss of appetite, pain in the upper right part of the stomach, yellowing of the skin or eyes, or flu-like symptoms.
Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your body's response to lamivudine and zidovudine.
Why is this medication prescribed?
The combination of lamivudine and zidovudine is used along with other medications to treat human immunodeficiency virus (HIV) infection. Lamivudine and zidovudine are in a class of medications called nucleoside reverse transcriptase inhibitors (NRTIs). They work by decreasing the amount of HIV in the blood. Although the combination of lamivudine and zidovudine does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Taking these medications along with practicing safer sex and making other life-style changes may decrease the risk of transmitting (spreading) the HIV virus to other people.
How should this medicine be used?Â
The combination of lamivudine and zidovudine comes as a tablet to take by mouth. It is usually taken twice a day with or without food. To help you remember to take this medication, take it around the same time every day. Follow the directions on your prescription label carefully and ask your doctor to explain any part you do not understand. Take this medication exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Lamivudine and zidovudine controls HIV infection but does not cure it. Continue to take lamivudine and zidovudine even if you feel well. Do not stop taking lamivudine and zidovudine without talking to your doctor.
Other uses for this medicine
This medication may be prescribed for other uses; ask your doctor for more information.
What special precautions should I follow?
Before taking lamivudine and zidovudine,
- tell your doctor if you are allergic to lamivudine; zidovudine; lamivudine, zidovudine and abacavir or any other medications.
- you should know that lamivudine and zidovudine are also available individually with the brand names Epivir, Epivir HBV, and Retrovir, and in another combination as Trizivir. Tell your doctor if you are taking any of these medications, to be sure you do not receive the same medication twice.
- tell your doctor what prescription and nonprescription medications, vitamins, nutritional supplements and herbal products you are taking. Be sure to mention any of the following: acetaminophen, acyclovir, atovaquone, cancer chemotherapy drugs, cidofovir, dapsone, didanosine, doxorubicin, fluconazole, foscarnet, ganciclovir, interferon alpha, interferon beta-1b, methadone, nelfinavir, probenecid, ribavarin, rifabutin, rifampin, ritonavir, stavudine, trimethoprim, trimethoprim and sulfamethoxazole, valproic acid and zalcitabine. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- in addition to the conditions listed in the IMPORTANT WARNING section, tell your doctor if you have or have ever had kidney disease.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking lamivudine and zidovudine, call your doctor. You should not breast-feed while taking lamivudine and zidovudine.
- you should be aware that your body fat may increase or move to different areas of your body, such as your breasts and your upper back.
What special dietary instructions should I follow?
Unless your doctor tells you otherwise, continue your normal diet.
What should I do if I forget a dose?
Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
What side effects can this medication cause?
Lamivudine and zidovudine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
loss of appetite
difficulty falling asleep or staying asleep
- hair loss
Some side effects can be serious. The following side effects are uncommon, but if you experience any of them, or any of those listed in the IMPORTANT WARNING section, call your doctor immediately:
difficulty breathing or swallowing
numbness, tingling, or burning in your fingers or toes
Lamivudine and zidovudine may cause other side effects. Call your doctor if you have any unusual problems while taking lamivudine and zidovudine.
What should I know about storage and disposal of this medication?
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.
In case of emergency/overdose
In case of overdose,Â consult your doctor. If the victim has collapsed or is not breathing, consult local medical emergency services.
What other information should I know?
Keep all appointments with your doctor and the laboratory. Your doctor will order certain lab tests to check your response to this medicine.
Do not let anyone else use your medication. If you still have symptoms and need further treatment, consult your doctor.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
Ref:Â Â U.S. National Library of Medicine.
This information is provided for reference only and not a replacement for and should only be used in conjunction with full consultation with a registered medical practitioner. It may not contain all the available information you require and cannot substitute professional medical care, nor does it take into account all individual circumstances. Although great effort has been made to ensure content accuracy, mph-bd shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise.