PACKAGE LEAFLET Page 1 of 14
PACKAGE LEAFLET: INFORMATION FOR THE USER Abacavir Sulfate, Lamivudine and Zidovudine Tablets * Abacavir (as sulfate), lamivudine, zidovudine Read all of this leaflet carefully before you start taking this medicine. - Keep this leaflet. You may need to read it again. - If you have any further questions, ask your doctor, health care provider or pharmacist. - This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours. - If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor, health care provider or pharmacist. HYPERSENSITIVITY REACTION Patients taking Abacavir Sulfate, Lamivudine and Zidovudine Tablets may develop a hypersensitivity reaction (serious allergic reaction) to the component drug abacavir, which can be life-threatening if treatment with Abacavir Sulfate, Lamivudine and Zidovudine Tablets is continued. It is essential you read the information on this reaction under Take special care with Abacavir Sulfate, Lamivudine and Zidovudine Tablets in section 2 of this leaflet. There is also an Alert Card included in the Abacavir Sulfate, Lamivudine and Zidovudine Tablets pack, to remind you and medical staff about abacavir hypersensitivity. This card should be removed and kept with you at all times. CONTACT YOUR DOCTOR OR HEALTH CARE PROVIDER IMMEDIATELY for advice on whether you should stop taking Abacavir Sulfate, Lamivudine and Zidovudine Tablets if: 1) you get a skin rash OR 2) you get one or more symptoms from at least TWO of the following groups - fever - shortness of breath, sore throat or cough - nausea or vomiting or diarrhoea or abdominal pain - severe tiredness or achiness or generally feeling ill If you have discontinued Abacavir Sulfate, Lamivudine and Zidovudine Tablets due to a hypersensitivity reaction, YOU MUST NEVER TAKE Abacavir Sulfate, Lamivudine and Zidovudine Tablets or any other medicine containing abacavir (e.g.. Ziagen, Kivexa, Trizivir) again, as within hours you may experience a life-threatening lowering of your blood pressure or death. * Trade names are not prequalified by WHO. This is under local DRA responsibility. Throughout this WHOPAR the proprietary name is given as an example only. Page 2 of 14
In this leaflet: 1. What Abacavir Sulfate, Lamivudine and Zidovudine Tablets is and what it is used for 2. Before you take Abacavir Sulfate, Lamivudine and Zidovudine Tablets 3. How to take Abacavir Sulfate, Lamivudine and Zidovudine Tablets 4. Possible side effects 5. How to store Abacavir Sulfate, Lamivudine and Zidovudine Tablets 6. Further information 1. WHAT Abacavir Sulfate, Lamivudine and Zidovudine Tablets IS AND WHAT IT IS USED FOR Abacavir Sulfate, Lamivudine and Zidovudine Tablets contains three active component drugs: abacavir, lamivudine and zidovudine. All of these belong to a group of antiviral medicines, also known as antiretrovirals, called nucleoside analogue reverse transcriptase inhibitors (NRTIs). three active component drugs: abavacir, lamivudine and zidovudine. All of these belong to a group of antiviral medicines, also known as antiretrovirals, called nucleoside analogue reverse transcriptase inhibitors (NRTIs). Abacavir Sulfate, Lamivudine and Zidovudine Tablets reduces the amount of HIV in your body and keeps it at a low level. It also increases CD4 cell counts. CD4 cells are a type of white blood cell that plays an important role in maintaining a healthy immune system to help fight infection. Response to treatment with Abacavir Sulfate, Lamivudine and Zidovudine Tablets varies between patients. Your doctor or health care provider will be monitoring the effectiveness of your treatment. 2. BEFORE YOU TAKE Abacavir Sulfate, Lamivudine and Zidovudine Tablets Do not take Abacavir Sulfate, Lamivudine and Zidovudine Tablets if: - you are allergic (hypersensitive) to the active substance abacavir (which is also included in other medicines, called e.g. Ziagen, Kivexa and Trizivir) or to any of the other two active components: lamivudine and zidovudine. - if you are allergic to any of the other ingredients in Abacavir Sulfate, Lamivudine and Zidovudine Tablets (see What Abacavir Sulfate, Lamivudine and Zidovudine Tablets contains ) - if you have very low red blood cell count (severe anaemia) or very low white blood cell count (neutropenia). - if you have severe liver disease. Take special care with Abacavir Sulfate, Lamivudine and Zidovudine Tablets 300 mg/150 mg/ 300 mg It is important that your doctor or health care provider knows about all your symptoms even when you think they are not related to HIV infection. Your doctor or health care provider may decide to Page 3 of 14
prescribe abacavir, lamivudine or zidovudine as separate medicines instead of Abacavir Sulfate, Lamivudine and Zidovudine Tablets. Hypersensitivity reaction (serious allergic reaction) About 5 in every 100 patients, who are treated with Abacavir Sulfate, Lamivudine and Zidovudine Tablets, develop a hypersensitivity reaction to the active ingredient abacavir. People with a gene called HLA-B (type 5701) are more likely to have a hypersensitivity reaction to abacavir. However, even if you do not have this gene type it is still possible for you to get this reaction. If you know you have this gene type, be sure to tell your doctor or health care provider before you take abacavir. The most common symptoms of this reaction are high temperature (fever) and a skin rash. Other frequently observed signs or symptoms include nausea, vomiting, diarrhoea, abdominal pain and severe tiredness. Other symptoms may include joint or muscle pain, swelling of the neck, shortness of breath, sore throat, cough and headache. Occasionally, inflammation of the eye (conjunctivitis), mouth ulcers or low blood pressure may occur. The symptoms of this allergic reaction can occur at any time during treatment with Abacavir Sulfate, Lamivudine and Zidovudine Tablets. However they usually occur in the first six weeks of treatment. The symptoms worsen with continued treatment and may be life-threatening if treatment is continued. CONTACT YOUR DOCTOR OR HEALTH CARE PROVIDER IMMEDIATELY for advice on whether you should stop taking Abacavir Sulfate, Lamivudine and Zidovudine Tablets if: 1) you get a skin rash OR 2) you get one or more symptoms from at least TWO of the following groups -fever -shortness of breath, sore throat or cough -nausea or vomiting or diarrhoea or abdominal pain -severe tiredness or achiness or generally feeling ill. If you have discontinued Abacavir Sulfate, Lamivudine and Zidovudine Tablets due to a hypersensitivity reaction, YOU MUST NEVER TAKE Abacavir Sulfate, Lamivudine and Zidovudine Tablets or any other medicine containing abacavir (i.e. Ziagen, Kivexa, Trizivir) again, as within hours you may experience a life-threatening lowering of your blood pressure or death. If you have stopped taking Abacavir Sulfate, Lamivudine and Zidovudine Tablets for any reason, particularly because you think you are having side effects or for other illness, it is important that you contact your doctor or health care provider before restarting. Your doctor or health care provider will check whether any symptoms you had may be related to this hypersensitivity reaction. If your doctor or health care provider thinks there is a possibility that they were related, you will be instructed never to take Abacavir Sulfate, Lamivudine and Zidovudine Tablets or any other medicine containing abacavir (e.g. Ziagen, Kivexa, Trizivir) again. It is important that you follow this advice. Occasionally life-threatening hypersensitivity reactions have occurred when abacavir was restarted in patients who reported only one of the symptoms on the Alert Card before stopping. Page 4 of 14
On very rare occasions hypersensitivity has been reported when abacavir was restarted in patients who had no symptoms of hypersensitivity before stopping. If you are hypersensitive to abacavir you should return all of your unused Abacavir Sulfate,Lamivudine and Zidovudine Tablets for disposal. Ask your doctor, health care provider or pharmacist for advice. Kidney or liver disease Before using Abacavir Sulfate, Lamivudine and Zidovudine Tablets, you should have told your doctor or health care provider: if you have ever had or still have a liver disease (such as hepatitis) if you are suffering from or have ever suffered from kidney disease. Patients with chronic hepatitis B or C and treated with antiretroviral agents are at increased risk for severe and potentially fatal liver adverse events and may require blood tests for control of liver function. If you have a chronic hepatitis B infection, you should not stop your treatment without instructions from your doctor or health care provider, as you may have a recurrence of your hepatitis. This recurrence may be more severe if you have serious liver disease. Blood cell count Since low red blood cell count (anaemia) as well as low white blood cell count (neutropenia/leucopenia) may occur due to treatment with Abacavir Sulfate, Lamivudine and Zidovudine Tablets, regular blood tests will be arranged to check whether there is a problem. Lactic acidosis Females, particularly if very overweight and patients with liver disease may be more at risk of getting a rare, but serious side effect called lactic acidosis, a build up of lactic acid in the body. If lactic acidosis occurs, it usually develops after a few months of treatment. Deep rapid breathing, drowsiness, and non specific symptoms such as nausea, vomiting and stomach pain, might indicate the development of this condition. While you are being treated with Abacavir Sulfate, Lamivudine and Zidovudine Tablets your doctor or health care provider will monitor you for any signs that you may be developing lactic acidosis. Fat distribution Redistribution, accumulation or loss of body fat may occur in patients receiving combination antiretroviral therapy. Contact your doctor or health care provider if you notice loss of fat from legs, arms and face, increased fat in the belly (abdomen), breast enlargement and fatty lumps on the back of the neck ('buffalo hump'). Immune Reactivation Syndrome In some patients with advanced HIV infection (AIDS) and a history of opportunistic infection, signs and symptoms of inflammation from previous infections may occur soon after anti-hiv treatment is started. It is believed that these symptoms are due to an improvement in the body s immune response, enabling the body to fight infections that may have been present with no obvious symptoms. If you notice any symptoms of infection, please inform your doctor or health care provider immediately. Page 5 of 14
Bone problems Some patients taking combination antiretroviral therapy may develop a bone disease called osteonecrosis (death of bone tissue). Your risk of developing this disease may be higher: - if your immune system is severely compromised, - if you have been taken combination antiretroviral therapy for a long time, - if you drink alcohol regularly, - if you use corticosteroids (certain medicines suppressing your immune system), - if you are overweight. If you notice joint stiffness, aches and pains (especially of the hip, knee and shoulder) and difficulty in movement, inform your doctor or health care provider. General You will need to take Abacavir Sulfate, Lamivudine and Zidovudine Tablets every day. This medicine helps to control your condition, but it is not a cure for HIV infection. You may continue to develop other infections and other illnesses associated with HIV disease (e.g. opportunistic infections). These will require specific and sometimes preventive treatment. You should keep in regular contact with your doctor or health care provider. Do not stop taking your medicine without first talking to your doctor or health care provider. Treatment with Abacavir Sulfate, Lamivudine and Zidovudine Tablets has not been shown to reduce the risk of passing HIV infection on to others by sexual contact or by blood transfer. You should continue to use appropriate precautions to prevent this. Taking other medicines Please tell your doctor, health care provider or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. Abacavir Sulfate, Lamivudine and Zidovudine Tablets is unlikely to significantly interact with other medicines you are being treated with. However, in some cases the component drugs in Abacavir Sulfate, Lamivudine and Zidovudine Tablets may affect the actions of other drug, or be affected in their actions by other drugs. Abacavir Sulfate, Lamivudine and Zidovudine Tablets should not be taken with stavudine, emtricitabine or ribavirin (antiviral agents). Abacavir Sulfate, Lamivudine and Zidovudine Tablets may also interact with the following medicines and may make side effects worse or may impact on the either agent s efficacy -oral vitamin A related medicines, e.g. isotretinoin (medicine to treat acne) - rifampicin, co-trimoxazole (antibacterial agents), - phenobarbital, phenytoin, valproic acid (medicines to treat epileptic seizures),. - lopinavir with ritonavir, tipranavir with ritonavir (anti HIV-medicines) - ganciclovir, interferon (antiviral agents), - fluconazole, flucytosine, amphotericin (antifungal agents), - intravenously administered pentamidine, dapsone [unless used for prophylaxis] (antiparasitic agents), Page 6 of 14
- methadone (a medicine used in the treatment of opioid addiction and as a pain killer) - vicristine, vinblastine, doxorubicin (anti-cancer medicines), - probecenid (medicine for treatment of gout). -alcohol may increase the amount of abacavir in your blood Taking Abacavir Sulfate, Lamivudine and Zidovudine Tablets with food and drink Abacavir Sulfate Lamivudine and Zidovudine Tablets may be taken with our without food. Pregnancy and breastfeeding If you become pregnant, or are planning to become pregnant, you must contact your doctor or health care provider to discuss the potential adverse effects and the benefits and risks of your antiretroviral therapy to you and your child. Abacavir Sulfate, Lamivudine and Zidovudine Tablets therapy should not be started during pregnancy. If you have taken abacavir during your pregnancy, your doctor or health care provider may request regular visits to monitor the development of your child. Such visits may include blood tests and other diagnostic tests. In children whose mothers took nucleoside and nucleotide analogues during pregnancy, the benefit from the reduced chance of being infected with HIV was greater than the risk of suffering from side effects. Abacavir, lamivudine and zidovudine, the active agents in Abacavir Sulfate, Lamivudine and Zidovudine Tablets, are likely to be found in human breast milk. No safety data are available for the use of Abacavir Sulfate, Lamivudine and Zidovudine Tablets in babies under three months of age. Therefore, and since also the virus (HIV), pass into breast milk, it is recommended that HIV infected women taking Abacavir /Lamivudine /Zidovudine Tablets do not breastfeed their infants under any circumstances in order to avoid transmission of HIV as well as side effects of abacavir. Driving and using machines No studies on the effects of Abacavir Sulfate, Lamivudine and Zidovudine Tablets on the ability to drive and use machines have been performed. However, you should take into account the state of your health and the possible side effects of Abacavir Sulfate, Lamivudine and Zidovudine Tablets before considering driving or using machines. 3. HOW TO TAKE Abacavir Sulfate, Lamivudine and Zidovudine Tablets Always take Abacavir Sulfate, Lamivudine and Zidovudine Tablets exactly as your doctor or health care provider has told you. You should check with your doctor, health care provider or pharmacist if you are not sure. Page 7 of 14
The usual daily dose of Abacavir Sulfate, Lamivudine and Zidovudine Tablets in adults, adolescents and children weighing 25 kg or more is two tablets per day, one tablet in the morning and one tablet in the evening. Abacavir Sulfate, Lamivudine and Zidovudine Tablets should not be used for the treatment of children weighing less than 25 kg, since appropriate dose adjustments cannot be made. Swallow the tablet(s) with water. Abacavir /Lamivudine /Zidovudine Tablets may be taken with or without food. If you take more Abacavir Sulfate,/Lamivudine and Zidovudine Tablets than you should If you accidentally take too much of your medicine you should tell your doctor, health care provider or pharmacist, or contact your nearest hospital emergency department for further advice. If you forget to take Abacavir Sulfate Lamivudine and Zidovudine Tablets If you forget to take a dose of your medicine, take it as soon as you remember, and then continue as before. If your next dose is due in less than 6 hours, do not take the forgotten dose, but take the next regular dose when it is due. Do not take a double dose to make up for a forgotten dose. It is important to take Abacavir Sulfate, Lamivudine and Zidovudine Tablets regularly because irregular intake may increase the risk of hypersensitivity reactions. If you stop taking Abacavir Sulfate, Lamivudine and Zidovudine Tablets If you have stopped taking Abacavir Sulfate, Lamivudine and Zidovudine Tablets for any reason, particularly because you think you are having side effects or for other illness, it is important that you contact your doctor or health care provider before restarting. 4. POSSIBLE SIDE EFFECTS Like all medicines, Abacavir Sulfate, Lamivudine and Zidovudine Tablets can cause side effects, although not everybody gets them. When treating HIV infection, it is not always possible to tell whether some of the undesirable effects that occur are caused by Abacavir Sulfate, Lamivudine and Zidovudine Tablets by other medicines you are taking at the same time, or by the HIV disease. For this reason it is very important that you inform your doctor or health care provider about any changes in your health. A hypersensitivity reaction (serious allergic reaction) has been reported in about 5 in every 100 patients who have been treated with abacavir. This is described under Take special care with Abacavir Sulfate, Lamivudine and Zidovudine Tablets in section 2 of this leaflet. It is important that you read and understand the information about this serious reaction. Page 8 of 14
Common side effects (reported in 1 to 10 out of 100 patients): - skin rash (without any other illness) - decreased red blood cell count (anaemia). If the number of red blood cells is reduced, you may have symptoms of tiredness or breathlessness. - decreased white blood cell count. A reduction in your white blood cell count can make you more prone to infection. - nausea, vomiting, abdominal pain, diarrhoea - headache - fever, lethargy, fatigue, loss of appetite - raised blood levels of liver enzymes - muscle pain Uncommon side effects (reported in 1 to 10 out of 1000 patients): - low platelet count. If you have a low platelet count you may notice that you bruise more easily. - difficulties breathing - skin itching - a certain condition with low red and white blood cell counts and with low cell levels in the bone marrow (pure red cell aplasia). Rare side effects (reported in less than 1 in 1000 patients): - inflammation of the pancreas (pancreatitis) - insomnia, somnolence, convulsions - tingling in the limbs - disease of the heart muscle (cardiomyopathy) - chest pain, cough - pigmentation of nails and skin, pigmentation inside the mouth, taste disturbance - inflammation of the liver - breakdown of muscle tissue - breast enlargement in male patients Very rare side effects (reported in less than 1 in 10,000 patients): - serious skin reactions Frequency not known: The following side effects have been reported in patients treated with medicines of the group of NRTIs, to which also the components of Abacavir Sulfate, Lamivudine and Zidovudine Tablets belong. However, frequency estimates for these effects are not available: - lactic acidosis (a build up of lactic acid in the body, that can cause dehydration and coma). Deep, rapid breathing, drowsiness, and non specific symptoms such as nausea, vomiting and stomach pain, may indicate the development of lactic acidosis. - changes in body shape due to changes in fat distribution. These may include loss of fat from legs, arms and face, increased fat in the abdomen (belly) and other internal organs, breast enlargement and fatty lumps on the back of the neck ('buffalo hump'). The cause and long-term health effects of these conditions are not known at this time. - raised lactic acid and sugar in the blood, increased fats in the blood. - osteonecrosis (death of bone tissue) Page 9 of 14
- immune reactivation syndrome (see Take special care with Abacavir /Lamivudine /Zidovudine Tablets ). If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor, health care provider or pharmacist. 5. HOW TO STORE Abacavir Sulfate, Lamivudine and Zidovudine Tablets Keep out of the reach and sight of children. Store below 25º C, protected from moisture. Do not use Abacavir Sulfate, Lamivudine and Zidovudine Tablets after the expiry date which is stated on the package. The expiry date refers to the last day of that month. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment. 6. FURTHER INFORMATION What Abacavir Sulfate, Lamivudine and Zidovudine Tablets contains Each Abacavir Sulfate, Lamivudine and Zidovudine Tablets contains 300 mg abacavir, 150 mg lamivudine and 300 mg zidovudine. The other ingredients are colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose and sodium starch glycolate, Opadry 03B52874 Yellow (containing hypromellose, iron oxide red, iron oxide yellow, polyethylene glycol 400 and titanium dioxide). What Abacavir Sulfate, Lamivudine and Zidovudine Tablets looks like and contents of the pack Peach coloured, oval shaped, biconvex, unscored film-coated tablets, debossed with RC70 on one side and plain on the other side. The tablets should not be divided. White opaque HDPE bottle with white opaque polypropylene fine ribbed screw cap with induction sealing liner, containing 60 tablets. Page 10 of 14
Supplier and Manufacturer Supplier: Ranbaxy Laboratories Limited Paonta Sahib District Simour Himachal Pradesh 173025 India TEL : (+91-1704) 222462 222834 222720 223493 Fax. (+91-1704) 223492, 222832 Email: ramesh.parekh@ranbaxy.com Manufacturer: Ranbaxy Laboratories Limited Paonta Sahib District Simour Himachal Pradesh 173025 India TEL : (+91-1704) 222462 222834 222720 223493 Fax. (+91-1704) 223492, 222832 Email: ramesh.parekh@ranbaxy.com For any information about this medicinal product, please contact the local representative of the supplier: Dr Saikiran Leekha Head, Medical Affairs- Asia Pacific, Middle East & CIS Countries Ranbaxy Laboratories Limited Peti # 8, 5th Floor, South Block, Wisma Selangor Dredging, 142-A, Jalan Ampang, Kuala Lampur, Malaysia Tel: +603 2161 4181 e.mail: saikiran.leekha@ranbaxy.com Dr. Prashant Dongre Manager- Medical Services Ranbaxy Laboratories Ltd. Ranbaxy House, Plot no. 89, 15th Road, M.I.D.C., Andheri (East), Mumbai -400093. Ph: 91-22-67806400 Ext:226 91-22-28237832 (Direct ) Fax:91-22-28214463 e.mail: prashant.dongre@ranbaxy.com Page 11 of 14
This leaflet was last approved in March 2009 Detailed information on this medicine is available on the World Health Organization (WHO) web site: http://www.who.int/prequal/. Page 12 of 14
Attachment: ALERT CARD TEXT SIDE 1 IMPORTANT - ALERT CARD Abacavir Sulfate, Lamivudine and Zidovudine Tablets Carry this card with you at all times Patients taking Abacavir Sulfate, Lamivudine and Zidovudine Tablets may develop a hypersensitivity reaction (serious allergic reaction) which can be life-threatening if treatment with Abacavir Sulfate, Lamivudine and Zidovudine Tablets is continued. CONTACT YOUR DOCTOR OR HEALTH CARE PROVIDER IMMEDIATELY for advice on whether you should stop taking Abacavir Sulfate, Lamivudine and Zidovudine Tablets if: 1) you get a skin rash OR 2) you get one or more symptoms from at least TWO of the following groups - fever - shortness of breath, sore throat or cough - nausea or vomiting or diarrhoea or abdominal pain - severe tiredness or achiness or generally feeling ill If you have discontinued Abacavir /Lamivudine /Zidovudine Tablets due to this reaction, YOU MUST NEVER TAKE Abacavir Sulfate, Lamivudine and Zidovudine Tablets or any other abacavir-containing medicine (e.g. Ziagen, Kivexa, Trizivir) again, as within hours you may experience a life-threatening lowering of your blood pressure or death. (see reverse of card) SIDE 2 You should immediately contact your doctor or health care provider if you think you are having a hypersensitivity reaction to Abacavir Sulfate, Lamivudine and Zidovudine Tablets. Write your doctor/health care provider s details below: Doctor/health care provider:... Tel:..... If your doctor or health care provider is not available, you must urgently seek alternative medical advice (e.g. the emergency unit of the nearest hospital). For general information enquiries on Abacavir Sulfate, Lamivudine and Zidovudine Tablets, contact Dr Saikiran Leekha Head, Medical Affairs- Asia Pacific, Middle East & CIS Countries Ranbaxy Laboratories Limited Peti # 8, 5th Floor, South Block, Wisma Selangor Dredging, 142-A, Jalan Ampang, Page 13 of 14
Kuala Lampur, Malaysia Tel: +603 2161 4181 e.mail: saikiran.leekha@ranbaxy.com Dr. Prashant Dongre Manager- Medical Services Ranbaxy Laboratories Ltd. Ranbaxy House, Plot no. 89, 15th Road, M.I.D.C., Andheri (East), Mumbai -400093. Ph: 91-22-67806400 Ext:226 91-22-28237832 (Direct ) Fax:91-22-28214463 e.mail: prashant.dongre@ranbaxy.com Page 14 of 14