Lamivudine + zidovudine accord

Package leaflet: Information for the patient

Lamivudine + Zidovudine Accord, 150 mg + 300 mg, film-coated tablets
Lamivudinum + Zidovudinum
Please read this leaflet carefully before taking this medicine, because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Table of contents

1. What Lamivudine + Zidovudine Accord is and what it is used for
2. What you need to know before taking Lamivudine + Zidovudine Accord
3. How to take Lamivudine + Zidovudine Accord
4. Possible side effects
5. How to store Lamivudine + Zidovudine Accord
6. Contents of the pack and other information

1. What Lamivudine + Zidovudine Accord is and what it is used for

Lamivudine + Zidovudine Accord is used to treat human immunodeficiency virus (HIV) infection in adults and children.
Lamivudine + Zidovudine Accord contains two active substances used in the treatment of HIV infection: lamivudine and zidovudine. Both substances belong to a group of antiretroviral medicines called nucleoside reverse transcriptase inhibitors (NRTIs).
Lamivudine + Zidovudine Accord does not cure HIV infection; it reduces the amount of virus and maintains it at a low level. It also increases the number of CD4 cells in the blood. CD4 cells are a type of white blood cell that plays an important role in helping the body fight infections.
Not all patients respond to treatment with Lamivudine + Zidovudine Accord in the same way. The effectiveness of treatment will be monitored by your doctor.

2. Important information before using Lamivudine + Zidovudine Accord

When not to use Lamivudine + Zidovudine Accord

• if the patient is allergic to lamivudine, zidovudine, or any of the other ingredients of this medicine (listed in section 6);
• if the patient has very low red blood cell count (anaemia) or very low white blood cell count (neutropenia).

Consult your doctor if you suspect that any of the above conditions apply to you.
Warnings and precautions
Some patients taking Lamivudine + Zidovudine Accord or other combination treatments for HIV are at higher risk of developing serious side effects. You should be aware of this additional risk:

• if you have ever had liver disease, including hepatitis B or C (if you have hepatitis B, do not stop taking Lamivudine + Zidovudine Accord without medical advice, as hepatitis may worsen);
• if you have kidney disease;
• if you have significant overweight (particularly in women).

Inform your doctor if any of the above conditions apply to you. Your doctor may recommend additional monitoring tests during treatment, including blood tests. See section 4 for more information.
Be alert to important symptoms
Some patients taking medicines for HIV infection may develop other complications, which can be serious. You should read about the important signs and symptoms to watch for while taking Lamivudine + Zidovudine Accord.
Please read the information titled ‘Other possible side effects of combination HIV treatment’
in section 4 of this leaflet.
Protecting other people
HIV infection can be transmitted through sexual contact with infected individuals or through infected blood (e.g. by sharing injecting needles). You may still transmit HIV while taking this medicine, although effective antiretroviral therapy reduces this risk.
You should discuss with your doctor the necessary precautions to avoid infecting others.
Lamivudine + Zidovudine Accord and other medicines
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including herbal products and medicines available without a prescription.
If you start taking a new medicine while using Lamivudine + Zidovudine Accord, remember to inform your doctor or pharmacist.
Do not take the following medicines with Lamivudine + Zidovudine Accord:

• other medicinal products containing lamivudine, used in the treatment of HIV infection or hepatitis B virus infection,
• emtricitabine, used in the treatment of HIV infection,
• stavudine, used in the treatment of HIV infections,
• ribavirin or ganciclovir injections, used in the treatment of viral infections,
• high doses of co-trimoxazole, used as an antibiotic,
• cladribine, used in the treatment of hairy cell leukaemia.

Inform your doctor if you are being treated with any of these medicines.
Some medicines may increase the likelihood of side effects
or worsen existing ones.
These include:

• sodium valproate, used in the treatment of epilepsy,
• interferon, used in the treatment of viral infections,
• pyrimethamine, used in the treatment of malaria and other parasitic infections,
• dapsone, used to prevent pneumonia and in the treatment of skin infections,
• fluconazole or flucytosine, used in the treatment of fungal infections, such as candidiasis,
• pentamidine or atovaquone, used in the treatment of parasitic infections, such as pneumonia caused by Pneumocystis jirovecii (often called Pneumocystis pneumonia),
• amphotericin or co-trimoxazole, used in the treatment of bacterial and fungal infections,
• probenecid, used in the treatment of gout and similar conditions, and also used together with certain antibiotics to increase their effectiveness,
• methadone, used as a heroin substitute,
• vincristine, vinblastine or doxorubicin, used in the treatment of cancer.

Inform your doctor if you are being treated with any of these medicines.
Some medicines interact with Lamivudine + Zidovudine Accord
These include:

• clarithromycin, an antibiotic. If you are taking clarithromycin, take it at least 2 hours before or after taking Lamivudine + Zidovudine Accord.
• phenytoin, used in the treatment of epilepsy.

If you are taking phenytoin, inform your doctor. Your doctor may recommend monitoring you while you are taking Lamivudine + Zidovudine Accord.

• medicines (usually in liquid form) containing sorbitol or other sugar alcohols (such as xylitol, mannitol, lactitol or maltitol), if used long-term.

If you are taking any of these medicines, tell your doctor or pharmacist.
Pregnancy and breastfeeding
Pregnancy
If you are pregnant, think you may be pregnant, or are planning to have a baby, contact your doctor to discuss the benefits and risks for you and your baby of taking Lamivudine + Zidovudine Accord during pregnancy.
Lamivudine + Zidovudine Accord and similar medicines may cause side effects in unborn children. If you took Lamivudine + Zidovudine Accord during pregnancy, your doctor may recommend regular blood tests and other diagnostic tests to monitor your child's development. For children whose mothers took NRTIs during pregnancy, the benefit of reduced risk of HIV transmission outweighs the risk of side effects.
Breastfeeding
Women with HIV must not breastfeed their babies, because HIV infection can be passed to the baby through breast milk.
A small amount of the active substances in Lamivudine + Zidovudine Accord may also pass into breast milk.
If you are breastfeeding or planning to breastfeed, you should seek immediate advice from your doctor.
Driving and using machines
Lamivudine + Zidovudine Accord may cause dizziness and other side effects that may impair concentration.
Do not drive or operate machinery unless you feel well.
Lamivudine + Zidovudine Accord contains sodium
This medicine contains 48.15 mg of sodium (the main component of table salt) in each tablet.
This corresponds to 2.4% of the recommended maximum daily intake of sodium for an adult.

3. How to take Lamivudine + Zidovudine Accord

This medicine should always be taken exactly as prescribed by the doctor or pharmacist.
If in doubt, contact the treating physician or pharmacist.
The coated tablet should be swallowed with water. Lamivudine + Zidovudine Accord may be taken
with or without food.
If a patient is unable to swallow the tablet, it may be crushed and mixed with a small amount of food or liquid, and the entire dose should be taken immediately after preparation.
Regular contact with the treating physician
Lamivudine + Zidovudine Accord helps control the disease. It should be taken daily to prevent disease progression. Other infections and illnesses related to HIV infection may still occur.
It is important to maintain regular contact with the treating physician and not discontinue
treatment with Lamivudine + Zidovudine Accord without medical advice.
What dose should be taken
Adults and adolescents weighing at least 30 kg
The usual dose of Lamivudine + Zidovudine Accord is 1 tablet twice daily.
The tablets should be taken at regular intervals, approximately 12 hours apart.
Children weighing between 21 kg and 30 kg
The usual initial dose of Lamivudine + Zidovudine Accord is half (1/2) tablet in the morning and one whole tablet in the evening.
Children weighing between 14 kg and 21 kg
The usual initial dose of Lamivudine + Zidovudine Accord is half (1/2) tablet in the morning and half (1/2) tablet in the evening.
For children weighing less than 14 kg, lamivudine and zidovudine (the components of Lamivudine + Zidovudine Accord) should be administered separately.
The tablet can be divided into two equal doses.
Taking more Lamivudine + Zidovudine Accord than prescribed
If a patient accidentally takes more Lamivudine + Zidovudine Accord than prescribed, inform the treating physician or pharmacist immediately, or contact the nearest hospital emergency department for further advice.
Missing a dose of Lamivudine + Zidovudine Accord
If a dose is missed, take it as soon as possible. Continue treatment as before. Do not take a double dose to make up for a missed dose.

4. Possible side effects

Treatment of HIV infection may lead to increased body weight and increased levels of lipids and glucose in the blood. This is partly related to improved health and lifestyle, and sometimes, in the case of blood lipid levels, to the effect of anti-HIV drugs. Your doctor will recommend tests to detect these changes.

Treatment with Lamivudine + Zidovudine Accord frequently causes loss of fat tissue in the legs, arms, and face (lipoatrophy). Loss of fat tissue is not fully reversible after discontinuation of zidovudine. Your doctor should monitor you for signs of lipoatrophy. If you notice any loss of fat tissue in the legs, arms, or face, inform your doctor. If such symptoms occur, Lamivudine + Zidovudine Accord should be discontinued and alternative treatment for HIV infection initiated.

Like all medicines, this medicine can cause side effects, although not everybody will experience them. During treatment of HIV infection, it is not always possible to determine whether an adverse symptom is caused by Lamivudine + Zidovudine Accord, by other medicines taken at the same time, or by the HIV infection itself. For this reason, it is very important to inform your doctor
about any changes in your health status.
In addition to the side effects listed below for Lamivudine + Zidovudine Accord,
other symptoms may also occur during combination treatment for HIV infection.
It is important to read the information provided below under 'Other possible side effects of combination treatment for HIV infection'.

Very common: may occur in more than 1 in 10 patients:

• headache,
• nausea.

Common: may occur in not more than 1 in 10 patients:

• vomiting,
• diarrhoea,
• abdominal pain,
• loss of appetite,
• dizziness,
• fatigue, weakness,
• fever (high temperature),
• general malaise,
• difficulty sleeping (insomnia),
• muscle pain and discomfort,
• joint pain,
• cough,
• nasal irritation or watery nasal discharge,
• rash,
• hair loss (alopecia).

Common side effects that may be revealed by blood tests:

• low number of red blood cells (anaemia) or low number of white blood cells (neutropenia or leukopenia),
• increased liver enzyme activity,
• increased blood levels of bilirubin (a substance produced in the liver), which may cause yellowing of the skin.

Uncommon: may occur in not more than 1 in 100 patients:

• shortness of breath,
• flatulence (bloating),
• itching,
• muscle weakness.

Uncommon side effects that may be revealed by blood tests:

• reduced number of platelets involved in blood clotting (thrombocytopenia) or reduced number of all types of blood cells (pancytopenia).

Rare: may occur in not more than 1 in 1000 patients:

• severe allergic reactions causing swelling of the face, tongue or throat, which may lead to difficulty in swallowing or breathing,
• liver disorders such as jaundice, liver enlargement or fatty liver, hepatitis,
• lactic acidosis (excess lactic acid in the blood; see next section, "Other possible side effects of combination treatment for HIV infection"),
• pancreatitis,
• chest pain, heart muscle disease (cardiomyopathy),
• seizures (epileptic fits),
• feeling depressed or anxious, difficulty concentrating, drowsiness,
• indigestion, taste disturbances,
• change in nail, skin or oral mucosa pigmentation,
• influenza-like symptoms – chills and excessive sweating,
• skin tingling, numbness,
• feeling of limb weakness,
• muscle breakdown,
• tingling sensations,
• frequent urination,
• breast enlargement in men.

Rare side effects that may be revealed by blood tests:

• increased activity of an enzyme called amylase,
• bone marrow failure to produce new red blood cells (pure red cell aplasia).

Very rare: may occur in not more than 1 in 10,000 patients:
Very rare side effects that may be revealed by blood tests:

• bone marrow failure to produce new red or white blood cells (aplastic anaemia).

If you experience any side effects
Inform your doctor or pharmacist if any of the side effects worsen or if you experience any side effects not listed in this leaflet.

Other possible side effects of combination treatment for HIV infection
Combination therapy, including the use of Lamivudine + Zidovudine Accord, may lead to the development of other conditions during HIV treatment.

Old infections may flare up suddenly
Patients with advanced HIV infection (AIDS) have a weakened immune system and are more prone to developing severe infections (opportunistic infections). Shortly after starting treatment, previously hidden infections may flare up, causing symptoms of inflammation. These symptoms are likely due to immune reconstitution, whereby the strengthened immune system begins to fight the infections. Additionally, apart from opportunistic infections, autoimmune diseases (conditions in which the immune system attacks healthy body tissues) may occur after starting anti-HIV drugs. These may appear many months after starting treatment. If you notice symptoms of infection or other symptoms such as muscle weakness, weakness starting in the hands or feet and progressing towards the trunk, palpitations, tremor or hyperactivity, contact your doctor immediately to initiate necessary treatment.

If you notice any signs of infection while taking Lamivudine + Zidovudine Accord:
Contact your doctor immediately. Do not take any other medicines for infections without your doctor's advice.

Lactic acidosis is a rare but serious side effect
Some patients taking Lamivudine + Zidovudine Accord may develop a condition called lactic acidosis, accompanied by liver enlargement.
Lactic acidosis is caused by a build-up of lactic acid in the body. It is rare; if it occurs, it usually develops after several months of treatment. It may be life-threatening due to damage to internal organs.
Lactic acidosis is more likely in patients with liver disease or obesity (excess weight), particularly in women.

Symptoms of lactic acidosis include:

• deep, rapid breathing, difficulty breathing,
• drowsiness,
• numbness or weakness in limbs,
• nausea, vomiting,
• abdominal pain.

During treatment, your doctor will monitor you for symptoms that may indicate the development of lactic acidosis. If you experience any of the symptoms listed above or other concerning symptoms, contact your doctor as soon as possible.

Bone disorders may occur
Some patients receiving combination anti-HIV therapy may develop a bone disorder called avascular necrosis. This involves the death of bone tissue due to reduced blood supply to the bone.

The risk of developing this condition is higher in patients who:

• have been on long-term combination therapy,
• are also taking anti-inflammatory medicines called corticosteroids,
• drink alcohol,
• have a very weak immune system,
• are overweight.

Symptoms of avascular necrosis include:

• joint stiffness,
• pain (especially in the hips, knees and shoulders),
• difficulty moving. If any of these symptoms occur, inform your doctor.

Other effects that may be detected in laboratory tests
Combination anti-HIV therapy may also cause:

• increased blood lactic acid levels, which rarely may lead to lactic acidosis.

Reporting of side effects
If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. Side effects can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
tel: + 48 22 49 21 301
fax: + 48 22 49 21 309
e-mail: [email protected]
Side effects can also be reported to the marketing authorisation holder.
Reporting side effects helps provide more information on the safety of the medicine.

5. How to store Lamivudine + Zidovudine Accord

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after: Expiry (EXP). The expiry date refers to the last day of the stated month.
No special storage conditions are required for this medicine.
Medicines must not be disposed of via the sewage system. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Lamivudine + Zidovudine Accord contains
The active substances in this medicine are lamivudine and zidovudine.
Each film-coated tablet contains 150 mg of lamivudine and 300 mg of zidovudine.
The other ingredients are:

• microcrystalline cellulose, sodium carboxymethyl starch (type A), magnesium stearate
• coating Opadry White YS-1-7003: titanium dioxide (E 171), hypromellose 3 cP, hypromellose 6 cP, macrogol 400, polysorbate 80.

What Lamivudine + Zidovudine Accord looks like and contents of the pack
Lamivudine + Zidovudine Accord is available in blister packs made of PVC/PVDC/Aluminium foil containing 60, 120 or 200 film-coated tablets, or in HDPE bottles with PP screw caps and child-resistant closure, containing 60 or 500 film-coated tablets.
Lamivudine + Zidovudine Accord is a white or almost white, biconvex, capsule-shaped film-coated tablet, with a central breakline, marked with "H" on one side and "L" and "9" on the other side. The tablet is approximately 17.5 mm long and 8.0 mm wide.
Not all pack types and sizes may be marketed.
Marketing Authorisation Holder:
Accord Healthcare Polska Sp. z o.o.
Taśmowa Street 7
02-677 Warsaw
Poland
Manufacturer/Importer:
Accord Healthcare Limited
Sage House, 319 Pinner Road
North Harrow
Middlesex, HA1 4HF
United Kingdom
Pharmadox Healthcare Limited
KW20A Kordin Industrial Park
Paola, PLA 3000
Malta
This medicinal product is authorised in the European Economic Area countries under the following names: