Patient leaflet - Lamivudine/zidovudine 150 mg/300 mg film-coated tablets

1. What Lamivudine/Zidovudine is and what it is used for

Lamivudine/Zidovudine is used to treat HIV (human immunodeficiency virus) infection in adults and children.

Lamivudine/Zidovudine contains two active ingredients that are used to treat HIV infection: lamivudine and zidovudine. Both of these belong to a group of antiretroviral medicines called nucleoside analogue reverse transcriptase inhibitors (NRTIs).

Lamivudine/Zidovudine does not completely cure HIV infection; it reduces the amount of virus in your body, and keeps it at a low level. It also increases the CD4 cell count in your blood. CD4 cells are a type of white blood cells that are important in helping your body to fight infection.

Not everyone responds to treatment with Lamivudine/ Zidovudine in the same way. Your doctor will monitor the effectiveness of your treatment.

2. What you need to know before you take Lamivudine/Zidovudine

Do not take Lamivudine/Zidovudine

if you are allergic to lamivudine or zidovudine, or
any of the other ingredients of this medicine (listed in section 6).
if you have a very low red blood cell count
(anaemia) or a very low white blood cell count (neutropenia).

Check with your doctor if you think any of these apply to you.

Warnings and precautions

Talk to your doctor or pharmacist before taking Lamivudine/Zidovudine.

Some people taking Lamivudine/Zidovudine or other combination treatments for HIV are more at risk of serious side effects. You need to be aware of the extra risks:

if you have ever had liver disease, including
hepatitis B or C (if you have hepatitis B infection, do not stop Lamivudine/Zidovudine without your doctor’s advice, as your hepatitis may come back)
if you have kidney disease
if you are seriously overweight (especially if you’re
a woman)

Talk to your doctor if any of these apply to you. Your doctor will decide if the active substances are suitable for you. You may need extra check-ups, including blood tests, while you’re taking your medicine. See Section 4 for more information.

Look out for important symptoms

Some people taking medicines for HIV infection develop other conditions, which can be serious. You need to know about important signs and symptoms to look out for while you’re taking Lamivudine/Zidovudine.

Read the information ‘Other possible side effects of combination therapy for HIV’ in Section 4 of this leaflet.

Other medicines and Lamivudine/Zidovudine Tell your doctor or pharmacist if you are taking,

have recently taken or might take any other medicines, or if you have taken any recently, including herbal medicines or other medicines you bought without a prescription.

Remember to tell your doctor or pharmacist if you begin taking a new medicine while you’re taking Lamivudine/Zidovudine.

These medicines should not be used with Lamivudine/Zidovudine:

other medicinal products containing lamivudine, to
treat HIV infection or hepatitis B infection
emtricitabine, to treat HIV infection
stavudine to treat HIV infection
ribavirin, or injections of ganciclovir to treat viral
infections
high doses of co-trimoxazole, an antibiotic.
cladribine, used to treat hairy cell leukaemia Tell your doctor if you’re being treated with any of these.

Some medicines can make it more likely that you’ll have side effects, or make side effects worse.

These include:

sodium valproate, to treat epilepsy
interferon, to treat viral infections
pyrimethamine, to treat malaria and other parasitic
infections
dapsone, to prevent pneumonia and treat skin
infections
fluconazole or flucytosine, to treat fungal
infections such as candida
pentamidine or atovaquone to treat parasitic
infections such as Pneumocystis jirovecii pneumonia (often referred to as PCP)
amphotericin or co-trimoxazole, to treat fungal and
bacterial infections
- probenecid, to treat gout and similar conditions, and given with some antibiotics to make them more effective
- methadone, used as a heroin substitute
- vincristine, vinblastine or doxorubicin, to treat cancer

Tell your doctor if you’re taking any of these.

Some medicines interact with Lamivudine/ Zidovudine

These include:

clarithromycin, an antibiotic
if you’re taking clarithromycin, take your dose at least 2 hours before or after you take your Lamivudine/Zidovudine.
phenytoin, for treating epilepsy
Tell your doctor if you’re taking phenytoin. Your doctor may need to monitor you while you’re taking Lamivudine/Zidovudine.
medicines (usually liquids) containing sorbitol and other sugar alcohols (such as xylitol, mannitol, lactitol or maltitol), if taken regularly.

Tell your doctor or pharmacist if you are being treated with any of these.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

If you are pregnant, if you become pregnant or if you are planning to become pregnant talk to your doctor about the risks and benefits to you and your baby of taking Lamivudine/Zidovudine.

Lamivudine/Zidovudine and similar medicines may cause side effects in unborn babies. If you have taken Lamivudine/Zidovudine during your pregnancy, your doctor may request regular blood tests and other diagnostic tests to monitor the development of your child. In children whose mothers took NRTIs during pregnancy, the benefit from the protection against HIV outweighed the risk of side effects.

Breast-feeding

Breast-feeding is not recommended in women living with HIV, because HIV infection can be passed on to the baby in breast milk.

A small amount of the ingredients in Lamivudine/ Zidovudine can also pass into your breast-milk. If you’re breast-feeding or thinking about breast-eeding, you should feeding, you should discuss it with your doctor as soon as possible.

Driving and using machines

Lamivudine/Zidovudine can make you dizzy and have other side effects that make you less alert.

Do not drive or operate machines unless you’re feeling well.

Lamivudine/Zidovudine contains Sodium

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium free’.

3. How to take Lamivudine/Zidovudine

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Swallow Lamivudine/Zidovudine tablets, with some water. Lamivudine/Zidovudine can be taken with or without food.

If you cannot swallow the tablets whole, you may crush and combine them with a small amount of food or drink, and take all the dose immediately.

Stay in regular contact with your doctor

Lamivudine/Zidovudine helps to control your condition. You need to keep taking it every day to stop your illness getting worse. You may still develop other infections and illnesses linked to HIV infection.

Keep in touch with your doctor, and do not stop taking Lamivudine/Zidovudine without your doctor’s advice.

How much to take

Adults and adolescents 30 kg or more

The usual dose of Lamivudine/Zidovudine is one tablet twice a day.

Take the tablets at regular times, leaving approximately 12 hours between each tablet.

Children who weigh between 21 and 30 kg

The usual starting dose of Lamivudine/Zidovudine is one half tablet (½) taken in the morning and one whole tablet taken in the evening.

Children who weigh between 14 and 21 kg

The usual starting dose of Lamivudine/Zidovudine is one half tablet (½) taken in the morning and one half tablet (½) taken in the evening.

For children who weigh less than 14 kg lamivudine and zidovudine (the ingredients of Lamivudine/Zidovudine) should be taken separately.

If you take more Lamivudine/Zidovudine than you should

If you accidentally take too much Lamivudine/ Zidovudine, tell your doctor or your pharmacist, or contact your nearest hospital emergency department for further advice.

If you forget to take Lamivudine/Zidovudine

If you forget to take a dose, take it as soon as you remember. Then continue your treatment as before. Do not take a double dose to make up for a forgotten dose.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

During HIV therapy there may be an increase in weight and in levels of blood lipids and glucose. This is partly linked to restored health and life style, and in the case of blood lipids sometimes to the HIV medicines themselves. Your doctor will test for these changes. Treatment with Lamivudine/Zidovudine often causes a loss of fat from legs, arms and face (lipoatrophy). This loss of body fat has been shown to be not fully reversible after discontinuation of zidovudine. Your doctor should monitor for signs of

lipoatrophy. Tell your doctor if you notice any loss of fat from your legs, arms, and face. When these Package leaflet: Information for the user

Lamivudine/Zidovudine 150 mg/

300 mg film-coated tablets

lamivudine/zidovudine signs occur, Lamivudine/Zidovudine should be stopped and your HIV treatment changed. Like all medicines, this medicine can cause side effects, but not everyone gets them. When you’re being treated for HIV, it can be hard to tell whether a symptom is a side effect of Lamivudine/Zidovudine or other medicines you’re taking, or an effect of the HIV disease itself. So it is very important to talk to your doctor about any changes in your health. As well as the side effects listed below for Lamivudine/Zidovudine, other conditions can develop during combination therapy for HIV. It is important to read the information later in this section under ‘Other possible side effects of combination therapy for HIV’.

Very common side effects

These may affect more than 1 in 10 people:

headache
feeling sick (nausea)

Common side effects

These may affect up to 1 in 10 people:

being sick (vomiting)
diarrhoea
stomach pains
loss of appetite
feeling dizzy
tiredness, lack of energy
fever (high temperature)
general feeling of being unwell
difficulty in sleeping (insomnia)
muscle pain and discomfort
joint pain
cough
irritated or runny nose
skin rash
hair loss (alopecia)

Common side effects that might show up in blood tests are:

a low red blood cell count (anaemia) or low white
blood cell count (neutropenia or Leukopenia)
an increase in the level of liver enzymes
an increased amount in the blood of bilirubin (a
substance produced in the liver) which may make your skin appear yellow.

Uncommon side effects

These may affect up to 1 in 100 people:

feeling breathless
wind (flatulence)
itching
muscle weakness

An uncommon side effect that may show up in blood test is:

a decrease in the number of cells involved in blood
clotting (thrombocytopenia) or in all kinds of blood cells (pancytopenia).

Rare side effects

These may affect up to 1 in 1,000 people:

serious allergic reaction causing swelling of the
face, tongue or throat which may cause difficulty in swallowing or breathing
liver disorders, such as jaundice, enlarged liver or
fatty liver, inflammation (hepatitis)
lactic acidosis (excess lactic acid in the blood see
the next section, ‘Other possible side effects of combination therapy for HIV’)
inflammation of the pancreas (pancreatitis)
chest pain; disease of the heart muscle
(cardiomyopathy)
fits (convulsions)
feeling depressed or anxious, not being able to
concentrate, feeling drowsy
indigestion, taste disturbance
changes in the colour of your nails, your skin or the
skin inside your mouth
a flu-like feeling – chills and sweating
tingly feelings in the skin (pins and needles)
sensation of weakness in the limbs
breakdown of muscle tissue
numbness
passing urine more often
enlarged breasts in men

Rare side effects that may show up in blood tests are:

an increase in an enzyme called amylase
a failure of the bone marrow to produce new red
blood cells (pure red cell aplasia).

Very rare side effects

These may affect up to 1 in 10,000 people: A very rare side effect that may show up in blood tests is:

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

If you get side effects

Tell your doctor or pharmacist if any of the side effects get severe or troublesome, or if you notice any side effects not listed in this leaflet.

Other possible side effects of combination therapy for HIV

Combination therapy such as Lamivudine/Zidovudine may cause other conditions to develop during HIV treatment.

Old infections may flare up

People with advanced HIV infection (AIDS) have weak immune systems, and are more likely to develop serious infections (opportunistic infections). When these people start treatment, they may find that old, hidden infections flare up, causing signs and symptoms of inflammation. These symptoms are probably caused by the body’s immune system becoming stronger, so that the body starts to fight these infections.

In addition to the opportunistic infections, autoimmune disorders (a condition that occurs when the immune system attacks healthy body tissue) may also occur after you start taking medicines for the treatment of your HIV infection. Autoimmune disorders may occur many months after the start of treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness beginning in the hands and feet and moving up towards the trunk of the body, palpitations, tremor or hyperactivity, please inform your doctor immediately to seek necessary treatment. If you get any symptoms of infection while you’re taking Lamivudine/Zidovudine:

Tell your doctor immediately. Do not take other medicines for the infection without your doctor’s

advice.

Lactic acidosis is a rare but serious side effect

Some people taking Lamivudine/Zidovudine, develop a condition called lactic acidosis, together with an enlarged liver.

Lactic acidosis is caused by a build-up of lactic acid in the body. It is rare; if it happens, it usually develops after a few months of treatment. It can be life-threatening, causing failure of internal organs. Lactic acidosis is more likely to develop in people who have liver disease, or in obese (very overweight) people, especially women.

Signs of lactic acidosis include:

deep, rapid, difficult breathing
drowsiness
numbness or weakness in the limbs
feeling sick (nausea), being sick (vomiting)
stomach pain

During your treatment, your doctor will monitor you for signs of lactic acidosis. If you have any of the symptoms listed above, or any other symptoms that worry you:

See your doctor as soon as possible.

You may have problems with your bones

Some people taking combination therapy for HIV develop a condition called osteonecrosis. With this condition, parts of the bone tissue die because of reduced blood supply to the bone. People may be more likely to get this condition:

if they have been taking combination therapy for a long time
if they are also taking anti-inflammatory medicines called corticosteroids
if they drink alcohol
if their immune systems are very weak
if they are overweight.

Signs of osteonecrosis include:

stiffness in the joints
aches and pains (especially in the hip, knee or shoulder)
difficulty moving

If you notice any of these symptoms:

Tell your doctor.

Other effects may show up in blood tests

Combination therapy for HIV can also cause:

increased levels of lactic acid in the blood, which on rare occasions can lead to lactic acidosis

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via Yellow Card Scheme Website: http://www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Lamivudine/Zidovudine

Keep this medicine out of the sight and reach of children.

This medicine does not require any special storage conditions.

Do not use this medicine after the expiry date which is stated on the label, carton, and blister after EXP. The expiry date refers to the last day of that month. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Lamivudine/Zidovudine contains

The active substances are lamivudine and zidovudine. Each film-coated tablet contains lamivudine 150 mg and zidovudine 300 mg.
The other ingredients are
Tablet core: Cellulose microcrystalline, sodium starch glycolate (Type A), silica colloidal anhydrous, magnesium Stearate
Tablet film-coat: Hypromellose (E464), titanium dioxide (E171), macrogol 400, polysorbate 80.

What Lamivudine/Zidovudine looks like and contents of the pack

Film-coated tablet.

White to off-white modified capsule-shaped, biconvex film-coated tablets with deep break line in between ‘J’ and ’59 on one side and break line on other side. The tablet can be divided into equal doses.

Lamivudine/Zidovudine film-coated tablets are available in PVC/PVdC- Aluminium foil blisters and HDPE bottle with polypropylene closures. Pack sizes:

Blister pack: 60 & 180 film-coated tablets HDPE pack: 60 film-coated tablets

Marketing Authorisation Holder

Milpharm Limited

Ares Block, Odyssey Business Park

West End Road

Ruislip HA4 6QD

United Kingdom

Manufacturer

APL Swift Services (Malta) Limited

HF26, Hal Far Industrial Estate, Hal Far

Birzebbugia, BBG 3000

Malta