Eviplera (Emtricitabine, rilpivirine, tenofovir)

How do I take it?

Eviplera tablets contain three active ingredients, emtricitabine, rilpivirine and tenofovir disoproxil. Rilpivirine is a type of medicine called a non-nucleoside reverse transcriptase inhibitor. Emtricitabine is a type of medicine called a nucleoside reverse transcriptase inhibitor. Tenofovir is a very closely related medicine, called a nucleotide reverse transcriptase inhibitor. All three medicines are used in the treatment of HIV (human immunodeficiency virus) infection.

AIDS (acquired immune deficiency syndrome) is caused by infection with HIV. This virus invades cells of the immune system, particularly the white blood cells known as CD4 T-helper lymphocytes. These cells normally work to activate other cells in the immune system to fight infection. Since HIV kills CD4 T-helper cells, over time the body becomes less able to fight the virus or subsequent infections.

Once the virus is inside the CD4 T-cell it multiplies. Part of the process of viral multiplication involves the conversion of the virus genetic material, RNA, into DNA. This is achieved by a compound essential to the virus, called reverse transcriptase. Reverse transcriptase is a compound known as an enzyme. Emtricitabine, rilpivirine and tenofovir all work by blocking the action of this enzyme. Each medicine blocks the enzyme in a slightly different way. Blocking the action of the enzyme interferes with the conversion of viral RNA into DNA, which stops the virus from multiplying.

There is no cure for HIV, but emtricitabine, rilpivirine and tenofovir are three of a number of medicines that lower the amount of virus in the body (viral load) and therefore slow down the progression of the disease from HIV to AIDS. A combination of several anti-HIV medicines is required to fight the infection because the virus can become resistant to one agent very quickly. Emtricitabine, rilpivirine and tenofovir are used together to help prevent resistance occurring.

This combination preparation reduces the number of tablets to be taken and therefore simplifies treatment.

A test known as a tropism assay will be carried out before treatment with this medication is started. This involves a blood test to determine the strain of HIV.

What is it used for?

  • HIV infection.

How do I take it?

  • Eviplera tablets must be taken with a meal. They should be swallowed whole with a drink of water and not broken, crushed or chewed.
  • The usual dose for Eviplera tablets is one tablet daily with a meal.
  • If you vomit less than four hours after taking this medicine, you should take another tablet with a meal. If you vomit more than four hours after taking this tablet you don'’t need to worry about taking an extra dose, just take your next dose as usual.
  • Eviplera tablets should be taken at the same time each day. If you forget to take a dose you can take it up to 12 hours late. However, if you are more than 12 hours late you should not take the missed dose. Take the next dose at the usual time the following day.

Warning!

  • This medicine must be taken with a meal. If the tablets are taken on an empty stomach or with just a nutritional drink, the medicine is not absorbed very well from the gut and could be less effective as a result.
  • The HIV virus is very good at becoming resistant to anti-HIV medicines. For this reason it is very important that you carefully follow your doctor's instructions for taking your anti-HIV medicines, in order to maintain effective levels of the medicines in your blood. If the blood levels drop, the virus will be given more chance to replicate and develop resistance to the drugs. Skipping even a few doses increases the risk of treatment failure, so you should try to make sure that you take all your doses at the correct time, and that you visit your doctor for repeat prescriptions before you run out of medicine.
  • Treatment of HIV infection with anti-HIV medicines such as this one does not reduce the risk of transmitting the virus to other people through sexual contact or blood contamination. You should continue to use condoms to prevent transmitting the virus to your sexual partner.
  • Combination antiretroviral therapy has been associated with a redistribution of body fat (lipodystrophy) in people with HIV. The long-term consequences of this are currently unknown, however your doctor may wish to monitor your body fat, and the levels of lipids (eg cholesterol) and sugar (glucose) in your blood, and may prescribe additional medicines for any lipid disorders that occur during treatment with this medicine. Contact your doctor if you notice any changes in your body fat during treatment with your HIV medicines.
  • Some people being treated with combination antiretroviral therapy may develop a bone condition called osteonecrosis. This condition is caused by loss of blood supply to a bone, causing death of the bone tissue. The risk of the condition is thought to be increased by corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index, advanced HIV disease and long-term use of antiretroviral medicines. If you notice any joint stiffness, aches and pains (especially of the hip, knee and shoulder) or difficulty in movement while using this medicine, you should tell your doctor so this can be investigated.
  • If you have advanced HIV and a history of opportunistic infections such as pneumocystis carinii pneumonia (PCP) or cytomegalovirus (CMV), you may experience signs and symptoms of inflammation from previous infections soon after you start combination anti-HIV treatment. It is believed that these symptoms are due to an improvement in the body’s immune response, which enables the body to fight infections that may have been present with no obvious symptoms. You should tell your doctor immediately if you experience any signs or symptoms of infection, such as inflammation or high temperature, after starting treatment with this medicine.
  • The class of medicines that emtricitabine and tenofovir belong to can cause a rare but serious condition called lactic acidosis, which is an excess of lactic acid in the blood, together with an enlarged liver. This side effect is more likely to occur in overweight women and people with liver disease (particularly hepatitis C treated with alpha interferon and ribavirin). If it occurs, lactic acidosis usually develops after a few months of treatment. Your doctor will monitor you for this side effect, but symptoms that might indicate its development include rapid and/or deep breathing and non-specific symptoms such as feeling weak, sick or generally unwell, vomiting, abdominal pain, loss of appetite or weight loss. You should tell your doctor if you experience any of these.
  • You will need to have regular blood tests to monitor your liver function while you are taking this medicine. This is especially important if you already have any problems with your liver, in particular chronic hepatitis B or C. Symptoms that may suggest a liver problem include persistent nausea and vomiting, abdominal pain, or the development of jaundice (a yellow colouring to the skin and the whites of the eyes). Consult your doctor if you experience any of these symptoms.
  • Your kidney function should be monitored prior to starting and regularly throughout treatment with this medicine. Monitoring is recommended every four weeks during the first year of treatment, and then every three months. Your doctor may want to monitor your kidney function more frequently than this if you already have, or are at risk of, kidney problems. Eviplera tablets are not recommended for people with more severe kidney problems or those needing dialysis, as lower doses of the medicines are needed in these cases and this cannot be achieved with the combination Eviplera tablet.
  • Eviplera tablets contain the colouring sunset yellow (E110), which can cause an allergic-type reaction. This allergy is more common in people who are allergic to aspirin.

Use with caution in

  • Elderly people.
  • People with mildly decreased kidney function.
  • People with moderately decreased liver function.
  • Liver disease, particularly hepatitis B or C.
  • People with an enlarged liver (hepatomegaly).
  • History of alcohol abuse.
  • People who are overweight or obese.
  • Diabetes.
  • People with raised cholesterol levels.

Not to be used in

  • People with moderate to severely decreased kidney function.
  • People with severely decreased liver function.
  • Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption (Eviplera tablets contain lactose).
  • Eviplera is not recommended for children and adolescents under 18 years of age, as its safety and efficacy have not been studied in this age group.

This medicine should not be used if you are allergic to any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy.

If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.

Pregnancy and breastfeeding

Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby. Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.

  • Women taking this medicine should use effective contraception to avoid getting pregnant. Condoms should also be used as a regular safe sex practice, to prevent transmitting the virus to your sexual partner. Seek further medical advice from your doctor.
  • The safety of this medicine for use during pregnancy has not been established. It should not be used during pregnancy unless considered essential by your doctor. Seek further medical advice from your doctor.
  • It is recommended that women infected with the HIV virus must not breastfeed their infants under any circumstances, in order to avoid transmission of the virus to the baby. Seek further medical advice from your doctor.

Label warnings

  • This medication is to be swallowed whole, do not chew or crush.

Side effects

Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Just because a side effect is stated here, it does not mean that all people using this medicine will experience that or any side effect.

Very common (affect more than 1 in 10 people)

  • Headache.
  • Dizziness.
  • Diarrhoea.
  • Nausea and vomiting.
  • Feeling weak.
  • Low blood phosphate level (hypophosphataemia).
  • Elevated levels of creatinine in the blood.
  • Increased level of cholesterol in the blood.

Common (affect between 1 in 10 and 1 in 100 people)

  • Difficulty sleeping (insomnia).
  • Abnormal dreams and sleep disorders.
  • Increased level of sugar or fats called triglycerides in the blood.
  • Tiredness.
  • Disturbances of the gut such as stomach pain, bloating of the stomach, dry mouth and wind.
  • Depression.
  • Loss of appetite.
  • Skin reactions such as rash, itching, changes in pigmentation and dermatitis.
  • Decrease in the number of white blood cells or platelets in the blood (neutropenia or thrombocytopenia).
  • Increased liver enzymes.
  • Allergic reactions.

Uncommon (affect between 1 in 100 and 1 in 1000 people)

  • Low red blood cell count (anaemia).
  • Inflammation of the pancreas (pancreatitis).
  • Pain and weakness of muscles.
  • Decreased blood potassium levels.

Rare (affect between 1 in 1000 and 1 in 10,000 people)

  • Kidney problems such as inflammation of the kidneys or kidney failure.
  • Passing more urine and feeling thirsty (tell your doctor if you experience these symptoms, they are signs of a condition called nephrogenic diabetes insipidus).
  • Inflammation of the liver (hepatitis).
  • Changes in the liver (fatty liver).
  • Lactic acidosis (see warning section above).
  • Softening of the bones (osteomalacia) that may result in fractures (tell your doctor if you notice any bone pain while you are taking this medicine).

The side effects listed above may not include all of the side effects reported by the medicine's manufacturer.

For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.

How can this medicine affect other medicines?

It is important to tell your doctor or pharmacist what medicines you are already taking, including those bought without a prescription and herbal medicines, before you start treatment with this medicine. Similarly, check with your doctor or pharmacist before taking any new medicines while taking this one, to make sure that the combination is safe.

There may be an increased risk of kidney problems if Eviplera is taken in combination with other medicines that may have side effects on the kidneys, such as those listed below, or by people who have recently taken one of these medicines. These medicines should not be taken by people taking Eviplera:

  • adefovir
  • aminoglycoside antibiotics, eg gentamicin, neomycin
  • amphotericin B
  • cidofovir
  • foscarnet
  • ganciclovir
  • interleukin-2
  • pentamidine
  • vancomycin.

Emtricitabine and tenofovir are removed from the body by the kidneys. The manufacturer of Eviplera states that it should be used with caution in combination with medicines that are known to affect kidney function, or that are also eliminated from the body by the kidneys, because the safety of such combinations have not yet been evaluated. Your doctor or pharmacist will check the combination of medicines you are taking and perform extra monitoring if considered necessary.

Eviplera is not recommended for use in combination with the following anti-HIV medicines:

  • delavirdine
  • didanosine
  • efavirenz
  • etravirine
  • lamivudine
  • nevirapine
  • other medicines containing emtricitabine, tenofovir or rilpivirine

The following medicines should not be used in combination with Eviplera tablets as they can decrease the amount of rilpivirine in the blood, thus making it less effective:

  • the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital and phenytoin
  • the antibiotics rifabutin, rifampicin and rifapentine
  • dexamethasone (except when this is used as a single dose treatment)
  • proton pump inhibitors, such as omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole
  • the herbal remedy St John's wort (Hypericum perforatum).

H2 receptor antagonists such as ranitidine and cimetidine should be used with caution in people taking Eviplera, as these can also decrease the blood levels of rilpivirine. If you are taking one of these medicines it should be taken at least 12 hours before your dose of Eviplera tablets or at least four hours after.

Antacids such as calcium carbonate, aluminium hydroxide or magnesium hydroxide can also decrease the blood levels of rilpivirine. Antacids should therefore only be taken at least two hours before or at least four hours after Eviplera tablets.

The rilpivirine in Eviplera tablets may increase the amount of digoxin, dabigatran or metformin in the blood. Your doctor will need to monitor the levels of these medicines in your blood if you are taking any of these in combination with Eviplera tablets.

The rilpivirine in Eviplera tablets may increase the breakdown of methadone, which may produce withdrawal symptoms in injecting drug users who have been prescribed methadone. Your doctor may need to change your dose of methadone.

The following medicines may prevent the breakdown of rilpivirine by the liver and so could potentially increase its blood levels and risk of side effects. Tell your doctor if you experience any new or increased side effects if you are prescribed one of these in combination with Eviplera:

  • azole antifungals such as itraconazole or ketoconazole
  • macrolide antibiotics such as clarithromycin or erythromycin
  • protease inhibitors such as ritonavir.

Other medicines containing the same active ingredients

There are currently no other medicines available in the UK that contain this combination of emtricitabine, rilpivirine and tenofovir. However, the ingredients are available separately.

Edurant contains rilpivirine.

Emtriva contains emtricitabine.

Viread contains tenofovir.