Atripla (Efavirenz, emtricitabine, tenofovir)

How does it work?

Atripla tablets contain three active ingredients, efavirenz, emtricitabine, and tenofovir disoproxil. Efavirenz 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. Efavirenz, emtricitabine 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 efavirenz, emtricitabine 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. Efavirenz, emtricitabine 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.

Atripla is reserved for people who have had their HIV-1 infection under control for at least three months and have not experienced any failure to previous HIV therapy. 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.

Warning!

  • Atripla tablets should preferably be taken on an empty stomach. They should be swallowed whole with water and not crushed or chewed.
  • Atripla tablets should be taken at the same time each day (preferably bedtime). 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.
  • 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 ensure that you take all your doses at the correct time, and that you visit your doctor for repeat prescriptions before you run out.
  • It is recommended that you avoid drinking grapefruit juice while taking this medicine, as it could alter the blood level of the 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. This may include loss of fat from the face and limbs, increased fat in the abdomen and internal organs, breast enlargement and fatty lumps at the back of the neck (buffalo hump). 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.
  • A rash is one of the most common side effects of this medicine. If the rash is mild to moderate your doctor may decide that the medicine can be continued, in which case the rash will usually resolve with continued treatment. However, sometimes a more severe rash with blistering, scaling and fever can occur, in which case the medicine will need to be stopped. Consult your doctor immediately if you experience a rash while taking this medicine.
  • Efavirenz can sometimes cause side effects such as severe depression, delusions, paranoia and psychosis, and some people have had thoughts of suicide or actually committed suicide. These problems are more likely to occur in people who have a history of mental illness. You should contact your doctor immediately if you think you are experiencing any of these psychiatric side effects, so that your doctor can decide if it is appropriate for you to continue to take this medicine.
  • You may experience side effects such as dizziness, insomnia, sleepiness, difficulty concentrating and unusual dreams while taking this medicine. These side effects tend to resolve after the first two to four weeks of treatment and may be improved if you take your dose at bedtime. If affected you should avoid potentially hazardous activities such as driving or operating machinary. If you experience these side effects it does not mean you are more likely to experience the rarer psychiatric side effects of efavirenz mentioned above, such as severe depression.
  • You should 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 also 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.
  • 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.

Use with caution in

  • Elderly people.
  • Decreased kidney function.
  • People at risk of, or with a history of kidney problems.
  • Liver disease, particularly hepatitis B or C.
  • People with an enlarged liver (hepatomegaly).
  • History of alcohol abuse.
  • History of depression.
  • History of psychiatric illness or substance abuse.
  • History of fits (seizures), eg epilepsy.
  • Obese women.
  • People on a low sodium diet.

Not to be used in

  • Moderate to severely decreased kidney function.
  • Severely decreased liver function.
  • Pregnancy.
  • Breastfeeding.
  • This medicine has not been studied in children and adolescents under 18 years of age. It is not recommended for these age groups.

This medicine should not be used if you are allergic to one or 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.

  • 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 because there are no other treatment options. Seek 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 medical advice from your doctor.

Label warnings

  • This medication should 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. See also the warnings listed above.

  • Dizziness.
  • Disturbances of the gut such as nausea, vomiting, diarrhoea or abdominal pain.
  • Abnormal dreams.
  • Rash (see warning above).
  • Difficulty sleeping (insomnia) .
  • Fatigue.
  • Headache.
  • Sleepiness (somnolence).
  • Concentration difficulties.
  • Changes in appetite.
  • Balance problems involving the inner ear (vertigo).
  • Skin reactions such as itching, changes in pigmentation and dermatitis.
  • Hot flushes.
  • Depression, suicidal feelings, anxiety, agitation, mania, paranoia, delusions, hallucinations (see warning above).
  • Shortness of breath (dyspnoea).
  • Blurred vision.
  • Increased level of cholesterol or triglycerides in the blood.
  • Kidney problems.
  • Liver problems.
  • Severe blistering skin reaction affecting the tissues of the eyes, mouth, throat and genitals (Stevens-Johnson Syndrome).

The side effects listed above may not include all of the side effects reported by the drug'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 ensure that the combination is safe.

The following medicines must not be taken in combination with Atripla, because the efavirenz in Atripla can cause the amount of these medicines in the blood to increase, causing serious or life-threatening side effects:

  • astemizole
  • bepridil
  • cisapride
  • ergot alkaloids such as ergotamine, dihydroergotamine
  • midazolam
  • pimozide
  • terfenadine
  • triazolam.

The herbal remedy St John's wort (Hypericum perforatum) should also not be taken with this medicine, as it may decrease the blood level of efavirenz. This could make efavirenz less effective against the virus, and could also allow the virus to become resistant to the medicine.

The antifungal medicine voriconazole should not be taken with this medicine, because it can increase the blood level of efavirenz, increasing the risk of side effects. Efavirenz can also reduce the blood level of voriconazole, thus making it ineffective.

Efavirenz can also decrease the blood level of the antifungal medicine itraconazole, which could make it less effective. As a result, itraconazole is not recommended for people taking Atripla.

There may be an increased risk of kidney problems if Atripla 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. Where possible these medicines should be avoided in people taking Atripla. However, if they are considered necessary by your doctor then your kidney function should be monitored weekly:

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

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

  • atazanavir with ritonavir
  • didanosine
  • lamivudine
  • lopinavir with ritonavir
  • nevirapine
  • saquinavir with ritonavir.

The antibiotic rifampicin may decrease the blood level of efavirenz, and your doctor may need to prescribe you additional doses of efavirenz if you need to take this antibiotic while taking Atripla.

Efavirenz may reduce the blood level of the antibiotic rifabutin. If you need to take this antibiotic while taking Atripla your doctor may need to prescribe you a larger than normal dose of the antibiotic.

Efavirenz may alter the effectiveness of the combined oral contraceptive pill. If you are taking the pill you should also use a barrier method of contraception, such as a condom, to prevent pregnancy. Condoms should also be used as a regular safe sex practice, to avoid transmitting HIV to your sexual partner.

Efavirenz may alter the blood levels of the antiepileptic medicines phenytoin, carbamazepine and phenobarbital. In addition, carbamazepine may decrease the blood level of efavirenz. The blood levels of these antiepileptics should be monitored if they are taken in combination with Atripla.

Efavirenz may decrease the blood level of the antidepressant sertraline. If you are taking sertraline with Atripla your doctor may increase your dose of sertraline if it becomes less effective.

Efavirenz may decrease the blood level of methadone, which may produce withdrawal symptoms in injecting drug users who have been prescribed methadone.

Efavirenz may decrease the blood levels of statin medicines that are used to treat high cholesterol levels, such as atorvastatin, pravastatin or simvastatin. If you are taking a statin in combination with Atripla, your cholesterol levels should be regularly monitored to make sure the statin is still producing an effect. Your doctor may need to adjust your statin dose.

Efavirenz may also decrease the blood levels of calcium channel blockers such as diltiazem, used for treating high blood pressure and angina. If you take a calcium channel blocker with this medicine your doctor may want to perform extra monitoring to make sure it is still producing an effect.

Other medicines containing the same active ingredients

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

Sustiva contains efavirenz.

Emtriva contains emtricitabine.

Viread contains tenofovir.