Riva-Efavirenz/Emtricitabine/Tenofovir: Uses, Side Effects and Dosage

ABOUT THIS MEDICATION

What the medication is used for:

RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR contains 3 medicines, Sustiva^® (efavirenz), EMTRIVA^® (emtricitabine) and VIREAD^® (tenofovir disoproxil fumarate; tenofovir DF), combined in one pill. EMTRIVA® and VIREAD^® are HIV (human immunodeficiency virus) nucleoside / nucleotide analog reverse transcriptase inhibitors (NRTIs) and Sustiva is an HIV non-nucleoside analog reverse transcriptase inhibitor (NNRTI). VIREAD^® and EMTRIVA® are components of TRUVADA^®. RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR can be used alone as a complete regimen or in combination with other medications to treat people with HIV infection. RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR is for adults age 18 and older. RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR has not been studied in children under age 18 or adults over age 65.

What it does:

RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR helps block HIV reverse transcriptase, a chemical in your body (enzyme) that is needed for HIV to multiply. RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR lowers the amount of HIV in the blood (viral load). Lowering the amount of HIV in the blood lowers the chance of infections that happen when your immune system is weak (opportunistic infections).

HIV infection destroys CD₄ (T) cells, which are important to the immune system. The immune system helps fight infection. After a large number of T cells are destroyed, acquired immune deficiency syndrome (AIDS) develops. RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR may also help to increase the number of T cells (CD₄ cells).

RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR does not cure HIV infection or AIDS. The long-term effects of RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR are not known at this time. People taking RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR may still get opportunistic infections or other conditions that happen with HIV infection. Opportunistic infections are infections that develop because the immune system is weak. Some of these conditions are pneumonia, herpes virus infections, and Mycobacterium avium complex (MAC) infections. It is very important that you see your doctor regularly while taking RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR.

RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR has not been shown to reduce the risk of passing HIV to others through sexual contact or blood contamination. Continue to practice safe sex and do not use or share dirty needles.

When it should not be used:

Together with your doctor, you need to decide whether RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR is right for you.

Do not take RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR if:

• you are taking any medication that is listed in this pamphlet under “Drugs that must not be taken with RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR” (see INTERACTIONS WITH THIS MEDICATION).
• you have or are at known risk for any type of bone disease or bone-related problems and have not discussed this with your doctor.
• you are allergic to RIVA-EFAVIRENZ/EMTRICITABINE/TENOFO VIR or any of its ingredients. The medicinal ingredients are efavirenz, emtricitabine and tenofovir DF (see What the non-medicinal ingredients are).

What the medicinal ingredients are:

• efavirenz
• emtricitabine
• tenofovir disoproxil fumarate (tenofovir DF)

What the non-medicinal ingredients are:

Black Iron Oxide, Croscarmellose Sodium, Hydroxypropyl Cellulose, Magnesium Stearate, Microcrystalline Cellulose, Polyethylene Glycol, Polyvinyl Alcohol, Pregelatinized Starch, Red Iron Oxide, Sodium Lauryl Sulfate, Talc and Titanium Dioxide.

What dosage forms it comes in:

RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR is available as tablets. Each tablet contains 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate (which is equivalent to 245 mg of tenofovir disoproxil), as active ingredients.

WARNINGS AND PRECAUTIONS

Serious Warnings and Precautions

• Tenofovir DF, a component of RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR, caused harm to the bones of animals. If you notice bone pain, suffer a bone fracture, or other bone problem, consult your doctor. If you have bone problems, you may wish to discuss calcium and / or vitamin D supplementation with your doctor. The effect of supplementation with calcium and / or vitamin D is unknown.

• Patients who experience dizziness, trouble concentrating or drowsiness should avoid driving or operating machinery.

• Women should not become pregnant while taking RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR and for 12 weeks after stopping it. Serious birth defects have been seen in animals and women treated with efavirenz (a component of RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR) during pregnancy. It is not known whether efavirenz caused these defects. A reliable form of barrier contraception must always be used even if you or your partner are using other methods of contraception such as the pill or other hormonal therapy (e.g., implants, injections). RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR may remain in your blood for a time after therapy is stopped. Therefore, you should continue use of a reliable form of contraception for 12 weeks after stopping treatment with RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR. If you are pregnant or become pregnant while taking RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR, your doctor may register you in the Antiretroviral Pregnancy Registry. The Registry monitors fetal outcomes in pregnant women using antiretroviral medicines.

• A small number of patients taking efavirenz, one of the components of RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR, have had severe depression, strange thoughts, or angry behavior. Some patients have had thoughts of suicide and a few patients have actually committed suicide. These problems tend to occur more often in patients with a history of mental illness. You should contact your doctor immediately if you think you are having these symptoms, so your doctor can decide whether you should continue to take RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR.
• Consult your doctor if you have a rash, since some rashes may be serious.

BEFORE you use RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR (efavirenz / emtricitabine / tenofovir DF), talk to your doctor or pharmacist:

If you have ever had a previous life-threatening skin reaction (e.g., Stevens-Johnson syndrome).

If you are breast-feeding or plan to breast-feed: Do not breast-feed if you have HIV or are taking RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR. HIV can be passed to your baby in your breast milk. All components of

RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR (efavirenz, emtricitabine and tenofovir DF) can be passed to your baby in your breast milk and may cause harm to your baby. Talk to your doctor about the best way to feed your baby.

If you have other medical conditions: Let your doctor know if you have other medical conditions, especially liver or kidney problems, pancreatitis (inflammation of the pancreas), seizures or mental illness, or have or are at risk for bone disease or bone-related problems.

If you have or have had a heart rhythm disorder such as:

• lengthening of QT interval
• irregular heartbeat
• a heart condition, Torsades de Pointes

If you are taking other medicines: Some medicines can interact when taken together, including prescription and non-prescription medicines, herbal products and dietary supplements (see INTERACTIONS WITH THIS MEDICATION).

Other Special Warnings: Your blood sugar levels (glucose) or levels of fats (lipids) in your blood may increase with HIV treatment. Your doctor may order blood tests for you.

INTERACTIONS WITH THIS MEDICATION

No drug interaction studies have been done with RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR.

Drugs that must not be taken with RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR:

• Propulsid^TM (cisapride)*, Versed^® (midazolam), Halcion^® (triazolam), ergot medications (for example, Wigraine^® and Cafergot^®), Hismanal (astemizole)*, Seldane^® (terfenadine)*, Vascor^® (bepridil)* or Orap^® (pimozide). Taking these medications with RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR could create the potential for serious or life-threatening side effects.
• Zepatier^® (elbasvir / grazoprevir), since Zepatier^® may lose its effect.
• Vfend^® (voriconazole), since it may lose its effect or may increase the chance of having side effects from RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR.
• Do not take RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR if you are taking St. John’s Wort (Hypericum perforatum), or products containing St. John’s Wort. St. John’s Wort is an herbal product sold as a dietary supplement. Taking St. John’s Wort may decrease RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR levels and may lead to increased viral load and possible resistance to efavirenz or resistance to the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs).

*Not marketed in Canada.

It is also important to tell your doctor if you are taking any of the following:

• RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR should not be used with 3TC^®, Combivir^®, COMPLERA^®, DESCOVY^®, EMTRIVA^®, GENVOYA^®, Heptovir^®, HEPSERA^®, Kivexa^®, ODEFSEY^®, Triumeq^®, Trizivir^®, TRUVADA^®, STRIBILD^®, VEMLIDY^®, or VIREAD^®.
• RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR also should not be used with Sustiva^® unless your doctor decides a dose adjustment is needed (e.g., with rifampin).
• Do not take RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR if you are on other medications that may affect your kidneys and you have not discussed this with your doctor. RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR should not be used at the same time or shortly after cidofovir, ganciclovir, vancomycin or aminoglycosides as this may harm the kidneys.
• Reyataz^® (atazanavir sulfate), Fortovase^®* or Invirase^® (saquinavir); these medicines need to be replaced with another medicine when taken with RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR. If your doctor does prescribe Reyataz and RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR, you may need to be monitored more carefully for side effects.
• Biaxin^® (clarithromycin). Biaxin^® may interact with RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR to affect the electrical activity of your heart. Biaxin needs to be replaced with another medicine when taken with RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR.
• Celsentri^® (maraviroc).
• Crixivan^® (indinavir), methadone, Mycobutin^® (rifabutin), Zoloft^® (sertraline), Wellbutrin^® SR, Wellbutrin^® XL, or Zyban^® (bupropion); these medicines may need to have their dose changed when taken with RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR.
• Videx^® or Videx EC^® (didanosine); tenofovir DF (a component of RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR) may increase the amount of didanosine in your blood, which could result in more side effects. You may need to be monitored more carefully if you are taking RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR and didanosine together. Also, the dose of didanosine may need to be changed.
• Kaletra^® (lopinavir / ritonavir) or HARVONI^® (ledipasvir / sofosbuvir) may increase the amount of tenofovir DF (a component of RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR) in your blood, which could result in more side effects. You may need to be monitored more carefully if you are taking RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR and
• Kaletra^® together or RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR and HARVONI^® together. Also, the dose of Kaletra^® may need to be changed.
• EPCLUSA^® (sofosbuvir / velpatasvir) or VOSEVI^® (sofosbuvir / velpatasvir / voxilaprevir) should not be used with RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR as it is expected to decrease the amount of velpatasvir (a component of EPCLUSA^® and VOSEVI^®) and voxilaprevir (a component of VOSEVI^®) in your blood, which may reduce the effectiveness of EPCLUSA^® or VOSEVI^®.
• Medicines for seizures [for example, Dilantin^® (phenytoin), Tegretol^® (carbamazepine), or phenobarbital]; your doctor may want to switch you to another medicine or check drug levels in your blood from time to time.
• Sporanox^® (itraconazole) and Posanol^® (posaconazole) may need to be replaced by another medicine when taken with RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR.
• The cholesterol-lowering medicines Lipitor^® (atorvastatin), Pravachol^® (pravastatin sodium), and Zocor^® (simvastatin).
• Rifadin^® (rifampin) or the rifampin-containing medicines Rofact^® and Rifater^®.
• Calcium channel blockers such as Cardizem^® or Tiazac^® (diltiazem), Covera HS^®, Isoptin^® SR or Tarka^® (verapamil), and others.
• Immunosuppressants such as Neoral^® (cyclosporine), Advagraf^® or Prograf^® (tacrolimus), Rapamune^® or Torisel^® (sirolimus).
• Hepatitis C antiviral agents such as Galexos^® (simeprevir).
• Antimalarials such as Coartem^®* and Riamet^®* (artemether / lumefantrine). These medicines may interact with RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR to affect your heart. Malarone^® (atovaquone / proguanil) (an antimalarial).
• The effect of combining alcohol or recreational (street, illicit) drugs with efavirenz has not been studied. Because they may interact with each other, speak with your doctor before you combine RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR with these drugs.

*Not marketed in Canada.

These are not all the medicines that may cause problems if you take RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR. Be sure to tell your doctor about all the medicines you take.

Keep a complete list of all the prescription and non-prescription medicines as well as any herbal medicines that you are taking, how much you take and how often you take them. Make a new list when medicines or herbal medicines are added or stopped, or if the dose changes. Give copies of this list to all your doctors and pharmacists every time you visit them or fill a prescription. This will give your doctor a complete picture of the medicines you use. Then he or she can decide the best approach for the situation.

PROPER USE OF THIS MEDICATION

Stay under a doctor’s care when taking RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR. Do not change your treatment or stop treatment without first talking with your doctor.

Take RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR every day exactly as your doctor prescribed it. Follow the directions from your doctor, exactly as written on the label. Set up a dosing schedule and follow it carefully.

When your RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR supply starts to run low, get more from your doctor or pharmacy. This is very important because the amount of virus in your blood may increase if the medicine is stopped for even a short time. The virus may develop resistance to RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR and become harder to treat.

Only take medicine that has been prescribed specifically for you. Do not give RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR to others or take medicine prescribed for someone else.

Do not use if seal over bottle opening is broken or missing.

Usual Adult dose:

• The usual dose of RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR is one tablet orally (by mouth) once a day.

• RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR should be taken on an empty stomach. Taking RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR at bedtime may make some side effects less bothersome.

Overdose:

Missed Dose:

It is important that you do not miss any doses. If you miss a dose of RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR, take it as soon as you remember that day. Do not take more than 1 dose of RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR in a day. Do not take 2 doses at the same time. Call your doctor or pharmacist if you are not sure what to do.

SIDE EFFECTS AND WHAT TO DO ABOUT THEM

The most common side effects of Sustiva, EMTRIVA^® and VIREAD^® are:

• Nervous system symptoms such as dizziness, trouble sleeping, drowsiness, trouble concentrating, unusual dreams
• Headache
• Diarrhea
• Nausea
• Vomiting
• Rash
• Flatulence (intestinal gas)
• Tiredness
• Itching
• Allergic reaction (including swelling of the face, lips, tongue or throat)
• Abdominal pain

Other side effects may include pancreatitis (inflammation of the pancreas) and shortness of breath.

Skin discoloration (small spots or freckles) may also happen with RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR.

A small number of patients taking efavirenz, one of the components of RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR, have had severe depression, strange thoughts, or angry behavior. Some patients have had thoughts of suicide and a few patients have actually committed suicide. These problems tend to occur more often in patients with a history of mental illness. Contact your doctor immediately if you think you are having these symptoms so your doctor can decide whether you should continue to take RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR.

Changes in body fat have been seen in some patients taking antiretroviral therapy. These changes may include increased amounts of fat in the upper back and neck (“buffalo hump”), breast, and around the trunk. Loss of fat from the legs, arms and face may also happen. The cause and long-term health effects of these conditions are not known at this time.

Some patients have experienced serious liver problems including liver failure, resulting in transplantation or death. Most of these serious side effects occurred in patients with a chronic liver disease such as a hepatitis infection, but there have also been a few reports in patients without any existing liver disease.

Changes in your immune system (Immune Reconstitution Inflammatory Syndrome) can happen when you start taking HIV medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time, or you could develop an autoimmune disease in which your immune system reacts against your own body [e.g., Grave's disease (which affects the thyroid gland), Guillain-Barre syndrome (which affects the nervous system) or polymyositis (which affects the muscles)] and it may develop at any time, sometimes months after the start of HIV therapy. Sometimes symptoms can be severe, so if you develop high temperature (fever), joint or muscle pain, redness, rash, swelling or fatigue, or any new symptoms, contact your doctor right away.

Lactic acidosis is a medical emergency and must be treated in the hospital. You may be more likely to get lactic acidosis or serious liver problems if you are very overweight (obese) or have been taking nucleoside analog medicines, like RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR, for a long time.

Muscle pain, muscle weakness, bone pain and softening of the bone (infrequently contributing to fractures) have also been reported due to tenofovir DF (a component of RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR).

There have been other side effects in patients taking Sustiva, EMTRIVA^® or VIREAD^®. This is not a complete list of side effects. If you have questions about side effects, ask your doctor, nurse, or pharmacist. You should report any new or continuing symptoms to your doctor right away. Your doctor may be able to help you manage these side effects.

HOW TO STORE IT

• Keep RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR and all other medications out of reach and sight of children.

• RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR should be stored at 15–30 °C. It should remain stable until the expiration date printed on the label.

  • Do not keep your medicine in places that are too hot or cold.
  • Do not keep medicine that is out of date or that you no longer need. If you throw any medicines away, make sure that children will not find them.
  • Keep RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR in its original container and keep the container tightly closed.

Reporting Side Effects

MORE INFORMATION

If you want more information about RIVA-EFAVIRENZ/EMTRICITABINE/TENOFOVIR:

• Talk to your healthcare professional
• Find the full product monograph that is prepared for health professionals and includes this Consumer Information by visiting the Health Canada website (https://health-products.canada.ca/dpd-bdpp/index-eng.jsp), or by contacting the sponsor, Laboratoire Riva Inc. at, 1-800-363-7988.

Laboratoire Riva Inc.

660 Boul. Industriel

Blainville, Quebec

J7C 3V4

www.labriva.com

Last revised: July 30, 2021

ATRIPLA^®, COMPLERA^®, DESCOVY^®, EMTRIVA^®,

EPCLUSA^®, GENVOYA^®, HARVONI^®, HEPSERA^®,

ODEFSEY^®, SOVALDI^®, STRIBILD^®, TRUVADA^®,

VEMLIDY^®, VIREAD^®, and VOSEVI^® are trademarks of

Gilead Sciences, Inc. or its related companies. Gilead Sciences, Inc. is not affiliated with and does not endorse Laboratoire Riva Inc. or its products.

All other trademarks referenced herein are the property of their respective owners.