Rizene 600 mg/200 mg/300 mg Film-Coated Tablets

RIZENE contains three active substances that are used to treat human immunodeficiency virus (HIV) infection: efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI), emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) and tenofovir is a nucleotide reverse transcriptase inhibitor (NRTI).

Each of these active substances, also known as antiretroviral medicines, work by interfering with an enzyme (reverse transcriptase) that is essential for the virus to multiply.

RIZENE can be used alone as a complete regimen or in combination with other anti-retroviral medicines for the treatment of HIV-1 infection in adults.

Do not take RIZENE:

• If you are hypersensitive (allergic) to efavirenz, emtricitabine and/or tenofovir disoproxil fumarate or any of the other ingredients of RIZENE (listed in section 6).
• You had a liver disorder or liver failure attributed to treatment with RIZENE.
• If you have moderate to severe kidney failure.
• If you are pregnant or breastfeeding.
• If you have a heart condition, such as an abnormal electrical signal called prolongation of the QT interval that puts you at high risk for severe heart rhythm problems (Torsade de Pointes).
• If any member of your family (parents, grandparents, brothers or sisters) has died suddenly due to a heart problem or was born with heart problems.
• If your doctor has told you that you have high or low levels of electrolytes such as low potassium or low magnesium in your blood.
• If you are also taking the following medicines: antiarrhythmics of classes IA and III, neuroleptics, antidepressants, terfenadine, astemizole, bepridil, cisapride, ergot derivatives, midazolam, pimozide, triazolam, voriconazole, St. John’s wort, flecainide, certain antibiotics (macrolides, fluoroquinolones, imidazole), triazole antifungals, certain antimalarial medicines and methadone.

Do not take RIZENE with the following related medicines:

• Medicines containing the same active ingredients as RIZENE such as emtricitabine, tenofovir disoproxil fumarate, emtricitabine/tenofovir disoproxil fumarate and efavirenz.
• Medicines containing lamivudine, which is similar to emtricitabine including lamivudine/zidovudine, lamivudine, abacavir sulphate/lamivudine or abacavir sulphate/lamivudine/zidovudine (see Other medicines and RIZENE).

Warnings and precautions

Take special care with RIZENE:

• If you have been diagnosed with chronic hepatitis B or have a history of hepatitis B infections as you may experience a severe exacerbation of hepatitis upon discontinuation of treatment.
• If you have a history of liver disease or risk factors for liver disease because you may be at risk for lactic acidosis (low pH in the blood and bodily tissues accompanied by a build-up of lactic acid) and severe hepatomegaly with steatosis (enlargement of liver with fatty deposits in it). This risk is higher if you are female, obese and have had long term exposure to antiretrovirals.
• If you have kidney failure.
• If you have a history of psychiatric disorders, the use of psychiatric medication, injection medicine use or if you start experiencing psychiatric disturbance such as severe depression, suicidal thoughts, suicide attempts, aggressive behaviour, paranoid reactions and manic reactions.
• Because you may experience nervous system symptoms such as dizziness, difficulty sleeping, impaired concentration, drowsiness or a strong desire to sleep, abnormal dreams, hallucinations, being intensely happy and excited for no apparent reason, confusion, agitation, loss of memory, stupor, abnormal thinking and feeling detached from one’s self. These symptoms would normally subside within 2 to 4 weeks of starting treatment. Beware of simultaneous intake of alcohol and other central nervous system depressants or operating hazardous machinery (see Driving and using machines).
• Tell your doctor if you develop or see signs of opportunistic infections or other complications even when you are on RIZENE treatment as such could be detrimental to your health.
• As the use of RIZENE does not eliminate the risk of HIV transmission to others through sexual contact or blood contamination, therefore you must always take appropriate precautions when involved in activities such as sexual intercourse or handling blood.
• You may experience skin rash in the first month of treatment with RIZENE, tell your doctor about your skin rash if it is persistent. You must stop taking RIZENE if your rash becomes severe with symptoms such as fever, blistering or skin peeling.
• Tell your doctor if you are suffering from osteomalacia (bone disorder indicated by bone pain especially in the hips, bone fractures with no known cause or injury and also by muscle weakness) as RIZENE can aggravate your condition.
• Take RIZENE with caution if you have a history of seizures and let your doctor know about them.
• RIZENE is known to lead to fat redistribution in your body and this is usually indicated by gaining weight around the midriff, formation of buffalo hump-like structure on the trunk (also called enlargement of dorsocervical fat), facial wasting, losing weight on the arms and legs and breast enlargement.
• If you are under the age of 18 years because RIZENE is not recommended for use in patients under the age of 18 years.
• If you are an elderly patient over the age of 65 years as this population tends to experience decreased kidney, liver and heart functioning and are usually taking other medications.
• If you are also taking products containing St. John’s wort (Hypericum perforatum) because St. John’s wort can reduce the effect of RIZENE against HIV infection (see Other medicines and RIZENE).
• You should not use RIZENE if you are at increased risk of Torsade de Pointes (fast heartbeat) or if you are using medicine with a known risk for Torsade de Pointes.
• Tenofovir disoproxil may also cause loss of bone mass.
• Overall, the effects of tenofovir disoproxil on long term bone health and future fracture risk in adult and paediatric patients are uncertain.

Do not share medicines prescribed for you with any other person.

Always take RIZENE exactly as your doctor or pharmacist has instructed you. You should check with your doctor or pharmacist if you are unsure.

Take one tablet daily on an empty stomach. Taking RIZENE at bedtime may improve the tolerability of nervous system symptoms. Take your dose with water. Do not stop taking RIZENE unless your doctor has told you so. Taking your dose at the same time each day will have the best effect in controlling your viral load and will help you remember when to take the tablets. Always get more tablets before your current supply is finished in order to avoid ever skipping a dose.

Children

RIZENE is not recommended for use in patients under the age of 18 years.

Kidney failure

RIZENE should not be used by patients who need dose adjustment because it is a fixed dose tablet. If your creatinine clearance is less than 50 ml/min you may not use RIZENE.

If you have the impression that the effect of RIZENE is too strong or too weak, tell your doctor or pharmacist.

If you take more RIZENE than you should

In the event of overdosage, consult your doctor or pharmacist. If neither is available, contact the nearest hospital or poison control centre.

If you forget to take RIZENE

Take a missed dose as soon as you remember it. However, if it is almost time for your next dose rather leave it and continue with your normal schedule. Do not take a double dose to make up for forgotten individual doses. If you miss more than one dose, rather leave those doses and resume with the normal schedule when the time comes to take your normal dose. Please consult your doctor or pharmacist if you are not sure about your dosing.

RIZENE can have side effects. Not all side effects reported for RIZENE are included in this leaflet. Should your general health worsen or if you experience any untoward effects while taking RIZENE, please consult your healthcare provider for advice.

If any of the following happens, stop taking RIZENE and tell your doctor immediately or go to the casualty department at your nearest hospital:

• Allergic reaction, e.g. skin rash, itching.
• Erythema multiforme (skin disorder occurring due to allergic reaction and its symptoms may include fever, itching, joint aches and multiple skin lesions).
• Stevens-Johnson syndrome (life-threatening skin disorder whereby the outmost part of skin peels off). These are all very serious side effects. If you have them, you may have had a serious allergic reaction to RIZENE. You may need urgent medical attention or hospitalisation.

Tell your doctor immediately or go to the casualty department at your nearest hospital if you notice any of the following:

• Suicidal thoughts or attempts.
• Increased susceptibility to infection, for example, coughing, flu-like symptoms, pneumonia.
• Diarrhoea.
• Shortness of breath.
• Irregular heartbeat.
• Seizures or fits.
• Bone pain.
• Loss of bone mass.

These are all serious side effects. You may need urgent medical attention.

Tell your doctor if you notice any of the following:

• Anorexia (severely resisting food due to irrational fear of gaining weight).
• Aggressive behaviour.
• Impaired concentration.
• Anxiety.
• Nervousness.
• Sleeplessness.
• Euphoria (intense feeling of happiness and excitement for no apparent reason).
• Confusion.
• Depersonalisation.
• Hallucination.
• Agitation.
• Being paranoid.
• Partial loss of sensation and drowsiness.
• Forgetfulness.
• Abnormal thoughts or dreams.
• Headache.
• Fatigue.
• Increased sweating.
• Mild to severe depression, or mania.
• Feeling of tingling or prickling, or numbness.
• Vomiting.
• Flatulence.
• Breast growth in men and females.
• Indigestion.
• Constipation.
• Bloatedness.
• Abdominal pain.
• Abnormal vision.
• Back pain.
• Joint pain and muscle pain.
• Dizziness.
• Feeling weak or sickly.
• Sensation of ringing in the ears.
• Frequent urination.
• Lack of voluntary coordination of movements, speech and movements such as walking may be affected.
• Tremors.
• Changes in body fat resulting in formation of buffalo hump-like structure on the trunk, weight gain in and around the stomach area, loss of weight on the limbs and face.
• Skin discolouration.
• Photoallergic skin reactions.

If you notice any side effects not mentioned in this leaflet, please inform your doctor or pharmacist.

Reporting of side effects

If you get side effects, talk to your doctor, pharmacist or nurse. You can also report side effects to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website. By reporting side effects, you can help provide more information on the safety of RIZENE.

• Store all medicines out of the reach of children.

• Store at or below 25 °C.

• Store RIZENE in the original container.

• Keep the container tightly closed in order to protect the medicine from light and moisture.

• Do not store in a bathroom.

• Do not use after the expiry date stated on the label/carton/bottle.

• Return all unused medicine to your pharmacist.

• Do not dispose of unused medicine in drains or sewerage systems (e.g. toilets).