LOPINAVIR/RITONAVIR VIATRIS 100 mg/25 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Lopinavir/Ritonavir Mylan 100 mg/25 mg film-coated tablets EFG

lopinavir/ritonavir

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you or your child.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you or your child only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is Lopinavir/Ritonavir Mylan and what is it used for
2. What you need to know before you or your child takes Lopinavir/Ritonavir Mylan
3. How to take Lopinavir/Ritonavir Mylan
4. Possible side effects
5. Storing Lopinavir/Ritonavir Mylan
6. Contents of the pack and further information

1. What is Lopinavir/Ritonavir Mylan and what is it used for

• Your doctor has prescribed lopinavir/ritonavir to help control your human immunodeficiency virus (HIV) infection. This is possible because lopinavir/ritonavir works by preventing the infection from spreading quickly.
• Lopinavir/Ritonavir Mylan does not cure HIV infection or AIDS
• Lopinavir/ritonavir is used in children aged 2 years or older, adolescents and adults infected with HIV, the virus that causes AIDS.
• Lopinavir/ritonavir contains the active substances lopinavir and ritonavir. Lopinavir/ritonavir is an antiretroviral medicine that belongs to a group of medicines called protease inhibitors.
• Lopinavir/ritonavir is prescribed for use in combination with other antiviral medicines. Your doctor will inform you and decide which medicines are best for you.

2. What you need to know before you or your child takes Lopinavir/Ritonavir Mylan

Do not take Lopinavir/Ritonavir Mylan if:

• You are allergic to lopinavir, ritonavir or any of the other ingredients of this medicine (listed in section 6).
• You have severe liver problems.

Do not take Lopinavir/Ritonavir Mylan with any of the following medicines:

• astemizole or terfenadine (usually used to treat allergy symptoms – these medicines may not require a prescription);
• oral midazolam or triazolam (used to relieve anxiety and/or sleep problems);

• pimozide (used to treat schizophrenia);
• quetiapine (used to treat schizophrenia, bipolar disorder and major depressive disorder);
• lurasidone (used to treat depression);
• ranolazine (used to treat chronic chest pain [angina pectoris]);
• cisapride (used to relieve certain stomach problems);
• ergotamine, dihydroergotamine, ergonovine and methylergonovine (used to treat headache);
• amiodarone, dronedarone (used to treat heart rhythm disorders);
• lovastatin, simvastatin (used to lower blood cholesterol);
• alfuzosin (used in men to treat symptoms of enlarged prostate [benign prostatic hyperplasia (BPH)]);
• fusidic acid (used to treat skin infections caused by the bacterium Staphylococcussuch as impetigo and infected dermatitis. Fusidic acid is also used to treat long-term bone and joint infections under medical supervision (see Using Lopinavir/Ritonavir Mylan with other medicines);
• colchicine (a medicine used to treat gout). If you have liver or kidney problems (see Using Lopinavir/Ritonavir Mylan with other medicines);
• elbasvir/grazoprevir (used to treat chronic hepatitis C virus [HCV] infection);
• ombitasvir/paritaprevir/ritonavir with or without dasabuvir (used to treat chronic hepatitis C virus [HCV] infection);
• avanafil or vardenafil (used to treat impotence);
• sildenafil used for the treatment of pulmonary hypertension (high blood pressure in the pulmonary artery). Sildenafil may be used for the treatment of erectile dysfunction under medical supervision (see Taking Lopinavir/Ritonavir Mylan with other medicines);
• products containing St. John's Wort (Hypericum perforatum).

For more information on other medicines that require special precautions, see the list of medicines included in “Using Lopinavir/Ritonavir Mylan with other medicines” below.

If you are currently taking any of these medicines, consult your doctor to see if you need to change your treatment for other conditions or your antiretroviral treatment.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Lopinavir/Ritonavir Mylan.

Important information

• People taking lopinavir/ritonavir can still develop infections or other diseases associated with HIV and AIDS. Therefore, it is important that you remain under the supervision of your doctor while taking lopinavir/ritonavir.
• Although effective antiviral treatment reduces the risk of transmission, while taking this medicine you can still transmit HIV to others. Consult your doctor about what precautions are necessary to avoid infecting others.

Tell your doctor if you or your child have or have had

• Hemophiliatype A and B, as lopinavir/ritonavir may increase the risk of bleeding.
• Diabetes, as increases in blood sugar have been reported in patients taking lopinavir/ritonavir.
• A history of liver problems, as patients with a history of liver disease, including chronic hepatitis B or C, have a greater risk of suffering from serious and potentially life-threatening liver side effects.

Tell your doctor if you or your child are experiencing

• nausea, vomiting, abdominal pain, difficulty breathing, and severe muscle weakness in the legs and arms, as these may be symptoms of increased lactic acid levels.
• thirst, frequent urination, blurred vision or weight loss, as this may indicate high blood sugar levels.
• nausea, vomiting, abdominal pain, as significant increases in triglycerides (fats in the blood) are considered a risk factor for pancreatitis (inflammation of the pancreas) and the described symptoms may suggest this condition.
• In some patients with advanced HIV infection and a history of opportunistic infections, signs and symptoms of inflammation of previous infections may occur shortly after starting anti-HIV treatment. These symptoms are believed to be due to an improvement in the body's immune response, allowing it to fight infections that were present without apparent symptoms.

In addition to opportunistic infections, you may also experience autoimmune disorders (a problem that occurs when the immune system attacks healthy body tissue) after starting treatment for your HIV infection. Autoimmune disorders may appear several months after starting treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and moving up the trunk, palpitations, tremors, or hyperactivity, please inform your doctor immediately to seek necessary treatment.

• Stiffness in the joints, pain and discomfort(especially in the hip, knee, and shoulder) and difficulty moving, as some patients taking these medicines may develop a bone disease called osteonecrosis (death of bone tissue caused by loss of blood supply to the bone). Among the many risk factors for developing this disease are the duration of combination antiretroviral therapy, the use of corticosteroids, ethanol consumption, severe immunosuppression, and high body mass index.
• Muscle pain,discomfort or pain, particularly in combination with these medicines. In rare cases, these muscle disorders have been severe.
• Symptoms of dizziness, dizziness, fainting, or abnormal heartbeats. Lopinavir/ritonavir may cause changes in heart rhythm and electrical activity of the heart. These changes can be seen on an ECG (electrocardiogram).

Using Lopinavir/Ritonavir Mylan with other medicines

Tell your doctor or pharmacist if you or your child are taking, have recently taken, or might take any other medicines.

• antibiotics (e.g., rifampicin, rifabutin, clarithromycin);
• cancer medicines (e.g., afatinib, ceritinib, ibrutinib, venetoclax, most tyrosine kinase inhibitors such as dasatinib and nilotinib, and also vincristine and vinblastine);
• anticoagulants (e.g., warfarin, rivaroxaban, vorapaxar);
• antidepressants (e.g., trazodone, bupropion);
• • antiepileptic medicines (e.g., carbamazepine, phenytoin, phenobarbital, lamotrigine, and valproate);
  • medicines for treating fungal infections (e.g., ketoconazole, itraconazole, voriconazole);
  • medicines for treating gout (e.g., colchicine). You must not take Lopinavir/Ritonavir Mylan with colchicine if you have liver or kidney problems (see also “Do not take Lopinavir/Ritonavir Mylan” above);
  • medicines for treating tuberculosis (e.g., bedaquiline, delamanid);
  • antiviral medicines used to treat chronic hepatitis C virus (HCV) infection in adults (e.g., boceprevir, simeprevir, and telaprevir);
  • medicines for erectile dysfunction (e.g., sildenafil and tadalafil);
• fusidic acid used in the long-term treatment of bone and joint infections (e.g., osteomyelitis);
• heart medicines including:
• • digoxin;
  • calcium channel blockers (e.g., felodipine, nifedipine, nicardipine);
  • medicines used to correct heart rhythm (e.g., bepridil, systemic lidocaine, quinidine);
• HIV CCR5 antagonist (e.g., maraviroc);
• HIV-1 integrase inhibitor (e.g., raltegravir);
• levothyroxine (used to treat thyroid problems);
• medicines used to lower blood cholesterol (e.g., atorvastatin, lovastatin, rosuvastatin, or simvastatin);
• medicines used to treat asthma and other lung-related problems, such as chronic obstructive pulmonary disease (COPD) (e.g., salmeterol);
• medicines used to treat pulmonary arterial hypertension (high blood pressure in the pulmonary artery) (e.g., bosentan, riociguat, sildenafil, tadalafil);
• medicines that affect the immune system (e.g., cyclosporine, sirolimus [rapamycin], tacrolimus);
• medicines used to help stop smoking (e.g., bupropion);
• analgesics (e.g., fentanyl);
• medicines similar to morphine (e.g., methadone);
• non-nucleoside reverse transcriptase inhibitors (NNRTIs) (e.g., efavirenz, nevirapine);
• oral contraceptives or contraceptive patches to prevent pregnancy (see section “Contraceptives”below);
• protease inhibitors (e.g., fosamprenavir, indinavir, ritonavir, saquinavir, tipranavir);
• sedatives (e.g., injectable midazolam);
• corticosteroids (e.g., budesonide, dexamethasone, fluticasone propionate, ethinylestradiol, triamcinolone).

For more information on other medicines that you must not take if you are taking lopinavir/ritonavir, see the list of medicines above included in “Do not take Lopinavir/Ritonavir Mylan with any of the following medicines”.

Tell your doctor or pharmacist if you or your child are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.

Medicines for erectile dysfunction (e.g., avanafil, vardenafil, sildenafil, and tadalafil)

• Do not take lopinavir/ritonavirif you are currently taking avanafil or vardenafil.
• Do not take lopinavir/ritonavir with sildenafil when used for the treatment of pulmonary hypertension (high blood pressure in the pulmonary artery) (see also the previous section Do not take Lopinavir/Ritonavir Mylan).
• If you are taking sildenafil or tadalafil and lopinavir/ritonavir together, you may be at risk of adverse reactions such as a decrease in blood pressure, fainting, changes in vision, and an erection of the penis that lasts more than 4 hours. If the erection of the penis lasts more than 4 hours, you must go immediatelyto the doctor to avoid permanent damage to the penis. Your doctor can explain these symptoms to you.

Contraceptives

• If you are taking oral contraceptives or a contraceptive patch to prevent pregnancy, you must use an additional or different type of contraception (e.g., condom), as lopinavir/ritonavir may reduce the effectiveness of oral contraceptives.
• Lopinavir/ritonavir does not reduce the risk of transmitting HIV to others. You must use appropriate precautions (e.g., using a condom) to prevent the transmission of the disease through sexual contact.

Pregnancy and breastfeeding

• Tell your doctor immediatelyif you plan to become pregnant, are pregnant, think you may be pregnant, or are breastfeeding.
• Mothers who are breastfeeding should not take lopinavir/ritonavir unless specifically recommended by the doctor.
• It is recommended that HIV-infected women do not breastfeed their children, as there is a risk that the child may become infected with HIV through breast milk.

Driving and using machines

No studies have been conducted on the effects of lopinavir/ritonavir on the ability to drive and use machines. Do not drive or use machines if you experience any side effects (e.g., nausea) that may affect your ability to do so safely. Consult your doctor.

Lopinavir/Ritonavir Mylan contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per tablet; this is essentially “sodium-free”.

3. How to take Lopinavir/Ritonavir Mylan

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, ask your doctor or pharmacist.

How and when to take Lopinavir/Ritonavir Mylan

Use in adults

• The usual dose in adults is 400 mg/100 mg twice a day, e.g., every 12 hours, in combination with other HIV medications. Adult patients who have not previously been treated with another antiviral medication may also take lopinavir/ritonavir once a day in a dose of 800 mg/200 mg. Your doctor will tell you how many tablets to take. If your doctor decides it is appropriate, adult patients who have been previously treated with other antiviral medications may take lopinavir/ritonavir tablets once a day in a dose of 800 mg/200 mg.
• Lopinavir/ritonavir should not be taken once a day with efavirenz, nevirapine, carbamazepine, phenobarbital, and phenytoin.
• Lopinavir/ritonavir tablets can be taken with or without food.

Use in children 2 years of age or older

• For children, your doctor will decide the correct dose (number of tablets) based on the child's weight and height.
• Lopinavir/ritonavir tablets can be taken with or without food.

Lopinavir/ritonavir is also available in a 200 mg/50 mg film-coated tablet form. Other forms of this medication may be more suitable for children; ask your doctor or pharmacist.

If you or your child take more Lopinavir/Ritonavir Mylan than you should

• If you realize you have taken more lopinavir/ritonavir than indicated, inform your doctor immediately.
• If you cannot contact your doctor, go to the hospital.

If you or your child forget to take Lopinavir/Ritonavir Mylan

If you are taking lopinavir/ritonavir twice a day

• If you realize you have forgotten to take a dose within 6 hours of the usual time, take it as soon as possible and then continue with the normal dosing schedule, taking the next dose at the time it is due, as prescribed by your doctor.

• If more than 6 hours have passed since the usual time of your dose, do not take the missed dose. Take the next dose at the usual time. Do not take a double dose to make up for the missed doses.

If you are taking lopinavir/ritonavir once a day

• If you realize you have forgotten to take a dose within 12 hours of the usual time, take it as soon as possible and then continue with the normal dosing schedule at the time it is due, as prescribed by your doctor.

• If more than 12 hours have passed since the usual time of your dose, do not take the missed dose. Take the next dose at the usual time. Do not take a double dose to make up for the missed doses.

If you or your child stop taking Lopinavir/Ritonavir Mylan

• Do not stop taking or change your daily dose of lopinavir/ritonavir without consulting your doctor first.
• Lopinavir/ritonavir must be taken every day to help control HIV, regardless of how much better you feel.
• Taking lopinavir/ritonavir as recommended is the best way to delay the development of resistance to the medication.
• If an adverse reaction prevents you from taking lopinavir/ritonavir as indicated, tell your doctor promptly.
• Always have a sufficient supply of lopinavir/ritonavir so you do not run out of medication. When traveling or needing to be in the hospital, make sure you have enough medication until you can get more.
• Continue taking this medication until your doctor tells you to stop.

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

4. Possible side effects

Like all medications, lopinavir/ritonavir can cause side effects, although not everybody gets them. It is difficult to distinguish between side effects caused by lopinavir/ritonavir and those caused by other medications you are taking at the same time or those derived from complications of HIV infection.

During HIV treatment, there may be an increase in weight and levels of glucose and lipids in the blood. This may be partly related to the recovery of health and lifestyle, and in the case of blood lipids, sometimes to HIV medications themselves. Your doctor will monitor these changes.

The following side effects have been reported by patients taking this medication.You should inform your doctor promptly about these or any other symptoms. Go to the doctor if they persist or worsen.

Very common:may affect more than 1 in 10 people

• diarrhea;
• nausea;
• upper respiratory tract infection.

Common:may affect up to 1 in 10 people

• pancreatitis;
• vomiting, abdominal distension, abdominal pain in the upper and lower stomach, passing gas, indigestion, decreased appetite, reflux from the stomach to the esophagus that can cause pain;
• tell your doctor if you experience nausea, vomiting, or abdominal pain, as these can be symptoms of pancreatitis (inflammation of the pancreas);
• swelling or inflammation of the stomach, intestine, and colon;
• increase in your blood cholesterol levels, increase in your blood triglyceride levels, high blood pressure;
• decreased ability of the body to metabolize sugar, such as diabetes mellitus, weight loss;

• low red blood cell count, low white blood cell count that is used to fight infections;
• rash, eczema, accumulation of scaly skin;
• dizziness, anxiety, difficulty sleeping;
• feeling tired, loss of strength and energy, headache including migraine;
• hemorrhoids;
• liver inflammation and increased liver enzymes;
• allergic reactions including hives and inflammation in the mouth;
• lower respiratory tract infection;
• increase in lymph nodes;
• impotence, abnormally heavy or prolonged menstrual bleeding or lack of menstruation;
• muscle problems such as muscle weakness and spasms, joint pain, muscle and back pain;
• nerve damage in the peripheral nervous system;
• night sweats, itching, rash including raised bumps on the skin, skin infection, skin inflammation or hair follicle inflammation, fluid accumulation in cells and tissues.

Uncommon:may affect up to 1 in 100 people

• abnormal dreams;
• loss or change of taste;
• hair loss;
• a heart rhythm disorder called atrioventricular block;
• accumulation of platelets in the arteries that can lead to a heart attack and stroke;
• inflammation of blood vessels and capillaries;
• inflammation of the bile duct;
• uncontrollable body shakes;
• constipation;
• inflammation of the veins related to a blood clot;
• dry mouth;
• inability to control the sphincters;
• inflammation of the first section of the small intestine just after the stomach, ulcer or wound in the digestive tract, bleeding from the intestinal or rectal tract;
• red blood cells in the urine;
• fat deposits in the liver, increased liver size;
• testicular dysfunction;
• sudden onset of symptoms related to an inactive infection in your body (immune reconstitution);
• increased appetite;
• abnormally high level of bilirubin (a pigment produced by the breakdown of red blood cells) in the blood;
• decreased sexual desire;
• kidney inflammation;
• death of bone tissue caused by poor blood supply to the area;
• mouth ulcers, stomach and intestine inflammation;
• kidney failure;
• breakdown of muscle fibers that releases the contents of these fibers (myoglobin) into the bloodstream;
• a sound in one or both ears, such as ringing, buzzing, or whistling;
• tremor;
• abnormal closure of one of the heart valves (tricuspid valve of the heart);
• vertigo (feeling of spinning);
• eye disorder, abnormal vision;
• weight gain.

Side effects with unknown frequency

Other side effects that have been reported with lopinavir/ritonavir: yellowing of the skin or the whites of the eyes (jaundice), skin rash and severe or potentially life-threatening blisters (Stevens-Johnson syndrome and erythema multiforme).

If you consider that any of the side effects you are suffering from is serious, or if you notice any side effect not mentioned in this leaflet, tell your doctor or pharmacist.

Reporting of side effects

If you experience any side effects, consult your doctor or pharmacist, even if it is a possible side effect not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting side effects, you can help provide more information on the safety of this medication.

5. Storage of Lopinavir/Ritonavir Mylan

Keep this medication out of sight and reach of children.

This medication does not require special storage conditions.

Do not use this medication after the expiration date stated on the carton after EXP. The expiration date is the last day of the month indicated.

In the case of plastic containers, use the medication within 120 days of initial opening.

Medications should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medication. This will help protect the environment.

6. Package contents and additional information

Composition of Lopinavir/Ritonavir Mylan

• The active ingredients are lopinavir and ritonavir.
• The other ingredients are sorbitan laurate, colloidal anhydrous silica, copovidone, sodium stearyl fumarate, hypromellose, titanium dioxide (E171), macrogol, hydroxypropylcellulose, talc, polysorbate 80.

Appearance of Lopinavir/Ritonavir Mylan and package contents

Lopinavir/Ritonavir Mylan 100 mg/25 mg film-coated tablets are white, oval, biconvex, film-coated tablets with a beveled edge and engraved with "MLR4" on one face and smooth on the other.

They are available in multiple packs of 60 or 60x1 (2 packs of 30 or 30x1) film-coated tablets and in plastic bottles (containing a desiccant that should not be ingested) of 60 film-coated tablets.

Not all pack sizes may be marketed.

Marketing authorization holder

Mylan SAS

117 Allée des Parcs

69800 Saint-Priest

France

Manufacturers

Mylan Hungary Kft

H-2900 Komárom, Mylan utca 1

Hungary

McDermott Laboratories Limited trading as Gerard Laboratories

35/36 Baldoyle Industrial Estate, Grange Road, Dublin 13

Ireland

Mylan B.V.

Dieselweg 25, 3752 LB Bunschoten

Netherlands

You can obtain further information on this medication by contacting the local representative of the marketing authorization holder.

Date of last revision of this leaflet:

Detailed information on this medication is available on the European Medicines Agency website http://www.emea.europa.eu/.