Package Leaflet: Information for the User

Lopinavir/Ritonavir Accord 200 mg/50 mg Film-Coated Tablets

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

− Keep this leaflet, as you may need to read it again.

− If you have any questions, ask your doctor or pharmacist.

− This medicine has been prescribed for you or your child only. Do not give it to others even if they have the same symptoms as you, as it may harm them.

− If you experience any side effects, consult your doctor or pharmacist even if they are not listed in this leaflet. See section 4.

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

2. What you need to know before you or your child take Lopinavir/Ritonavir Accord

3. How to take Lopinavir/Ritonavir Accord

4. Possible side effects

5. Storage of Lopinavir/Ritonavir Accord

6. Contents of the pack and additional information

- Your doctor has prescribed Lopinavir/Ritonavir Accord to help control your human immunodeficiency virus (HIV) infection. This is possible because Lopinavir/Ritonavir Accord acts by preventing the infection from spreading rapidly.

- Lopinavir/Ritonavir Accord is not a cure for HIV or AIDS infection.

- Lopinavir/Ritonavir Accord is used in children aged 2 years or older, adolescents, and adults infected with HIV, the virus that causes AIDS. Lopinavir/Ritonavir Accord should not be administered to children under 2 years of age unless your doctor specifically instructs you to do so.

- Lopinavir/Ritonavir Accord is an antiretroviral medication. It belongs to the group of drugs known as protease inhibitors.

- Lopinavir/Ritonavir Accord is prescribed for use in combination with other antiviral medications. Your doctor will inform and decide which medications are best for your case.

Do not take Lopinavir/Ritonavir Accord

- If you are allergic to lopinavir, ritonavir, or any of the other components of this medication (listed in section 6).

- If you have severe liver problems.

Do not take Lopinavir/Ritonavir Accord with any of the following medications:

- Astemizol or terfenadine (usually used to treat allergy symptoms – these medications may not require a prescription);

- Midazolam oral (taken by mouth), triazolam (used to relieve anxiety and/or sleep problems);

- Pimozide (used to treat schizophrenia);

- Quetiapina (used to treat schizophrenia, bipolar disorder, and major depressive disorder);

- Lurasidona (used to treat depression);

- Ranolazina (used to treat chronic chest pain [angina pectoris]);

- Cisaprida (used to relieve certain stomach problems);

- Ergotamina, dihidroergotamina, ergonovina, and metilergonovina (used to treat headaches);

- Amiodarona, dronedarona (used to treat arrhythmias);

- Lovastatina, simvastatina (used to lower cholesterol in the blood);

- Lomitapida (used to lower cholesterol in the blood);

- Alfuzosina (used in men to treat symptoms of an enlarged prostate (benign prostatic hyperplasia (BPH));

- Ácido fusídico (used to treat skin infections caused by the bacteria Staphylococcus, such as impétigo and infected dermatitis. Ácido fusídico is also used to treat long-term bone and joint infections under medical supervision (see Use of Lopinavir/Ritonavir Accord with other medications);

- Colchicina (medication used to treat gout). If you have liver or kidney problems (see Use of Lopinavir/Ritonavir Accord with other medications);

- Elbasvir/grazoprevir (used to treat chronic hepatitis C [HCV]);

- Ombitasvir/paritaprevir/ritonavir with or without dasabuvir (used to treat chronic hepatitis C [HCV]);

- Neratinib (used to treat breast cancer);

- Avanafilo or Vardenafilo (used to treat erectile dysfunction);

- Sildenafilo used to treat pulmonary hypertension (high blood pressure in the pulmonary artery). Sildenafilo may be used to treat erectile dysfunction under medical supervision (see Be careful with Lopinavir/Ritonavir Accord);

- Products containing St. John's Wort (Hypericum perforatum).

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

If you are currently taking any of these medications, 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.

Important information

- People taking Lopinavir/Ritonavir Accord may still develop infections or other diseases associated with HIV and AIDS. Therefore, it is essential to remain under the supervision of your doctor while taking Lopinavir/Ritonavir Accord.

Inform your doctor if you or your child have or have had:

- Hemophilia type A and B, as Lopinavir/Ritonavir Accord may increase the risk of bleeding.

- Diabetes, as there have been reports of increased blood sugar levels in patients taking Lopinavir/Ritonavir Accord.

- A history of liver problems, as patients with a history of liver disease, including chronic hepatitis B or C, have a higher risk of severe and potentially life-threatening liver damage.

Inform 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 large increases in triglyceride levels (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, symptoms and signs of previous infections may appear shortly after starting antiretroviral treatment. It is believed that these symptoms are due to an improvement in the body's immune response, allowing it to fight off infections that were present without apparent symptoms.

Additionally, autoimmune disorders (a condition that occurs when the immune system attacks healthy body tissue) may occur after starting antiretroviral treatment. These autoimmune disorders may occur many months after starting treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, starting in the hands and feet and extending to the trunk of the body, palpitations, tremors, or hyperactivity, inform your doctor immediately to seek necessary treatment.

- Joint stiffness, pain, and discomfort (especially in the hip, knee, and shoulder) and difficulty moving, as some patients taking these medications may develop a bone disease called osteonecrosis (death of bone tissue caused by a loss of blood supply to the bone). Several risk factors for developing this disease include the duration of combined antiretroviral treatment, the use of corticosteroids, alcohol consumption, severe immunodepression (weakened immune system), and a high body mass index.

- Muscle pain, discomfort, or pain, particularly in combination with these medications. In rare cases, these muscle changes have been severe.

- Symptoms of dizziness, dizziness, fainting, or abnormal heartbeats. Lopinavir/Ritonavir Accord may cause changes in heart rhythm and cardiac activity. These changes may be seen on an ECG (electrocardiogram).

Use of Lopinavir/Ritonavir Accord with other medications

Inform your doctorif you or your child are taking any of the following medications, as special precautions are required:

- Antibiotics (e.g. rifampicin, rifabutina, claritromicina);

- Cancer medications (e.g. abemaciclib, afatinib, apalutamida, ceritinib, encorafenib, ibrutinib, venetoclax, most tyrosine kinase inhibitors such as dasatinib and nilotinib, and also vinblastine and vincristine);

- Anticoagulants (e.g. warfarina, rivaroxaban, vorapaxar);

- Antidepressants (e.g. trazodona, bupropión);

- Antiepileptic medications (e.g. carbamazepina, fenítoina, fenobarbital, lamotrigina, and valproato);

- Antifungals (e.g. ketoconazol, itraconazol, voriconazol);

- Medications for gout (e.g. colchicina). You should not take lopinavir/ritonavir with colchicina if you have liver or kidney problems (see also “Do not take Lopinavir/Ritonavir Accord” above);

- Medications for tuberculosis (e.g. bedaquilina, delamanida);

- Antiviral medications used in the treatment of chronic hepatitis C (HCV) in adults (e.g. glecaprevir/pibrentasvir, simeprevir, and sofosbuvir/velpatasvir/voxilaprevir);

- Medications for erectile dysfunction (e.g. sildenafilo and tadalafilo);

- Ácido fusídico used in the treatment of long-term bone and joint infections (e.g. osteomielitis);

- Medications for the heart, including:

o Digoxina;

o Calcium channel blockers (e.g. felodipino, nifedipino, nicardapino);

o Medications used to correct heart rhythm (e.g. bepridil, systemic lidocaine, quinidina);

- Antagonist HIV CCR5 (e.g. maraviroc)

- Medications used to treat low platelet counts in the blood (e.g. fosfatimib);

- Integravir inhibitor HIV-1 (e.g. raltegravir)

- Medications used to lower cholesterol in the blood (e.g. atorvastatina, lovastatina, rosuvastatina, or simvastatina);

- Medications used to treat asthma and other lung problems, such as chronic obstructive pulmonary disease (COPD) (e.g. salmeterol);

- Medications used to treat pulmonary hypertension (high blood pressure in the pulmonary artery) (e.g. bosentan, riociguat, sildenafilo, tadalafilo);

- Medications that affect the immune system (e.g. ciclosporina, sirolimus (rapamicina), tacrolimus);

- Analgesics (e.g. fentanilo);

- Medications used to quit smoking (e.g. bupropión);

- Medications similar to morphine (e.g. metadona);

- Non-nucleoside reverse transcriptase inhibitors (NNRTIs) (e.g. efavirenz, nevirapina);

- Contraceptives (e.g. oral contraceptives or contraceptive patches to prevent pregnancy (see Contraceptives below);

- Protease inhibitors (e.g. fosamprenavir, indinavir, ritonavir, saquinavir, tripanavir);

- Sedatives (e.g. midazolam injectable);

- Steroids (e.g. budesonida, dexametasona, propionato de fluticasona, etinilestradiol, triamcinolona);

- Levotiroxina (used to treat thyroid problems)

For more information on other medications that should not be taken with Lopinavir/Ritonavir Accord, see the list of medications included above in “Do not take Lopinavir/Ritonavir Accord with any of the following medications.”

Inform your doctor or pharmacist if you or your child are taking or have taken recentlyor may need to take other medications, including those obtained without a prescription.

Medications for erectile dysfunction (e.g. vardenafilo, sildenafilo, and tadalafilo

- Do not take Lopinavir/Ritonavir Accord if you are currently taking vardenafilo.

- You should not take Lopinavir/Ritonavir Accord with sildenafilo when used to treat pulmonary hypertension (high blood pressure in the pulmonary artery) (see also the section above Do not take Lopinavir/Ritonavir Accord).

- If you are taking sildenafilo or tadalafilo and Lopinavir/Ritonavir Accord together, you may have an increased risk of adverse reactions such as decreased blood pressure, fainting, changes in vision, and prolonged erection of the penis. If the erection of the penis lasts more than 4 hours, you should seek medical attention immediately to avoid permanent damage to the penis. Your doctor may explain these symptoms.

Contraceptives

- If you are taking oral contraceptives or a contraceptive patch to prevent pregnancy, you should use an additional or different type of contraception (e.g. condom), as Lopinavir/Ritonavir Accord may reduce the effectiveness of oral contraceptives.

Pregnancy and breastfeeding

- Inform your doctor immediately if you plan to become pregnant, are pregnant, or think you may be pregnant.

- If you are breastfeeding or plan to do so, you should discuss this with your doctor as soon as possible.

- Women living with HIV should not breastfeed their children, as there is a possibility that the child may become infected with HIV through breast milk.

Driving and using machines

You have not been involved in specific studies on the effects of Lopinavir/Ritonavir Accord on your ability to drive and use machines. Do not drive or use machines if you experience any adverse effects (e.g. nausea) that may affect your ability to do so safely. Consult your doctor.

Lopinavir/Ritonavir Accord contains sodium

This medication contains less than 23 mg of sodium (1 mmol) per dose; it is essentially “sodium-free.”

How and when to take Lopinavir/Ritonavir Accord

-Follow exactly the administration instructions for this medication as indicated by your doctor or pharmacist.

-Consult your doctor or pharmacist again if you are unsure about how to take your medication.

Use in adults

-The usual dose in adults is 400mg/100mg twice a day, for example, every 12 hours, in combination with other HIV medications. Adult patients who have not been previously treated with another antiviral medication may also take Lopinavir/Ritonavir Accord once a day in a dose of 800 mg/ 200 mg. Your doctor will tell you how many tablets you should take. If your doctor decides that it is appropriate, adult patients who have been previously treated with other antiretroviral medications may take Lopinavir/Ritonavir Accord tablets once a day in doses of 800 mg/200 mg.

-Lopinavir/Ritonavir Accord should not be taken once a day with efavirenz, nevirapina, carbamazepina, phenobarbital, and phenytoin.

-Lopinavir/Ritonavir Accord tablets can be taken with or without food.

Use in children

-Your doctor will decide on the correct dose (number of tablets) for children based on their weight and height.

-Lopinavir/Ritonavir Accord can be taken with or without food.

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

-If you realize that you have taken more Lopinavir/Ritonavir Accord than indicated, inform your doctor immediately.

-If you cannot find your doctor, go to the hospital.

For cases of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

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

-If you forget a dose, take it as soon as possible and then continue with the normal dosing as prescribed by your doctor.

-Do not take a double dose to compensate for the missed doses.

If you or your child stop taking Lopinavir/Ritonavir Accord

-Do not stop taking or change your daily dose of Lopinavir/Ritonavir Accord without consulting your doctor first.

-Lopinavir/Ritonavir Accord must be taken every day to help control HIV, regardless of how you feel.

-The use of Lopinavir/Ritonavir Accord 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 Accord as indicated, tell your doctor quickly.

-Always have a sufficient amount of Lopinavir/Ritonavir Accord so that you do not run out of medication. When traveling or needing to be in the hospital, make sure you have enough Lopinavir/Ritonavir Accord until you can get more.

-Continue taking this medication until your doctor tells you to.

Like all medicines, Lopinavir/Ritonavir Accord can cause side effects, although not everyone will experience them. It is difficult to distinguish between side effects caused by Lopinavir/Ritonavir Accord and those of other medicines you are taking at the same time or those resulting 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 recovery of health and lifestyle, and in the case of lipids in the blood, sometimes to HIV medicines themselves. Your doctor will monitor these changes.

The following side effects have been reported by patients who took this medicine.You should inform your doctor quickly about these or any other symptoms. Attend the doctor if they persist or worsen.

Very commonmay affect more than 1 in 10 people:

- Diarrhea;

- Nausea;

- Upper respiratory tract infection.

Commonmay affect up to 1 in 10 people:

- Pancreatitis (inflammation of the pancreas);

- Vomiting, increased abdominal size, upper and lower abdominal pain, temporary flatulence, indigestion, decreased appetite, reflux from the stomach to the esophagus that can cause pain;

-Inform your doctorif you experience nausea, vomiting, or abdominal pain, as they may be symptoms of pancreatitis (inflammation of the pancreas).

- Swelling or inflammation of the stomach, intestines, and colon;

- Increased levels of cholesterol in the blood, increased levels of triglycerides (a type of fat) in the blood, 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 are usually used to fight infections;

- Rash, eczema, accumulation of greasy skin scales;

- Dizziness, anxiety, difficulty sleeping;

- Feeling of fatigue, loss of strength and energy, headache including migraine;

- Hemorrhoids;

- Inflammation of the liver and increased liver enzymes;

- Allergic reactions including urticaria and inflammation in the mouth;

- Lower respiratory tract infection;

- Increased lymph nodes;

- Impotence, abnormally heavy or prolonged menstrual flow or amenorrhea,

- Muscle problems such as muscle weakness and spasms, joint, muscle, and back pain;

- Damage to the peripheral nervous system;

- Nocturnal sweating, itching, hives including raised skin bumps, skin infection, inflammation of the skin or capillaries, accumulation of fluid in cells and tissues.

Uncommonmay affect up to 1 in 100 people:

- Abnormal dreams;

- Loss or change of sense of taste;

- Hair loss;

- Abnormal electrocardiogram (ECG) called atrioventricular block.

- Accumulation of platelets in arteries that can lead to heart attack and stroke;

- Inflammation of blood vessels and capillaries;

- Inflammation of the bile duct;

- Uncontrollable body tremors;

- 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, wound or ulcer in the digestive tract, intestinal or rectal bleeding;

- Red blood cells in the urine;

- Yellowish color of the skin or white of the eyes (jaundice);

- Deposition of fat in the liver, increased liver size;

- Decreased testicular function;

- Sudden reappearance of symptoms related to an inactive infection in your body (immune reconstitution);

- Increased appetite;

- Abnormal increase in bilirubin levels (a pigment produced by the breakdown of red blood cells) in the blood;

- Decreased sexual desire;

- Inflammation of the kidney;

- Bone death caused by poor blood supply to the area;

- Mouth ulcers, inflammation of the stomach and intestines;

- Kidney failure;

- Release of muscle fibers contents (myoglobin) into the bloodstream;

- Sound in one ear or both ears, such as buzzing, ringing, or hissing;

- Tremor;

- Abnormal closure of one of the valves (tricuspid valve of the heart);

- Vertigo (sensation of spinning);

- Eye disorder, abnormal vision;

- Weight gain.

Rare:may affect up to 1 in 1,000 people:

• Severe or potentially life-threatening skin eruptions and blisters (Stevens-Johnson syndrome and erythema multiforme).

Frequency not known: cannot be estimated from available data

• kidney stones

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

-Keep this medication out of the sight and reach of children.

-Do not use Lopinavir/Ritonavir Accord after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

-No special storage conditions are required.

-Do not use this medication if you observe any color change.

How to dispose of unused Lopinavir/Ritonavir Accord

-Unused medications should not be flushed down the drain or thrown away.

-Ask your pharmacist how to dispose of medications that you no longer need.

By doing so, you will help protect the environment.

Composition of Lopinavir/Ritonavir Accord

The active ingredients are lopinavir and ritonavir.

Each Lopinavir/Ritonavir Accord tablet contains 200 mg of lopinavir and 50 mg of ritonavir.

The other components are:

Tablet:Copovidone, sorbitan laurate, anhydrous colloidal silica, stearate of stearic acid and sodium.

Covering:Hydroxypropylmethylcellulose (E464),dióxido de titanio (E171), macrogol (polyethylene glycol 400), hydroxypropylcellulose (E463), talc (E553b), anhydrous colloidal silica (E551), macrogol (polyethylene glycol 3350), yellow iron oxide (E-172), polisorbate 80 (E433).

Appearance of the product and contents of the package

Lopinavir/Ritonavir Accord 200 mg/50 mg coated tablets are yellow, oval, biconvex, marked with “H” on one side and with “L3” on the other.

Lopinavir/Ritonavir Accord 200 mg/50 mg coated tablets with a film coating are presented in packages of 120 tablets (1 plastic bottle with 120 tablets) and multiple package with 360 tablets (3 plastic bottles with 120 tablets each). They are also available in packages with blisters containing 60 and 120 tablets (1 package with 120 tablets or multiple package with 3 packages of 40 tablets).

Not all package sizes may be marketed.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est, 6th floor

08039 Barcelona

Manufacturers responsible

Pharmadox Healthcare, Ltd

KW20A Kordin Industrial Park,

Paola, PLA 300

Malta

This medicine was authorized in the EEA member states with the following names:

Last review date of this leaflet: April 2023

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/