RITONAVIR ACCORD 100 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Ritonavir Accord 100 mg film-coated tablets EFG

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

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

Ritonavir Accord contains the active substance ritonavir. Ritonavir is a protease inhibitor used to control HIV infection. Ritonavir is used in combination with other anti-HIV medicines (antiretrovirals) to control HIV infection. Your doctor will discuss with you which combination of medicines is best for you.

Ritonavir Accord is used in children from 2 years of age and in adolescents and adults infected with HIV, the virus that causes AIDS.

2. What you need to know before you take Ritonavir Accord

Do not take Ritonavir Accord

• if you are allergic to ritonavir or any of the other ingredients of this medicine (listed in section 6).
• if you have severe liver disease.
• if you are currently taking any of the following medicines:
• astemizole or terfenadine (usually used to treat allergy symptoms – these medicines can be bought without a prescription);
• amiodarone, bepridil, dronedarone, encainide, flecainide, propafenone, quinidine (used to correct irregular heartbeats);
• dihydroergotamine, ergotamine (used to treat migraine headaches);
• ergonovine, methylergonovine (used to stop bleeding that may occur after childbirth or abortion);
• chlorazepate, diazepam, estazolam, flurazepam, triazolam, or oral midazolam (used to help you sleep and/or relieve anxiety);
• clozapine, pimozide (used to treat abnormal thoughts or feelings):
• quetiapine (used to treat schizophrenia, bipolar disorder, and major depressive disorder);
• meperidine, propoxyphene (used to relieve pain);
• cisapride (used to relieve certain stomach pains);
• rifabutin (used to prevent/treat certain infections)*;
• voriconazole (used to treat fungal infections)*;
• simvastatin, lovastatin, (used to lower blood cholesterol);
• neratinib (used to treat breast cancer);
• lomitapide (used to lower blood cholesterol);
• alfuzosin (used to treat enlarged prostate);
• fusidic acid (used to treat bacterial infections).
• sildenafil if you have a lung disease called pulmonary arterial hypertension that makes it difficult to breathe. Patients without this disease may use sildenafil for impotence (erectile dysfunction) under the supervision of their doctor (see section "Taking Ritonavir Accord with other medicines");
• avanafil or vardenafil (used to treat impotence);
• colchicine (used to treat gout) if you have liver and/or kidney problems (see also "Do not take Ritonavir Accord" above);
• products containing St. John's Wort (Hypericum perforatum) as they may cause Ritonavir Accord to stop working properly. St. John's Wort is often used in herbal medicines that you can buy yourself.

*Your doctor may decide that you can take rifabutin and/or voriconazole with a booster dose (low dose) of ritonavir, but a full dose of Ritonavir Accord should not be taken with these two medicines.

If you are currently taking any of these medicines, ask your doctor if you could change the medicine while taking this medicine.

For the use of other medicines that require special care, see the list included in the section "Taking Ritonavir Accord with other medicines"

Warnings and precautions

Consult your doctor before starting to take this medicine

Important information

• If you take Ritonavir Accord with other antiretroviral medicines, it is important that you carefully read the package leaflets of these other medicines. In these package leaflets, you may find additional important information about situations in which you should avoid taking Ritonavir. If you have any further questions about this medicine or the other medicines that you have been prescribed, ask your doctor or pharmacist.
• Ritonavir is not a cure for HIV infection or AIDS
• People taking Ritonavir may still develop infections or other illnesses related to HIV infection or AIDS. It is therefore important that you remain under the supervision of your doctor while taking this medicine.

Tell your doctor if you have or have had:

• A history of liver disease.

• Hepatitis B or C and are being treated with a combination of antiretroviral medicines, as you have a greater risk of suffering from serious and potentially life-threatening side effects due to the effect on the liver. You may need to have blood tests to check your liver function.

• Haemophilia, as there have been cases of patients with haemophilia being treated with this type of medicine (protease inhibitors) with increased bleeding. The reason for this is not known. You may need to be given additional medicine to help your blood clot (Factor VIII) to control any bleeding.

• Erectile dysfunction: as medicines used to treat erectile dysfunction can cause low blood pressure and prolonged erection.

• Diabetes, as there have been cases of worsening or development of diabetes (diabetes mellitus) in some patients taking protease inhibitors.

• Kidney disease (renal): as your doctor may need to check the dose of other medicines you are taking (such as protease inhibitors)

Tell your doctor if you experience:

• Diarrhoea or vomiting that does not improve (persistent), as this may reduce the effectiveness of the medicines you are taking.

• Nausea, vomiting, or stomach pain, as these can be signs of pancreatitis (inflammation of the pancreas). Some patients taking Ritonavir Accord may develop pancreas problems. Tell your doctor as soon as possible if this is the case

• Infection symptoms - tell your doctor immediately. Some patients with advanced HIV infection (AIDS) who start anti-HIV treatment may develop symptoms of infections they have had in the past, even if they did not know they had them. It is believed that this occurs because the body's immune response improves and helps the body fight off these infections. In addition to opportunistic infections, you may also experience autoimmune disorders (a problem that occurs when the immune system attacks the body's healthy tissue) after you start taking medicines for the treatment of your HIV infection. Autoimmune disorders may occur 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 towards the trunk, palpitations, tremor, or hyperactivity, please tell your doctor immediately to seek the necessary treatment.

• Joint stiffness, discomfort, and pain (especially of the hip, knee, and shoulder) and difficulty moving, tell your doctor, as this may be a sign of a problem that can destroy bone (osteonecrosis). Some patients taking antiretroviral medicines may develop this disease.

• Muscle pain, discomfort, or weakness, particularly in combination with antiretroviral therapy including protease inhibitors and nucleoside analogues. In rare cases, these muscle disorders have been serious (see section 4. Possible side effects)

• Dizziness, drowsiness, fainting, or abnormal heartbeat: Some patients taking Ritonavir Accord may experience changes in the electrocardiogram (ECG). Tell your doctor if you have any heart problems or heart conduction problems

• If you have any other health problems, consult your doctor as soon as possible.

Children and adolescents

Ritonavir Accord is not recommended for use in children under 2 years of age

Taking Ritonavir Accord with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those bought without a prescription. There are some medicines that you cannot take with Ritonavir Accord. These medicines are listed in section 2 "Do not take Ritonavir Accord". There are some medicines that can only be taken under certain circumstances as described below.

When this medicine is used at full dose, the following precautions will be taken. However, these precautions may also be necessary when low doses (boosting) of Ritonavir Accord are taken with other medicines.

Tell your doctor if you are taking any of the medicines listed below, special precautions are needed.

• Sildenafil or tadalafil for impotence (erectile dysfunction).

You should reduce the dose of these medicines to avoid low blood pressure and prolonged erection. You should not take Ritonavir Accord with sildenafil if you have pulmonary arterial hypertension (see section 2. What you need to know before you take Ritonavir Accord). Tell your doctor if you are taking tadalafil for the treatment of pulmonary arterial hypertension.

• Colchicine (for gout) as ritonavir may increase the levels of this medicine in the blood. You should not take ritonavir with colchicine if you have liver and/or kidney problems (see also "Do not take Ritonavir Accord" above).

• Digoxin (heart medicine). To prevent heart problems, your doctor may need to adjust the dose of digoxin and monitor you while you are taking digoxin and Ritonavir Accord.

• Hormonal contraceptivesthat contain ethinyl estradiol, as Ritonavir Accord may reduce the effectiveness of these medicines. It is recommended to use a condom or another non-hormonal contraceptive method instead. You may also experience irregular uterine bleeding if you take this type of hormonal contraceptive with Ritonavir Accord.

• Atorvastatin or rosuvastatin(for high cholesterol) as Ritonavir Accord may increase the levels of these medicines in the blood. Tell your doctor before taking cholesterol-lowering medicines with Ritonavir Accord (see "Do not take Ritonavir Accord" above).

• Corticosteroids(e.g. dexamethasone, fluticasone propionate, prednisolone, triamcinolone), as Ritonavir Accord may increase the levels of these medicines in the blood, which can lead to Cushing's syndrome (development of a rounded face) and reduced production of the cortisol hormone. Your doctor may want to reduce the dose of corticosteroids or monitor their side effects more closely.

• Trazodone(depression medicine) as unwanted effects such as nausea, dizziness, low blood pressure, and fainting may occur when taken with Ritonavir Accord.

• Rifampicin and saquinavir(used for tuberculosis and HIV respectively) as they may cause serious liver damage when taken with Ritonavir Accord.

• Bosentan, riociguat(used for pulmonary arterial hypertension) with Ritonavir Accord may increase the amount of this medicine (Bosentan) in the blood.

There are medicines that should not be taken with Ritonavir Accord because their effects may increase or decrease when taken together. In some cases, your doctor may need to perform certain tests, change the dose, or monitor you regularly. For this reason, you should tell your doctor if you are taking any medicine, including those you have bought yourself or herbal products, especially the following:

• amphetamines or amphetamine derivatives;
• antibiotics (e.g. erythromycin, clarithromycin);
• cancer treatments (e.g. abemaciclib, afatinib, apalutamide, ceritinib, encorafenib, dasatinib, ibrutinib, nilotinib, vincristine, vinblastine)
• medicines used to treat low blood platelet count (e.g. fostamatinib)
• anticoagulants (e.g. dabigatran etexilate, edoxaban, rivaroxaban, vorapaxar, warfarin)
• antidepressants (e.g. amitriptyline, desipramine, fluoxetine, imipramine, nefazodone, nortriptyline, paroxetine, sertraline, trazodone);
• antifungals (e.g. ketoconazole, itraconazole);
• antihistamines (e.g. loratadine, fexofenadine);
• antiretroviral medicines including HIV protease inhibitors (amprenavir, atazanavir, darunavir, fosamprenavir, indinavir, nelfinavir, saquinavir, tipranavir) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) (delavirdine, efavirenz, nevirapine), and others (didanosine, maraviroc, raltegravir, zidovudine);
• medicines for tuberculosis (bedaquiline and delamanid);
• antiviral medicines for the treatment of chronic hepatitis C virus (HCV) infection in adults (e.g. glecaprevir/pibrentasvir and simeprevir);
• medicines for anxiety, buspirone;
• medicines for asthma, theophylline, salmeterol;
• atovaquone, a medicine used to treat certain types of pneumonia and malaria;
• buprenorphine, a medicine used for chronic pain;
• bupropion, a medicine used to help stop smoking;
• medicines for epilepsy (e.g. carbamazepine, divalproex, lamotrigine, phenytoin);
• medicines for the heart (e.g. disopyramide, mexiletine, and calcium channel blockers such as amlodipine, diltiazem, and nifedipine);
• medicines that affect the immune system (e.g. cyclosporin, tacrolimus, everolimus);
• levothyroxine (used to treat thyroid problems);
• morphine and morphine derivatives used to treat severe pain (methadone, fentanyl);
• sleeping pills (e.g. alprazolam, zolpidem) and also midazolam given by injection;
• tranquillisers (e.g. haloperidol, risperidone, thioridazine);
• colchicine, a treatment for gout.

There are some medicines that you cannot take with Ritonavir Accord. These are listed earlier in section 2 "Do not take Ritonavir Accord"

Taking Ritonavir Accord with food and drink

Ritonavir Accord tablets should be taken with food.

Pregnancy and breast-feeding

If you are pregnant, think you may be pregnant, or are planning to have a baby, you should consult your doctor before taking this medicine.

There is very little information on the use of ritonavir (the active substance of Ritonavir Accord) during pregnancy. In general, pregnant women received low doses (boosting) of ritonavir together with another protease inhibitor after the first three months of pregnancy. Ritonavir Accord does not appear to increase the risk of birth defects compared to the general population.

It is not recommended that women with HIV infection breast-feed their babies because HIV infection can be transmitted to the baby through breast milk.

If you are breast-feeding or think you may want to breast-feed, you should consult your doctor as soon as possible.

Driving and using machines

Ritonavir Accord may cause dizziness. If you experience these effects, do not drive or use machines.

Ritonavir Accord contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per tablet, which is essentially "sodium-free".

3. How to take Ritonavir Accord

Follow exactly the administration instructions of Ritonavir Accord indicated by your doctor or pharmacist. Consult your doctor or pharmacist if you have any doubts. Take this medication once or twice a day every day with food.

It is essential that Ritonavir Accord tablets be swallowed whole and not chewed, broken, or crushed.

The recommended doses of Ritonavir Accord are:

• If Ritonavir Accord is used to boost the effect of other antiretroviral medications, the dose for adults is 1 to 2 tablets once or twice a day. For more information on dosage recommendations, including those for children, read the package insert of the anti-HIV medications taken in combination with Ritonavir Accord.

• If your doctor prescribes a full dose, adults can start with a dose of 3 tablets in the morning and 3 tablets 12 hours later, which will be gradually increased over a period of up to 14 days to reach the full dose of 6 tablets twice a day (a total of 1200 mg per day). Children (2-12 years) will start with a lower dose and continue until the maximum allowed dose for their height.

Your doctor will indicate the appropriate dose you should take.

You must take Ritonavir Accord every day to control HIV, regardless of whether you feel better. If there are any side effects that prevent you from taking Ritonavir Accord as indicated, inform your doctor immediately. During episodes of diarrhea, your doctor may decide that you need additional monitoring.

Always have a sufficient amount of Ritonavir Accord on hand to avoid running out. When traveling or needing to stay in the hospital, check that you have enough Ritonavir Accord until you can get more.

If you take more Ritonavir Accord than you should

If you take too much Ritonavir Accord, you may experience numbness, tingling, or a sensation of pins and needles. If you realize you have taken more Ritonavir Accord than you should, contact your doctor or the Emergency Service of the nearest hospital immediately.

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

If you forget to take Ritonavir Accord

If you have forgotten to take a dose, take it as soon as possible. If the time of the next dose is near, take only one dose.

Do not take a double dose to make up for forgotten doses.

If you interrupt treatment with Ritonavir Accord

Even if you feel better, do not stop taking Ritonavir Accord without consulting your doctor.

If you take Ritonavir Accord as indicated, you will have more chances of delaying the development of resistance to this medication.

4. Possible adverse effects

During HIV treatment, there may be an increase in weight and glucose and lipid levels 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.

Like all medications, Ritonavir Accord can cause adverse effects, although not all people experience them.

When Ritonavir Accord is used with other antiretroviral medications, the adverse effects also depend on those other medications. Therefore, it is very important that you carefully read the section on adverse reactions in the package insert of these medications.

Tell your doctor if you feel dizzy (nauseous), are vomiting, or have stomach pain, as these can be symptoms of pancreatitis. Also, inform your doctor if you experience joint stiffness, discomfort, and pain (especially in the hip, knee, and shoulder) and difficulty moving, as this may be a sign of osteonecrosis. See section 2. What you need to know before taking Ritonavir Accord.

There have been cases of increased bleeding in patients with hemophilia A and B during treatment with this or another protease inhibitor. If this happens to you, consult your doctor immediately.

It has been reported that patients taking Ritonavir Accord have presented with alterations in liver function tests, hepatitis (liver inflammation), and rarely, jaundice. Some people had other diseases or were taking other medications. Some people with liver disease or hepatitis may have worsened.

There have been reports of muscle pain, discomfort, or weakness, particularly when taking cholesterol-reducing medications in combination with combined antiretroviral therapy, including protease inhibitors and nucleoside analogs. In rare cases, these muscle disorders were severe (rhabdomyolysis). In case of muscle pain, discomfort, weakness, or cramps of unknown cause or continuous, stop taking the medication, contact your doctor as soon as possible, or go to the Emergency Service of the nearest hospital.

Tell your doctor immediately if after taking Ritonavir Accord you experience any symptoms that may suggest an allergic reaction, such as skin rash, hives, or difficulty breathing.

If you consider that any of the side effects you are experiencing is serious or if you notice any side effect not mentioned in this package insert, inform your doctor, pharmacist, or go to the emergency room, or if it is urgent, seek immediate medical attention.

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 not listed in this package insert. You can also report them directly through the Spanish Pharmacovigilance System for human use medications:

https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Ritonavir Accord

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date shown on the box and on the bottle after CAD. The expiration date is the last day of the month indicated.

Once the bottle is opened, use within the next 4 months.

Store below 25°C

Medications should not be disposed of through wastewater or household waste. Deposit the packaging and medications you no longer need at the SIGRE point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. This way, you will help protect the environment.

6. Package contents and additional information

Composition of Ritonavir Accord

• The active ingredient is ritonavir. Each film-coated tablet contains 100 mg of ritonavir.

• The other ingredients are: copovidone, sorbitan laurate (E493), colloidal anhydrous silica (E551), anhydrous calcium hydrogen phosphate, and sodium stearyl fumarate.

• The ingredients of the film coating are: hypromellose (E464), titanium dioxide (E171), macrogol, hydroxypropyl-cellulose (E463), talc (E553b), colloidal anhydrous silica (E551), and polysorbate 80 (E433).

Appearance of the product and package contents

Ritonavir Accord film-coated tablets are white or pale white, capsule-shaped, and marked with "H" on one side and "R9" on the other side.

Ritonavir Accord tablets are available in white HDPE bottles with child-resistant polypropylene caps and Alu-Alu blisters.

Package sizes:

HDPE bottle: 30, 90, and 120 film-coated tablets.

Box containing single-dose precut blisters: 30, 90, and 120 film-coated 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, 6ª planta,

08039 Barcelona,

Spain

Manufacturers:

Pharmadox Healthcare Ltd.

KW20A Kordin Industrial Park, Paola

Malta

This package insert was revised in: January 2025

Detailed information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS): http://www.aemps.gob.es/