Darunavir Sandoz 600 mg film-coated tablets EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Darunavir Sandoz 600 mg film-coated tablets EFG

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

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only and must not be given to other people. It may harm them, even if their symptoms are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any side effects not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Darunavir Sandoz is and what it is used for
2. What you need to know before taking Darunavir Sandoz
3. How to take Darunavir Sandoz
4. Possible side effects
5. How to store Darunavir Sandoz
6. Contents of the pack and other information

1. What Darunavir Sandoz is and what it is used for

What is Darunavir Sandoz?

Darunavir Sandoz contains the active substance darunavir.

Darunavir is an antiretroviral medicine used to treat Human Immunodeficiency Virus (HIV) infection. It belongs to a group of medicines called protease inhibitors. Darunavir reduces the amount of HIV in your body. As a result, your immune system improves and the risk of developing HIV-related illnesses decreases.

What is it used for?

Darunavir is used to treat adults and children from 3 years of age and weighing at least
15 kilograms who are infected with HIV and who have previously used other antiretroviral medicines.

Darunavir must be taken together with a low dose of ritonavir and other HIV medicines. Your doctor will advise you on the most appropriate combination of medicines for you.

2. What you need to know before starting Darunavir Sandoz

Do not take Darunavir Sandoz:

• if you are allergic to darunavir or to any of the other ingredients of this medicine (listed in section 6) or to ritonavir.
• if you have severe liver problems. Ask your doctor if you are unsure about the severity of your liver disease. Additional tests may be required.

Inform your doctor about all the medicines you are taking, including those taken orally, inhaled, injected, or applied to the skin.

Do not combine Darunavir Sandoz with any of the following medicines

If you are taking any of these medicines, consult your doctor to switch to another medicine.

Medicine	Purpose of the medicine
Avanafil	treatment of erectile dysfunction
Astemizole or terfenadine	treatment of allergy symptoms
Triazolam and oral midazolam	help you sleep and/or relieve anxiety
Cisapride	treatment of stomach problems
Colchicine (if you have kidney and/or liver problems)	treatment of gout or familial Mediterranean fever
Lurasidone, pimozide, quetiapine or sertindole	treatment of psychiatric disorders
Ergot alkaloids such as ergotamine, dihydroergotamine, ergometrine and methylergonovine	treatment of migraine headaches
Amiodarone, bepridil, dronedarone, ivabradine, quinidine, ranolazine	treatment of certain heart conditions, for example irregular heartbeats
Lovastatin, simvastatin and lomitapide	reduce cholesterol levels
Rifampicin	treatment of certain infections such as tuberculosis
Combination of medicines lopinavir/ritonavir	this HIV medicine belongs to the same class as Darunavir
Elbasvir/grazoprevir	to treat hepatitis C infection
Alfuzosin	treatment of enlarged prostate
Sildenafil	treatment of high blood pressure in the pulmonary circulation
Ticagrelor	to help prevent platelet aggregation during treatment of patients with history of heart attack
Naloxegol	to treat opioid-induced constipation
Dapoxetine	To treat premature ejaculation
Domperidone	to treat nausea and vomiting

Do not combine darunavir with products containing St. John's wort (Hypericum perforatum).

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting darunavir.

Darunavir does not cure HIV infection.

Patients taking darunavir may develop other infections or diseases associated with HIV infection. You must maintain regular contact with your doctor.

Patients taking darunavir may develop a skin rash. It is uncommon for the rash to be severe or potentially life-threatening. Please consult your doctor if you develop a rash.

Patients taking darunavir and raltegravir (for HIV infection) may experience rashes (usually mild or moderate) more frequently than patients taking either medication separately.

Inform your doctor about your condition BEFORE and DURING treatment

Ensure you check the following points and inform your doctor if any apply to you.

• Inform your doctor if you have had any liver disease, including hepatitis B or C infection. Your doctor will assess the severity of liver disease before deciding whether you can take darunavir.
• Inform your doctor if you have diabetes. Darunavir may cause an increase in blood sugar levels.
• Inform your doctor immediately if you notice any signs of infection (e.g., swollen lymph nodes and fever). In some patients with advanced HIV infection and a history of opportunistic infections, signs and symptoms of inflammation due to previous infections may appear shortly after starting treatment. These symptoms are believed to result from an improved immune response, enabling the body to fight infections that were previously present without apparent symptoms.
• In addition to opportunistic infections, autoimmune disorders (a condition in which the immune system attacks healthy body tissue) may also occur after you have started taking medications for HIV infection. Autoimmune disorders may appear many months after starting treatment. If you notice any signs of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and moving upward toward the trunk, palpitations, tremors, or hyperactivity, inform your doctor immediately to receive appropriate treatment.
• Inform your doctor if you have haemophilia. Darunavir may increase the risk of bleeding.
• Inform your doctor if you are allergic to sulfonamides (e.g., used to treat certain infections).
• Inform your doctor if you notice any musculoskeletal problems. Some patients using combination antiretroviral therapy may develop a bone disorder called osteonecrosis (bone tissue death caused by reduced blood supply to the bone). Among the many risk factors for this condition are duration of combination antiretroviral therapy, corticosteroid use, alcohol consumption, severe immunosuppression, and higher body mass index. Signs of osteonecrosis include joint pain and stiffness (especially in the hips, knees, and shoulders) and difficulty moving. If you notice any of these symptoms, please consult your doctor.
• Inform your doctor if you have hepatitis B or C infection.

Advanced age

Darunavir has only been used in a limited number of patients aged 65 years or older. If you belong to this age group, please discuss with your doctor whether you can use darunavir.

Children

Darunavir is not used in children under 3 years of age or weighing less than 15 kilograms.

Other medicines and Darunavir Sandoz

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

Some medicines must not be combined with darunavir. This list can be found in the section “Do not combine Darunavir Sandoz with any of the following medicines:”

In most cases, darunavir can be combined with HIV medicines belonging to other classes [e.g., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists, and FIs (fusion inhibitors)]. Darunavir with ritonavir has not been tested with all protease inhibitors (PIs) and must not be used with other HIV protease inhibitors. In some cases, the dose of other medicines may need to be adjusted. Therefore, if you are taking other anti-HIV medicines, always inform your doctor and carefully follow their instructions regarding which medicines can be combined.

The effects of darunavir may be reduced if you take any of the following products.

Inform your doctor if you take:

• phenobarbital, phenytoin (to prevent seizures),
• dexamethasone (a corticosteroid),
• efavirenz (HIV infection),
• rifapentine, rifabutin (medicines to treat certain infections such as tuberculosis),
• saquinavir (for HIV infection).

Darunavir may also affect the effects of other medicines, and your doctor may want to perform additional tests. Inform your doctor if you take:

• amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (for heart disorders), as the therapeutic or adverse effects of these medicines may be increased,
• apixaban, dabigatran etexilate, edoxaban, rivaroxaban, warfarin, clopidogrel (to reduce blood clotting), as the therapeutic or adverse effects of these medicines may be altered;
• hormonal contraceptives based on oestrogens and hormone replacement therapies. Darunavir may reduce their effectiveness. For contraception, non-hormonal alternative contraceptive methods are recommended,
• ethinylestradiol/drospirenone. Darunavir may increase the risk of elevated potassium levels due to drospirenone,
• atorvastatin, pravastatin, rosuvastatin (to reduce blood cholesterol). There may be an increased risk of muscle damage. Your doctor will determine the most appropriate cholesterol-lowering treatment based on your individual circumstances,
• clarithromycin (antibiotic),
• cyclosporine, everolimus, tacrolimus, sirolimus (to suppress your immune system), as the therapeutic or adverse effects of these medicines may be increased,
• corticosteroids, including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel diseases, inflammatory skin, eye, joint, and muscle conditions, and other inflammatory disorders. These medicines are usually taken orally, inhaled, injected, or applied to the skin. If alternatives cannot be used, their use should only occur after clinical evaluation and with close monitoring by your doctor to assess corticosteroid adverse effects,
• buprenorphine/naloxone (medicines for opioid dependence treatment),
• salmeterol (medicine for asthma treatment),
• artemether/lumefantrine (a combination of medicines for treating malaria),
• dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (for treating cancer),
• sildenafil, tadalafil, vardenafil (for erectile dysfunction or for treating a heart and lung disorder called pulmonary arterial hypertension),
• glecaprevir/pibrentasvir (for treating hepatitis C infection),
• fentanyl, oxycodone, tramadol (for treating pain),
• fesoterodine, solifenacin (for treating urological disorders).

Your doctor may want to perform additional blood tests and, in certain cases, it may be necessary to adjust the dose of some medicines, as combining them may affect their therapeutic or adverse effects or those of darunavir.

Inform your doctor if you take:

• dabigatran etexilate, edoxaban, warfarin (to reduce blood clotting),
• alfentanil (injectable strong, short-acting analgesic used in surgical procedures),
• digoxin (for treatment of certain heart disorders),
• clarithromycin (antibiotic),
• itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (to treat fungal infections). Voriconazole may only be administered after medical evaluation,
• rifabutin (for bacterial infections),
• sildenafil, vardenafil, tadalafil (for erectile dysfunction or high blood pressure in the pulmonary circulation),
• amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (for treating depression and anxiety),
• maraviroc (for treating HIV infection),
• methadone (for treating narcotic dependence),
• carbamazepine, clonazepam (to prevent epileptic seizures or to treat certain types of neuropathic pain),
• colchicine (for treating gout or familial Mediterranean fever),
• bosentan (for treating high blood pressure in the pulmonary circulation),
• buspirone, chlordiazepoxide, diazepam, estazolam, flurazepam, midazolam administered by injection, zolpidem (sedatives),
• perphenazine, risperidone, thioridazine (for treating psychiatric conditions).

This is not a complete list of medicines. Inform your doctor about all medicines you are taking.

Taking Darunavir Sandoz with food and drink

See section 3 “How to take Darunavir Sandoz.”

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

Pregnant women should not take darunavir with ritonavir unless specifically instructed by their doctor.

Pregnant women should not take darunavir with cobicistat. Considering the potential adverse effects on the infant, women should not breastfeed while receiving darunavir.

Breastfeeding is not recommended for women living with HIV because HIV infection can be transmitted to the baby through breast milk. If you are breastfeeding or considering breastfeeding, you should consult your doctor as soon as possible.

Driving and using machines

Do not operate tools or machinery or drive if you experience dizziness after taking Darunavir Sandoz.

Darunavir Sandoz contains sunset yellow FCF (E-110)

It may cause allergic reactions.

3. How to take Darunavir Sandoz

Follow exactly the instructions for taking this medicine as described in this leaflet or as directed by your doctor, pharmacist, or nurse. If you are unsure, consult your doctor, pharmacist, or nurse again. Do not stop taking darunavir or ritonavir without first talking to your doctor, even if you feel better.

Once treatment has started, the dose or dosing regimen must not be changed or treatment interrupted without consulting your doctor.

Dose for children aged 3 years and older, weighing at least 15 kilograms, who have not previously taken antiretroviral medicines (your child's doctor will determine this)

Your doctor will calculate the correct daily dose based on the child's weight (see table below).

This dose must not exceed the recommended adult dose, which is 800 milligrams of darunavir together with 100 milligrams of ritonavir once daily.

Your doctor will inform you about the amount of darunavir tablets and the amount of ritonavir (capsules, tablets, or solution) the child should take.

Weight	A dose of Darunavir is	A dose of Ritonavir is
between 15 and 30 kilograms	600 milligrams	100 milligrams
between 30 and 40 kilograms	675 milligrams	100 milligrams
over 40 kilograms	800 milligrams	100 milligrams

Ritonavir oral solution: 80 milligrams per milliliter

Dosage for children aged 3 years and older, weighing at least 15 kilograms, who have previously taken antiretroviral medications (your child's doctor will determine this)

The doctor will determine the correct dose based on the child's weight (see table below). The doctor will decide whether a once-daily or twice-daily dosing regimen is appropriate for the child. This dose must not exceed the recommended adult dose, which is 600 milligrams of darunavir together with 100 milligrams of ritonavir twice daily, or 800 milligrams of darunavir together with 100 milligrams of ritonavir once daily.

Your doctor will inform you how many darunavir tablets and how much ritonavir (capsules, tablets, or solution) the child should take. Other tablet strengths are available, and your doctor may prescribe a specific combination of tablets to achieve the appropriate dosing schedule.

Twice-daily dosing regimen

Weight	Dose is
between 15 and 30 kilograms	375 milligrams of darunavir + 50 milligrams of ritonavir twice daily
between 30 and 40 kilograms	450 milligrams of darunavir + 60 milligrams of ritonavir twice daily
over 40 kilograms*	600 milligrams of darunavir + 100 milligrams of ritonavir twice daily

• Your child's doctor will determine whether children aged 12 years and older and weighing at least 40 kilograms can use the once-daily darunavir dose of 800 milligrams. This dose cannot be administered with the 600-milligram tablets. Other darunavir formulations are available.

Once-daily dosing

Weight	Darunavir dose is	Ritonavir dose is
between 15 and 30 kilograms	600 milligrams	100 milligrams
between 30 and 40 kilograms	675 milligrams	100 milligrams
more than 40 kilograms	800 milligrams	100 milligrams

Ritonavir oral solution: 80 milligrams per milliliter

Instructions for children

• The child must always take darunavir together with ritonavir. Darunavir cannot work properly without ritonavir.
• The child must take the correct dose of darunavir and ritonavir twice a day or once a day. If darunavir has been prescribed twice daily, the child should take one dose in the morning and another at night. Your child's doctor will determine the appropriate dosing schedule for your child.
• The child must take darunavir with food. Darunavir cannot work properly without food. The type of food does not matter.
• The child should swallow the tablets with a drink such as water or milk.

Dosage for adults who have not previously taken antiretroviral medicines (to be determined by your doctor)

You will require a different dose of darunavir that cannot be administered with these
tablets of 600 milligrams. Other concentrations of darunavir are available.

Dosage for adults who have previously taken antiretroviral medicines (to be determined by your doctor)

The dose is:

• 600 milligrams of darunavir (2 tablets containing 300 milligrams of darunavir or 1 tablet containing 600 milligrams of darunavir) together with 100 milligrams of ritonavir twice daily.

or

• 800 milligrams of darunavir (2 tablets containing 400 milligrams of darunavir or 1 tablet containing 800 milligrams of darunavir) together with 100 milligrams of ritonavir once daily. The 400-milligram and 800-milligram darunavir tablets are used only to achieve the 800-milligram once-daily dosing regimen.

Please consult your doctor to determine which dose is correct for you.

Instructions for adults

• Take darunavir always together with ritonavir. Darunavir does not work properly without ritonavir.
• In the morning, take one tablet of 600 milligrams of darunavir together with 100 milligrams of ritonavir.
• In the evening, take one tablet of 600 milligrams of darunavir together with 100 milligrams of ritonavir.
• Take darunavir with food. Darunavir does not work properly without food. The type of food is not important.
• Swallow the tablets with a drink, which can be water or milk.
• The 75-milligram and 150-milligram darunavir tablets have been developed for use in children, but in some cases they may also be used in adults.

Removing the child-resistant cap

The plastic bottle has a child-resistant safety closure and opens as follows:

Push the plastic cap down while turning it counterclockwise.

Remove the cap by unscrewing it.

If you take more Darunavir Sandoz than you should

If you have taken more darunavir than you should, contact your doctor, pharmacist, or call the Toxicology Information Service immediately at telephone number: 91 562 04 20, indicating the medication and amount taken.

If you forget to take Darunavir Sandoz

If you remember within 6 hours, take the tablets immediately. Always take them with
ritonavir and with food. If you remember after 6 hours, skip that dose and take the next one as usual. Do not take a double dose to make up for missed doses.

If you vomit after taking Darunavir Sandoz and ritonavir

If you vomit within 4 hours after taking the medicine, you should take another dose of darunavir and ritonavir with some food as soon as possible. If you vomit more than 4 hours after taking the medicine, you do not need to take another dose of darunavir and ritonavir until your next scheduled dose.

Contact your doctor if you have any doubts about what you should do if you miss a dose or vomit.

Do not stop taking Darunavir Sandoz without first talking to your doctor

HIV medicines may make you feel better. Even if you feel well, do not stop taking darunavir. Talk to your doctor first.

If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

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

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Tell your doctor if you develop any of the following adverse effects.

Cases of liver problems have been reported, which may occasionally be serious. Your doctor will perform a blood test before you start treatment with darunavir. If you have a chronic infection caused by hepatitis B or C, your doctor will frequently check your blood tests, as you have a higher risk of developing liver problems. Talk to your doctor about the signs and symptoms of liver problems. These may include yellowing of the skin and whites of the eyes, dark (tea-colored) urine, pale stools (bowel movements), nausea, vomiting, loss of appetite, or pain, tenderness, or discomfort on the right side under your ribs.

Skin rash (more common when used in combination with raltegravir), itching. Skin rash is usually mild to moderate. However, a skin rash may also be a symptom of a rare but serious condition. Therefore, it is important to speak with your doctor if you develop a rash. Your doctor will advise you on how to manage symptoms or whether darunavir should be discontinued.

Other serious adverse effects included diabetes (frequent) and inflammation of the pancreas (uncommon).

Very common adverse effects (may affect more than 1 in 10 patients):

• Diarrhea.

Common adverse effects (may affect up to 1 in 10 patients):

• Vomiting, nausea, abdominal pain or bloating, upper abdominal pain (dyspepsia), flatulence,
• Headache, fatigue, dizziness, drowsiness, tingling or numbness or pain in the hands or feet, loss of strength, difficulty falling asleep.

Uncommon adverse effects (may affect up to 1 in 100 patients):

• Chest pain, changes in electrocardiogram, rapid heartbeat,
• Decreased or abnormal skin sensitivity, tingling, attention disorder, memory loss, difficulty maintaining balance,
• Breathing difficulty, cough, nosebleed, throat irritation,
• Stomach or mouth inflammation, heartburn, retching, dry mouth, abdominal discomfort, constipation, belching,
• Kidney failure, kidney stones, difficulty urinating, excessive or frequent urination, sometimes at night,
• Urticaria, severe swelling of the skin and other tissues (especially lips or eyes), eczema, excessive sweating, night sweats, alopecia, acne, scaly skin, nail discoloration,
• Muscle pain, muscle cramps or weakness, limb pain, osteoporosis,
• Reduced thyroid gland function. This can be seen in a blood test,
• Hypertension (increased blood pressure), flushing,
• Red or dry eyes,
• Fever, swelling of the lower limbs due to fluid retention, malaise, irritability, pain,
• Symptoms of infection, herpes simplex,
• Erectile dysfunction, breast enlargement,
• Difficulty falling asleep, drowsiness, depression, anxiety, abnormal dreams, decreased sexual desire.

Rare adverse effects (may affect up to 1 in 1,000 patients):

• A reaction called DRESS [severe rash, which may be accompanied by fever, fatigue, facial swelling or swollen lymph nodes, increased eosinophils (a type of white blood cell), liver, kidney, or lung damage],
• Myocardial infarction, slow heart rate, palpitations,
• Visual disturbance,
• Chills, unusual sensation,
• A feeling of confusion or disorientation, altered mood, agitation,
• Fainting, epileptic seizure, changes or loss of taste,
• Mouth ulcers, vomiting blood, lip swelling, dry lips, coated tongue,
• Nasal discharge,
• Skin lesions, dry skin,
• Muscle or joint stiffness, joint pain with or without inflammation,
• Changes in certain blood cell or biochemical values. These changes can be seen in blood and/or urine tests. Your doctor will explain them to you. For example:

Increase in certain white blood cells,

• Darunavir crystals in the kidney causing kidney disease.

Some adverse effects are typical of HIV medicines belonging to the same class as darunavir. These include:

• Muscle pain, tenderness, or weakness. Rarely, these muscle disorders may be serious.

Reporting of adverse effects

If you experience any adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Darunavir Sandoz

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the carton, blister pack, and bottle after "CAD/EXP". The expiry date refers to the last day of the month indicated.

For blister packs: Do not store above 30 °C.

For bottles: This medicine does not require any special storage conditions.

Storage conditions after first opening the bottle:

Do not store above 25 °C.

Storage period after first opening the bottle: 6 months.

Medicines should not be disposed of via wastewater or household waste. Dispose of empty containers and unused medicines at the SIGRE point in your pharmacy. If you have any doubts, ask your pharmacist how to dispose of unused containers and medicines. This will help protect the environment.

6. Contents of the container and other information

Composition of Darunavir Sandoz

• The active substance is darunavir. Each tablet contains 600 mg of darunavir.
• The other components are:

microcrystalline cellulose (E 460), colloidal anhydrous silica (E 551), crospovidone (type A) (E 1202), magnesium stearate (E 470b), poly(vinyl alcohol) (E 1203), macrogol (3350) (E 1521), titanium dioxide (E 171), talc (E 553b), orange yellow S (E110).

Appearance of the product and contents of the container

Film-coated orange oval tablet, engraved with "600" on one side and smooth on the other.

Dimensions: approximately 20.1 mm x 10.1 mm

Film-coated tablets are available in perforated aluminum-PVC/PE/PVDC blisters, in single-dose perforated aluminum-PVC/PE/PVDC blisters, or in HDPE bottles with polypropylene (PP) closures, child-resistant cap.

Pack sizes:

Bottle: 60, 120 (2x60), 180 (3x60), 240 (4x60) film-coated tablets

Blister packs: 10, 30, 60, 90 and 120 film-coated tablets

Single-dose blister: 60x1 film-coated tablets

Only certain pack sizes may be commercially available.

Marketing Authorization Holder

Sandoz Farmacéutica, S.A.

Centro Empresarial Parque Norte

Edificio Roble

C/ Serrano Galvache, 56

28033 Madrid

Spain

Manufacturer responsible for manufacturing

Lek Pharmaceuticals d.d.

Verovskova, 57

1526 Ljubljana

Slovenia

or

Salutas Pharma GmbH

Otto-von-Guericke-Allee 1

39179 Barleben

Germany

or

Remedica Ltd

Aharnon Street, Limassol

Industrial Estate

3056 Limassol

Cyprus

Date of the most recent revision of this leaflet: May 2023

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