Darunavir sandoz

Package leaflet: Information for the patient

Darunavir Sandoz, 600 mg, film-coated tablets
Darunavir
Read this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet for future reference.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not give it to others. It may harm them, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet

1. What Darunavir Sandoz is and what it is used for
2. Important information 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 Darunavir Sandoz is
Darunavir Sandoz contains the active substance darunavir. Darunavir Sandoz is an antiretroviral medicine used in the treatment of human immunodeficiency virus (HIV) infection.
It belongs to a group of medicines called protease inhibitors. It works by reducing the amount of HIV in the body. This helps the immune system and reduces the risk of developing HIV-related illnesses.

What it is used for
Darunavir Sandoz is used to treat HIV-infected adults and children over 3 years of age weighing more than 15 kg, who have previously received other antiretroviral medicines.
Darunavir Sandoz must be taken together with a low dose of ritonavir and other anti-HIV medicines. Your doctor will determine the most appropriate combination of medicines for you.

2. Important information before using Darunavir Sandoz

When not to use Darunavir Sandoz
if the patient is allergic to darunavir, to any of the other ingredients of this medicine (listed in section 6) or to ritonavir.
If the patient has severe liver function disorders. If in doubt whether the patient's liver function disorders are severe, consult a doctor. Additional tests may be necessary.
Tell the doctor about all medicines being taken, including those taken orally, by inhalation, by injection or applied to the skin.
Do not use Darunavir Sandoz with any of the following medicines.
If the patient is already taking any of these medicines, consult a doctor about switching to an alternative treatment.

Concomitant use of Darunavir Sandoz with medicinal products containing St. John's wort (Hypericum perforatum) is not recommended.
Warnings and precautions
Before starting treatment with Darunavir Sandoz, discuss this with your doctor, pharmacist, or nurse.
Darunavir Sandoz does not cure HIV infection.
Patients taking Darunavir Sandoz remain at risk of developing infections or other HIV-related illnesses. Therefore, regular medical follow-up is essential.
Skin rash may occur in patients taking Darunavir Sandoz. Rarely, this rash may become severe or potentially life-threatening. If a rash develops, contact your doctor.
Rash (usually mild or moderate) may occur more frequently in patients taking Darunavir Sandoz together with raltegravir (in the treatment of HIV infection) than in patients taking either of these medicines alone.
Informing the doctor about health status BEFORE and DURING treatment
Please review the following information and inform your doctor if any of these conditions apply to you.

• Inform your doctor if you have previously had liver disease, including hepatitis B or C. Your doctor may assess the severity of the condition before deciding whether you can take Darunavir Sandoz.
• Inform your doctor if you have diabetes. Darunavir Sandoz may increase blood glucose levels.
• Immediately inform your doctor if you notice signs of infection (e.g., swollen lymph nodes and fever). In some patients with advanced HIV infection and a history of opportunistic infections, inflammatory symptoms may occur soon after starting antiretroviral therapy. These symptoms are believed to result from an enhanced immune response, enabling the body to fight previously asymptomatic infections.
• Besides opportunistic infections, autoimmune disorders (conditions in which the immune system attacks healthy body tissues) may also occur after starting treatment for HIV infection. Autoimmune disorders may appear several months after initiating treatment. If you experience symptoms of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and progressing toward the trunk, palpitations, tremors, or hyperexcitability, seek immediate medical attention.
• Inform your doctor if you have haemophilia. Darunavir Sandoz may increase the risk of bleeding.
• Inform your doctor if you are allergic to sulfonamides (e.g., used in the treatment of certain infections).
• Inform your doctor if you develop musculoskeletal disorders. In some patients receiving combination antiretroviral therapy, bone disease, known as osteonecrosis (a condition caused by inadequate blood supply to bone tissue), may develop. Risk factors for osteonecrosis include prolonged use of combination antiretroviral therapy, corticosteroid use, alcohol consumption, severe immunosuppression, high body mass index, and others. Symptoms of osteonecrosis include joint stiffness and pain (particularly in hips, knees, and shoulders) and difficulty moving. If any of these symptoms occur, inform your doctor.

Elderly patients
Darunavir Sandoz has been used in only a limited number of patients aged 65 years or older.
If you belong to this age group, consult your doctor to discuss the possibility of using this medicine.
Children
Darunavir Sandoz is not intended for use in children under 3 years of age or weighing less than 15 kg.
Darunavir Sandoz and other medicines
Inform your doctor or pharmacist about all medicines you are currently taking or have recently taken.
Certain medicines must not be combined with Darunavir Sandoz. These are listed in the section “Do not use Darunavir Sandoz with any of the following medicines”.
In most cases, Darunavir Sandoz can be used together with antiretroviral medicines belonging to other classes [i.e., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists, and FIs (fusion inhibitors)]. Concurrent use of darunavir with ritonavir has not been studied with all PIs (protease inhibitors), and it must not be used together with other HIV protease inhibitors. In some cases, dosage adjustments of other medicines may be necessary. Therefore, always inform your doctor about taking other antiretroviral medicines and strictly follow your doctor’s instructions regarding concomitant use of other medicines.
The effect of Darunavir Sandoz may be reduced if taken together with any of the following medicines.
Inform your doctor if you are taking:

• phenobarbital, phenytoin (anticonvulsants);
• dexamethasone (a corticosteroid);
• efavirenz (a medicine used in the treatment of HIV infection);
• rifapentine, rifabutin (medicines used in the treatment of certain infections, e.g., tuberculosis);
• saquinavir (a medicine used in the treatment of HIV infection).

Darunavir Sandoz may affect the action of other medicines, and your doctor may order additional blood tests.
Inform your doctor if you are taking:

• amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (medicines used in the treatment of heart conditions) due to the risk of increased therapeutic effects and adverse reactions;
• apixaban, edoxaban, dabigatran etexilate, rivaroxaban, warfarin, clopidogrel (anticoagulants), as there is a risk of altered therapeutic effects and adverse reactions;
• hormonal contraceptives containing estrogens and hormone replacement therapy. Darunavir Sandoz may reduce their effectiveness. To avoid pregnancy, use alternative non-hormonal contraceptive methods;
• ethinylestradiol with drospirenone, as Darunavir Sandoz may increase the risk of elevated potassium levels associated with drospirenone;
• atorvastatin, pravastatin, rosuvastatin (cholesterol-lowering medicines). There is an increased risk of muscle damage. Your doctor will determine which cholesterol-lowering medicine is appropriate for you in this situation;
• clarithromycin (an antibiotic);
• cyclosporine, everolimus, tacrolimus, sirolimus (immunosuppressants), due to the risk of increased therapeutic effects and adverse reactions;
• corticosteroids, including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel diseases, skin, eye, joint, and muscle inflammation, and other inflammatory conditions. They are usually taken orally, inhaled, injected, or applied to the skin. If no alternative medicines are available, their use is possible only after consultation with your doctor and under strict monitoring for corticosteroid-related adverse effects;
• buprenorphine/naloxone (medicines used in the treatment of opioid dependence);
• salmeterol (a medicine used in the treatment of asthma);
• artemether/lumefantrine (a combination medicine used in the treatment of malaria);
• dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (medicines used in cancer treatment);
• sildenafil, tadalafil, vardenafil (medicines used in the treatment of erectile dysfunction or pulmonary arterial hypertension);
• glecaprevir with pibrentasvir (medicines used in the treatment of hepatitis C);
• fentanyl, oxycodone, tramadol (analgesics);
• fesoterodine, solifenacin (medicines used in the treatment of urinary disorders).

Concomitant administration of other medicines with Darunavir Sandoz may affect their therapeutic effects and adverse reactions. Therefore, your doctor may order additional blood tests and dosage adjustments may be necessary. Inform your doctor if you are taking:

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

This is not a complete list of medicines. Inform your doctor about all medicines you are taking.
Darunavir Sandoz with food and drink
See section 3 “How to take Darunavir Sandoz”.
Pregnancy and breastfeeding
If you are pregnant or planning to become pregnant, inform your doctor immediately.
Pregnant women should not take Darunavir Sandoz with ritonavir without specific medical advice. Pregnant women should not take Darunavir Sandoz with cobicistat.
Due to the risk of adverse effects in breastfed infants, women should not breastfeed while taking Darunavir Sandoz.
Breastfeeding is not recommended for women infected with HIV, as HIV can be transmitted to the infant through breast milk. If you are breastfeeding or considering breastfeeding, consult your doctor as soon as possible.
Driving and using machines
If you experience dizziness after taking Darunavir Sandoz, do not drive or operate machinery.
Darunavir Sandoz contains Sunset Yellow FCF (E 110), which may cause allergic reactions.

3. How to take Darunavir Sandoz

This medicine should always be taken exactly as described in this leaflet or as directed by your doctor,
pharmacist, or nurse. If in doubt, consult your doctor, pharmacist, or nurse.
Even if the patient feels better, do not stop taking Darunavir Sandoz or ritonavir without consulting
your doctor.
After starting treatment, do not change the dose or formulation of the medicine, or stop treatment,
without your doctor's instruction.
Dose for children aged 3 years and older, weighing at least 15 kilograms, who have not previously
received antiretroviral therapy (to be determined by the treating physician)
Your doctor will determine the appropriate once-daily dose based on the child's body weight (see table
below). This dose must not exceed the recommended adult dose, which is 800 milligrams of Darunavir
Sandoz and 100 milligrams of ritonavir once daily.
Your doctor will tell you how many darunavir tablets and how much ritonavir (capsules, tablets, or
oral solution) the child must take.

ritonavir oral solution at a strength of 80 milligrams per millilitre
Dose for children aged 3 years and older, weighing at least 15 kg, who have previously received
antiretroviral medicines (this will be determined by the treating physician)
The physician will determine the appropriate dose of the medicine based on the child's body weight (see table below)
and will assess whether once-daily or twice-daily dosing is suitable for the child. This dose must not exceed
the recommended dose for adult patients, which is 600 milligrams of Darunavir Sandoz and 100 milligrams of ritonavir twice daily,
or 800 milligrams of Darunavir Sandoz and 100 milligrams of ritonavir once daily.
The physician will advise how many tablets of Darunavir Sandoz and how much ritonavir (capsules, tablets or oral solution)
the child should take. Other-strength darunavir tablets are also available, so the physician may prescribe
a combination of tablets to achieve the required dose for the child.
Twice-daily dosing

* The treating physician will determine whether Darunavir Sandoz can be administered to children aged at least 12 years and weighing at least 40 kg at a dose of 800 milligrams once daily. This dose cannot be given using 600-milligram tablets.
Once-daily dosing

ritonavir in an oral solution at a strength of 80 milligrams per millilitre
Instructions for use in children

• The child must always take the medicine Darunavir Sandoz together with ritonavir. Without ritonavir, Darunavir Sandoz does not work properly.
• The child must take the appropriate doses of Darunavir Sandoz and ritonavir twice daily or once daily. If your doctor has prescribed Darunavir Sandoz twice daily, the child must take one dose in the morning and another in the evening. Your doctor will determine the appropriate dosing schedule for the child.
• Darunavir Sandoz should be given to the child during a meal. Darunavir Sandoz taken without food does not work properly. The type of food is not important.
• The child should swallow the tablets with a drink, e.g. water or milk.

Dose for adults who have not previously taken antiretroviral medicines
(to be determined by the attending physician)
The recommended dose cannot be administered using Darunavir Sandoz tablets of
600 milligrams. Darunavir is also available in another strength.
Dose for adults who have previously taken antiretroviral medicines (to be determined by the
attending physician)
The dose is:

• 600 milligrams of Darunavir Sandoz (1 tablet containing 600 milligrams of darunavir) together with 100 milligrams of ritonavir twice daily. OR
• 800 milligrams of Darunavir Sandoz (1 tablet containing 800 milligrams of darunavir) together with 100 milligrams of ritonavir once daily. To use the 800 milligram once-daily regimen, only 800 milligram tablets should be used.

Discuss with your doctor which dose is appropriate for the patient.
Recommendations for adults

• Darunavir Sandoz must always be taken together with ritonavir. Without ritonavir, Darunavir Sandoz does not work properly.
• In the morning, take 600 milligrams of Darunavir Sandoz together with 100 milligrams of ritonavir.
• In the evening, take 600 milligrams of Darunavir Sandoz together with 100 milligrams of ritonavir.
• Darunavir Sandoz should be taken with food. Darunavir Sandoz taken without food does not work properly. The type of food is not important.
• Swallow the tablets with a drink, e.g. water or milk.
• Darunavir 75 milligrams and 150 milligrams is intended for use in children, but in certain cases may also be used in adults.

Removing the child-resistant cap
The plastic bottle is closed with a child-resistant cap. It is opened as follows:

1. Press down on the plastic cap with your hand while turning it counter-clockwise;

2. Remove the unscrewed cap.

Taking more than the recommended dose of Darunavir Sandoz
Contact your doctor, pharmacist, or nurse immediately.
Missing a dose of Darunavir Sandoz
If the patient realizes within 6 hours that a dose has been missed, they should take the forgotten tablets immediately. Each dose must be taken with ritonavir and food. If more than 6 hours have passed since the missed dose, skip the missed dose and take the next dose at the usual time. Do not take a double dose to make up for a missed dose.
Vomiting after taking Darunavir Sandoz and ritonavir
If vomiting occurs within 4 hours after taking the medicine, take another dose of Darunavir Sandoz and ritonavir as soon as possible, together with food. If vomiting occurs more than 4 hours after taking the medicine, take the next dose of Darunavir Sandoz and ritonavir at the usual time.
If in doubt about what to do when a dose is missed or vomiting occurs, contact your doctor.
Do not stop taking Darunavir Sandoz without consulting your doctor.
HIV medicines may make you feel better, but even if you feel well, you should not stop taking the medicine without discussing it with your doctor.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

During treatment for HIV infection, patients may experience increased body weight and increased levels of lipids and glucose in the blood. This is partly related to improved health and lifestyle, and in the case of lipids, sometimes to the use of antiretroviral drugs themselves. Your doctor will monitor these changes.

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If the patient experiences any of the side effects listed below, inform the doctor immediately.

Liver function disorders have been reported, occasionally with severe outcomes. Before starting treatment with Darunavir Sandoz, the doctor will perform blood tests. In patients with chronic hepatitis B or C, the doctor should perform blood tests more frequently due to an increased risk of liver complications. Discuss with your doctor symptoms of liver problems, which may include: yellowing of the skin or eyes, dark-coloured urine (like tea), pale stools, nausea, vomiting, loss of appetite, or pain or discomfort under the ribs on the right side.

Skin rash (more common when used concomitantly with raltegravir), itching. Skin rash is usually mild or moderate but may also be a sign of a rare, serious condition. It is important to report any rash to the doctor. The doctor will recommend appropriate management or decide whether to discontinue Darunavir Sandoz.

Other serious side effects include: diabetes (frequent) and pancreatitis (uncommon).

Very common side effects (may affect more than 1 in 10 people):

• diarrhoea

Common side effects (may affect up to 1 in 10 people):

• vomiting, nausea, abdominal pain or bloating, indigestion, flatulence
• headache, fatigue, dizziness, somnolence, numbness, tingling or pain in hands or feet, weakness, difficulty sleeping

Uncommon side effects (may affect up to 1 in 100 people):

• chest pain, changes in electrocardiogram (ECG), rapid heartbeat
• reduced or altered skin sensitivity, tingling, attention disorders, memory loss, balance disorders
• difficulty breathing, cough, nosebleeds, sore throat
• inflammation of the stomach or oral mucosa, heartburn, retching (without vomiting), dry mouth, abdominal discomfort, constipation, belching
• kidney failure, kidney stones, difficulty urinating, frequent or excessive urination, sometimes at night
• urticaria, severe swelling of the skin and other tissues (most commonly lips or eyes), rash, excessive sweating, night sweats, hair loss, acne, skin peeling, pigment deposition in nails
• muscle pain, muscle cramps or weakness, limb pain, osteoporosis
• reduced thyroid function, as indicated by blood test results
• high blood pressure, sudden facial flushing
• eye redness or dryness
• fever, leg swelling due to fluid retention, malaise, irritability, pain
• signs of infection, herpes
• erectile dysfunction, breast enlargement in men
• sleep disorders, drowsiness, depression, anxiety, unusual dreams, decreased libido

Rare side effects (may affect up to 1 in 1000 people):

• DRESS syndrome [severe rash accompanied by fever, fatigue, facial swelling or swollen lymph nodes, increased eosinophil count (a type of white blood cell), signs of liver, kidney or lung involvement]
• heart attack, slow heartbeat, palpitations
• visual disturbances
• chills, unusual sensations
• feeling lost or disoriented, mood changes, restlessness (mainly motor)
• fainting, seizures, changes or loss of taste
• oral ulceration, bloody vomiting, inflammation of the lips, dry lips, coated tongue
• catarrh
• skin disorders, dry skin
• muscle or joint stiffness, inflammatory or non-inflammatory joint pain
• changes in the count of certain blood cells or biochemical test results. These changes may be detected in blood and/or urine tests. Your doctor will provide detailed explanations. Examples include increased levels of certain white blood cells
• darunavir crystals in the kidneys causing kidney disease

Some side effects are typical of antiretroviral medicines belonging to the same class as Darunavir Sandoz. These include:

• muscle pain, tenderness or weakness. Rarely, such disorders have been severe.

Reporting of side effects
If any side effects occur, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. Side effects can also be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw
tel.: +48 22 49 21 301 / fax: +48 22 49 21 309 / website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the responsible entity.

Reporting side effects helps provide more information on the safety of this medicine.

5. How to store 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 outer carton,
blister pack, and bottle after EXP. The expiry date refers to the last day of the stated month.
The batch number on the packaging is marked as "Lot".
No special storage conditions are required for this medicine.
Storage conditions after first opening of the bottle:
Do not store above 25°C.
Expiry date after first opening of the bottle: 6 months
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures will help protect the environment.

6. Contents of the pack and other information

What Darunavir Sandoz contains
The active substance is darunavir. Each coated tablet contains 600 mg of darunavir.
The other ingredients are: microcrystalline cellulose (type 102), crospovidone (type A),
anhydrous colloidal silica, magnesium stearate.
Film-coating of the tablet Opadry II Orange 85F530078 composition: polyvinyl alcohol,
macrogol 3350, titanium dioxide (E 171), talc, sunset yellow (E 110).
What Darunavir Sandoz looks like and contents of the pack
Orange, oval, film-coated tablets with the inscription '600' debossed on one side and smooth on the other side.
Dimensions: approximately 20.1 mm x 10.1 mm.
The tablets are packed in HDPE bottles with a child-resistant PP closure, placed in a cardboard box.
Pack size:
60 film-coated tablets
Marketing Authorisation Holder
Sandoz GmbH
Biochemiestrasse 10
6250 Kundl, Austria
Manufacturer
Lek Pharmaceuticals d.d.
Verovškova 57
1526 Ljubljana, Slovenia
Salutas Pharma GmbH
Otto-von-Guericke-Allee 1
39179 Barleben, Germany
Remedica Ltd
Aharnon Street, Limassol Industrial Estate
3056 Limassol, Cyprus
For more detailed information about the medicine and its names in the countries of the European Economic Area, please contact:
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warsaw
tel. 22 209 70 00