Darunavir sandoz

Package leaflet: Information for the patient

Darunavir Sandoz, 800 mg, film-coated tablets
Darunavirum
Please read all of this leaflet carefully before 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 or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet contents

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 adults and children (aged 3 years and older, weighing at least 40 kg):

• who have HIV infection and have not previously received antiretroviral treatment;
• in certain patients who have previously received antiretroviral treatment (your doctor will decide).

Darunavir Sandoz must be taken together with a low dose of cobicistat or ritonavir, and with other medicines for HIV infection. Your doctor will discuss the most appropriate combination of medicines with 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 cobicistat or ritonavir.
If the patient has severe liver function impairment. If there is any doubt whether the patient's liver function impairment is severe, a doctor should be consulted. 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 medicines listed below.
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.
Individuals taking Darunavir Sandoz may still develop infections or other illnesses associated with HIV infection. Therefore, it is important to maintain regular contact with your doctor.
Skin rash may occur in individuals 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 the following applies to you.

• Inform your doctor if you have previously had liver disease, including viral 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 sugar levels.
• Inform your doctor immediately 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 initiating antiretroviral therapy. These symptoms are believed to result from an improved immune response, enabling the body to fight infections that were previously asymptomatic.
• In addition to opportunistic infections, autoimmune diseases (conditions in which the immune system attacks healthy body tissues) may also occur after starting antiretroviral therapy. Autoimmune disorders may develop several months after starting treatment. If 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 hyperactivity occur, 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 experience 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 developing osteonecrosis include prolonged use of combination antiretroviral therapy, corticosteroid use, alcohol consumption, significant immunosuppression, increased body mass index, and others. Symptoms of osteonecrosis include joint stiffness and pain (particularly in hips, knees, and shoulders) and difficulty in moving. If any of these symptoms occur, inform your doctor.

Elderly patients
Darunavir Sandoz has been used in only a small number of patients aged 65 years or older.
If you belong to this age group, you should consult your doctor to discuss the possibility of taking this medicine.
Children and adolescents
Darunavir Sandoz 800 mg tablets are not intended for use in children under 3 years of age or weighing less than 40 kg.
Darunavir Sandoz and other medicines
Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken.
Some medicines must not be combined with Darunavir Sandoz. These are listed in the section titled “Do not take Darunavir Sandoz with any of the following medicines”.
In most cases, Darunavir Sandoz can be used together with anti-HIV medicines from other classes [i.e. NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists, and FIs (fusion inhibitors)]. Concomitant use of darunavir and cobicistat or ritonavir with all PIs (protease inhibitors) has not been studied and 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 anti-HIV medicines and strictly follow your doctor’s instructions regarding concomitant use of other medicines.
The effect of Darunavir Sandoz may be reduced if you take any of the following medicines concomitantly.
Tell your doctor if you are taking any of the following medicines:

• 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 recommend additional blood tests.
Tell your doctor if you are taking any of the following medicines:

• 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, rivaroxaban, warfarin, clopidogrel (anticoagulants), as there is a risk of altered therapeutic effect 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 (immunosuppressive medicines), due to the possibility of increased therapeutic effects and adverse reactions;
• Corticosteroids, including betamethasone, budesonide, fluticasone, mometasone, prednisone, and triamcinolone. These medicines are used in the treatment of allergies, asthma, inflammatory bowel diseases, skin, eye, joint, and muscle inflammation, and other inflammatory conditions. These medicines are usually taken orally, inhaled, injected, or applied to the skin. If alternative medicines are not available, their use is possible only after consultation with a 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 heart and lung disorders, known as 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 tract disorders).

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

• Edoxaban dabigatran, 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 a 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 in the treatment of 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);
• Metformin (a medicine used in the treatment of type 2 diabetes).

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 potential 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, you should not operate machinery or drive a vehicle.

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 you feel better, do not stop taking Darunavir Sandoz, cobicistat, 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 advice.
The 800 mg tablets are intended for once-daily administration only.

Dose for adults who have not previously taken antiretroviral medicines
(this will be determined by your doctor)
The usual dose of Darunavir Sandoz is 800 milligrams (1 tablet containing 800 milligrams of darunavir) once daily. Darunavir Sandoz should be taken every day with food and always in combination with 150 milligrams of cobicistat or 100 milligrams of ritonavir. Darunavir Sandoz does not work properly without cobicistat or ritonavir and without food. A meal or snack should be consumed within 30 minutes before taking Darunavir Sandoz and cobicistat or ritonavir. The type of food does not matter. Do not stop taking Darunavir Sandoz with cobicistat or ritonavir without consulting your doctor, even if you feel better.

Instructions for adults

• Take one 800-milligram tablet once daily.
• Always take Darunavir Sandoz together with 150 milligrams of cobicistat or 100 milligrams of ritonavir.
• Take Darunavir Sandoz with food.
• Swallow the tablets with liquid, such as water or milk.
• Take other anti-HIV medicines in combination with Darunavir Sandoz and cobicistat or ritonavir, as directed by your doctor.

Dose for adults who have previously taken antiretroviral medicines
(this will be determined by your doctor)
The dose is:

• 800 milligrams of Darunavir Sandoz (1 tablet containing 800 milligrams of darunavir) together with 150 milligrams of cobicistat or 100 milligrams of ritonavir once daily, OR
• 600 milligrams of Darunavir Sandoz (1 tablet containing 600 milligrams of darunavir) together with 100 milligrams of ritonavir twice daily.

Discuss with your doctor which dose is appropriate for you.

Dose with ritonavir for children aged 3 years and older and with cobicistat for children aged 12 years and older, weighing at least 40 kilograms, who have not previously received antiretroviral medicines
(this will be determined by your doctor)
The usual dose of Darunavir Sandoz is 800 milligrams (1 tablet containing 800 milligrams of darunavir) together with 100 milligrams of ritonavir or 150 milligrams of cobicistat once daily.

Dose with ritonavir for children aged 3 years and older and with cobicistat for children aged 12 years and older, weighing at least 40 kilograms, who have previously received antiretroviral medicines
(this will be determined by your doctor)
The dose is:

• 800 milligrams of Darunavir Sandoz (1 tablet containing 800 milligrams of darunavir) together with 100 milligrams of ritonavir or 150 milligrams of cobicistat once daily, OR
• 600 milligrams of Darunavir Sandoz (1 tablet containing 600 milligrams of darunavir) together with 100 milligrams of ritonavir twice daily.

Discuss with your doctor which dose is appropriate for you.

Instructions for use with ritonavir in children aged 3 years and older, and with cobicistat in children aged 12 years and older, weighing at least 40 kilograms

• The child should receive Darunavir Sandoz 800 milligrams (1 tablet containing 800 milligrams of darunavir) once daily, at the same time each day.
• Darunavir Sandoz must always be taken together with 100 milligrams of ritonavir or 150 milligrams of cobicistat.
• Darunavir Sandoz should be taken with food.
• Swallow the tablets with liquid, such as water or milk.
• Take other anti-HIV medicines in combination with Darunavir Sandoz and ritonavir or cobicistat, as directed by your doctor.

How to open the child-resistant cap
The plastic bottle is closed with a child-resistant cap. Open it as follows:

1. Press down on the plastic cap with your hand while turning it anticlockwise;

2. Remove the unscrewed cap.

Taking more Darunavir Sandoz than prescribed
Contact your doctor, pharmacist, or nurse immediately.

If you forget to take Darunavir Sandoz
If you realize within 12 hours that you missed a dose, take the missed tablets as soon as possible. Take the dose with cobicistat or ritonavir and with food. If more than 12 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 of 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 you are unsure about what to do in case of a missed dose or vomiting, contact your doctor.

Do not stop taking Darunavir Sandoz without consulting your doctor.
Anti-HIV medicines may improve how you feel, but even if you feel better, 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 adverse reactions

During HIV treatment, patients may experience an increase in body weight as well as increased blood levels of lipids and glucose. This is partly related to improved health and lifestyle, and in the case of lipids, sometimes to the use of anti-HIV drugs themselves. The doctor will order tests to monitor these changes.

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them. If the patient experiences any of the adverse reactions listed below, the doctor should be informed.

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 virus infection, the doctor should order blood tests more frequently due to an increased risk of liver complications. Symptoms of liver dysfunction should be discussed with the doctor. These may include: yellowing of the skin or eyes, dark-coloured urine (tea-coloured), pale stools, nausea, vomiting, loss of appetite, or pain or discomfort under the ribs on the right side.

Skin rash (more frequent when used concomitantly with raltegravir), itching. Skin rash is usually mild or moderate but may also be a symptom 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 treatment with Darunavir Sandoz.

Other serious adverse reactions included: diabetes (frequent) and pancreatitis (uncommon).

Very common adverse reactions (may affect more than 1 in 10 people):

• diarrhoea

Common adverse reactions (may affect less than 1 in 10 people):

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

Uncommon adverse reactions (may affect less than 1 in 100 people):

• chest pain, changes in electrocardiogram (ECG), rapid heartbeat
• reduced or altered skin sensation, 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 muscle weakness, limb pain, osteoporosis
• reduced thyroid function, detected based on blood test results
• high blood pressure, sudden flushing of the face
• eye redness or dryness
• fever, leg swelling due to fluid retention, malaise, irritability, pain
• infection symptoms, herpes
• erectile dysfunction, gynaecomastia in men
• sleep disorders, somnolence, depression, anxiety, unusual dreams, decreased libido

Rare adverse reactions (may affect less than 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), liver, kidney or lung involvement]
• myocardial infarction, slow heart rate, palpitations
• visual disturbances
• chills, unusual feelings
• feeling confused or disoriented, mood changes, restlessness (mainly motor)
• fainting, seizures, changes or loss of taste
• oral ulceration, vomiting blood, inflammation of the lips, dry lips, coated tongue
• catarrh
• skin disorders, dry skin
• muscle or joint stiffness, joint pain with or without inflammation
• changes in the number of certain blood cells or biochemical test results. These changes can be detected in blood and/or urine tests. The doctor will provide detailed explanations. Examples include increased numbers of a certain type of white blood cell
• darunavir crystals in the kidneys causing kidney disease

Some adverse reactions are typical for anti-HIV medicines belonging to the same class as Darunavir Sandoz. These include:

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

Reporting of adverse reactions
If any adverse symptoms occur, including any not listed in this leaflet, the doctor, pharmacist or nurse should be informed. Adverse reactions can 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
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Darunavir Sandoz

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the outer carton,
blister, and bottle following 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 requirements for storage of the medicine.
Storage conditions after first opening of the bottle:
Do not store above 25°C.
Shelf life after first opening of the bottle: 6 months.
Medicines should 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 800 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 Brown 85F565101 with the following composition: polyvinyl alcohol, polyethylene glycol 3350, titanium dioxide (E 171), talc, and iron oxide red (E 172).
What Darunavir Sandoz looks like and contents of the pack
Dark red, oval film-coated tablets with the inscription '800' embossed on one side and smooth on the other side. Dimensions: approximately 20.2 mm x 10.1 mm.
The tablets are packed in HDPE bottles with a PP child-resistant closure, placed in a cardboard box.
Pack size:
30 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 further information about the medicinal product and its names in the Member States of the European Economic Area, please contact:
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warsaw, Poland
Tel. 22 209 70 00