Darunavir aurovitas

Package leaflet: Information for the user

Darunavir Aurovitas, 600 mg, film-coated tablets
Darunavirum
Read the entire leaflet carefully before using this medicine, as it contains
important information for the patient.

• Keep this leaflet for possible future reference.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on 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, pharmacist, or nurse. See section 4.

Leaflet contents:

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

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

What Darunavir Aurovitas is
Darunavir Aurovitas contains the active substance darunavir. Darunavir Aurovitas is an antiretroviral medicine used in the treatment of human immunodeficiency virus (HIV) infection. It belongs to a class of medicines called protease inhibitors. Darunavir Aurovitas 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 Aurovitas is used to treat HIV-infected adults and children (aged 3 years and older with a body weight of at least 15 kg) who have previously been treated with other antiretroviral medicines.
Darunavir Aurovitas must be taken in combination with a low dose of ritonavir and other antiviral medicines for HIV. Your doctor will determine the most appropriate combination of medicines for you.

2. Important information before using Darunavir Aurovitas

When not to use Darunavir Aurovitas

• if the patient is allergic to darunavir, or to any of the other ingredients of this medicine (listed in section 6), or to ritonavir;
• if the patient has severe liver function disorders. In case of doubt regarding liver disorders and their nature, 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 Aurovitas with the following medicines.
If any of the medicines listed below are being taken, consult a doctor about changing the treatment regimen.

Do not use preparations containing St John's wort (Hypericum perforatum) during treatment with Darunavir Aurovitas.
Warnings and precautions
Before starting treatment with Darunavir Aurovitas, discuss this with your doctor, pharmacist, or nurse.
Darunavir Aurovitas is not a medicine for HIV infection.
Patients taking Darunavir Aurovitas remain at risk of developing infections or other diseases associated with HIV infection, so regular contact with a doctor should be maintained.
Skin rash may occur in patients taking Darunavir Aurovitas. Rarely, it may become severe or potentially life-threatening. If a rash occurs, contact your doctor.
Rash (usually mild or moderately severe) may occur more frequently in patients taking Darunavir Aurovitas and raltegravir (for the treatment of HIV infection) than in patients taking either medicine alone.
When to inform the doctor about health status BEFORE and DURING treatment
After reviewing the points below, the patient should inform the doctor if any of them apply.

• Inform your doctor if you have previously had liver disease, including hepatitis B or C. The doctor will assess the severity of the disease before deciding whether Darunavir Aurovitas can be taken.
• Inform your doctor if you have diabetes. Darunavir Aurovitas may increase blood sugar levels.
• Inform your doctor immediately if you notice symptoms of infection (e.g. swollen lymph nodes, fever). In some patients with advanced HIV infection and a history of opportunistic infections, subjective and objective inflammatory symptoms related to previous infections may appear shortly after starting antiretroviral therapy. These symptoms are believed to be due to a strengthened immune response, enabling the body to fight previously asymptomatic infections.
• In addition to opportunistic infections, autoimmune diseases (diseases occurring when the immune system attacks healthy body tissues) may also occur after starting antiretroviral therapy for HIV infection. Autoimmune diseases 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 towards the trunk, palpitations, tremor, or hyperexcitability occur, contact your doctor as soon as possible to initiate necessary treatment.
• Inform your doctor if you have haemophilia. Darunavir Aurovitas may increase the risk of bleeding.
• Inform your doctor about sulfonamide allergy (e.g. used in the treatment of certain infections).
• Inform your doctor about musculoskeletal disorders. In some patients receiving combination antiretroviral therapy, bone disease called osteonecrosis (bone death caused by impaired blood supply to bone tissue) may develop. Risk factors for developing this disease include: duration of combination antiretroviral therapy, corticosteroid use, alcohol consumption, profound immunosuppression, increased body mass index, and others. Symptoms of osteonecrosis include: joint pain and stiffness (especially in hips, knees, or shoulders) and difficulty moving. Inform your doctor if any of these symptoms occur.

Elderly patients
Darunavir Aurovitas has been used in only a small number of patients aged 65 years or older. If you belong to this age group, consult your doctor whether you can take Darunavir Aurovitas.
Children and adolescents
Do not use Darunavir Aurovitas in children under 3 years of age or weighing less than 15 kg.
Darunavir Aurovitas and other medicines
Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
Some medicines must not be used with Darunavir Aurovitas. A list of these substances is provided in the section titled “Do not use Darunavir Aurovitas with the following medicines”.
In most cases, Darunavir Aurovitas can be used 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)]. Studies have not been conducted on the concomitant use of Darunavir Aurovitas and ritonavir with all PIs (protease inhibitors), and it must not be used in combination with other protease inhibitors. In some cases, dosage adjustment of other medicines may be necessary. Therefore, always inform your doctor about taking other HIV medicines and strictly follow the doctor’s instructions regarding concomitant use of other medicines.
The effectiveness of Darunavir Aurovitas may be reduced when taken together with any of the following products. Inform your doctor if you are taking:

• phenobarbital, phenytoin (anticonvulsants);
• dexamethasone (corticosteroid);
• efavirenz (used in the treatment of HIV infection);
• rifapentine, rifabutin (medicines used to treat certain infections, such as tuberculosis);
• saquinavir (used in the treatment of HIV infection).

Taking Darunavir Aurovitas may affect the effectiveness 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 to treat heart conditions) due to the possibility of increased therapeutic effect and adverse reactions of these medicines;
• apixaban, edoxaban, dabigatran etexilate, rivaroxaban, warfarin, clopidogrel (anticoagulants), due to the possibility of increased therapeutic effect and adverse reactions of these medicines;
• hormonal contraceptives and hormone replacement therapy containing oestrogens; Darunavir Aurovitas may reduce their effectiveness; when used to prevent pregnancy, non-hormonal contraceptive methods are recommended;
• ethinylestradiol/drospirenone. Darunavir Aurovitas may increase the risk of elevated potassium levels caused by drospirenone;
• atorvastatin, pravastatin, rosuvastatin (cholesterol-lowering medicines); there is an increased risk of muscle damage – your doctor will assess which cholesterol-lowering medicine is appropriate in your case;
• clarithromycin (antibiotic);
• cyclosporine, everolimus, tacrolimus, sirolimus (medicines that suppress the immune system) due to the possibility of increased therapeutic effect and adverse reactions of these medicines – your doctor may recommend additional tests;
• corticosteroids, including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These are medicines used to treat allergies, asthma, inflammatory bowel disease, inflammatory skin, eye, joint, and muscle conditions, and other inflammatory conditions. These medicines are usually taken orally, inhaled, injected, or applied to the skin. If alternative treatment cannot be used, these medicines may only be used after consultation with your doctor and under strict monitoring for corticosteroid adverse effects by the doctor;
• buprenorphine/naloxone (medicines used in opioid addiction treatment);
• salmeterol (a medicine used to treat asthma);
• artemether/lumefantrine (a combination medicine used to treat malaria);
• dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (medicines used to treat cancer);
• sildenafil, tadalafil, vardenafil (for erectile dysfunction or in the treatment of heart and lung disorders, so-called pulmonary arterial hypertension);
• glecaprevir/pibrentasvir (a medicine used to treat hepatitis C virus infection);
• fentanyl, oxycodone, tramadol (for pain treatment);
• fesoterodine, solifenacin (for urological disorders).

Concomitant administration of other medicines with Darunavir Aurovitas may affect their therapeutic effect and adverse reactions. Therefore, your doctor may order additional blood tests, and dosage adjustment of other medicines may be required.
Inform your doctor if you are taking:

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

This is not a complete list of medicines. Inform your doctor about all medicines you are taking.
Darunavir Aurovitas with food and drink
See section 3 “How to take Darunavir Aurovitas”.
Pregnancy and breastfeeding
Inform your doctor immediately about pregnancy or plans for pregnancy. Pregnant women should not take Darunavir Aurovitas with ritonavir without specific medical advice.
Pregnant women should not take Darunavir Aurovitas with cobicistat.
Due to the risk of adverse effects in breastfed infants, women should not breastfeed while taking Darunavir Aurovitas.
Breastfeeding is not recommended for women infected with HIV, as HIV can be transmitted to the child through breast milk. If you are breastfeeding or considering breastfeeding, consult your doctor as soon as possible.
Driving and operating machinery
Do not drive or operate machinery if taking Darunavir Aurovitas causes dizziness.
Darunavir Aurovitas contains propylene glycol
This medicine contains 83.34 mg of propylene glycol in each coated tablet. Consult your doctor or pharmacist before administering this medicine to a child under 4 weeks of age, especially if the child is taking other medicines containing propylene glycol or alcohol.

3. How to take Darunavir Aurovitas

This medicine should always be taken exactly as instructed by your doctor or pharmacist. If you have any doubts,
you should consult your doctor or pharmacist. Your doctor will inform you how much Darunavir Aurovitas
you should take.
Do not stop taking Darunavir Aurovitas with ritonavir without consulting your doctor, even if you feel noticeably better.
After starting treatment, do not change the dose, formulation, or interrupt treatment without first consulting
your doctor.

Dose for adults who have not previously taken antiretroviral medicines (to be determined by the doctor)
The patient may require a different dose of Darunavir Aurovitas that cannot be administered using these
tablets containing 600 mg of the medicine. Another strength of Darunavir Aurovitas is available.

Dose for adults who have previously taken antiretroviral medicines (to be determined by the doctor)
The dose is:

• 600 mg of Darunavir Aurovitas together with 100 mg of ritonavir twice daily. OR
• 800 mg of Darunavir Aurovitas (1 tablet containing 800 mg of Darunavir Aurovitas) together with 100 mg of ritonavir once daily. The 800 mg Darunavir Aurovitas medicine should only be used to establish a once-daily dosing regimen.

Please discuss with your doctor which dose is appropriate for you.

Instructions for adults

• Always take Darunavir Aurovitas together with ritonavir. Darunavir Aurovitas does not work properly without ritonavir.
• Take 600 mg of Darunavir Aurovitas in the morning together with 100 mg of ritonavir.
• Take 600 mg of Darunavir Aurovitas in the evening together with 100 mg of ritonavir.
• Take Darunavir Aurovitas with food. Darunavir Aurovitas does not work properly when taken without food. The type of food is not important.
• Swallow the tablets with water or milk.

Dose for children aged 3 years and older, weighing at least 15 kilograms, who have not previously taken antiretroviral medicines (to be determined by the child's doctor)
The doctor will determine the appropriate once-daily dose of the medicine based on the child's body weight (see table below). This dose must not exceed the recommended dose for adult patients, which is 800 mg of darunavir and 100 mg of ritonavir once daily.
The doctor will inform you how many tablets of darunavir and how much ritonavir (capsules, tablets, or oral solution) the child should take. Tablets of other strengths are available to construct the appropriate dosing regimen.

with ritonavir in oral solution: 80 milligrams/millilitre
Dose for children aged 3 years and older, weighing at least 15 kg, who have previously
received antiretroviral therapy (this will be determined by the child's physician)
The physician will select the appropriate dose of the medicine based on the child's body weight (see table
below). The physician will assess whether once-daily or twice-daily dosing is appropriate for the
child. This dose must not exceed the recommended dose for adult patients, which is
600 mg for Darunavir Aurovitas and 100 mg ritonavir twice daily, or 800 mg for Darunavir Aurovitas and 100 mg ritonavir once daily. The physician will inform you how many tablets
of darunavir and how much ritonavir (capsules, tablets or solution) the child should take.
Tablets with lower strengths are available to allow construction of the appropriate dosing regimen.
The physician will determine whether Darunavir Aurovitas tablets are suitable for the child.
Twice-daily dosing

For adolescents above 12 years of age and weighing at least 40 kg, the physician will determine whether the medicinal product Darunavir Aurovitas 800 mg once daily can be used. This dose cannot be administered using tablets containing 600 mg. Another strength of Darunavir Aurovitas is available.
Once-daily dosing

with ritonavir as an oral solution: 80 milligrams/millilitre
Instructions for using Darunavir Aurovitas in children:

• The child must always take Darunavir Aurovitas in combination with ritonavir. Darunavir Aurovitas does not work properly without ritonavir.
• The child must take the appropriate dose of Darunavir Aurovitas and ritonavir twice daily or once daily. If Darunavir Aurovitas has been prescribed twice daily, the child must take one dose in the morning and another in the evening. The doctor will determine the correct dosing schedule for the child.
• The child must take Darunavir Aurovitas with a meal. Darunavir Aurovitas does not work properly when taken without food. The type of food is not important.
• The child must swallow the tablets with water or milk.

Picture of child-resistant cap

The plastic bottle is supplied with a child-resistant cap and should be opened as follows:

• Press down on the plastic cap while turning it to the left.
• Remove the loosened cap.

Use of a higher than recommended dose of Darunavir Aurovitas
Contact your doctor, pharmacist, or nurse immediately.
Missed dose of Darunavir Aurovitas
If a missed dose is noticed within 6 hours, take the forgotten tablets immediately. Each dose must be taken with ritonavir and with food. If a missed dose is noticed after 6 hours, 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 Aurovitas and ritonavir
If vomiting occurs within 4 hours of taking the medicine, take another dose of Darunavir Aurovitas and ritonavir as soon as possible, together with food. If vomiting occurs more than 4 hours after taking the medicine, do not take another dose of Darunavir Aurovitas and ritonavir until the next regularly scheduled dose.
If in doubt about what to do in case of a missed dose or vomiting, contact your doctor.
Do not stop taking Darunavir Aurovitas without consulting your doctor
HIV medicines can improve well-being, but even if the child feels better, do not stop taking Darunavir Aurovitas without first consulting the doctor.
If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

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

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
You should inform your doctor if any of the following side effects occur.

Hepatic complications have been observed, which in rare cases may be severe. Your doctor will perform blood tests before starting treatment with Darunavir Aurovitas. If you have chronic viral hepatitis B or C, your doctor should perform blood tests more frequently, as there is an increased risk of liver complications. You should discuss with your doctor symptoms of liver dysfunction, which may include: yellowing of the skin or eyes, dark urine (tea-colored), pale stools (faeces), nausea, vomiting, loss of appetite, or pain and discomfort below the ribs on the right side.

Skin rash (more commonly occurring when used concomitantly with raltegravir), itching. Skin rash is usually mild to moderate in severity. However, skin rash may also be a symptom of a rare but serious condition. Therefore, you should consult your doctor if a rash develops. Your doctor will decide on appropriate symptomatic treatment or whether to discontinue Darunavir Aurovitas.

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

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

• Diarrhea

Common (may affect up to 1 in 10 people)

• Vomiting, nausea, abdominal pain or bloating, indigestion, flatulence;
• Headache, fatigue, dizziness, drowsiness, numbness, tingling or pain in hands or feet, weakness, difficulty sleeping.

Uncommon (may affect up to 1 in 100 people)

• Chest pain, changes in ECG, rapid heartbeat;
• Sensory disturbances or reduced skin sensation, tingling, difficulty concentrating, memory loss, balance disorders;
• Breathing difficulties, cough, nosebleeds, sore throat;
• Gastritis or oral inflammation, 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, scaly skin, pigment deposition in nails;
• Muscle pain, muscle cramps or reduced muscle strength, limb pain, osteoporosis;
• Slowed thyroid activity, detectable from blood test results;
• Hypertension, sudden flushing of the face;
• Redness or dryness of the eyes;
• Fever, swelling of the lower limbs due to fluid retention, feeling unwell, irritability, pain;
• Infection symptoms, herpes;
• Erectile dysfunction, gynaecomastia (enlargement of breast glands in men);
• Sleep disturbances, somnolence, depression, anxiety, strange dreams, reduced libido.

Rare (may affect up to 1 in 1,000 people)

• DRESS syndrome [severe rash accompanied by fever, fatigue, facial or lymph node swelling, increased eosinophil count (a type of white blood cell), and liver, kidney or lung involvement];
• Heart attack, slow heartbeat, palpitations;
• Visual disturbances;
• Chills, malaise;
• Feeling confused or disoriented, mood changes, restlessness;
• Fainting, seizures, changes or loss of taste;
• Mouth pain, vomiting blood, inflammation of lips, dry lips, coated tongue;
• Catarrh;
• Skin disorders, dry skin;
• Muscle or joint stiffness, joint pain with or without inflammation;
• Blood cell count and biochemical abnormalities. Changes may be observed in blood or urine tests. Your doctor will provide detailed explanations. Examples include increased levels of a certain type of white blood cells;
• Darunavir crystals in the kidneys causing kidney disease.

Side effects typical for antiretroviral drugs in the same class as Darunavir Aurovitas include:

• Muscle pain, tenderness or weakness. In rare cases, such disorders have been severe.

Reporting of side effects

If you experience any side effects, including any not listed in this leaflet, you should inform your doctor or pharmacist. Side effects can also be reported directly to the Department of Monitoring Adverse Drug Reactions, 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

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

Side effects can also be reported to the marketing authorization holder.

5. How to store Darunavir Aurovitas

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister pack, label, carton or bottle: EXP. The expiry date refers to the last day of the stated month.
No special storage conditions apply for this medicine.
Do not use this medicine if you notice any changes in the appearance of the tablets.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Darunavir Aurovitas contains

• The active substance is darunavir (as darunavir propylene glycol solvate).

Darunavir Aurovitas, 600 mg, film-coated tablets
Each film-coated tablet contains 600 mg of darunavir (as darunavir propylene glycol solvate).

• Other ingredients are:

Tablet core:
Microcrystalline cellulose (Type-101), hydroxypropyl cellulose, crospovidone (Type-B), colloidal anhydrous silica, magnesium stearate.
Tablet coating:
Ready-to-use coating material (white colour):
Polyvinyl alcohol, macrogol 3350, titanium dioxide (E 171) and talc.

What Darunavir Aurovitas looks like and contents of the pack
Darunavir Aurovitas, 600 mg, film-coated tablets
White or almost white, oval, biconvex film-coated tablets, embossed with the code "D" on one side and "600" on the other side of the tablet.
Darunavir Aurovitas is available in blister packs and HDPE bottles with a PP child-resistant closure.
Pack sizes:
Blister packs: 30, 50, 60, 90, 100 or 120 film-coated tablets.
HDPE bottle: 60 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Aurovitas Pharma Polska Sp. z o.o.
ul. Sokratesa 13D, lok. 27
01-909 Warsaw
email: [email protected]

Manufacturer/Importer:
APL Swift Services (Malta) Ltd.
HF26, Hal Far Industrial Estate, Hal Far
Birzebbugia, BBG 3000
Malta
Generics Farmacêutica, S.A.
Rua João de Deus 19, Venda Nova
2700-487 Amadora
Portugal
Arrow Génériques
26 Avenue Tony Garnier
69007 Lyon
France

This medicinal product is authorised in the European Economic Area under the following names:
France: Darunavir Arrow 600 mg comprimé pelliculé
Germany: Darunavir PUREN 600 mg Filmtabletten
Netherlands: Darunavir Aurobindo 600 mg filmomhulde tabletten
Poland: Darunavir Aurovitas
Portugal: Darunavir Generis
Romania: Darunavir Aurobindo 600 mg comprimate filmate
Spain: Darunavir Aurovitas 600 mg comprimidos recubiertos con película EFG