Darunavir Aurobindo

Package leaflet: Information for the patient

Darunavir Aurobindo 400 mg film-coated tablets, 800 mg film-coated tablets

Equivalent medicine
Please read 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 questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

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

What Darunavir Aurobindo is
Darunavir Aurobindo contains the active substance darunavir. Darunavir Aurobindo is an
antiretroviral medicine used to treat human immunodeficiency virus (HIV) infection. It
belongs to a group of medicines called protease inhibitors. Darunavir Aurobindo works by
reducing the amount of HIV in the body, improving the immune system, and reducing the
risk of developing HIV-related illnesses.
What it is used for
The 400 mg and 800 mg tablets of Darunavir Aurobindo are used to treat adults and children (aged 3 years and older, and weighing at least 40 kilograms) with HIV infection:

• who have not previously used other antiretroviral medicines, or
• in certain patients who have previously used antiretroviral medicines (your doctor will determine to whom it should be given).

Darunavir Aurobindo must be taken in combination with a low dose of cobicistat or
ritonavir and with other anti-HIV medicines. Your doctor will discuss with you the best combination of medicines for your treatment.

2. What you need to know before taking Darunavir Aurobindo

Do not take Darunavir Aurobindo

• If you are allergic to darunavir or to any of the other ingredients of this medicine (listed in section 6), or to cobicistat or ritonavir.
• If you have severe liver problems. Ask your doctor for advice if you are unsure about the severity of your liver disease. You may need additional tests.

Inform your doctor about all the medicines you are taking, including medicines taken orally,
inhaled, injected, or applied to the skin.
Do not take Darunavir Aurobindo with any of the following medicines.
If you are currently taking one of these medicines, ask your doctor how to switch to another
medicine.

Do not co-administer Darunavir Aurobindo with products containing St. John's wort ( Hypericum
perforatum ).
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Darunavir Aurobindo.
Darunavir Aurobindo is not a cure for HIV infection.
People taking Darunavir Aurobindo may still develop infections or other HIV-related illnesses.
You should maintain regular contact with your doctor.
People taking Darunavir Aurobindo may develop a rash.
Rarely, a rash may become severe or potentially life-threatening.
Contact your doctor whenever you develop a rash.
In people taking Darunavir Aurobindo and raltegravir (for HIV infection), rashes (usually mild or moderate) may occur more frequently than in patients taking these medicines separately.
Inform your doctor about your condition BEFORE and DURING treatment.
Make sure to check the following points and inform your doctor if any of them apply to you.

• Inform your doctor if you have previously had liver problems, including hepatitis B or C infection. Your doctor may assess the severity of your liver disease before deciding whether to prescribe Darunavir Aurobindo.
• Inform your doctor if you have diabetes. Darunavir Aurobindo may increase blood sugar levels.
• Inform your doctor immediately if you notice any symptoms 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 from previous infections may occur shortly after starting anti-HIV treatment. These symptoms are believed to result from an improved immune response, enabling the body to fight infections that may have been present without causing obvious symptoms.
• In addition to opportunistic infections, autoimmune disorders (a condition in which the immune system attacks healthy body tissue) may also occur after starting medications for the treatment of HIV infection. Autoimmune disorders may occur several months after starting treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and progressing toward the trunk of the body, palpitations, tremor, or hyperactivity, inform your doctor immediately to receive necessary treatment.
• Inform your doctor if you have haemophilia. Darunavir Aurobindo may increase the risk of bleeding.
• Inform your doctor if you are allergic to sulfonamides (used to treat certain infections).
• Inform your doctor if you experience any musculoskeletal problems. Some patients taking a combination of antiretroviral medicines may develop a bone disease called osteonecrosis (death of bone tissue caused by reduced blood supply to the bone). Some of the many risk factors for developing this condition may include duration of combined antiretroviral use, corticosteroid use, alcohol consumption, severe immunosuppression, and high body mass index. Signs of osteonecrosis include joint swelling, pain, and stiffness (especially in the hip, knee, and shoulders) and difficulty moving. If you notice any of these symptoms, inform your doctor immediately.

Elderly
Darunavir Aurobindo has been administered to only a limited number of patients aged 65 years or older. If you belong to this age group, ask your doctor whether you can use Darunavir Aurobindo.
Children and adolescents
Darunavir Aurobindo must not be used in children under 3 years of age or with a body weight below 40 kilograms.
Other medicines and Darunavir Aurobindo
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
There are medicines that must not be co-administered with Darunavir Aurobindo. These medicines have been listed earlier in the section “Do not co-administer Darunavir Aurobindo with any of the following medicines.”
In most cases, Darunavir Aurobindo can be co-administered with other anti-HIV medicines belonging to a different class [e.g., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists, and FIs (fusion inhibitors)]. Darunavir Aurobindo in combination with cobicistat or ritonavir has not been studied with all PIs (protease inhibitors) and must not be used with other HIV PIs. In some cases, the dose of other medicines may need to be adjusted. Therefore, always inform your doctor if you are taking other anti-HIV medicines and carefully follow your doctor’s instructions regarding which medicines you may take.
The effects of Darunavir Aurobindo may be reduced if you take any of the following medicines. Inform your doctor if you are taking:

• Phenobarbital, phenytoin (to prevent epileptic seizures).
• Dexamethasone (a corticosteroid).
• Efavirenz (to treat HIV infection).
• Rifapentine, rifabutin (medicines to treat certain infections such as tuberculosis).
• Saquinavir (to treat HIV infection).

The effects of other medicines may be affected by taking Darunavir Aurobindo, and your doctor may wish to perform additional blood tests. Inform your doctor if you are taking:

• Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nifedipine, nicardipina, propafenone, timolol, verapamil (for heart conditions), as the therapeutic effect or side effects of these medicines may be altered.
• Apixaban, dabigatran etexilate, edoxaban, rivaroxaban, warfarin, clopidogrel (to reduce blood clotting), because both the therapeutic effect and side effects may be altered.
• Hormonal contraceptives containing oestrogen or hormone replacement therapy. Darunavir Aurobindo may reduce their effectiveness. When hormonal therapy is used for contraception, use of alternative contraceptive methods other than hormonal therapy is recommended.
• Ethinylestradiol/drospirenone. Darunavir Aurobindo may increase the risk of elevated potassium levels due to drospirenone.
• Atorvastatin, pravastatin, rosuvastatin (to lower cholesterol levels). The risk of muscle damage may increase. Your doctor will evaluate which cholesterol-lowering medicine is most appropriate for your specific condition.
• Clarithromycin (an antibiotic).
• Cyclosporine, everolimus, tacrolimus, sirolimus (to reduce immune system activity), as the therapeutic effect or side effects of these medicines may be increased. Your doctor may wish to perform additional tests.
• 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 disorders, and other types of inflammatory conditions. These medicines are generally taken orally, by inhalation, by injection, or applied to the skin. If alternative treatments cannot be used, these medicines may only be taken after evaluation by your doctor and under careful monitoring for corticosteroid-related side effects.
• Buprenorphine/naloxone (to treat opioid dependence).
• Salmeterol (to treat asthma).
• Artemether/lumefantrine (a combination of medicines to treat malaria).
• Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (to treat cancer).
• Sildenafil, tadalafil, vardenafil (for erectile dysfunction or for treating a heart or lung condition called pulmonary arterial hypertension).
• Glecaprevir/pibrentasvir (to treat hepatitis C infection).
• Fentanyl, oxycodone, tramadol (to treat pain).
• Fesoterodine, solifenacin (to treat urological disorders).

Your doctor may wish to perform additional blood tests and it may be necessary to adjust the dosage of other medicines, as the therapeutic effect and side effects of these medicines or of Darunavir Aurobindo may be affected when used together.
Inform your doctor if you are taking:

• Dabigatran etexilate, edoxaban, warfarin (to reduce blood clotting).
• Alfentanil (a potent, short-acting injectable painkiller used during surgery).
• Digoxin (to treat certain heart conditions).
• Clarithromycin (an antibiotic).
• Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (to treat fungal infections). Voriconazole may only be taken after evaluation by your doctor.
• Rifabutin (to treat bacterial infections).
• Sildenafil, vardenafil, tadalafil (for erectile dysfunction or for high blood pressure in the lung circulation).
• Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (to treat depression and anxiety).
• Maraviroc (to treat HIV infection).
• Methadone (to treat opioid dependence).
• Carbamazepine, clonazepam (to prevent epileptic seizures or to treat certain types of neuropathic pain).
• Colchicine (to treat gout or familial Mediterranean fever).
• Bosentan (to treat high blood pressure in the lung circulation).
• Buspirone, clorazepate, diazepam, estazolam, flurazepam, midazolam when used by injection, zolpidem (sedatives).
• Perphenazine, risperidone, thioridazine (to treat psychiatric conditions).
• Metformin (to treat type 2 diabetes). This is not a complete list of medicines. Inform your doctor about all medicines you are taking.

Darunavir Aurobindo with food and drinks
See section 3, “How to take Darunavir Aurobindo”.
Pregnancy and breastfeeding
Inform your doctor immediately if you are pregnant or planning to become pregnant. Pregnant women should not take Darunavir Aurobindo with ritonavir unless specifically instructed by their doctor. Pregnant women should not take Darunavir Aurobindo with cobicistat.
Due to potential adverse effects in infants, women must not breastfeed while receiving Darunavir Aurobindo.
Breastfeeding is not recommended for women with HIV infection, as the infection can be transmitted to the child through breast milk. If you are breastfeeding or considering breastfeeding, discuss this with your doctor as soon as possible.
Driving and using machines
Do not drive or operate machinery if you experience dizziness after taking Darunavir Aurobindo.
Darunavir Aurobindo 400 mg film-coated tablets contain propylene glycol
This medicine contains 55.56 mg of propylene glycol in each film-coated tablet.
If your child is less than 4 weeks old, talk to your doctor or pharmacist before administering this medicine, especially if the child is taking other medicines containing propylene glycol or alcohol.
Darunavir Aurobindo 800 mg film-coated tablets contain propylene glycol
This medicine contains 111.12 mg of propylene glycol in each film-coated tablet.
If your child is less than 4 weeks old, talk to your doctor or pharmacist before administering this medicine, especially if the child is taking other medicines containing propylene glycol or alcohol.

3. How to take Darunavir Aurobindo

Take this medicine exactly as directed by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist. Even if you feel better, do not stop taking Darunavir Aurobindo together with cobicistat or ritonavir without first talking to your doctor.
Once treatment has been started, the dose or dosing regimen must not be changed, nor should treatment be stopped, without instructions from your doctor.
The 400-milligram tablets of Darunavir Aurobindo must be used only to achieve the 800-milligram daily dose regimen; the 800-milligram tablets of Darunavir Aurobindo are intended exclusively for daily use.
This medicine is available only as film-coated tablets and is therefore not suitable for patients unable to swallow whole tablets, such as young children. For use in these patients, availability of more appropriate formulations containing darunavir should be checked.

Dose for adults who have not previously taken antiretroviral medicines (your doctor will assess this)
The usual dose of Darunavir Aurobindo is 800 milligrams (2 tablets of 400 milligrams of Darunavir Aurobindo or 1 tablet of 800 milligrams of Darunavir Aurobindo) once daily.
You must take Darunavir Aurobindo every day, always in combination with 150 milligrams of cobicistat or 100 milligrams of ritonavir and with food. Darunavir Aurobindo cannot work optimally without cobicistat or ritonavir and without food. You must eat a meal or snack within 30 minutes before taking Darunavir Aurobindo and cobicistat or ritonavir. The type of food does not matter. Even if you feel better, do not stop taking Darunavir Aurobindo and cobicistat or ritonavir before speaking with your doctor.

Instructions for adults

• Take two 400-milligram tablets or one 800-milligram tablet at the same time each day, every day.
• Take Darunavir Aurobindo always with 150 milligrams of cobicistat or 100 milligrams of ritonavir.
• Take Darunavir Aurobindo with food.
• Swallow the tablets with a drink such as water or milk.
• Take other HIV medicines used in combination with Darunavir Aurobindo and cobicistat or ritonavir, following your doctor’s instructions.

Adults who have previously taken antiretrovirals (your doctor will assess this)
A different dose of Darunavir Aurobindo may be required, which cannot be administered with these 400- or 800-milligram tablets. However, other strengths of Darunavir Aurobindo are available.
The dose is:

• 800 milligrams of Darunavir Aurobindo (2 tablets of 400 milligrams of Darunavir Aurobindo or 1 tablet of 800 milligrams of Darunavir Aurobindo) together with 150 milligrams of cobicistat or 100 milligrams of ritonavir, once daily. OR
• 600 milligrams of Darunavir Aurobindo (1 tablet of 600 milligrams of Darunavir Aurobindo) together with 100 milligrams of ritonavir, twice daily.

Discuss with your doctor which dose is most appropriate for you.

Dose for children aged 3 years and older taking ritonavir and aged 12 years and older taking cobicistat, weighing more than 40 kilograms, who have not previously taken antiretroviral medicines (your child’s doctor will determine this condition)

• The usual dose of Darunavir Aurobindo is 800 milligrams (2 tablets of 400 milligrams of Darunavir Aurobindo or 1 tablet of 800 milligrams of Darunavir Aurobindo) together with 100 milligrams of ritonavir or 150 milligrams of cobicistat, once daily.

Dose for children aged 3 years and older taking ritonavir and aged 12 years and older taking cobicistat, weighing more than 40 kilograms, who have previously taken antiretroviral medicines (your child’s doctor will determine this condition)
The dose is:

• 800 milligrams of Darunavir Aurobindo (2 tablets of 400 milligrams of Darunavir Aurobindo or 1 tablet of 800 milligrams of Darunavir Aurobindo) together with 100 milligrams of ritonavir or 150 milligrams of cobicistat, once daily. OR
• 600 milligrams of Darunavir Aurobindo (1 tablet of 600 milligrams of Darunavir Aurobindo) together with 100 milligrams of ritonavir, twice daily.

Discuss with your doctor which dose is most appropriate.

Instructions for children aged 3 years and older taking ritonavir and aged 12 years and older taking cobicistat, weighing more than 40 kilograms

• Take 800 milligrams of Darunavir Aurobindo (2 tablets of 400 milligrams of Darunavir Aurobindo or 1 tablet of 800 milligrams of Darunavir Aurobindo) at the same time each day, every day.
• Take Darunavir Aurobindo always together with 100 milligrams of ritonavir or 150 milligrams of cobicistat.
• Take Darunavir Aurobindo with food.
• Swallow the tablets with a drink, such as water or milk.
• Take other HIV medicines used in combination with Darunavir Aurobindo and ritonavir or cobicistat, following your doctor’s instructions.

Removing the child-resistant cap

The plastic bottle comes with a child-resistant cap, which must be opened as follows:

• Press down on the plastic cap and turn it counterclockwise.
• Remove the unscrewed cap.

If you take more Darunavir Aurobindo than you should
Contact your doctor, pharmacist, or nurse immediately.

If you forget to take Darunavir Aurobindo
If you remember within 12 hours, take the missed tablets immediately. Always take the tablets together with cobicistat or ritonavir and with food. If you remember after 12 hours, skip the missed dose and take the next dose at your usual time. Do not take a double dose to make up for a forgotten dose.

If you vomit after taking Darunavir Aurobindo and cobicistat or ritonavir
If you vomit within 4 hours of taking the medicine, take another dose of Darunavir Aurobindo and cobicistat or ritonavir with 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 Aurobindo and cobicistat or ritonavir until your next scheduled dose.
Contact your doctor if you are unsure what to do if you miss a dose or vomit.

Do not stop treatment with Darunavir Aurobindo without first talking to your doctor
Anti-HIV medicines may make you feel better. Do not stop taking Darunavir Aurobindo, even if you feel better. Talk to your doctor first.
If you have any questions about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

During HIV treatment, weight gain and increases in blood lipid and glucose levels may occur. This is partly related to improved health status 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 side effects, although not everybody gets them.

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

Liver problems have been reported, which occasionally can be serious. Your doctor will carry out blood tests before you start taking Darunavir Aurobindo. If you have chronic hepatitis B or C, your doctor must check your blood tests more frequently, 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 or whites of the eyes, dark-coloured urine (tea-coloured), pale stools (bowel movements), nausea, vomiting, loss of appetite, or pain, tenderness, or discomfort on the right side under the ribs.

Skin rashes (more frequent when used in combination with raltegravir), itching. Rashes are generally mild or moderate in severity. However, a rash may also be a symptom of a rare but more serious condition. It is important that you consult your doctor if you develop a skin rash. Your doctor will advise you on how to manage symptoms, or whether Darunavir Aurobindo should be discontinued.

Other serious side effects include diabetes (common) and inflammation of the pancreas (uncommon).

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

• diarrhoea

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, loss of strength, difficulty falling asleep

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

• chest pain, changes in electrocardiogram, rapid heartbeat
• decreased or abnormal skin sensitivity, sensation of pins and needles, attention disorders, memory loss, balance problems
• shortness of breath, cough, nosebleeds, sore throat
• inflammation of the stomach or mouth, heartburn, retching, 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 or other tissues (especially lips and eyes), eczema, excessive sweating, night sweats, hair loss, acne, scaly skin, nail pigmentation
• muscle pain, muscle cramps or weakness, pain in limbs, osteoporosis
• reduced thyroid function. This may be detected by blood test
• high blood pressure, hot flushes
• red or dry eyes
• fever, swelling of legs due to fluid retention, malaise, irritability, pain
• symptoms of infection, herpes simplex
• erectile dysfunction, breast enlargement
• sleep disorders, drowsiness, depression, anxiety, altered dreams, decreased sexual desire

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

• 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), and effects on liver, kidneys or lungs]
• heart attack, slow heartbeat, palpitations
• vision disorders
• chills, feeling unwell
• a feeling of confusion or disorientation, mood changes, restlessness
• fainting, seizures, change or loss of taste
• mouth ulcers, vomiting blood, inflammation of the lips, dry lips, coated tongue
• runny nose
• skin lesions, dry skin
• stiffness of muscles or joints, joint pain with or without inflammation
• changes in certain blood cell or chemical values. These may be seen in blood and/or urine tests. Your doctor will explain these results to you. Examples include: increase in certain white blood cells
• deposition of darunavir crystals in the kidney causing kidney disease

Some side effects are typical of anti-HIV medicines in the same class as Darunavir Aurobindo. These are:

• muscle pain, fragility or weakness. In rare cases, these muscle disorders have been severe.

Reporting of side effects

If you get any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at
www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Darunavir Aurobindo

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label of the bottle
and on the carton after EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not use this medicine if you notice any changes in the appearance of the tablets.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist
how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Darunavir Aurobindo contains
The active substance is darunavir (as propylene glycol).
Darunavir Aurobindo 400 mg film-coated tablets
Each film-coated tablet contains 400 mg of darunavir (as propylene glycol).
Darunavir Aurobindo 800 mg film-coated tablets
Each film-coated tablet contains 800 mg of darunavir (as propylene glycol).
The other components are:
Tablet core:
Microcrystalline cellulose (Grade-101), hydroxypropylcellulose, crospovidone (Type-B), anhydrous colloidal silica and magnesium stearate.
Tablet coating:
For 400 mg
Ready-to-use brown coating material:
Polyvinyl alcohol, macrogol 3350, titanium dioxide (E171), talc and red iron oxide (E172).
For 800 mg
Ready-to-use brown coating material:
Polyvinyl alcohol, macrogol 3350, red iron oxide (E172), titanium dioxide (E171) and talc.

Description of the appearance of Darunavir Aurobindo and pack contents
Darunavir Aurobindo 400 mg film-coated tablets
Brown film-coated, oval-shaped, biconvex tablets, with “D” engraved on one side and “400” on the other side.
Darunavir Aurobindo 800 mg film-coated tablets
Dark brown film-coated, oval-shaped, biconvex tablets, with “D” engraved on one side and “800” on the other side.
Darunavir Aurobindo film-coated tablets are available in white opaque HDPE bottles with a child-resistant closure made of polypropylene.

Pack sizes
HDPE bottles:
For 400 mg: 60 film-coated tablets.
For 800 mg: 30 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Aurobindo Pharma (Italia) S.r.l.
Via San Giuseppe, 102
21047 - Saronno (VA), Italy

Manufacturers
APL Swift Services (Malta) Ltd
HF26, Hal Far Industrial Estate, Hal Far,
Birzebbugia, BBG 3000, Malta
Generis Farmacêutica SA
Rua João de Deus, 19
2700-487 Amadora, Portugal

This medicinal product is authorised in the European Economic Area countries under the following names:
Portugal: Darunavir Generis Phar
Italy: Darunavir Aurobindo

Package leaflet: Information for the patient

Darunavir Aurobindo 600 mg film-coated tablets

Generic medicine
Please read all of this leaflet carefully before you take this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

7. What Darunavir Aurobindo is and what it is used for
8. What you need to know before taking Darunavir Aurobindo
9. How to take Darunavir Aurobindo
10. Possible side effects
11. How to store Darunavir Aurobindo
12. Contents of the pack and other information

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

What Darunavir Aurobindo is
Darunavir Aurobindo contains the active substance darunavir. Darunavir Aurobindo is an
antiretroviral medicine used to treat human immunodeficiency virus (HIV) infection. It
belongs to a group of medicines called protease inhibitors. Darunavir Aurobindo works by
reducing the amount of HIV in the body, improving the immune system, and reducing the
risk of developing diseases associated with HIV infection.
What it is used for
Darunavir Aurobindo is used to treat HIV infection in adults and children aged 3 years and
older who weigh at least 15 kilograms and who have previously been treated with other
antiretroviral medicines.
Darunavir Aurobindo must be taken in combination with a low dose of ritonavir and other
anti-HIV medicines. Your doctor will discuss with you the best combination of medicines for
your treatment.

2. What you need to know before taking Darunavir Aurobindo

Do not take Darunavir Aurobindo

• 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. Consult 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 medicines taken orally,
inhaled, injected, or applied to the skin.
Do not take Darunavir Aurobindo with any of the following medicines.
If you are currently taking one of these medicines, ask your doctor how to switch to another
medicine.

Do not co-administer Darunavir Aurobindo with products containing St. John’s wort ( Hypericum
perforatum ).
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Darunavir Aurobindo.
Darunavir Aurobindo is not a cure for HIV infection.
People taking Darunavir Aurobindo may still develop infections or other illnesses associated with HIV infection. Regular follow-up with your doctor is necessary.
People taking Darunavir Aurobindo may develop a skin rash.
Rarely, a rash may become severe or potentially life-threatening. Contact your doctor whenever you develop a skin rash.
Skin rashes (usually mild or moderate) may occur more frequently in people taking Darunavir Aurobindo and raltegravir (for HIV infection) compared to patients taking these medicines separately.
Inform your doctor about your condition BEFORE and DURING treatment
Please check the following points and inform your doctor if any of them apply to you.

• Inform your doctor if you have previously had liver problems, including hepatitis B or C infection. Your doctor may assess the severity of your liver disease before deciding whether to prescribe Darunavir Aurobindo.

• Inform your doctor if you have diabetes. Darunavir Aurobindo may increase blood sugar levels.

• Inform your doctor immediately if you notice any symptoms 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 from prior infections may occur shortly after starting anti-HIV treatment. These symptoms are believed to result from an improved immune response, enabling the body to fight infections that may have been present without causing obvious symptoms.

• In addition to opportunistic infections, autoimmune disorders (a condition occurring when the immune system attacks healthy body tissue) may also occur after starting medications for the treatment of HIV infection. Autoimmune disorders may occur several months after starting treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and progressing toward the trunk, palpitations, tremor, or hyperactivity, inform your doctor immediately to receive necessary treatment.

• Inform your doctor if you have haemophilia. Darunavir Aurobindo may increase the risk of bleeding.

• Inform your doctor if you are allergic to sulfonamides (used to treat certain infections).

• Inform your doctor if you experience any musculoskeletal problems. Some patients taking a combination of antiretroviral medicines may develop a
  bone disease called osteonecrosis (death of bone tissue caused by reduced blood flow to the bone). Among the many risk factors for developing this condition are prolonged use of combination antiretrovirals, corticosteroid use, alcohol consumption, severe immunosuppression, and high body mass index. Signs of osteonecrosis include joint swelling, pain, and stiffness (particularly in the hip, knee, and shoulders) and difficulty moving. If you notice any of these symptoms, inform your doctor immediately.
  Elderly
  Darunavir Aurobindo has been administered to only a limited number of patients aged 65 years or older. If you belong to this age group, ask your doctor whether you can use Darunavir Aurobindo.
  Children
  Darunavir Aurobindo must not be used in children under 3 years of age or weighing less than 15 kilograms.
  Other medicines and Darunavir Aurobindo
  Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
  There are medicines that must not be co-administered with Darunavir Aurobindo. These medicines have been listed previously in the section “Do not co-administer Darunavir Aurobindo with any of the following medicines”.
  In most cases, Darunavir Aurobindo can be co-administered with other anti-HIV medicines belonging to a different class [e.g., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists, and FIs (fusion inhibitors)]. Darunavir Aurobindo in combination with ritonavir has not been studied with all PIs (protease inhibitors) and must not be used with other HIV PIs. In some cases, the dose of other medicines may need to be adjusted. Therefore, always inform your doctor if you are taking other anti-HIV medicines and follow your doctor’s instructions carefully regarding which medicines you may take.
  The effects of Darunavir Aurobindo may be reduced if you take any of the following medicines. Inform your doctor if you are taking:

• Phenobarbital, phenytoin (to prevent epileptic seizures).

• Dexamethasone (a corticosteroid).

• Efavirenz (to treat HIV infection).

• Rifapentine, rifabutin (medicines to treat certain infections such as tuberculosis).

• Saquinavir (to treat HIV infection).

The effects of other medicines may be affected by taking Darunavir Aurobindo, and your doctor may wish to perform additional blood tests. Inform your doctor if you are taking:

• Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (for
  heart conditions), as the therapeutic effect or side effects of these medicines may be altered.

• Apixaban, dabigatran etexilato, edoxaban, rivaroxaban, warfarin, clopidogrel (to reduce blood clotting), because both the therapeutic effect and side effects may be altered.

• Hormonal contraceptives containing oestrogens or hormone replacement therapy. Darunavir Aurobindo may reduce their effectiveness. When hormonal therapy is used for contraception, use of alternative contraceptive methods other than hormonal therapy is recommended.

• Ethinylestradiol/drospirenone. Darunavir Aurobindo may increase the risk of elevated potassium levels due to drospirenone.

• Atorvastatin, pravastatin, rosuvastatin (to lower cholesterol levels). The risk of muscle damage may increase. Your doctor will evaluate which cholesterol-lowering medicine is most appropriate for your specific condition.

• Clarithromycin (an antibiotic).

• Cyclosporine, everolimus, tacrolimus, sirolimus (to reduce immune system activity), as the therapeutic effect or side effects of these medicines may be increased. Your doctor may wish to perform additional tests.

• 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 disorders, and other types of inflammatory conditions. These medicines are generally taken orally, by inhalation, by injection, or applied to the skin. If alternative treatments cannot be used, these medicines may only be taken after evaluation by your doctor and under close monitoring for corticosteroid-related side effects.

• Buprenorphine/naloxone (to treat opioid dependence).

• Salmeterol (to treat asthma).

• Artemether/lumefantrine (a combination of medicines to treat malaria).

• Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (to treat cancer).

• Sildenafil, tadalafil, vardenafil (for erectile dysfunction or for treating a heart or lung condition called pulmonary arterial hypertension).

• Glecaprevir/pibrentasvir (to treat hepatitis C infection).

• Fentanyl, oxycodone, tramadol (to treat pain).

• Fesoterodine, solifenacin (to treat urological disorders).

Your doctor may wish to perform additional blood tests and it may be necessary to adjust the dosage of other medicines, as the therapeutic effect and side effects of these medicines or of Darunavir Aurobindo may be affected when co-administered.
Inform your doctor if you are taking:

• Dabigatran etexilato, edoxaban, warfarin (to reduce blood clotting).
• Alfentanil (a potent, short-acting injectable painkiller used during surgery).
• Digoxin (to treat certain heart conditions).
• Clarithromycin (an antibiotic).
• Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (to treat fungal infections). Voriconazole may only be taken after evaluation by your doctor.
• Rifabutin (for bacterial infections).
• Sildenafil, vardenafil, tadalafil (for erectile dysfunction or for high blood pressure in the lung circulation).
• Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (to treat depression and anxiety).
• Maraviroc (to treat HIV infection).
• Methadone (to treat opioid dependence).
• Carbamazepine, clonazepam (to prevent epileptic seizures or to treat certain types of neuropathic pain).
• Colchicine (to treat gout or familial Mediterranean fever).
• Bosentan (to treat high blood pressure in the lung circulation).
• Buspirone, clorazepate, diazepam, estazolam, flurazepam, midazolam when used by injection, zolpidem (sedatives).
• Perphenazine, risperidone, thioridazine (to treat psychiatric conditions).

This is not a complete list of medicines. Inform your doctor about all medicines you are taking.
Darunavir Aurobindo with food and drinks
See section 3, “How to take Darunavir Aurobindo”.
Pregnancy and breastfeeding
Inform your doctor immediately if you are pregnant or planning a pregnancy. Pregnant women should not take Darunavir Aurobindo with ritonavir unless specifically instructed by their doctor. Pregnant women should not take Darunavir Aurobindo with cobicistat.
Due to potential adverse effects in infants, women must not breastfeed while receiving Darunavir Aurobindo.
Breastfeeding is not recommended for women with HIV infection, as the infection can be transmitted to the child through breast milk. If you are breastfeeding or considering breastfeeding, discuss this with your doctor as soon as possible.
Driving and using machines
Do not drive or operate machinery if you feel dizzy after taking Darunavir Aurobindo.
Darunavir Aurobindo contains propylene glycol
This medicine contains 83.34 mg of propylene glycol in each film-coated tablet.
If your child is less than 4 weeks old, speak with your doctor or pharmacist before administering this medicine, especially if the child is taking other medicines containing propylene glycol or alcohol.

3. How to take Darunavir Aurobindo

Take this medicine exactly as instructed by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist.
Even if you feel better, do not stop taking Darunavir Aurobindo and ritonavir without speaking to your doctor.
Once treatment has been started, the dose or dosage regimen must not be changed, nor should treatment be stopped, without medical advice.

Dose for adults who have not previously taken antiretroviral medicines (this will be assessed by your doctor)
Different doses of Darunavir Aurobindo may be required that cannot be achieved with these 600 mg tablets. Other formulations of Darunavir Aurobindo are available.

Dose for adults who have previously taken antiretrovirals (this will be assessed by your doctor)
The dose is:

• 600 milligrams of Darunavir Aurobindo together with 100 milligrams of ritonavir, twice daily. OR
• 800 milligrams of Darunavir Aurobindo (2 tablets of 400 milligrams of Darunavir Aurobindo or 1 tablet of 800 milligrams of Darunavir Aurobindo) together with 100 milligrams of ritonavir, once daily. The 400 mg and 800 mg tablets of Darunavir Aurobindo must only be used to achieve the 800 mg once-daily regimen.

Discuss with your doctor which dose is correct for you.

Instructions for adults

• Always take Darunavir Aurobindo with ritonavir. Darunavir Aurobindo does not work adequately without ritonavir.
• In the morning, take one 600 milligram tablet of Darunavir Aurobindo together with 100 milligrams of ritonavir.
• In the evening, take one 600 milligram tablet of Darunavir Aurobindo together with 100 milligrams of ritonavir.
• Take Darunavir Aurobindo with food. Darunavir Aurobindo does not work adequately without food. The type of food taken is not important.
• Swallow the tablets with a drink, such as water or milk.

Dose for children aged 3 years and older and weighing at least 15 kilograms who have not previously taken antiretroviral medicines (your child's doctor will determine this condition)
The doctor will calculate the appropriate 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 together with 100 milligrams of ritonavir once daily. The doctor will inform you how many tablets, capsules, or amount of solution of darunavir and ritonavir the child should take. Lower-dose tablets are available to achieve the appropriate therapeutic regimen.

ritonavir oral solution: 80 milligrams per millilitre.
Dose for children aged 3 years and older and weighing at least 15
kilograms who have previously taken antiretroviral medicines (this condition will be determined by your
child's doctor)
The doctor will calculate the appropriate 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 Aurobindo together with 100 milligrams of ritonavir twice daily or 800 milligrams of Darunavir Aurobindo together with 100 milligrams of ritonavir once daily. The doctor will inform you how many darunavir tablets and how much ritonavir (capsules, tablets or solution) the child should take. Tablets with different strengths are available to achieve the appropriate treatment regimen. The doctor will determine whether Darunavir Aurobindo tablets are suitable for the child.
Dose twice daily

* For children aged 12 years and older and weighing at least 40 kilograms, the physician will determine whether Darunavir Aurobindo 800 milligrams once daily can be used. This must not be administered with 600-milligram tablets. Other dosage strengths of Darunavir Aurobindo are available.
Once-daily dosing

ritonavir oral solution: 80 milligrams per millilitre.
Instructions for adults

• The child must always take Darunavir Aurobindo together with ritonavir. Darunavir Aurobindo cannot work effectively without ritonavir.
• The child must take the appropriate doses of Darunavir Aurobindo and ritonavir twice daily or once daily. If Darunavir Aurobindo is prescribed twice daily, the child should take one dose in the morning and one dose in the evening. The doctor will determine which regimen is most appropriate for the child.
• The child must always take Darunavir Aurobindo with food. Darunavir Aurobindo cannot work effectively without food. The type of food does not matter.
• The child must swallow the tablets with a drink, such as water or milk.

Removing the child-resistant cap

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

• Press down on the plastic cap and turn it counterclockwise.
• Remove the unscrewed cap.

If you take more Darunavir Aurobindo than you should
Contact your doctor, pharmacist, or nurse immediately.
If you forget to take Darunavir Aurobindo
If you remember within 6 hours, take the missed dose immediately. Always take the tablets together with ritonavir and with food. If you remember 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 forgotten dose.
If the child vomits after taking Darunavir Aurobindo and ritonavir
If the child vomits within 4 hours of taking the medicine, another dose of Darunavir Aurobindo and ritonavir should be taken with food as soon as possible. If the child vomits more than 4 hours after taking the medicine, there is no need to take another dose of Darunavir Aurobindo and ritonavir until the next scheduled dose.
Contact your doctor if you are unsure what to do if a dose is missed or if vomiting occurs.
Do not stop treatment with Darunavir Aurobindo without first consulting your doctor
Anti-HIV medicines can make you feel better. Do not stop taking Darunavir Aurobindo, even if you feel better. Consult your doctor first.
If you have any questions about how to use this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

During HIV treatment, weight gain and increased levels of lipids and glucose in the blood may occur. This is partly related to the recovery of health and lifestyle, and in the case of blood lipids, sometimes also to the HIV medications themselves. Your doctor will monitor these changes.

Like all medicines, this medicine can cause side effects, although not everybody gets them.

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

Liver problems have been reported, which occasionally can be serious. Your doctor will need to carry out blood tests before starting Darunavir Aurobindo. If you have chronic hepatitis B or C, your doctor must check your blood tests more frequently, 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 or whites of the eyes, dark urine (tea-coloured), pale stools (bowel movements), nausea, vomiting, loss of appetite, or pain, tenderness, or discomfort on the right side under the ribs.

Skin rashes (more frequent when used in combination with raltegravir), itching. Skin rashes are generally mild or moderate in severity. However, a rash may also be a symptom of a more serious and rare condition. It is important that you consult your doctor if you develop a skin rash. Your doctor will advise you on how to manage the symptoms or whether Darunavir Aurobindo should be discontinued.

Other serious side effects included diabetes (common) and inflammation of the pancreas (uncommon).

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

• diarrhoea.

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, loss of strength, difficulty falling asleep.

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

• chest pain, changes in electrocardiogram, rapid heartbeat.
• decreased or abnormal skin sensation, sensation of pins and needles, attention disorders, memory loss, balance problems.
• difficulty breathing, cough, nosebleeds, sore throat.
• inflammation of the stomach or mouth, heartburn, retching, dry mouth, abdominal discomfort, constipation, belching.
• kidney failure, kidney stones, difficulty urinating, frequent or excessive urination, sometimes at night.
• hives, severe swelling of the skin or other tissues (especially lips and eyes), eczema, excessive sweating, night sweats, hair loss, acne, scaly skin, nail pigmentation.
• muscle pain, muscle cramps or weakness, pain in extremities, osteoporosis.
• slowing of thyroid function. This may be detected by blood test.
• high blood pressure, hot flushes.
• red or dry eyes.
• fever, leg swelling due to fluid accumulation, malaise, irritability, pain.
• symptoms of infection, herpes simplex.
• erectile dysfunction, breast enlargement.
• sleep disorders, drowsiness, depression, anxiety, altered dreams, decreased sexual desire.

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

• 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), and effects on the liver, kidneys or lungs].
• heart attack, slow heartbeat, palpitations.
• vision disorders.
• chills, feeling unwell.
• a feeling of confusion or disorientation, mood changes, restlessness.
• fainting, seizures, altered or loss of taste.
• mouth ulcers, vomiting blood, inflammation of the lips, dry lips, coated tongue.
• runny nose.
• skin lesions, dry skin.
• stiffness of muscles or joints, joint pain with or without inflammation.
• changes in certain blood cell or chemical values. These may be seen in blood and/or urine tests. Your doctor will explain these results to you. Examples include: increase in certain white blood cells.
• deposition of darunavir crystals in the kidney causing kidney disease.

Some side effects are typical of anti-HIV medicines in the same class as Darunavir Aurobindo. These include:

• muscle pain, fragility or weakness. In rare cases, these muscle disorders have been severe.

Reporting of side effects

If you get any side effects, including any not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Darunavir Aurobindo

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the bottle label and carton after EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not use this medicine if you notice any changes in the appearance of the tablets.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

7. Contents of the pack and other information

What Darunavir Aurobindo contains
The active substance is darunavir (as propylene glycol).
Darunavir Aurobindo 600 mg film-coated tablets
Each film-coated tablet contains 600 mg of darunavir (as propylene glycol).
The other components are:
Tablet core:
Microcrystalline cellulose (Grade-101), hydroxypropylcellulose, crospovidone (Type-B), anhydrous colloidal silica and magnesium stearate.
Tablet coating:
Ready-to-use coating material (white colour):
Polyvinyl alcohol, macrogol 3350, titanium dioxide (E171) and talc.

Description of the appearance of Darunavir Aurobindo and pack contents
Darunavir Aurobindo 600 mg film-coated tablets
Orange, oval-shaped, biconvex film-coated tablets, with “D” engraved on one side and “600” on the other.
Darunavir Aurobindo film-coated tablets are available in white opaque HDPE bottles with a child-resistant polypropylene cap.

Pack sizes
HDPE bottles: 60 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Aurobindo Pharma (Italia) S.r.l.
Via San Giuseppe, 102
21047 - Saronno (VA), Italy

Manufacturers
APL Swift Services (Malta) Ltd
HF26, Hal Far Industrial Estate, Hal Far,
Birzebbugia, BBG 3000, Malta
Generis Farmacêutica SA
Rua João de Deus, 19
2700-487 Amadora, Portugal

This medicinal product is authorised in the European Economic Area Member States under the following names:
Portugal: Darunavir Generis Phar
Italy: Darunavir Aurobindo