Darunavir accord

Package leaflet: Information for the user

Darunavir Accord, 400 mg, film-coated tablets
Darunavir Accord, 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, pharmacist, or nurse.
• This medicine has been prescribed for you personally. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Leaflet contents

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

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

What Darunavir Accord is
Darunavir Accord contains the active substance darunavir. Darunavir Accord is an antiretroviral medicine used in the treatment of human immunodeficiency virus (HIV) infection.
Darunavir Accord 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 Accord 400 mg and 800 mg film-coated tablets are used to treat HIV infection in adults and children (aged 3 years and older and weighing more than 40 kg) who:

• have not previously been treated with antiretroviral medicines, or
• in some patients who have previously been treated with antiretroviral medicines (your doctor will decide).

Darunavir Accord must be taken in combination with a low dose of cobicistat or ritonavir and other antiviral medicines for HIV. Your doctor will decide the most appropriate combination of medicines for you.

Tell your doctor about all medicines you are taking, including those taken orally, by inhalation, by injection, or applied to the skin.

2. What you need to know before taking Darunavir Accord

Do not take Darunavir Accord

• if you are allergic to darunavir, or any of the other ingredients of this medicine (listed in section 6), or to cobicistat or ritonavir,
• if you have severe liver problems. If you are unsure about the nature of your liver condition, consult your doctor. Additional tests may be needed.

Do not take Darunavir Accord with the following medicines
If you are taking any of the medicines listed below, talk to your doctor about changing your treatment.

Products containing St John’s wort (Hypericum perforatum) must not be used during treatment with Darunavir Accord.
Warnings and precautions
Before starting treatment with Darunavir Accord, discuss this with your doctor, pharmacist, or nurse.
Darunavir Accord will not cure HIV infection.
Patients taking Darunavir Accord remain at risk of developing infections or other HIV-related diseases; therefore, regular contact with a doctor is essential.
Skin rash may occur in patients treated with Darunavir Accord. Rarely, it may become severe or potentially life-threatening. If a rash occurs, contact your doctor immediately.
Rash (usually mild or moderate) may occur more frequently in patients taking Darunavir Accord together with raltegravir (for treatment of HIV infection) than in patients taking either drug 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 virus infection. Your doctor will assess the severity of the condition before deciding whether Darunavir Accord can be taken.
• Inform your doctor if you have diabetes. Darunavir Accord may increase blood glucose levels.
• Inform your doctor immediately if you notice signs of infection (e.g. swollen lymph nodes, fever). In some patients with advanced HIV infection and a history of opportunistic infections, inflammatory symptoms related to prior infections may appear soon after starting anti-HIV therapy. These symptoms are believed to result from an enhanced immune response, enabling the body to fight previously asymptomatic infections.
• In addition to opportunistic infections, autoimmune diseases (conditions arising when the immune system attacks healthy body tissues) may occur after starting anti-HIV treatment. Autoimmune diseases may manifest several months after initiation of therapy. If signs of infection or other symptoms such as muscle weakness, ascending weakness starting in hands and feet progressing toward the trunk, palpitations, tremor, or hyperexcitability occur, contact your doctor immediately to initiate necessary treatment.
• Inform your doctor if you have haemophilia. Darunavir Accord may increase the risk of bleeding.
• Inform your doctor about hypersensitivity to sulfonamides (e.g. used in the treatment of certain infections).
• Inform your doctor about musculoskeletal disorders. In some patients receiving combination antiretroviral therapy, a bone disease called osteonecrosis (bone tissue death due to impaired blood supply) may develop. Risk factors for developing this condition include: prolonged use 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 Accord 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 to discuss the possibility of taking this medicine.
Children
Darunavir Accord 400 mg, 800 mg tablets are not intended for children under 3 years of age or weighing less than 40 kg.
Darunavir Accord 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 Accord. A list of these medicines is provided in the section “Do not use Darunavir Accord with the following medicines”.
In most cases, Darunavir Accord can be used together with anti-HIV medicines from 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 Accord with cobicistat or ritonavir together with all PIs (protease inhibitors), and it must not be used in combination with other protease inhibitors. In some cases, dosage adjustments of other medicines may be necessary. Therefore, always inform your doctor about concomitant anti-HIV medicines and strictly follow your doctor’s instructions regarding their combined use.
The effectiveness of Darunavir Accord may be reduced when taken simultaneously with any of the following products. Inform your doctor if you are taking:

• phenobarbital, phenytoin (anticonvulsants);
• dexamethasone (corticosteroid);
• efavirenz (HIV-1 infection);
• rifapentine, rifabutin (antituberculosis agents);
• saquinavir (HIV-1 infection).

Taking Darunavir Accord may affect the effectiveness of other medicines; 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 (cardiovascular medicines), due to the risk of increased therapeutic effects and adverse reactions of these drugs;
• apixaban, dabigatran etexilate, edoxaban, rivaroxaban, warfarin, clopidogrel (anticoagulants), due to the risk of increased therapeutic effects and adverse reactions of these drugs;
• hormonal contraceptives and hormone replacement therapies containing estrogens; Darunavir Accord may reduce their effectiveness; to avoid unintended pregnancy, use of alternative non-hormonal methods of contraception is recommended;
• ethinylestradiol with drospirenone. Darunavir Accord 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 evaluate which cholesterol-lowering medicine is appropriate for you in this situation;
• clarithromycin (antibiotic);
• cyclosporine, everolimus, tacrolimus, sirolimus (immunosuppressants), due to the risk of increased therapeutic effects and adverse reactions of these drugs;
• corticosteroids including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel diseases, skin, eye, joint, and muscle inflammation, and other inflammatory conditions. They are usually taken orally, inhaled, injected, or applied to the skin. If no alternative medicines are available, use of these drugs is possible only after evaluation by the doctor and under strict monitoring for corticosteroid-related adverse effects;
• buprenorphine/naloxone (medicines used in opioid dependence treatment);
• salmeterol (medicine used in asthma treatment);
• artemether/lumefantrine (combination medicine used in malaria treatment);
• dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (medicines used in cancer treatment);
• sildenafil, tadalafil, vardenafil (medicines used in erectile dysfunction or in heart and lung disorders, so-called pulmonary arterial hypertension);
• glecaprevir/pibrentasvir (used in the treatment of hepatitis C virus);
• fentanyl, oxycodone, tramadol (analgesics);
• fesoterodine, solifenacin (in the treatment of urological disorders).

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

• dabigatran etexilate, edoxaban, warfarin (medicines affecting blood coagulation);
• alfentanil (injection, a potent, short-acting analgesic used in surgical procedures);
• digoxin (medicine used in the treatment of certain heart conditions);
• clarithromycin (antibiotic);
• itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (antifungal agents). Voriconazole may be taken only after consultation with a doctor;
• rifabutin (antibacterial agent);
• sildenafil, vardenafil, tadalafil (medicines for erectile dysfunction or pulmonary hypertension);
• amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (antidepressants and anxiolytics);
• maraviroc (medicine used in HIV infection);
• methadone (medicine used in opioid dependence treatment);
• carbamazepine, clonazepam (anticonvulsants or used in certain types of neuralgia);
• colchicine (in the treatment of gout or familial Mediterranean fever);
• bosentan (medicine used in the treatment of pulmonary hypertension);
• buspirone, chlordiazepoxide, diazepam, estazolam, flurazepam, midazolam administered by injection, zolpidem (sedatives);
• perphenazine, risperidone, thioridazine (antipsychotics);
• metformin (antidiabetic medicine for type 2 diabetes).

This is not a complete list of medicines. Inform your doctor about all medicines you are taking.
Darunavir Accord with food and drink
See section 3 “How to take Darunavir Accord”.
Pregnancy and breastfeeding
Inform your doctor immediately if you are pregnant or planning to become pregnant. Pregnant women should not take Darunavir Accord with ritonavir without specific medical advice.
Pregnant women should not take Darunavir Accord with cobicistat.
Due to the risk of adverse effects in breastfed infants, women should not breastfeed while taking Darunavir Accord.
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 using machines
Do not drive or operate machinery if Darunavir Accord causes dizziness.
Darunavir Accord 400 mg film-coated tablets contain sunset yellow (E110), which may cause allergic reactions.
Darunavir Accord 400 mg film-coated tablets contain lactose
This medicine contains lactose. If you have been previously diagnosed with intolerance to certain sugars, consult your doctor before taking this medicine.
Darunavir Accord 400 mg film-coated tablets contain propylene glycol
This medicine contains 55.55 mg of propylene glycol in each film-coated tablet.
If the child being treated is less than 4 weeks old, talk to the child’s doctor or pharmacist before administering this medicine, especially if the child is receiving other medicines containing propylene glycol or alcohol.
Darunavir Accord 800 mg film-coated tablets contain lactose
This medicine contains lactose. If you have been previously diagnosed with intolerance to certain sugars, consult your doctor before taking this medicine.
Darunavir Accord 800 mg film-coated tablets contain propylene glycol
This medicine contains 111.1 mg of propylene glycol in each film-coated tablet.
If the child being treated is less than 4 weeks old, talk to the child’s doctor or pharmacist before administering this medicine, especially if the child is receiving other medicines containing propylene glycol or alcohol.

3. How to take Darunavir Accord

This medicine should always be taken exactly as described in the patient information leaflet or as directed by your doctor, pharmacist, or nurse. If in doubt, consult your doctor, pharmacist, or nurse. Even if a noticeable improvement occurs, do not stop taking Darunavir Accord together with cobicistat or ritonavir without consulting your treating doctor.

Do not change the dose, formulation, or discontinue treatment without your doctor's recommendation.

Darunavir Accord 400 mg, film-coated tablets are intended only for use in creating an 800 mg dosing regimen once daily.

Darunavir Accord 800 mg, film-coated tablets are intended only for once-daily administration.

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

The usual dose of Darunavir Accord is 800 mg (two 400 mg tablets or one 800 mg tablet) once daily.

Take Darunavir Accord every day, always together with cobicistat 150 mg or ritonavir 100 mg, and with food. Darunavir Accord will not provide the desired therapeutic effect if taken without cobicistat or ritonavir and without food.

Eat a meal or snack within 30 minutes before taking Darunavir Accord and cobicistat or ritonavir. The type of food is not important. Even if a noticeable improvement occurs, do not stop taking Darunavir Accord with cobicistat or ritonavir without consulting your doctor.

Recommendations for adults

• Take two 400 mg tablets at the same time, once daily (every day).
• Always take Darunavir Accord at the same time as 150 mg cobicistat or 100 mg ritonavir.
• Take Darunavir Accord with food.
• Swallow the tablets with water or milk.
• Take other anti-HIV medicines in combination with Darunavir Accord and cobicistat or ritonavir as directed by your doctor.
• Darunavir 100 milligrams per millilitre oral suspension is also available for use in children and may be used in certain cases in adults.

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

The dose is:

• 800 mg Darunavir Accord (two 400 mg tablets or one 800 mg tablet) taken together with 150 mg cobicistat or 100 mg ritonavir once daily. OR
• 600 mg Darunavir Accord taken together with 100 mg ritonavir twice daily.

Discuss with your doctor which dose is appropriate for you.

Dosage for children aged 3 years and older taking ritonavir, and aged 12 years and older taking cobicistat, weighing at least 40 kilograms, who have not previously taken antiretroviral medicines (to be determined by your treating doctor)

• The recommended dose of Darunavir Accord is 800 mg (two 400 mg tablets or one 800 mg tablet) taken together with ritonavir 100 mg or cobicistat 150 mg once daily.

Dosage for children aged 3 years and older taking ritonavir, and aged 12 years and older taking cobicistat, weighing at least 40 kilograms, who have previously taken antiretroviral medicines (to be determined by your treating doctor)

The dose is:

• 800 mg Darunavir Accord (two 400 mg tablets or one 800 mg tablet) taken together with 100 mg ritonavir once daily. OR
• 600 mg Darunavir Accord taken together with 100 mg ritonavir twice daily.

Discuss with your doctor which dose is appropriate for you.

Recommendations for children aged 3 years and older taking ritonavir, and aged 12 years and older taking cobicistat, weighing at least 40 kilograms

• Take the 800 mg dose of Darunavir Accord (two 400 mg tablets or one 800 mg tablet) at the same time, once daily, every day.
• Always take Darunavir Accord at the same time as 100 mg ritonavir.
• Take Darunavir Accord with food.
• Swallow the tablets with water or milk.
• Take other anti-HIV medicines in combination with Darunavir Accord and ritonavir as directed by your doctor.

Opening the child-resistant cap

The plastic bottle is equipped with a child-resistant cap.

To open it, follow these steps:

• Press down on the plastic cap while turning it counterclockwise;
• Remove the loosened cap.

Taking more Darunavir Accord than recommended

Contact your doctor, pharmacist, or nurse immediately.

If you miss a dose of Darunavir Accord

If you notice the missed dose within 12 hours, take the missed tablets as soon as possible. Each dose must be taken with ritonavir and food. If you notice the missed dose after 12 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.

If you vomit after taking Darunavir Accord and cobicistat or ritonavir

If vomiting occurs within 4 hours of taking the medicine, take another dose of Darunavir Accord and cobicistat or 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 Accord and cobicistat or ritonavir until the next regularly scheduled dose.

If you are unsure about what to do if you miss a dose or vomit, contact your doctor.

Do not stop taking Darunavir Accord without consulting your doctor

HIV medicines may improve your well-being, but even if you feel better, do not stop taking the medicine without first discussing it with your doctor.

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

4. Possible side effects

During HIV treatment, increases in body weight, blood lipid levels, and blood glucose levels may occur. This is partly due to improved health and lifestyle, and in the case of blood lipid levels, sometimes due to the antiretroviral medications themselves. Your doctor will order tests to monitor these changes.

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If any of the side effects listed below occur, you should inform your doctor.

Hepatic complications have been observed, which in rare cases may be severe. Your doctor will order blood tests before starting treatment with Darunavir Accord. If you have chronic viral hepatitis B or C, your doctor should order 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 (stools), nausea, vomiting, loss of appetite, or pain or discomfort under the ribs on the right side.

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

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

Very common side effects (may occur in more than 1 in 10 patients):

• Diarrhea.

Common side effects (may occur in up to 1 in 10 patients):

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

Uncommon side effects (may occur in up to 1 in 100 patients):

• Chest pain, changes in ECG, rapid heartbeat;
• Sensory disturbances or reduced sensation, tingling, difficulty concentrating, memory loss, balance disorders;
• Breathing difficulties, cough, nosebleeds, throat irritation;
• Inflammation of the stomach or mouth, heartburn, retching (without vomiting), dry mouth, abdominal discomfort, constipation, belching;
• Kidney failure, kidney stones, difficulty urinating, excessive or frequent urination, sometimes at night;
• Urticaria, severe swelling of the skin and other tissues (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, which may be detected through blood test results;
• Hypertension, sudden flushing of the face;
• Redness or dryness of the eyeballs;
• Fever, swelling of the lower limbs due to fluid retention, feeling unwell, irritability, pain;
• Signs of infection, herpes;
• Erectile dysfunction, breast enlargement in men;
• Sleep disturbances, somnolence, depression, anxiety, strange dreams, decreased libido.

Rare side effects (may occur in up to 1 in 1000 patients):

• DRESS syndrome [severe rash associated with 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;
• Vision disturbances;
• Chills, malaise;
• Feeling confused or disoriented, mood changes, restlessness;
• Fainting, seizures, changes or loss of taste;
• Mouth pain, vomiting blood, inflammation of the lips, dry lips, coated tongue;
• Nasal congestion;
• Skin disorders, dry skin;
• Muscle or joint stiffness, joint pain with or without inflammation;
• Blood cell count and biochemical test abnormalities. These changes may be observed in blood or urine tests. Your doctor will provide detailed explanations. An example is an increase in a certain type of white blood cells;
• Darunavir crystals in the kidneys causing kidney disease.

Side effects typical for antiretroviral medicines in the same class as Darunavir Accord include:

• Muscle pain, tenderness or weakness. In rare cases, such disorders may be severe.

Reporting of side effects
If you experience any side effects, including any not listed in this leaflet, inform your doctor or pharmacist. Side effects can be reported directly to the Department of Monitoring Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw
Tel: +48 22 49 21 301, Fax: +48 22 49 21 309, Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Darunavir Accord

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and bottle after "EXP". The expiry date refers to the last day of the stated month.
No special precautions for storage of Darunavir Accord.
Medicines should 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 Accord contains

• The active substance is darunavir. Each Darunavir Accord 400 mg coated tablet contains 400 mg of darunavir (as darunavir propylene glycol solvate).

Each Darunavir Accord 800 mg coated tablet contains 800 mg of darunavir (as darunavir propylene glycol solvate).

• Other ingredients are:

Darunavir Accord, 400 mg, coated tablets
Monohydrate lactose, microcrystalline cellulose, povidone K30, crospovidone, colloidal anhydrous silica, magnesium stearate.
Coating Coating (orange-2): polyvinyl alcohol (E1203), titanium dioxide (E171), macrogol 3350 (E1521), talc (E553b), yellow orange FCF, aluminium lake (E110).

Darunavir Accord, 800 mg, coated tablets
Monohydrate lactose, microcrystalline cellulose, povidone K30, crospovidone, colloidal anhydrous silica, magnesium stearate.
Coating Coating (red): polyvinyl alcohol (E1203), macrogol 3350 (E1521), iron oxide red (E172), talc (E553b), titanium dioxide (E171).

What Darunavir Accord looks like and contents of the pack
Darunavir Accord, 400 mg, coated tablets
Light orange, oval tablets with the embossed mark "400" on one side,
dimensions: length 18.2 ± 0.2 mm, width 9.2 ± 0.2 mm, and thickness 5.7 ± 0.4 mm.

Darunavir Accord, 800 mg, coated tablets
Dark red, oval tablets with the embossed mark "800" on one side,
dimensions: length 21.4 ± 0.2 mm, width 10.8 ± 0.2 mm, and thickness 8.0 ± 0.4 mm.

Carton containing a white, opaque high-density polyethylene (HDPE) bottle with a polypropylene child-resistant cap and seal, and a leaflet.

Pack sizes:
Darunavir Accord, 400 mg, coated tablets
One bottle containing 60 tablets.

Darunavir Accord, 800 mg, coated tablets
One or three bottles containing 30 tablets.

Not all pack types may be marketed.

Marketing Authorisation Holder
Accord Healthcare Polska Sp. z o.o.
Taśmowa 7 Street
02-677 Warsaw
Tel: +48 22 577 28 00

Manufacturer / Importer
Pharmadox Healthcare Ltd.
KW20A Kordin Industrial Park
Paola, PLA3000
Malta

Pharmathen International S.A.
6, Dervenakion Street
Pallini, Attiki, 153 51
Greece

Pharmathen International S.A.
Industrial Park Sapes
Rodopi Prefecture, Block No 5
Rodopi, 69300
Greece

LABORATORI FUNDACIÓ DAU
C/ C, 12-14 Pol. Ind. Zona Franca,
Barcelona, 08040
Spain

This medicinal product is authorised in the Member States of the European Economic Area under the following names: