Darunavir 400 mg film-coated tablets

• 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 only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

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

This medicine contains the active substance darunavir. Darunavir is an antiretroviral medicine used in the treatment of Human Immunodeficiency Virus (HIV) infection. It belongs to a group of medicines called protease inhibitors. Darunavir works by reducing the amount of HIV in your body. This will improve your immune system and reduces the risk of developing illnesses linked to HIV infection.

Darunavir is used to treat adults and children (3 years of age and above, at least 40 kilograms body weight) who are infected by HIV and

• who have not used antiretroviral medicines before.
• in certain patients who have used antiretroviral medicines before (your doctor will determine this).

Darunavir must be taken in combination with a low dose of ritonavir and other anti-HIV medicines.

Your doctor will discuss with you which combination of medicines is best for you.

• 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. Ask your doctor if you are unsure about the severity of your liver disease. Some additional tests might be necessary.

Tell your doctor about all medicines you take including medicines taken orally, inhaled, injected or applied to the skin.

If you are taking any of these, ask your doctor about switching to another medicine.

Medicine Purpose of the medicine

Avanafil to treat erectile dysfunction

Astemizole or terfenadine to treat allergy symptoms

Triazolam and oral (taken by mouth) midazolam to help you sleep and/or relieve anxiety

Cisapride to treat some stomach conditions

Colchicine (if you have kidney and/or liver problems) to treat gout or familial Mediterranean fever

Lurasidone, pimozide, quetiapine or sertindole to treat psychiatric conditions

Ergot alkaloids like ergotamine, dihydroergotamine, ergometrine and methylergonovine to treat migraine headaches

Amiodarone, bepridil, dronedarone, ivabradine, quinidine, ranolazine to treat certain heart disorders e.g. abnormal heart beat

Lovastatin, simvastatin and lomitapide to lower cholesterol levels

Rifampicin to treat some infections such as tuberculosis

The combination product lopinavir/ritonavir this anti-HIV medicine belongs to the same class as darunavir

Elbasvir/grazoprevir to treat hepatitis C infection

Alfuzosin to treat enlarged prostate

Sildenafil to treat high blood pressure in the pulmonary circulation

Ticagrelor to help stop the clumping of platelets in the treatment of patients with a history of a heart attack

Naloxegol to treat opioid induced constipation

Dapoxetine to treat premature ejaculation

Domperidone to treat nausea and vomiting

Do not combine darunavir with products that contain St John’s Wort (Hypericum perforatum).

Talk to your doctor, pharmacist or nurse before taking darunavir.

Darunavir is not a cure for HIV infection.

People taking darunavir may still develop infections or other illnesses associated with HIV infection.

You must keep in regular contact with your doctor.

People taking darunavir may develop a skin rash. Infrequently a rash may become severe or potentially life-threatening. Please contact your doctor whenever you develop a rash.

In patients taking darunavir and raltegravir (for HIV infection), rashes (generally mild or moderate) may occur more frequently than in patients taking either medicine separately.

Make sure that you check the following points and tell your doctor if any of these apply to you.

• Tell your doctor if you have had problems with your liver before, including hepatitis B or C infection. Your doctor may evaluate how severe your liver disease is before deciding if you can take darunavir.
• Tell your doctor if you have diabetes. Darunavir might increase sugar levels in the blood.
• Tell your doctor immediately if you notice any symptoms of infection (for example enlarged lymph nodes and fever). In some patients with advanced HIV infection and a history of opportunistic infection, signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is started. It is believed that these symptoms are due to an improvement in the body’s immune response, enabling the body to fight infections that may have been present with no obvious symptoms.
• In addition to the opportunistic infections, autoimmune disorders (a condition that occurs when the immune system attacks healthy body tissue) may also occur after you start taking medicines for the treatment of your HIV infection. Autoimmune disorders may occur many months after the start of treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness beginning in the hands and feet and moving up towards the trunk of the body, palpitations, tremor or hyperactivity, please inform your doctor immediately to seek necessary treatment.
• Tell your doctor if you have haemophilia. Darunavir might increase the risk of bleeding.
• Tell your doctor if you are allergic to sulphonamides (e.g. used to treat certain infections).
• Tell your doctor if you notice any musculoskeletal problems. Some patients taking combination antiretroviral therapy may develop a bone disease called osteonecrosis (death of bone tissue caused by loss of blood supply to the bone). The length of combination antiretroviral therapy, corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index, among others, may be some of the many risk factors for developing this disease. Signs of osteonecrosis are joint stiffness, aches and pains (especially of the hip, knee and shoulder) and difficulty in movement. If you notice any of these symptoms please inform your doctor.

Darunavir has only been used in limited numbers of patients 65 years or older. If you belong to this age group, please discuss with your doctor if you can use darunavir.

Darunavir is not for use in children younger than 3 years of age or weighing less than 40 kilograms.

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines.

There are some medicines that you must not combine with darunavir. These are mentioned above under the heading ‘Do not combine Darunavir with any of the following medicines:’

In most cases, darunavir can be combined with anti-HIV medicines belonging to another class [e.g. NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists and FIs (fusion inhibitors)]. Darunavir with cobicistat or ritonavir has not been tested with all PIs (protease inhibitors) and must not be used with other HIV PIs. In some cases dosage of other medicines might need to be changed. Therefore always tell your doctor if you take other anti-HIV medicines and follow your doctor’s instruction carefully on which medicines can be combined.

The effects of darunavir might be reduced if you take any of the following products. Tell your doctor if you take:

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

The effects of other medicines might be influenced if you take darunavir and your doctor might want to do some additional blood tests. Tell your doctor if you take:

• Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (for heart disease) as the therapeutic effect or side effects of these medicines may be increased.
• Apixaban, dabigatran etexilate, edoxaban, rivaroxaban, warfarin, clopidogrel (to reduce clotting of the blood) as their therapeutic effect or side effects may be altered.
• Oestrogen-based hormonal contraceptives and hormonal replacement therapy. Darunavir might reduce its effectiveness. When used for birth control, alternative methods of non-hormonal contraception are recommended.
• Ethinylestradiol/drospirenone. Darunavir might increase the risk for elevated potassium levels by drospirenone.
• Atorvastatin, pravastatin, rosuvastatin (to lower cholesterol levels). The risk of muscle damage might be increased. Your doctor will evaluate which cholesterol lowering regimen is best for your specific situation.
• Clarithromycin (antibiotic).
• Ciclosporin, everolimus, tacrolimus, sirolimus (for dampening down your immune system) as the therapeutic effect or side effects of these medicines might be increased.
• Corticosteroids including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel diseases, inflammatory conditions of the skin, eyes, joints and muscles and other inflammatory conditions. These medicines are generally taken orally, inhaled, injected or applied to the skin. If alternatives cannot be used, its use should only take place after medical evaluation and under close monitoring by your doctor for corticosteroid side effects.
• Buprenorphine/naloxone (medicines to treat opioid dependence).
• Salmeterol (medicine to treat asthma).
• Artemether/lumefantrine (a combination medicine to treat malaria).
• Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (to treat cancer).
• Sildenafil, tadalafil, vardenafil (for erectile dysfunction or to treat a heart and lung disorder called pulmonary arterial hypertension).
• Glecaprevir/pibrentasvir (to treat hepatitis C infection).
• Fentanyl, oxycodone, tramadol (to treat pain).
• Fesoterodine, solifenacin (to treat urologic disorders).

Your doctor might want to do some additional blood tests and the dosage of other medicines might need to be changed since either their own or darunavir’s therapeutic effect or side effects may be influenced when combined. Tell your doctor if you take:

• Dabigatran etexilate, edoxaban, warfarin (to reduce clotting of the blood)
• Alfentanil (injectable strong and short-acting painkiller that is used for surgical procedures).
• Digoxin (to treat certain heart disorders).
• Clarithromycin (antibiotic).
• Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (to treat fungal infections). Voriconazole should only be taken after medical evaluation.
• Rifabutin (against bacterial infections).
• Sildenafil, vardenafil, tadalafil (for erectile dysfunction or high blood pressure in the pulmonary circulation).
• Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (to treat depression and anxiety).
• Maraviroc (to treat HIV infection).
• Methadone (to treat opiate dependence).
• Carbamazepine, clonazepam (to prevent seizures or to treat certain types of nerve pain).
• Colchicine (to treat gout or familial Mediterranean fever).
• Bosentan (to treat high blood pressure in the pulmonary circulation).
• Buspirone, clorazepate, diazepam, estazolam, flurazepam, midazolam when used as injection, zolpidem (sedative agents).
• Perphenazine, risperidone, thioridazine (to treat psychiatric conditions).
• Metformin (to treat type 2 diabetes).

This is not a complete list of medicines. Tell your healthcare provider about all medicines that you are taking.

See section 3 ‘How to take Darunavir’

Tell your doctor immediately if you are pregnant or planning to become pregnant. Pregnant women should not take darunavir with ritonavir unless specifically directed by the doctor. Pregnant women should not take darunavir with cobicistat.

Because of the potential for side effects in breast-fed infants, women should not breast-feed if they are receiving darunavir.

Breast-feeding is not recommended in women living with HIV because HIV infection can be passed on to the baby in breast milk. If you are breast-feeding, or thinking about breast-feeding, you should discuss it with your doctor as soon as possible.

Do not operate machines or drive if you feel dizzy after taking darunavir.

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

The usual dose of darunavir is 800 milligram (2 tablets containing 400 milligram of darunavir or 1 tablet containing 800 milligram of darunavir) once daily.

You must take darunavir every day and always in combination with 100 milligram of ritonavir and with food. Darunavir cannot work properly without ritonavir and food. You must eat a meal or a snack within 30 minutes prior to taking your darunavir and ritonavir. The type of food is not important. Even if you feel better, do not stop taking darunavir and ritonavir without talking to your doctor.

• Take two 400 milligram tablets at the same time, once a day, every day.
• Take darunavir always together with 100 milligram of ritonavir.
• Take darunavir with food.
• Swallow the tablets with a drink such as water or milk.
• Take your other HIV medicines used in combination with darunavir and ritonavir as recommended by your doctor.
• Darunavir 100 milligram per milliliter oral suspension has been developed by different marketing authorization holder for use in children, but can also be used in adults in some cases.

The dose is either:

• 800 milligram darunavir (2 tablets containing 400 milligram of darunavir or 1 tablet containing 800 milligram of darunavir) together with 100 milligram ritonavir once daily.
  OR
• 600 milligram darunavir together with 100 milligram ritonavir twice daily.

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

• The usual dose of darunavir is 800 milligram (2 tablets containing 400 milligram of darunavir or 1 tablet containing 800 milligram of darunavir) together with 100 milligram ritonavir once daily.

The dose is either:

• 800 milligram darunavir (2 tablets containing 400 milligram of darunavir or 1 tablet containing 800 milligram of darunavir) together with 100 milligram ritonavir once daily.
  OR
• 600 milligram darunavir together with 100 milligram ritonavir twice daily.

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

• Take 800 milligram darunavir (2 tablets containing 400 milligram of darunavir or 1 tablet containing 800 milligram of darunavir) at the same time, once a day, every day.
• Take darunavir always together with 100 milligram of ritonavir.
• Take darunavir with food.
• Swallow the tablets with a drink such as water or milk.
• Take your other HIV medicines used in combination with darunavir and ritonavir as recommended by your doctor.

The plastic bottle comes with a child resistant cap and must be opened as follows:

• Push the plastic screw cap down while turning it counter clockwise.
• Remove the unscrewed cap.

Contact your doctor, pharmacist or nurse immediately.

If you notice within 12 hours, you must take the tablets immediately. Always take with ritonavir and food. If you notice after 12 hours, then skip the intake and take the next doses as usual. Do not take a double dose to make up for a forgotten dose.

If you vomit within 4 hours of taking the medicine, another dose of darunavir and ritonavir should be taken with food as soon as possible. If you vomit more than 4 hours after taking the medicine, then you do not need to take another dose of darunavir and ritonavir until the next regularly scheduled time.

Contact your doctor if you are uncertain about what to do if you miss a dose or vomit.

Anti-HIV medicines may make you feel better. Even when you feel better, do not stop taking darunavir. Talk to your doctor first.

Liver problems that may occasionally be severe have been reported. Your doctor should do blood tests before you start darunavir. If you have chronic hepatitis B or C infection, your doctor should check your blood tests more often because you have an increased chance of developing liver problems. Talk to your doctor about the signs and symptoms of liver problems. These may include yellowing of your skin or whites of your eyes, dark (tea coloured) urine, pale coloured stools (bowel movements), nausea, vomiting, loss of appetite, or pain, aching, or pain and discomfort on your right side below your ribs.

Skin rash (more often when used in combination with raltegravir), itching. The rash is usually mild to moderate. A skin rash might also be a symptom of a rare severe situation. It is important to talk to your doctor if you develop a rash. Your doctor will advise you how to deal with your symptoms or whether darunavir must be stopped.

Other severe side effects were diabetes (common) and inflammation of the pancreas (uncommon).

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

• diarrhoea.

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

• vomiting, nausea, abdominal pain or distension, dyspepsia, flatulence
• headache, tiredness, dizziness, drowsiness, numbness, tingling or pain in hands or feet, loss of strength, difficulty falling asleep.

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

• chest pain, changes in electrocardiogram, rapid heart beating
• decreased or abnormal skin sensibility, pins and needles, attention disturbance, loss of memory, problems with your balance
• difficulty breathing, cough, nosebleed, throat irritation
• inflammation of the stomach or mouth, heartburn, retching, dry mouth, discomfort of the abdomen, constipation, belching
• kidney failure, kidney stones, difficult discharge of urine, frequent or excessive passage of urine, sometimes at night
• urticaria, severe swelling of the skin and other tissues (most often the lips or the eyes), eczema, excessive sweating, night sweats, hair loss, acne, scaly skin, colouration of nails
• muscle pain, muscle cramps or weakness, pain in extremity, osteoporosis
• slowing down of the thyroid gland function. This can be seen in a blood test.
• high blood pressure, flushing
• red or dry eyes
• fever, swelling of lower limbs due to fluids, malaise, irritability, pain
• symptoms of infection, herpes simplex
• erectile dysfunction, enlargement of breasts
• sleeping problems, sleepiness, depression, anxiety, abnormal dreams, decrease in sexual drive

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

• a reaction called DRESS [severe rash, which may be accompanied by fever, fatigue, swelling of the face or lymph glands, increase of eosinophils (type of white blood cells), effects on liver, kidney or lung]
• heart attack, slow heart beating, palpitations
• visual disturbance
• chills, feeling abnormal
• a feeling of confusion or disorientation, altered mood, restlessness
• fainting, epileptic fits, changes or loss of taste
• mouth sores, vomiting blood, inflammation of the lips, dry lips, coated tongue
• running nose
• skin lesions, dry skin
• stiffness of muscles or joints, joint pain with or without inflammation
• changes in some values of your blood cells or chemistry. These can be seen in the results of blood and/or urine tests. Your doctor will explain these to you. Examples are: increase in some white blood cells
• darunavir crystals in the kidney causing kidney disease.

Some side effects are typical for anti-HIV medicines in the same family as darunavir. These are:

• muscle pain, tenderness or weakness. On rare occasions, these muscle disorders have been serious.

If you get any side effects talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at http://www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

The active substance is darunavir. Each tablet contains 400 mg of darunavir.

The other ingredients are:

Tablet core

Silicified microcrystalline cellulose, crospovidone B, hydroxypropyl cellulose, sodium chloride, silica colloidal anhydrous, magnesium stearate, polacrilin potassium.

Tablet coating

Polyvinyl alcohol partially hydrolysed, titanium dioxide (E171), macrogol/PEG 3350, talc, iron oxide yellow (E172), iron oxide red (E172).

Beige coloured, oval shaped (approximately 17 mm long and 8 mm wide), biconvex, film-coated tablets, debossed with “D” on one side and “400” on the other side.

Pack size:

30 film-coated tablets or 60 film-coated tablets (2 bottles containing 30 tablets each) in a HDPE bottle with child-resistant closure.

Darunavir is also available as 600 milligrams and 800 milligrams film-coated tablets.

Marketing Authorisation Holder

Manufacturer