Patient leaflet - Darunavir 800 mg film-coated tablets
1 What Darunavir is and what it is used for
What is Darunavir
Darunavir 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. This medicine 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.
What it is used for
The Darunavir 800mg tablet is used to treat adults and children (3 years of age and above and 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 cobicistat or ritonavir and other anti-HIV medicines. Your doctor will discuss with you which combination of medicines is best for you.
2 What you need to know before you take Darunavir
Do not take Darunavir
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.
Do not combine Darunavir with any of the following medicines
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 heartbeat
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).
Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking Darunavir.
Darunavir is not a cure for HIV infection. You can still pass on HIV when taking this medicine, although the risk is lowered by effective antiretroviral therapy. Discuss with your physician the precautions needed to avoid infecting other people.
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.
Tell your doctor about your situation BEFORE and DURING your treatment
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.
Elderly
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.
Children
The Darunavir 800mg tablet is not for use in children younger than 3 years of age or weighing less than 40 kilograms.
Other medicines and Darunavir
Tell your doctor or pharmacist if you are taking, have recently taken or might take 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, dose 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 dose 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 it is 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.
Darunavir with food and drink
See section 3 ‘How to take Darunavir.’
Pregnancy and breast-feeding
Tell your doctor immediately if you are pregnant or are 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.
Driving and using machines
Do not operate machines or drive if you feel dizzy after taking Darunavir.
Darunavir 800mg contains lactose
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
Darunavir 800mg contains propylene glycol (E1520)
This medicine contains 111.1 mg propylene glycol (E1520) in each film-coated tablet. If your baby is less than 4 weeks old, talk to your doctor or pharmacist before giving them this medicine, in particular if the baby is given other medicines that contain propylene glycol or alcohol.
3 How to take Darunavir
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.
Even if you feel better, do not stop taking Darunavir and cobicistat or ritonavir without talking to your doctor. After therapy has been initiated, the dose or dosage form must not be changed or therapy must not be stopped without instruction of the doctor.
Darunavir 800 milligram tablets are intended for once daily use only.
Dose for children 3 years of age and above with ritonavir, and 12 years of age and above with cobicistat, weighing more than 40 kilograms who have not taken antiretroviral medicines before (your child’s doctor will determine this)
The recommended 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 or 150 milligram of cobicistat once daily.
Dose for children 3 years of age and above with ritonavir, and 12 years of age and above with cobicistat, weighing more than 40 kilograms who have taken antiretroviral medicines before (your child’s doctor will determine this)
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 or 150 milligram of cobicistat once daily. OR
600 milligram Darunavir together with 100 milligram
ritonavir twice daily.
Please discuss with your child’s doctor which dose is right for your child.
Instructions for children 3 years of age and above with ritonavir, and 12 years of age and above with cobicistat, weighing more than 40 kilograms
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 or 150 milligram of cobicistat.
- 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 or cobicistat as recommended by your doctor.
Dose for adults who have not taken antiretroviral medicines before (your doctor will determine this)
The recommended 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 150 milligram of cobicistat or 100 milligram of ritonavir and with food. Darunavir cannot work properly without cobicistat or ritonavir and food. You must eat a meal or a snack within 30 minutes prior to taking your Darunavir and cobicistat or ritonavir. The type of food is not important. Even if you feel better, do not stop taking Darunavir and cobicistat or ritonavir without talking to your doctor.
Dose for adults who have taken antiretroviral medicines before (your doctor will determine this)
The dose is either:
800 milligram Darunavir (2 tablets containing 400
milligram of Darunavir or 1 tablet containing 800 milligram of Darunavir) together with 150 milligram cobicistat or 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.
Instructions for adults
Take two 400 milligram tablets or one 800 milligram tablet
at the same time, once a day, every day.
Take Darunavir always together with 150 milligram of
cobicistat or 100 milligram of ritonavir.
- Take Darunavir with food.
- Swallow the tablet with a drink such as water or milk.
Take your other HIV medicines used in combination with
Darunavir and cobicistat or ritonavir as recommended by your doctor.
Darunavir oral suspension may be available for use in
children, but can also be used in adults in some cases.
Removing the child resistant cap
2
1 The plastic bottle comes with a child
resistant cap and must be opened as
follows:
Push the plastic screw cap down
while turning it anti-clockwise.
- Remove the unscrewed cap.
If you take more Darunavir than you should
Contact your doctor, pharmacist or nurse immediately.
If you forget to take Darunavir
If you notice within 12 hours, you must take the tablets immediately. Always take with cobicistat or ritonavir and food. If you notice after 12 hours, then skip the missed dose and take the next doses as usual. Do not take a double dose to make up for a forgotten dose.
If you vomit after taking Darunavir and cobicistat or ritonavir
If you vomit within 4 hours of taking the medicine, another dose of Darunavir and cobicistat or 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 cobicistat or 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.
Do not stop taking Darunavir without talking to your doctor first
Anti-HIV medicines may make you feel better. Even when you feel better, do not stop taking Darunavir. Talk to your doctor first.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.
4 Possible side effects
During HIV therapy there may be an increase in weight and in levels of blood lipids and glucose. This is partly linked to restored health and life style, and in the case of blood lipids sometimes to the HIV medicines themselves. Your doctor will test for 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 serious side effects
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, 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 therefore 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).
Other side effects
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 distension,
dyspepsia, flatulence
headache, tiredness, 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 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 (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. E.g. 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.
Reporting of side effects
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 Website: 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.
5 How to store Darunavir
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and on the bottle after EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
6 Contents of the pack and other information
What Darunavir contains
The active substance is darunavir.
Each film-coated tablet of Darunavir 800mg contains
800 milligram of darunavir (as propylene glycolate).
The other ingredients are:
- Internal Phase: Lactose monohydrate, Microcrystalline cellulose, Povidone K30, Crospovidone, Silica, colloidal anhydrous
- External Phase: Magnesium stearate
- Coating (red): Polyvinyl alcohol, Macrogols, Iron oxide red (E172), Talc, Titanium dioxide (E171).
What Darunavir looks like and contents of the pack Darunavir 800mg film-coated tablets
Dark red oval shaped tablet, debossed with “800” on one side with dimensions: Length: 21.4±0.2 mm, Width: 10.8 ± 0.2 mm and Thickness: 8.0±0.4mm.
Darunavir tablets are supplied in a cardboard box containing a white, opaque high density polyethylene bottle with polypropylene (PP) child resistant screw cap and induction sealing and an instruction leaflet.
Pack size: One bottle of 30 tablets.
Marketing Authorisation Holder
Accord-UK Ltd
Whiddon Valley
Barnstaple
Devon
EX32 8NS
Manufacturer
Pharmathen International SA
Industrial Park Sapes
Rodopi Prefecture, Block no 5,
Rodopi 69300
Greece