Package leaflet: Information for the user

REZOLSTA 800 mg/150 mg - film-coated tablets

darunavir/cobicistat

Read all of this leaflet carefully before you start 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 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.

What is in this leaflet

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

1. What REZOLSTA is and what it is used for

What is REZOLSTA?
REZOLSTA contains the active substances darunavir and cobicistat.
Darunavir belongs to a group of HIV medicines called ‘protease inhibitors’ which work by reducing
the amount of HIV in your body to a very low level. It is given with cobicistat, which increases the
amount of darunavir in your blood.
Treatment with REZOLSTA will improve your immune system (your body’s natural defences) and
reduce the risk of developing illnesses linked to HIV infection, but REZOLSTA is not a cure for HIV
infection.

What it is used for?

REZOLSTA is used to treat adults and adolescents aged 12 years and older who weigh at least
40 kilograms and who are infected by HIV (see How to take REZOLSTA).

REZOLSTA must be taken in combination with other 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 REZOLSTA

Do not take REZOLSTA

- if you are allergic to darunavir, cobicistat or any of the other ingredients of this medicine (listed
in section 6).
- 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.

Do not combine REZOLSTA 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

Alfuzosin to treat enlarged prostate
Amiodarone, bepridil, dronedarone, ivabradine, to treat certain heart disorders e.g. abnormal
quinidine, ranolazine heart beat
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 Carbamazepine, phenobarbital and phenytoin to prevent seizures
Astemizole or terfenadine to treat allergy symptoms
Colchicine (if you have kidney/liver problems) to treat gout or familial Mediterranean fever
The combination product lopinavir/ritonavir anti-HIV medicine
Rifampicin to treat some infections such as tuberculosis
Lurasidone, pimozide, quetiapine or sertindole to treat psychiatric conditions
Ergot alkaloids like ergotamine, to treat migraine headaches
dihydroergotamine, ergometrine and
methylergonovine
Cisapride to treat some stomach conditions
St John’s wort (Hypericum perforatum) a herbal product used for depression
Elbasvir/grazoprevir to treat hepatitis C infection
Lovastatin, simvastatin, and lomitapide to lower cholesterol levels
Triazolam or oral (taken by mouth) midazolam to help you sleep and/or relieve anxiety
Sildenafil to treat a heart and lung disorder called
pulmonary arterial hypertension. There are other
uses for sildenafil. Please see section ‘Other
medicines and REZOLSTA’.
Avanafil to treat erectile dysfunction
Dabigatran, 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

Warnings and precautions

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

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 REZOLSTA may still develop infections or other illnesses associated with HIV
infection. You must keep in regular contact with your doctor.

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

REZOLSTA 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 REZOLSTA.

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 REZOLSTA.
- Tell your doctor if you have had problems with your kidneys. Your doctor will carefully
consider whether to treat you with REZOLSTA.
- Tell your doctor if you have diabetes. REZOLSTA 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 unusual
infections due to a weakened immune system (opportunistic infection), signs and symptoms of
inflammation from previous infections may occur soon after HIV treatment is started. It is

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 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
so you can be given the necessary treatment.
- Tell your doctor if you have haemophilia. REZOLSTA 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). This may be more likely with long-term
HIV treatment, more severe damage to the immune system, overweight, or the use of alcohol or
other medicines called corticosteroids. 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.

Children and adolescents

REZOLSTA is not for use in children younger than 12 years, or weighing less than
40 kilograms.

Other medicines and REZOLSTA

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 REZOLSTA. These are mentioned above
under the heading ‘Do not combine REZOLSTA with any of the following medicines:’

REZOLSTA must not be used with another antiviral medicine that contains a booster or another
antiviral that requires boosting. 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 REZOLSTA might be reduced if you take any of the following products. Tell your
doctor if you take:
- Bosentan (to treat heart disease)
- Dexamethasone (injectable) (corticosteroid)
- Efavirenz, etravirine, nevirapine (to treat HIV infection)
- Rifapentine, rifabutin (to treat bacterial infections).

The effects of other medicines might be influenced if you take REZOLSTA. Tell your doctor if you
take:
- Amlodipine, carvedilol, diltiazem, disopyramide, felodipine, flecainide, lidocaine, metoprolol,
mexiletine, nicardipine, nifedipine, propafenone, timolol, verapamil (for heart disease) as the
therapeutic effect or side effects of these medicines may be increased.
- Apixaban, edoxaban, rivaroxaban, warfarin (to reduce clotting of the blood) as their therapeutic
effect or side effects may be altered; your doctor may have to check your blood.
- Clonazepam (to prevent seizures).
- Oestrogen-based hormonal contraceptives and hormone replacement therapy. REZOLSTA
might reduce its effectiveness. When used for birth control, alternative methods of
non-hormonal contraception are recommended.
- Ethinylestradiol/drospirenone. REZOLSTA might increase the risk for elevated potassium
levels by drospirenone.
- Atorvastatin, fluvastatin, pitavastatin, 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.
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- Ciclosporin, everolimus, tacrolimus, sirolimus (for dampening down your immune system) as
the therapeutic effect or side effects of these medicines might be increased. Your doctor might
want to do some additional tests.
- Corticosteroids including betamethasone, budesonide, fluticasone, mometasone, prednisone,
triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel
diseases, inflammatory conditions of the eyes, joints and muscles and other inflammatory
conditions. 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, methadone (medicines to treat opioid dependence)
- Salmeterol (medicine to treat asthma)
- Artemether/lumefantrine (a combination medicine to treat malaria)
- Dasatinib, irinotecan, nilotinib, vinblastine, vincristine (medicines to treat cancer)
- Perphenazine, risperidone, thioridazine (psychiatric medicines)
- Clorazepate, diazepam, estazolam, flurazepam (medicines to treat sleeping disorders or anxiety)
- 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)
- Fesoterodine, solifenacin (to treat urologic disorders).

The dosage of other medicines might need to be changed since either their own or REZOLSTA’s
therapeutic effect or side effects may be influenced when combined.
Tell your doctor if you take:
- Alfentanil (injectable, strong and short-acting, painkiller that is used for surgical procedures)
- Digoxin (to treat certain heart disorders)
- Clarithromycin (antibiotic)
- Clotrimazole, fluconazole, itraconazole, isavuconazole, posaconazole (against fungal
infections). Voriconazole should only be taken after medical evaluation.
- Rifabutin (against bacterial infections)
- Tadalafil, sildenafil, vardenafil (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)
- Colchicine (to treat gout or familial Mediterranean fever). If you have renal and/or hepatic
impairment see section ‘Do not combine REZOLSTA with any of the following medicines’.
- Bosentan (to treat high blood pressure in the pulmonary circulation)
- Buspirone, clorazepate, diazepam, estazolam, flurazepam, zolpidem, midazolam when used as
injection (medicines to treat trouble with sleeping and/or anxiety)
- Metformin (to treat type 2 diabetes)
- Fentanyl, oxycodone, tramadol (to treat pain).

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

Pregnancy and breast-feeding

Tell your doctor immediately if you are pregnant, planning to become pregnant or if you are
breast-feeding. Pregnant or breast-feeding mothers should not take REZOLSTA. It is recommended
that HIV infected women must not breast-feed their infants because of both the possibility of your
baby becoming infected with HIV through your breast milk and because of the unknown effects of the
medicine on your baby.

Driving and using machines

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

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3. How to take REZOLSTA

Always use this medicine exactly as your doctor, pharmacist or nurse has told you. Check with your
doctor, pharmacist or nurse if you are not sure.

You must take REZOLSTA every day and always with food. REZOLSTA cannot work properly
without food. You must eat a meal or a snack within 30 minutes prior to taking your REZOLSTA. The
type of food is not important.

- Swallow the tablet whole with a drink such as water or milk. If you have difficulty swallowing
REZOLSTA, tell your doctor. The tablet may be split using a tablet-cutter. After splitting the
tablet, the entire dose (both halves) should then be taken right away with a drink such as water
or milk.

- Take your other HIV medicines used in combination with REZOLSTA as recommended by
your doctor.

Removing the child resistant cap

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.

If you take more REZOLSTA than you should

Contact your doctor, pharmacist or nurse immediately.

If you forget to take REZOLSTA

If you notice within 12 hours, you must take the tablet immediately. Always take with 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 after taking REZOLSTA

If you vomit within 4 hours of taking the medicine, another dose of REZOLSTA 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 REZOLSTA 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 REZOLSTA without talking to your doctor first

After therapy has started, it must not be stopped without instruction of the doctor.

Anti-HIV medicines may make you feel better. Even when you feel better, do not stop taking
REZOLSTA. 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.

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Tell your doctor if you develop any of the following side effects
Liver problems that may occasionally be severe have been reported. Your doctor should do blood tests
before you start REZOLSTA. 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.

A common side effect of REZOLSTA is 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 REZOLSTA must be stopped.

Other severe side effects, seen up to 1 patient in 10, were diabetes. Inflammation of the pancreas
(pancreatitis) has been reported in up to 1 patient in 100.

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

- headache
- diarrhoea, nausea.

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

- allergic reactions such as itching
- decreased appetite
- abnormal dreams
- vomiting, pain or swelling of the belly, indigestion, flatulence
- muscle pain
- tiredness
- abnormal blood test results such as some tests for your liver or kidney. Your doctor will explain
these to you.
- weakness.

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

- symptoms of infection or of autoimmune disorders (immune reconstitution inflammatory
syndrome)
- osteonecrosis (death of bone tissue caused by loss of blood supply to the bone)
- enlargement of breasts
- abnormal blood test results such as some tests for your pancreas, high level of sugar, abnormal
levels of ‘lipids’ (fats). Your doctor will explain these to you.
- allergic reactions such as nettle rash (urticaria), severe swelling of the skin and other tissues
(most often the lips or the eyes)
- severe rash with blisters and peeling skin, particularly around the mouth, nose, eyes and
genitals.

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].

Side effects with unknown frequency: a rash may become severe or potentially life-threatening:
- rash with blisters and peeling skin over much of the body
- red rash covered with small pus-filled bumps that can spread over the body, sometimes with a
fever.

Some side effects are typical for HIV medicines in the same family as REZOLSTA. These are:
- muscle pain, tenderness or weakness. On rare occasions, these muscle disorders have been
serious.
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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 at:
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 REZOLSTA

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.

Do not use this medicine after 6 weeks of first opening the bottle.

REZOLSTA 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 any medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What REZOLSTA contains

- The active substances are darunavir and cobicistat. Each tablet contains 800 mg of darunavir (as
ethanolate) and 150 mg cobicistat.
- The other ingredients are hypromellose, silicified microcrystalline cellulose, colloidal silicon
dioxide, crospovidone and magnesium stearate. The film-coating contains polyvinyl
alcohol - partially hydrolyzed, titanium dioxide, polyethylene glycol (macrogol), talc, iron oxide
red, and iron oxide black.
- This medicine contains less than 1 mmol sodium (23 mg) per dosage unit, that is to say
essentially ‘sodium-free’.

What REZOLSTA looks like and contents of the pack

Film-coated, pink, oval shaped tablet, mentioning TG on one side, 800 on the other side.
30 tablets in a plastic bottle.

Marketing Authorisation Holder

Janssen-Cilag International NV, Turnhoutseweg 30, 2340 Beerse, Belgium

Manufacturer
Janssen-Cilag SpA, Via C. Janssen, Borgo San Michele, 04100 Latina, Italy

For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder:

United Kingdom
Janssen-Cilag Ltd.
Tel: +44 1 494 567 444

This leaflet was last revised in March 2020.

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Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu.