Darunavir Tarbis 400 mg film-coated tablets EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Darunavir Tarbis 400 mg film-coated tablets EFG

Read the entire leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist or nurse, even if these adverse effects are not listed in this leaflet. See section 4.

Leaflet contents

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

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

What is Darunavir Tarbis?

Darunavir Tarbis contains the active substance darunavir. Darunavir Tarbis 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 Tarbis reduces the amount of HIV in your body. As a result, your immune system will improve and the risk of developing HIV-related illnesses will decrease.

What is it used for?

The Darunavir Tarbis 400 milligram tablet is used to treat adults and children (from 3 years of age, weighing at least 40 kilograms) infected with HIV and who

• have not previously used antiretroviral medicines, or
• in certain patients who have previously used antiretroviral medicines (this will be determined by your doctor).

This medicine must be taken together with a low dose of cobicistat or ritonavir and other anti-HIV medicines. Your doctor will advise you on the most appropriate combination of medicines for you.

2. What you need to know before taking Darunavir Tarbis

Do not take Darunavir Tarbis

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

Do not combine Darunavir Tarbis with any of the following medicines

If you are taking any of these drugs, consult your doctor to switch to another medicine.

Do not combine this medicine with products containing St. John's wort (Hypericum perforatum).

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting treatment with Darunavir Tarbis.

Darunavir does not cure HIV infection. While taking this medicine, you may still transmit HIV to others, although effective antiviral treatment reduces this risk. Please consult your doctor about the necessary precautions to avoid infecting others.

People taking darunavir may develop other infections or other conditions associated with HIV infection. You should maintain regular contact with your doctor.

People taking darunavir may develop a skin rash. It is uncommon for the rash to be severe or potentially life-threatening. Please consult your doctor if you develop a rash.

Patients taking darunavir and raltegravir (for HIV infection) may experience rashes (usually mild or moderate) more frequently than patients taking either medicine separately.

Inform your doctor about your condition BEFORE and DURING treatment

Please ensure you check the following points and inform your doctor if any apply to you.

• Inform your doctor if you have any liver disease, including hepatitis B or C infection. Your doctor will assess the severity of liver disease before deciding whether you can take this medicine.
• Inform your doctor if you have diabetes. Darunavir may cause an increase in blood sugar levels.
• Inform your doctor immediately if you notice any signs of infection (e.g., swollen lymph nodes and fever). In some patients with advanced HIV infection and a history of opportunistic infections, signs and symptoms of inflammation due to previous infections may appear shortly after starting anti-HIV treatment. These symptoms are believed to result from improved immune response, enabling the body to fight infections that were previously present without apparent symptoms.
• In addition to opportunistic infections, autoimmune disorders (a condition occurring when the immune system attacks healthy body tissue) may also occur after you have started taking medicines for your HIV infection. Autoimmune disorders may appear many months after starting treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and moving upward toward the trunk, palpitations, tremors, or hyperactivity, inform your doctor immediately to receive appropriate treatment.
• Inform your doctor if you have haemophilia. Darunavir may increase the risk of bleeding.
• Inform your doctor if you are allergic to sulfonamides (e.g., used to treat certain infections).
• Inform your doctor if you notice any bone or muscle problems. Some patients receiving combination antiretroviral therapy may develop a bone disorder called osteonecrosis (bone tissue death caused by reduced blood supply to the bone). Many risk factors contribute to this condition, including duration of combination antiretroviral therapy, corticosteroid use, alcohol consumption, severe immunosuppression, and higher body mass index. Signs of osteonecrosis include joint pain, discomfort, and stiffness (especially in the hips, knees, and shoulders) and difficulty moving. If you notice any of these symptoms, please see your doctor.
• Inform your doctor if you are elderly. Darunavir has only been used in a limited number of patients aged 65 years or older. If you belong to this age group, please discuss with your doctor whether you can use this medicine.

Children and adolescents

The Darunavir Tarbis 400 mg tablet must not be used in children under 3 years of age or weighing less than 40 kilograms.

Taking Darunavir Tarbis with other medicines

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

Some medicines must not be combined with this medicine. The list can be found in the section “Do not combine Darunavir Tarbis with any of the following medicines:”

In most cases, darunavir can be combined with HIV medicines belonging to other classes [e.g., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists, and FIs (fusion inhibitors)]. Darunavir has not been tested with cobicistat or ritonavir in combination with all protease inhibitors (PIs) and must not be used with other HIV protease inhibitors. In some cases, the dose of other medicines may need to be adjusted. Therefore, if you are taking other anti-HIV medicines, always inform your doctor and carefully follow their instructions regarding which medicines can be combined.

The following products may reduce the effectiveness of darunavir. Inform your doctor if you are taking:

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

Darunavir may also affect the effects of other medicines. Inform your doctor if you are taking:

• Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (for heart conditions), because the therapeutic or adverse effects of these medicines may be increased.
• Apixaban, edoxaban, rivaroxaban, warfarin (to reduce blood clotting), because the therapeutic or adverse effects of these medicines may be altered; your doctor may perform blood tests.
• Hormonal contraceptives based on oestrogens and hormone replacement therapies. Darunavir may reduce their effectiveness. For contraception, non-hormonal contraceptive methods are recommended.
• Ethinylestradiol/drospirenone. Darunavir may increase the risk of elevated potassium levels caused by drospirenone.
• Atorvastatin, pravastatin, rosuvastatin (to reduce blood cholesterol). There may be an increased risk of muscle damage. Your doctor will determine the most suitable cholesterol-lowering treatment based on your individual circumstances.
• Clarithromycin (an antibiotic)
• Cyclosporine, everolimus, tacrolimus, sirolimus (to suppress the immune system), because the therapeutic or adverse effects of these medicines may be increased. Your doctor may perform additional tests.
• Corticosteroids, including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel diseases, inflammatory eye, joint, and muscle conditions, and other inflammatory disorders. If alternatives cannot be used, their use should only occur after clinical evaluation and with close monitoring by your doctor to assess corticosteroid-related adverse effects.
• Buprenorphine/naloxone (medicines for opioid dependence treatment)
• Salmeterol (a medicine for asthma treatment)
• Artemether/lumefantrine (a combination of medicines for treating malaria)
• Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (for cancer treatment)
• Sildenafil, tadalafil, vardenafil (for erectile dysfunction or for treating a heart and lung disorder called pulmonary arterial hypertension)
• Glecaprevir/pibrentasvir, simeprevir (for treating hepatitis C infection)
• Fentanyl, oxycodone, tramadol (for pain treatment)
• Fesoterodine, solifenacin (for treating urological disorders).

In certain cases, the dose of some medicines may need to be adjusted, as their therapeutic or adverse effects—or those of darunavir—may be affected when combined.

Inform your doctor if you are taking:

• Alfentanil (a short-acting, potent injectable analgesic used in surgical procedures)
• Digoxin (for treating certain heart conditions)
• Clarithromycin (an antibiotic)
• Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (for treating fungal infections). Voriconazole may only be administered after medical evaluation.
• Rifabutin (for bacterial infections)
• Sildenafil, vardenafil, tadalafil (for erectile dysfunction or pulmonary hypertension)
• Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (for treating depression and anxiety)
• Maraviroc (for treating HIV infection)
• Methadone (for treating narcotic dependence)
• Carbamazepine, clonazepam (to prevent epileptic seizures or to treat certain types of neuropathic pain)
• Colchicine (for treating gout or familial Mediterranean fever)
• Bosentan (for treating pulmonary hypertension)
• Buspirone, chlordiazepoxide, diazepam, estazolam, flurazepam, midazolam when administered by injection, zolpidem (sedative agents)
• Perphenazine, risperidone, thioridazine (for treating psychiatric conditions)
• Metformin (for treating type 2 diabetes).

This is not a complete list of medicines. Inform your doctor about all medicines you are taking.

Taking Darunavir Tarbis with food and drinks

See section 3 “How to take Darunavir Tarbis”

Pregnancy and breastfeeding

Inform your doctor immediately if you are pregnant, planning to become pregnant, or breastfeeding. Pregnant or breastfeeding women must not take darunavir with ritonavir unless specifically instructed by their doctor. Pregnant or breastfeeding women must not take darunavir with cobicistat.

It is recommended that HIV-infected women do not breastfeed their infants, as there is a risk of transmitting HIV through breast milk, as well as potential unknown effects of the medicine on infants.

Driving and using machines

Do not operate tools, machinery, or drive if you experience dizziness after taking this medicine.

3. How to take Darunavir Tarbis

Follow exactly the instructions for using this medicine provided in this leaflet or those given by your doctor, pharmacist, or nurse. If in doubt, ask your doctor, pharmacist, or nurse. Do not stop taking darunavir, cobicistat, or ritonavir without first consulting your doctor, even if you feel better.

After treatment has started, the dose or dosing schedule must not be changed or treatment interrupted without your doctor's instructions.

The Darunavir Tarbis 400 milligram tablets are used only to achieve the 800 milligram once-daily dosage regimen.

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

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

You must take darunavir every day and always in combination with 150 milligrams of cobicistat or 100 milligrams of ritonavir and with food. Darunavir does not work properly without cobicistat or ritonavir and food. You must eat a meal 30 minutes before taking the darunavir tablets together with cobicistat or ritonavir. The type of food is not important. Do not interrupt treatment with darunavir or with cobicistat or ritonavir without first consulting your doctor, even if you feel better.

Instructions for adults

• Take two 400 milligram tablets at the same time, once daily, every day.
• Take darunavir always together with 150 milligrams of cobicistat or 100 milligrams of ritonavir.
• Take the tablets with food.
• Swallow the tablets with a drink, which can be water or milk.
• Take the other HIV medicines used in combination with darunavir and cobicistat or ritonavir as recommended by your doctor.
• The oral suspension of darunavir 100 milligrams per milliliter has been developed for use in children, but in some cases may also be used in adults.

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

The dose is:

• 800 milligrams of darunavir (2 tablets containing 400 milligrams of darunavir or 1 tablet containing 800 milligrams of darunavir) together with 150 milligrams of cobicistat or 100 milligrams of ritonavir once daily.

Or

• 600 milligrams of darunavir (1 tablet containing 600 milligrams of darunavir) together with 100 milligrams of ritonavir twice daily.

Please speak with your doctor about which dose is correct for you.

Dosage for children aged 3 years and older, weighing more than 40 kilograms, who have not previously taken antiretroviral medicines (to be determined by your child's doctor)

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

Dosage for children aged 3 years and older, weighing more than 40 kilograms, who have previously taken antiretroviral medicines (to be determined by your child's doctor)

The dose is:

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

Or

• 600 milligrams of darunavir (1 tablet containing 600 milligrams of darunavir) together with 100 milligrams of ritonavir twice daily.

Please speak with your doctor about which dose is correct for you.

Instructions for children aged 3 years and older, weighing more than 40 kilograms

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

Removing the child-resistant cap

The plastic bottle has a child-resistant safety closure and opens as follows:

• Push the plastic cap down while turning it counterclockwise.
• Remove the cap by unscrewing it.

If you take more Darunavir Tarbis than you should

Inform your doctor, pharmacist, or nurse immediately.

In case of overdose or accidental ingestion, consult your doctor or pharmacist or call the Toxicology Information Service at telephone number: 91 562 04 20, indicating the medicine and the amount ingested.

If you forget to take Darunavir Tarbis

If you remember within 12 hours, take the tablets immediately. Always take the dose with cobicistat or ritonavir and with food. If you remember after 12 hours, skip that dose and take the next one as usual. Do not take a double dose to make up for a missed dose.

Do not stop taking Darunavir Tarbis without first talking to your doctor

HIV medicines may make you feel better. Even if you feel better, do not stop taking this medicine. Consult your doctor first.

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

4. Possible adverse effects

During HIV treatment, there may be an increase in weight and in blood glucose and lipid levels. This may be partly related to improved health, lifestyle, and, in the case of blood lipids, sometimes to the HIV medicines themselves. Your doctor will monitor these changes.

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

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

Cases of liver problems, occasionally serious, have been reported. Your doctor will perform a blood test before you start treatment with darunavir. If you have a chronic infection caused by hepatitis B or C, your doctor will frequently check your blood tests, as you have a higher risk of developing liver problems. Talk to your doctor about the signs and symptoms of liver problems. These may include yellowing of the skin and whites of the eyes, dark (tea-colored) urine, pale stools (bowel movements), nausea, vomiting, loss of appetite, or pain, tenderness, or discomfort on the right side under your ribs.

Skin rash (more common when used in combination with raltegravir), itching. Skin rash is usually mild to moderate. However, a skin rash may also be a symptom of a rare but serious condition. Therefore, it is important to speak with your doctor if you develop a rash. Your doctor will advise you on how to manage symptoms or whether darunavir should be discontinued.

Other serious adverse effects included diabetes (frequent) and inflammation of the pancreas (uncommon). Very common adverse effects (may affect more than 1 in 10 patients):

• diarrhea

Common adverse effects (may affect up to 1 in 10 patients):

• vomiting, nausea, abdominal pain or bloating, upper abdominal pain (dyspepsia), flatulence
• headache, fatigue, dizziness, somnolence, numbness, tingling, or pain in the hands or feet, loss of strength, difficulty falling asleep

Uncommon adverse effects (may affect up to 1 in 100 patients):

• chest pain, changes in electrocardiogram, rapid heartbeat
• decreased or abnormal skin sensitivity, tingling, attention disorder, memory loss, difficulty maintaining balance
• difficulty breathing, cough, nosebleed, throat irritation
• stomach or mouth inflammation, heartburn, retching, 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 (especially lips or eyes), eczema, excessive sweating, night sweats, alopecia, acne, scaly skin, nail discoloration
• muscle pain, muscle cramps or weakness, limb pain, osteoporosis
• reduced thyroid gland function. This can be seen in a blood test.
• hypertension (increased blood pressure), flushing
• red or dry eyes
• fever, swelling of the lower limbs due to fluid retention, malaise, irritability, pain
• symptoms of infection, herpes simplex
• erectile dysfunction, breast enlargement
• difficulty falling asleep, somnolence, depression, anxiety, abnormal dreams, decreased sex drive

Rare adverse effects (may affect up to 1 in 1,000 patients):

• a reaction called DRESS [severe rash, which may be accompanied by fever, fatigue, facial swelling or swollen lymph nodes, increased eosinophils (a type of white blood cell), damage to the liver, kidney, or lung]
• myocardial infarction, slow heartbeat, palpitations
• visual disturbance
• chills, unusual sensation
• a feeling of confusion or disorientation, altered mood, agitation
• fainting, epileptic seizure, changes or loss of taste
• mouth ulcers, vomiting blood, lip inflammation, dry lips, coated tongue
• nasal discharge
• skin lesions, dry skin
• muscle or joint stiffness, joint pain with or without inflammation
• changes in certain blood cell or biochemical values. These changes can be seen in blood and/or urine tests. Your doctor will explain them to you. For example: increase in certain white blood cells.

Some adverse effects are typical of HIV medicines belonging to the same class as darunavir. These include:

• muscle pain, tenderness, or weakness. In rare cases, these muscle disorders may be severe.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet.

You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Darunavir Tarbis

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 on the bottle, after EXP. The expiry date refers to the last day of the month indicated.

This medicine does not require any special storage conditions.

Medicines must not be disposed of via wastewater or household waste. Dispose of unused medicines and their containers at the SIGRE Point at your pharmacy. If you are unsure, ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the container and other information

Composition of Darunavir Tarbis 400 mg film-coated tablets EFG

• The active substance is darunavir. Each tablet contains 400 mg of darunavir.
• The other components are colloidal anhydrous silica (E551), silicified microcrystalline cellulose (E460), crospovidone (E1202) and magnesium stearate (E470b). The tablet coating contains partially hydrolysed polyvinyl alcohol, macrogol, titanium dioxide (E171), talc (E553b) and yellow iron oxide (E172).

Appearance of Darunavir Tarbis 400 mg film-coated tablets EFG and contents of the pack

Yellow, oval, biconvex film-coated tablets, approximately 15.7 mm long and 7.9 mm wide, marked with a 'V' on one side and a '4' on the other.

Blister pack:

Aluminum blisters in cardboard box. Each box contains unit doses of film-coated tablets in blisters of 30 x 1, 60 x 1 or 90 x 1 tablets.

Plastic bottle:

White opaque high-density polypropylene (HDPE) bottle in a cardboard box. The bottle contains a container with silica gel desiccant. This container must be left inside the bottle to protect the tablets and must not be swallowed.

Each box contains 60 film-coated tablets.

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

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Tarbis Farma S.L.

Gran Vía Carlos III, 94

08028 Barcelona

Spain

Manufacturer

Pharmadox Healthcare Ltd.

KW20A Kordin Industrial Park

PLA 3000 Paola

Malta

Amarox Pharma B.V.

Rouboslaan 32

2252 TR Voorschoten

The Netherlands

This medicinal product is authorized in EEA Member States under the following names:

The Netherlands: Darunavir Amarox 400 mg filmomhulde tabletten

Sweden: Darunavir Amarox 400 mg Filmdragerade tabletter

Germany: Darunavir Amarox 400 mg Filmtabletten

Spain: Darunavir Tarbis 400 mg comprimidos recubiertos con película EFG

Date of the most recent revision of this leaflet: March 2020

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/)