Darunavir Tarbis 600 mg film-coated tablets EFG: detailed information

Patient Information Leaflet

Introduction

Patient Information Leaflet

Darunavir Tarbis 600 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 they are adverse effects not listed in this leaflet. See section 4.

Leaflet Contents

What Darunavir Tarbis is and what it is used for
What you need to know before taking Darunavir Tarbis
How to take Darunavir Tarbis
Possible side effects
How to store Darunavir Tarbis
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 improves and the risk of developing HIV-related illnesses decreases.

What is it used for?

Darunavir Tarbis is used to treat adults and children aged 3 years and older who weigh at least 15 kilograms and who have previously been treated with other antiretroviral medicines.

Darunavir Tarbis must be taken together with a low dose of ritonavir and other HIV medicines. Your doctor will advise you on the most appropriate combination of medicines for you.

2. What you need to know before starting to take Darunavir Tarbis

Do not take Darunavir Tarbis

if you are allergic to darunavir or to any of the other components of this medicine (listed in section 6) or to 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 required.

Do not combine Darunavir Tarbis with any of the following medicines

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

Medication	Purpose of the medication
Avanafil	treatment of erectile dysfunction
Astemizole or terfenadine	treatment of allergy symptoms
Triazolam and midazolam (oral)	help you sleep and/or relieve anxiety
Cisapride	treatment of stomach problems
Colchicine (if you have kidney and/or	treatment of gout or familial Mediterranean fever
liver problems)
Lurasidone, pimozide, quetiapine or sertindole	treatment of psychiatric disorders
Ergot alkaloids such as ergotamine, dihydroergotamine, ergometrine and methylergonovine	treatment of migraine-type headaches
Amiodarone, bepridil, dronedarone, ivabradine, quinidine, ranolazine	treatment of certain cardiac disorders, for example irregular heartbeats
Lovastatin, simvastatin and lomitapide	reduce cholesterol levels
Rifampicin	treatment of certain infections such as tuberculosis
The combination of medications lopinavir/ritonavir	this HIV medicine belongs to the same class as Darunavir Tarbis 600 mg film-coated tablets EFG
Elbasvir/grazoprevir	to treat hepatitis C infection
Alfuzosin	treatment of enlarged prostate
Sildenafil	treatment of high blood pressure in the pulmonary circulation
Dabigatran, ticagrelor	to help prevent platelet aggregation during treatment of patients with a history of heart attack
Naloxegol	to treat opioid-induced constipation
Dapoxetine	to treat premature ejaculation
Domperidone	to treat nausea and vomiting

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 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

Ensure you review the following points and inform your doctor if any apply to you.

Inform your doctor if you have had 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 prior 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 in which the immune system attacks healthy body tissue) may also occur after you start 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). Among the many risk factors for this condition are duration of combination antiretroviral therapy, use of corticosteroids, alcohol consumption, severe immunosuppression, and higher body mass index. Signs of osteonecrosis include pain, discomfort, and stiffness in the joints (especially the hips, knees, and shoulders) and difficulty moving. If you notice any of these symptoms, please see your doctor.

Elderly population

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

Darunavir Tarbis is not used in children under 3 years of age or weighing less than 15 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 anti-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 co-administered with ritonavir has not been studied with all protease inhibitors (PIs) and should 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 follow their instructions carefully 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 (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 disorders), as the therapeutic or adverse effects of these medicines may be increased.
Apixaban, edoxaban, rivaroxaban, warfarin (to reduce blood clotting), as 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 alternative methods are recommended.
Ethinylestradiol/drospirenone. Darunavir may increase the risk of elevated potassium levels due to drospirenone.
Atorvastatin, pravastatin, rosuvastatin (to lower blood cholesterol). There may be an increased risk of muscle damage. Your doctor will determine the most appropriate cholesterol-lowering treatment based on your individual circumstances.
Clarithromycin (antibiotic)
Ciclosporin, everolimus, tacrolimus, sirolimus (to suppress the immune system), as 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 for corticosteroid-related adverse effects.
Buprenorphine/naloxone (medicines for opioid dependence treatment)
Salmeterol (medicine for asthma treatment)
Artemether/lumefantrine (a combination of medicines 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, simeprevir (to treat hepatitis C infection)
Fentanyl, oxycodone, tramadol (to treat pain)
Fesoterodine, solifenacin (to treat 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 (injectable strong, short-acting analgesic used during surgical procedures)
Digoxin (for treatment of certain heart disorders)
Clarithromycin (antibiotic)
Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (to treat fungal infections). Voriconazole may only be administered after medical evaluation.
Rifabutin (for 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 narcotic dependence)
Carbamazepine, clonazepam (to prevent epileptic seizures or to treat certain types of neuropathic pain)
Colchicine (for treatment of gout or familial Mediterranean fever)
Bosentan (for treatment of high blood pressure in the pulmonary circulation)
Buspirone, chlordiazepoxide, diazepam, estazolam, flurazepam, midazolam administered by injection, zolpidem (sedatives)
Perphenazine, risperidone, thioridazine (to treat psychiatric conditions).

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 should not take darunavir with ritonavir unless specifically instructed by their doctor. Pregnant women or women who are breastfeeding should not take darunavir with cobicistat.

It is recommended that HIV-infected women do not breastfeed their infants, as there is a risk that the infant may become infected with HIV through breast milk, as well as due to the unknown effects of the medicine on infants.

Driving and using machines

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

3. How to take Darunavir Tarbis

Follow exactly the dosing instructions provided in this leaflet or those given by your doctor, pharmacist, or nurse. If in doubt, please consult your doctor, pharmacist, or nurse.

Do not stop taking darunavir or ritonavir without first consulting your doctor, even if you feel better.

Once treatment has started, the dose or dosing regimen must not be changed or treatment interrupted without consulting your doctor.

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

You will require a different darunavir dose that cannot be administered with these 600-milligram tablets. Other strengths of Darunavir Tarbis are available.

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

The dose is:

600 milligrams of darunavir (1 tablet of 600 milligrams of darunavir) together with 100 milligrams of ritonavir, taken twice daily; or
800 milligrams of darunavir (2 tablets of 400 milligrams of darunavir or 1 tablet of 800 milligrams of darunavir) together with 100 milligrams of ritonavir, taken once daily. The 400-milligram and 800-milligram darunavir tablets are only used to achieve the 800-milligram once-daily dosing regimen.

Please speak with your doctor to determine which dose is right for you.

Instructions for adults

Always take darunavir together with ritonavir. Darunavir does not work properly without ritonavir.
In the morning, take one 600-milligram darunavir tablet together with 100 milligrams of ritonavir.
In the evening, take one 600-milligram darunavir tablet together with 100 milligrams of ritonavir.
Take the tablets with food. Darunavir does not work properly without food. The type of food is not important.
Swallow the tablets with a drink, which may be water or milk.
Darunavir tablets have been developed in lower strengths and as an oral suspension for patients who have difficulty swallowing.

Dose for children aged 3 years and older, weighing at least 15 kilograms, who have not previously taken antiretroviral medicines (to be determined by your child's doctor)

The doctor will calculate the correct daily dose based on the child's body weight (see table below). This dose must not exceed the recommended adult dose of 800 milligrams of darunavir together with 100 milligrams of ritonavir once daily.

Your doctor will advise you on how many darunavir tablets and how much ritonavir (capsules, tablets, or solution) the child should take.

Weight	A dose of Darunavir is	A dose of Ritonavir is
between 15 and 30 kilograms	600 milligrams	100 milligrams
between 30 and 40 kilograms	675 milligrams	100 milligrams
more than 40 kilograms	800 milligrams	100 milligrams

Ritonavir oral solution: 80 milligrams per milliliter

Dosage for children from 3 years of age weighing at least 15 kilograms who have previously taken antiretroviral medications (your child's doctor will determine this)

The correct dose will be established by the doctor based on the child's weight (see table below). The doctor will determine whether a once-daily or twice-daily dosing regimen is appropriate for the child. This dose must not exceed the recommended adult dose, which is 600 milligrams of darunavir together with 100 milligrams of ritonavir twice daily, or 800 milligrams of darunavir together with 100 milligrams of ritonavir once daily. Your child's doctor will inform you how many darunavir tablets and how much ritonavir (in capsules, tablets, or solution) your child should take. Lower-strength tablets are available to achieve the appropriate dosing regimen. Darunavir oral suspension is also available. Your doctor will tell you whether darunavir tablets or oral suspension are suitable for your child.

Dosage twice daily

Weight	One dose is
between 15 and 30 kilograms	375 milligrams of darunavir + 50 milligrams of ritonavir twice daily
between 30 and 40 kilograms	450 milligrams of darunavir + 60 milligrams of ritonavir twice daily
over 40 kilograms*	600 milligrams of darunavir + 100 milligrams of ritonavir twice daily

The doctor will determine whether the 800-milligram once-daily dose can be used for children 12 years of age or older and weighing at least 40 kilograms. This dose cannot be administered with the 600-milligram tablets. Other darunavir presentations are available.

Once-daily dosing

Weight	A dose of darunavir is	A dose of ritonavir is
between 15 and 30 kilograms	600 milligrams	100 milligrams
between 30 and 40 kilograms	675 milligrams	100 milligrams
over 40 kilograms	800 milligrams	100 milligrams

Ritonavir oral solution: 80 milligrams per milliliter

Instructions for children

The child must always take darunavir together with ritonavir. Darunavir cannot work properly without ritonavir.
The child must take the correct dose of darunavir and ritonavir twice daily or once daily. If darunavir has been prescribed twice daily, the child should take one dose in the morning and one at night. Your child's doctor will determine the appropriate dosing schedule for your child.
The child must take darunavir with food. Darunavir cannot work properly without food. The type of food does not matter.
The child should swallow the tablets with a drink such as water or milk.
Darunavir is available in lower strengths and as an oral suspension for patients who have difficulty swallowing.

Removing the child-resistant cap

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

Push down on the plastic cap while turning it counterclockwise.
Unscrew and remove the cap.

If you take more Darunavir Tarbis than you should

Inform your doctor, pharmacist, or nurse immediately.

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

If you forget to take Darunavir Tarbis

If you realize within 6 hours, take the missed dose immediately. Always take it with ritonavir and with food. If you realize after 6 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 can make you feel better. Even if you feel well, 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 and 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 may cause adverse effects, although not everyone experiences them.

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

Cases of liver problems have been reported, which occasionally may be serious. 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 or whites of the eyes, darkening (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 frequent when used in combination with raltegravir), itching. Skin rash is usually mild to moderate. 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 the 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
Inflammation of the stomach or mouth, heartburn, retching, dry mouth, abdominal discomfort, constipation, belching
Renal 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 libido

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), liver, kidney, or lung damage]
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, swollen lips, 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 serious.

Reporting of adverse effects

If you experience any adverse effect, talk to 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, indicated as EXP. The expiry date refers to the last day of the month shown.

This medicine does not require any special storage conditions.

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

6. Contents of the pack and other information

Composition of Darunavir Tarbis 600 mg film-coated tablets EFG

The active substance is darunavir. Each tablet contains 600 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 polyvinyl alcohol – partially hydrolysed, macrogol, titanium dioxide (E171), talc (E553b) and yellow iron oxide (E172).

Appearance of Darunavir Tarbis 600 mg film-coated tablets EFG and contents of the pack

Oval, biconvex, film-coated yellow tablets, approximately 17.9 mm in length and 9.0 mm in width, engraved with a 'V' on one side and a '5' on the other.

Blister pack:

Aluminum blisters in cardboard box. Each box contains unit-dose 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 400 mg and 800 mg film-coated tablets.

Marketing Authorisation 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 authorised in EEA Member States under the following names:

The Netherlands: Darunavir Amarox 600 mg filmomhulde tabletten

Sweden: Darunavir Amarox 600 mg Filmdragerade tabletter

Germany: Darunavir Amarox 600 mg Filmtabletten

Spain: Darunavir Tarbis 600 mg comprimidos recubiertos con película EFG

Date of the most recent review 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 Health Products (AEMPS) (http://www.aemps.gob.es/)