Document Details

Generated Narrative: Bundle TEST PURPOSES ONLY - aptivus

Document Subject

Generated Narrative: MedicinalProductDefinition mpa8020a852a9fed523fd88e0aa8dbc86d

identifier: http://ema.europa.eu/identifier/EU/1/05/315/001

type: Medicinal Product

domain: Human use

status: active

legalStatusOfSupply: Medicinal product subject to medical prescription

name

productName: Aptivus 250 mg soft capsules

type: Full name

part

part: nan

type: Invented name part

part

part: nan

type: Scientific name part

part

part: nan

type: Strength part

part

part: nan

type: Pharmaceutical dose form part

Usages

-	Country	Jurisdiction	Language
*	EU	EU	en

Document Content

Generated Narrative: Composition composition-en-a8020a852a9fed523fd88e0aa8dbc86d

identifier: http://ema.europa.eu/identifier/EU/1/05/315/001

status: Final

type: Package Leaflet

category: Raw

date: 2022-02-16 13:28:17+0000

author: Organization ACME industry

title: TEST PURPOSES ONLY - aptivus

Attesters

If Aptivus has been prescribed for your child, please note that all information in this leaflet is addressed to your child (in this case please read your child instead of you ).

What is in this leaflet

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

Aptivus contains the active substance tipranavir. It belongs to a group of medicines called protease inhibitors and is used in the treatment of Human Immunodeficiency Virus (HIV) infection. It blocks an enzyme called protease that is involved in the reproduction of HIV. When the enzyme is blocked, the virus does not reproduce normally, slowing down the infection. You must take Aptivus together with:

low dose ritonavir (this helps Aptivus to reach a high enough level in your blood)

other HIV medicines. Your doctor, together with you, will decide which other medicines you should take. This will depend on, for example:

which other medicines you have already taken for HIV

which medicines your HIV is resistant to. If your HIV is resistant to some HIV medicines, this means that the medicine will not work so well, or will not work at all. Aptivus is specifically used for the treatment of HIV which is resistant to most other protease inhibitors. Before starting treatment, your doctor will have taken blood samples to test the resistance of your HIV. These tests will have confirmed that the HIV in your blood is resistant to most other protease inhibitors. Aptivus treatment is therefore appropriate for you. You should not use Aptivus if you have never received antiretroviral therapy or have other antiretroviral options available. Aptivus soft capsules are indicated for:

adolescents 12 years of age or older who have a Body Surface Area (BSA) of 1.3 m2 or weight 36 kg

adults

You must take Aptivus in combination with low dose ritonavir and other antiretroviral medicines. It is therefore important that you know about these medicines too. You should therefore carefully read the Package Leaflets of ritonavir and your other antiretroviral medicines. If you have any further questions about ritonavir or the other medicines you are prescribed, please ask your doctor or pharmacist. Do not take Aptivus

if you are allergic to tipranavir or any of the other ingredients of this medicine (listed in section 6)

if you have moderate to severe liver problems. Your doctor will take a blood sample to test how well your liver is working (your liver function). Depending on your liver function you may have to delay or stop Aptivus treatment

if you are currently taking products containing:

rifampicin (used to treat tuberculosis)

cisapride (used to treat stomach problems)

pimozide or sertindole (used to treat schizophrenia)

quetiapine (used to treat schizophrenia, bipolar disorder and major depressive disorder)

lurasidone (used to treat schizophrenia)

triazolam or oral midazolam (taken by mouth). These medicines are used to treat anxiety or sleep disorders

ergot derivatives (used to treat headaches)

astemizole or terfenadine (used to treat allergies or hay fever)

simvastatin or lovastatin (used to lower blood cholesterol)

amiodarone, bepridil, flecainide, propafenone or quinidine (used to treat heart disorders)

metoprolol (used to treat heart failure)

alfuzosin and sildenafil (when used to treat a rare blood vessel disorder characterized by increased pressure in the pulmonary artery)

colchicine (when used to treat gout flares in patients with kidney or liver disease). Do not take products containing St John s wort (a herbal remedy for depression). This may stop Aptivus from working properly. Warnings and precautions Talk to your doctor or pharmacist before taking Aptivus. Tell your doctor if you have:

type A or B haemophilia

diabetes

liver disease. If you have:

high liver function test results

hepatitis B or C infection you are at increased risk of severe and potentially fatal liver damage while taking Aptivus. Your doctor will monitor your liver function by blood tests before and during Aptivus treatment. If you have liver disease or hepatitis, your doctor will decide if you need additional testing. You should inform your doctor as soon as possible if you notice the signs or symptoms of hepatitis:

fever

malaise (feeling generally unwell)

nausea (upset stomach)

vomiting

abdominal pain

tiredness

jaundice (yellowing of the skin or the eyeballs) Rash: Mild to moderate rash, including:

hives

rash with flat or raised small red spots

sensitivity to the sun have been reported in approximately 1 in 10 patients receiving Aptivus. Some patients who developed rash also had:

joint pain or stiffness

throat tightness

generalized itching In some patients with advanced HIV infection (AIDS) 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. If you notice any symptoms of infection (for example fever, enlarged lymph nodes), please inform your doctor immediately. 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 experience fainting or a sensation of abnormal heart beats. Aptivus in combination with low dose ritonavir may cause changes in your heart rhythm and the electrical activity of your heart. These changes may be seen on an ECG (electrocardiogram). Bone 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. Children Aptivus soft capsules should not be used by children under 12 years of age. Older people If you are older than 65 years your doctor will exercise caution when prescribing Aptivus soft capsules to you and will closely monitor your therapy. Tipranavir has been used in limited number of patients 65 years or older. Other medicines and Aptivus Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription. This is very important. If you take other medicines at the same time as Aptivus and ritonavir, this can strengthen or weaken the effect of the medicines. These effects are called interactions, and can lead to serious side effects, or prevent proper control of other conditions you may have. Interactions with other HIV medicines:

etravirine belongs to a class of HIV medicines called non-nucleoside reverse transcriptase inhibitors (NNRTIs). Taking Aptivus with etravirine is not recommended.

abacavir and zidovudine. These belong to a class of HIV medicines called nucleoside reverse transcriptase inhibitors (NRTIs). Your doctor will only prescribe you abacavir and zidovudine if you are unable to take other NRTIs.

didanosine: If you are taking didanosine enteric coated tablets, you should take them at least two hours before or after Aptivus.

emtricitabine: If you are taking emtricitabine your kidney function should be checked before initiation of Aptivus.

rilpivirine: If you are taking rilpivirine, your doctor will monitor you closely.

Protease Inhibitors (PIs): Taking Aptivus may cause large decreases in the blood levels of other HIV protease inhibitors. For example the protease inhibitors amprenavir, atazanavir, lopinavir and saquinavir will be decreased. Taking Aptivus, with atazanavir, may cause the blood levels of Aptivus and ritonavir to increase a lot. Your doctor will carefully consider whether to treat you with combinations of Aptivus and protease inhibitors. Other medicines with which Aptivus may interact include:

oral contraceptives/hormone replacement therapy (HRT): If you are taking the contraceptive pill to prevent pregnancy you should use an additional or different type of contraception (e.g. barrier contraception like condoms). Generally, it is not recommended to take Aptivus, with ritonavir, together with oral contraceptives or hormone replacement therapy (HRT). You should check with your doctor if you do wish to continue taking oral contraceptives or HRT. If you use oral contraceptives or HRT you have an increased chance of developing a skin rash while taking Aptivus. If a rash occurs, it is usually mild to moderate. You should talk to your doctor as you may need to temporarily stop taking either Aptivus or your oral contraceptives or HRT

carbamazepine, phenobarbital and phenytoin (used to treat epilepsy). These may decrease the effectiveness of Aptivus.

sildenafil, vardenafil, tadalafil (medicines used to produce and maintain an erection). The effects of sildenafil and vardenafil are likely to be increased if you take them with Aptivus. You should not be prescribed tadalafil until you have been taking Aptivus for 7 days or more.

omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole (proton pump inhibitors used to reduce the gastric acid production)

metronidazole (used to treat infections)

disulfiram (used to treat alcohol dependence)

buprenorphine/naloxone (medicines used to treat severe pain)

cyclosporin, tacrolimus, sirolimus (used to prevent organ rejection (to suppress the immune system))

warfarin (used to treat and prevent thrombosis)

digoxin (used to treat heart arrhythmias and heart failure)

antifungal medications including fluconazole, itraconazole, ketoconazole or voriconazole The following medicines are not recommended:

fluticasone (used to treat asthma)

atorvastatin (used to lower blood cholesterol)

salmeterol (used to achieve long-term asthma control, bronchospasm prevention with COPD)

bosentan (used to treat pulmonary artery hypertension)

halofantrine or lumefantrine (used to treat malaria)

tolterodine (used to treat overactive bladder (with symptoms of urinary frequency, urgency, or urge incontinence))

cobicistat and products containing cobicistat (used to increase effectiveness of HIV medicines). Aptivus may lead to a loss of effectiveness of some medicines including:

methadone, meperidine (pethidine), used as morphine substitutes Your doctor may have to increase or decrease the dose of other medicines which you take together with Aptivus. Examples include:

rifabutin and clarithromycin (antibiotics)

theophylline (used to treat asthma)

desipramine, trazodone and bupropion (used to treat depression; bupropion is also used for smoking cessation)

midazolam (when given by injection); midazolam is a sedative used to treat anxiety and to help you sleep

rosuvastatin or pravastatin (used to lower blood cholesterol)

colchicine (used to treat gout flares with normal kidney and liver function)

raltegravir (used to treat HIV infection)

dolutegravir (used to treat HIV infection). If you take aluminium- and magnesium-based antacid (used to treat dyspepsia/gastrooesophageal reflux), the time interval between Aptivus and antacid should be at least two hours. Tell your doctor if you receive medicines such as blood-thinning agents, or if you are taking vitamin E. Your doctor may wish to consider certain precautionary measures in such circumstances. Pregnancy, breast-feeding and fertility If you are pregnant or think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. It is not known whether Aptivus may be used safely during pregnancy. 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. See also Section 2, under Oral contraceptives/hormone replacement therapy (HRT) . Aptivus contains very small amounts of alcohol (see Aptivus capsules contain ethanol). Driving and using machines Some of the side effects of Aptivus may affect your ability to drive or operate machinery (e.g. dizziness and sleepiness). If affected, you should not drive or operate machinery. Aptivus capsules contain ethanol, macrogolglycerol ricinoleate and sorbitol (E420) Aptivus contains 100 mg of alcohol (ethanol) in each capsule. The amount in 250 mg of this medicine (i.e. one capsule) is equivalent to less than 3 ml of beer, or than 1 ml of wine. The small amount of alcohol in this medicine will not have any noticeable effects. Aptivus also contains macrogolglycerol ricinoleate which may cause stomach upset and diarrhoea. This medicine contains 12.6 mg of sorbitol in each capsule.

Always take this medicine exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure. You must take Aptivus together with ritonavir. The recommended dose for an adult or an adolescent 12 years and above who have a Body Surface Area (BSA) of 1.3 m2 or weight 36 kg is:

500 mg (two 250 mg capsules) Aptivus together with

200 mg (two 100 mg capsules) ritonavir twice per day with food. Oral use. Aptivus capsules should be taken with food, swallowed whole and must not be opened or chewed. Always take this medicine in combination with other antiretroviral medicines. You should follow the instructions for these medicines within the supplied Package Leaflets. You should continue to take Aptivus for as long as your doctor tells you. If you take more Aptivus than you should Inform your doctor as soon as possible if you take more than the prescribed dose of Aptivus. If you forget to take Aptivus If you miss a dose of Aptivus or ritonavir by more than 5 hours, wait and then take the next dose of Aptivus and ritonavir at the regularly scheduled time. If you miss a dose of Aptivus and/or ritonavir by less than 5 hours, take your missed dose immediately. Then take your next dose of Aptivus and ritonavir at the regularly scheduled time. Do not take a double dose to make up for a forgotten dose. If you stop taking Aptivus It has been shown that taking all doses at the appropriate times:

greatly increases the effectiveness of your combination antiretroviral medicines

reduces the chances of your HIV becoming resistant to your antiretroviral medicines Therefore, it is important that you continue taking Aptivus correctly, as described above. Do NOT stop taking Aptivus unless your doctor instructs you to do so. If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

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. It may be difficult to tell the difference between:

side effects caused by Aptivus

side effects caused by the other medicines you are also taking

complications of HIV infection. For this reason it is very important that you tell your doctor about any changes in your health. Serious side effects associated with Aptivus:

Abnormal liver function

Hepatitis and fatty liver

Liver failure. This can lead to death

Increased blood levels of bilirubin (a breakdown product of haemoglobin) You should inform your doctor if you experience:

Loss of appetite

Nausea (upset stomach)

Vomiting and/or jaundice which may be symptoms of abnormal liver function

Bleeding

*Bleeding in the brain. This can lead to permanent disability or death, and has occurred in some patients treated with Aptivus in clinical trials. In the majority of these patients the bleeding may have had other causes. For example they had other medical conditions or were receiving other medicine that may have caused the bleeding. Possible side effects: Very common: may affect more than 1 in 10 people

Diarrhoea

Nausea (upset stomach) Common: may affect up to 1 in 10 people

Vomiting

Abdominal pain (tummy pain)

Flatulence (when you break wind more often)

Tiredness

Headache

Mild rashes e.g. with hives or with flat or raised small red spots

Increases in blood lipid (fat) levels

Dyspepsia Uncommon: may affect up to 1 in 100 people

Reduction in red and white blood cells

Reduction in blood platelets

Allergic (hypersensitivity) reactions

Decreased appetite

Diabetes

Increased blood sugar

Increased blood levels of cholesterol

Sleeplessness and other sleep disorders

Sleepiness

Dizziness

Numbness and/or tingling and/or pain in the feet or hands

Breathing difficulties

Heartburn

Inflammation of the pancreas

Skin inflammation

Itching

Muscle cramp

Muscle pain

Kidney disease

Flu like symptoms (feeling unwell)

Fever

Weight loss

Increased blood levels of the pancreas enzyme amylase

Increases in liver enzyme activity

Hepatitis with liver cell damage due to influence of a toxin Rare: may affect up to 1 in 1,000 people

Liver failure (including fatal outcome)

Hepatitis

Fatty liver

Increased blood levels of bilirubin (a breakdown product of haemoglobin)

Dehydration (when your body does not have enough water)

Thinning of the face

Bleeding in the brain* (see above)

Increased blood levels of the pancreas enzyme lipase Further information on possible side effects related to combination antiretroviral treatment:

Bleeding

Increased bleeding. If you have haemophilia type A and B, you may experience increased bleeding. This may be in the skin or joints. If you suffer increased bleeding you should see your doctor immediately. Muscle disorders There have been reports of muscle pain, tenderness or weakness. These occur particularly when Aptivus or other protease inhibitors are taken together with nucleoside analogues. Rarely these muscle disorders have been serious, involving breakdown of muscle tissue (rhabdomyolysis). Additional side effects in children and adolescents The most common side effects were generally similar to those described in adults. Vomiting, rash and fever were observed more frequently in children than in adults. Reporting of side effects If you get any side effects, please talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.

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 bottle after EXP. The expiry date refers to the last day of that month. Store in a refrigerator (2 C to 8 C). Once the bottle is opened the contents must be used within days (stored below 25 C). You should write the date of opening the bottle on the label and/or outer carton. 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.

What Aptivus contains

The active substance is tipranavir. Each capsule contains 250 mg tipranavir.

The other ingredients are macrogolglycerol ricinoleate, ethanol (alcohol), mono/diglycerides of caprylic/capric acid, propylene glycol, purified water, trometamol and propyl gallate. The capsule shell contains gelatin, red iron oxide, propylene glycol, purified water, sorbitol special-glycerin blend (d-sorbitol, 1,4 sorbitan, mannitol and glycerin) and titanium dioxide. The black printing ink contains propylene glycol, black iron oxide, polyvinyl acetate phthalate, macrogol and ammonium hydroxide. What Aptivus looks like and contents of the pack Aptivus soft capsules are pink coloured, oblong soft gelatin capsules with a black print imprint of TPV 250 . Each Aptivus capsule contains 250 mg of the active substance tipranavir. Aptivus is supplied in bottles containing 120 capsules. Marketing Authorisation Holder Boehringer Ingelheim International GmbH Binger Strasse 55216 Ingelheim am Rhein Germany Manufacturer Boehringer Ingelheim Pharma GmbH & Co. KG Binger Strasse 55216 Ingelheim am Rhein Germany or Boehringer Ingelheim France 100-104 avenue de France 75013 Paris France For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder: Belgi /Belgique/Belgien Boehringer Ingelheim SComm T l/Tel: +32 2 773 33 Lietuva Boehringer Ingelheim RCV GmbH & Co KG Lietuvos filialas Tel.: +370 5 2595 -

: +359 2 958 79 Luxembourg/Luxemburg Boehringer Ingelheim SComm T l/Tel: +32 2 773 33 esk republika Boehringer Ingelheim spol. s r.o. Tel: +420 234 655 Magyarorsz g Boehringer Ingelheim RCV GmbH & Co KG Magyarorsz gi Fi ktelepe Tel.: +36 1 299 89 Danmark Boehringer Ingelheim Danmark A/S Tlf: +45 39 15 88 Malta Boehringer Ingelheim Ireland Ltd. Tel: +353 1 295 9Deutschland Boehringer Ingelheim Pharma GmbH & Co. KG Tel: +49 (0) 800 77 90 Nederland Boehringer Ingelheim b.v. Tel: +31 (0) 800 22 55 Eesti Boehringer Ingelheim RCV GmbH & Co KG Eesti filiaal Tel: +372 612 8Norge Boehringer Ingelheim Norway KS Tlf: +47 66 76 13
Boehringer Ingelheim . . T : +30 2 10 89 06 sterreich Boehringer Ingelheim RCV GmbH & Co KG Tel: +43 1 80 105-7Espa a Boehringer Ingelheim Espa a, S.A. Tel: +34 93 404 51 Polska Boehringer Ingelheim Sp.zo.o. Tel.: +48 22 699 0 France Boehringer Ingelheim France S.A.S. T l: +33 3 26 50 45 Portugal Boehringer Ingelheim Portugal, Lda. Tel: +351 21 313 53 Hrvatska Boehringer Ingelheim Zagreb d.o.o. Tel: +385 1 2444 Rom nia Boehringer Ingelheim RCV GmbH & Co KG Viena - Sucursala Bucuresti Tel: +40 21 302 2Ireland Boehringer Ingelheim Ireland Ltd. Tel: +353 1 295 9Slovenija Boehringer Ingelheim RCV GmbH & Co KG, Podru nica Ljubljana Tel: +386 1 586 40 sland Vistor hf. S mi: +354 535 7Slovensk republika Boehringer Ingelheim RCV GmbH & Co KG, organiza n zlo ka Tel: +421 2 5810 1Italia Boehringer Ingelheim Italia S.p.A. Tel: +39 02 5355 1 Suomi/Finland Boehringer Ingelheim Finland Ky Puh/Tel: +358 10 3102
Boehringer Ingelheim . . T : +30 2 10 89 06 Sverige Boehringer Ingelheim AB Tel: +46 8 721 21 Latvija Boehringer Ingelheim RCV GmbH & Co KG Latvijas fili le Tel: +371 67 240 United Kingdom (Northern Ireland) Boehringer Ingelheim Ireland Ltd. Tel: + 353 1 295 9This leaflet was last approved in {MM/YYYY} Detailed information on this medicine is available on the European Medicines Agency web site: