Document Details

Generated Narrative: Bundle TEST PURPOSES ONLY - stocrin

Document Subject

Generated Narrative: MedicinalProductDefinition mpa192389a9068e61de77d4f090e108cd6

identifier: http://ema.europa.eu/identifier/EU/1/99/111/005

type: Medicinal Product

domain: Human use

status: active

legalStatusOfSupply: Medicinal product subject to medical prescription

name

productName: STOCRIN 30 mg/mL oral solution

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-a192389a9068e61de77d4f090e108cd6

identifier: http://ema.europa.eu/identifier/EU/1/99/111/005

status: Final

type: Package Leaflet

category: Raw

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

author: Organization ACME industry

title: TEST PURPOSES ONLY - stocrin

Attesters

What is in this leaflet

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

Stocrin, which contains the active substance efavirenz, belongs to a class of antiretroviral medicines called non-nucleoside reverse transcriptase inhibitors (NNRTIs). It is an antiretroviral medicine that fights human immunodeficiency virus (HIV) infection by reducing the amount of the virus in blood. It is used by adults, adolescents and children 3 years of age and older. Your doctor has prescribed Stocrin for you because you have HIV infection. Stocrin taken in combination with other antiretroviral medicines reduces the amount of the virus in the blood. This will strengthen your immune system and reduce the risk of developing illnesses linked to HIV infection.

Do not take Stocrin

if you are allergic to efavirenz or any of the other ingredients of this medicine (listed in section 6). Contact your doctor or pharmacist for advice.

if you have severe liver disease.

if you have a heart condition, such as changes in the rhythm or rate of the heart beat, a slow heart beat, or severe heart disease.

if any member of your family (parents, grandparents, brothers or sisters) has died suddenly due to a heart problem or was born with heart problems.

if your doctor has told you that you have high or low levels of electrolytes such as potassium or magnesium in your blood.

if you are currently taking any of the following medicines (see also Other medicines and Stocrin ):

• astemizole or terfenadine (used to treat allergy symptoms)
• bepridil (used to treat heart disease)
• cisapride (used to treat heartburn)
• ergot alkaloids (for example, ergotamine, dihydroergotamine, ergonovine, and methylergonovine) (used to treat migraine and cluster headaches)
• midazolam or triazolam (used to help you sleep)
• pimozide, imipramine, amitriptyline or clomipramine (used to treat certain mental conditions)
• St. John's wort (Hypericum perforatum) (a herbal remedy used for depression and anxiety)
• flecainide, metoprolol (used to treat irregular heart beat)
• certain antibiotics (macrolides, fluoroquinolones, imidazole)
• triazole antifungal agents
• certain antimalarial treatments
• methadone (used to treat opiate addiction)
• elbasvir/grazoprevir If you are taking any of these medicines, tell your doctor immediately. Taking these medicines with Stocrin could create the potential for serious and/or life-threatening side-effects or stop Stocrin from working properly. Warnings and precautions Talk to you doctor before taking Stocrin

Stocrin must be taken with other medicines that act against the HIV virus. If Stocrin is started because your current treatment has not prevented the virus from multiplying, another medicine you have not taken before must be started at the same time.

This medicine is not a cure for HIV infection and you may continue to develop infections or other illnesses associated with HIV disease.

You must remain under the care of your doctor while taking Stocrin.

Tell your doctor:

• if you have a history of mental illness, including depression, or of substance or alcohol abuse. Tell your doctor immediately if you feel depressed, have suicidal thoughts or have strange thoughts (see section 4, Possible side effects).
• if you have a history of convulsions (fits or seizures) or if you are being treated with anticonvulsant therapy such as carbamazepine, phenobarbital and phenytoin. If you are taking any of these medicines, your doctor may need to check the level of anticonvulsant medicine in your blood to ensure that it is not affected while taking Stocrin. Your doctor may give you a different anticonvulsant.
• if you have a history of liver disease, including active chronic hepatitis. Patients with chronic hepatitis B or C and treated with combination antiretroviral agents have a higher risk for severe and potentially life-threatening liver problems. Your doctor may conduct blood tests in order to check how well your liver is working or may switch you to another medicine. If you have severe liver disease, do not take Stocrin (see section 2, Do not take Stocrin).
• if you have a heart disorder, such as abnormal electrical signal called prolongation of the QT interval.

Once you start taking Stocrin, look out for:

• signs of dizziness, difficulty sleeping, drowsiness, difficulty concentrating or abnormal dreaming. These side effects may start in the first 1 or 2 days of treatment and usually go away after the first 2 to 4 weeks.
• signs of confusion, slow thoughts and physical movement, and delusions (false beliefs) or hallucinations (seeing or hearing things that others do not see or hear). These side effects may occur months to years after beginning Stocrin therapy. If you notice any symptoms, please inform your doctor.
• any signs of skin rash. If you see any signs of a severe rash with blistering or fever, stop taking Stocrin and tell your doctor at once. If you had a rash while taking another NNRTI, you may be at a higher risk of getting a rash with Stocrin.
• any signs of inflammation or infection. 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, please tell 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.
• 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 and adolescents Stocrin is not recommended for children under the age of 3 years or weighing less than 13 kg because it has not been adequately studied in these patients. Other medicines and Stocrin You must not take Stocrin with certain medicines. These are listed under Do not take Stocrin, at the start of Section 2. They include some common medicines and a herbal remedy (St. John s wort) which can cause serious interactions. Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Stocrin may interact with other medicines, including herbal preparations such as Ginkgo biloba extracts. As a result, the amounts of Stocrin or other medicines in your blood may be affected. This may stop the medicines from working properly, or may make any side effects worse. In some cases, your doctor may need to adjust your dose or check your blood levels. It is important to tell your doctor or pharmacist if you are taking any of the following:

• Other medicines used for HIV infection:

• protease inhibitors: darunavir, indinavir, lopinavir/ritonavir, ritonavir, ritonavir boosted atazanavir, saquinavir or fosamprenavir/saquinavir. Your doctor may consider giving you an alternative medicine or changing the dose of the protease inhibitors.
• maraviroc
• the combination tablet containing efavirenz, emtricitabine and tenofovir should not be taken with Stocrin unless recommended by your doctor since it contains efavirenz, the active ingredient of Stocrin.

• Medicines used to treat infection with the hepatitis C virus: boceprevir, telaprevir, simeprevir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir and sofosbuvir/velpatasvir/voxilaprevir.
• Medicines used to treat bacterial infections, including tuberculosis and AIDS-related mycobacterium avium complex: clarithromycin, rifabutin, rifampicin. Your doctor may consider changing your dose or giving you an alternative antibiotic. In addition, your doctor may prescribe a higher dose of Stocrin.
• Medicines used to treat fungal infections (antifungals):

• voriconazole. Stocrin may reduce the amount of voriconazole in your blood and voriconazole may increase the amount of Stocrin in your blood. If you take these two medicines together, the dose of voriconazole must be increased and the dose of efavirenz must be reduced. You must check with your doctor first.
• itraconazole. Stocrin may reduce the amount of itraconazole in your blood.
• posaconazole. Stocrin may reduce the amount of posaconazole in your blood.

• Medicines used to treat malaria:

• artemether/lumefantrine: Stocrin may reduce the amount of artemether/lumefantrine in your blood.
• atovaquone/proguanil: Stocrin may reduce the amount of atovaquone/proguanil in your blood.

• Medicines used to treat convulsions/seizures (anticonvulsants): carbamazepine, phenytoin, phenobarbital. Stocrin can reduce or increase the amount of anticonvulsant in your blood. Carbamazepine may make Stocrin less likely to work. Your doctor may need to consider giving you a different anticonvulsant.
• Medicines used to lower blood fats (also called statins): atorvastatin, pravastatin, simvastatin. Stocrin can reduce the amount of statins in your blood. Your doctor will check your cholesterol levels and will consider changing the dose of your statin, if needed.
• Methadone (a medicine used to treat opiate addiction): your doctor may recommend an alternative treatment.
• Sertraline (a medicine used to treat depression): your doctor may need to change your dose of sertraline.
• Bupropion (a medicine used to treat depression or to help you stop smoking): your doctor may need to change your dose of bupropion.
• Diltiazem or similar medicines (called calcium channel blockers which are medicines typically used for high blood pressure or heart problems): when you start taking Stocrin, your doctor may need to adjust your dose of the calcium channel blocker.
• Immunosuppressants such as cyclosporine, sirolimus, or tacrolimus (medicines used to prevent organ transplant rejection): when you start or stop taking Stocrin, your doctor will closely monitor your plasma levels of the immunosuppressant and may need to adjust its dose.
• Hormonal contraceptive, such as birth control pills, an injected contraceptive (for example, Depo-Provera), or a contraceptive implant (for example, Implanon): you must also use a reliable barrier method of contraception (see Pregnancy, breast-feeding and fertility). Stocrin may make hormonal contraceptives less likely to work. Pregnancies have occurred in women taking Stocrin while using a contraceptive implant, although it has not been established that the Stocrin therapy caused the contraceptive to fail.
• Warfarin or acenocoumarol (medicines used to reduce clotting of the blood): your doctor may need to adjust your dose of warfarin or acenocoumarol.
• Ginkgo biloba extracts (herbal preparation).
• Medicines that impact heart rhythm:

• Medicines used to treat heart rhythm problems such as flecainide or metoprolol.
• Medicines used to treat depression such as imipramine, amitriptyline or clomipramine.
• Antibiotics, including the following types: macrolides, fluoroquinolones or imidazole.

• Metamizole (a medicine used to treat pain and fever).
• Praziquantel (a medicine used to treat parasitic worm infections). Pregnancy and breast-feeding Women should not get pregnant during treatment with Stocrin and for 12 weeks thereafter. Your doctor may require you to take a pregnancy test to ensure you are not pregnant before starting treatment with Stocrin. If you could get pregnant while receiving Stocrin, you need to use a reliable form of barrier contraception (for example, a condom) with other methods of contraception including oral (pill) or other hormonal contraceptives (for example, implants, injection). Efavirenz may remain in your blood for a time after therapy is stopped. Therefore, you should continue to use contraceptive measures, as above, for 12 weeks after you stop taking Stocrin. Tell your doctor immediately if you are pregnant or intend to become pregnant. If you are pregnant, you should take Stocrin only if you and your doctor decide it is clearly needed. Ask your doctor or pharmacist for advice before taking any medicine. Serious birth defects have been seen in unborn animals and in the babies of women treated with efavirenz or a combination medicine containing efavirenz, emtricitabine and tenofovir during pregnancy. If you have taken Stocrin or the combination tablet containing efavirenz, emtricitabine, and tenofovir during your pregnancy, your doctor may request regular blood tests and other diagnostic tests to monitor the development of your child. Breast-feeding is not recommended in women living with HIV because HIV infection can be passed on to the baby in breast milk. If you are breast-feeding, or thinking about breast-feeding, you should discuss it with your doctor as soon as possible. Driving and using machines Stocrin contains efavirenz and may cause dizziness, impaired concentration, and drowsiness. If you are affected, do not drive and do not use any tools or machines. Stocrin 30 mg/mL oral solution contains benzoic acid This medicine contains 1 mg of benzoic acid (E210) per mL. Stocrin 30 mg/mL oral solution contains benzyl alcohol This medicine contains benzyl alcohol (E1519) up to 0.816 mg per mL. Benzyl alcohol may cause allergic reactions.

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure. Your doctor will give you instructions for proper dosing.

The dose for adults is 24 mL once daily.

The dose for Stocrin may need to be increased or decreased if you are also taking certain medicines (see Other medicines and Stocrin).

Stocrin oral solution may be taken with or without food. The dose of Stocrin oral solution in mg is not the same as for Stocrin film-coated tablets.

Stocrin must be taken every day.

Stocrin should never be used alone to treat HIV. Stocrin must always be taken in combination with other anti-HIV medicines. The dose of Stocrin oral solution must be measured using the oral syringe supplied in the carton.

On first use, the bottle adapter must be fitted into the neck of the bottle. To do this, remove the child-resistant cap and the foil seal. The bottle adapter, which is already fixed to the nozzle of the syringe, can then be fitted into the neck of the bottle and pressed firmly down.

Separate the syringe from the adapter. The adapter should now fit closely to the neck so that the cap can be replaced without removing it.

With the bottle upright, fit the tip of the syringe into the bottle adapter.

Turn the bottle upside down with the syringe still in place. Hold the bottle and the syringe firmly in one hand and with the other hand pull back the plunger slightly beyond the mark for the dose required. If air bubbles appear in the syringe, keep the bottle upside down and slowly push in the plunger and pull it back again. Repeat until there are no bubbles in the syringe.

To measure the dose accurately, keep the bottle upside down and push the plunger in slowly until the top of the black ring (the edge nearest the syringe tip) lines up with the dose. Turn the bottle the right way up and remove the syringe. Wipe the adapter and replace the cap tightly over it.

Before giving the dose of the oral solution make sure that the patient is sitting or standing upright. Put the tip of the syringe just inside the mouth, pointing it towards the cheek. Press the plunger slowly to allow time for the medicine to be swallowed. Rapid squirting into the mouth may cause choking. After use, soak the syringe in warm soapy water for at least a minute. Draw the warm soapy water into the syringe until full and then empty completely. Repeat at least three times. Remove the plunger rod from the barrel and thoroughly rinse both parts with warm running water. If parts of the syringe are not clean, repeat the cleaning instructions. Allow the parts to dry completely prior to reassembly. Do not put the syringe in a dishwasher. Use in children and adolescents

The dose for children weighing 40 kg or more is 24 mL once daily.

The dose for children weighing less than 40 kg is calculated by body weight and is taken once daily as shown below: Body Weight Stocrin oral solution (30 mg/mL) kg Dose (mL) 3 - < 5 years 5 years or more 13 to < 9 15 to < 20 to < 25 to < 32.5 32.5 to < -

If you take more Stocrin than you should If you take too much Stocrin contact your doctor or nearest emergency department for advice. Keep the medicine container with you so that you can easily describe what you have taken. If you forget to take Stocrin Try not to miss a dose. If you do miss a dose, take the next dose as soon as possible, but do not take a double dose to make up for a forgotten dose. If you need help in planning the best times to take your medicine, ask your doctor or pharmacist. If you stop taking Stocrin When your Stocrin supply starts to run low, get more from your doctor or pharmacist. This is very important because the amount of virus may start to increase if the medicine is stopped for even a short time. The virus may then become harder to treat. If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

Like all medicines, this medicine can cause side effects, although not everybody gets them. When treating HIV infection, it is not always possible to tell whether some of the unwanted effects are caused by Stocrin or by other medicines that you are taking at the same time, or by the HIV disease itself. 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. The most notable unwanted effects reported with Stocrin in combination with other anti-HIV medicines are skin rash and nervous system symptoms. You should consult your doctor if you have a rash, since some rashes may be serious; however, most cases of rash disappear without any change to your treatment with Stocrin. Rash was more common in children than in adults treated with Stocrin. The nervous system symptoms tend to occur when treatment is first started, but generally decrease in the first few weeks. In one study, nervous system symptoms often occurred during the first 1-3 hours after taking a dose. If you are affected your doctor may suggest that you take Stocrin at bedtime. Some patients have more serious symptoms that may affect mood or the ability to think clearly. Some patients have actually committed suicide. These problems tend to occur more often in those who have a history of mental illness. In addition, some nervous system symptoms (e.g., confusion, slow thoughts and physical movement, and delusions [false beliefs] or hallucinations [seeing or hearing things that others do not see or hear]) may occur months to years after beginning Stocrin therapy. Always notify your doctor immediately if you have these symptoms or any side effects while taking Stocrin. Diarrhoea occurred in children who took Stocrin oral solution and nelfinavir in combination with other antiretroviral medicines. Tell your doctor if you notice any of the following side effects: Very common (affects more than 1 user in 10)

• skin rash Common (affects 1 to 10 users in 100)

• abnormal dreams, difficulty concentrating, dizziness, headache, difficulty sleeping, drowsiness, problems with coordination or balance

• stomach pain, diarrhoea, feeling sick (nausea), vomiting

• itching

• tiredness

• feeling anxious, feeling depressed Tests may show:

• increased liver enzymes in the blood

• increased triglycerides (fatty acids) in the blood Uncommon (affects 1 to 10 users in 1,000)

• nervousness, forgetfulness, confusion, fitting (seizures), abnormal thoughts

• blurred vision

• a feeling of spinning or tilting (vertigo)

• pain in the abdomen (stomach) caused by inflammation of the pancreas

• allergic reaction (hypersensitivity) that may cause severe skin reactions (erythema multiforme, Stevens-Johnson syndrome)

• yellow skin or eyes, itching, or pain in the abdomen (stomach) caused by inflammation of the liver

• breast enlargement in males

• angry behaviour, mood being affected, seeing or hearing things that are not really there (hallucinations), mania (mental condition characterised by episodes of overactivity, elation or irritability), paranoia, suicidal thoughts, catatonia (condition in which the patient is rendered motionless and speechless for a period)

• whistling, ringing or other persistent noise in the ears

• tremor (shaking)

• flushing Tests may show:

• increased cholesterol in the blood Rare (affects 1 to 10 users in 10,000)

• itchy rash caused by a reaction to sunlight

• liver failure, in some cases leading to death or liver transplant, has occurred with efavirenz. Most cases occurred in patients who already had liver disease, but there have been a few reports in patients without any existing liver disease.

• unexplained feelings of distress not associated with hallucinations, but it may be difficult to think clearly or sensibly

• suicide 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 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 and on the carton after EXP. The expiry date refers to the last day of that month. The bottle of Stocrin oral solution should be used within one month after first opening. 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 Stocrin contains

Each mL of Stocrin oral solution contains 30 mg of the active substance efavirenz.

The other ingredients are: medium chain triglycerides, benzoic acid (E210) and strawberry/mint flavour [containing benzyl alcohol (E1519) and propylene glycol (E1520)]. What Stocrin looks like and contents of the pack Stocrin 30 mg/mL oral solution is supplied in bottles of 180 mL. An oral syringe with a push-in bottle-neck adapter is included in the carton. Marketing Authorisation Holder Manufacturer Merck Sharp & Dohme B.V. Merck Sharp & Dohme B.V. Waarderweg Waarderweg 2031 BN Haarlem Postbus The Netherlands 2003 PC Haarlem The Netherlands For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder: Belgique/Belgi /Belgien MSD Belgium T l/Tel: +32(0)27766dpoc_belux@merck.com Lietuva UAB Merck Sharp & Dohme Tel.: +370 5 278 02 msd_lietuva@merck.com

.: +359 2 819 3info-msdbg@merck.com Luxembourg/Luxemburg MSD Belgium T l/Tel: +32(0)27766dpoc_belux@merck.com esk republika Merck Sharp & Dohme s.r.o. Tel.: +420 233 010 dpoc_czechslovak @merck.com Magyarorsz g MSD Pharma Hungary Kft. Tel.: +361 888 53 hungary_msd@merck.com Danmark MSD Danmark ApS Tlf: +45 44 82 40 dkmail@merck.com Malta Merck Sharp & Dohme Cyprus Limited Tel: 8007 4433 (+356 99917558) malta_info@merck.com Deutschland MSD Sharp & Dohme GmbH Tel: 0800 673 673 673 (+49 (0) 89 4561 0) e-mail@msd.de Nederland Merck Sharp & Dohme B.V. Tel: 0800 9999000 (+31 23 5153153) medicalinfo.nl@merck.com Eesti Merck Sharp & Dohme O Tel.: +372 6144 msdeesti@merck.com Norge MSD (Norge) AS Tlf: +47 32 20 73 msdnorge@msd.no E MSD . . . . : + 30-210 98 97 dpoc_greece@merck.com sterreich Merck Sharp & Dohme Ges.m.b.H. Tel: +43 (0) 1 26 dpoc_austria@merck.com Espa a Merck Sharp & Dohme de Espa a, S.A. Tel: +34 91 321 06 msd_info@merck.com Polska MSD Polska Sp. z o.o. Tel.: +48 22 549 51 msdpolska@merck.com France MSD France T l: + 33 (0) 1 80 46 40 Portugal Merck Sharp & Dohme, Lda Tel: +351 21 4465inform_pt@merck.com Hrvatska Merck Sharp & Dohme d.o.o. Tel: + 385 1 6611 croatia_info@merck.com Rom nia Merck Sharp & Dohme Romania S.R.L. Tel: + 4021 529 29 msdromania@merck.com Ireland Merck Sharp & Dohme Ireland (Human Health) Limited Tel: +353 (0)1 2998medinfo_ireland@merck.com Slovenija Merck Sharp & Dohme, inovativna zdravila d.o.o. Tel: + 386 1 5204msd_slovenia@merck.com sland Vistor hf. S mi: +354 535 7Slovensk republika Merck Sharp & Dohme, s. r. o. Tel.: +421 2 58282dpoc_czechslovak@merck.com talia MSD Italia S.r.l. Tel: 800 23 99 89 (+39 06 361911) medicalinformation.it@msd.com Suomi/Finland MSD Finland Oy Puh/Tel: +358 (0) 9 804info@msd.fi

Merck Sharp & Dohme Cyprus Limited : 80000 673 (+357 22866700) cyprus_info@merck.com Sverige Merck Sharp & Dohme (Sweden) AB Tel: +46 (0)77 5700medicinskinfo@merck.com Latvija SIA Merck Sharp & Dohme Latvija Tel: +371 67364 msd_lv@merck.com United Kingdom (Northern Ireland) Merck Sharp & Dohme Ireland (Human Health) Limited Tel: +353 (0)1 2998medinfoNI@msd.com This leaflet was last revised in Other sources of information Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu. Package leaflet: Information for the user Stocrin 600 mg film-coated tablets efavirenz 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.