Prospect: Information for the Patient

Rimstar Film-Coated Tablets

rifampicina/isoniazida/pirazinamida/etambutol hydrochloride

Read this prospect carefully before starting to take this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed to you alone, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospect. See section 4.

Rimstar belongs to a group of medications known as antitubercular medications.

It is a fixed combination of four highly effective antitubercular medications. It is used to treat infections caused by mycobacteria. These mycobacteria cause tuberculosis.

Rimstar is used in the initial treatment of tuberculosis.

Do not take Rimstar if:

• You are allergic (hypersensitive) to rifampicin, isoniazid, pyrazinamide, ethambutol hydrochloride, or any of the other components of this medication (listed in section 6),
• You have acute liver problems or have had a previous liver problem caused by medication use,
• You have been confirmed to have a condition called porphyria,
• You have acute gouty arthritis,
• You have severe kidney problems,
• You are currently taking any of the following medications:
• • Voriconazole,
  • Protease inhibitors except ritonavir when prescribed the full dose or 600 mg twice a day.

Do not take Rimstar if you are in any of the above circumstances.

If you are unsure, consult your doctor or pharmacist.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Rimstar.

Inform your doctor if you have any of the following conditions before taking this medication:

• Liver problems and chronic liver disease,
• Kidney problems,
• Gout,
• Diabetes mellitus,
• Epilepsy,
• Peripheral nerve inflammation or optic nerve inflammation,
• Eye defects,
• Chronic alcoholism,
• Malnutrition.

You should not take Rimstar if your body weight is less than 30 kg.

You should not interrupt treatment with Rimstar without consulting your doctor.

You should use additional contraceptive methods apart from the pill while taking Rimstar.

Other medications and Rimstar

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication, including over-the-counter medications.

Inform your doctor if you are taking any of the following medications:

You should not take Rimstar with any of the following medications:

• Voriconazole,
• Protease inhibitors except ritonavir, if prescribed a full dose or 600 mg twice a day.

• You should not take Rimstar with any of the following medications: Simvastatin,
• Ritonavir,
• Oral contraceptives. You should use additional contraceptive methods while taking Rimstar.

Inform your doctor if you are taking any of the following medications:

• Medications for irregular heartbeatsuch as class Ia antiarrhythmics (quinidine, disopyramide), propafenone, mexiletine, tocainide, lorcainide,
• Medications for the heart or blood pressure:Calcium channel blockers (such as diltiazem, nifedipine, verapamil, nimodipine, isradipine, nicardipine, nisoldipine, amlodipine), digoxin, digoxin, beta-blockers (such as bisoprolol, metoprolol, propranolol, carvedilol), losartan, imidapril, enalapril,
• Diureticssuch as eplerenone,
• Immunosuppressive medicationssuch as cyclosporine, tacrolimus, sirolimus, leflunomide, azathioprine,
• Corticosteroids,
• Antifungal medications(such as fluconazole, itraconazole, ketoconazole, voriconazole, terbinafine),
• Antibioticssuch as clarithromycin, telithromycin, dapsone, doxycycline, fluoroquinolones, chloramphenicol, linezolid,
• Malaria medications: atovaquone, quinine,
• Mood medicationssuch as haloperidol, clozapine, aripiprazole, tricyclic antidepressants (such as amitriptyline, nortriptyline),
• Medications to prevent blood clotssuch as oral anticoagulants, warfarin,
• Hormonal treatmentssuch as antiestrogens (such as gestrinone, tamoxifen, toremifene), estrogens, and progestogens administered as hormone replacement therapy or contraceptives, thyroid hormones (levothyroxine),
• Pain medicationssuch as morphine, etoricoxib, rofecoxib,
• Medications for HIVsuch as saquinavir, indinavir, efavirenz, amprenavir, nelfinavir, atazanavir, lopinavir, zidovudine, nevirapine, stavudine,
• Medications for epilepsysuch as tiagabine, carbamazepine, phenytoin, ethosuximide,
• Medications for sleep disorderssuch as diazepam, benzodiazepines, buspirone, zopiclone, zolpidem, zaleplon, hexobarbital,
• Medications for asthmasuch as theophylline,
• Medications for diabetessuch as repaglinide and nateglinide or oral antidiabetic agents of the sulfonilurea type,
• Acid p-aminosalicylic(a medication for tuberculosis and inflammatory bowel disease),
• Methadone(a medication for heroin addiction),
• Medications for stomach problemssuch as cimetidine,
• Medications for hyperlipidemiasuch as clofibrate, fluvastatin, simvastatin,
• Medications for nauseasuch as tropisetron, ondansetron,
• Medications for anesthesiasuch as volatile halogenated anesthetics,
• Cancer medicationssuch as imatinib, gefitinib, irinotecan,
• Fexofenadine(a medication for hay fever),
• Praziquantel(an antihelmintic medication),
• Oral typhoid vaccine.

If you are currently taking any of these medications, ask your doctor if you can change your medication while taking Rimstar. Often, there are other products you can take instead.

If you need to take a medication for indigestion, such as an antacid, take the tablets at least one hour before taking the antacids.

While taking this medication, the following methods of exploration or the results should be interpreted with caution:

• Radiographic examination of the gallbladder with contrast medium,
• Microbiological determination of plasma concentrations of folic acid,
• Microbiological determination of plasma concentrations of cyanocobalamin (vitamin B12).

Taking Rimstar with food and drinks

Do not drink alcohol while taking this medication.

You should not take foods with high histamine and tyramine content (such as aged cheese, cured meat, some fish such as tuna, salmon, and mackerel, wine, and beer). Taking these foods with Rimstar can cause headache, sweating, flushing, hunger, irregular or forceful heartbeat, dizziness, or fainting (due to low blood pressure) or redness. These foods should be avoided while taking this medication.

Your doctor may provide more information.

Take this medication at least one hour before eating.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, or intend to become pregnant, consult your doctor or pharmacist before using this medication.

Your doctor will determine if it is possible to continue treatment with this medication. If you take Rimstar during pregnancy, your doctor should give you vitamin B6 supplements during pregnancy and vitamin K supplements during the last month of pregnancy.

This medication passes into breast milk, so you should not take Rimstar during breastfeeding. It is essential to inform your doctor if you are breastfeeding or intend to do so before taking Rimstar.

Driving and using machines

This medication may cause adverse reactions such as dizziness, confusion, and blurred vision. This may limit your ability to do certain things, such as driving or using machines.

Rimstar contains sodium

This medication contains less than 1 mmol (23 mg) of sodium per coated tablet, which is essentially "sodium-free".

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again. These doses correspond to adults and children weighing more than 30 kg. Children weighing less than 30 kg should not take these tablets.

The recommended dose is:

Adults:

The amount of Rimstar administered to each person may be different, depending on their body weight. Normally, you will receive the following amount of tablets:

• If you weighbetween 30 kilograms (kg) and 39 kg:take 2 tablets daily.
• If you weighbetween 40 kg and 54 kg:take 3 tablets daily.
• If you weighbetween 55 kg and 70 kg:take 4 tablets daily.
• If you weighmore than 70 kg:take 5 tablets daily.

Your doctor will prescribe the correct dose for you.

Use in children

This medication is not recommended for children under 8 years old or with a body weight less than 30 kg.

Advanced age

Rimstar is well tolerated by most elderly patients, but you should inform your doctor if you have liver or kidney disease. In some cases, your doctor may recommend that you take more vitamin B6 while taking this medication.

Administration form

You should take Rimstar once a day for the first two months of treatment.

Swallow the tablets whole with a little water.

Rimstar should be taken at least one hour before eating.

Treatment duration

Rimstar is usually administered for two months at the beginning of tuberculosis treatment. Your doctor will decide the treatment duration for you.

If you take more Rimstar than you should

If you accidentally take an extra tablet, it is unlikely to cause any harm. If you take several extra tablets, contact your doctor or pharmacist and speak with the hospital's emergency department immediately. If possible, bring the tablets or the box to show the doctor what you have taken.

You can also call the Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount used.

If you forget to take Rimstar

If you forget to take a dose, take it as soon as possible. However, if it is almost time to take the next dose, skip the missed dose and take the next tablet at the usual time.

If you interrupt the treatment with Rimstar

Continue taking the tablets until you complete the treatment, even if you feel better. If you stop taking the tablets too soon, the infection may reappear. Additionally, the bacteria may become resistant to the medication.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Severe side effects:

If you experience any of the following symptoms or a severe allergic reaction, stop taking the medicine and inform your doctor or visit the nearest hospital emergency department immediately:

• sudden difficulty breathing, speaking, and swallowing; swelling of the lips, tongue, face, or neck (may affect up to 1 in 1,000 people),
• extreme dizziness or collapse (may affect up to 1 in 1,000 people).

If you experience any of the following side effects, inform your doctor as soon as possible:

• pancreatitis, which causes intense pain in the abdomen and back (frequency unknown),
• extensive and severe skin damage (separation of the epidermis and superficial mucous membranes) (toxic epidermal necrolysis, NET, may affect up to 1 in 1,000 people),
• a medication reaction that causes skin rash, fever, internal organ inflammation, hematological abnormalities, and systemic disease (DRESS syndrome, may affect up to 1 in 1,000 people),
• yellow discoloration of the skin or the white part of the eyes, or darkening of the urine and pale-colored stools, fatigue, weakness, discomfort, loss of appetite, nausea, or vomiting due to liver problems (hepatitis, may affect up to 1 in 100 people),
• severe diarrhea, prolonged duration, or containing blood with stomach pain or fever: it may be a sign of severe intestinal inflammation (may affect up to 1 in 1,000 people),
• bleeding in the skin; if you continue taking Rimstar, you are at risk of suffering a brain hemorrhage (bleeding, may affect up to 1 in 1,000 people),
• vision problems such as blurred vision, eye pain, red-green color blindness, or even loss of vision (may affect up to 1 in 1,000 people),
• reduction in the number of white blood cells, accompanied by sudden high fever, intense throat pain, and mouth ulcers (agranulocytosis, may affect up to 1 in 1,000 people).

This is a severe side effect. You may need urgent medical attention.

Other side effects:

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

• fatigue, drowsiness, headache, dizziness, nausea, vomiting, loss of appetite, stomach pain, swelling, epigastric discomfort,
• peripheral nerve damage,
• redness of the eyes, permanent color change of soft contact lenses,
• nausea, vomiting, loss of appetite, stomach pain, swelling, epigastric discomfort,
• flushing, itching with or without skin rash, urticaria,
• allergic or other reactions such as skin rash, fever, muscle or joint pain,
• elevation of liver enzymes,
• alteration of liver function that may manifest as loss of appetite, nausea, vomiting, fatigue, discomfort, and weakness,
• change to a reddish color of bodily fluids and secretions such as urine, tears, sweat, sputum, feces, and saliva,
• increase in blood uric acid, acute gouty arthritis (chills, pain, and swelling of joints, especially the big toe, ankle, or knee).

Rare side effects:(may affect up to 1 in 1,000 people):

• hallucinations, disorientation, confusion, discomfort.

Very rare side effects:(may affect up to 1 in 1,000 people):

• changes in white blood cell, red blood cell, and platelet counts, anemia, coagulation disorders, spleen swelling,
• edema/ swelling due to fluid retention,
• diarrhea,
• menstrual disorders, breast swelling, precocious puberty, difficulty controlling diabetes, hyperglycemia, Cushing's syndrome (a disease caused by corticosteroid hormones), induction of crises in patients with Addison's disease (patients with a special form of hormonal disorder),
• psychosis, hyperactivity, euphoria, insomnia, seizures,
• muscle weakness, myopathy, muscle coordination problems (ataxia), increased frequency of epileptic seizures,
• vision problems, optic nerve damage,
• numbness, tingling, burning, or weakness in hands or feet,
• gastritis, jaundice, liver hypertrophy, liver inflammation (severe in isolated cases),
• allergic and other reactions such as dry mouth, stomach burning, urinary disorders, rheumatic syndromes and symptoms, pellagra (a condition characterized by gastrointestinal disorders, skin redness, nervous and mental disorders), lymph node swelling, acne, skin rash, photosensitivity,
• elevation of liver enzymes, acute renal failure, kidney inflammation, urination problems,
• induction of a condition called porphyria (a group of disorders characterized by photosensitivity, skin lesions, anemia, psychosis, and acute abdominal pain).

Unknown frequency:(cannot be estimated from available data):

• inflammation of blood vessels.

If you resume treatment after a temporary interruption of treatment with Rimstar, you may experience what is known as pseudogripal syndrome.

It is characterized by fever, chills, and possibly headache, dizziness, and bone and muscle pain. In rare cases, it may develop into skin bleeding, respiratory difficulties, asthma-like crises, shock, and renal insufficiency.

Reporting side effects:

If you experience side effects, consult your pediatrician or pharmacist, even if they do not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the box, label, or blister after “CAD/EXP”. The expiration date is the last day of the month indicated.

Do not store above 25 °C.

Blister: Store in the original packaging to protect it from moisture.

Bottle: Keep the container perfectly closed to protect it from moisture.

Medicines should not be disposed of through drains or trash. Dispose of containers and medications you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of containers and medications you no longer need. By doing so, you will help protect the environment.

Composition of Rimstar

The active principles are: rifampicin, isoniazid, pyrazinamide, and ethambutol hydrochloride.

Each tablet contains 150 mg of rifampicin, 75 mg of isoniazid, 400 mg of pyrazinamide, and 275 mg of ethambutol hydrochloride.

- The other components are:

pregelatinized cornstarch, cornstarch, sodium lauryl sulfate, microcrystalline cellulose,

polyvinylpyrrolidone K 30, crospovidone, magnesium stearate, talc, copovidone, hypromellose, titanium dioxide (E171), macrogol 400, macrogol 6000, and red iron oxide (E172).

Appearance of the product and contents of the package

Rimstar, film-coated tablets are brown, oval, biconvex, film-coated, and smooth on both sides.

The tablets are packaged in aluminum/aluminum or PVC/PE/PVDC-aluminum blisters that are packaged in a cardboard box or in a white and opaque polypropylene bottle with a polyethylene cap or in a white and opaque polypropylene bottle with a polyethylene cap.

Blister packs containing 30, 60, 120, 240, 672, or 1,000 film-coated tablets.

Bottles containing 500 film-coated tablets.

The packaging sizes of 500 and 1,000 film-coated tablets are for clinical use.

Only some packaging sizes may be commercially available.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Sandoz GmbH

Biochemiestrasse, 10

A-6250-Kundl

Austria

Responsible for manufacturing

Sandoz GmbH

Biochemiestrasse, 10

A-6250-Kundl

Austria

or

Sandoz S.R.L.

Livezeni Street, 7

540472-Targu Mures

Romania

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

SANDOZ FARMACEUTICA, S.A.

Gran Via de les Corts Catalanes, 764

Barcelona - 08013 Spain

This medication is authorized in the member states of the European Economic Area and in the United Kingdom (Northern Ireland) with the following names:

Denmark:Rimstar

FranceRimstar film-coated tablet

Norway:Rimstar, film-coated tablet

Spain:Rimstar, film-coated tablets

Sweden:Rimstar 150 mg/75 mg/400 mg/275 mg film-coated tablet

United KingdomRimstar, film-coated tablet

(Northern Ireland):

Revision date of this leaflet: July 2019

More detailed information about this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/