PATIENT INFORMATION LEAFLET

Rifinah 300 mg/150 mg Film-Coated Tablets

Rifampicin/Isoniazid

Read this 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 or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Contents of the pack and additional information

Rifinah 300 mg/150 mg film-coated tablets are presented in a blister pack of 60 film-coated tablets and are an antibiotic belonging to the group of antitubercular associations. Antibiotics stop the growth of bacteria that cause infections.

It is used for the treatment of tuberculosis in all its forms.

Do not takeRifinah

• If you are allergic to rifamycins, isoniazid, or any of the other components of this medication (see section 6).
• If you have liver disease or jaundice (yellowing of the skin and/or conjunctiva of the eye).
• If you are pregnant or breastfeeding.
• If you are under 12 years old.
• If you are taking medications that contain:

- Combinations of saquinavir/ritonavir or elvitegravir/cobicistat (antiretroviral medications).

- Atazanavir, darunavir, fosamprenavir, tipranavir, rilpivirina, or dolutegravir/rilpivirina (antiretroviral medications).

- Nifedipino, nimodipino, nisoldipino, or nitrendipino (anti-hypertensive medications).

- Glecaprevir/pibrentasvir or elbasvir/grazoprevir (hepatitis C medications).

- Voriconazol (antifungal medication).

- Artemetero/lumefantrina (antimalarial medication).

- BCG live dried culture (interferon).

• If you are taking a medication called lurasidona for schizophrenia and bipolar disorders, (see section “Use of Rifaldin with other medications” below).

Warnings and precautions

Consult your doctor or pharmacist before starting to take Rifinah:

- If the symptoms of tuberculosis return or worsen (see 4. Possible side effects).

- If you are diabetic.The treatment with rifampicina may make it difficult to manage diabetic patients.

- This medication is the association of two drugs (rifampicina and isoniazid), each of which has been associated with liver function alteration. Therefore,your doctor will monitor your liver periodically by performing blood tests before treatment and every 2-4 weeks during treatment. If any liver cell damage appears, your doctor will suspend treatment.

- If you experience itching, weakness, loss of appetite, nausea, vomiting, abdominal pain, yellowing of the eyes or skin, or dark urine, inform your doctor immediately. These symptoms may be related to severe liver damage.

• During treatment, severe skin reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SSJ), and toxic epidermal necrolysis (NET) may occur, some of which are fatal (see section 4. Possible side effects). If you present symptoms of hypersensitivity to Rifinah such as fever, lymphadenopathy (swelling of the lymph nodes), biological alterations (eosinophilia - increase of a certain group of white blood cells -, liver disorders), with or without skin rash, blisters, and mucosal lesions, contact your doctor immediately.

Rifinah should be discontinued if the origin of these symptoms cannot be established.

• If you present a severe generalized blistering skin rash, with blister formation or skin peeling, as well as signs of flu and fever (Stevens-Johnson syndrome), general discomfort, fever, chills, and muscle pain (toxic epidermal necrolysis) or a red, scaly rash with subcutaneous nodules and blisters (acute generalized pustular psoriasis), consult your doctor as soon as possible, as treatment with rifampicina should be discontinued immediately.
• If you are elderly, malnourished, or have a predisposition to neuropathy (e.g., if you are diabetic), you may need to take a vitamin B6 supplement.
• Due to rifampicina, discoloration (yellow, orange, red, brown) may occur in your teeth, urine, sweat, sputum, tears, and feces without clinical significance. Similarly, it may cause permanent discoloration of soft contact lenses.

• Rifampicinamay compete with several medications at the level of absorption, biochemical change, and metabolism, and therefore may decrease or increase the exposure, safety, and efficacy of these medications (see “Use of Rifinah with other medications”).

• If you have a bleeding disorder or tendency to bruise easily. Rifampicina may cause vitamin K-dependent coagulopathy (this means that it may decreasethe blood's ability to coagulate)and severe bleeding (see section “Possible side effects”).

• If you are taking other antibiotics at the same time.
• If you have a history of pulmonary inflammation (interstitial lung disease/pneumonitis).
• If you present a new or sudden worsening of difficulty breathing, possibly with dry cough or fever that does not respond to antibiotic treatment. These may be symptoms of pulmonary inflammation (interstitial lung disease/pneumonitis) and may cause severe respiratory problems and interfere with normal breathing due to fluid accumulation in the lungs, which may lead to life-threatening conditions.
• If you notice any of the symptoms related to cerebellar syndrome described in section 4- Possible side effects. This syndrome has been reported mainly in patients with chronic kidney disease. Your healthcare professional may reduce the dose or ask you to discontinue treatment.

Use of Rifinah with other medications

Rifinah may modify the effects of many medications, so it is very important thatyou inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication, even those purchased without a prescription.

Rifampicina increases the elimination of many medications from the body, so it may decrease or increase the activity of these medications. Among these medications are:

•medications for the treatment of epilepsy: phenytoin, phenobarbital

•medications to treat the heart when it beats irregularly (arrhythmias of the heart): disopyramide, mexiletine, quinidine, propafenone, tocainide

•medications to treat other heart problems: beta-blockers and losartan (for the treatment of high blood pressure), medications called calcium channel blockers such as diltiazem, nifedipine, or verapamil, cardiac glycosides such as digoxin (for the treatment of heart failure)

•medications to treat blood clotting disorders: warfarin

•medications to treat mental disorders: haloperidol

•medications to treat fungal infections:caspofungin,fluconazole, itraconazole, ketoconazole

•medications for HIV infection: zidovudine, saquinavir, indinavir, efavirenz

•medications used as anesthetics: thiopental

•some antibiotics: chloramphenicol, clarithromycin, doxycycline, fluoroquinolones, telithromycin

•corticosteroids (e.g., prednisolone)

•medications to prevent transplant rejection: cyclosporine, tacrolimus, sirolimus

•hormonal contraceptives (including estrogens and progestogens)

•other medications for the treatment of infections: dapsone (for the treatment of leprosy and/or malaria) and quinine (for the treatment of malaria)

•medications for the treatment of diabetes: sulfonylureas (glipizide, glibenclamide), rosiglitazone

•medications for the treatment of depression: nortriptyline

•medications for the treatment of anxiety and/or insomnia: diazepam, zopiclone, zolpidem

•medications for pain relief: opioid analgesics (oxycodone, morphine)

•medications to treat high cholesterol levels: clofibrate, statins (e.g., simvastatin)

•medications for the treatment of vomiting: ondansetron

•medications for the treatment of cancer: irinotecan

•medications for the treatment of degenerative nervous system diseases such as amyotrophic lateral sclerosis: riluzole

•medications with estrogenic and antiestrogenic activity (tamoxifen, toremifene)

•medications for the treatment of hepatitis C (daclatasvir, simeprevir, sofosbuvir, telaprevir, velpatasvir, voxilaprevir)

•Other medications: hexobarbital (barbiturate), levothyroxine (for the treatment of hypothyroidism), methadone, theophylline (for the treatment of asthma), praziquantel (for the treatment of helminthic parasites)

•some medications used to thin the blood, such as clopidogrel

•dapsone: if you are taking dapsone (an antibiotic) with rifampicina, it may cause hematologic toxicity, including a decrease in blood cells and bone marrow, and methemoglobinemia (decrease in oxygen in the blood caused by changes in red blood cells).

• lurasidona for schizophrenia and bipolar disorders, as rifampicina may reduce lurasidona blood levels.

In the case of taking any of these medications, your doctor may need to modify your dose.

If you are taking paracetamol and rifampicina, it may increase the risk of liver damage.

The association of rifampicina with isoniazid increases the potential for liver toxicity. There is a high frequency of association between this association and hepatitis in people over 35 years old, so your doctor will monitor your liver function periodically (see section 2. Warnings and precautions).

When Rifinah is taken with the combination saquinavir / ritonavir, it increases the risk of hepatotoxicity. Therefore, the concomitant use of Rifinah with the combination saquinavir/ritonavir is contraindicated.

Isoniazid inhibits the metabolism of carbamazepine and phenytoin (medications for the treatment of epilepsy), so a dose adjustment will be required for these medications.

Acid para-aminosalicylic increases the blood levels of isoniazid and decreases those of rifampicina.

Interference with laboratory tests

This medication modifies the results of some laboratory tests such as:

• the determination of folates and vitamin B12 in blood,
• the bromosulfthalein test (transient elevations),
• blood bilirubin levels,
• may interfere with the elimination of contrast methods used to examine your gallbladder.

Therefore, if necessary, these tests will be performed in the morning and before taking your dose of Rifinah.

In patients treated with rifampicina, cases of falsely positive results for the presence of opiates in urine have been reported when the test was performed with a test called ICMS (Interacción Cinética de Micropartículas en Solución). With this in mind, it is recommended to use other techniques in these patients, such as gas chromatography and mass spectrometry.

Inform your doctor or pharmacist if you are pregnant and if you are planning or need to undergo mifepristone-induced abortion

Taking Rifinah with food, drinks, and alcohol

Isoniazid interacts with foods that contain a substance called tyramine and found in foods such as cheese and red wine. Similarly, if you take foods that contain a substance called histamine (e.g., tuna or other tropical fish), you may experience an exaggerated response with headache, sweating, palpitations, flushing, and decreased blood pressure. Therefore, your doctor will advise you not to take foods that contain tyramine or histamine during your treatment with Rifinah.

Pregnancy, lactation, and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor before using this medication.

This medication should not be taken during pregnancy.

Rifampicina and isoniazid are excreted in breast milk, so you should not breastfeed your child during treatment.

Consult your doctor or pharmacist before taking a medication.

No data are available in humans on thelong-term ability of Rifinah to alter fertility.

Driving and operating machinery

Rifampicina may cause certain side effects that may interfere with driving and operating machinery. If you experience these side effects (difficulty breathing, nausea, vomiting, muscle weakness), do not drive or operate machinery.

Important information about some of the components of Rifinah

This medication contains saccharose. If your doctor has told you that you have an intolerance to certain sugars, consult with him before taking this medication.

Patients with diabetes mellitus should note that this medication contains 181 mg of saccharose per coated tablet.

This medication may cause allergic reactions because it contains Yellow Orange S (E-110). It may cause asthma, especially in patients allergic to acetylsalicylic acid.

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

Follow exactly the medication administration instructions contained in this leaflet or those indicated by your doctor or pharmacist. If in doubt, ask your doctor or pharmacist.Remember to take your medication.

Your doctor will inform you of your daily dose and the duration of your treatment. Do not discontinue your treatment prematurely. The dosage is individual for you and may be modified by your doctor based on your response to treatment.

Swallow the tablets with a sufficient amount of liquid (a glass of water).

The absorption of Rifinah is affected by food, therefore, to ensure proper absorption, you should take Rifinah with an empty stomach, that is:

• at least 30 minutes before meals, or
• at least 2 hours after meals.

If you estimate that the action of Rifinah is too strong or too weak, inform your doctor or pharmacist.

The dose for adultsof more than 50 kg of body weight and with normal liver function is 2 tablets (600 mg of rifampicin and 300 mg of isoniazid) in a single daily dose, in the morning, and with an empty stomach.

This medication is not recommended for use in children due to different dosage needs.

If you take more Rifinah than you should

Consult your doctor immediately or go to the nearest hospital emergency service accompanied by this leaflet.

After a massive intake of this medication, you can expect the appearance of nausea, vomiting, stomach pain, itching, headache, and progressive drowsiness; in case of suffering from a severe liver disease, it could lead to loss of consciousness. Vertigo, difficulty speaking, blurred vision, and visual hallucinations (bright colors and strange shapes, and even severe breathing difficulties and severe convulsions) may also occur.

Additionally, due to rifampicin, a reddish color may appear in: skin, urine, sweat, saliva, tears, and feces; the intensity of this color will vary depending on the amount of medication taken. It may also cause permanent discoloration of soft contact lenses.

Your doctor will perform the treatment of symptoms they consider appropriate, such as gastric lavage and/or induction of vomiting and administration of medications for symptoms, as well as monitoring your liver and kidney functions.

In case of overdose or accidental ingestion, consult the Toxicological Information Service. Phone: 91 5620420.

If you forgot to take Rifinah

Do not take a double dose to compensate for the missed doses.

If you interrupt the treatment with Rifinah

It is essential that you follow your doctor's instructions, as taking the treatment intermittently (less than 2 or 3 times a week) may cause severe allergic reactions. If you interrupt the treatment and restart it, you will do so with small doses that will be gradually increased.

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

Due to Rifinah

Side effectsfrequent(may affect up to 1 in 10 patients):

• Paradoxical reaction to the drug: during treatment, symptoms of tuberculosis may reappear or new symptoms may appear after initial improvement. Paradoxical reactions have been reported 2 weeks and up to 18 months after starting antituberculous treatment. Paradoxical reactions are usually associated with fever, lymphadenitis (inflammation of lymph nodes), difficulty breathing, and cough. Patients with a paradoxical reaction to the drug may also experience headaches, loss of appetite, and weight loss.

Due to rifampicin:

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

If any of the following serious side effects appear, stop taking Rifinah and consult your doctor immediately (see section 2 - Warnings and precautions):

• Renal insufficiency (kidneys are unable to filter out toxins properly).
• Thrombocytopenia (decrease in the number of platelets in the blood).
• Hemolytic anemia (destruction of red blood cells before normal).

Your doctor will instruct you to stop the treatment with rifampicin immediately and not to take this medicine again.

Side effectsvery frequent(may affect more than 1 in 10 patients):

• Fever, chills.

Side effectsfrequent(may affect up to 1 in 10 patients):

• Thrombocytopenia (reduction in the number of platelets), with or without the appearance of red skin patches formed by small subcutaneous blood hemorrhages (purpura).
• Headache, dizziness.
• Nausea, vomiting.
• Elevation of bilirubin in the blood, elevation of transaminases (aspartate aminotransferase (AST), alanine aminotransferase (ALT)).

Side effectsinfrequent(may affect up to 1 in 100 patients):

• Leucopenia (decrease in the number of white blood cells).
• Dyspepsia.

Other side effectsfrequency unknown(cannot be estimated from available data)that may occur with rifampicin are:

• Pseudomembranous colitis (severe inflammation of the intestine that may appear after antibiotic treatment).
• Influenza.
• Disseminated intravascular coagulation (problems with coagulation in the blood vessels in general).
• Eosinophilia (increase in a certain group of white blood cells).
• Agranulocytosis (decrease in a type of white blood cells, granulocytes).
• Hemolytic anemia (decrease in the number of red blood cells produced by their destruction).
• Vitamin K-dependent coagulopathy.
• Anaphylactic reaction(severe allergic reaction that may cause difficulty breathing and even loss of consciousness).
• Adrenal insufficiency (alteration of the function of the adrenal glands in patients with renal impairment).
• Loss of appetite.
• Psychotic disorder (mental state characterized by a loss of contact with reality).
• Cerebral hemorrhage and death, in cases where, after the appearance of purpura (purple skin patches), treatment with rifampicin was continued or resumed.
• Change in tear color.
• Shock (cardiocirculatory insufficiency syndrome), rubefaction (skin redness), vasculitis (inflammation of blood vessels), severe bleeding.
• Dyspnea (shortness of breath), wheezing (sounds during breathing), change in sputum color.
• Gastrointestinal disorder, abdominal discomfort, discoloration of teeth (which may be permanent).
• Hepatitis (inflammation of the liver), hyperbilirubinemia (elevation of bilirubin in the blood), cholestasis (reduction of bile flow) (see section 2. Warnings and precautions).
• Erythema multiforme.
• Severe skin reactions such as acute generalized exanthematous pustulosis (red and scaly rash with blisters under the skin and vesicles), Stevens-Johnson syndrome (generalized rash with blisters and peeling of the skin, particularly around the mouth, nose, eyes, and genitals) and toxic epidermal necrolysis (generalized rash with blisters and peeling of the skin, particularly around the mouth, nose, eyes, and genitals causing generalized peeling of the skin (more than 30% of the body surface)),Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) (flu-like symptoms with rash, fever, lymphadenopathy, and abnormal blood test results such as eosinophilia and elevated liver enzymes).
• Reactions to the skin, itching, pruritic rash, urticaria, allergic dermatitis, skin lesions with blisters (pemphigus).
• Change in sweat color.
• Muscle weakness, myopathy (muscle disorder).
• Bone pain.
• Acute kidney damage due to normal cell death in the kidneys (tubular necrosis) or inflammation of the kidneys (tubulointerstitial nephritis).
• Chromaturia (abnormal urine color).
• Postpartum hemorrhage.
• Fetomaternal hemorrhage (entry of fetal blood into the mother).
• Menstrual disorder.
• Porphyria.
• Edema (skin swelling due to accumulation of fluids).
• Decreased blood pressure.
• Elevation of creatinine in the blood.
• Elevation of liver enzymes.
• Pulmonary inflammation (interstitial lung disease/pneumonitis): report to your doctor immediately if you develop a new or sudden worsening of difficulty breathing, possibly with cough or fever.

Due to isoniazid:

Side effectsinfrequent(may affect up to 1 in 100 patients):

• Convulsions, toxic encephalopathy (brain damage due to a neurological disorder caused by toxic substances), optic neuritis (inflammation of the optic nerve that may cause sudden partial or complete loss of vision, although in many cases visual ability is recovered), optic nerve atrophy, memory impairment, and toxic psychosis (psychotic disorder caused by substance abuse).
• Nausea, vomiting, stomach pain.

• Hepatitis: symptoms such as yellowing of the skin and eyes (jaundice), dark urine, and pale stools, fatigue, weakness, discomfort, loss of appetite, nausea, or vomiting, which may be severe and sometimes fatal.

Side effectsrare(may affect up to 1 in 1,000 patients):

• Generalized rash with blisters and peeling of the skin, particularly around the mouth, nose, eyes, and genitals, causing generalized peeling of the skin (more than 30% of the body surface) (Toxic Epidermal Necrolysis or NET).
• Flu-like symptoms with rash, fever, lymphadenopathy, and abnormal blood test results such as eosinophilia and elevated liver enzymes (Drug Reaction with Eosinophilia and Systemic Symptoms or DRESS).
• Anemia (decrease in the number of red blood cells in the blood).

Side effectsvery rare(may affect up to 1 in 10,000 patients):

• Thrombocytopenia (reduction in the number of platelets), eosinophilia (increase in white blood cells), agranulocytosis (decrease in a type of white blood cells, granulocytes).
• Anaphylactic reactions (severe allergic reaction that may cause difficulty breathing and even loss of consciousness).
• Pelagra (digestive disorders, pain in the extremities, weakness, and redness with peeling of the skin and nervous system alterations).
• Polineuritis (inflammation of multiple nerves) that presents as paresthesia (tingling sensation), muscle weakness, and loss of reflexes at the junction of tendons and bones.
• Rash (skin rash), acne, exfoliative dermatitis (inflammation of the skin with peeling), Stevens-Johnson syndrome (SSJ) (generalized rash with blisters and peeling of the skin, particularly around the mouth, nose, eyes, and genitals), pemphigus (skin alteration with blisters).
• Syndrome similar to systemic lupus erythematosus (serious skin and mucous membrane disease of unknown origin that may cause fatigue, weight loss, fever, arthritis, kidney damage, convulsions, mental disorders, and gastrointestinal disorders).
• Fever.

Side effects offrequency unknown(cannot be estimated from available data):

• Pancreatitis (inflammation of the pancreas that causes severe abdominal and back pain).
• Gynecomastia (pathological enlargement of one or both breast glands).
• Vasculitis (inflammation of blood vessels).
• Cerebellar syndrome that includes: poor coordination of movements, lack of balance, changes in speech, involuntary eye movements.

If you observe any other reaction not described in this prospectus, consult your doctor or pharmacist.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus.You can also report them directly through theSpanish System for the Reporting of Adverse Reactions to Medicinal Products 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 store at a temperature above 25°C.

Do not use Rifinah after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

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

Composition of Rifinah300 mg/150 mg film-coated tablets

The active principles are rifampicin and isoniazid. Each film-coated tablet contains 300 mg of rifampicin and 150 mg of isoniazid.

The other components are: sodium lauryl sulfate, magnesium stearate, calcium stearate, sodium carmellose, microcrystalline cellulose.

Coating: gum arabic, povidone K30, sucrose, talc, magnesium carbonate, titanium dioxide, kaolin, gelatin, aerosil 200, yellow FDC colorant No. 6, 17% aluminum lacquer (Yellow orange S (E-110)).

Appearance of the product and content of the packaging

Rifinah is presented in the form of oblong, orange-pink, film-coated tablets with a smooth and shiny surface.

Each package contains 60 tablets in blisters.

The holder of the marketing authorization is:

sanofi-aventis, S.A.

C/ Rosselló i Porcel, 21

08016 Barcelona

Spain

The manufacturer is:

Sanofi S.r.l.

Via Valcanello, 4

03012 Anagni (FR) Italy

Date of the last review of this leaflet: August2024

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