RIFALDIN 300 mg CAPSULES

2. What you need to know before you take Rifaldin 300 mg Capsules

Do not take Rifaldin:

• if you are allergic to rifamycins or any of the other components of this medication (listed in section 6).
• if you have liver disease and jaundice.

• if you are taking medications that contain:

• Combinations of saquinavir/ritonavir or elvitegravir/cobicistat (antiretroviral medications).
• Atazanavir, darunavir, fosamprenavir, tipranavir, rilpivirine, or dolutegravir/rilpivirine (antiretroviral medications).
• Nifedipine, nimodipine, nisoldipine, or nitrendipine (antihypertensive medications).
• Glecaprevir/pibrentasvir or elbasvir/grazoprevir (medications for hepatitis C).
• Voriconazole (antifungal medication).
• Artemether/lumefantrine (antimalarial medication).
• BCG live attenuated vaccine (interferon).
• if you are taking a medication called lurasidone for schizophrenia and bipolar disorder (see section "Use of Rifaldin with other medications" below).

Warnings and precautions

Consult your doctor or pharmacist before starting to take Rifaldin.

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

• If you have any liver function disorders. In this case, your doctor will reduce the dose and periodically monitor your liver function with blood tests before 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.

• If you are taking rifampicin with isoniazid (a medication for tuberculosis), or if you are an elderly patient, adolescent, malnourished, or have a predisposition to nervous system disorders (e.g., if you are diabetic), your doctor may prescribe a vitamin B6 supplement.

• During treatment, a severe reaction such as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) may occur (see section 4. Possible side effects). If you present early symptoms of hypersensitivity to Rifaldin such as fever, lymphadenopathy, or biological alterations (eosinophilia, liver disorders) with or without skin rash, contact your doctor immediately.

Rifaldin should be discontinued if a different origin for these symptoms cannot be established.

• If you present a severe, generalized, blistering skin rash with blisters or skin peeling, as well as flu-like symptoms and fever (Stevens-Johnson syndrome), general discomfort, fever, chills, and muscle pain (toxic epidermal necrolysis), or a red, scaly rash with bumps under the skin and blisters (acute generalized exanthematous pustulosis), consult your doctor as soon as possible, as treatment with rifampicin should be suspended immediately.

• If you are diabetic. Treatment with rifampicin may make it difficult to manage diabetic patients.

• Due to rifampicin, a discoloration (yellow, orange, red, brown) may appear in your teeth, urine, sweat, sputum, tears, and feces without clinical significance. Similarly, it may cause permanent discoloration of soft contact lenses.

• Rifampicin may compete with several medications at the level of absorption and biochemical/metabolic change, and therefore may decrease or increase the exposure, safety, and efficacy of these medications (see "Use of Rifaldin with other medications").

• If you have a bleeding problem or tend to bruise easily. Rifampicin may cause vitamin K-dependent coagulopathy (decreased blood clotting ability) 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 experience a new or sudden worsening of breathing difficulties, 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 serious respiratory problems and interfere with normal breathing due to fluid accumulation in the lungs, which can lead to life-threatening conditions.

Use of Rifaldin with other medications

Inform your doctor or pharmacist if you are using, have recently used, or may need to use any other medication.

Rifampicin increases the elimination of many medications from the body, which may result in a decrease in their activity. These medications include:

• medications for the treatment of epilepsy: phenytoin, phenobarbital

• medications for the treatment of heart arrhythmias: disopyramide, mexiletine, quinidine, propafenone, tocainide

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

medications for the treatment of blood coagulation disorders: warfarin

• medications for the treatment of mental disorders: haloperidol

• medications for the treatment of fungal infections: caspofungin, fluconazole, itraconazole, ketoconazole

• medications for the treatment of HIV infection: zidovudine, saquinavir, indinavir, efavirenz

• medications used as anesthetics: thiopental

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

• corticosteroids (e.g., prednisolone)

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

• systemic 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, glyburide), rosiglitazone

• medications for the treatment of depression: nortriptyline

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

• medications for the treatment of pain: opioid analgesics (oxycodone, morphine)

• medications for the treatment of high cholesterol: clofibrate, statins (e.g., simvastatin)

• medications for the treatment of nausea and 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 anti-estrogenic activity (tamoxifen, toremifene)

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

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

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

• dapsone: if you are taking dapsone (an antibiotic) with rifampicin, hematologic toxicity, including decreased blood cells and bone marrow, and methemoglobinemia (decreased oxygen in the blood due to changes in red blood cells) may occur.

• lurasidone for schizophrenia and bipolar disorder, as rifampicin may reduce lurasidone blood levels.

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

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

If you are taking systemic hormonal contraceptives, you should use a non-hormonal contraceptive method during treatment with Rifaldin.

The simultaneous use of ketoconazole and rifampicin decreases the serum levels of both drugs.

The simultaneous use of Rifaldin and enalapril decreases the activity of enalapril. If your clinical condition allows, your doctor may need to modify the dose.

When atovaquone and Rifaldin are used simultaneously, a decrease in atovaquone concentrations and an increase in rifampicin concentrations are observed.

You should not take Rifaldin with para-aminosalicylic acid (a medication used for the treatment of tuberculosis), as it decreases the blood levels of rifampicin. It is advisable to leave an interval of 8 hours between the administration of both medications.

Antacids reduce the absorption of rifampicin, so you should take your daily dose of Rifaldin at least one hour before taking antacids.

The simultaneous use of rifampicin with halothane or isoniazid increases the potential for liver toxicity. You should not use Rifaldin with halothane. If you are being treated with rifampicin and isoniazid, your doctor will periodically monitor your liver function (see section 2. Warnings and precautions).

Concomitant use with a group of antiretroviral medications, non-nucleoside reverse transcriptase inhibitors such as etravirine, nevirapine, or any protease inhibitor (alone or in combination with an antiretroviral medication called ritonavir), is not recommended.

Concomitant use with maraviroc, another antiretroviral medication, is also not recommended; if clinically justified, a dose adjustment is required.

Concomitant use of rifampicin with other antibiotics that cause vitamin K-dependent coagulopathy (decreased blood clotting ability), such as cefazolin (or other cephalosporins of the same group), should be avoided, as it may cause severe coagulation disorders (when blood loses its fluidity and becomes a gel to form a clot) that can lead to a fatal outcome (especially with high doses).

You should not take Rifaldin with the combination saquinavir/ritonavir (antiretroviral medications).

Rifaldin alters the results of some laboratory tests, such as:

• folate and vitamin B12 determination in blood,
• bromsulfalein test,
• bilirubin levels in blood,
• it may interfere with the elimination of contrast media used to examine your gallbladder.

Therefore, if necessary, these tests will be performed in the morning and before you take your dose of Rifaldin.

In patients treated with rifampicin, cases of false-positive results for the presence of opiates in urine have been reported when the analysis was performed with a test called ICMS (Interaction Kinetic of Microparticles in Solution). For this reason, 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 abortion with mifepristone.

Taking Rifaldin with food, drinks, and alcohol

The absorption of Rifaldin is affected by food, so to ensure adequate absorption, you should take Rifaldin on an empty stomach, i.e.:

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

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medication.

Pregnancy

Since rifampicin crosses the placental barrier and there is insufficient data to establish its safety during pregnancy, your doctor will carefully weigh the benefits and risks of using Rifaldin during pregnancy. In no case will it be administered during the first three months of pregnancy.

Breastfeeding

Rifampicin is excreted in breast milk, so it should only be used in breastfeeding mothers if the potential benefit outweighs the potential risk to the child.

Fertility

There are no data on the long-term ability of rifampicin to alter fertility.

Driving and using machines

Rifampicin may cause certain side effects that can interfere with your ability to drive and use machines. If you experience these side effects (difficulty breathing, nausea, vomiting, muscle weakness), do not drive or use machines.

Rifaldin 300 mg Capsules contain sodium

This medication contains less than 23 mg of sodium (1 mmol) per capsule; it is essentially "sodium-free".

3. How to take Rifaldin 300 mg capsules

Follow the administration instructions of this medication exactly as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Your doctor will indicate your daily dose and the duration of your treatment. Do not stop your treatment beforehand. The dosage is individualized for you and may be modified by your doctor based on your response to treatment.

If you think the effect of Rifaldin is too strong or too weak, inform your doctor or pharmacist.

Adults:

The recommended dose in adults depends on the disease for which this medication has been prescribed and is:

• Tuberculosis:the recommended daily dose is 10 mg per kg of body weight in a single dose,

this is a dose of 600 mg (2 capsules of 300 mg) in the case of weighing 50 kg or more and a dose of 450 mg if your weight is less than 50 kg. As a general rule for the treatment of tuberculosis, Rifaldin will be administered in combination with other antitubercular medications such as ethambutol or isoniazid.

• Brucellosis:The recommended daily dose in case of acute brucellosis is

600 to 900 mg of Rifaldin per day (2 to 3 capsules of 300 mg) along with 200 mg of doxycycline orally for 6 weeks.

• Meningococcal carriers:A dose of 600 mg of Rifaldin (2 capsules

of 300 mg) every 12 hours for 2 consecutive days is recommended.

• Other non-tuberculous infections:The recommended daily dose is 450 to 600 mg.

Your doctor may increase this dose up to 900 to 1,200 mg per day divided into two administrations.

Children:

The dose for children is based on their weight. It usually ranges between 10 mg and 20 mg per kg of body weight per day.

The usual dose for children for the treatment of tuberculosis is 15 mg. In children with weight alteration, a dose reduction may be necessary. In severe infections, such as meningitis, a higher dose, such as 20 mg per kg of body weight per day, may be used.

If you take more Rifaldin than you should

Consult your doctor immediately or go to the emergency department of the nearest hospital accompanied by this prospectus.

After taking a large amount of this medication, you can expect the appearance of nausea, vomiting, stomach pain, itching, headache, and progressive drowsiness; in case of having a severe liver disease (hepatic), loss of consciousness could occur. In pediatric patients, facial or periorbital edema has also been detected. In some fatal cases, hypotension, sinus tachycardia, ventricular arrhythmias, convulsions, and cardiac arrest have been reported. A transient increase in liver enzymes and/or bilirubin may also occur.

Additionally, a reddish-brown or orange 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.

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

In case of overdose or accidental ingestion, consult your doctor or pharmacist or call the Toxicological Information Service, phone: 91 5620420, indicating the medication and the amount ingested.

If you forgot to take Rifaldin

Do not take a double dose to make up for forgotten doses.

4. Possible adverse effects

Like all medications, this medication can cause adverse effects, although not all people experience them.

If any of the following serious adverse effects occur, stop taking Rifaldin and consult your doctor immediately:

• Kidney failure (the kidneys are not able to filter toxins properly).
• Thrombocytopenia (decrease in the number of platelets in the blood).
• Hemolytic anemia (destruction of red blood cells in the blood, before normal).

Your doctor will indicate that you immediately interrupt treatment with rifampicin and do not take this medication again.

Adverse effects very frequent(may affect more than 1 in 10 patients):

• Fever.
• Chills.

Adverse effects frequent(may affect up to 1 in 10 patients):

• Thrombocytopenia (reduction in the number of platelets), with or without the appearance of red spots on the skin formed by small subcutaneous hemorrhages (purpura).
• Headache, dizziness.
• Nausea, vomiting.
• Elevation of bilirubin in the blood, elevation of transaminases [aspartate aminotransferase (AST), elevation of alanine aminotransferase (ALT)].
• Paradoxical reaction to the medication: during treatment, the 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 antitubercular treatment. Paradoxical reactions are usually associated with fever, inflammation of the lymph nodes (lymphadenitis), difficulty breathing, and cough. Patients with a paradoxical reaction to the medication may also experience headaches, loss of appetite, and weight loss.

Adverse effects infrequent(may affect up to 1 in 100 patients):

• Leukopenia (decrease in the number of white blood cells).
• Diarrhea.

Adverse effects of unknown frequency(cannot be estimated from available data):

• Pseudomembranous colitis (severe inflammation of the intestine that may appear after antibiotic treatment)
• Flu.
• Disseminated intravascular coagulation (coagulation problems within blood vessels in a generalized manner), eosinophilia (increase in a certain group of white blood cells), granulocytopenia (decrease in a type of white blood cell, granulocytes), hemolytic anemia (decrease in the number of red blood cells produced by their destruction), vitamin K-dependent coagulation disorders.
• Anaphylactic reaction (severe allergic reaction that causes difficulty breathing and even loss of consciousness).
• Adrenal insufficiency (alteration of the function of the adrenal glands in patients with renal alteration).
• Decreased appetite.
• Psychotic disorder (mental state that consists of a loss of contact with reality).
• Cerebral hemorrhage and death, in cases where, after the appearance of purpura (purple spots on the skin), treatment with rifampicin has been continued or resumed.
• Change in tear color.
• Shock (cardiocirculatory failure syndrome), flushing (redness of the skin), vasculitis (inflammation of blood vessels), severe bleeding.
• Dyspnea (shortness of breath or difficulty breathing), wheezing (sounds during breathing), change in sputum color.
• Gastrointestinal disorder, abdominal discomfort, tooth discoloration (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 bumps under the skin and blisters), 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 skin rash, fever, gland inflammation, and abnormal blood test results such as increased leukocytes (eosinophilia) and elevated liver enzymes] (see section 2. Warnings and precautions).

• Skin reactions, itching, pruriginous skin rash, urticaria, allergic dermatitis, blistering skin lesions (pemphigus).
• Change in sweat color.
• Muscle weakness, myopathy (muscle disorder).
• Bone pain.
• Acute kidney damage usually due to death of kidney cells (tubular necrosis) or kidney inflammation (tubulointerstitial nephritis).
• Chromaturia (abnormal urine color).
• Postpartum hemorrhage.
• Feto-maternal hemorrhage (entry of blood from the fetus to the mother).
• Menstrual disorder.
• Porphyria.
• Edema (skin swelling due to fluid accumulation).
• Decrease in blood pressure.
• Increased creatinine in the blood.
• Increased liver enzymes.
• Lung inflammation (interstitial lung disease/pneumonitis): inform your doctor immediately if you develop a new or sudden worsening of difficulty breathing, possibly with cough or fever.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Rifaldin 300 mg capsules

Keep this medication out of sight and reach of children.

Do not store at a temperature above 25°C.

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

Medications should not be thrown away through the sewers or in the trash. Deposit the packaging and medications you no longer need at the SIGRE point of the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. This way, you will help protect the environment.

6. Package contents and additional information

Composition of Rifaldin 300 mg capsules

• The active ingredient is rifampicin. Each hard capsule contains 300 mg of rifampicin.
• The other components (excipients) are: cornstarch and magnesium stearate. Components of the hard capsule: gelatin; erythrosine (E-127); indigo carmine (E-132); titanium dioxide (E-171).

Appearance of the product and package contents

Rifaldin 300 mg hard capsules are presented in packages with 24 capsules.

Marketing authorization holder and manufacturer

Marketing authorization holder

sanofi-aventis, S.A.

C/ Rosselló i Porcel, 21

08016 Barcelona

Spain

Manufacturer

Sanofi S.r.l.

Via valcanello, 4

03012 Anagni (FR)

Italy

Date of the last revision of this prospectus: August 2024

Detailed information about this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.