Leaflet: information for the user

Rifaldin 300 mg hard capsules

Rifampicin

Read this leaflet carefully before you start taking this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult 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 you, 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.

1. What Rifaldin 300 mg hard capsules are and what they are used for

2. What you need to know before you start taking Rifaldin 300 mg hard capsules

3. How to take Rifaldin 300 mg hard capsules

4. Possible side effects

5. Storage of Rifaldin 300 mg hard capsules

6. Contents of the pack and additional information

Rifaldin is an antibiotic belonging to a group of antibiotics called rifampicins. It acts by stopping the growth of bacteria that cause infections.

Rifaldin is indicated for the treatment of infections caused by bacteria against which this medication is active, such as:

• Tuberculosis in all its forms (in association with other antitubercular agents).

• Brucellosis.

• Elimination of meningococci in people who do not have symptoms of the disease (asymptomatic carriers). It is not indicated for the treatment of established meningococcal infection.

Infections in which previous sensitivity to Rifaldin has been demonstrated, and when it is not advisable to administer other antibiotics or chemotherapeutic agents to the patient, either due to allergy or existing contraindications that make them not advisable.

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 yellow skin (jaundice).

• 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 (medications for hepatitis C).

- 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 Rifaldin.

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

• If you have any liver function abnormalities. In this case, your doctor will reduce the dose and monitor your liver function 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.

• If you are taking rifampicine with isoniazid (tuberculosis medication), or are elderly, or adolescent, or 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 experience early symptoms of hypersensitivity to Rifaldin such as fever, lymphadenopathy (swelling of lymph nodes) or biological abnormalities (eosinophilia - increase in a certain group of white blood cells -, liver disorders), with or without skin rash, contact your doctor immediately.

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

• If you experience a severe generalized blistering skin rash, with blistering or skin peeling, as well as signs of flu and fever (Stevens-Johnson syndrome), general malaise, fever, chills, and muscle pain (toxic epidermal necrolysis), or a red and scaly rash with subcutaneous nodules and blisters (acute generalized pustular psoriasis), consult your doctor as soon as possible, as treatment with rifampicine should be suspended immediately.

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

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

• Rifampicine may compete with various medications at the level of absorption and biochemical change / metabolism, 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 tendency to easily bruise. Rifampicine may cause vitamin K-dependent coagulopathy (this means it may decrease the 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 experience 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.

Use of Rifaldin with other medications

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

Rifampicine increases the elimination of many medications from the body, which may result in a decrease in their activity. Among these medications are:

• medications for the treatment of epilepsy: phenytoin, phenobarbital

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

• medications for 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 for the treatment of blood clotting disorders: warfarin

• medications for the treatment of mental disorders: haloperidol

• medications for the treatment of 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 the treatment of pain: 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)

• 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)

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

• dapsone: if you are taking dapsone (an antibiotic) with rifampicine, toxicity may occur, 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 rifampicine may reduce lurasidona blood levels.

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

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

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

The simultaneous use of ketoconazole and rifampicine decreases the serum levels of both medications.

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

When atovacuona and Rifaldin are used simultaneously, a decrease in atovacuona concentrations and an increase in rifampicine concentrations are observed.

You should not take Rifaldin with acid para-aminosalicylic acid (a medication used to treat tuberculosis) as this decreases rifampicine blood levels, so it is recommended to leave an 8-hour interval between taking both medications.

Antacids reduce the absorption of rifampicine, so you should take your daily dose of Rifaldin at least 1 hour before taking antacids.

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

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

The concomitant use of rifampicine with maraviroc, another antiretroviral medication, is not recommended; if clinically justified, dose adjustment may be required.

The concomitant use of rifampicine with other antibiotics that cause vitamin K-dependent coagulopathy (decrease in blood's ability to coagulate) such as cefazolin (or other cefalosporins in the same group) should be avoided, as it may cause severe coagulation disorders that may lead to a fatal outcome (especially with high doses).

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

Rifaldin may affect the results of some laboratory tests, such as:

• blood folate and vitamin B12 determinations,
• bromosulfthalein test,
• blood bilirubin levels,
• 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 taking your dose of Rifaldin.

In patients treated with rifampicine, cases of falsely positive results for the presence of opiates in urine have been reported when the analysis 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 abortion with mifepristone

Taking Rifaldin with food, drinks, and alcohol

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

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

Pregnancy, breastfeeding, and fertility

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

Pregnancy

Rifampicine crosses the placental barrier and there is not enough data to establish its safety during pregnancy, your doctor will carefully evaluate the need to use Rifaldin during pregnancy. In no case should it be administered during the first three months of pregnancy.

Breastfeeding

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

Fertility

There is no data on the long-term ability of rifampicine to alter fertility.

Driving and operating machinery

Rifampicine 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), you should not drive or operate machinery.

Rifaldin 300 mg capsules contain sodium

This medication contains less than 23 mg of sodium (1 mmol) per capsule; this 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.

Your doctor will indicate your daily dose and the duration of your treatment. Do not stop your treatment before. The dosage is individual for you and may be modified by your doctor according to your response to treatment.

If you estimate that the action 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 you have been prescribed this medication and is:

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

whichis 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, you will be administered Rifaldin associated with other antitubercular medications such as ethambutol or isoniazid.

• Brucelosis: The recommended daily dose in case of acute brucelosis 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.

Portadores de meningococos:A recommended dose of 600 mg of Rifaldin (2 capsules

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

• Otras infecciones no tuberculosas:The recommended daily dose is 450 to 600 mg.

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

Children:

The dose for children is based on their weight. Normally it ranges from 10 mg to 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 reduction in dose may be necessary. In severe infections, for example 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 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 severe liver disease, it could lead to loss of consciousness.In pediatric patients, facial or periorbital edema has also been detected. In some fatal cases, hypotension, sinus tachycardia, ventricular arrhythmias, seizures, 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 compensate for the missed doses.

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

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

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

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

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

• Fever.
• Chills.

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

• Thrombocytopenia (decrease in the number of platelets), with or without the appearance of red skin spots formed by small subcutaneous blood 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 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 antitubercular treatment. Paradoxical reactions are usually associated with fever, lymph node inflammation (lymphadenitis), difficulty breathing, and cough. Patients with a paradoxical reaction to the drug may also experience headaches, loss of appetite, and weight loss.

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

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

Side effects ofunknown frequency(cannot be estimated from available data):

• Pseudomembranous colitis (severe inflammation of the intestine that may appear after treatment with antibiotics).
• Influenza.
• Disseminated intravascular coagulation (problems with coagulation within blood vessels in general), eosinophilia (increase in a certain group of white blood cells), granulocytosis (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 coagulation disorders.
• 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 consisting 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 was continued or resumed.
• Change in the color of tears.
• Shock (cardiocirculatory insufficiency syndrome), rubefaction (redness of the skin), vasculitis (inflammation of blood vessels), severe bleeding.
• Dyspnea (shortness of breath), sibilant sounds (sounds during breathing), change in the color of sputum.
• Gastrointestinal disorders, 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 bumps under the skin and blisters), Stevens-Johnson syndrome (generalized rash with blisters and skin peeling, particularly around the mouth, nose, eyes, and genitals) and toxic epidermal necrolysis [generalized rash with blisters and skin peeling, particularly around the mouth, nose, eyes, and genitals, causing generalized skin peeling (more than 30% of the body surface)],drug reaction with eosinophilia and systemic symptoms [(DRESS)flu-like symptoms with skin rash, fever, lymph node inflammation, and abnormal blood test results such as increased white blood cells (eosinophilia) and elevated liver enzymes](see section 2.Warnings and precautions).

• Reactions to the skin, itching, pruritic skin 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 death of kidney cells (tubular necrosis) or inflammation of the kidneys (tubulointerstitial nephritis).
• Chromaturia (abnormal urine color).
• Postpartum hemorrhage.
• Fetomaterna hemorrhage (entry of fetal blood into the mother).
• Menstrual disorder.
• Porphyria.
• Edema (skin swelling due to accumulation of fluids).
• Decrease in blood pressure.
• Increased creatinine in the blood.
• Increased 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.

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 leaflet. You can also report them directly through the Spanish System for the Vigilance 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 store at a temperature above 25°C.

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

Medications should not be disposed of through drains or in the trash. Dispose of the packaging and medications 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 medications you no longer need. By doing so, you will help protect the environment.

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 disulfonate (E-132); titanium dioxide (E-171).

Appearance of the product and content of the container

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

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

sanofi-aventis, S.A.

C/ Rosselló i Porcel, 21

08016 Barcelona

Spain

Responsible for manufacturing

Sanofi S.r.l.

Via valcanello, 4

03012 Anagni (FR)

Italy

Last review date of this leaflet: August 2024

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