Label: information for the user

Rifaldin 600 mg powder and solvent for solution for infusion

Rifampicin

Read this label carefully before starting to use this medicine, as it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed to you alone, and you must 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 label. See section 4.

6. Contents of the pack and additional information

Rifaldin is an antibiotic belonging to a group of antibiotics called rifampicinas. 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 and locations, when the clinical situation (loss of consciousness, surgical intervention, gastrointestinal absorption alteration, etc.) or the patient's gastric tolerance conditions do not allow or advise the oral administration of the drug.

In non-tuberculous infections, it may be used, exceptionally, only in a hospital setting and after precise etiological confirmation and performance of the appropriate antibiogram, those caused by staphylococci (S. aureus, S. epidermidis, poliresistant strains) and by enterococci (E.faecalis, E. faecium), and when it is not possible to administer other antibiotics or chemotherapeutic agents to the patient.

Do not use Rifaldin:

• if you are allergic to rifamycins, or to any of the other components of this medicine

(see section 6),

• if you have liver disease and yellow skin (jaundice),

• if you are taking medicines that contain:

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

- Atazanavir, darunavir, fosamprenavir, tipranavir, rilpivirina or dolutegravir/rilpivirina (antiviral medicines).

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

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

- Voriconazol (antifungal medicine).

- Artemetero/lumefantrina (antimalarial medicine).

- BCG live dried culture (interferon).

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

Warnings and precautions

This presentation is only for intravenous infusion.It should not be administered by intramuscular or subcutaneous route.

Consult your doctor or pharmacist before starting to use Rifaldin.

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

• If you have liver dysfunction. In this case, your doctor will reduce the dose and monitor your liver function regularly 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, yellow discoloration 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 medicine), or are elderly, or adolescent, undernourished, or predisposed to nervous system disorders (e.g. diabetic), your doctor may prescribe a vitamin B6 supplement.
• During treatment, a severe reaction such as drug reaction with eosinophilia and systemic symptoms (DRESS) (see section 4. Possible side effects) may occur. If you experience early symptoms of hypersensitivity to Rifaldin such as fever, lymphadenopathy (swelling of lymph nodes) or biological abnormalities (eosinophilia - increase of 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 and 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 and scaly rash with skin 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. Rifampicine treatment 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. It may also cause permanent discoloration of soft contact lenses.

• Rifampicine may compete with various medicines at the level of absorption and biochemical/biochemical metabolism, and therefore may decrease or increase exposure, safety, and efficacy of these medicines (see “Use of Rifaldin with other medicines”).

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

• If you are taking other antibiotics at the same time.
• If you have a history of lung 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 lung 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 medicines

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

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

• medicines for other heart problems: beta-blockers and losartan (for the treatment of high blood pressure), medicines called calcium channel blockers such as diltiazem, nifedipine or verapamil, cardiac glycosides such as digoxin (for the treatment of heart failure)
• medicines for the treatment of blood clotting disorders: warfarin
• medicines for the treatment of mental disorders: haloperidol
• medicines for the treatment of fungal infections: caspofungin, fluconazole, itraconazole, ketoconazole
• medicines for HIV infection: zidovudine, saquinavir, indinavir, efavirenz
• medicines used as anesthetics: thiopental
• some antibiotics: chloramphenicol, clarithromycin, doxycycline, fluoroquinolones, telithromycin
• corticosteroids (e.g. prednisolone)
• medicines to prevent transplant rejection: cyclosporine, tacrolimus, sirolimus
• hormonal contraceptives (including estrogens and progestogens)
• other medicines for the treatment of infections: dapsone (for the treatment of leprosy and/or malaria) and quinine (for the treatment of malaria)
• medicines for the treatment of diabetes: sulfonylureas (glipizide, glibenclamide), rosiglitazone
• medicines for the treatment of depression: nortriptyline
• medicines for the treatment of anxiety and/or insomnia: diazepam, zopiclone, zolpidem
• medicines for the treatment of pain: opioid analgesics (oxycodone, morphine)
• medicines to treat high cholesterol levels: clofibrate, statins (e.g. simvastatin)
• medicines for the treatment of vomiting: ondansetron
• medicines for the treatment of cancer: irinotecan
• medicines for the treatment of degenerative nervous system disorders such as amyotrophic lateral sclerosis: riluzole

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

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

• other medicines: hexobarbital (barbiturates), levothyroxine (for the treatment of hypothyroidism), methadone, theophylline (for the treatment of asthma), praziquantel (for the treatment of helminthic parasites)
• some medicines 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 case you are taking any of these medicines, 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 Rifaldin treatment.

The use of ketoconazole and rifampicine simultaneously decreases the serum levels of both medicines.

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

When used simultaneously, atovacuona and Rifaldin are observed to decrease atovacuona concentrations and increase rifampicine concentrations.

Do not take Rifaldin with acid para-aminosalicylic (medicine used for the treatment of tuberculosis) as this decreases rifampicine blood levels, so it is advisable to leave an 8-hour interval between the two medicines.

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

The use of rifampicine with halothane or isoniazid increases the potential for liver toxicity. Do not use Rifaldin with halothane. If you have a treatment with rifampicine and isoniazid, your doctor will monitor your liver function regularly (see section 2. Warnings and precautions).

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

It is also not recommended to use concomitantly with maraviroc, another antiretroviral medicine; if clinically justified, dose adjustment may be required.

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

Do not take Rifaldin with the combination saquinavir/ritonavir (antiretroviral medicines).

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

• blood folate and vitamin B12 determination,
• bromosulfthalein test,
• 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 you have taken 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 test was performed with a method 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

Pregnancy, lactation and fertility

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

Pregnancy

As 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.

Lactation

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

Fertility

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

Rifaldin contains sodium

This medicine contains 13.84 mg of sodium per vial, equivalent to 0.692% of the maximum daily intake of 2 g of sodium recommended by the WHO for an adult.

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), do not drive or operate machinery.

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

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

Dissolve the lyophilized powder by transferring 10 ml of water for injectable preparations to a 600 mg vial of rifampicin. Gently roll the vial between your hands until the antibiotic is completely dissolved. The resulting solution contains 60 mg of rifampicin per ml and remains stable at room temperature for 30 hours. Before administration, remove a volume equivalent to the calculated amount of rifampicin to be administered from the reconstituted solution and add it to 250 or 500 ml of infusion medium. Mix well and infuse at a rate that allows for complete perfusion within three hours. Alternatively, the calculated amount of rifampicin may be added to 100 ml of infusion medium and infused over 30 minutes.

After dilution with the vial of water for injectable preparations, the resulting rifampicin solution remains stable at a temperature not exceeding 25°C for 24 hours.

After dilution in 5% glucose solution, it remains stable for 8 hours at a temperature not exceeding 25°C, so it must be prepared and used within this period. Beyond this period, precipitation of rifampicin may occur in the infusion solution.

Dilutions in normal saline solution remain stable for 6 hours at a temperature not exceeding 25°C, so they must be prepared and used within this period.

It is not recommended to use other infusion solutions.

The intravenous presentation should not be diluted in solutions other than 5% glucose solution and normal saline solution. Intravenous solutions containing sodium bicarbonate and/or sodium lactate are physically incompatible with rifampicin.

Physical incompatibility (precipitation) has been observed with undiluted clorhidrato de diltiazem (5 mg/ml) and diluted (1 mg/ml in saline solution) and rifampicin (6 mg/ml in saline solution) during simulated Y administration.

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 600 mg in a single administration. If you have impaired liver function or are elderly or if your general condition is not very good, lower doses will be administered. As a general rule for the treatment of tuberculosis, Rifaldin will be administered associated with other antitubercular medications such as etambutol or isoniazid.

-Other infections:The recommended daily dose is 900 to 1200 mg administered in two slow infusions (1-3 hours).

Children:

The dose for children is based on their weight. It usually ranges from 10 mg to 20 mg per kilogram of body weight per day.

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

Rifaldin 600 mg powder and diluent for solution for infusion is only for intravenous infusion. It should not be administered by intramuscular or subcutaneous route.

If you use more Rifaldin than you should

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

After massive use of this medication, you may expect the appearance of nausea, vomiting, stomach pain, itching, headache, and progressive drowsiness; in case of severe liver disease, loss of consciousness may occur. 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 used.

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 your doctor or pharmacist or call the Toxicology Information Service, phone: 91 5620420, indicating the medication and the amount ingested.

If you forgot to use Rifaldin

Do not administer 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 appear, stop taking Rifaldin and consult your doctor immediately:

• Renal insufficiency (the kidneys are unable to filter out toxins properly).
• Trombocytopenia (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 taking 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):

• Trombocytopenia (reduction 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), 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 antituberculosis 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 intestinal inflammation that may appear after antibiotic treatment).
• Influenza.
• Disseminated intravascular coagulation (generalized blood clotting problems within blood vessels).
• Eosinophilia (increase in a certain group of white blood cells).
• Agranulocytosis (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 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 spots on the skin), 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 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 widespread skin peeling (more than 30% of the body surface)],DRESS (symptoms of a flu-like illness with skin rash, fever, lymph node inflammation, and abnormal blood test results such as 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, usually due to 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).
• Decrease in blood pressure.
• Elevation of creatinine in the blood.
• Elevation of liver enzymes.
• Pulmonary inflammation (interstitial lung disease/neumonitis): 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 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.

Do not store at a temperature above 25°C.

The solution obtained after reconstituting the vial with 10 ml of injection water has been demonstrated to be stable from a chemical and physical point of view for 30 hours at a temperature not exceeding 25°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, the times and conditions of storage before administration are the responsibility of the user and should not normally exceed 24h between 2 and 8°C (or the times previously set for the physical and chemical stability of the reconstituted solution, whichever is shorter), unless reconstitution, dilution, etc. have taken place in validated aseptic conditions.

The solution obtained by diluting the reconstituted vial subsequently with 500 ml of 5% glucose solution has been demonstrated to be stable from a chemical and physical point of view for 8 hours at a temperature not exceeding 25°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, the times and conditions of storage before administration are the responsibility of the user and should not normally exceed 24h between 2 and 8°C (or the times previously set for the physical and chemical stability of the diluted solution, whichever is shorter), unless reconstitution, dilution, etc. have taken place in validated aseptic conditions.

The solution obtained by diluting the reconstituted vial subsequently with 500 ml of 0.9% NaCl has been demonstrated to be stable from a chemical and physical point of view for 6 hours at a temperature not exceeding 25°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, the times and conditions of storage before administration are the responsibility of the user and should not normally exceed 24h between 2 and 8°C (or the times previously set for the physical and chemical stability of the diluted solution, whichever is shorter), unless reconstitution, dilution, etc. have taken place in validated aseptic conditions.

Medicines should not be thrown down the drain or in the trash. Dispose of the packaging and the medicines you do not need at the SIGRE point of the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and the medicines you do not need. In this way, you will help protect the environment.

Composition of Rifaldin

The active principle is rifampicin. Each vial of lyophilized powder contains 600 mg of rifampicin sodium.

The other components (excipients) are: formaldehyde sulfoxylate of sodium and sodium hydroxide. The composition of the injection vial is water for injection preparations.

Appearance of the product and content of the container

Rifaldin 600 mg powder and solvent for perfusion solution is presented in a container with 1 vial of lyophilized powder and an injection vial.

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

Date of the last review of this leaflet: August 2024

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