RIFALDIN 600 mg POWDER AND SOLVENT FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Rifaldin 600 mg powder and solvent for solution for infusion

Rifampicin

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

1. What Rifaldin 600 mg powder and solvent for solution for infusion is and what it is used for
2. What you need to know before you use Rifaldin 600 mg powder and solvent for solution for infusion
3. How to use Rifaldin 600 mg powder and solvent for solution for infusion
4. Possible side effects
5. Storing Rifaldin 600 mg powder and solvent for solution for infusion

1. Contents of the pack and other information

1. What Rifaldin 600 mg powder and solvent for solution for infusion is and what it is used for

Rifaldin is an antibiotic belonging to a group of antibiotics called rifamycins. It works

by stopping the growth of the bacteria that cause infections.

Rifaldin is indicated for the treatment of infections caused by bacteria that are susceptible to this medication, such as:

• Tuberculosis in all its forms and locations, when the clinical situation (loss of consciousness, surgical intervention, alteration of gastrointestinal absorption, etc.) or the patient's gastric tolerance conditions do not allow or advise oral administration of the drug.

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

2. What you need to know before you use Rifaldin 600 mg powder and solvent for solution for infusion

Do not use Rifaldin:

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

(including those listed in section 6),

• if you have liver disease and have yellow skin (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 (antiviral 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 "Using Rifaldin with other medications" 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 any liver function impairment. 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 along with isoniazid (a medication for tuberculosis), or are an elderly patient, or adolescent, are malnourished, or have a predisposition to nervous system disorders (e.g., if you are diabetic), your doctor may prescribe a supplementary intake of vitamin B6.
• 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 present early symptoms of hypersensitivity to Rifaldin such as fever, lymphadenopathy (swelling of lymph nodes), or biological alterations (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 a different origin for these symptoms cannot be established.

• If you present a severe, generalized, blistering skin rash, with blister formation 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, which is of no clinical importance. 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 could decrease or increase the exposure, safety, and efficacy of these medications (see "Using Rifaldin with other medications").

• If you have a bleeding problem or tend to bruise easily. Rifampicin may cause vitamin K-dependent coagulopathy (i.e., 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 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.

Using Rifaldin with other medications

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medications.

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 rhythm disorders: 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 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 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)
• certain medications used to thin the blood, such as clopidogrel
• dapsone: if you are taking dapsone (an antibiotic) with rifampicin, 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) may occur.

• lurasidone for schizophrenia and bipolar disorder, since rifampicin may reduce the blood levels of lurasidone.

In case you are taking any of these medications, it may be necessary for your doctor 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 another 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, it may be necessary for your doctor 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) since it decreases the blood levels of rifampicin. It is advisable to leave an interval of 8 hours between taking 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 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 (decrease in 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 liquidity 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:

• the determination of folates and vitamin B12 in blood,
• the bromosulfophthalein test,
• the levels of bilirubin 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 have taken 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 (Kinetic Interaction of Microparticles in Solution). For this reason, it is recommended to use other techniques in these patients, such as gas chromatography and mass spectrometry.

Tell your doctor or pharmacist if you are pregnant and if you are planning or need to have an abortion with mifepristone.

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 medicine.

Pregnancy

Since rifampicin crosses the placental barrier and there is not enough data to establish its safety during pregnancy, your doctor will carefully assess the convenience 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 is no data on the long-term ability of rifampicin to alter fertility.

Rifaldin contains sodium

This medication 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 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.

3. How to use Rifaldin 600 mg powder and solvent for solution for infusion

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 suspend your treatment beforehand. The dosage is individual 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 vial of 600 mg of rifampicin. Roll the vial slowly 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 from the reconstituted solution a volume equivalent to the calculated amount of rifampicin to be administered and add to 250 or 500 ml of infusion medium. Mix well and infuse at a rate that allows complete perfusion within 3 hours. Alternatively, the amount of rifampicin to be administered can be added to 100 ml of infusion medium and infused in 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 should be prepared and used within this period. After this period, precipitation of rifampicin in the infusion solution may occur.

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

The use of other infusion solutions is not recommended.

Dilution of the intravenous formulation in solutions other than 5% glucose solution and normal saline solution is not recommended. Intravenous solutions containing sodium bicarbonate and/or sodium lactate are physically incompatible with rifampicin.

Physical incompatibility (precipitation) has been observed with undiluted diltiazem hydrochloride solutions (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 decreased liver function or are elderly or if your general condition is not very good, you will be administered lower doses than the previous one. As a general rule for the treatment of tuberculosis, Rifaldin will be administered in combination with other antitubercular medications such as ethambutol 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 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.

Rifaldin 600 mg powder and solvent for solution for infusion is only for intravenous infusion. It should not be administered intramuscularly or subcutaneously.

If you use more Rifaldin than you should

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

After massive use of this medication, nausea, vomiting, stomach pain, itching, headache, and progressive drowsiness may be expected; 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, convulsions, and cardiac arrest have been reported.

A transient increase in liver enzymes and/or bilirubin may also occur.

A reddish-brown or orange color may also 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 treat the symptoms as deemed appropriate, such as stomach lavage and/or vomiting and administration of medications for symptoms, as well as monitoring your liver and kidney function.

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 forget to use Rifaldin

A double dose is not administered to compensate for forgotten doses.

4. Possible adverse effects

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

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

• Renal 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.

Very frequent adverse effects (may affect more than 1 in 10 patients):

• Fever, chills.

Frequent adverse effects (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 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 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, lymph node inflammation (lymphadenitis), difficulty breathing, and cough. Patients with a paradoxical reaction to the medication may also experience headaches, loss of appetite, and weight loss.

Uncommon adverse effects (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).
• 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 coagulation disorders.
• Anaphylactic reaction (severe allergic reaction that causes respiratory difficulty and even loss of consciousness).
• Adrenal insufficiency (alteration of adrenal gland function in patients with renal impairment).
• 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, 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).
• Skin reactions, itching, pruritic 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 fetal blood into the mother).
• Menstrual disorder.
• Porphyria.
• Edema (skin swelling due to fluid accumulation).
• Decrease in blood pressure.
• Increased creatinine in the blood.
• Increased liver enzymes.
• Interstitial lung disease (pulmonary disease): inform your doctor immediately if you develop 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 leaflet. You can also report them directly through the Spanish Medicines Monitoring System for Human Use: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Conservation of Rifaldin 600 mg powder and solvent for solution for infusion

Keep this medication out of 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 reconstitution of the vial with 10 ml of water for injection has been shown 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 storage times and conditions before administration are the responsibility of the user and should not normally exceed 24 hours between 2 and 8°C (or the times established earlier 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 with 500 ml of 5% glucose solution has been shown 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 storage times and conditions before administration are the responsibility of the user and should not normally exceed 24 hours between 2 and 8°C (or the times established earlier 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 with 500 ml of 0.9% NaCl has been shown 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 storage times and conditions before administration are the responsibility of the user and should not normally exceed 24 hours between 2 and 8°C (or the times established earlier 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 away through wastewater or household waste. Deposit the packaging and medicines that you no longer need in the SIGRE collection point at the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines that you no longer need. This way, you will help protect the environment.

6. Package contents and additional information

Rifaldin composition

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

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

Appearance of the product and package contents

Rifaldin 600 mg powder and solvent for solution for infusion is presented in a package with 1 vial of lyophilized powder and a solvent ampoule.

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 leaflet: August 2024

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