Package Leaflet: Information for the User

Rifaldin 20 mg/ml Oral Suspension

Rifampicin

Read this package leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this package leaflet, as 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 even if they have similar symptoms, as it may harm them.

If any of the following happen, stop taking the medicine and tell your doctor or pharmacist:

• 1. What Rifaldin 20 mg/ml Oral Suspension is and what it is used for

• 2. What you need to know before you start taking Rifaldin 20 mg/ml Oral Suspension

• 3. How to take Rifaldin 20 mg/ml Oral Suspension

• 4. Possible side effects

• 5. Storage of Rifaldin 20 mg/ml Oral Suspension

• 6. Contents of the pack and other 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 (in association with other antitubercular agents).

• Brucellosis.

• Elimination of meningococci in individuals 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

(see section 6).

• if you have liver disease and yellowing of the 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 attenuated 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 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 your 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 rifampicina with isoniazida (medication for tuberculosis), or you are elderly, or an 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) (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 generalized blistering skin rash, with blister formation 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, scaly rash with subcutaneous nodules and blisters (acute generalized pustular psoriasis), consult your doctor as soon as possible, as treatment with rifampicina should be suspended immediately.

• If you are diabetic. Treatment with rifampicina may make it difficult to manage diabetic patients.
• Due to rifampicina, discoloration (yellow, orange, red, brown) may occur in your teeth, urine, sweat, sputum, tears, and feces without clinical significance. Similarly, it may cause permanent discoloration of soft contact lenses.
• Rifampicina may compete with various medications at the level of absorption and biochemical/biochemical 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 disorder or tendency to easily bruise. Rifampicina 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.

Rifampicina 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 irregular heartbeat (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 systemic 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 disorders such as amyotrophic lateral sclerosis: riluzole
• medications with estrogenic and antiestrogenic activity (tamoxifen, toremifene)
• medications for the treatment of hepatitis C (daclatasvir, simeprevir, sofosbuvir, telaprevir, velpatasvir, voxilaprevir)
• other medications: hexobarbital (barbiturate) levothyroxine (for the treatment of hypothyroidism), methadone, theophylline (for the treatment of asthma), praziquantel (for the treatment of helminthic parasites)
• some medications used to thin the blood, such as clopidogrel
• dapsone: if you are taking dapsone (an antibiotic) with rifampicina, 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 rifampicina may reduce lurasidona blood levels.

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

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

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

The simultaneous use of ketoconazol and rifampicina 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 modify your dose.

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

You should not take Rifaldin with acid para-aminosalicylic (medication used for the treatment of tuberculosis) as this decreases rifampicina blood levels, so it is advisable to leave an 8-hour interval between taking both medications.

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

The simultaneous use of rifampicina with halotano or isoniazida increases the potential for liver toxicity. Do not use Rifaldin with halotano. If you have a treatment with rifampicina and isoniazida, your doctor will monitor your liver function periodically (see section 2. Warnings and precautions).

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

Maraviroc, another antiretroviral medication, should not be used simultaneously with rifampicina. If clinically justified, dose adjustment is required.

The simultaneous use of rifampicina with other antibiotics that cause vitamin K-dependent coagulopathy (decrease in blood's ability to coagulate) such as cefazolina (or other cefalosporins in the same group) may cause severe coagulation disorders (when blood loses its liquidity and becomes a gel to form a clot) that may lead to a fatal outcome (especially with high doses).

You should not take Rifaldin with the combination 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 agents 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 rifampicina, cases of falsely positive results for the presence of opiates in urine have been reported when the test was performed with a test called ICMS (Interaction Kinetics of Microparticles in Solution). With this in mind, it is recommended to use other techniques in these patients, such as gas chromatography and mass spectrometry.

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

Taking 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, that is:

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

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

Rifampicina 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

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

Fertility

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

Driving and operating machinery

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

Rifaldin 20 mg/ml oral suspension contains saccharose, ethanol, metabisulfito de sodio, parahidroxibenzoato de metilo, and parahidroxibenzoato de propilo.

This medication contains saccharose. If your doctor has told you that you are intolerant to certain sugars, consult with them before taking this medication.

Patients with diabetes mellitus should note that this medication contains 2 g of saccharose per 5 ml of oral suspension. It may cause caries.

This medication contains 0.95 mg of alcohol (ethanol) per ml of oral suspension, which is equivalent to 0.1% (p/v). The amount in 1 ml of oral suspension of this medication is equivalent to less than 0.023 ml of beer or 0.009 ml of wine.

The small amount of alcohol in this medication does not produce any perceptible effect.

This medication may cause severe allergic reactions and bronchospasm (sudden sensation of choking) because it contains metabisulfito de sodio (E223).

This medication may cause delayed allergic reactions and, exceptionally, bronchospasm (sudden sensation of choking) because it contains parahidroxibenzoato de metilo (E218) and parahidroxibenzoato de propilo (E216).

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

Follow exactly the administration instructions for 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 stop treatment prematurely. Dosage is individualized for you and may be modified by your doctor based on your response to treatment.

Shake before use.

Under no circumstances will more than 600 mg be taken per day.

Use in Children:

Dosage for children is based on their weight. Typically ranges from 10 mg to 20 mg per kilogram of body weight per day.

The usual dosage for children for tuberculosis treatment is 15 mg. In children with weight alterations, a dose reduction 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.

If You Take More Rifaldin Than You Should

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

After a massive intake of this medication, nausea, vomiting, stomach pain, itching, headache, and progressive drowsiness may be expected; in cases 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 temporary increase in liver enzymes and/or bilirubin may also occur.

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 symptoms they deem appropriate, such as stomach 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 Toxicological Information Service, phone: 915620420, indicating the medication and the amount ingested.

If You Forget to Take Rifaldin

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

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 (see section 2 - Warnings and precautions):

• 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 normal).

Your doctor will tell 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 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.

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

• Pseudomembranous colitis (severe inflammation of the intestine that may appear after antibiotic treatment).
• Influenza.
• Disseminated intravascular coagulation (problems with coagulation in the blood vessels in general).
• Eosinophilia (increase in a certain group of white blood cells).
• Agranulocytosis (decrease in a type of white blood cells, granulocytes).
• Hemolytic anemia (decrease in the number of red blood cells produced by their destruction).
• Vitamin K-dependent coagulopathy.
• Anaphylactic reaction(severe allergic reaction that may cause difficulty breathing and even loss of consciousness).
• Adrenal insufficiency (alteration of the function of the adrenal glands in patients with renal impairment).
• Loss of appetite.
• Psychotic disorder (mental state 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 tear color.
• Shock (cardiocirculatory insufficiency syndrome), rubefaction (redness of the skin), vasculitis (inflammation of the 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).
• Multi-form erythema.
• Severe skin reactions such as acute generalized exanthematous pustulosis (red and scaly rash with blisters under the skin and vesicles), Stevens-Johnson syndrome (generalized rash with vesicles and peeling of the skin, particularly around the mouth, nose, eyes, and genitals) and toxic epidermal necrolysis [generalized rash with vesicles 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 eosinophilia and elevated liver enzymes](see section 2. Warnings and precautions).
• Reactions, itching, pruritic rash, urticaria, allergic dermatitis, skin lesions with vesicles (pemphigus).
• Change in sweat color.
• Muscle weakness, myopathy (muscle disorder).
• Bone pain.
• Acute kidney damage due to normal cell death in the kidneys (tubular necrosis) or inflammation of the kidneys (tubulointerstitial nephritis).
• Chromaturia (abnormal urine color).
• Postpartum hemorrhage.
• Fetomaternal hemorrhage (entry of fetal blood into the mother).
• Menstrual disorder.
• Porphyria.
• Edema (skin swelling due to accumulation of fluids).
• Decreased blood pressure.
• Elevation of creatinine in the blood.
• Elevation of liver enzymes.
• Pulmonary inflammation (interstitial lung disease/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 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.

Medicines should not be disposed of through drains or in the trash. Dispose of the packaging and unused medicines at the SIGRE collection point of the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and unused medicines. By doing so, you will help protect the environment.

Composition of Rifaldin

• The active ingredient is rifampicin. Each ml of suspension contains 20 mg of rifampicin.
• The other components (excipients) are: agar-agar, sucrose, potassium sorbate (E202),

monopotassium salt of 4-hydroxybenzoic acid (E218), monopotassium salt of 4-hydroxybenzoic acid propyl ester (E216), sodium metabisulphite (E223), polysorbate, saccharin, diethanolamine (c.s.p. pH = 4.65), raspberry essence (contains ethanol) and purified water.

Appearance of the product and contents of the packaging

Rifaldin 20 mg/ml oral suspension is presented in bottles with 120 ml.

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 website of the Spanish Agency of Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/.