Rifinah

Package leaflet: Information for the user

Rifinah 150 mg/100 mg film-coated tablets, 300 mg/150 mg film-coated tablets

rifampicin/isoniazid
Please read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Rifinah is and what it is used for
2. What you need to know before taking Rifinah
3. How to take Rifinah
4. Possible side effects
5. How to store Rifinah
6. Contents of the pack and other information

1. What Rifinah is and what it is used for

Rifinah is a medicine that contains two active substances: rifampicin and isoniazid. These belong to a class of medicines called antibacterials, which work by suppressing the bacteria that cause tuberculosis (an infectious disease). Rifinah is used in the treatment of pulmonary and extrapulmonary tuberculosis.

2. What you need to know before taking Rifinah

Do not take Rifinah

• if you are allergic to the active substances or to any of the other ingredients of this medicine (listed in section 6);
• if you have a disease causing yellowing of the skin or eyes (jaundice);
• if you are taking a medicine containing saquinavir and ritonavir used to treat HIV infection, the virus that causes AIDS (see section “Other medicines and Rifinah”);
• if you are taking a medicine for schizophrenia and bipolar disorder called lurasidone (see section “Other medicines and Rifinah”).

Warnings and precautions
Talk to your doctor or pharmacist before taking Rifinah if:

• you have liver problems;
• you have severe kidney problems;
• you regularly drink alcohol or have alcoholism, if you inject drugs intravenously, if you are a black or Hispanic woman, as these conditions increase the likelihood of developing liver inflammation (hepatitis), sometimes fatal. If you experience fatigue, weakness, malaise, loss of appetite (anorexia), nausea or vomiting, inform your doctor, as these may be symptoms of liver inflammation;
• you suffer from porphyria (a rare inherited blood metabolism disorder);
• you are malnourished, elderly, adolescent, or have diabetes or nerve diseases (neuropathies): your doctor may decide to administer vitamin B6 at the same time;
• you have bleeding problems or a tendency to bruise easily (as this medicine may cause blood clotting disorders);
• you are taking other antibiotics (as some of them may increase the risk of blood clotting disorders);
• you have a history of lung inflammation (interstitial lung disease/pneumonitis).

If you are unsure whether any of these conditions apply to you, consult your doctor or pharmacist before taking Rifinah.
If you experience itching, fatigue, weakness, malaise, loss of appetite, nausea, vomiting, abdominal pain, yellowing of the eyes or skin, or dark urine, contact your doctor immediately. These symptoms may be related to liver inflammation or serious liver problems (hepatitis or cholestasis).
This medicine may cause a drug reaction (DRESS syndrome) characterized by rash, fever, internal organ inflammation, hematological abnormalities, and systemic diseases.
If you develop any of these symptoms, stop taking the medicine and contact your doctor as soon as possible; your doctor will assess whether treatment should be discontinued.
This medicine may cause severe skin reactions. If you notice any skin changes (e.g., mouth, throat, nose, or genital ulcers, widespread blisters and peeling), red and swollen eyes (Stevens-Johnson Syndrome – SJS), or severe and extensive skin damage with separation of the epidermis and superficial mucous membranes (toxic epidermal necrolysis – TEN), or a red, scaly rash with pustules and blisters (acute generalized exanthematous pustulosis – AGEP), stop taking the medicine and contact your doctor immediately.
If you notice any of the symptoms related to cerebellar syndrome described in section 4 – Possible side effects, consult your doctor or pharmacist. This syndrome has been mainly reported in patients with chronic kidney disease. Your doctor may reduce the dose or advise stopping treatment.
If you develop new or sudden worsening of breathlessness, possibly with dry cough or fever unresponsive to antibiotic treatment, inform your doctor immediately. These may be symptoms of lung inflammation (interstitial lung disease/pneumonitis) and may lead to serious breathing problems due to fluid accumulation in the lungs, interfering with normal respiration and potentially leading to life-threatening conditions.
If, while taking this medicine, tuberculosis symptoms return or worsen, inform your doctor immediately (see section 4. Possible side effects).
This medicine, when taken concomitantly with other medicines, may reduce their effectiveness. If you are taking Rifinah, always inform your doctor before taking any other medicine (also see section “Other medicines and Rifinah”).
This medicine may cause discoloration (yellow, orange, red, brown) of teeth, urine, sweat, sputum, and tears, and may permanently stain soft contact lenses.

Laboratory tests
Before taking this medicine, your doctor will prescribe blood tests.
Additionally, during treatment, your doctor will examine you monthly.
If you are over 35 years old, your doctor will prescribe specific monthly blood tests to monitor liver function.

Children
This medicine is not suitable for use in children.

Other medicines and Rifinah
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
The use of Rifinah must be avoided when taking saquinavir/ritonavir (used to treat HIV infection), halothane (an anesthetic), and daclatasvir, simeprevir, sofosbuvir, telaprevir (used to treat hepatitis C, a liver infection caused by a virus).
The use of Rifinah must be avoided when taking lurasidone, a medicine for schizophrenia and bipolar disorder, as rifampicin may reduce blood levels of lurasidone.
The use of Rifinah with other antibiotics that affect blood clotting mechanisms (such as cefazolin) may lead to severe, even fatal, blood clotting disorders and must therefore be avoided. If this combination cannot be avoided, your doctor will perform clinical monitoring, including hemostasis monitoring.
In particular, inform your doctor if you are taking any of the following medicines, as dose adjustments may be necessary:

• anticonvulsants or epilepsy medicines (e.g., phenytoin or carbamazepine);
• medicines for heart rhythm disorders (e.g., disopyramide, mexiletine, quinidine, propafenone, tocainide);
• medicines for treating certain cancers (e.g., tamoxifen, toremifene, irinotecan);
• medicines used to thin the blood (e.g., warfarin, clopidogrel);
• medicines for depression and other nervous system disorders (e.g., nortriptyline, haloperidol);
• antifungal medicines (e.g., caspofungin, fluconazole, itraconazole, ketoconazole);
• medicines for treating HIV infection (e.g., zidovudine, saquinavir, indinavir, efavirenz);
• medicines used to treat anxiety and sleep disorders (e.g., zopiclone, zolpidem, diazepam, or barbiturates);
• medicines for high blood pressure or other heart diseases (e.g., enalapril, losartan, diltiazem, nifedipine, verapamil, cardiac glycosides, and beta-blockers);
• antibiotics (e.g., fluoroquinolones such as telithromycin, quinine, dapsone, doxycycline, chloramphenicol, clarithromycin, para-aminosalicylic acid);
• anti-inflammatory medicines, such as cortisone;
• cholesterol-lowering medicines (e.g., clofibrate, statins);
• hormone-containing medicines (e.g., gestrinone, oral contraceptives such as the pill, estrogens, and progestins);
• medicines to reduce the body's immune response (e.g., tacrolimus, cyclosporine);
• diabetes medicines (e.g., sulfonylureas, thiazolidinediones such as rosiglitazone);
• a thyroid medicine (levothyroxine);
• narcotics used to treat pain (e.g., oxycodone, morphine) or to treat drug addiction (e.g., methadone);
• medicines for parasitic infections (e.g., praziquantel, atovaquone);
• a medicine used in amyotrophic lateral sclerosis (riluzole);
• a medicine for nausea and vomiting (ondansetron);
• a medicine for respiratory diseases (theophylline).

Pay special attention if you are taking:

• antacids: Rifinah should be taken at least 1 hour before taking an antacid;
• oral contraceptives: to avoid unintended pregnancy, switch to a different type of contraception, using a reliable barrier method such as condoms or an intrauterine device (IUD), as Rifinah reduces the effectiveness of oral contraceptives;
• dapsone (an antibiotic): when used with rifampicin, it may cause hematological toxicity, including bone marrow suppression and reduced red blood cells, and methemoglobinemia (reduced oxygen in the blood due to red blood cell abnormalities);
• paracetamol: when used with rifampicin, it may increase the risk of liver damage.

Inform your doctor or pharmacist if you are pregnant and planning or undergoing a medical abortion using mifepristone.

Diagnostic tests
Rifinah contains rifampicin and isoniazid. This combination may increase the risk of liver problems; therefore, your doctor may prescribe periodic blood tests.
Rifinah may interfere with certain diagnostic and laboratory tests. Inform your doctor if you need to undergo medical or laboratory tests, especially:

• a test to measure vitamin B12 or folate levels in the blood;
• a gallbladder examination;
• a urine test to detect opiates.
  It is possible that, especially during the first days of treatment, liver-related laboratory values such as bilirubin and transaminases may increase; your doctor will arrange appropriate monitoring.

Rifinah with food, drinks, and alcohol
If you are taking Rifinah, consuming the following foods and drinks may cause headache, sweating, flushing, palpitations, and low blood pressure:

• cheese;
• tuna or other tropical fish;
• red wine.

Therefore, it is advisable to avoid the above-mentioned foods and drinks during treatment with Rifinah.

Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, use this medicine only if your doctor considers it necessary and under their direct supervision.
Pregnancy
Rifampicin has shown teratogenic effects (i.e., may cause fetal malformations) at high doses in rodent studies; it crosses the placenta and is present in umbilical cord blood, but its effect on the fetus is unknown.
When rifampicin is administered during the last weeks of pregnancy, it may cause postnatal hemorrhage in both mother and newborn; therefore, its use must be closely monitored by qualified healthcare personnel. In rats and rabbits, isoniazid has been shown to affect embryonic heart development when administered orally during pregnancy, although congenital anomalies were not observed in reproductive studies in mammals (mouse, rat, rabbit).
Breastfeeding
Rifampicin and isoniazid pass into breast milk. Therefore, Rifinah should be used during breastfeeding only if the potential benefit outweighs the risk to the newborn.

Driving and using machines
Rifinah may cause certain side effects (e.g., dizziness and low blood pressure) that may impair your ability to concentrate and perform tasks requiring attention. If this occurs, avoid driving vehicles or operating machinery.

Rifinah contains sucrose – if your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.

Rifinah 300 mg/150 mg tablets contain sunset yellow which may cause allergic reactions.

Rifinah 300 mg/150 mg tablets contain sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially “sodium-free”.

3. How to take Rifinah

Take this medicine exactly as prescribed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
The recommended dose is:
Use in adults and elderly
Rifinah 150 mg/100 mg coated tablets: 3 to 4 tablets per day.
Rifinah 300 mg/150 mg coated tablets: 2 tablets per day.
Take all tablets at the same time, as a single daily dose.
The tablets should be taken at least 30 minutes before a meal or 2 hours after a meal.
Use in children
This medicine is NOT recommended for use in children.
If you take more Rifinah than you should
If you take more Rifinah than prescribed, inform your doctor immediately or go to the nearest hospital.
Take the medicine package with you so that the doctor knows what you have taken.
Some symptoms of overdose may include: nausea, vomiting, stomach pain, itching, headache, drowsiness,
dizziness, speech disturbances, blurred vision or hallucinations (seeing things that are not there, such as
bright colors and strange shapes), loss of consciousness (in case of severe liver disease). Other symptoms
include: brownish-red or orange discoloration of the skin, urine, sweat, saliva, tears and faeces, the
intensity of which is proportional to the dose taken, changes in liver blood tests (elevated liver enzymes
and bilirubin). In children, swelling of the face, eyes or eyelids may occur. Less commonly, you may
experience: low blood pressure, rapid and/or irregular heartbeat, seizures and cardiac arrest.
In cases where the dose taken is much higher than prescribed, breathing difficulties and decreased activity
of the central nervous system (which may include slowed breathing, speech disturbances, slowed
heartbeat, delayed reflexes, etc.) may occur, potentially leading to coma and severe, intractable seizures.
If you forget to take Rifinah
Do not take a double dose to make up for a missed tablet.
If you stop taking Rifinah
Do not stop treatment without consulting your doctor, as sudden discontinuation may cause allergic
reactions and anaphylactic shock (a severe allergic reaction causing breathing difficulties, swelling of
the face and lips, tongue and other body parts).
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
If you experience any of the following side effects, contact your doctor immediately and
stop taking the medicine:

• Inflammation of the pancreas causing severe abdominal and back pain (pancreatitis, frequency not known);
• Severe and widespread skin damage (separation of the epidermis and superficial mucous membranes) (toxic epidermal necrolysis - TEN, may affect up to 1 in 1,000 people);
• A drug reaction causing redness of the skin, fever, internal organ inflammation, blood abnormalities, and systemic illness (DRESS syndrome, may affect up to 1 in 1,000 people);
• Yellowing of the skin and whites of the eyes, dark urine, pale stools, fatigue, weakness, malaise, loss of appetite, nausea or vomiting due to liver problems (hepatitis, may affect up to 1 in 100 people);
• Skin disorders, difficulty swallowing or breathing, shortness of breath, swelling of the lips, face, throat or tongue. These may be symptoms of anaphylactic shock (a severe allergic reaction);
• Any skin changes (e.g. mouth, throat, nose, genital ulcers, widespread blisters and peeling), conjunctivitis (red and swollen eyes). These may be symptoms of a serious skin reaction called “Stevens-Johnson syndrome” - SJS;
• Red, scaly rash with pustules and blisters (acute generalised exanthematous pustulosis - AGEP);
• Inflammation of small blood vessels in the skin causing a reddish-purple skin rash called “purpura”. The medicine may reduce the number of certain blood cells called platelets (thrombocytopenia, may affect up to 1 in 10 people), which can lead to this abnormal accumulation of blood under the skin. This condition usually resolves upon discontinuation of treatment, but may worsen, potentially leading to brain bleeding and death, if treatment is not stopped or is restarted after the onset of this “purpura”.

The following side effects have also been reported with the use of this medicine:
Very common side effects (may affect more than 1 in 10 people)

• Fever, chills.

Common side effects (may affect up to 1 in 10 people)

• Headache, dizziness;
• Nausea, vomiting;
• Increased bilirubin in the blood (hyperbilirubinemia);
• Abnormal liver function tests (increased aspartate aminotransferase; increased alanine aminotransferase);
• Paradoxical reaction to the drug: during treatment, after initial improvement, tuberculosis symptoms may reappear or new symptoms may arise. Paradoxical reactions have been reported as early as 2 weeks and up to 18 months after starting anti-tuberculosis treatment. These reactions are typically associated with fever, enlarged lymph nodes (lymphadenitis), shortness of breath and cough. Patients with a paradoxical drug reaction may also experience headache, loss of appetite and weight loss.

Uncommon side effects (may affect up to 1 in 100 people)

• Changes in blood cells (leucopenia);
• Diarrhea.

Side effects with unknown frequency (frequency cannot be estimated from the available data):

• Painful inflammatory condition of the colon (last part of the intestine), characterized by cramps, persistent diarrhea, weakness and fever (pseudomembranous colitis);
• Changes in blood cells (agranulocytosis, eosinophilia, anaemia);
• Blood clotting disorders (vitamin K-dependent);
• Bleeding;
• Allergic reactions;
• Breast enlargement in men (gynaecomastia);
• A disease called “pellagra” characterized by gastrointestinal disorders (e.g. diarrhoea), nervous and mental disorders (e.g. mental confusion, insomnia, nervousness, psychomotor slowing, apathy, depression, dementia, delirium), and skin lesions (e.g. scaly skin);
• Inflammation of nerves (polyneuritis) which may cause tingling in limbs, muscle weakness, loss of tendon reflexes, etc.;
• Severe liver inflammation (hepatitis), sometimes fatal;
• Impaired bile flow (cholestasis);
• Decreased appetite (anorexia);
• Stomach and intestinal disorders, abdominal discomfort;
• Inflammation of the pancreas (pancreatitis);
• Skin redness and other skin disorders, with itching, hives, acne;
• Severe and widespread skin redness with peeling (exfoliative dermatitis);
• A rare disease affecting the skin and mucous membranes characterized by blister formation (pemphigus);
• A chronic disease that may affect various organs of the body (systemic lupus erythematosus-like syndrome);
• Muscle weakness, diseases affecting muscles (myopathies);
• Bleeding after childbirth (in mother and foetus);
• Menstrual cycle disturbances;
• Fluid retention leading to swelling in certain parts of the body (oedema);
• Malaise and fever;
• Flushing;
• Inflammation of blood vessels causing skin disorders, weakness, fever, joint and muscle pain (vasculitis);
• Changes in the colour of tears, sputum, sweat or urine;
• Tooth discolouration (which may be permanent);
• Attacks of porphyria in patients who already suffer from this condition (a rare inherited blood metabolism disorder);
• Abnormal liver function tests (increased liver enzymes, increased alkaline phosphatase);
• Increased blood creatinine levels (creatinine indicates kidney function);
• Influenza-like symptoms with bone pain and general malaise;
• Breathing difficulties (dyspnoea) and wheezing;
• Low blood pressure;
• Low blood pressure leading to impaired consciousness and other mental functions (shock);
• Acute kidney injury due to onset of kidney diseases (e.g. renal tubular necrosis or tubulo-interstitial nephritis);
• A serious condition characterized by widespread blood clot formation (disseminated intravascular coagulation);
• Seizures;
• A condition characterized by mental confusion, altered level of consciousness and coma due to accumulation of toxic substances (toxic encephalopathy);
• Inflammation of nerves (neuritis) affecting the eye, causing blurred vision and reduced visual field (optic atrophy);
• Memory disorders;
• Mental disorders;
• Poor coordination of movements, imbalance, changes in speech, involuntary eye movements (cerebellar syndrome);
• Impaired adrenal function in patients who already have adrenal problems;
• Inflammation of the lungs (interstitial lung disease/pneumonitis): inform your doctor immediately if you develop a new or sudden worsening of breathlessness, possibly with cough or fever;
• Hair loss.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the website
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Rifinah

Do not store above 30°C.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after "Exp.". The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Rifinah contains
Rifinah 150 mg/100 mg film-coated tablets

• The active substances are: rifampicin and isoniazid. Each tablet contains 150 mg of rifampicin and 100 mg of isoniazid.
• The other components are: sodium lauryl sulfate, calcium stearate, sodium carmellose, microcrystalline cellulose, gelatin, sucrose, talc, magnesium carbonate, titanium dioxide (E171), kaolin, aluminium lake of erythrosine (E127), magnesium stearate, arabic gum, anhydrous colloidal silica, povidone.

Rifinah 300 mg/150 mg film-coated tablets

• The active substances are: rifampicin and isoniazid. Each tablet contains 300 mg of rifampicin and 150 mg of isoniazid.
• The other components are: sodium lauryl sulfate, calcium stearate, sodium carmellose, microcrystalline cellulose, gelatin, sucrose, talc, magnesium carbonate, titanium dioxide (E171), kaolin, aluminium lake of sunset yellow (E110), magnesium stearate, arabic gum, anhydrous colloidal silica, povidone.

Description of the appearance of Rifinah and package contents
Rifinah 150 mg/100 mg film-coated tablets are supplied in a box containing 8 tablets.
Rifinah 300 mg/150 mg film-coated tablets are supplied in a box containing either 8 tablets or 24 tablets.

Marketing Authorisation Holder and Manufacturer
Sanofi S.r.l. – Viale L. Bodio, 37/B – 20158 Milan, Italy
Manufacturer
Sanofi S.r.l. - Via Valcanello, 4 – 03012 Anagni (FR) - Italy