CIPROFLOXACIN COMBIX 500 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

Ciprofloxacin Combix 500 mg Film-Coated Tablets EFG

Read the entire package leaflet carefully before starting to take this medication, as it contains important information for you.

• Keep this package leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed to you only, and you should not give it to others, even if they have the same symptoms as you, as it may harm them.
• If you experience side effects, consult your doctor or pharmacist, even if they are not listed in this package leaflet. See section 4.

Contents of the Package Leaflet

1. What is Ciprofloxacin Combix and what is it used for
2. What you need to know before taking Ciprofloxacin Combix
3. How to take Ciprofloxacin Combix
4. Possible side effects
5. Storage of Ciprofloxacin Combix
6. Package Contents and Additional Information

1. What is Ciprofloxacin Combix and what is it used for

Ciprofloxacin Combix contains the active ingredient ciprofloxacin. Ciprofloxacin is an antibiotic that belongs to the fluoroquinolone family. Ciprofloxacin works by eliminating the bacteria that cause infections. It only acts on specific strains of bacteria.

Adults

Ciprofloxacin is used in adults to treat the following bacterial infections:

• respiratory tract infections
• long-term or recurrent ear or sinus infections
• urinary tract infections
• male and female genital tract infections
• gastrointestinal and intra-abdominal infections
• skin and soft tissue infections
• bone and joint infections
• prevention of infections caused by the bacteria Neisseria meningitidis
• inhalation exposure to anthrax.

Ciprofloxacin may be used in the treatment of patients with a low white blood cell count (neutropenia) who have fever suspected to be due to a bacterial infection.

In the case of a severe infection or if the infection is caused by more than one type of bacteria, you may be given additional antibiotic treatment, in addition to ciprofloxacin.

Children and Adolescents

Ciprofloxacin is used in children and adolescents, under specialized medical supervision, to treat the following bacterial infections:

• lung and bronchial infections in children and adolescents with cystic fibrosis
• complicated urinary tract infections, including those that have reached the kidneys (pyelonephritis)
• inhalation exposure to anthrax.

Ciprofloxacin may also be used to treat severe infections in children and adolescents when your doctor considers it necessary.

2. What you need to know before taking Ciprofloxacin Combix

Do not take Ciprofloxacin Combix

• if you are allergic to ciprofloxacin, other quinolones, or any of the other ingredients of this medication (listed in section 6),
• if you are taking tizanidine (see section 2: "Other medications and Ciprofloxacin Combix").

Warnings and Precautions

Before starting to take this medication

You should not take antibacterial medications that contain fluoroquinolones or quinolones, including ciprofloxacin, if you have experienced a severe adverse reaction in the past when taking a quinolone or fluoroquinolone. If this is the case, you should inform your doctor as soon as possible.

Quinolone antibiotics may cause an increase in your blood sugar levels above normal levels (hyperglycemia) or a decrease in your blood sugar levels below normal levels, which in severe cases can lead to loss of consciousness (hypoglycemic coma) (see section 4). This is important for people with diabetes. If you have diabetes, your blood sugar levels should be carefully monitored.

Consult your doctor before starting to take this medication

• if you have ever had kidney problems, as your treatment may need to be adjusted,
• if you have epilepsy or other neurological conditions,
• if you have a history of tendon problems during previous treatment with antibiotics such as ciprofloxacin,
• if you are diabetic, as you may be at risk of hypoglycemia with ciprofloxacin,
• if you have severe myasthenia (a type of muscle weakness), as symptoms may worsen,
• if you have been diagnosed with an enlarged or "bulging" blood vessel (aortic aneurysm or large peripheral vessel aneurysm),
• if you have had a previous episode of aortic dissection (tear in the aortic wall),
• if you have been diagnosed with heart valve insufficiency (regurgitation of the heart valves),
• if you have a family history of aortic dissection or aneurysm, congenital heart valve disease, or other risk factors or predisposing conditions (e.g., Marfan syndrome, Ehlers-Danlos syndrome, Turner syndrome, or Sjögren's syndrome (an autoimmune inflammatory disease), vascular disorders such as Takayasu arteritis, giant cell arteritis, Behçet's disease, hypertension, atherosclerosis, rheumatoid arthritis (a joint disease), or endocarditis (a heart infection)),
• if you have heart problems. Caution should be exercised when administering ciprofloxacin if you have been born with or have a family history of prolonged QT interval (seen on the ECG, the electrical recording of the heart), have an electrolyte imbalance (especially low potassium or magnesium levels in the blood), have a very slow heart rate (known as bradycardia), have a delicate heart (heart failure), have a history of heart attacks (myocardial infarction), are a woman, or are an elderly patient, or are taking other medications that result in abnormal ECG changes (see section 2: "Other medications and Ciprofloxacin Combix"),
• if you or a family member has a deficiency of glucose-6-phosphate dehydrogenase (G6PD), you may be at risk of anemia with ciprofloxacin.

For the treatment of some genital tract infections, your doctor may prescribe another antibiotic in addition to ciprofloxacin. If there is no improvement in symptoms after 3 days of treatment, please consult your doctor.

During treatment with this medication

Inform your doctor immediately if any of the following situations occur while taking ciprofloxacin. Your doctor will decide whether it is necessary to interrupt treatment with ciprofloxacin.

• If you experience sudden and severe abdominal, chest, or back pain, which may be symptoms of aortic dissection or aneurysm, go to the emergency room immediately.

The risk may increase if you are receiving systemic corticosteroid treatment.

• If you start experiencing sudden shortness of breath, especially when lying down, or if you notice swelling in your ankles, feet, or abdomen, or the appearance of heart palpitations (feeling of rapid or irregular heartbeat), inform your doctor immediately.

• Severe and sudden allergic reaction(anaphylactic reaction or shock, angioedema). There is a reduced possibility that, even with the first dose, you may experience a severe allergic reaction, with the following symptoms: chest tightness, feeling of dizziness, nausea, or fainting, or experiencing dizziness when standing up. If this happens, do not take more ciprofloxacin and contact your doctor immediately.

Severe, disabling, and potentially irreversible side effects

• Antibacterial medications that contain fluoroquinolones or quinolones, including ciprofloxacin, have been associated with very rare but severe side effects, some of which were long-lasting (persistent for months or years), disabling, or potentially irreversible. This includes pain in the tendons, muscles, and joints of the upper and lower limbs, difficulty walking, abnormal sensations such as pinching, tingling, prickling, numbness, or burning (paresthesia), sensory disorders such as decreased vision, taste, smell, or hearing, depression, decreased memory, intense fatigue, and severe sleep disorders.

If you experience any of these side effects after taking ciprofloxacin, contact your doctor immediately, before continuing treatment. You and your doctor will decide whether to continue or not continue treatment, also considering the use of an antibiotic from another class.

• In rare cases, joint and tendon pain and swelling or tendon inflammation or rupturemay occur. The risk is higher if you are an elderly person (over 60 years old), have received an organ transplant, have kidney problems, or are being treated with corticosteroids. Tendon inflammation and rupture can occur within the first 48 hours of treatment and even several months after stopping treatment with ciprofloxacin. At the first sign of pain or tendon inflammation (e.g., in the ankle, wrist, elbow, shoulder, or knee), stop taking ciprofloxacin, contact your doctor, and rest the affected area. Avoid any unnecessary exercise, as this may increase the risk of tendon rupture.

• If you have epilepsyor another neurological condition, such as cerebral ischemia or infarction, you may experience side effects associated with the central nervous system. If seizures occur, stop taking ciprofloxacin and contact your doctor immediately.

• In rare cases, you may experience symptoms of nerve damage (neuropathy)such as pain, burning, tingling, numbness, and/or weakness, especially in the feet and legs or hands and arms. If this happens, stop taking ciprofloxacin and inform your doctor immediately to prevent the development of a potentially irreversible disorder.

• You may experience psychiatric reactionsthe first time you take ciprofloxacin. If you have depressionor psychosis, your symptoms may worsen with ciprofloxacin treatment. In rare cases, depression or psychosis may progress to suicidal thoughts, attempted suicide, or completed suicide. If this happens, stop taking ciprofloxacin and contact your doctor immediately.

• Diarrheamay develop while taking antibiotics, including ciprofloxacin, or even several weeks after stopping them. If diarrhea becomes severe or persistent, or if you notice that the stool contains blood or mucus, stop taking ciprofloxacin and contact your doctor immediately, as this can be life-threatening. Do not take medications that stop or slow down bowel movements.

• If your visionworsens or if you have any other eye disorders, consult an ophthalmologist immediately.

• Your skin becomes more sensitive to sunlight or ultraviolet (UV) lightwhen taking ciprofloxacin. Avoid exposure to intense sunlight or artificial UV light, such as tanning beds.

• While taking ciprofloxacin, inform your doctor or laboratory personnel if you need to undergo a blood or urine test.

• If you have kidney problems, inform your doctor, as your dose may need to be adjusted.

• Ciprofloxacin may cause liver damage. If you notice symptoms such as loss of appetite, jaundice (yellowing of the skin), dark urine, itching, or stomach pain, consult your doctor immediately.

• Ciprofloxacin may cause a decrease in the white blood cell count and may decrease your resistance to infections. If you experience an infection with symptoms such as fever and severe deterioration of your general condition, or fever with symptoms of local infection such as sore throat/pharynx/mouth, or urinary problems, consult your doctor immediately. They will perform a blood test to examine the possible decrease in white blood cells (agranulocytosis). It is essential to inform your doctor about your medication.

Other medications and Ciprofloxacin Combix

Inform your doctor or pharmacist if you are taking, have recently taken, or may need to take any other medication.

Do not take ciprofloxacin at the same time as tizanidine, as this may cause side effects such as low blood pressure and drowsiness (see section 2: "What you need to know before taking Ciprofloxacin Combix").

It is known that the following medications interact with ciprofloxacin in your body. If you take ciprofloxacin at the same time as these medications, this may affect the therapeutic effect of these medications. It may also increase the likelihood of experiencing side effects.

Inform your doctor if you are taking:

• vitamin K antagonists (e.g., warfarin, acenocoumarol, phenprocoumon, or fluindione) or other oral anticoagulants (to thin the blood),
• probenecid (for gout),
• methotrexate (for certain types of cancer, psoriasis, rheumatoid arthritis),
• theophylline (for respiratory problems),
• tizanidine (for muscle spasticity in multiple sclerosis),
• olanzapine (an antipsychotic),
• clozapine (an antipsychotic),
• ropinirole (for Parkinson's disease),
• phenytoin (for epilepsy),
• metoclopramide (for nausea and vomiting),
• cyclosporine (for skin diseases, rheumatoid arthritis, and organ transplants),
• other medications that may alter your heart rhythm: antiarrhythmic medications (e.g., quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide), tricyclic antidepressants, some antimicrobials (belonging to the macrolide group), some antipsychotics,
• zolpidem (for sleep disorders).

Ciprofloxacin may increaseblood levels of the following medications:

• pentoxifylline (for circulatory disorders),
• caffeine,
• duloxetine (for depression, diabetic neuropathy, or incontinence),
• lidocaine (for heart diseases or anesthetic use),
• sildenafil (e.g., for erectile dysfunction),
• agomelatine (for depression).

Some medications decreasethe effect of ciprofloxacin. Inform your doctor if you are taking or plan to take:

• antacids,
• omeprazole,
• mineral supplements,
• sucralfate,
• a polymeric phosphate binder (e.g., sevelamer or lanthanum carbonate),
• medications or supplements containing calcium, magnesium, aluminum, or iron.

If these preparations are essential, take ciprofloxacin approximately two hours before or four hours aftertaking these preparations.

Taking Ciprofloxacin Combix with food and drinks

Although you can take ciprofloxacin with meals, you should not eat or drink any dairy products (such as milk or yogurt) or beverages with added calcium when taking the tablets, as they may affect the absorption of the active ingredient.

Pregnancy and breastfeeding

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

It is recommended to avoid using ciprofloxacin during pregnancy.

Do not take ciprofloxacin during breastfeeding, as ciprofloxacin is excreted in breast milk and may harm your baby.

Driving and using machines

Ciprofloxacin may decrease your alertness. Some neurological effects may occur. Therefore, make sure you know how you react to ciprofloxacin before driving a vehicle or using a machine. If in doubt, consult your doctor.

3. How to take Ciprofloxacino Combix

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

Your doctor will explain exactly how much ciprofloxacin you should take, how often, and for how long. This will depend on the type of infection you have and its severity.

Inform your doctor if you have kidney problems, as it may be necessary to adjust your dose.

Treatment usually lasts from 5 to 21 days, but it can last longer for severe infections.

• Swallow the tablets with a large amount of liquid. Do not chew the tablets because their taste is not pleasant.
• Try to take the tablets at the same time every day.
• You can take the tablets with or between meals. The calcium you take as part of a meal will not seriously affect the absorption of the medication. However, do not take ciprofloxacin tablets with dairy products such as milk or yogurt, or with fruit juices enriched with calcium (e.g., calcium-enriched orange juice).

Remember to drink a large amount of liquids while taking this medication.

The score line is only for breaking the tablet if you find it difficult to swallow it whole.

If you take moreCiprofloxacino Combixthan you should

If you take more than the prescribed amount, seek medical help immediately. If possible, take the tablets or the box with you to show the doctor.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

If you forget to takeCiprofloxacino Combix

Take the normal dose as soon as possible and then continue treatment as prescribed. However, if it is almost time for your next dose, do not take the missed dose and continue as usual. Do not take a double dose to make up for missed doses. Make sure to complete the treatment cycle.

If you stop treatment with Ciprofloxacino Combix

It is important that you complete the full treatment, even if you start to feel better after a few days. If you stop taking this medication too soon, your infection may not be completely cured, and symptoms may return or worsen. You may develop resistance to the antibiotic.

If you have any other questions about using this medication, ask your doctor or pharmacist.

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone will experience them.

The following section contains the most serious side effects that you may recognize yourself:

Stop taking ciprofloxacin and contact your doctor immediatelyto consider another treatment with antibiotics if you notice any of the following serious side effects:

Rare(may affect up to 1 in 1,000 people):

• seizures (see section 2: "Warnings and precautions").

Very rare(may affect up to 1 in 10,000 people):

• severe allergic reaction with symptoms such as chest tightness, dizziness, nausea, or fainting, or experiencing dizziness when standing up (anaphylactic reaction) (see section 2: "Warnings and precautions"),
• muscle weakness, tendon inflammation that can lead to tendon rupture, especially the long tendon in the back of the ankle (Achilles tendon) (see section 2: "Warnings and precautions"),
• skin rashes with a risk of death, usually in the form of blisters or ulcers in the mouth, throat, nose, eyes, and other mucous membranes, such as the genitals, which can progress to generalized blistering or skin peeling (Stevens-Johnson syndrome, toxic epidermal necrolysis).

Frequency not known(cannot be estimated from available data):

• unusual sensations of pain, burning, tingling, numbness, or muscle weakness in the limbs (neuropathy) (see section 2: "Warnings and precautions"),
• a drug reaction that causes skin rash, fever, inflammation of internal organs, blood alterations, and systemic disease (DRESS - Drug Reaction with Eosinophilia and Systemic Symptoms, PEAG - Generalized Acute Pustular Exanthem).

Other side effects that have been observed during treatment with ciprofloxacin are listed below according to their probability:

Frequent(may affect up to 1 in 10 people):

• nausea, diarrhea,
• joint pain and joint inflammation in children.

Uncommon(may affect up to 1 in 100 people):

• joint pain in adults,
• fungal superinfections,
• an elevated concentration of eosinophils, a type of white blood cell,
• decreased appetite,
• hyperactivity or agitation,
• headache, dizziness, sleep problems, or taste disorders,
• vomiting, abdominal pain, digestive problems such as slow digestion (indigestion/heartburn) or flatulence,
• increased levels of certain substances in the blood (transaminases and/or bilirubin),
• skin rash, itching, or hives,
• renal impairment,
• muscle and bone pain, feeling of discomfort (asthenia) or fever,
• increased alkaline phosphatase in the blood.

Rare(may affect up to 1 in 1,000 people):

• muscle pain, joint inflammation, increased muscle tone, and cramps,
• inflammation of the intestine (colitis) associated with the use of antibiotics (can be life-threatening in very rare cases) (see section 2: "Warnings and precautions"),
• changes in blood cell count (leukopenia, leukocytosis, neutropenia, anemia), increased or decreased levels of a blood clotting factor (thrombocytes),
• allergic reaction, swelling (edema), or rapid swelling of the skin and mucous membranes (angioedema) (see section 2: "Warnings and precautions"),
• increased blood sugar (hyperglycemia),
• decreased blood sugar (hypoglycemia) (see section 2: "Warnings and precautions"),
• confusion, disorientation, anxiety reactions, unusual dreams, depression (potentially leading to suicidal thoughts, suicide attempts, or completed suicides) (see section 2: "Warnings and precautions"), or hallucinations,
• tingling and numbness, unusual sensitivity to sensory stimuli, decreased skin sensitivity, tremors, or dizziness,
• vision problems (including double vision) (see section 2: "Warnings and precautions"),
• tinnitus (ringing in the ears), hearing loss, deterioration of hearing,
• increased heart rate (tachycardia),
• expansion of blood vessels (vasodilation), decreased blood pressure, or fainting,
• difficulty breathing, including asthma-like symptoms,
• liver disorders, jaundice (cholestatic jaundice), hepatitis,
• sensitivity to light (see section 2: "Warnings and precautions"),
• renal failure, blood or crystals in the urine, inflammation of the urinary tract,
• fluid retention or excessive sweating,
• increased amylase enzyme levels.

Very rare(may affect up to 1 in 10,000 people):

• a special type of decrease in red blood cell count (hemolytic anemia), a dangerous decrease in a type of white blood cell (agranulocytosis) (see section 2: "Warnings and precautions"), a decrease in the number of white and red blood cells and platelets (pancytopenia), with a risk of death, and bone marrow depression, also with a risk of death,
• an allergic reaction called a serum sickness-like reaction (see section 2: "Warnings and precautions"),
• mental disorders (psychotic reactions potentially leading to suicidal thoughts, suicide attempts, or completed suicides) (see section 2: "Warnings and precautions"),
• migraine, coordination disorder, instability when walking (gait disorders), disorders of the sense of smell (olfactory disorders); brain pressure (intracranial pressure and pseudotumor cerebri),
• visual color distortions,
• inflammation of the blood vessel walls (vasculitis),
• pancreatitis,
• death of liver cells (necrosis), which very rarely leads to liver failure with a risk of death (see section 2: "Warnings and precautions"),
• small pinpoint hemorrhages under the skin (petechiae), various skin rashes or exanthems,
• worsening of myasthenia gravis symptoms (see section 2: "Warnings and precautions").

Frequency not known(cannot be estimated from available data):

• syndrome associated with deficient water secretion and low sodium concentrations (SIADH),
• feeling very excited (mania) or feeling very optimistic and hyperactive (hypomania),
• abnormally fast heart rate, irregular heart rate with life-threatening risk, heart rhythm disorder (called "prolonged QT interval", observed in the ECG, heart electrical activity),
• influence on blood coagulation (in patients treated with vitamin K antagonists),
• loss of consciousness due to a severe decrease in blood sugar levels (hypoglycemic coma). See section 2.

The administration of antibiotics containing quinolones and fluoroquinolones has been associated with very rare cases of long-lasting (even months or years) or permanent adverse reactions, such as tendon inflammation, tendon rupture, joint pain, limb pain, difficulty walking, abnormal sensations such as pinching, tingling, burning, numbness, or pain (neuropathy), fatigue, decreased memory and concentration, effects on mental health (including sleep disorders, anxiety, panic attacks, depression, and suicidal ideas), as well as decreased hearing, vision, taste, and smell, in some cases regardless of the presence of pre-existing risk factors.

There have been reports of increased size and weakening or tearing of the aortic wall (aneurysms and dissections), which could lead to rupture and be fatal, and heart valve failure in patients who have received fluoroquinolones. See also section 2.

Reporting of side effects

If you experience any side effects, consult your doctor or pharmacist, even if it is a possible side effect not listed in this leaflet. You can also report them directly through the Spanish Medication Pharmacovigilance System https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medication.

5. Storage of Ciprofloxacino Combix

Keep this medication out of sight and reach of children.

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

This medication does not require special storage conditions.

Medications should not be thrown down the drain or into the trash. Deposit the packaging and unused medications at the SIGRE collection point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and unused medications. This will help protect the environment.

6. Package contents and additional information

Composition of Ciprofloxacino Combix

• The active ingredient is ciprofloxacin. Each film-coated tablet contains 500 mg of ciprofloxacin (as ciprofloxacin hydrochloride monohydrate).
• The other ingredients are:

Tablet core: microcrystalline cellulose, crospovidone, anhydrous colloidal silica, and magnesium stearate.

Coating material: Opadry white 02B28654 (composed of: hypromellose, macrogol, and titanium dioxide (E171)).

Appearance of the product and package contents

Ciprofloxacino Combix are white or yellowish film-coated tablets, oval, biconvex, with a score line on both sides, notched on one face, and engraved with "C500" on the other.

The score line is only for breaking the tablet to facilitate swallowing, but not for dividing into equal doses.

Ciprofloxacino Combix 500 mg is presented in PVC/Aluminum blisters, in packages of 14 tablets.

Marketing authorization holder and manufacturer

Marketing authorization holder

Laboratorios Combix, S.L.U.

C/ Badajoz 2, Edificio 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer

Zydus France

ZAC Les Hautes Patures

Parc d'activités des Peupliers

25 Rue des Peupliers

92000 Nanterre

France

O

Pharmex Advanced Laboratories S.L.

Ctra. A-431 Km. 19

14720 Almodóvar del Río (Córdoba)

Spain

O

Centre Spécialités Pharmaceutiques

ZAC des Suzots

35 rue de la Chapelle

63450 Saint Amant Tallende

France

O

Netpharmalab Consulting Services S.L.

Carretera de Fuencarral 22,

Alcobendas,

28108 Madrid

Spain

O

Flavine Pharma France

3 Voie d’Allemagne

13127 Vitrolles

France

Date of the last revision of this leaflet: May 2025

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

Medical advice/education

Antibiotics are used to cure bacterial infections. They are not effective against viral infections.

If your doctor has prescribed antibiotics, you need them precisely for your current illness.

Despite antibiotics, some bacteria may survive or grow. This phenomenon is known as resistance: some antibiotic treatments become ineffective.

Misuse of antibiotics increases resistance. You can even help bacteria become more resistant and, therefore, delay your recovery or decrease the effectiveness of antibiotics if you do not respect:

• the dose,
• the schedule,
• the treatment duration.

Consequently, to maintain the effectiveness of this medication:

1. Use antibiotics only when prescribed.
2. Follow the prescription strictly.
3. Never reuse an antibiotic without a medical prescription, even if you want to treat a similar illness.
4. Never give your antibiotic to another person; it may not be suitable for their illness.
5. After completing a treatment, return all unused medications to the pharmacy to ensure they are disposed of correctly.