Patient Information Leaflet: Information for the User

MACAR 250 mg film-coated tablets, 500 mg film-coated tablets, 750 mg film-coated tablets

Ciprofloxacin
Please read this leaflet carefully before 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, because it could be harmful.
If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist.

Contents of this leaflet:

What MACAR is and what it is used for
What you need to know before taking MACAR
How to take MACAR
Possible side effects
How to store MACAR
Contents of the pack and other information

1. What MACAR is and what it is used for

MACAR is an antibiotic belonging to the fluoroquinolone family. The active substance is
ciprofloxacin.
Ciprofloxacin works by killing the bacteria that cause infections. It is effective only against certain
strains of bacteria.
Adults
MACAR is used in adults to treat the following bacterial infections:

Acute infection occurring in a chronic respiratory disease called chronic obstructive pulmonary disease (COPD), including chronic bronchitis, and community-acquired pneumonia (lung infection acquired outside hospital)
chronic or recurrent ear infections (chronic suppurative otitis media and malignant external otitis)
acute bacterial infection of the nose and paranasal sinuses occurring in chronic sinusitis (acute exacerbation of chronic sinusitis)
acute bladder infection (uncomplicated acute cystitis), complicated urinary tract infections, acute pyelonephritis (kidney and upper urinary tract infection)
infections of the prostate (bacterial prostatitis) and testis (epididymo-orchitis) caused by bacteria
urethritis (acute infection of the urethra, the tube connecting the bladder to the outside) and cervicitis (infection of the cervix, the lower part of the uterus) caused by a bacterium called Neisseria gonorrhoeae (gonococcal urethritis and cervicitis)
infections of the female genital organs
stomach and intestinal infections (e.g. traveller’s diarrhoea) and infections of other abdominal organs
complicated skin and soft tissue infections (infections of the skin and underlying soft tissues)
bone and joint infections
fever of suspected bacterial origin in patients with weakened immune defenses due to very low white blood cell count (neutropenia)
prevention of infections in patients with weakened immune defenses due to very low white blood cell count (neutropӕnia)
prevention of infections caused by the bacterium Neisseria meningitidis
prevention and treatment of infections following exposure to inhaled anthrax spores

If you have a severe infection, or one caused by more than one type of bacteria, your doctor may prescribe another antibiotic treatment in addition to MACAR.
Children and adolescents
MACAR is used in children and adolescents, under specialist supervision, to treat the following
bacterial infections:

lung and bronchial infections caused by a bacterium called Pseudomonas aeruginosa in children and adolescents with a genetic disease called cystic fibrosis
complicated urinary tract infections, including acute kidney and upper urinary tract infections (pyelonephritis)
prevention and treatment of infections following exposure to inhaled anthrax spores

MACAR may also be used to treat other specific severe infections in children and adolescents, when considered necessary by the physician.

2. What you need to know before taking MACAR

Do not take MACAR if:

you are allergic (hypersensitive) to the active substance, to other quinolones, or to any of the excipients of MACAR (see section 6)
you are taking tizanidine (see section 2: Taking MACAR with other medicines)

Warnings and precautions
Before taking this medicine
Do not take quinolone/fluoroquinolone antibacterial medicines, including MACAR, if you have previously experienced any serious adverse reaction during treatment with a quinolone or fluoroquinolone. In such a case, inform your doctor as soon as possible.
Quinolone antibiotics may cause an increase above your normal blood sugar levels (hyperglycemia) or a decrease below your normal blood sugar levels, which in severe cases could potentially lead to loss of consciousness (hypoglycemic coma) (see section 4). This is particularly important for people with diabetes. If you have diabetes, your blood sugar levels must be closely monitored.
Talk to your doctor or pharmacist before taking MACAR:

if you have been diagnosed with an enlargement or "bulging" of a large blood vessel (aortic aneurysm or peripheral aneurysm of a large blood vessel);
if you have previously experienced episodes of aortic dissection (a tear in the aortic wall);
if you have been diagnosed with insufficiency of one of the heart valves (aortic or mitral regurgitation);
if you have a family history of aortic aneurysm or aortic dissection, congenital heart valve disease, or other risk factors or predisposing conditions (e.g., connective tissue disorders such as Marfan syndrome, Ehlers-Danlos syndrome, Turner syndrome, Sjögren's syndrome [an autoimmune inflammatory disease], or vascular disorders such as Takayasu arteritis, giant cell arteritis, Behçet's disease, known high blood pressure or atherosclerosis, rheumatoid arthritis [an autoimmune inflammatory disease], or endocarditis [inflammation of the heart]). If you experience sudden pain in the abdomen, chest, or back, go immediately to the emergency room.

Before taking MACAR
Inform your doctor if:

you have had kidney problems, as your treatment may need to be adjusted to avoid increased adverse reactions due to accumulation of ciprofloxacin
you suffer from epilepsy or other neurological disorders
you have had tendon problems during previous treatment with antibiotics such as MACAR
you have myasthenia gravis (a type of muscle weakness)
you have experienced disturbances in heart rhythm (arrhythmias)

Heart problems
Particular caution is required when using this type of medicine if you were born with or have a family history of prolonged QT interval (seen on ECG, an electrical recording of the heart), if you have an electrolyte imbalance in the blood (especially low levels of potassium or magnesium), if you have a very slow heart rate (called bradycardia), if you have a weak heart (heart failure), if you have a history of heart attacks (myocardial infarction), if you are female or elderly, or if you are taking other medicines that may cause abnormal changes in the ECG (see section "Taking MACAR with other medicines").

While taking MACAR
Inform your doctor immediately if any of the following conditions occur while taking MACAR. Your doctor will decide whether to discontinue treatment with MACAR.

A severe and sudden allergic reaction (an anaphylactic reaction/anaphylactic shock, angioedema). There is a remote possibility that a severe and sudden allergic reaction may occur even with the first dose, with symptoms such as chest tightness, dizziness, nausea or fainting, or dizziness when standing. In such a case, stop taking MACAR and contact your doctor immediately.

Rarely, joint pain and swelling, and inflammation or rupture of tendons may occur. The risk is higher if you are elderly (over 60 years of age), if you have received an organ transplant, if you have kidney problems, or if you are taking corticosteroids. Tendon inflammation and rupture may occur within the first 48 hours of treatment and up to several months after stopping treatment with MACAR. At the first sign of tendon pain or inflammation (e.g., in the ankle, wrist, elbow, shoulder, or knee), stop taking MACAR, consult your doctor, and rest the affected area. Avoid any unnecessary movement, as the risk of tendon rupture may increase.
If you suffer from epilepsy or other neurological disorders, such as cerebral ischemia or stroke, you may experience adverse effects on the central nervous system. In such a case, stop taking MACAR and contact your doctor immediately.
Psychiatric reactions may occur the first time you take MACAR. If you suffer from depression or psychosis, your symptoms may worsen during treatment with MACAR. In such a case, stop taking MACAR and contact your doctor immediately.
Rarely, symptoms of nerve damage (neuropathy) such as pain, burning, tingling, numbness, and/or weakness, particularly in the feet and legs or hands and arms, may occur. In such a case, stop taking MACAR and inform your doctor immediately to prevent permanent nerve damage.
During treatment with antibiotics, including MACAR, or even several weeks afterwards, diarrhea may develop. If it worsens or persists, or if you notice blood or mucus in your stool, stop taking MACAR immediately, as this could be a life-threatening condition. Do not take medicines that block or reduce intestinal movements and contact your doctor.
Inform your doctor or laboratory staff that you are taking MACAR if you need to undergo blood or urine tests.
MACAR may cause liver damage. If you notice symptoms such as loss of appetite, jaundice (yellowing of the skin), dark urine, itching, or abdominal pain, stop taking MACAR and contact your doctor immediately.
MACAR may cause a reduction in the number of white blood cells, which may reduce resistance to infections. If you develop an infection with symptoms such as fever and marked deterioration in your general condition, or fever with signs of localized infection such as sore throat, mouth or throat pain, or urinary problems, consult your doctor immediately. A blood test will be performed to check for a possible reduction in white blood cells (agranulocytosis). It is important that you inform your doctor about the medicine.
Inform your doctor if you or a family member has glucose-6-phosphate dehydrogenase (G6PD) deficiency, as you may be at risk of anemia with ciprofloxacin.
While taking MACAR, your skin may become more sensitive to sunlight or ultraviolet (UV) light. Avoid exposure to intense sunlight and artificial UV light, such as tanning beds.
if you experience sudden, severe pain in the abdomen, chest, or back, which may be a symptom of aortic aneurysm or dissection, go immediately to the emergency room. The risk may be higher if you are taking systemic corticosteroid medicines.
Inform your doctor immediately if you notice a sudden onset of shortness of breath, especially when lying down, or swelling of the ankles, feet, or abdomen, or new episodes of palpitations (sensation of rapid or irregular heartbeat).

If your vision deteriorates or if your eyes are otherwise affected in any way, consult an ophthalmologist immediately.

Serious, prolonged, disabling, and potentially irreversible adverse effects
Fluoroquinolone/quinolone antibacterial medicines, including MACAR, have been associated with very rare but serious adverse effects, some of which are prolonged (lasting months or years), disabling, or may not improve. These include tendon, muscle, and joint pain in the arms and legs, difficulty walking, abnormal sensations such as pricking, tingling, tickling, numbness, or burning (paresthesia), sensory organ disturbances such as changes in vision, taste, smell, or hearing, depression, memory impairment, severe fatigue, and severe sleep disturbances.
If you experience any of these adverse effects after taking MACAR, consult your doctor immediately before continuing treatment. Your doctor will decide together with you whether to continue treatment and may consider using an antibiotic from another class.

Taking MACAR with other medicines
Inform your doctor or pharmacist if you are taking or have recently taken any other medicines, including those without a prescription.
Do not take MACAR with tizanidine, as it may cause adverse effects such as low blood pressure and drowsiness (see section 2: "Do not take MACAR").
You must inform your doctor if you are taking other medicines that may alter heart rhythm: medicines belonging to the antiarrhythmic class (e.g., quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide), tricyclic antidepressants, some antimicrobials (belonging to the macrolide group), or some antipsychotics.
The following medicines interact with MACAR in the body. Taking MACAR together with these medicines may affect their therapeutic effect and increase the likelihood of adverse effects.
Additionally, inform your doctor if you are taking:

vitamin K antagonists (e.g., warfarin) or other oral anticoagulants (to thin the blood)
probenecid (for gout)
methotrexate (for certain types of cancer, psoriasis, or 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 conditions, rheumatoid arthritis, and organ transplants)
glibenclamide (for diabetes)

MACAR may increase blood levels of the following medicines:

pentoxifylline (for circulatory disorders)
caffeine
duloxetine (for depression, diabetic neuropathy, or incontinence)
lidocaine (for heart problems or as an anesthetic)
sildenafil (for erectile dysfunction or high blood pressure)
agomelatine
zolpidem

Certain medicines reduce the effect of MACAR. Inform your doctor if you are taking or plan to take:

antacids
omeprazole
mineral supplements
sucralfate
a polymeric phosphate binder (e.g., sevelamer)
medicines or supplements containing calcium, magnesium, aluminium, or iron. If these preparations are essential, take MACAR approximately two hours before or no less than four hours after taking them.

Taking MACAR with food and drinks
Unless otherwise directed, do not eat or drink dairy products (such as milk or yogurt) or calcium-fortified beverages at the same time as taking the tablets, as they may interfere with the absorption of the active substance.

Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
It is preferable to avoid using MACAR during pregnancy. Inform your doctor if you are planning a pregnancy.
Do not take MACAR while breastfeeding, as ciprofloxacin is excreted in breast milk and may be harmful to your baby.

Driving and using machines
MACAR may affect your level of alertness. Since neurological adverse events may occur, check how you react to MACAR before driving or operating machinery. If in doubt, discuss this with your doctor.

3. How to take MACAR

Your doctor will explain exactly how much MACAR you should take, how often, and for how long. This will depend on the type and severity of the infection you have.
Inform your doctor if you have kidney problems, as your dosage may need to be adjusted.
Treatment usually lasts from 5 to 21 days, but may last longer for severe infections. Always take the tablets exactly as directed by your doctor. If you are unsure about how many tablets to take or how to take MACAR, consult your doctor or pharmacist.
a. Swallow the tablets with plenty of liquid. Do not chew the tablets, as they have an unpleasant taste.
b. Try to take the tablets at approximately the same time each day.
c. You may take the tablets with meals or between meals. Calcium taken during meals does not significantly affect absorption. However, do not take MACAR tablets with dairy products such as milk or yoghurt, or with fruit juices fortified with minerals (e.g. calcium-fortified orange juice).
Remember to drink plenty of fluids during treatment with MACAR.

If you take more MACAR than you should

If you take more than the prescribed dose, contact your doctor immediately. If possible, bring the tablets or the pack with you to show the doctor.

If you forget to take MACAR

Take the missed dose as soon as possible, then continue taking the tablets as prescribed. However, if it is almost time for the next dose, skip the missed dose and continue with your regular schedule. Do not take a double dose to make up for a forgotten dose. Be sure to complete the full course of treatment.

If you stop taking MACAR

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

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 experiences them.
If any of the side effects worsen, or if you notice any side effect not listed in this leaflet, inform your doctor or pharmacist.

Common side effects (may affect from 1 to 10 people in 100):

nausea, diarrhoea
joint pain in children

Uncommon side effects (may affect from 1 to 10 people in 1,000):

fungal superinfections
high concentration of eosinophils, a type of white blood cells
loss of appetite (anorexia)
hyperactivity, agitation
headache, dizziness, sleep disturbances, taste disturbances
vomiting, abdominal pain, digestive problems (stomach discomfort, indigestion/heartburn), intestinal gas
increase in certain blood substances (transaminases and/or bilirubin)
skin rash, itching, urticaria
joint pain in adults
reduced kidney function
muscle and bone pain, malaise (asthenia), fever
increased alkaline phosphatase in the blood (a certain substance present in the blood)

Rare side effects (may affect from 1 to 10 people in 10,000):

inflammation of the intestine (colitis) associated with antibiotic use (in very rare cases may be fatal) (see section 2: Special warnings and precautions for use with MACAR)
changes in blood cell counts (leucopenia, leucocytosis, neutropenia, anaemia), increase or decrease in a blood coagulation factor (platelets)
allergic reaction, swelling (oedema), acute swelling of the skin and mucous membranes (angioedema)
increased blood sugar (hyperglycaemia)
confusion, disorientation, anxious reaction, unusual dreams, depression (which may potentially lead to suicidal ideation/thoughts, attempted suicide or completed suicide. See section 2: Special warnings and precautions for use with MACAR), hallucinations
tingling, unusual sensitivity to sensory stimuli, reduced skin sensitivity, tremor, seizures (see section 2: Special warnings and precautions for use with MACAR), dizziness
visual disturbances (e.g. diplopia)
tinnitus, hearing loss, decreased hearing
rapid heartbeat (tachycardia)
dilation of blood vessels (vasodilation), low blood pressure, fainting
shortness of breath, including asthma-like symptoms
liver disorders, jaundice (cholestatic jaundice), hepatitis
sensitivity to light (see section 2: Special warnings and precautions for use with MACAR)
muscle pain, joint inflammation, increased muscle tone, cramps
kidney failure, blood or crystals in urine (see section 2: Special warnings and precautions for use with MACAR), inflammation of the urinary tract
fluid retention, excessive sweating
abnormal levels of a coagulation factor (prothrombin), increased levels of amylase enzyme

Very rare side effects (may affect less than 1 person in 10,000):

a specific type of reduction in red blood cells (haemolytic anaemia); a dangerous reduction in a type of white blood cells (agranulocytosis); reduction in red blood cells, white blood cells and platelets (pancytopenia), which may be fatal; bone marrow suppression, which may also be fatal (see section 2: Special warnings and precautions for use with MACAR)
severe allergic reaction (anaphylactic reaction or anaphylactic shock, which may be fatal – serum sickness) (see section 2: Special warnings and precautions for use with MACAR)
psychiatric disorders (psychotic reactions which may potentially lead to suicidal ideation/thoughts, attempted suicide or completed suicide. See section 2: Special warnings and precautions for use with MACAR)
migraine, coordination disorders, unsteady gait (gait disturbances), disturbances in smell (olfactory disturbances), pressure on the brain (intracranial hypertension)
distortions in colour perception
inflammation of blood vessel walls (vasculitis)
pancreatitis
death of liver cells (hepatic necrosis), which very rarely may lead to life-threatening liver failure
pinpoint bleeding under the skin (petechiae); various types of skin rashes (e.g. Stevens-Johnson syndrome or toxic epidermal necrolysis, potentially fatal)
muscle weakness, tendon inflammation, tendon rupture – especially of the large tendon at the back of the ankle (Achilles tendon) (see section 2: Special warnings and precautions for use with MACAR); worsening of symptoms of myasthenia gravis (see section 2: Special warnings and precautions for use with MACAR)

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

nervous system disorders such as pain, burning, tingling, numbness and/or weakness of the extremities
heart problems: abnormally fast heart rate, life-threatening irregular heartbeat, changes in heart rhythm (called “QT interval prolongation”, seen on ECG, electrical activity of the heart)
Acute Generalized Exanthematous Pustulosis (AGEP)
Increased International Normalized Ratio (in patients treated with vitamin K antagonists)
Feelings of over-excitement (manic agitation) or sensations of excitement and hyperactivity (hypomanic agitation)
Hypersensitivity reactions called DRESS (rash with eosinophilia and systemic symptoms)
Syndrome associated with impaired water excretion and low sodium levels (SIADH)
Loss of consciousness due to severe decrease in blood sugar levels (hypoglycaemic coma). See section 2.

Very rare cases of prolonged (lasting months or years) or permanent adverse drug reactions, such as tendon inflammation, tendon rupture, joint pain, pain in arms or legs, difficulty walking, abnormal sensations such as pricking, tingling, tickling, burning, numbness or pain (neuropathy), depression, fatigue, sleep disturbances, memory impairment and changes in hearing, vision, taste and smell, have been associated with the use of quinolone and fluoroquinolone antibiotics, in some cases regardless of pre-existing risk factors.

Cases of aortic wall dilation and weakening or aortic wall tear (aneurysms and dissections), with possible rupture that may be fatal, as well as cases of backflow of blood from heart valves, have been reported in patients treated with fluoroquinolones. See also section 2.

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 national reporting system at: 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 MACAR

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and carton after "Exp.". The expiry date refers to the last day of the month.
Do not dispose of medicines 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 MACAR contains
MACAR 250 mg film-coated tablets
One film-coated tablet contains:
Active substance: ciprofloxacin hydrochloride monohydrate: 291 mg (equivalent to 250 mg ciprofloxacin)
Excipients: microcrystalline cellulose (E460), pregelatinized starch, crospovidone (E1202), maize starch, anhydrous colloidal silica, magnesium stearate (E572), titanium dioxide (E171), hypromellose (E464), macrogol 4000.

MACAR 500 mg film-coated tablets
One film-coated tablet contains:
Active substance: ciprofloxacin hydrochloride monohydrate: 582 mg (equivalent to 500 mg ciprofloxacin)
Excipients: microcrystalline cellulose (E460), pregelatinized starch, crospovidone (E1202), maize starch, anhydrous colloidal silica, magnesium stearate (E572), titanium dioxide (E171), hypromellose (E464), macrogol 4000.

MACAR 750 mg film-coated tablets
One film-coated tablet contains:
Active substance: ciprofloxacin hydrochloride monohydrate: 873 mg (equivalent to 750 mg ciprofloxacin)
Excipients: microcrystalline cellulose (E460), pregelatinized starch, crospovidone (E1202), maize starch, anhydrous colloidal silica, magnesium stearate (E572), titanium dioxide (E171), hypromellose (E464), macrogol 4000.

Description of the appearance of MACAR and contents of the pack
MACAR 250 mg film-coated tablets
White, oval, film-coated tablets with a break line.
Pack size: 10 tablets

MACAR 500 mg film-coated tablets
White, oval, film-coated tablets with a break line.
Pack size: 6 tablets

MACAR 750 mg film-coated tablets
White, oval, film-coated tablets with a break line.
Pack size: 12 tablets

Marketing Authorization Holder and Manufacturer
Dymalife Pharmaceutical S.r.l. – Via Bagnulo, 95 - 80063 - Piano di Sorrento (NA)

Manufacturer
SPECIAL PRODUCT’S LINE S.P.A.
Strada Paduni, 240-03012, Anagni (FR)

Macar