Active ingredients: Ciprofloxacin
Ciproxin 250 mg film-coated tablets
Ciproxin package inserts are available for pack sizes:- Ciproxin 250 mg film-coated tablets
- Ciproxin 500 mg film-coated tablets
- Ciproxin 750 mg film-coated tablets
- Ciproxin 250 mg / 5 mL granules and solvent for oral suspension
Why is Ciproxin used? What is it for?
Ciproxin contains the active substance ciprofloxacin. Ciproxin is an antibiotic belonging to the fluoroquinolone family. Ciprofloxacin works by killing bacteria that cause infections. It only works with particular strains of bacteria.
Adults
Ciproxin is used in adults to treat the following bacterial infections:
- respiratory tract infections
- long-lasting or recurring ear or sinus infections
- urinary tract infections
- infections of the genital organs in men and women
- gastrointestinal and intra-abdominal infections
- skin and soft tissue infections
- bone and joint infections
- to prevent infections caused by the bacterium Neisseria meningitidis
- exposure to inhalation of anthrax spores
Ciprofloxacin can be used to manage patients with low white blood cell counts (neutropenia) who have a fever that is suspected to be due to bacterial infection.
If you have a severe infection, or infection caused by more than one type of bacteria, you may be prescribed another antibiotic treatment in addition to Ciproxin.
Children and adolescents
Ciproxin is used in children and adolescents under specialist supervision to treat the following bacterial infections:
- lung and bronchial infections in children and adolescents suffering from cystic fibrosis
- complicated urinary tract infections, including infections that have reached the kidneys (pyelonephritis)
- exposure to inhalation of anthrax spores
Ciproxin can also be used to treat other specific serious infections in children and adolescents, if considered necessary by your doctor.
Contraindications When Ciproxin should not be used
Do not take Ciproxin:
- If you are allergic to the active substance, to other quinolones or to any of the other ingredients of this medicine
- If you take tizanidine (see section: Other medicines and Ciproxin)
Precautions for use What you need to know before taking Ciproxin
Before taking Ciproxin Tell your doctor if:
- have had kidney problems, as your treatment may need to be adjusted
- suffer from epilepsy or other neurological disorders
- have had tendon problems during previous treatment with antibiotics such as Ciproxin
- suffer from myasthenia gravis (a type of muscle weakness)
- if you have heart problems. Particular care should be taken when using Ciproxin, if you were born with or have a family history of prolonged QT interval (displayed on the ECG, an electrical recording of the heart), have a saline imbalance in the blood (especially a low level of potassium or blood), have a very slow heart rhythm (called bradycardia), have a weak heart (heart failure), have a history of heart attack (myocardial infarction), are a woman or an elderly patient or are taking other medicines that may cause abnormal changes in the ECG (see section "Other medicines and Ciproxin").
- Tell your doctor if you or a family member know you have glucose-6-phosphate dehydrogenase (G6PD) deficiency, as you may be at risk of anemia with ciprofloxacin.
To treat some genital tract infections, your doctor may prescribe another antibiotic in addition to ciprofloxacin. If there are no symptoms of improvement after 3 days of treatment, consult your doctor
Tell your doctor immediately if any of the conditions listed below occur while taking Ciproxin. Your doctor will decide if you should stop taking Ciproxin.
- A severe and sudden allergic reaction (anaphylactic reaction / anaphylactic shock, angioedema). There is a remote chance that a severe and sudden allergic reaction will occur even at the first dose, with the following symptoms: chest tightness, lightheadedness, nausea or fainting, dizziness on standing. In this case, stop taking Ciproxin and contact doctor immediately.
- Occasionally Ciproxin can cause joint pain and swelling and tendonitis, especially if you are elderly and are being treated with corticosteroids. Inflammation and rupture of tendons can also occur within 48 hours of starting treatment or up to several months after ending treatment with Ciproxin. At the first sign of pain or inflammation stop taking Ciproxin and rest the part. sore. Avoid any unnecessary physical activity, as it may increase the risk of a tendon rupture.
- If you suffer from epilepsy or other neurological disorders, such as cerebral ischaemia or stroke, you may experience undesirable central nervous system effects. If this happens, stop taking Ciproxin and contact your doctor immediately.
- Psychiatric reactions may occur the first time you take Ciproxin. If you suffer from depression or psychosis, your symptoms may get worse during treatment with Ciproxin. In rare cases, depression and psychosis can develop into thoughts of suicide or suicide or suicide attempts. If this happens, stop taking Ciproxin and contact your doctor immediately.
- You may experience symptoms of neuropathy, such as pain, burning, tingling, numbness and / or weakness. If this happens, stop taking Ciproxin and contact your doctor immediately.
- Hypoglycaemia has been reported very often in diabetic patients, predominantly in the elderly population. If this occurs contact your doctor immediately.
- Diarrhea may develop during treatment with antibiotics, including Ciproxin, or even several weeks later. If it gets worse or persists, or if you notice blood or mucus in your stools, you should stop taking Ciproxin immediately, as it can be life-threatening. Do not take medicines that stop or reduce bowel movements and contact your doctor.
- Tell your doctor or laboratory staff that you are taking Ciproxin if you need to have a blood or urine test.
- If you have kidney problems, please tell your doctor as you may need a change in dosage.
- Ciproxin can cause liver damage. If you notice symptoms such as loss of appetite, jaundice (yellowing of the skin), dark urine, itching or tenderness in the abdomen, stop taking Ciproxin and contact your doctor immediately.
- Ciproxin can cause a reduction in the number of white blood cells which can lead to lower resistance to infections. If you experience an infection with symptoms such as fever and marked deterioration of your general condition, or fever with symptoms of localized infection, such as sore throat or pain in the pharynx or mouth or urinary problems, you should see your doctor immediately. You will be examined for an examination. of the blood to check for a possible reduction in white blood cells (agranulocytosis). It is important that you tell your doctor about the medicine.
- While taking Ciproxin your skin becomes more sensitive to sunlight or ultraviolet (UV) light. Avoid exposure to intense sunlight and artificial UV light, such as from sun beds.
Interactions Which drugs or foods may change the effect of Ciproxin
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Do not take Ciproxin together with tizanidine, as it may cause side effects such as low blood pressure and sleepiness (see section: Do not take Ciproxin. The following medicines interact with Ciproxin in the body.
Taking Ciproxin together with these medicines can influence their therapeutic effect and increase the likelihood of experiencing side effects. Tell 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 cancers, psoriasis or "rheumatoid arthritis)
- theophylline (for breathing 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 problems, rheumatoid arthritis and in organ transplants)
- other drugs that can alter the heart rhythm: drugs that belong to the group of antiarrhythmics (e.g. quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide), tricyclic antidepressants, some antimicrobials (which belong to the macrolides group), some antipsychotics .
Ciproxin may increase the levels of the following medicines in the blood:
- pentoxifylline (for circulatory disorders)
- caffeine
- duloxetine (for depression, diabetic neuropathy or incontinence)
- lidocaine (for heart problems or for anesthetic use)
- sildenafil (e.g. for erectile dysfunction)
Certain medicines reduce the effect of Ciproxin. Tell your doctor if you take or intend to take:
- antacids
- omeprazole
- mineral supplements
- sucralfate
- a polymeric phosphate chelator (e.g. sevelamer or lanthanum carbonate)
- medicines or supplements containing calcium, magnesium, aluminum or iron
If these preparations are essential, take Ciproxin approximately two hours before their intake, or no earlier than four hours after.
Ciproxin with food and drink
Unless you take Ciproxin with a meal, do not eat or drink dairy products (such as milk or yogurt) or calcium-fortified drinks when taking the tablets, as they can interfere with the absorption of the active substance.
Warnings It is important to know that:
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
The use of Ciproxin is not recommended during pregnancy.
Tell your doctor if you are pregnant or planning to become pregnant. The use of Ciproxin is not recommended during breastfeeding because ciprofloxacin is excreted in breast milk and may be harmful to your baby.
Driving and using machines
Ciproxin can interfere with your alertness. As neurological adverse events can occur, check your reactions to Ciproxin before driving a vehicle or operating machinery, especially if you have been drinking alcohol. If in doubt, talk to your doctor.
Dose, Method and Time of Administration How to use Ciproxin: Posology
Your doctor will explain to you exactly how much Ciproxin you should take, how often and for how long. This will depend on the type of infection you are suffering from and its severity.
- Tell your doctor if you have kidney problems as your dosage may need to be adjusted.
- Treatment usually lasts 5 to 21 days, but it can take longer for severe infections. Always take this medicine exactly as your doctor has told you. Consult your doctor or pharmacist if you are not sure how many tablets to take and how to take Ciproxin.
- Swallow the tablets with plenty of liquid. Do not chew the tablets as they have an unpleasant taste.
- Try to take the tablets at about the same time each day.
- You can take the tablets at or between mealtimes. Calcium taken with meals does not significantly affect absorption. However, do not take Ciproxin tablets with dairy products such as milk or yogurt or with mineral-fortified fruit juices (eg calcium-fortified orange juice).
Remember to drink plenty of water while taking this medicine.
Overdose What to do if you have taken an overdose of Ciproxin
If you take more Ciproxin than you should
If you take more than the prescribed dose, consult your doctor immediately. If possible, take your tablets or the box with you to show the doctor.
If you forget to take Ciproxin
Take the normal dose as soon as possible and then continue 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 a forgotten dose. Be sure to complete the course of treatment.
If you stop taking Ciproxin
It is important that you complete the course of treatment even if you begin to feel better after a few days. If you stop taking this medicine too soon, the infection may not be completely cured and the symptoms of the infection may come back or get worse. It could also develop antibiotic resistance.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Ciproxin
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Common:
(may affect up to 1 in 10 people):
- nausea, diarrhea
- joint pain in children
Uncommon:
(may affect up to 1 in 100 people):
- fungal superinfections
- high concentration of eosinophils, a type of white blood cell
- decreased appetite
- hyperactivity, agitation
- headache, dizziness, sleep disturbances, taste disturbances
- vomiting, abdominal pain, digestive problems (stomach upset, indigestion / heartburn), gas
- increase in certain substances in the blood (transaminases and / or bilirubin)
- rash, itching, hives
- joint pain in adults
- reduced kidney function
- pain in the muscles and bones, indisposition (asthenia), fever
- increase in blood alkaline phosphatase (a certain substance in the blood)
Rare:
(may affect up to 1 in 1000 people):
- inflammation of the intestine (colitis) associated with the use of antibiotics (in very rare cases it can be fatal) (see section: Warnings and precautions)
- changes in the number of blood cells (leukopenia, leukocytosis, neutropenia, anemia), increase or decrease in a blood clotting factor (platelets)
- allergic reaction, swelling (edema), acute swelling of the skin and mucous membranes (angioedema)
- increased blood sugar (hyperglycaemia)
- decreased blood sugar (hypoglycaemia) (see section: Warnings and precautions)
- confusion, disorientation, anxious reaction, unusual dreams, depression (which in rare cases can develop into thoughts of suicide or suicide or suicide attempts), hallucinations
- tingling, unusual sensitivity to sensory stimuli, decreased skin sensitivity, tremors, convulsions (see section: Warnings and precautions), lightheadedness
- visual disturbances including double vision
- tinnitus, hearing loss, hearing loss
- rapid heartbeat (tachycardia)
- dilation of blood vessels (vasodilation), low blood pressure, fainting
- shortness of breath, including asthma symptoms
- liver disorders, jaundice (cholestatic jaundice), hepatitis
- sensitivity to light (see section: Warnings and precautions)
- muscle pain, joint inflammation, increased muscle tone, cramps
- kidney failure, blood or crystals in the urine (see section 2: Warnings and precautions), inflammation of the urinary tract
- water retention, excessive sweating
- increased levels of the enzyme amylase
Very rare:
(may affect up to 1 in 10,000 people):
- a particular type of decrease in red blood cells (haemolytic anemia); a dangerous decrease in a type of white blood cell (agranulocytosis); a decrease in red blood cells, white blood cells and platelets (pancytopenia), which can be fatal; bone marrow depression, which can also be fatal (see section: Warnings and precautions)
- severe allergic reaction (anaphylactic reaction or anaphylactic shock, which can be fatal - serum sickness) (see section: Warnings and precautions)
- mental disorders (psychotic reactions which in rare cases may develop into thoughts of suicide or suicide attempts or suicide) (see section: Warnings and precautions)
- migraine, coordination disturbances, unsteady gait (gait disturbances), smell disturbances (olfactory disturbances), pressure on the brain (intracranial hypertension including pseudotumor cerebri)
- distortions in the perception of colors
- inflammation of the blood vessel walls (vasculitis)
- pancreatitis
- death of liver cells (liver necrosis), which very rarely can lead to life-threatening liver failure
- pinpoint bleeding under the skin (petechiae); different types of skin rashes (for example, Stevens-Johnson syndrome or toxic epidermal necrolysis, which are potentially fatal)
- muscle weakness, tendon inflammation, tendon rupture
- especially the large tendon located at the back of the ankle (Achilles tendon) (see section: Warnings and precautions); worsening of symptoms of myasthenia gravis (see section: Warnings and precautions)
Not known:
(Frequency cannot be estimated from the available data)
- disorders associated with the nervous system, such as pain, burning, tingling, numbness and / or weakness in the extremities (peripheral neuropathy and polyneuropathy)
- abnormal fast heart rhythm, life-threatening irregular heart rhythm, altered heart rhythm (called "prolongation of the" QT interval ", displayed on the ECG, electrical activity of the heart)
- pustular rash
- influence on blood clotting (in patients treated with vitamin K antagonists)
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects you can help provide more information on safety. of this medicine.
Expiry and Retention
No particular storage conditions are required.
Keep out of the sight and reach of children.
Do not use Ciproxin after the expiry date which is stated on the blister or carton after "EXP". The expiry date refers to the last day of the month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
What Ciproxin contains
The active ingredient is ciprofloxacin.
Each film-coated tablet contains 250 mg of ciprofloxacin (as hydrochloride). The other ingredients are: Tablet core: microcrystalline cellulose, crospovidone, magnesium stearate, corn starch, anhydrous colloidal silica. Film-coating: hypromellose, macrogol 4000, titanium dioxide (E 171).
Description of what Ciproxin looks like and contents of the pack
Ciproxin 250 mg tablets: Round, off-white or slightly yellowish film-coated tablets marked with "CIP score line 250" on one side and the Bayer cross on the other.
The tablets can be divided into equal halves.
Packs of 6, 8, 10, 12, 14, 16, 20, 28, 50, 100, 160, or 500 film-coated tablets.
Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
CIPROXIN 250 MG
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each film-coated tablet contains 250 mg of ciprofloxacin (as hydrochloride).
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Film-coated tablet.
Round, almost white or slightly yellowish tablets, marked with "CIP score line 250" on one side and the Bayer cross on the other.
The tablets can be divided into equal halves.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Ciproxin 250 mg film-coated tablets are indicated for the treatment of the infections listed below (see sections 4.4 and 5.1). Prior to initiating therapy, particular attention should be paid to available information on resistance to ciprofloxacin.
It is recommended to refer to official guidelines on the appropriate use of antibacterial agents.
Adults
• Lower respiratory tract infections caused by Gram-negative bacteria
- exacerbations of chronic obstructive pulmonary disease
- bronchopulmonary infections in cystic fibrosis or bronchiectasis
- pneumonia
• Chronic purulent otitis media
• Flare-ups of chronic sinusitis, particularly if caused by Gram-negative bacteria
• Urinary tract infections
• Infections of the genital system
• Gonococcal urethritis and cervicitis from Neisseria gonorrhoeae
• Epididymo-orchitis, including cases from Neisseria gonorrhoeae
• Pelvic inflammatory disease, including cases from Neisseria gonorrhoeae
• Infections of the gastrointestinal tract (eg traveler's diarrhea)
• Intra-abdominal infections
• Skin and soft tissue infections caused by Gram-negative bacteria
• Malignant external otitis
• Bone and joint infections
• Prophylaxis of invasive infections from Neisseria meningitidis
• Inhalation anthrax (prophylaxis and post-exposure therapy)
Ciprofloxacin can be used to manage neutropenic patients with fever suspected to be due to bacterial infection.
Children and adolescents
• Bronchopulmonary infections in cystic fibrosis, caused by Pseudomonas aeruginosa
• Complicated urinary tract infections and pyelonephritis
• Inhalation anthrax (prophylaxis and post-exposure therapy)
Ciprofloxacin can also be used to treat serious infections in children and adolescents if this is considered necessary.
Treatment should only be initiated by physicians experienced in the treatment of cystic fibrosis and / or severe infections in children and adolescents (see sections 4.4 and 5.1).
04.2 Posology and method of administration
Dosage
The posology varies according to the indication, the severity and site of the infection, the sensitivity of the pathogen to ciprofloxacin, the patient's renal function and, in children and adolescents, body weight.
The duration of treatment depends on the severity of the disease, as well as on its clinical and bacteriological course.
The treatment of infections caused by certain bacteria (eg. Pseudomonas aeruginosa, Acinetobacter or Staphylococci) may require higher ciprofloxacin doses and combination with other appropriate antibacterial agents.
Treatment of certain infections (eg pelvic inflammatory disease, intra-abdominal infections, infections in neutropenic patients, and bone and joint infections) may require combination with other appropriate antibacterial agents.
Adults
Pediatric population
Elderly patients
Elderly patients should be treated with a dose established according to the severity of the infection and the patient's creatinine clearance.
Patients with impaired renal and hepatic function
Recommended starting and maintenance doses for patients with impaired renal function:
No dosage adjustment is required in patients with impaired hepatic function.
Administration to children with impaired renal and / or hepatic function has not been investigated.
Method of administration
The tablets must be swallowed with a little liquid, without chewing them, and can be taken regardless of meals. Taking it on an empty stomach accelerates the absorption of the active ingredient. Ciprofloxacin tablets should not be ingested with milk, derivatives (eg yogurt) or drinks enriched with mineral salts (eg orange juice with added calcium) (see section 4.5).
If the patient is unable to take the tablets due to the severity of the disease or for other reasons (e.g. patients on enteral feeding), it is recommended that intravenous ciprofloxacin be initiated until it is possible to switch to administration. oral.
04.3 Contraindications
• Hypersensitivity to the active substance, to other quinolones or to any of the excipients (listed in section 6.1).
• Concomitant administration of ciprofloxacin and tizanidine (see section 4.5).
04.4 Special warnings and appropriate precautions for use
Severe infections and mixed infections with the presence of Gram-positive and anaerobic pathogens
Ciprofloxacin monotherapy is not adequate for the treatment of severe infections and infections potentially caused by Gram-positive or anaerobic pathogens. In these infections, ciprofloxacin should be administered in combination with other appropriate antibacterial agents.
Streptococcal infections (including Streptococcus pneumoniae)
Ciprofloxacin is not recommended for the treatment of streptococcal infections due to insufficient efficacy.
Infections of the genital system
Gonococcal urethritis, cervicitis, epididymo-orchitis, and pelvic inflammatory disease can be caused by Neisseria gonorrhoeae isolated resistant to fluoroquinolones. Therefore, ciprofloxacin should be administered for the treatment of gonococcal urethritis or cervicitis only if the Neisseria gonorrhoeae resistant to fluoroquinolones.
For epididymo-orchitis and pelvic inflammatory disease, ciprofloxacin should be administered together with another appropriate antibacterial (e.g. a cephalosporin), unless the presence of Neisseria gonorrhoeae resistant to ciprofloxacin based on local prevalence data. If clinical improvement is not achieved after 3 days of treatment, therapy should be reconsidered.
Urinary tract infections
The resistance of the " Escherichia coli - the most common pathogen involved in urinary tract infections - to fluoroquinolones, varies across the European Union. Prescribers are advised to consider the prevalence of local resistance to this.Escherichia coli to fluoroquinolones.
The single dose of ciprofloxacin which can be used in uncomplicated cystitis in premenopausal women is expected to be associated with less efficacy than with longer treatment.
This is all the more to take into consideration due to the increasing resistance level of Escherichia coli to quinolones.
Intra-abdominal infections
There are limited data on the efficacy of ciprofloxacin in the treatment of post-surgical intra-abdominal infections.
Traveler's diarrhea
The choice of ciprofloxacin should take into account information on resistance to ciprofloxacin of relevant pathogens in the countries visited.
Bone and joint infections
Ciprofloxacin should be used in combination with another antimicrobial agent, depending on the results of the microbiological documentation.
Inhalation anthrax
Use in humans is based on in vitro sensitivity data and experimental data in animals, together with some data in humans. Physicians should refer to national and / or international official documents on anthrax treatment.
Pediatric population
Official guidelines should be followed when using ciprofloxacin in children and adolescents. Treatment with ciprofloxacin should only be initiated by physicians experienced in the treatment of cystic fibrosis and / or severe infections in children and adolescents.
Ciprofloxacin causes arthropathy in the weight-bearing joints of growing animals. Safety data from a double-blind randomized study on the use of ciprofloxacin in children (ciprofloxacin: n = 335, mean age = 6.3 years; comparator drugs: n = 349, mean age = 6.2 years ; age range = 1-17 years), revealed an "incidence of suspected drug-related arthropathy (inferred from clinical signs and joint symptoms) of 7.2% and 4.6% at day +42. At one year, the incidence of drug-related arthropathy was 9.0% and 5.7%, respectively. The increase in incidence over time was not statistically significant between the 2 groups. Treatment should be initiated. after a "careful risk / benefit assessment, due to the possibility of adverse events affecting the joints and surrounding tissues.
Bronchopulmonary infections in cystic fibrosis
Clinical trials were conducted in children and adolescents aged between 5 and 17 years. Experience in the treatment of children aged 1 to 5 years is more limited.
Complicated urinary tract infections and pyelonephritis
Treatment of urinary tract infections with ciprofloxacin should be considered when other treatments cannot be used and should be based on the results of microbiological tests.
Clinical trials were conducted in children and adolescents aged 1 to 17 years.
Other particular serious infections
Other serious infections in accordance with official guidelines or after careful risk-benefit assessment, when other treatments cannot be used or after failure of conventional therapy and when the microbiological documentation justifies the use of ciprofloxacin.
The use of ciprofloxacin for particular serious infections, with the exception of those mentioned above, has not been the subject of clinical trials and clinical experience is limited. Therefore, caution is advised when treating patients with these infections.
Hypersensitivity
Allergic and hypersensitivity reactions, including anaphylaxis and anaphylactoid reactions, can occur after a single dose (see section 4.8) and can be life threatening. In this event, the administration of ciprofloxacin should be discontinued and a treatment initiated. adequate therapy.
Musculoskeletal system
Ciprofloxacin should not normally be used in patients with a history of tendon disease / disorder related to quinolone treatment. However, in very rare circumstances, after microbiological documentation of the causative agent and assessment of the risk / benefit ratio, the ciprofloxacin can be prescribed to these patients for the treatment of certain serious infections, particularly in the case of failure of standard therapy or bacterial resistance, when the microbiological data justifies the use of ciprofloxacin.
With the use of ciprofloxacin, tendonitis and tendon rupture (especially affecting the Achilles tendon) can occur, sometimes bilateral, already in the first 48 hours of treatment. Inflammation and tendon ruptures can also occur up to several months later the discontinuation of ciprofloxacin therapy. The risk of tendinopathy may be increased in elderly patients or in those receiving concomitant treatment with corticosteroids (see section 4.8).
When the first signs of tendonitis appear (pain and / or edema, inflammation), stop treatment with ciprofloxacin. Keep the affected limb at rest.
Ciprofloxacin should be used with caution in patients with myasthenia gravis as symptoms may be aggravated (see section 4.8).
Photosensitivity
Ciprofloxacin can cause photosensitivity reactions. During treatment, patients taking ciprofloxacin should avoid direct exposure to excessive sunlight or ultraviolet rays (see section 4.8).
Central nervous system
Ciprofloxacin like other quinolones is known to cause seizures or lower the seizure threshold. Cases of status epilepticus have been reported. Ciprofloxacin should be used with caution in patients with CNS disorders that may predispose to seizures. If these occur, ciprofloxacin should be discontinued (see section 4.8). Psychiatric reactions also occurred after the first administration of ciprofloxacin. In rare cases, depression or psychotic reactions may progress to suicidal ideations / thoughts culminating in suicide or suicide attempts. If this happens, stop the treatment.
Cases of polyneuropathy (based on neurological symptoms such as pain, burning, sensory disturbances or muscle weakness, alone or in combination) have been reported in patients treated with ciprofloxacin. In patients experiencing symptoms of neuropathy, such as pain, burning, tingling, numbness and / or weakness, ciprofloxacin should be discontinued to prevent the condition from becoming irreversible (see section 4.8).
Heart ailments
Particular care should be taken when using fluoroquinolones, including ciprofloxacin, in patients with known risk factors for QT interval prolongation, such as:
- congenital long QT syndrome
- concomitant use of drugs that are known to prolong the QT interval (eg class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics)
- incorrect electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia)
- heart disease (e.g. heart failure, myocardial infarction, bradycardia)
Elderly patients and women may be more sensitive to QTc-prolonging medications. Therefore, special care should be taken when administering fluoroquinolones, including ciprofloxacin, to these populations.
- (See sections 4.2 Elderly patients, section 4.5, section 4.8 and section 4.9).
Hypoglycemia
As with other quinolones, hypoglycaemia has been reported more often in diabetic patients, predominantly in the elderly population. Close monitoring of blood glucose is recommended in all diabetic patients (see section 4.8).
Digestive system
The onset of severe and persistent diarrhea during or after treatment (even several weeks apart) could indicate the presence of antibiotic-induced colitis (life-threatening, possibly fatal), which should be treated immediately (see section 4.8. In these cases, immediately discontinue ciprofloxacin and adopt adequate therapy. In this situation, the use of drugs that inhibit peristalsis is contraindicated.
Kidney and urinary tract
Crystalluria has been reported in association with the use of ciprofloxacin (see section 4.8). Patients receiving ciprofloxacin should be well hydrated and excessive urine alkalinity should be avoided in such patients.
Impaired renal function
As ciprofloxacin is extensively excreted unchanged via the kidney, dose adjustment is required in patients with impaired renal function as described in section 4.2 to avoid an increase in adverse reactions due to accumulation of ciprofloxacin.
Liver and biliary tract
Cases of hepatic necrosis and life-threatening liver failure have been reported in association with the use of ciprofloxacin (see section 4.8). If signs and symptoms of liver disease appear (such as anorexia, jaundice, dark urine, pruritus, palpable abdomen ), stop the treatment.
Deficit of glucose-6-phosphate dehydrogenase
Haemolytic reactions have been reported with ciprofloxacin in patients with glucose-6-phosphate dehydrogenase deficiency. Ciprofloxacin should be avoided in these patients unless the potential benefit is considered to outweigh the possible risk. In this case, the possible occurrence of haemolysis should be monitored.
Resistence
Bacteria showing resistance to ciprofloxacin may be isolated during or following treatment with ciprofloxacin, with or without clinically manifest superinfection. There may be a particular risk of selecting bacteria resistant to ciprofloxacin during long-term treatments and in the treatment of nosocomial infections and / or infections caused by the species Staphylococcus And Pseudomonas.
Cytochrome P450
Ciprofloxacin inhibits CYP1A2 and may thus cause an increase in the serum concentrations of substances metabolised by this enzyme (e.g. theophylline, clozapine, olanzapine, ropinirole, tizanidine, duloxetine) when administered concomitantly. Concomitant administration of ciprofloxacin and tizanidine is contraindicated. Therefore, patients taking these substances together with ciprofloxacin should be monitored constantly for clinical signs of overdose and determination of serum concentrations (e.g. theophylline) may be necessary (see section 4.5).
Methotrexate
The concomitant use of ciprofloxacin with methotrexate is not recommended (see section 4.5).
Interaction with laboratory tests
The activity in vitro of ciprofloxacin against Mycobacterium tuberculosis could give rise to false negatives in bacteriological tests performed on samples taken from patients treated with ciprofloxacin.
04.5 Interactions with other medicinal products and other forms of interaction
Effects of other medicinal products on ciprofloxacin :
Medicines known to prolong the QT interval
Ciprofloxacin, like other fluoroquinolones, should be used with caution in patients taking medicinal products known to prolong the QT interval (eg class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics) (see section 4.4).
Formation of chelating complexes
Concomitant administration of ciprofloxacin (oral) and drugs containing multivalent cations and mineral supplements (e.g. calcium, magnesium, aluminum, iron), polymeric phosphate chelators (e.g. sevelamer or lanthanum carbonate), sucralfate or antacids and highly buffered formulations (eg didanosine tablets), containing magnesium, aluminum or calcium, reduces the absorption of ciprofloxacin. Consequently, ciprofloxacin should be administered 1-2 hours before or at least 4 hours after taking these preparations. These restrictions of use do not apply to antacids belonging to the class of H2 antagonists.
Food and dairy products
Calcium taken with food during meals does not significantly affect absorption. However, fasting concomitant administration of ciprofloxacin with milk, derivatives or mineral-enriched beverages (eg yogurt or orange juice should be avoided). added calcium), as absorption of ciprofloxacin may be reduced.
Probenecid
Probenecid interferes with the renal secretion of ciprofloxacin; their simultaneous administration causes an increase in the serum concentrations of ciprofloxacin.
Metoclopramide
Metoclopramide accelerates the absorption of ciprofloxacin (oral) leading to a decrease in the time to reach plasma peak. No effects on the bioavailability of ciprofloxacin have been found.
Omeprazole
Concomitant administration of ciprofloxacin and omeprazole-containing medicinal products leads to a slight decrease in Cmax and AUC of ciprofloxacin.
Effects of ciprofloxacin on other medicinal products :
Tizanidine
Tizanidine should not be administered together with ciprofloxacin (see section 4.3). An increase in serum concentrations of tizanidine was observed in a clinical study in healthy volunteers (increase in Cmax by a factor of 7, range 4 - 21; "AUC by a factor of 10, range 6 - 24), administered concomitantly with ciprofloxacin. The increase in serum concentrations of tizanidine is associated with an enhanced hypotensive and sedative effect.
Methotrexate
Renal tubular transport of methotrexate may be inhibited by concomitant administration of ciprofloxacin, resulting in a potential increase in plasma methotrexate levels and an increased risk of methotrexate-associated toxic reactions. Concomitant use is not recommended (see section 4.4).
Theophylline
The concomitant administration of ciprofloxacin and theophylline can cause an undesirable increase in the plasma concentration of the latter and, consequently, the appearance of theophylline-induced undesirable effects which, rarely, can be life threatening or fatal. in combination therapy, theophyllinemia should be controlled, possibly by reducing the theophylline dose (see section 4.4).
Other xanthines
Following concomitant administration of ciprofloxacin and caffeine or pentoxifylline, an increase in the serum concentrations of these xanthines was observed.
Phenytoin
Concomitant administration of ciprofloxacin and phenytoin may result in decreased or increased serum phenytoin levels. It is therefore recommended to monitor serum levels of the drug.
Cyclosporine
A transient increase in serum creatinine concentration was observed when ciprofloxacin and cyclosporine containing medicinal products were administered concomitantly. Therefore, serum creatinine concentrations in these patients should be checked periodically (twice weekly).
Vitamin K antagonists
The concomitant administration of ciprofloxacin and vitamin K antagonists may increase the action of the latter. The risk may vary according to the underlying infection, age and general condition of the patient, so that the contribution of ciprofloxacin to the increase in "INR (international standardized ratio) is difficult to assess. Frequent monitoring of INR is recommended during and in the period immediately following concomitant administration of ciprofloxacin with a vitamin K antagonist (eg: warfarin, acenocoumarol, phenprocoumon or fluindione).
Duloxetine
In clinical studies it has been shown that concomitant use of duloxetine with strong CYP450 1A2 isozyme inhibitors such as fluvoxamine may result in increased AUC and Cmax of duloxetine. Although no clinical data are available on a possible interaction with ciprofloxacin, similar effects can be expected when administered concomitantly (see section 4.4).
Ropinirole
In a clinical study, concomitant use of ropinirole and ciprofloxacin, a moderate inhibitor of the CYP450 1A2 isoenzyme, was shown to increase the Cmax and AUC of ropinirole by 60% and 84%, respectively. It is advisable to monitor the possible occurrence of undesirable effects induced by ropinirole and to adjust its dosage accordingly during co-administration with ciprofloxacin and in the immediately following period (see section 4.4).
Lidocaine
In healthy subjects, concomitant use of ciprofloxacin with medicinal products containing lidocaine, a moderate inhibitor of CYP450 1A2 isozyme, has been shown to reduce clearance of intravenous lidocaine by 22%. Although lidocaine treatment is well tolerated, an interaction with ciprofloxacin, associated with side effects, may occur after concomitant administration.
Clozapine
Following concomitant administration of 250 mg ciprofloxacin and clozapine for 7 days, an increase in serum concentrations of clozapine and N-desmethylclozapine by 29% and 31%, respectively, was observed. It is recommended that the patient be monitored and the dosage of clozapine adjusted accordingly during co-administration with ciprofloxacin and immediately thereafter (see section 4.4).
Sildenafil
In healthy subjects, after oral administration of 50 mg of sildenafil concomitantly with 500 mg of ciprofloxacin, the Cmax and AUC of sildenafil were increased by approximately double. Therefore, particular caution should be exercised when prescribing ciprofloxacin concomitantly with sildenafil. taking into account the risks and benefits.
04.6 Pregnancy and lactation
Pregnancy
Available data on the administration of ciprofloxacin to pregnant women do not indicate a teratogenic effect or fetus / neonatal toxicity of ciprofloxacin. Animal studies have not shown direct or indirect harmful effects in terms of reproductive toxicity. Effects on immature cartilage have been observed in animals exposed to quinolones at an early age and in the prenatal period, so it cannot be excluded that the drug may cause harm to the articular cartilages of the undeveloped human organism or fetus (see section 5.3).
As a precaution, it is preferable to avoid the use of ciprofloxacin during pregnancy.
Breastfeeding
Ciprofloxacin is excreted in breast milk. Due to the possible risk of joint damage, ciprofloxacin should not be used during breastfeeding.
04.7 Effects on ability to drive and use machines
Due to its neurological effects, ciprofloxacin can influence reaction times, in such a way as to compromise the ability to drive and use machines.
04.8 Undesirable effects
The most commonly reported adverse reactions are nausea and diarrhea.
Adverse reactions reported with Ciproxin (oral, intravenous and sequential therapy) in clinical trials and during the post-marketing phase are listed below, classified by frequency. The frequency analysis takes into account data from both oral and from intravenous administration of ciprofloxacin.
Pediatric population
The incidence of arthropathy reported above refers to data collected in adult studies. In children, arthropathy is common (see section 4.4).
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
04.9 Overdose
An overdose of 12 g resulted in mild symptoms of toxicity. An acute overdose of 16 g caused acute renal failure.
Symptoms of overdose consist of dizziness, tremor, headache, fatigue, convulsions, hallucinations, confusion, abdominal discomfort, impaired renal and hepatic function, crystalluria and haematuria. Reversible renal toxicity has been reported.
In addition to the usual emergency measures such as gastric emptying followed by the administration of activated charcoal, it is recommended to keep renal function and urinary pH under control, if necessary by acidifying the urine to prevent crystalluria. Maintain adequate hydration. Antacids containing calcium and magnesium can theoretically reduce the absorption of ciprofloxacin in the event of an overdose.
Only a small amount of ciprofloxacin (hemodialysis or peritoneal dialysis.
In the event of an overdose, symptomatic treatment should be taken. ECG monitoring should be performed because of the possibility of QT interval prolongation.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: fluoroquinolones.
ATC code: J01MA02.
Mechanism of action
The bactericidal action of ciprofloxacin, as a fluoroquinolone antibacterial, is the result of the inhibition of type II topoisomerase (DNA-gyrase) and topoisomerase IV, necessary for the processes of replication, transcription, repair and recombination of bacterial DNA.
Pharmacinetic / pharmacodynamic relationship
Efficacy depends primarily on the relationship between maximum serum concentration (Cmax) and minimum inhibitory concentration (MIC) of ciprofloxacin for a pathogenic bacterium and the relationship between area under the curve (AUC) and MIC.
Resistance mechanism
In vitro, resistance to ciprofloxacin can be acquired through a step-by-step process by target site mutations in DNA gyrase and topoisomerase IV, resulting in a variable degree of cross-resistance between ciprofloxacin and other fluoroquinolones. While single mutations may not result in clinical resistance, multiple mutations result in clinical resistance to most or all of the active substances belonging to the class. Resistance mechanisms such as barriers to penetration and / or efflux mechanisms can have a variable effect on the sensitivity to fluoroquinolones, depending on the physico-chemical properties of the different active ingredients of the class and the affinity of the transport systems for each of them. All in vitro resistance mechanisms are commonly observed in clinical isolates Resistance mechanisms that inactivate other antibiotics, such as barriers to penetration (common in Pseudomonas aeruginosa) and efflux mechanisms, may affect sensitivity to ciprofloxacin.
Plasmid-mediated resistance encoded by qnr genes was observed.
Spectrum of antibacterial activity :
Breakpoints separate susceptible strains from those with intermediate susceptibility and the latter from resistant strains:
EUCAST recommendations
The prevalence of acquired resistance, for selected species, can vary both in different geographic areas and over time. Therefore local resistance data should be known, particularly for the treatment of severe infections. As necessary, expert advice should be sought where the local prevalence of resistance is such that the utility of the drug, at least in certain types of infections, is questionable.
Classification of relevant species based on susceptibility to ciprofloxacin (for species Streptococcus see section 4.4)
05.2 Pharmacokinetic properties
Absorption
Following oral administration of a 250 mg, 500 mg and 750 mg tablet, ciprofloxacin is rapidly and extensively absorbed, predominantly in the small intestine, reaching peak serum concentrations in 1-2 hours.
Single doses of 100 - 750 mg resulted in dose-dependent maximum serum concentrations (Cmax) ranging from 0.56 to 3.7 mg / L. Serum concentrations increase proportionally for doses up to 1000 mg.
Absolute bioavailability is 70 - 80%.
An oral dose of 500 mg, administered every 12 hours, produces an "area under the concentration-time curve (AUC) equivalent to that produced by an" intravenous infusion of 400 mg of ciprofloxacin, administered over 60 minutes every 12 hours.
Distribution
Plasma protein binding of ciprofloxacin is low (20-30%). Ciprofloxacin is present in plasma largely in non-ionized form and has a large steady-state volume of distribution of 2-3 L / kg body weight. Ciprofloxacin reaches high concentrations in a variety of tissues, such as the lung (epithelial fluid, alveolar macrophages, biopsy tissue), sinuses and inflammatory lesions (cantharid blister fluid) and the urogenital system (urine, prostate, endometrium) , where total concentrations exceeding those in plasma are reached.
Biotransformation
Low concentrations of four metabolites were found, identified as desethyleneciprofloxacin (M1), sulfociprofloxacin (M2), oxyciprofloxacin (M3) and formylciprofloxacin (M4). The metabolites show antibacterial activity in vitro, but lower than that of the parent compound.
Ciprofloxacin is a moderate inhibitor of CYP 450 1A2 isoenzymes.
Elimination
Ciprofloxacin is mainly excreted unchanged by the kidney and, to a lesser extent, by the faecal route. The serum elimination half-life in subjects with normal renal function is approximately 4-7 hours.
Renal clearance is between 180 and 300 mL / kg / h and total body clearance between 480 and 600 mL / kg / h. Ciprofloxacin undergoes both glomerular filtration and tubular secretion. Severe renal impairment results in an increase in the half-life of ciprofloxacin, which can reach 12 hours.
Non-renal clearance of ciprofloxacin is mainly due to active transintestinal secretion and metabolism. 1% of the dose is excreted via the biliary route. Ciprofloxacin is present in the bile in high concentrations.
Pediatric patients
Pharmacokinetic data in pediatric patients are limited.
In a study in children, Cmax and AUC were not age-dependent (beyond 1 year of age). There was no appreciable increase in Cmax and AUC following multiple dosing (10 mg / kg 3 times a day).
In 10 children with severe sepsis, Cmax was 6.1 mg / L (range 4.6 - 8.3 mg / L) after a "one-hour intravenous infusion" of 10 mg / kg in children aged less than one year, while in children from one to 5 years of age it was equal to 7.2 mg / L (range 4.7 - 11.8 mg / L). The values of the AUC were, in the respective groups, equal at 17.4 mg * h / L (range 11.8 - 32.0 mg * h / L) and 16.5 mg * h / L (range 11.0 - 23.8 mg * h / L).
These values are within the range found in adults at therapeutic doses.Based on a population pharmacokinetic analysis of pediatric patients with various infections, the expected mean half-life in children is approximately 4 - 5 hours and the bioavailability of the oral suspension ranges from 50 to 80%.
05.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of single dose toxicity, repeated dose toxicity, carcinogenic potential, reproductive toxicity.
Like many other quinolones, ciprofloxacin is phototoxic in animals at exposure levels that have clinical relevance. Photomutagenicity / photocarcinogenicity data show weak photomutagenic and photocarcinogenic effect of ciprofloxacin in vitro and in animal experiments. This effect is comparable to that of other gyrase inhibitors.
Joint tolerability:
As is also known for other gyrase inhibitors, ciprofloxacin causes changes in the large weight-bearing joints in growing animals. The extent of cartilage damage varies with age, species and dose and can be reduced by relieving the joints. Studies on mature animals (rat, dog) did not show cartilage lesions. In a study in young beagle dogs, ciprofloxacin caused severe joint changes after two weeks of treatment at therapeutic doses, which were still visible after 5 months.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Core of the tablet:
Microcrystalline cellulose
Crospovidone
Cornstarch
Magnesium stearate
Anhydrous colloidal silica
Coating film:
Hypromellose
Macrogol 4000
Titanium dioxide (E 171).
06.2 Incompatibility
Not relevant.
06.3 Period of validity
5 years.
06.4 Special precautions for storage
This medicine does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
One of the following primary packaging materials is used:
Clear colorless or opaque white PVC / PVDC / Aluminum blister
Transparent colorless or opaque white PP / Aluminum blister
Aluminum / Aluminum blister
Packs of 6, 8, 10, 12, 14, 16, 20, 28, 50, 100, 160 or 500 film-coated tablets
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
Bayer S.p.A.
Viale Certosa, 130
20156 Milan
08.0 MARKETING AUTHORIZATION NUMBER
Ciproxin 250 mg film-coated tablets - 10 tablets AIC 026664019
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
March 1, 1989 / October 9, 2010
10.0 DATE OF REVISION OF THE TEXT
11/2013