Instructions for use Tsiprinol film-coated tablets 750 mg No. 10
Composition
active ingredient: ciprofloxacin;
1 film-coated tablet contains 750 mg of ciprofloxacin as ciprofloxacin hydrochloride monohydrate;
Excipients: microcrystalline cellulose, croscarmellose sodium, sodium starch glycolate (type A), povidone, colloidal anhydrous silica, magnesium stearate, talc, titanium dioxide (E 171), hypromellose, propylene glycol.
Dosage form
Film-coated tablets.
Main physicochemical properties: oval, white tablets, film-coated, with a score on both sides.
Pharmacotherapeutic group
Antibacterials for systemic use. Fluoroquinolones. ATX code J01M A02.
Pharmacological properties
Pharmacodynamics.
Mechanism of action
The bactericidal effect of ciprofloxacin as a fluoroquinolone antibacterial agent is due to its ability to inhibit type II topoisomerases (DNA gyrase and topoisomerase IV), which are essential in many processes of the DNA life cycle, such as replication, transcription, repair, and recombination.
Pharmacokinetic/pharmacodynamic relationships
Efficacy mainly depends on the ratio between the maximum serum concentration (Cmax) and the minimum inhibitory concentration (MIC) of ciprofloxacin for the bacterial pathogen and on the value of the area under the concentration-time curve (AUC) and the MIC.
Mechanism of resistance
Resistance to ciprofloxacin in vitro is usually associated with target site mutations that arise in topoisomerase IV and DNA gyrase by multistep mutations. The degree of cross-resistance between ciprofloxacin and other fluoroquinolones, as a result, varies. Single mutations do not usually result in clinical resistance, but multiple mutations usually result in clinical resistance to several or all members of the fluoroquinolone class.
Resistance mechanisms such as impermeability and/or efflux pumps may have a different impact on susceptibility to fluoroquinolones, depending on the physiochemical properties of the different members of the class and the affinity of the transport systems for each active substance. All in vitro resistance mechanisms are generally observed in clinical isolates. Resistance mechanisms that inactivate other antibacterial agents, such as the permeability barrier (inherent in Pseudomonas aeruginosa) and efflux mechanisms, may affect susceptibility to ciprofloxacin.
The development of plasmid-mediated resistance encoded by the qnr gene has been reported.
Spectrum of antibacterial activity
Breakpoints separate susceptible strains from strains with intermediate susceptibility, and the latter from resistant strains.
EUCAST recommendations
| Microorganisms | Sensitive | Resistant |
| Enterobacteriaceae | £ 0.25 mg/l | > 0.5 mg/l |
| Salmonella spp. | ≤ 0.06 mg/l | > 0.06 mg/l |
| Pseudomonas spp. | £ 0.5 mg/l | > 0.5 mg/l |
| Acinetobacter spp. | £ 1 mg/l | > 1 mg/l |
| Staphylococcus spp.1 | £ 1 mg/l | > 1 mg/l |
| Haemophilus influenzae | £ 0.06 mg/l | > 0.06 mg/l |
| Moraxella catarrhalis | £ 0.125 mg/l | > 0.125 mg/l |
| Neisseria gonorrhoeae | £ 0.03 mg/l | > 0.06 mg/l |
| Neisseria meningitidis | £ 0.03 mg/l | > 0.03 mg/l |
| Non-species related control points2 | £ 0.25 mg/l | > 0.5 mg/l |
1 Staphylococcus spp. – Ciprofloxacin breakpoints are relevant to high-dose therapy. 2 Non-species breakpoints were determined primarily based on pharmacokinetic and pharmacodynamic data and are independent of species-specific MICs. They are used only for species that do not have their own breakpoints and not for species in which susceptibility testing is not recommended. |
In vitro susceptibility to ciprofloxacin
The prevalence of acquired resistance of isolated species may vary with location and time, and local information on resistance is therefore necessary, particularly in the treatment of severe infections. Specialist advice should be sought when the local prevalence of resistance is such that the benefit of the medicinal product, at least in some types of infections, is questionable.
The following genera and species of bacteria are generally susceptible to ciprofloxacin:
(for Streptococcus species, see section "Special instructions for use")
| Sensitive (usually) types of microorganisms |
Gram-positive aerobic microorganisms Bacillus anthracis1) |
Gram-negative aerobic microorganisms Aeromonas spp. Brucella spp. Citrobacter koseri Francisella tularensis Haemophilus ducreyi Haemophilus influenzae2) Legionella spp. Moraxella catarrhalis2) Neisseria meningitidis Pasteurella spp. Salmonella spp. 2) Shigella spp. 2) Vibrio spp. Yersinia pestis |
Anaerobic microorganisms Mobiluncus |
Other microorganisms Chlamydia trachomatis3) Chlamydia pneumoniae3) Mycoplasma hominis3) Mycoplasma pneumoniae3) |
| Species for which acquired resistance may develop |
Aerobic Gram-positive microorganisms Staphylococcus spp. 1) 4) |
Aerobic Gram-negative microorganisms Acinetobacter baumannii5) Burkholderia cepacia2) 5) Campylobacter spp.2) 5) Citrobacter freundii2) Enterobacter aerogenes Enterobacter cloacae2) Escherichia coli2) Klebsiella oxytoca Klebsiella pneumoniae2) Morganella morganii2) Neisseria gonorrhoeae2) Proteus mirabilis2) Proteus vulgaris2) Providencia spp. Pseudomonas aeruginosa2) Pseudomonas fluorescens Serratia marcescens2) |
Anaerobic microorganisms Peptostreptococcus spp. Propionibacterium acnes |
| Microorganisms initially resistant to ciprofloxacin |
Aerobic Gram-positive microorganisms Actinomyces Enterococcus faecium Listeria monocytogenes |
Aerobic Gram-negative microorganisms Stenotrophomonas maltophilia |
Anaerobic microorganisms Except for the above |
Other microorganisms Mycoplasma genitalium Ureaplasma urealyticum |
1) It has been shown that taking antibiotics immediately after exposure to Bacillus anthracis spores helps prevent disease if the number of spores can be reduced below the infectious dose. Two months of oral ciprofloxacin 500 mg twice daily is considered effective in preventing anthrax infection in adults. The physician should refer to national and/or international protocols for the treatment of anthrax. 2) Clinical efficacy has been demonstrated for susceptible isolates in approved clinical indications. 3) Natural average sensitivity in the absence of an acquired resistance mechanism. 4) Methicillin-resistant S. aureus is very often simultaneously resistant to fluoroquinolones. The rate of methicillin resistance among all staphylococcal species is about 20–50% and is usually high in hospital isolates. 5) Resistance rate ≥ 50% in one or more EU countries. |
Pharmacokinetics.
Absorption
After oral administration of ciprofloxacin tablets at a dose of 250 mg, 500 mg and 750 mg, ciprofloxacin is rapidly and well absorbed, mainly from the upper small intestine. Maximum serum concentrations (Cmax) are reached after 1–2 hours.
Single doses of 100–750 mg resulted in dose-dependent Cmax between 0.56 mg/L and 3.7 mg/L. Serum concentrations increased proportionally with increasing dose up to 1000 mg.
The absolute bioavailability of the drug is 70-80%. An oral dose of ciprofloxacin 500 mg every 12 hours was characterized by a total area under the concentration-time curve (AUC) equivalent to that after intravenous infusion of 400 mg ciprofloxacin, which was carried out over 60 minutes every 12 hours.
Distribution
The percentage of ciprofloxacin binding to blood proteins is insignificant (20–30%). Ciprofloxacin is found in blood plasma mainly in the non-ionized form and has a significant volume of distribution at steady state, which is 2–3 l/kg of body weight, reaching high concentrations in various tissues, for example in the lungs (epithelial fluid, alveolar macrophages, biopsy specimens), sinuses, inflamed damaged tissues and in tissues of the genitourinary organs (urine, prostate, endometrium), where the total concentration exceeds that in blood plasma.
Metabolism
Low concentrations of the following 4 metabolites were recorded: diethylciprofloxacin (M1), sulfociprofloxacin (M2), oxociprofloxacin (M3) and formylciprofloxacin (M4). The metabolites demonstrate in vitro antimicrobial activity, but to a lesser extent than the parent compound.
Ciprofloxacin is known to be a moderate inhibitor of CYP 450 1A2 isoenzymes.
Breeding
Ciprofloxacin is excreted mainly unchanged by both the kidneys and the intestines. The plasma half-life in individuals with normal renal function is approximately 4–7 hours.
| Ciprofloxacin elimination (% dose) after oral administration |
| Name | Ways of withdrawal |
| with urine | with feces |
| Ciprofloxacin | 44.7 | 25.0 |
| Metabolites (M1-M4) | 11.3 | 7.5 |
Renal clearance is 180–300 ml/kg/h, and total clearance is 480–600 ml/kg/h. Ciprofloxacin is subject to glomerular filtration and tubular secretion. In severe renal impairment, the half-life of ciprofloxacin is up to 12 hours.
Non-renal clearance of ciprofloxacin is primarily due to transintestinal secretion and metabolism. 1% of the dose is excreted via the biliary tract. Ciprofloxacin is present in high concentrations in bile.
Children.
In studies in children, no age-related Cmax and AUC (in children aged 1 year and older) were observed. After multiple dosing (10 mg/kg three times a day), no significant increase in Cmax and AUC was observed. In 10 children aged less than 1 year with severe sepsis, Cmax was 6.1 mg/l (range 4.6–8.3 mg/l) after a 1-hour intravenous infusion of 10 mg/kg. This value was 7.2 mg/l (range 4.7–11.8 mg/l) in children aged 1 to 5 years. AUC values were 17.4 mg*h/l (range 11.8–32.0 mg*h/l) and 16.5 mg*h/l (range 11–23.8 mg*h/l) in the respective age groups. These values are within the normal range observed in adults at therapeutic doses. Based on pharmacokinetic analyses of pediatric patients with various infections, the predicted mean elimination half-life in children is approximately 4–5 hours and the bioavailability of the oral suspension is 50% to 80%.
Indication
Ciprofloxacin is indicated for the treatment of the following infections (see sections "Pharmacological properties", "Special instructions for use"). Before starting therapy, special attention should be paid to all available information on resistance to ciprofloxacin.
Official recommendations on the appropriate use of antibacterial drugs should be taken into account.
Adults
Lower respiratory tract infections caused by gram-negative bacteria:
exacerbation of chronic obstructive pulmonary disease (in exacerbation of chronic obstructive pulmonary disease, ciprofloxacin should be used only when it is considered inappropriate to use other antibacterial agents that are usually recommended for the treatment of these infections);
bronchopulmonary infections in cystic fibrosis or bronchiectasis;
pneumonia.
Chronic purulent otitis media.
Exacerbation of chronic sinusitis, especially if caused by gram-negative bacteria.
Severe course of otitis externa.
Urinary tract infections:
uncomplicated acute cystitis (in uncomplicated acute cystitis, ciprofloxacin should be used only when the use of other antibacterial agents that are usually recommended for the treatment of these infections is considered inappropriate);
- acute pyelonephritis;
- complicated urinary tract infections;
- bacterial prostatitis.
Genital tract infections:
gonococcal urethritis and cervicitis caused by susceptible strains of Neisseria gonorrhoeae;
epididymo-orchitis caused by susceptible strains of Neisseria gonorrhoeae;
pelvic inflammatory disease, particularly those caused by sensitive strains of Neisseria gonorrhoeae.
Gastrointestinal infections (e.g., traveler's diarrhea).
Intra-abdominal infections.
Skin and soft tissue infections caused by gram-negative bacteria.
Bone and joint infections.
Prevention of invasive infections caused by Neisseria meningitidis.
Pulmonary form of anthrax (post-exposure prophylaxis and radical treatment).
Ciprofloxacin can be used to treat patients with neutropenia and hyperthermia if a bacterial infectious etiology of fever is suspected in this category of patients.
Children and adolescents
Bronchopulmonary infections caused by Pseudomonas aeruginosa in patients with cystic fibrosis.
Complicated urinary tract infections and acute pyelonephritis.
Pulmonary form of anthrax (post-exposure prophylaxis and radical treatment).
Ciprofloxacin can also be used to treat severe infections in children and adolescents when the doctor considers it necessary.
Treatment should only be initiated by a physician experienced in the treatment of cystic fibrosis and/or severe infections in children and adolescents (see sections 5.1 and 5.2).
Contraindication
Ciprofloxacin should not be used in cases of hypersensitivity to the active substance of the drug or to other drugs of the fluoroquinolone group, or to any of the excipients of the drug.
The simultaneous use of ciprofloxacin and tizanidine is contraindicated (see section "Interaction with other medicinal products and other types of interactions").
Interaction with other medicinal products and other types of interactions
Effects of other medicinal products on ciprofloxacin
Drugs that prolong the QT interval
Ciprofloxacin, like other fluoroquinolones, should be administered with caution to patients receiving drugs that prolong the QT interval (e.g., class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics) (see section "Special warnings and precautions for use").
Chelate complex formation
The absorption of ciprofloxacin is reduced when ciprofloxacin is administered (orally) with drugs containing multivalent cations, mineral supplements (e.g. calcium, magnesium, aluminum, iron), phosphate-binding polymers (e.g. sevelamer or carbonate lactan), sucralfate or antacids, as well as drugs with a high buffer capacity (such as didanosine tablets) containing magnesium, aluminum or calcium. Therefore, ciprofloxacin should be taken 1-2 hours before or at least 4 hours after taking these drugs.
This restriction does not apply to antacids belonging to the class of H2-receptor blockers.
Calcium in food has little effect on the absorption of ciprofloxacin (oral). Therefore, ciprofloxacin tablets can be taken 1-2 hours before or at least 4 hours after dairy products or mineral-fortified drinks, as recommended for calcium-containing preparations (see section "Method of administration and dosage").
Probenecid
Probenecid affects the renal secretion of ciprofloxacin. Concomitant use of medicinal products containing probenecid and ciprofloxacin leads to an increase in the concentration of ciprofloxacin in the blood serum.
Metoclopramide
Metoclopramide accelerates the absorption of ciprofloxacin, resulting in a faster Cmax. No effect on the bioavailability of ciprofloxacin was observed.
Omeprazole
Concomitant use of ciprofloxacin and medicinal products containing omeprazole leads to a slight decrease in Cmax and AUC of ciprofloxacin.
Effect of ciprofloxacin on other drugs
Tizanidine
Tizanidine should not be administered concomitantly with ciprofloxacin (see section "Contraindications"). Concomitant administration of ciprofloxacin and tizanidine has been shown to increase plasma concentrations of tizanidine (7-fold increase in Cmax, range 4-21-fold; 10-fold increase in AUC, range 6-24-fold). Increased serum concentrations of tizanidine are associated with increased hypotensive and sedative effects.
Methotrexate
With simultaneous use of ciprofloxacin, a slowdown in tubular transport (renal metabolism) of methotrexate is possible, which can lead to an increase in the concentration of methotrexate in the blood plasma and an increase in the likelihood of adverse toxic reactions caused by methotrexate. Simultaneous use is not recommended (see section "Special instructions").
Theophylline
The simultaneous use of ciprofloxacin and drugs containing theophylline may lead to an undesirable increase in the concentration of theophylline in the blood serum, which in turn may cause the development of adverse reactions. In isolated cases, such adverse reactions may be fatal. If the simultaneous use of these drugs cannot be avoided, the concentration of theophylline in the blood serum should be monitored and its dose should be reduced appropriately (see section "Special instructions").
Other xanthine derivatives
Increased serum concentrations of these xanthines have been reported following concomitant use of ciprofloxacin and medicinal products containing caffeine or pentoxifylline (oxpentifylline).
Phenytoin
Concomitant use of ciprofloxacin and phenytoin may result in increased or decreased serum concentrations of phenytoin, therefore monitoring of drug levels is recommended.
Cyclosporine
A transient increase in plasma creatinine has been observed with concomitant use of ciprofloxacin and cyclosporine-containing medicinal products. Therefore, frequent (twice a week) monitoring of plasma creatinine concentration is necessary in these patients.
Vitamin K antagonists
Concomitant use of ciprofloxacin and vitamin K antagonists may potentiate their anticoagulant effects. Increased activity of oral anticoagulants has been reported in patients receiving antibacterial agents, particularly fluoroquinolones. The degree of risk may vary depending on the underlying infection, age, and general condition of the patient, and it is therefore difficult to accurately assess the effect of ciprofloxacin on the increase in the International Normalized Ratio (INR). Frequent monitoring of INR should be performed during and immediately after concomitant use of ciprofloxacin and vitamin K antagonists (e.g. warfarin, acenocoumarol, phenprocoumon, fluindione).
Duloxetine
In clinical studies, it has been shown that concomitant use of duloxetine with strong inhibitors of the CYP450 1A2 isoenzyme, such as fluvoxamine, may lead to an increase in duloxetine AUC and Cmax. Although there are no clinical data on a possible interaction with ciprofloxacin, similar effects can be expected with the simultaneous use of these drugs (see section "Special instructions").
Ropinirole
In clinical studies, it was found that concomitant use of ropinirole with ciprofloxacin, a moderate inhibitor of the CYP450 1A2 isoenzyme, leads to an increase in AUC and Cmax of ropinirole by 60% and 84%, respectively. Monitoring of side effects of ropinirole and appropriate dose adjustment are recommended during and immediately after concomitant use with ciprofloxacin (see section "Special warnings and precautions for use").
Lidocaine
Concomitant use of ciprofloxacin, a moderate inhibitor of CYP P450 1A2, and lidocaine-containing medicinal products has been reported to reduce the clearance of intravenous lidocaine by 22%. Although lidocaine treatment is generally well tolerated, an interaction with ciprofloxacin is possible with concomitant use, which is associated with adverse reactions and may occur with concomitant use of these medicinal products.
After concomitant administration of 250 mg ciprofloxacin with clozapine for 7 days, serum concentrations of clozapine and N-desmethylclozapine were increased by 29% and 31%, respectively. Clinical monitoring and appropriate dose adjustment of clozapine are recommended during and immediately after concomitant administration with ciprofloxacin (see section 4.4).
Sildenafil
Cmax and AUC of sildenafil increased approximately 2-fold in healthy volunteers after oral administration of 50 mg sildenafil and concomitant administration of 500 mg ciprofloxacin. Therefore, caution should be exercised when co-administering ciprofloxacin with sildenafil and taking into account the risk/benefit ratio.
Agomelatine
In clinical studies, fluvoxamine, a strong inhibitor of the CYP450 1A2 isoenzyme, was found to moderately inhibit the metabolism of agomelatine, resulting in a 60-fold increase in agomelatine exposure. Although no clinical data are available on a possible interaction with ciprofloxacin, a moderate inhibitor of CYP450 1A2, similar effects can be expected with concomitant use (see section 4.4).
Zolpidem
Concomitant use of ciprofloxacin may increase blood levels of zolpidem, therefore concomitant use is not recommended.
Application features
Ciprofloxacin should be avoided in patients who have previously experienced serious adverse reactions to quinolone or fluoroquinolone-containing drugs (see section 4.8). Ciprofloxacin should only be initiated in such patients if no alternative treatment is available and after careful benefit/risk assessment (see section 4.8).
Severe infections and/or mixed infections caused by Gram-positive or anaerobic bacteria
Ciprofloxacin should not be used as monotherapy for the treatment of severe infections and infections caused by Gram-positive or anaerobic bacteria.
For the treatment of such infections, ciprofloxacin should be used in combination with appropriate antibacterial agents.
Streptococcal infections (including Streptococcus pneumoniae)
Ciprofloxacin is not recommended for the treatment of streptococcal infections due to insufficient efficacy.
Genital tract infections
Gonococcal urethritis, cervicitis, epididymo-orchitis, and pelvic inflammatory disease may be caused by fluoroquinolone-resistant strains of Neisseria gonorrhoeae.
Empirical therapy with ciprofloxacin for epididymo-orchitis and pelvic inflammatory disease should only be used in combination with other appropriate antibacterial agents (e.g., cephalosporin), except in clinical situations where the presence of ciprofloxacin-resistant strains of Neisseria gonorrhoeae has been excluded.
If clinical improvement does not occur after 3 days, therapy should be reviewed.
Urinary tract infections
Fluoroquinolone resistance in Escherichia coli, the most common pathogen causing urinary tract infections, varies across the European Union. Physicians are advised to consider the local prevalence of fluoroquinolone resistance in Escherichia coli when prescribing treatment.
A single dose of ciprofloxacin, which may be used for uncomplicated cystitis in premenopausal women, is expected to be less effective than longer-term therapy with the drug. This fact should be taken into account in view of the increasing level of resistance of Escherichia coli to quinolones.
Intra-abdominal infections
Data on the efficacy of ciprofloxacin in the treatment of postoperative intra-abdominal infections are limited.
Traveler's diarrhea
When choosing a drug, information on the resistance to ciprofloxacin of relevant microorganisms in the countries visited by the patient should be taken into account.
Bone and joint infections
Ciprofloxacin should be used in combination with other antimicrobial agents depending on the results of microbiological testing.
Pulmonary form of anthrax
The use of the medicinal product in humans is based on in vitro susceptibility data, animal studies and limited data from human use. The physician should act in accordance with national and/or international protocols for the treatment of anthrax.
Children
Ciprofloxacin caused arthropathy of the supporting joints in immature animals. Safety data from a randomized, double-blind study of ciprofloxacin in children (ciprofloxacin: n=335, mean age = 6.3 years; comparator: n=349, mean age = 6.2 years; age range 1 to 17 years) showed that the incidence of arthropathy, which is probably related to the drug (as distinct from clinical signs and symptoms related to joint damage), at 42 days from the start of the drug was 7.2% and 4.6% for the main and comparator groups, respectively. The incidence of drug-related arthropathy after 1 year of follow-up was 9.0% and 5.7%, respectively. The increase in the number of cases of arthropathy related to the drug was not statistically significant. However, treatment with ciprofloxacin in children and adolescents should only be initiated after a careful benefit/risk assessment due to the possible risk of adverse reactions involving the joints and/or surrounding tissues.
Bronchopulmonary infections in cystic fibrosis
Clinical studies included children and adolescents aged 5–17 years. There is more limited experience in children aged 1–5 years.
Complicated urinary tract infections and pyelonephritis
Treatment of urinary tract infections with ciprofloxacin should be considered when other treatment options are not available. Treatment should be based on microbiological findings. Clinical trials have evaluated the use of ciprofloxacin in children and adolescents aged 1–17 years.
Other specific severe infections
The use of ciprofloxacin may be justified by microbiological evidence in other serious infections in accordance with official guidelines or after a careful benefit/risk assessment when other treatments are not suitable or when standard treatment has failed.
The use of ciprofloxacin in specific severe infections other than those mentioned above has not been evaluated in clinical trials and clinical experience is limited. Therefore, caution is recommended when treating patients with such infections.
Hypersensitivity to the drug
Hypersensitivity and allergic reactions, including anaphylaxis and anaphylactoid reactions, may occur after a single dose of ciprofloxacin (see section 4.8) and may be life-threatening.
In this case, ciprofloxacin should be discontinued and appropriate medical treatment should be initiated immediately.
Prolonged, disabling and potentially irreversible adverse reactions
Very rare cases of long-lasting (several months or years) disabling and potentially irreversible serious adverse reactions affecting various body systems (musculoskeletal, nervous, mental and sensory) have been reported in patients treated with quinolones and fluoroquinolones, regardless of age or the presence of risk factors. Ciprofloxacin should be discontinued immediately at the first sign or symptom of any serious adverse reaction and a doctor should be consulted.
Musculoskeletal system
In general, ciprofloxacin should not be used in patients with a history of tendon disease or disorders associated with the use of quinolones. However, in rare cases, after microbiological investigation of the pathogen and an assessment of the benefit/risk ratio, ciprofloxacin may be prescribed to these patients for the treatment of certain severe infections, particularly in cases of failure of standard therapy or bacterial resistance, when the results of microbiological investigations justify the use of ciprofloxacin.
Tendinitis and tendon rupture
Ciprofloxacin should generally not be used in patients with a history of tendon diseases/disorders associated with quinolone use. However, in rare cases, after microbiological investigation of the pathogen and an assessment of the benefit/risk ratio, ciprofloxacin may be prescribed to these patients for the treatment of certain severe infections, namely in cases of failure of standard therapy or bacterial resistance, when microbiological results justify the use of ciprofloxacin.
Tendinitis and tendon rupture (especially but not limited to the Achilles tendon), sometimes bilateral, may occur as early as 48 hours after starting treatment with quinolones and fluoroquinolones, and even up to several months after stopping treatment. The risk of tendonitis and tendon rupture is increased in elderly patients, patients with impaired renal function, patients with organ transplants and patients receiving corticosteroid therapy (see section 4.8). If any signs of tendinitis (e.g. painful swelling, inflammation) occur, ciprofloxacin should be discontinued and alternative treatment should be considered. The affected limb(s) should be treated appropriately (e.g. immobilization) at rest. Corticosteroids should not be used if signs of tendinopathy occur.
Patients with myasthenia gravis
Aortic aneurysm and dissection, regurgitation/valvular insufficiency
Epidemiological studies have shown an increased risk of aortic aneurysm and dissection, as well as aortic and mitral valve regurgitation after taking fluoroquinolones, especially in elderly patients. Rare cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal), and regurgitation/insufficiency of any of the heart valves have been reported in patients taking fluoroquinolones (see section "Adverse reactions").
Therefore, fluoroquinolones should only be used after careful benefit-risk assessment and after consideration of other therapeutic options in patients with a family history of aortic aneurysm or congenital heart valve disease, in patients with previously diagnosed aortic aneurysm and/or aortic dissection, in patients with valvular heart disease, and in the presence of other risk factors:
Risk factors for both aortic aneurysm and/or aortic dissection and heart valve regurgitation/insufficiency: connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome, Turner syndrome, Behçet's disease, hypertension, rheumatoid arthritis;
Risk factors for developing aortic aneurysm and dissection: vascular disorders such as Takayasu arteritis or giant cell arteritis, atherosclerosis, Sjögren's syndrome;
Risk factors for the development of regurgitation/heart valve insufficiency: infective endocarditis.
The risk of aortic aneurysm and dissection and rupture is also increased in patients receiving concomitant systemic corticosteroids.
In case of sudden abdominal, chest or back pain, patients should seek immediate medical attention in the emergency department.
Patients should also be advised to seek immediate medical attention in the event of acute shortness of breath, new onset of palpitations, or development of abdominal or lower extremity edema.
Vision impairment
If you experience blurred vision or any noticeable effect on your eyes, you should consult a doctor immediately.
Photosensitivity
Ciprofloxacin has been shown to cause photosensitivity reactions. Patients taking ciprofloxacin are advised to avoid direct sunlight or UV radiation during treatment (see section 4.8).
Convulsions
Ciprofloxacin, like other quinolones, causes convulsions or lowers the seizure threshold. Cases of epilepsy have been reported. Ciprofloxacin should be used with caution in patients with CNS disorders that may predispose to convulsions or status epilepticus. If convulsions occur, ciprofloxacin should be discontinued (see section 4.8).
Peripheral neuropathy
Cases of sensory or sensorimotor polyneuropathy resulting in paresthesia, hypoesthesia, dysesthesia, or weakness have been reported in patients treated with quinolones and fluoroquinolones, including ciprofloxacin. Patients taking ciprofloxacin should inform their physician before continuing treatment if they develop symptoms of neuropathy such as pain, burning, tingling, numbness, or weakness, to prevent the development of a potentially irreversible condition (see section "Adverse Reactions").
Psychotic reactions
Psychotic reactions may occur even after the first dose of ciprofloxacin. In rare cases, depression or psychosis may progress to suicidal thoughts and actions, such as suicide or attempted suicide. In such cases, ciprofloxacin should be discontinued and appropriate measures should be taken.
Heart disorders
Fluoroquinolones, including ciprofloxacin, should be used with caution in patients with known risk factors for QT prolongation, including:
with hereditary QT prolongation syndrome;
in case of simultaneous use of drugs that may prolong the QT interval (e.g., class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, neuroleptics);
with uncorrected electrolyte imbalance (e.g. hypokalemia, hypomagnesemia);
in the presence of heart disease (e.g., heart failure, myocardial infarction, bradycardia).
Elderly patients and women may be more sensitive to drugs that prolong the QT interval. Therefore, fluoroquinolones, including ciprofloxacin, should be used with caution in these patient groups (see sections "Interaction with other medicinal products and other types of interactions", "Method of administration and dosage", "Overdose", "Adverse reactions").
Dysglycemia
As with other quinolones, blood glucose disturbances, including both hypoglycaemia and hyperglycaemia, have been reported (see section 4.8), particularly in elderly patients with diabetes mellitus receiving concomitant oral hypoglycaemic therapy (e.g.
