Active ingredients: Moxifloxacin
Avalox 400 mg film-coated tablets
Avalox package inserts are available for pack sizes:- Avalox 400 mg film-coated tablets
- Avalox 400 mg / 250 ml solution for infusion
Why is Avalox used? What is it for?
Avalox contains the active substance moxifloxacin, which is part of a group of antibiotics called fluoroquinolones. Avalox works by killing the bacteria that cause infections.
Avalox is used in patients 18 years of age or older to treat the following bacterial infections, when they are caused by bacteria against which moxifloxacin is active. Avalox should only be used to treat these infections when commonly used antibiotics cannot be used or have not worked:
Sinus infection, sudden worsening of long-lasting inflammation of the airways, or lung infection (pneumonia) from outside the hospital (with the exception of severe cases).
Mild or moderate infections of the upper tract of the female genital tract (pelvic inflammatory disease), including infections of the fallopian tubes and uterine lining.
Avalox tablets alone are not sufficient to treat these types of infections and your doctor should therefore prescribe you another antibiotic to treat upper female genital tract infections in addition to Avalox tablets (see section 2. What you need to know before you take Avalox…, Warnings and precautions…, Tell your doctor before you take Avalox).
If the following bacterial infections have improved during initial treatment with Avalox solution for infusion, your doctor may also prescribe Avalox tablets to complete the course of therapy: lung infection (pneumonia) caught outside the hospital, skin infections and soft tissue.
Avalox tablets should not be used to initiate therapy for any type of skin and soft tissue infection or severe lung infections.
Contraindications When Avalox should not be used
Contact your doctor if you are unsure whether you belong to one of the patient groups described below.
Do not take Avalox
- If you are allergic to the active substance moxifloxacin, to any other quinolone antibiotic or to any of the other ingredients of this medicine (listed in section 6).
- If you are pregnant or breastfeeding.
- If you are under the age of 18.
- If you have a history of tendon disease or disorder related to treatment with quinolone antibiotics (see sections Warnings and precautions… and 4. Possible side effects).
- If you have or have had any conditions since birth that involve abnormal heart rhythms (seen on the ECG, electrical recording of the heart), have an imbalance of salts in the blood (especially low levels of potassium or magnesium in the blood) have heart rhythm very slow (called 'bradycardia'), have a weak heart (heart failure), have a history of heart rhythm abnormalities, or are taking other medicines that cause ECG changes (see section Other medicines and Avalox). This is because Avalox can cause ECG alterations, which consist in a prolongation of the QT interval, ie a delay in the conduction of electrical signals.
- If you have severe liver disease or an increase in liver enzymes (transaminases) of more than 5 times the upper limit of normal.
Precautions for use What you need to know before taking Avalox
Tell your doctor before taking Avalox
- Avalox can modify the ECG, especially in women and elderly people.
- If you are taking medicines that lower blood potassium levels, consult your doctor before taking Avalox (see also Do not take Avalox and Other medicines and Avalox).
- If you have epilepsy or a condition that makes you prone to seizures, consult your doctor before taking Avalox.
- If you have or have had mental problems in the past, consult your doctor before taking Avalox.
- If you suffer from myasthenia gravis, taking Avalox may worsen the symptoms of your disease. If you think you have it, contact your doctor immediately.
- If you, or someone in your family, have glucose-6-phosphate dehydrogenase deficiency (a rare inherited disease), please tell your doctor, who will tell you if Avalox is suitable for you.
- In case of complicated upper female genital tract infection (for example associated with an abscess of the fallopian tubes and ovaries or pelvis), for which the doctor considers intravenous treatment necessary, treatment with Avalox tablets is not appropriate.
- For the treatment of mild or moderate infections of the upper tract of the female genital tract, your doctor should prescribe another antibiotic in addition to Avalox. If your symptoms do not improve after 3 days of treatment, consult your doctor
While taking Avalox
- If you experience palpitations or an irregular heartbeat during the treatment period, tell your doctor immediately, who can give you an ECG to measure your heart rhythm.
- The risk of heart problems may increase with increasing dose. Therefore, you should stick to the recommended dosage.
- There is a remote chance that a severe and sudden allergic reaction (an anaphylactic reaction / anaphylactic shock) will occur even at the first dose, with the following symptoms: chest tightness, lightheadedness, nausea or fainting, dizziness on standing. , stop taking Avalox and consult your doctor immediately.
- Avalox can cause rapidly evolving severe inflammation of the liver, which can lead to life-threatening liver failure (including fatal cases, see section 4. Possible side effects). Contact your doctor before continuing treatment if you rapidly develop signs such as feeling sick and / or nausea associated with yellowing of the whites of the eyes, dark urine, itching, bleeding tendency or hepatic encephalopathy (symptoms of impaired liver function or rapidly evolving severe inflammation of the liver).
- In case of skin reaction, blistering and / or peeling of the skin and / or mucous reactions (see section 4. Possible side effects), contact your doctor immediately before continuing treatment.
- Quinolone antibiotics, including Avalox, can cause seizures. If this happens, Avalox treatment should be stopped.
- You may experience symptoms of neuropathy, such as pain, burning, tingling, numbness and / or weakness. If so, contact your doctor immediately before continuing treatment with Avalox.
- You may also experience mental problems when taking quinolone antibiotics, including Avalox, for the first time. In very rare cases, depression or mental problems have led to suicidal thoughts and self-aggressive behaviors, such as suicide attempts (see section 4. Possible side effects). If such reactions develop, Avalox treatment should be discontinued.
- Diarrhea may occur during or after taking antibiotics (including Avalox). If it gets worse or persists, or if you notice blood or mucus in your stool, you should stop taking Avalox immediately and consult your doctor. In this situation, you should not take medicines that block or reduce bowel movements.
- Occasionally Avalox can cause tendon pain and inflammation, even in the first 48 hours after starting treatment and up to several months after stopping Avalox therapy. The risk of inflammation and tendon ruptures is particularly increased if you are elderly or if you are being treated with corticosteroids. At the first sign of pain or inflammation, stop taking Avalox, rest the affected limb and consult your doctor immediately. Avoid any unnecessary physical activity, as it may increase the risk of a tendon rupture (see section Do not take Avalox… and 4 Possible side effects).
- If you are elderly and have kidney problems, try to get enough fluids, as dehydration can increase the risk of kidney failure.
- If you notice impaired vision or have any other eye problems while taking Avalox, consult an ophthalmologist immediately (see sections Driving and using machines and 4. Possible side effects).
- Quinolone antibiotics can make the skin more sensitive to sunlight or UV. Avoid prolonged exposure to sunlight, intense sunlight and do not use tanning beds or UV lamps while taking Avalox.
- The efficacy of Avalox in the treatment of severe burns, deep tissue infections, major purulent ulcers (abscesses) and diabetic foot infections with osteomyelitis (bone marrow infection) has not been demonstrated.
Children and adolescents
This medicine should not be given to children and adolescents under 18 years because the efficacy and safety of moxifloxacin have not been established in this age group (see section Do not use Avalox).
Interactions Which drugs or foods may change the effect of Avalox
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines besides Avalox.
Regarding Avalox know that:
- If you are taking Avalox and other medicines that affect the heart there is an increased risk of heart rhythm disturbances. Therefore do not take Avalox with the following medicines: medicines that belong to the group of antiarrhythmics (eg quinidine, hydroquinidine, disopyramide, amiodarone , sotalol, dofetilide, ibutilide), antipsychotics (e.g. phenothiazines, pimozide, sertindole, haloperidol, sultopride), tricyclic antidepressants, some antimicrobials (e.g. saquinavir, sparfloxacin, intravenous erythromycin, some altranamidine, particularly inimalofantramidine) antihistamines (e.g. terfenadine, astemizole, mizolastine) and other medicines (e.g. cisapride, intravenous vincamine, bepridyl, dihemanyl).
- You should tell your doctor if you are taking other medicines that can reduce blood potassium levels (for example some diuretics, some laxatives and enemas [high dose] or corticosteroids [anti-inflammatory drugs], amphotericin B) or slow the heart rate, because these may also increase the risk of serious heart rhythm disturbances while taking Avalox.
- Medicines that contain magnesium or aluminum, such as antacids for indigestion, iron or zinc, didanosine or sucralfate for the treatment of gastrointestinal disorders may reduce the action of Avalox tablets. If you take any of these medicines, take the Avalox tablet 6 hours before or 6 hours after.
- taking medicinal charcoal by mouth with Avalox tablets reduces the action of Avalox. It is therefore recommended not to use these medicines together.
- If you are taking oral anticoagulants (eg warfarin), your doctor may need to check your blood clotting time frequently.
Avalox with food and drink
The effect of Avalox is not affected by food, including milk, dairy products and cheeses.
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility
If you are pregnant or breast-feeding do not take Avalox.
If you are pregnant or breast-feeding, think you may be pregnant or are planning to become pregnant, ask your doctor or pharmacist for advice before taking this medicine.
Animal studies have not indicated that your fertility is impaired by this medicine.
Driving and using machines
Avalox may cause dizziness or light-headedness, sudden temporary loss of vision, or brief loss of consciousness. If it does this to you, you don't drive vehicles or operate machinery.
Avalox contains lactose
If you have been told by your doctor that you have "intolerance to some sugars, contact your doctor before taking Avalox
Dose, Method and Time of Administration How to use Avalox: Posology
Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
The recommended dose for adults is one 400 mg film-coated tablet once daily.
Avalox tablets are for oral use. Swallow the tablet whole (so as not to taste the bitter taste) with plenty of water or other drink. You can take Avalox with or without food. It is recommended that the tablet be taken at approximately the same time each day.
It is not necessary to adjust the dose in elderly patients, in patients with low body weight or in patients with kidney problems
The duration of treatment depends on the type of infection. Unless otherwise directed by your doctor, the recommended duration of use for Avalox film-coated tablets is:
- Sudden worsening of chronic bronchitis 5-10 days (flare-up of chronic bronchitis)
- Lung infection (pneumonia) contracted outside the hospital, 10 days with the exception of severe cases
- Acute sinus infection (acute bacterial sinusitis) 7 days
- Mild or moderate infections of the upper tract of the female genital tract (pelvic inflammatory disease), including infections of the fallopian tubes and uterine lining 14 days
When Avalox film-coated tablets are used to complement a course of therapy initiated with Avalox solution for infusion, the recommended doses are:
- Lung infection (pneumonia) caught outside the hospital, 7 to 14 days
Most patients with pneumonia are switched to oral treatment with Avalox film-coated tablets within 4 days
- Skin and soft tissue infection 7 - 21 days
Most patients with skin and soft tissue infection are switched to oral treatment with Avalox film-coated tablets within 6 days
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, your infection may not be completely cured, you may have a relapse or your condition may get worse, and it may also create bacterial resistance to the antibiotic.
You should not exceed either the recommended dose or duration of treatment (see section 2. What you need to know before you take Avalox, Warnings and precautions).
Overdose What to do if you have taken too much Avalox
If you take more Avalox than you should
If you take more than the prescribed dose of one tablet a day, consult a doctor immediately and, if possible, take any remaining tablets, the pack, or this leaflet with you to show the doctor or pharmacist what you have taken.
If you forget to take Avalox
If you forget to take your tablet, take it as soon as you remember on the same day. If you happen to miss a day, take your normal dose (one tablet) the next day. Do not take a double dose to make up for a forgotten dose.
If you are not sure what to do, consult your doctor or pharmacist.
If you stop taking Avalox
If you stop taking this medicine too soon, your infection may not be completely cured. Consult your doctor if you wish to stop taking the tablets before the end of the course of treatment.
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 Avalox
Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects have been observed during treatment with Avalox. The assessment of undesirable effects is based on the following frequency data:
Common: may affect up to 1 in 10 patients
Uncommon: may affect up to 1 in 100 patients
Rare: may affect up to 1 in 1,000 patients
Very rare: may affect up to 1 in 10,000 patients
Infections
Common: Infections caused by resistant bacteria or fungi, eg. oral and vaginal Candida infections
Blood and Lymphatic System
Uncommon: decrease in red blood cells, decrease in white blood cells, decrease in a particular type of white blood cell (neutrophils), decrease or increase in special cells needed for blood clotting, increase in specialized white blood cells (eosinophils) , decreased blood clotting
Very rare: increased blood clotting, major decrease in a particular type of white blood cell (agranulocytosis)
Allergic reactions
Uncommon: allergic reaction
Rare: severe and sudden generalized allergic reaction, including, in very rare cases, life-threatening shock (e.g. difficulty in breathing, drop in blood pressure, rapid pulse), swelling (including swelling of the airways, potentially life-threatening)
Alterations in Laboratory Test Results
Uncommon: increased blood lipids (fats)
Rare: blood sugar increased, blood uric acid increased
Psychiatric manifestations
Uncommon: anxiety, restlessness / agitation
Rare: emotional instability, depression (which in very rare cases can lead to self-harming behaviors, such as suicidal thoughts, suicidal thoughts or suicide attempts), hallucinations
Very rare: feeling of dissociation (not being oneself), insanity (which can lead to self-harming behaviors, such as suicidal thoughts, suicidal thoughts or suicide attempts)
Nervous system
Common: headache, dizziness
Uncommon: tingling and / or numbness, taste disturbances (in very rare cases loss of taste), confusion and disorientation, sleep disturbances (mainly insomnia), tremor, dizziness (dizziness, feeling of falling), somnolence
Rare: decreased tactile sensitivity, altered sense of smell (including loss of smell), disturbed dreams, disturbed balance and poor coordination (due to dizziness), convulsions, difficulty concentrating, speech disturbances, partial memory loss or total, disorders associated with the nervous system, such as pain, burning, tingling, numbness and / or weakness in the extremities
Very rare: increased tactile sensitivity
Eye
Uncommon: visual disturbances, including diplopia (double vision) and blurred vision
Very rare: temporary loss of vision
Ear
Rare: ringing / noise in the ears, hearing loss including deafness (usually reversible)
Heart System (see section 2. What you need to know before you take Avalox)
Common: change in heart rhythm (ECG) in patients with low blood potassium levels
Uncommon: change in heart rhythm (ECG), palpitations, irregular and fast heartbeat, severe heart rhythm abnormalities, angina pectoris
Rare: rapid heart rhythm, faintness
Very rare
abnormal heart rhythms life-threatening irregular heartbeat, cessation of heartbeat
Vascular system
Uncommon: dilation of blood vessels
Rare: high blood pressure, low blood pressure
Respiratory system
Uncommon: difficulty in breathing, including asthmatic conditions
Gastrointestinal system
Common: nausea, vomiting, stomach pain and abdominal pain, diarrhea
Uncommon: decreased appetite and food intake, bloating and constipation, stomach upset (indigestion, heartburn), stomach inflammation, increase in a particular digestive enzyme in the blood (amylase)
Rare: Difficulty swallowing, inflammation of the mouth, severe diarrhea containing blood and / or mucus (antibiotic-induced colitis, including pseudomembranous colitis), which in very rare circumstances can lead to life-threatening complications
Liver
Common: increase in a particular liver enzyme in the blood (transaminases)
Uncommon: impairment of liver function (including increase in a particular liver enzyme in the blood (LDH)), increase in bilirubin in the blood, increase in a particular liver enzyme in the blood (gamma-GT and / or alkaline phosphatase )
Rare: jaundice (yellowing of the whites of the eyes or skin), inflammation of the liver
Very rare: fulminant inflammation of the liver which can progress to life-threatening liver failure (including fatal cases)
Skin
Uncommon: pruritus, rash, urticaria, dry skin
Very rare: skin and mucosal changes (painful blisters in the mouth / nose or penis / vagina), potentially life-threatening (Stevens-Johnson syndrome, toxic epidermal necrolysis)
Muscular and Joint System
Uncommon: joint pain, muscle pain
Rare: tendon pain and swelling (tendonitis), muscle cramps, muscle spasms, muscle weakness
Very rare: tendon rupture, joint inflammation, muscle stiffness, worsening of the symptoms of myasthenia gravis
Kidney
Uncommon: dehydration
Rare: renal impairment (including increased laboratory parameters indicating renal function, such as urea and creatinine), renal failure
General Unwanted Effects
Uncommon: feeling unwell (predominantly weakness or tiredness), pain, such as lower back pain, chest pain, pelvic pain, pain in extremity, sweating
Rare: swelling (of hands, feet, ankles, lips, mouth, throat)
In addition, very rare cases of the following side effects, which cannot be excluded may also occur during treatment with Avalox, have been reported with other quinolone antibiotics: increased blood sodium levels, increased blood calcium levels, a particular type of decrease in red blood cells (haemolytic anemia), muscle reactions with injury to muscle cells, increased sensitivity of the skin to sunlight or UV light.
If you get any side effects, please tell your doctor or pharmacist This includes any side effects not listed in this leaflet.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the blister and carton. The expiry date refers to the last day of that month.
Do not store above 25 ° C.
Store in the original package to protect from moisture. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
What Avalox contains
- The active ingredient is moxifloxacin. Each film-coated tablet contains 400 mg of moxifloxacin as hydrochloride.
- The excipients are:
Tablet core: microcrystalline cellulose, croscarmellose sodium, lactose monohydrate (see section Avalox contains lactose) and magnesium stearate.
Film-coating: hypromellose, macrogol 4000, iron oxide (E172) and titanium dioxide (E171).
What Avalox looks like and contents of the pack
Each dull red, oblong shaped, convex, faceted, 17 x 7 mm film-coated tablet is marked with "M400" on one side and "BAYER" on the other.
Avalox is packaged in cartons containing colorless or opaque white / aluminum polypropylene blisters.
Avalox is available in retail packs of 5, 7 and 10 film-coated tablets, hospital packs of 25, 50 or 70 film-coated tablets, and hospital multipacks consisting of 5 cartons each containing 16 tablets or 10 cartons containing each 10 tablets.
Avalox is also available as a medical sample from a film-coated tablet in a carton box containing an aluminum / aluminum blister.
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
AVALOX 400 MG TABLETS COATED WITH FILM
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
1 film-coated tablet contains 400 mg of moxifloxacin (as hydrochloride).
Excipient with known effect: the film-coated tablet contains 68 mg of lactose monohydrate (equivalent to 66.56 mg of lactose) (see section 4.4).
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Film-coated tablet.
Dull red, oblong convex shaped faceted film-coated tablet, 17 x 7 mm in size and marked with "M400" on one side and "BAYER" on the other.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Avalox 400 mg film-coated tablets are indicated in patients of at least 18 years of age for the treatment of the following bacterial infections caused by bacteria susceptible to moxifloxacin (see sections 4.4, 4.8 and 5.1). Moxifloxacin should only be used if the antibacterial agents commonly recommended for the initial treatment of these infections are deemed inappropriate or have failed:
• Acute bacterial sinusitis (properly diagnosed)
• Exacerbation of chronic bronchitis (adequately diagnosed)
• Community-acquired pneumonia, with the exclusion of severe forms
• Mild or moderate pelvic inflammatory disease (ie upper tract infections of the female genital tract, including salpingitis and endometritis), not associated with tubo-ovarian or pelvic abscess.
Avalox 400 mg film-coated tablets are not recommended as monotherapy in mild or moderate pelvic inflammatory disease, but should be administered in combination with another appropriate antibacterial (e.g. a cephalosporin), due to increasing resistance to moxifloxacin of the Neisseria gonorrhoeae, unless the presence of Neisseria gonorrhoeae resistant to moxifloxacin (see sections 4.4 and 5.1).
Avalox 400 mg film-coated tablets can also be used to complete a course of therapy in patients who have experienced improvement during initial treatment with intravenous moxifloxacin for the following indications:
• Community-acquired pneumonia
• Complicated skin and soft tissue infections
Avalox 400 mg film-coated tablets should not be used as initial therapy for any type of skin and soft tissue infection or in severe, community-acquired pneumonia.
When prescribing antibiotic therapy, reference should be made to official guidelines on the appropriate use of antibacterial agents.
04.2 Posology and method of administration
Dosage (adults)
The recommended dose is one 400 mg film-coated tablet once a day.
Renal / hepatic insufficiency
No dosage adjustments are required in patients with mild to severe renal impairment or in patients on chronic dialysis, i.e. hemodialysis or continuous ambulatory peritoneal dialysis (see section 5.2 for more details).
Data in patients with impaired hepatic function are insufficient (see section 4.3).
Other special categories of patients
No dosage adjustments are necessary in the elderly and in patients with low body weight.
Pediatric population
Moxifloxacin is contraindicated in children and adolescents (under 18 years). The efficacy and safety of moxifloxacin have not been established in children and adolescents (see section 4.3).
Method of administration
The film-coated tablet should be swallowed whole with a sufficient amount of liquid and can be taken with or without meals.
Duration of administration
Avalox 400 mg film-coated tablets should be taken for the following treatment periods:
• Exacerbation of chronic bronchitis 5-10 days
• Community acquired pneumonia 10 days
• Acute bacterial sinusitis 7 days
• Mild or moderate pelvic inflammatory disease 14 days
Avalox 400 mg film-coated tablets have been studied in clinical trials for treatment periods of up to 14 days.
Sequential therapy (intravenous followed by oral administration)
In sequential therapy clinical trials, most patients switched from intravenous to oral therapy within 4 days (community acquired pneumonia) or 6 days (complicated skin and soft tissue infections). The total recommended duration for intravenous and oral administration is 7 - 14 days for community acquired pneumonia and 7 - 21 days for complicated skin and soft tissue infections.
It is recommended not to exceed the recommended dosage (400 mg once daily), nor the duration of therapy for the specific indication.
04.3 Contraindications
• Hypersensitivity to moxifloxacin, to other quinolones or to any of the excipients listed in section 6.1.
• Pregnancy and lactation (see section 4.6).
• Patients under the age of 18.
• Patients with a "history of tendon disease / disorder related to quinolone treatment."
In both preclinical trials and in humans, changes in cardiac electrophysiology, in the form of QT interval prolongation, have been observed following exposure to moxifloxacin. For safety reasons, moxifloxacin is therefore contraindicated in patients with:
- Documented prolongation of congenital or acquired QT
- Electrolyte changes, in particular uncorrected hypokalaemia
- Clinically relevant bradycardia
- Heart failure with reduced left ventricular ejection fraction, clinically relevant
- History of symptomatic arrhythmias.
Moxifloxacin should not be used concomitantly with other drugs that prolong the QT interval (see also section 4.5).
Due to insufficient clinical data, moxifloxacin is also contraindicated in patients with reduced hepatic function (Child Pugh C) and in patients with transaminase elevations> 5 x the upper limit of normal.
04.4 Special warnings and appropriate precautions for use
The benefit of moxifloxacin treatment, especially in the case of infections of low severity, should be weighed against the information contained in the "Warnings and precautions" section.
QTc interval prolongation and potentially related clinical conditions
In some patients, moxifloxacin resulted in a prolongation of the QTc interval of the electrocardiogram. In the analysis of ECGs obtained in the clinical trial program, QTc prolongation with moxifloxacin was 6 msec ± 26 msec, 1.4% of baseline. As women tend to have a longer baseline QTc interval than in men, they may be more sensitive to QTc prolonging drugs. Elderly patients may also be more susceptible to pharmacological effects on the QT interval.
In patients receiving moxifloxacin, potassium-lowering drugs should be used with caution (see also sections 4.3 and 4.5).
Moxifloxacin should be used with caution in patients with existing conditions that may favor the development of arrhythmias (especially women and elderly patients), such as acute myocardial ischaemia or QT prolongation, as these conditions may increase the risk of ventricular arrhythmias (including torsades de pointes) and cardiac arrest (see also section 4.3). The extent of QT prolongation may increase with increasing drug concentrations. Therefore, it is recommended not to exceed the recommended dosage.
If signs of cardiac arrhythmia occur during treatment with moxifloxacin, discontinue treatment and perform an ECG.
Hypersensitivity / allergic reactions
For fluoroquinolones, including moxifloxacin, allergic and hypersensitivity reactions have been reported after the first administration. Anaphylactic reactions can progress to shock, which can be life threatening, even after the first administration. In such cases, moxifloxacin therapy should be discontinued and appropriate treatment (e.g. shock treatment) initiated.
Severe liver disease
Cases of fulminant hepatitis potentially leading to hepatic failure (including fatal cases) have been reported with moxifloxacin (see section 4.8). Patients should be advised to contact their physician before continuing treatment if signs and symptoms of fulminant liver disease appear, such as rapidly evolving asthenia associated with jaundice, dark urine, haemorrhagic diathesis or hepatic encephalopathy.
If there are indications of hepatic dysfunction, liver function tests / investigations should be performed.
Severe blistering skin reactions
Cases of bullous skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, have been reported with moxifloxacin (see section 4.8). Patients should be advised to seek immediate medical attention before continuing treatment in the event of skin and / or mucosal reactions.
Patients with a predisposition to convulsions
Quinolones are known to cause seizures. The product should be used with caution in patients with CNS disorders or in the presence of other risk factors that may predispose to seizures or lower the seizure threshold. If seizures occur, treatment with moxifloxacin should be discontinued and appropriate therapeutic measures implemented.
Peripheral neuropathy
In patients treated with quinolones, including moxifloxacin, there have been reports of sensory or motor sensory polyneuropathy manifesting as paraesthesia, hypoesthesia, dysaesthesia or weakness.Patients taking moxifloxacin should be advised of the need to inform their physician before continuing treatment if symptoms of neuropathy such as pain, burning, tingling, numbness or weakness appear (see section 4.8).
Psychiatric reactions
Even after the first administration of quinolones, including moxifloxacin, psychiatric reactions may occur. In very rare cases, depression or psychotic reactions can develop into suicidal thoughts and self-aggressive behaviors, such as suicide attempts (see section 4.8). If the patient develops such reactions, moxifloxacin treatment should be discontinued and appropriate therapeutic measures implemented. Caution is advised if moxifloxacin is to be used in psychotic patients or in patients with a history of psychiatric illness.
Antibiotic associated diarrhea and colitis
Cases of antibiotic-associated diarrhea and colitis, including pseudomembranous colitis and diarrhea associated with Clostridium difficile, the severity of which can range from mild diarrhea to fatal colitis. Therefore, it is important that this diagnosis be considered in patients who develop severe diarrhea during or after use of moxifloxacin. If antibiotic-associated diarrhea or colitis is suspected or confirmed, ongoing treatment with antibacterial agents , including moxifloxacin, should be discontinued and appropriate therapeutic measures instituted immediately. In addition, appropriate infection control measures should be taken to reduce the risk of transmission. Drugs that inhibit peristalsis are contraindicated in patients who develop severe diarrhea.
Patients with myasthenia gravis
Moxifloxacin should be used with caution in patients with myasthenia gravis as an exacerbation of symptoms may occur.
Inflammation and rupture of the tendons
During therapy with quinolones, including moxifloxacin, inflammation and rupture of tendons (especially the Achilles tendon), sometimes bilateral, may occur even in the first 48 hours after starting treatment and up to several months after stopping. The risk of tendonitis and tendon rupture is increased, particularly in elderly patients and in those receiving concomitant corticosteroid treatment. At the first sign of pain or inflammation, patients should stop moxifloxacin treatment, rest the limb or affected limbs and consult a physician immediately in order to initiate appropriate treatment (eg immobilization) for the affected tendon (see sections 4.3 and 4.8).
Patients with impaired renal function
Elderly patients with renal disorders should use moxifloxacin with caution if they are unable to maintain adequate water supply, as dehydration may increase the risk of renal failure.
Visual disturbances
If visual impairment or any other eye effect is observed, an ophthalmologist should be consulted immediately (see sections 4.7 and 4.8).
Prevention of photosensitivity reactions
Quinolones have been shown to cause photosensitivity reactions in patients. However, studies have shown that moxifloxacin has a lower risk of inducing photosensitivity. Nevertheless, patients should be advised to avoid exposure to UV rays and intense and / or prolonged exposure to sunlight during treatment with moxifloxacin.
Patients with glucose-6-phosphate dehydrogenase deficiency
Patients with a family history of, or with, glucose-6-phosphate dehydrogenase deficiency may experience haemolytic reactions when treated with quinolones. Therefore, moxifloxacin should be used with caution in these patients.
Patients with galactose intolerance, lactase deficiency or glucose-galactose malabsorption
Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Patients with pelvic inflammatory disease
For patients with complicated pelvic inflammatory disease (e.g. associated with tubo-ovarian or pelvic abscess), for whom intravenous therapy is deemed necessary, treatment with Avalox 400 mg film-coated tablets is not recommended.
Pelvic inflammatory disease can be caused by Neisseria gonorrhoeae resistant to fluoroquinolones. In this hypothesis, another appropriate antibiotic (e.g. a cephalosporin) should be associated with empiric therapy with moxifloxacin, unless the presence of Neisseria gonorrhoeae resistant to moxifloxacin. If clinical improvement is not achieved after 3 days of treatment, therapy should be reconsidered.
Patients with particular types of complicated skin and soft tissue infections (cSSSI)
The clinical efficacy of moxifloxacin in the treatment of severe burn infections, major abscess fasciitis and diabetic foot infections with osteomyelitis has not been demonstrated.
Interference with biological tests
Moxifloxacin therapy may interfere with culture for Mycobacterium spp. by suppression of mycobacterial growth, resulting in false negative results in samples taken from patients undergoing treatment with moxifloxacin.
Patients with MRSA infections
Moxifloxacin is not recommended for the treatment of MRSA-related infections. In case of suspected or confirmed MRSA infection, treatment with an appropriate antibacterial should be initiated (see section 5.1).
Pediatric population
Due to adverse effects on cartilage in juvenile animals (see section 5.3), the use of moxifloxacin in children and adolescents below 18 years of age is contraindicated (see section 4.3).
04.5 Interactions with other medicinal products and other forms of interaction
Interactions with Medicines
An additive effect on QT interval prolongation by moxifloxacin and other medicinal products capable of prolonging the QTc interval cannot be excluded. This effect may lead to an increased risk of ventricular arrhythmias, including torsades de pointes. Therefore, co-administration of moxifloxacin with the following medicinal products is contraindicated (see also section 4.3):
- class IA antiarrhythmics (e.g. quinidine, hydroquinidine, disopyramide)
- class III antiarrhythmics (e.g. amiodarone, sotalol, dofetilide, ibutilide)
- antipsychotics (e.g. phenothiazines, pimozide, sertindole, haloperidol, sultopride)
- tricyclic antidepressants
- some antimicrobials (saquinavir, sparfloxacin, i.v. erythromycin, pentamidine, antimalarials, in particular halofantrine)
- some antihistamines (terfenadine, astemizole, mizolastine)
- others (cisapride, vincamine i.v., bepridyl, difemanyl).
Moxifloxacin should be used with caution in patients taking medicinal products capable of lowering potassium levels (eg loop diuretics and thiazides, laxatives and enemas (high doses), corticosteroids, amphotericin B) or medicinal products associated with clinically significant bradycardia .
An interval of approximately 6 hours should elapse between the administration of preparations containing divalent or trivalent cations (e.g. antacids containing magnesium or aluminum, didanosine tablets, sucralfate and preparations containing iron or zinc) and the administration of moxifloxacin.
The concomitant administration of charcoal with an oral dose of 400 mg of moxifloxacin significantly impeded the absorption of the drug and reduced its systemic availability by more than 80%. Therefore the concomitant use of these two drugs is not recommended (except in case of overdose, see also section 4.9).
After repeated administration in healthy volunteers, moxifloxacin caused an increase in digoxin Cmax of approximately 30%, without affecting its AUC or trough concentrations. No precautions are necessary for use with digoxin.
In studies conducted in diabetic volunteers, co-administration of oral moxifloxacin with glibenclamide reduced peak plasma concentrations of glibenclamide by approximately 21%. The combination of glibenclamide and moxifloxacin can theoretically give rise to mild and transient hyperglycaemia. However, the observed changes in the pharmacokinetics of glibenclamide did not result in changes in the pharmacodynamic parameters (glycaemia, insulinemia). Therefore, no clinically relevant interaction was observed between moxifloxacin and glibenclamide.
Alterations of the INR
Numerous cases of "increased" activity of oral anticoagulants have been reported in patients receiving antibacterial agents, particularly fluoroquinolones, macrolides, tetracyclines, cotrimoxazole and some cephalosporins. The infectious and inflammatory state, as well as the age and general condition of the patient, seem to constitute risk factors. In these circumstances, it is difficult to assess whether the disorder of the INR (international standardized report) is caused by the infection or by the therapy A precautionary measure is represented by a more frequent monitoring of the INR. If necessary, the dosage of the oral anticoagulant should be adjusted accordingly.
Clinical studies have shown that there are no interactions following concomitant administration of moxifloxacin with: ranitidine, probenecid, oral contraceptives, calcium supplements, injecting morphine, theophylline, cyclosporine or itraconazole.
Studies in vitro with human cytochrome P-450 enzymes supported these conclusions. In light of these findings, a "metabolic interaction mediated by cytochrome P-450 enzymes is unlikely.
Interaction with food
Moxifloxacin does not give rise to clinically relevant interactions with food, including milk and derivatives.
04.6 Pregnancy and lactation
Pregnancy
The safety of moxifloxacin in pregnancy has not been evaluated in humans. Animal studies have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Due to the experimental risk of injuries caused by fluoroquinolones on the cartilage of weight-bearing joints of growing animals and the reversible joint injuries described in children who have taken fluoroquinolones, moxifloxacin should not be administered during pregnancy (see section 4.3).
Breastfeeding
No data on use in lactating or lactating women are available. Preclinical data indicate that small amounts of moxifloxacin pass into milk. In the absence of human data and due to the experimental risk of injury caused by fluoroquinolones on joint cartilage carriers of growing animals, breastfeeding is contraindicated during moxifloxacin therapy (see section 4.3).
Fertility
Animal studies did not indicate impairment of fertility (see section 5.3).
04.7 Effects on ability to drive and use machines
Studies on the effects of moxifloxacin on the ability to drive and use machines have not been conducted. However, fluoroquinolones, including moxifloxacin, may cause an impairment of the patient's ability to drive or operate machinery due to reactions to CNS burden (e.g. dizziness, acute transient loss of vision, see section 4.8) or acute and short-lived loss of consciousness (syncope, see section 4.8). Patients should be advised to observe their reactions to moxifloxacin before drive vehicles or operate machinery.
04.8 Undesirable effects
Adverse reactions, based on all clinical trials with moxifloxacin 400 mg (oral and sequential therapy) and sorted by frequency, are listed below.
With the exception of nausea and diarrhea, all adverse reactions were observed with frequencies below 3%.
Within each frequency class, undesirable effects are reported in descending order of severity.
Frequencies are defined as:
- common (≥ 1/100,
- uncommon (≥ 1 / 1,000,
- rare (≥ 1 / 10,000,
- very rare (
Very rare cases of the following undesirable effects, which cannot be excluded may also occur during treatment with moxifloxacin, have been reported with other fluoroquinolones: hypernatremia, hypercalcaemia, haemolytic anemia, rhabdomyolysis, photosensitivity reactions (see section 4.4).
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions that occur after authorization of the medicinal product is important, as it allows continuous monitoring of the benefit / risk ratio of the medicinal product.Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose
No specific countermeasures are recommended in case of accidental overdose. In the event of an overdose, symptomatic treatment should be undertaken. Electrocardiographic monitoring should be performed, due to the possibility of QT interval prolongation. Co-administration of charcoal with a 400 mg dose of oral or intravenous moxifloxacin reduces the systemic bioavailability of the drug by more than 80%, respectively. The use of charcoal early in absorption may be useful in preventing an excessive increase in systemic exposure to moxifloxacin in cases of oral overdose.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: quinolone antibacterials, fluoroquinolones.
ATC code: J01MA14.
Mechanism of action
Moxifloxacin is active in vitro against a wide range of Gram-positive and Gram-negative pathogens.
The bactericidal action of moxifloxacin is the result of the inhibition of both type II topoisomerases (DNA gyrase and topoisomerase IV), necessary for the replication, transcription and repair of bacterial DNA. It appears that the methoxy group in position C8 contributes to increase the activity and to reduce the selection of resistant mutants in Gram-positive bacteria, compared to the hydrogen atom in the same position. The presence of the voluminous bicycloamine substituent in the C7 position prevents the active efflux associated with the genes norA or pmrA, seen in certain Gram-positive bacteria.
Pharmacodynamic studies have shown that moxifloxacin exhibits a concentration-dependent bacteriocidial rate. Bactericidal trough concentrations (MBCs) are within the minimum inhibitory concentration (MIC) range.
Effect on the intestinal flora in humans
The following changes in the intestinal flora were observed in volunteers following oral administration of moxifloxacin:Escherichia coli, Bacillus spp., Enterococcus spp. And Klebsiella spp. they had decreased, as were the anaerobes Bacteroides vulgatus, Bifidobacterium spp., Eubacterium spp. And Peptostreptococcus spp.. For Bacteroides fragilis c "was an increase. These changes returned to normal within two weeks.
Resistance mechanism
Resistance mechanisms that inactivate penicillins, cephalosporins, aminoglycosides, macrolides and tetracyclines do not interfere with the antibacterial activity of moxifloxacin. Other resistance mechanisms, such as barriers to penetration (common in Pseudomonas aeruginosa) and efflux mechanisms may also influence sensitivity to moxifloxacin.
In vitro, resistance to moxifloxacin is acquired through a stepwise process, by mutations at the target site in both type II topoisomerases, DNA gyrase and topoisomerase IV. Moxifloxacin is poorly subject to active efflux mechanisms in Gram-positive organisms.
Cross-resistance with other quinolones is observed. However, since moxifloxacin inhibits topoisomerase II and IV with similar activity in some Gram-positive bacteria, these bacteria may be resistant to other quinolones, but sensitive to moxifloxacin.
EUCAST clinical sensitivity breakpoints, in terms of MIC and disc diffusion tests, for moxifloxacin (01.01.2012):
Microbiological sensitivity
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.
05.2 Pharmacokinetic properties
Absorption and bioavailability
After oral administration, moxifloxacin is rapidly and almost completely absorbed. Absolute bioavailability is approximately 91%.
Pharmacokinetics are linear over the range of 50 to 800 mg as a single dose and up to 600 mg once daily for 10 days. After an oral dose of 400 mg peak concentrations of 3.1 mg / l are achieved within 0, 5 - 4 h post dose. Steady state peak and trough plasma concentrations (400 mg once daily) are 3.2 and 0.6 mg / L, respectively. interval between administrations is approximately 30% longer than after the first dose.
Distribution
Moxifloxacin is rapidly distributed in extravascular spaces; after a dose of 400 mg an AUC of 35 mg * h / l is observed. The steady-state volume of distribution (Vss) is approximately 2 L / kg. The experiments in vitro and ex vivo demonstrated a protein binding of approximately 40-42% regardless of drug concentration. Moxifloxacin binds primarily to serum albumin.
Following oral administration of a single 400 mg dose of moxifloxacin the following peak concentrations (geometric mean) were observed:
Biotransformation
Moxifloxacin undergoes phase II biotransformation and is excreted via the kidney and biliary / faecal route both as unchanged drug and in the form of a sulfur compound (M1) and a glucuronide (M2). M1 and M2 are the only important metabolites in humans, and both are microbiologically inactive.
In Phase I clinical trials and studies in vitro no metabolic pharmacokinetic interactions were observed with drugs subjected to phase I biotransformation dependent on cytochrome P-450. There is no indication of oxidative metabolism.
Elimination
Moxifloxacin is cleared from plasma with a mean terminal half-life of approximately 12 hours. The mean apparent total body clearance after a 400 mg dose is between 179 and 246 mL / min. Renal clearance is approximately 24 - 53 mL / min. min, suggesting partial tubular reabsorption of the drug by the kidneys.After a dose of 400 mg, the amount found in the urine (about 19% for unchanged drug, about 2.5% for M1 and about 14% for M & SUP2; ) and in the faeces (approximately 25% for unchanged drug, approximately 36% for M1, absent M & SUP2;) total approximately 96%.
Concomitant administration of moxifloxacin and ranitidine or probenecid does not alter the renal clearance of the parent drug.
Elderly and patients with low body weight
Higher plasma concentrations are seen in healthy low body weight volunteers (such as women) and elderly volunteers.
Renal impairment
The pharmacokinetic characteristics of moxifloxacin are not significantly different in patients with renal impairment (up to a creatinine clearance> 20 ml / min / 1.73 m2). As renal function decreases, concentrations of the metabolite M2 (glucuronide) increase by up to a factor of 2.5 (with creatinine clearance 2).
Hepatic impairment
Based on the pharmacokinetic studies conducted to date in patients with hepatic insufficiency (Child Pugh A, B) it is not possible to establish whether there are any differences compared to healthy volunteers. Impaired liver function was associated with higher exposure to M1 in plasma, while exposure to unchanged drug was comparable to that observed in healthy volunteers. There is insufficient experience in the clinical use of moxifloxacin in patients with impaired hepatic function. .
05.3 Preclinical safety data
Effects on the haematopoietic system (slight decrease in the number of erythrocytes and platelets) were observed in rats and monkeys. As with other quinolones, hepatotoxicity (elevated liver enzymes and vacuolar degeneration) was observed in rats, monkeys and dogs. CNS toxicity (convulsions) occurred in monkeys. These effects were observed only after treatment with high doses of moxifloxacin or after prolonged treatment.
Moxifloxacin, like other quinolones, was genotoxic in tests in vitro using bacteria or mammalian cells. Since these effects can be explained by an interaction with gyrase in bacteria and - at higher concentrations - with topoisomerase II in mammalian cells, a threshold concentration for genotoxicity can be postulated. in vivo, there was no evidence of genotoxicity, despite the fact that very high doses of moxifloxacin were used. A sufficient safety margin with respect to the therapeutic dose in humans can thus be ensured. Moxifloxacin was not carcinogenic in an initiation-promotion study in rats.
Many quinolones are photoreactive and can induce phototoxicity, photomutagenic and photocarcinogenic effects. On the contrary, moxifloxacin, subjected to a complete program of studies in vitro and in vivo, proved to be devoid of phototoxic and photogotoxic properties. Under the same conditions other quinolones caused effects.
At high concentrations, moxifloxacin is an inhibitor of the rapid component of the delayed rectifying potassium current in the heart and may therefore cause prolongation of the QT interval. Toxicological studies performed in dogs with oral doses ≥ 90 mg / kg, resulting in plasma concentrations ≥ 16 mg / l, caused QT prolongation but not arrhythmias. Only after very high cumulative intravenous administration of more than 50 times the human dose (> 300 mg / kg), which produced plasma concentrations ≥ 200 mg / l (more than 40 times the therapeutic level), reversible non-fatal ventricular arrhythmias have been observed.
Quinolones are known to induce lesions in the cartilage of major synovial joints in growing animals. The lowest oral dose of moxifloxacin that caused joint toxicity in juvenile dogs was four times the maximum recommended therapeutic dose of 400 mg (assuming a body weight of 50 kg) in terms of mg / kg, with plasma concentrations ranging from two to three times. higher than those reached at the maximum therapeutic dose.
Toxicological tests in rats and monkeys (repeated administration up to 6 months) did not reveal a risk of ocular toxicity. In dogs, high oral doses (≥ 60 mg / kg), resulting in plasma concentrations ≥ 20 mg / l, resulted in changes in the electroretinogram and, in isolated cases, atrophy of the retina.
Reproduction studies performed in rats, rabbits and monkeys indicate that there is a passage of moxifloxacin across the placenta. Studies in rats (p.o. and i.v.) and monkeys (p.o.) did not provide evidence of teratogenicity or impaired fertility following administration of moxifloxacin. In fetuses of rabbits, a modest increase in the incidence of vertebral and costal malformations was observed, but only at a dose (20 mg / kg i.v.) that was associated with severe maternal toxicity. There was an increase in the incidence of abortions in monkeys and rabbits at plasma concentrations corresponding to therapeutic levels in humans. In rats, at doses of 63 times the maximum recommended dose in terms of mg / kg, with plasma concentrations in the therapeutic dose range for humans, decreased fetal weight, increased prenatal loss, and mildly increased duration of pregnancy and increased spontaneous activity in some descendants of both sexes.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Core of the tablet:
microcrystalline cellulose;
croscarmellose sodium;
lactose monohydrate;
magnesium stearate.
Coating film:
hypromellose;
macrogol 4000;
iron oxide (E172);
titanium dioxide (E171).
06.2 Incompatibility
Not relevant.
06.3 Period of validity
5 years.
06.4 Special precautions for storage
Polypropylene / aluminum blister:
Do not store above 25 ° C.
Store in the original package to protect the medicine from moisture.
Aluminum / aluminum blister:
Store in the original package to protect the medicine from moisture.
06.5 Nature of the immediate packaging and contents of the package
Colorless or opaque white / aluminum polypropylene blister in cardboard box.
Packs of 5, 7 and 10 film-coated tablets, hospital packs of 25 (5x5), 50 (5x10), 70 (7x10), hospital packs of 80 (5 packs of 16), or 100 (10 packs of 16) are available. 10) film-coated tablets.
Cardboard cartons containing aluminum / aluminum blisters, are available in packs of one tablet.
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, Milan
08.0 MARKETING AUTHORIZATION NUMBER
5 film-coated tablets of 400 mg in blister PP / AL AIC 034436016
7 film-coated tablets of 400 mg in blister PP / AL AIC 034436028
10 film-coated tablets of 400 mg in blister PP / AL AIC 034436030
25 film-coated tablets of 400 mg in blister PP / AL AIC 034436042
50 film-coated tablets of 400 mg in blister PP / AL AIC 034436055
70 film-coated tablets of 400 mg in blister PP / AL AIC 034436067
80 film-coated tablets of 400 mg in blister PP / AL AIC 034436079
100 film-coated tablets of 400 mg in blister PP / AL AIC 034436081
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
First authorization: 13 June 2000
Renewal: November 30, 2008
10.0 DATE OF REVISION OF THE TEXT
05/2014
