AVELOX Solution for infusion Ref.[7000] Active ingredients: Moxifloxacin

Source: Medicines & Healthcare Products Regulatory Agency (GB)  Revision Year: 2019  Publisher: Bayer plc, 400 South Oak Way, Reading RG2 6AD

Contraindications

  • Hypersensitivity to moxifloxacin, other quinolones or to any of the excipients listed in section 6.1.
  • Pregnancy and lactation (see section 4.6).
  • Patients below 18 years of age.
  • Patients with a history of tendon disease/disorder related to quinolone treatment.

Both in preclinical investigations and in humans, changes in cardiac electrophysiology have been observed following exposure to moxifloxacin, in the form of QT prolongation. For reasons of drug safety, moxifloxacin is therefore contraindicated in patients with:

  • Congenital or documented acquired QT prolongation.
  • Electrolyte disturbances, particularly in uncorrected hypokalaemia.
  • Clinically relevant bradycardia.
  • Clinically relevant heart failure with reduced left-ventricular ejection fraction.
  • Previous history of symptomatic arrhythmias.

Moxifloxacin should not be used concurrently with other drugs that prolong the QT interval (see also section 4.5).

Due to limited clinical data, moxifloxacin is also contraindicated in patients with impaired liver function (Child Pugh C) and in patients with transaminases increase >5fold ULN.

Special warnings and precautions for use

The benefit of moxifloxacin treatment especially in infections with a low degree of severity should be balanced with the information contained in the warnings and precautions section.

Prolongation of QTc interval and potentially QTc-prolongation-related clinical conditions

Moxifloxacin has been shown to prolong the QTc interval on the electrocardiogram in some patients. The magnitude of QT prolongation may increase with increasing plasma concentrations due to rapid intravenous infusion. Therefore, the duration of infusion should not be less than the recommended 60 minutes and the intravenous dose of 400 mg once a day should not be exceeded. For more details see below and refer to sections 4.3 and 4.5.

Treatment with moxifloxacin should be stopped if signs or symptoms that may be associated with cardiac arrhythmia occur during treatment, with or without ECG findings.

Moxifloxacin should be used with caution in patients with any condition pre-disposing to cardiac arrhythmias (e.g. acute myocardial ischaemia) because they may have an increased risk of developing ventricular arrhythmias (incl. torsade de pointes) and cardiac arrest. See also sections 4.3 and 4.5.

Moxifloxacin should be used with caution in patients who are taking medications that can reduce potassium levels. See also sections 4.3 and 4.5.

Moxifloxacin should be used with caution in patients who are taking medications associated with clinically significant bradycardia. See also section 4.3.

Female patients and elderly patients may be more sensitive to the effects of QTc-prolonging medications such as moxifloxacin and therefore special caution is required.

Hypersensitivity/allergic reactions

Hypersensitivity and allergic reactions have been reported for fluoroquinolones including moxifloxacin after first administration. Anaphylactic reactions can progress to a life-threatening shock, even after the first administration. In cases of clinical manifestations of severe hypersensitivity reactions moxifloxacin should be discontinued and suitable treatment (e.g. treatment for shock) initiated.

Severe liver disorders

Cases of fulminant hepatitis potentially leading to liver failure (including fatal cases) have been reported with moxifloxacin (see section 4.8). Patients should be advised to contact their doctor prior to continuing treatment if signs and symptoms of fulminant hepatic disease develop such as rapidly developing asthenia associated with jaundice, dark urine, bleeding tendency or hepatic encephalopathy.

Liver function tests/investigations should be performed in cases where indications of liver dysfunction occur.

Serious bullous skin reactions

Cases of bullous skin reactions like Stevens-Johnson syndrome or toxic epidermal necrolysis have been reported with moxifloxacin (see section 4.8). Patients should be advised to contact their doctor immediately prior to continuing treatment if skin and/or mucosal reactions occur.

Patients predisposed to seizures

Quinolones are known to trigger seizures. Use should be with caution in patients with CNS disorders or in the presence of other risk factors which may predispose to seizures or lower the seizure threshold. In case of seizures, treatment with moxifloxacin should be discontinued and appropriate measures instituted.

Peripheral neuropathy

Cases of sensory or sensorimotor polyneuropathy resulting in paraesthesias, hypoaesthesias, dysaesthesias, or weakness have been reported in patients receiving quinolones including moxifloxacin. Patients under treatment with moxifloxacin should be advised to inform their doctor prior to continuing treatment if symptoms of neuropathy such as pain, burning, tingling, numbness, or weakness develop in order to prevent the development of an irreversible condition (see section 4.8).

Psychiatric reactions

Psychiatric reactions may occur even after the first administration of quinolones, including moxifloxacin. In very rare cases depression or psychotic reactions have progressed to suicidal thoughts and self-injurious behaviour such as suicide attempts (see section 4.8). In the event that the patient develops these reactions, moxifloxacin should be discontinued and appropriate measures instituted. Caution is recommended if moxifloxacin is to be used in psychotic patients or in patients with history of psychiatric disease.

Antibiotic-associated diarrhoea incl. colitis

Antibiotic-associated diarrhoea (AAD) and antibiotic-associated colitis (AAC), including pseudomembranous colitis and Clostridium difficile-associated diarrhoea, has been reported in association with the use of broad spectrum antibiotics including moxifloxacin and may range in severity from mild diarrhoea to fatal colitis. Therefore it is important to consider this diagnosis in patients who develop serious diarrhoea during or after the use of moxifloxacin. If AAD or AAC is suspected or confirmed, ongoing treatment with antibacterial agents, including moxifloxacin, should be discontinued and adequate therapeutic measures should be initiated immediately. Furthermore, appropriate infection control measures should be undertaken to reduce the risk of transmission. Drugs inhibiting peristalsis are contraindicated in patients who develop serious diarrhoea.

Patients with myasthenia gravis

Moxifloxacin should be used with caution in patients with myasthenia gravis because the symptoms can be exacerbated.

Tendon inflammation, tendon rupture

Tendon inflammation and rupture (especially Achilles tendon), sometimes bilateral, may occur with quinolone therapy including moxifloxacin, even within 48 hours of starting treatment and have been reported up to several months after discontinuation of therapy. The risk of tendinitis and tendon rupture is increased in elderly patients and in those treated concurrently with corticosteroids. At the first sign of pain or inflammation, patients should discontinue treatment with moxifloxacin, rest the affected limb(s) and consult their doctor immediately in order to initiate appropriate treatment (e.g. immobilisation) for the affected tendon (see sections 4.3 and 4.8).

Aortic aneurysm and dissection

Epidemiologic studies report an increased risk of aortic aneurysm and dissection after intake of fluoroquinolones, particularly in the older population. Therefore, fluoroquinolones should only be used after careful benefit-risk assessment and after consideration of other therapeutic options in patients with positive family history of aneurysm disease, or in patients diagnosed with pre-existing aortic aneurysm and/or dissection, or in presence of other risk factors or conditions predisposing for aortic aneurysm and dissection (e.g. Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, giant cell arteritis, Behcet ́s disease, hypertension, known atherosclerosis). In case of sudden abdominal, chest or back pain, patients should be advised to immediately consult a physician in an emergency department.

Patients with renal impairment

Elderly patients with renal disorders should use moxifloxacin with caution if they are unable to maintain adequate fluid intake, because dehydration may increase the risk of renal failure.

Vision disorders

If vision becomes impaired or any effects on the eyes are experienced, an eye specialist should be consulted immediately (see sections 4.7 and 4.8).

Dysglycemia

As with all fluoroquinolones, disturbances in blood glucose, including both hypoglycemia and hyperglycemia have been reported with moxifloxacin (see section 4.8). In moxifloxacin-treated patients, dysglycemia occurred predominantly in elderly diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (e.g. sulfonylurea) or with insulin. Cases of hypoglycaemic coma have been reported. In diabetic patients, careful monitoring of blood glucose is recommended.

Prevention of photosensitivity reactions

Quinolones have been shown to cause photosensitivity reactions in patients. However, studies have shown that moxifloxacin has a lower risk to induce photosensitivity. Nevertheless patients should be advised to avoid exposure to either UV irradiation or extensive and/or strong sunlight during treatment with moxifloxacin.

Patients with glucose-6-phosphate dehydrogenase deficiency

Patients with a family history of or actual glucose-6-phosphate dehydrogenase deficiency are prone to haemolytic reactions when treated with quinolones. Therefore, moxifloxacin should be used with caution in these patients.

Peri-arterial tissue inflammation

Moxifloxacin solution for infusion is for intravenous administration only. Intra-arterial administration should be avoided since preclinical studies demonstrated peri-arterial tissue inflammation following infusion by this route.

Patients with special cSSSI

Clinical efficacy of moxifloxacin in the treatment of severe burn infections, fasciitis and diabetic foot infections with osteomyelitis has not been established.

Patients on sodium diet

This medicinal product contains 787 mg (approximately 34 mmol) sodium per bottle with 250ml solution for infusion, equivalent to 39.35% of the WHO recommended maximum daily intake of 2g sodium for an adult.

Interference with biological tests

Moxifloxacin therapy may interfere with the Mycobacterium spp. culture test by suppression of mycobacterial growth causing false negative results in samples taken from patients currently receiving moxifloxacin.

Patients with MRSA infections

Moxifloxacin is not recommended for the treatment of MRSA infections. In case of a suspected or confirmed infection due to MRSA, treatment with an appropriate antibacterial agent should be started (see section 5.1).

Paediatric population

Due to adverse effects on the cartilage in juvenile animals (see section 5.3) the use of moxifloxacin in children and adolescents <18 years is contraindicated (see section 4.3).

Interaction with other medicinal products and other forms of interaction

Interactions with medicinal products

An additive effect on QT interval prolongation of moxifloxacin and other medicinal products that may prolong the QTc interval cannot be excluded. This might lead to an increased risk of ventricular arrhythmias, including torsade de pointes. Therefore, co-administration of moxifloxacin with any of the following medicinal products is contraindicated (see also section 4.3):

  • anti-arrhythmics class IA (e.g. quinidine, hydroquinidine, disopyramide)
  • anti-arrhythmics class III (e.g. amiodarone, sotalol, dofetilide, ibutilide)
  • antipsychotics (e.g. phenothiazines, pimozide, sertindole, haloperidol, sultopride)
  • tricyclic antidepressive agents
  • certain antimicrobial agents (saquinavir, sparfloxacin, erythromycin IV, pentamidine, antimalarials particularly halofantrine)
  • certain antihistaminics (terfenadine, astemizole, mizolastine)
  • others (cisapride, vincamine IV, bepridil, diphemanil).

Moxifloxacin should be used with caution in patients who are taking medication that can reduce potassium levels (e.g. loop and thiazide-type diuretics, laxatives and enemas [high doses], corticosteroids, amphotericin B) or medication that is associated with clinically significant bradycardia.

After repeated dosing in healthy volunteers, moxifloxacin increased C max of digoxin by approximately 30% without affecting AUC or trough levels. No precaution is required for use with digoxin.

In studies conducted in diabetic volunteers, concomitant administration of oral moxifloxacin with glibenclamide resulted in a decrease of approximately 21% in the peak plasma concentrations of glibenclamide. The combination of glibenclamide and moxifloxacin could theoretically result in a mild and transient hyperglycaemia. However, the observed pharmacokinetic changes for glibenclamide did not result in changes of the pharmacodynamic parameters (blood glucose, insulin). Therefore no clinically relevant interaction was observed between moxifloxacin and glibenclamide.

Changes in INR

A large number of cases showing an increase in oral anticoagulant activity have been reported in patients receiving antibacterial agents, especially fluoroquinolones, macrolides, tetracyclines, cotrimoxazole and some cephalosporins. The infectious and inflammatory conditions, age and general status of the patient appear to be risk factors. Under these circumstances, it is difficult to evaluate whether the infection or the treatment caused the INR (international normalised ratio) disorder. A precautionary measure would be to more frequently monitor the INR. If necessary, the oral anticoagulant dosage should be adjusted as appropriate.

Clinical studies have shown no interactions following concomitant administration of moxifloxacin with: ranitidine, probenecid, oral contraceptives, calcium supplements, morphine administered parenterally, theophylline, cyclosporine or itraconazole.

In vitro studies with human cytochrome P450 enzymes supported these findings. Considering these results a metabolic interaction via cytochrome P450 enzymes is unlikely.

Interaction with food

Moxifloxacin has no clinically relevant interaction with food including dairy products.

Fertility, pregnancy and lactation

Pregnancy

The safety of moxifloxacin in human pregnancy has not been evaluated. Animal studies have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Due to the experimental risk of damage by fluoroquinolones to the weight-bearing cartilage of immature animals and reversible joint injuries described in children receiving some fluoroquinolones, moxifloxacin must not be used in pregnant women (see section 4.3).

Breast-feeding

There is no data available in lactating or nursing women. Preclinical data indicate that small amounts of moxifloxacin are secreted in milk. In the absence of human data and due to the experimental risk of damage by fluoroquinolones to the weight-bearing cartilage of immature animals, breast-feeding is contraindicated during moxifloxacin therapy (see section 4.3).

Fertility

Animal studies do not indicate impairment of fertility (see section 5.3).

Effects on ability to drive and use machines

No studies on the effects of moxifloxacin on the ability to drive and use machines have been performed. However, fluoroquinolones including moxifloxacin may result in an impairment of the patient’s ability to drive or operate machinery due to CNS reactions (e.g. dizziness; acute, transient loss of vision, see section 4.8) or acute and short lasting loss of consciousness (syncope, see section 4.8). Patients should be advised to see how they react to moxifloxacin before driving or operating machinery.

Undesirable effects

Adverse reactions observed in clinical trials and derived from post-marketing reports with moxifloxacin 400 mg daily administered by the intravenous or oral route (intravenous only, sequential [IV/oral] and oral administration) sorted by frequencies are listed below:

Apart from nausea and diarrhoea all adverse reactions were observed at frequencies below 3%.

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Frequencies are defined as: Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000).

Infections and infestations

Common: Superinfections due to resistant bacteria or fungi e.g. oral and vaginal candidiasis

Blood and lymphatic system disorders

Uncommon: Anaemia, Leucopenia(s), Neutropenia, Thrombocytopenia, Thrombocythemia, Blood eosinophilia, Prothrombin time prolonged/INR increased

Very Rare: Prothrombin level increased/INR decreased, Agranulocytosis

Immune system disorders

Uncommon: Allergic reaction (see section 4.4)

Rare: Anaphylaxis incl. very rarely life-threatening shock (see section 4.4), Allergic oedema/angiooedema (incl. laryngeal oedema, potentially life-threatening, see section 4.4)

Metabolism and nutrition disorders

Uncommon: Hyperlipidemia

Rare: Hyperglycemia, Hyperuricemia

Very Rare: Hypoglycemia

Psychiatric disorders

Uncommon: Anxiety reactions, Psychomotor hyperactivity/agitation

Rare: Emotional lability, Depression (in very rare cases potentially culminating in self-injurious behaviour, such as suicidal ideations/ thoughts, or suicide attempts, see section 4.4), Hallucination

Very Rare: Depersonalization, Psychotic reactions (potentially culminating in self-injurious behaviour, such as suicidal ideations/thoughts, or suicide attempts, see section 4.4)

Nervous system disorders

Common: Headache, Dizziness

Uncommon: Par- and Dysaesthesia, Taste disorders (incl. ageusia in very rare cases), Confusion and disorientation, Sleep disorders (predominantly insomnia), Tremor, Vertigo, Somnolence

Rare: Hypoaesthesia, Smell disorders (incl. anosmia), Abnormal dreams, Disturbed coordination (incl. gait disturbances, esp. due to dizziness or vertigo), Seizures incl. grand mal convulsions (see section 4.4), Disturbed attention, Speech disorders, Amnesia, Peripheral neuropathy and polyneuropathy

Very Rare: Hyperaesthesia

Eye disorders

Uncommon: Visual disturbances incl. diplopia and blurred vision (especially in the course of CNS reactions, see section 4.4)

Rare: Photophobia

Very Rare: Transient loss of vision (especially in the course of CNS reactions, see sections 4.4 and 4.7), Uveitis and bilateral acute iris transillumination (see section 4.4)

Ear and labyrinth disorders

Rare: Tinnitus, Hearing impairment incl. deafness (usually reversible)

Cardiac disorders

Common: QT prolongation in patients with hypokalaemia (see sections 4.3 and 4.4)

Uncommon: QT prolongation (see section 4.4), Palpitations, Tachycardia, Atrial fibrillation, Angina pectoris

Rare: Ventricular tachyarrhythmias, Syncope (i.e. acute and short lasting loss of consciousness)

Very Rare: Unspecified arrhythmias, Torsade de Pointes (see section 4.4), Cardiac arrest (see section 4.4)

Vascular disorders

Uncommon: Vasodilatation

Rare: Hypertension, Hypotension

Very Rare: Vasculitis

Respiratory, thoracic and mediastinal disorders

Uncommon: Dyspnea (including asthmatic conditions)

Gastrointestinal disorders

Common: Nausea, Vomiting, Gastrointestinal and abdominal pains, Diarrhoea

Uncommon: Decreased appetite and food intake, Constipation, Dyspepsia, Flatulence, Gastritis, Increased amylase

Rare: Dysphagia, Stomatitis, Antibiotic-associated colitis (incl. pseudo-membranous colitis, in very rare cases associated with life-threatening complications, see section 4.4)

Hepatobiliary disorders

Common: Increase in transaminases

Uncommon: Hepatic impairment (incl. LDH increase), Increased bilirubin, Increased gamma-glutamyl-transferase, Increase in blood alkaline phosphatase

Rare: Jaundice, Hepatitis (predominantly cholestatic)

Very Rare: Fulminant hepatitis potentially leading to life-threatening liver failure (incl. fatal cases, see section 4.4)

Skin and subcutaneous tissue disorders

Uncommon: Pruritus, Rash, Urticaria, Dry skin

Very Rare: Bullous skin reactions like Stevens-Johnson syndrome or toxic epidermal necrolysis (potentially life-threatening, see section 4.4)

Musculoskeletal andconnective tissue disorders

Uncommon: Arthralgia, Myalgia

Rare: Tendonitis (see section 4.4), Muscle cramp, Muscle twitching, Muscle weakness

Very Rare: Tendon rupture (see section 4.4), Arthritis, Muscle rigidity, Exacerbation of symptoms of myasthenia gravis (see section 4.4)

Renal and urinary disorders

Uncommon: Dehydration

Rare: Renal impairment (incl. increase in BUN and creatinine), Renal failure (see section 4.4)

General disorders and administration site conditions

Common: Injection and infusion site reactions

Uncommon: Feeling unwell (predominantly asthenia or fatigue), Painful conditions (incl. pain in back, chest, pelvic and extremities), Sweating, Infusion site (thrombo-) phlebitis

Rare: Oedema

The following undesirable effects have a higher frequency category in the subgroup of IV treated patients with or without subsequent oral therapy:

Common: Increased gamma-glutamyl-transferase.

Uncommon: Ventricular tachyarrhythmias, hypotension, oedema, antibiotic-associated colitis (incl. pseudomembranous colitis, in very rare cases associated with life-threatening complications, see section 4.4), seizures incl. grand mal convulsions (see section 4.4), hallucination, renal impairment (incl. increase in BUN and creatinine), renal failure (see section 4.4).

There have been very rare cases of the following side effects reported following treatment with other fluoroquinolones, which might possibly also occur during treatment with moxifloxacin: increased intracranial pressure (including pseudotumor cerebri), hypernatraemia, hypercalcaemia, haemolytic anaemia, rhabdomyolysis, photosensitivity reactions (see section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Incompatibilities

The following solutions are incompatible with moxifloxacin solution for infusion:

  • Sodium chloride 10% and 20% solutions
  • Sodium bicarbonate 4.2% and 8.4% solutions

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.