Drugs List

Therapeutic Indications

Uses

Chronic bacterial prostatitis: treatment
Community acquired pneumonia when other treatment inappropriate
Complicated skin and soft tissue infections: other treatment inappropriate
Complicated urinary tract infections
Inhalation anthrax
Pyelonephritis

Administration

Levofloxacin solution is administered by slow intravenous infusion. The infusion time must be at least 60 minutes for 500mg levofloxacin solution for infusion.

Contraindications

Children under 18 years
Breastfeeding
Epileptic disorder
History of seizures
History of tendon disorder secondary to quinolone use
Long QT syndrome
Myasthenia gravis
Pregnancy
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
Organ transplant recipients
Patients over 60 years
Predisposition to aortic aneurysm
Predisposition to aortic dissection
Predisposition to seizures
Restricted sodium intake
Aortic aneurysm
Aortic dissection
Cardiac disorder
Diabetes mellitus
Electrolyte imbalance
G6PD deficiency
History of psychiatric disorder
History of torsade de pointes
Psychosis
Renal impairment

Correct electrolyte disorders before treatment
May exacerbate myasthenia gravis
Monitor for haemolysis in G6PD deficiency
Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Consult national/regional policy on the use of anti-infectives
Perform ECG before and during treatment
Consider pseudomembranous colitis if patient presents with severe diarrhoea
Discontinue at first sign of pain/inflammation of limb(possible tendonitis)
Discontinue treatment if patient develops seizures
If rash develops, consider possibility of Stevens-Johnson Syndrome
Monitor blood glucose closely in patients with diabetes mellitus
Monitor serum electrolytes
Reduce dose in patients with creatinine clearance below 51ml/min
Advise patient to report any changes in vision, taste, smell or hearing
Advise patient to report mucosal/skin reactions (blistering or peeling)
Advise patient to report new visual problems and symptoms
Advise patient to report signs of neuropathy
Advise patient to report signs of tendinitis
Advise patient to report tiredness, mood, memory or sleep disturbances
Advise patient to rest affected limb if tendonitis occurs
Advise patient to seek medical advice if joint aches or pain occur
Advise patient to stop therapy & contact Dr if hypersensitivity signs occur
Advise patients to report muscle pain/tenderness/weakness
Advise pt. to seek medical attention if sudden abdominal,chest or back pain
Discontinue if central nervous disturbances occur
Discontinue if psychiatric disturbances develop
May cause convulsions
Patient should report worrying psychological changes esp. suicidal thoughts
Patients over 60 years are prone to tendon inflammation
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Prolonged use may result in superinfection with non-susceptible organisms
May affect results of some laboratory tests
Discontinue at once if pseudomembranous colitis occurs
Discontinue if peripheral neuropathy occurs
Discontinue if symptoms of hepatic disease occur
Discontinue in patients showing suicidal behaviour
Interrupt infusion if hypotension occurs
Avoid exposure to sunlight/UV rays during and for 2 days after treatment

Levofloxacin is not recommended for the treatment of Methicillin-resistant S. aureus (MRSA) infection. In case of a suspected or confirmed infection due to MRSA, treatment with an appropriate antibacterial agent should be started.

In most severe cases of pneumococcal pneumonia, levofloxacin may not be the optimal therapy. Nosocomial infections due to Pseudomonas aeruginosa may require combination therapy.

There is an increased risk of aortic aneurysm and dissection following treatment with levofloxacin. Use levofloxacin only after careful benefit risk assessment in patients with positive family history of aneurysm disease, or in patients diagnosed with pre-existing aortic aneurysm and or aortic dissection, or in the presence of other risk factors or conditions predisposing for aneurysm and dissection (e.g. Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, giant cell arthritis, Behcet's disease, hypertension, known atherosclerosis.)

Disabling, long-lasting and potentially irreversible adverse reactions mainly affecting musculoskeletal and nervous systems have been reported with quinolone and fluoroquinolone antibiotics. Treatment should be discontinued at the first signs of a serious adverse reaction such as tendinitis, pain or inflammation.

Pregnancy and Lactation

Pregnancy

Levofloxacin is contraindicated during pregnancy.

At the time of writing there is limited published information regarding the use of levofloxacin during pregnancy. The manufacturer contraindicates the use of levofloxacin in pregnancy, citing the potential for damage to the weight-bearing cartilage of the foetus.

Reproductive studies in animals did not indicate reproductive toxicity.

Levofloxacin is known to cross the placenta, and is found in the amniotic fluid at low concentrations.

Schaefer advises that quinolones should only be used during pregnancy in cases of complicated infections resistant to the antibiotics of choice. In these occasions, Schaefer recommends the use better studied quinolones such as norfloxacin or ciprofloxacin. The use of a quinolone antibiotic is not grounds for termination of pregnancy but a detailed foetal ultrasonograph may be considered.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Levofloxacin is contraindicated in breastfeeding.

It is not known if levofloxacin is secreted in breast milk, but due to the secretion of similar fluoroquinolones in breast milk and the theoretical risk of damage to the weight-bearing cartilage of the foetus, use of levofloxacin in breastfeeding mothers is contraindicated by the manufacturer.

Schaefer recommends the use of standard antibiotic with a lower potential for risk over the use of levofloxacin in breastfeeding. However, when a complicated infection necessitates the use of quinolones, ciprofloxacin may be preferable.

LactMed suggests that the amount of the drug secreted in breast milk is low, and is unlikely to harm the breastfed infant. To limit exposure of the infant to levofloxacin, LactMed recommends delaying breastfeeding until 4 to 6 hours after each dose.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Acute hepatic failure
Acute renal failure
Aggravation of porphyria
Agitation
Agranulocytosis
Anaphylactoid reaction
Anaphylaxis
Angioedema
Anorexia
Antibiotic-associated colitis
Anxiety
Arthralgia
Arthritis
Asthenia
Benign raised intracranial pressure
Bronchospasm
Confusion
Constipation
Convulsions
Depression
Diarrhoea
Diarrhoea - bloody
Dizziness
Dyskinesia
Dyspepsia
Dyspnoea
Enterocolitis
Eosinophilia
Erythema multiforme
Exacerbation of myasthenia gravis
Extrapyramidal effects
Flatulence
Fungal superinfection
Haemolytic anaemia
Hallucinations
Headache
Hearing disturbances
Hepatic impairment
Hepatitis
Hyperglycaemia
Hyperhidrosis
Hypersensitivity reactions
Hypoglycaemia
Hypotension
Increases in hepatic enzymes
Injection site reactions
Insomnia
Interstitial nephritis
Jaundice
Leucopenia
Muscle weakness
Myalgia
Nausea
Nervousness
Neutropenia
Nightmares
Pain
Palpitations
Pancreatitis
Pancytopenia
Paraesthesia
Peripheral neuropathy
Phlebitis
Photosensitivity
Pneumonitis
Prolongation of QT interval
Pruritus
Pseudomembranous colitis
Psychotic reactions
Pyrexia
Rash
Rhabdomyolysis
Serum bilirubin increased
Serum creatinine increased
Sleep disturbances
Smelling disturbances
Somnolence
Stevens-Johnson syndrome
Stomatitis
Suicidal tendencies
Syncope
Tachycardia
Taste disturbances
Tendinitis
Tendon disorder
Tendon rupture
Thrombocytopenia
Tinnitus
Toxic epidermal necrolysis
Tremor
Urticaria
Vasculitis (allergic)
Vertigo
Visual disturbances
Vomiting

Presentation

Solution for infusion containing levofloxacin as levofloxacin hemihydrate.

Drugs List

Therapeutic Indications

Uses

Chronic bacterial prostatitis: treatment
Community acquired pneumonia when other treatment inappropriate
Complicated skin and soft tissue infections: other treatment inappropriate
Complicated urinary tract infections
Inhalation anthrax
Pyelonephritis

Dosage

It is possible to switch from initial intravenous treatment to the oral route after a few days depending on the condition of the patient. The same dosage can be used given the bioequivalence of the parenteral and oral forms.

Adults

Patients with Renal Impairment

Administration

Levofloxacin solution is administered by slow intravenous infusion. The infusion time must be at least 60 minutes for 500mg levofloxacin solution for infusion.

Contraindications

Children under 18 years
Breastfeeding
Epileptic disorder
History of seizures
History of tendon disorder secondary to quinolone use
Long QT syndrome
Myasthenia gravis
Pregnancy
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
Organ transplant recipients
Patients over 60 years
Predisposition to aortic aneurysm
Predisposition to aortic dissection
Predisposition to seizures
Restricted sodium intake
Aortic aneurysm
Aortic dissection
Cardiac disorder
Diabetes mellitus
Electrolyte imbalance
G6PD deficiency
History of psychiatric disorder
History of torsade de pointes
Psychosis
Renal impairment

Correct electrolyte disorders before treatment
May exacerbate myasthenia gravis
Monitor for haemolysis in G6PD deficiency
Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Consult national/regional policy on the use of anti-infectives
Perform ECG before and during treatment
Consider pseudomembranous colitis if patient presents with severe diarrhoea
Discontinue at first sign of pain/inflammation of limb(possible tendonitis)
Discontinue treatment if patient develops seizures
If rash develops, consider possibility of Stevens-Johnson Syndrome
Monitor blood glucose closely in patients with diabetes mellitus
Monitor serum electrolytes
Reduce dose in patients with creatinine clearance below 51ml/min
Advise patient to report any changes in vision, taste, smell or hearing
Advise patient to report mucosal/skin reactions (blistering or peeling)
Advise patient to report new visual problems and symptoms
Advise patient to report signs of neuropathy
Advise patient to report signs of tendinitis
Advise patient to report tiredness, mood, memory or sleep disturbances
Advise patient to rest affected limb if tendonitis occurs
Advise patient to seek medical advice if joint aches or pain occur
Advise patient to stop therapy & contact Dr if hypersensitivity signs occur
Advise patients to report muscle pain/tenderness/weakness
Advise pt. to seek medical attention if sudden abdominal,chest or back pain
Discontinue if central nervous disturbances occur
Discontinue if psychiatric disturbances develop
May cause convulsions
Patient should report worrying psychological changes esp. suicidal thoughts
Patients over 60 years are prone to tendon inflammation
Predisposition QT prolongation: Counsel patient on symptoms of arrhythmias
Prolonged use may result in superinfection with non-susceptible organisms
May affect results of some laboratory tests
Discontinue at once if pseudomembranous colitis occurs
Discontinue if peripheral neuropathy occurs
Discontinue if symptoms of hepatic disease occur
Discontinue in patients showing suicidal behaviour
Interrupt infusion if hypotension occurs
Avoid exposure to sunlight/UV rays during and for 2 days after treatment

Levofloxacin is not recommended for the treatment of Methicillin-resistant S. aureus (MRSA) infection. In case of a suspected or confirmed infection due to MRSA, treatment with an appropriate antibacterial agent should be started.

In most severe cases of pneumococcal pneumonia, levofloxacin may not be the optimal therapy. Nosocomial infections due to Pseudomonas aeruginosa may require combination therapy.

There is an increased risk of aortic aneurysm and dissection following treatment with levofloxacin. Use levofloxacin only after careful benefit risk assessment in patients with positive family history of aneurysm disease, or in patients diagnosed with pre-existing aortic aneurysm and or aortic dissection, or in the presence of other risk factors or conditions predisposing for aneurysm and dissection (e.g. Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, giant cell arthritis, Behcet's disease, hypertension, known atherosclerosis.)

Disabling, long-lasting and potentially irreversible adverse reactions mainly affecting musculoskeletal and nervous systems have been reported with quinolone and fluoroquinolone antibiotics. Treatment should be discontinued at the first signs of a serious adverse reaction such as tendinitis, pain or inflammation.

Pregnancy and Lactation

Pregnancy

Levofloxacin is contraindicated during pregnancy.

At the time of writing there is limited published information regarding the use of levofloxacin during pregnancy. The manufacturer contraindicates the use of levofloxacin in pregnancy, citing the potential for damage to the weight-bearing cartilage of the foetus.

Reproductive studies in animals did not indicate reproductive toxicity.

Levofloxacin is known to cross the placenta, and is found in the amniotic fluid at low concentrations.

Schaefer advises that quinolones should only be used during pregnancy in cases of complicated infections resistant to the antibiotics of choice. In these occasions, Schaefer recommends the use better studied quinolones such as norfloxacin or ciprofloxacin. The use of a quinolone antibiotic is not grounds for termination of pregnancy but a detailed foetal ultrasonograph may be considered.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Levofloxacin is contraindicated in breastfeeding.

It is not known if levofloxacin is secreted in breast milk, but due to the secretion of similar fluoroquinolones in breast milk and the theoretical risk of damage to the weight-bearing cartilage of the foetus, use of levofloxacin in breastfeeding mothers is contraindicated by the manufacturer.

Schaefer recommends the use of standard antibiotic with a lower potential for risk over the use of levofloxacin in breastfeeding. However, when a complicated infection necessitates the use of quinolones, ciprofloxacin may be preferable.

LactMed suggests that the amount of the drug secreted in breast milk is low, and is unlikely to harm the breastfed infant. To limit exposure of the infant to levofloxacin, LactMed recommends delaying breastfeeding until 4 to 6 hours after each dose.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Acute hepatic failure
Acute renal failure
Aggravation of porphyria
Agitation
Agranulocytosis
Anaphylactoid reaction
Anaphylaxis
Angioedema
Anorexia
Antibiotic-associated colitis
Anxiety
Arthralgia
Arthritis
Asthenia
Benign raised intracranial pressure
Bronchospasm
Confusion
Constipation
Convulsions
Depression
Diarrhoea
Diarrhoea - bloody
Dizziness
Dyskinesia
Dyspepsia
Dyspnoea
Enterocolitis
Eosinophilia
Erythema multiforme
Exacerbation of myasthenia gravis
Extrapyramidal effects
Flatulence
Fungal superinfection
Haemolytic anaemia
Hallucinations
Headache
Hearing disturbances
Hepatic impairment
Hepatitis
Hyperglycaemia
Hyperhidrosis
Hypersensitivity reactions
Hypoglycaemia
Hypotension
Increases in hepatic enzymes
Injection site reactions
Insomnia
Interstitial nephritis
Jaundice
Leucopenia
Muscle weakness
Myalgia
Nausea
Nervousness
Neutropenia
Nightmares
Pain
Palpitations
Pancreatitis
Pancytopenia
Paraesthesia
Peripheral neuropathy
Phlebitis
Photosensitivity
Pneumonitis
Prolongation of QT interval
Pruritus
Pseudomembranous colitis
Psychotic reactions
Pyrexia
Rash
Rhabdomyolysis
Serum bilirubin increased
Serum creatinine increased
Sleep disturbances
Smelling disturbances
Somnolence
Stevens-Johnson syndrome
Stomatitis
Suicidal tendencies
Syncope
Tachycardia
Taste disturbances
Tendinitis
Tendon disorder
Tendon rupture
Thrombocytopenia
Tinnitus
Toxic epidermal necrolysis
Tremor
Urticaria
Vasculitis (allergic)
Vertigo
Visual disturbances
Vomiting

Effects on Laboratory Tests

In patients treated with levofloxacin, determination of opiates in urine may give false-positive results. It may be necessary to confirm positive opiate screens by more specific methods.

Levofloxacin may inhibit growth of Mycobacterium tuberculosis and, may give false-negative results in the bacteriological diagnosis of tuberculosis.

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: September 2018

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Levofloxacin 500mg/100ml Solution for Infusion Vials. Bowmed Ibisqus Limited. Revised October 2015.
Summary of Product Characteristics: Levofloxacin 500mg/100ml Solution for Infusion Vials. Peckforton Pharmaceuticals Ltd. Revised July 2014.

MHRA Drug Safety Update March 2019
Available at: https://www.mhra.gov.uk
Last accessed: 20 May 2019

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 24 September 2018

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Levofloxacin. Last revised: 08 August, 2017
Last accessed: 24 September, 2018