Levofloxacin/ Dexamethasone

Registered South African indications:

• Prevention and treatment of inflammation
• Prevention of infection associated with cataract surgery

Contraindications

Registered contraindications in South Africa & other jurisdictions

• Hypersensitivity to the active ingredients or any of the excipients in this combination product (e.g. benzalkonium)
• Hypersensitivity to other quinolones or to other steroids
• Herpes simplex, keratitis, varicella and other viral disease of the cornea and conjunctiva
• Mycobacterial infections of the eye caused by, but not limited to, acid-fast bacilli such as Mycobacterium tuberculosis, Mycobacterium leprae, or Mycobacterium avium
• Fungal diseases of ocular structures
• Untreated purulent infection of the eye

Cautions

Recommendations in South Africa & other jurisdictions

• Pregnancy 
• Breastfeeding
• Renal impairment 
• Hepatic impairment
• Elderly
• Prolonged use
• Risk factors for tendon inflammation and rupture 
  - Elderly
  - Coadministration with corticosteroids
• Diabetes mellitus
• Diseases causing thinning of the cornea or sclera 
• Patients with dry eye
• Patients with compromised cornea
• Contact lenses (See additional prescribing points) (Recommendations in other jurisdictions)
• Risk factors for Cushing's syndrome and/or adrenal suppression after intensive or long-term continuous therapy (Recommendations in other jurisdictions)
  - Children 
  - Coadministration with CYP3A4 inhibitors (including ritonavir and cobicistat)
• May impair ability to drive and operate machinery 

Forms avail. in SA and covered in this monograph: opd

South African registered indications and dosages

Prevention and treatment of inflammation
Prevention of infection associated with cataract surgery

Levofloxacin/ Dexamethasone
5mg/1mg (per ml)

• Ophthalmic (opd): 1 drop into the conjunctival sac directly after surgery; Then: 6hrly thereafter; Treatment duration: 7 days

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Care should be taken not to discontinue therapy prematurely

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If one dose is missed, treatment should continue with the next dose as planned

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Method of administration: See additional prescribing points

Not established for use in children below 18 years

Pregnancy

South African recommendations

• Caution; not recommended
• The safety of levofloxacin/ dexamethasone in pregnancy has not been established
• Levofloxacin/ dexamethasone should not be used during pregnancy as there are no safety data

Recommendations in other jurisdictions

• Caution; not recommended
• There are no or limited amount of data from the use of dexamethasone and levofloxacin in pregnant women. Corticosteroids cross the placenta. Prolonged or repeated corticosteroid use during pregnancy has been associated with an increased risk of intra-uterine growth retardation, lower birth weight and risk for high blood pressure, vascular disorders and insulin resistance in the adulthood
• Infants born of mothers who have received substantial doses of corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism
• Studies in animals with corticosteroids have shown reproductive toxicity and teratogenic effects (including cleft palate). Since a relevant systemic corticosteroid exposure cannot be excluded after ocular administration, treatment with levofloxacin/ dexamethasone is not recommended during pregnancy, and especially during the first three months, should only take place after a careful benefit-risk assessment

Breastfeeding

South African recommendations

• Caution; not recommended 
• The safety of levofloxacin/ dexamethasone in breastfeeding has not been established
• Levofloxacin and dexamethasone, as contained in this combination product, are excreted in human milk. Levofloxacin/ dexamethasone should not be used during breastfeeding

Recommendations in other jurisdictions

• Caution 
• Systemic corticosteroids and levofloxacin are excreted into human milk. No data are available, to indicate whether relevant amounts of dexamethasone are transferred into human breast milk and which are capable of producing clinical effects in the infant
• A risk to the breastfeeding child cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from levofloxacin/ dexamethasone therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman

Fertility 

South African recommendations

• There are no data on potential effects of levofloxacin/ dexamethasone on fertility

Recommendations in other jurisdictions

• Systemically administered corticosteroids may impair male and female fertility by influencing hormonal secretion of the hypothalamus and pituitary gland as well as gametogenesis in testes and ovaries. It is unknown if dexamethasone impairs human fertility after ocular use
• Levofloxacin caused no impairment of fertility in rats at exposures considerably in excess of the maximum human exposure after ocular administration

• Caution; no information available

• Caution; no information available

• Caution; no dose adjustment recommended

Levofloxacin/ Dexamethasone 
Central Nervous System Disorders

• Headache

Musculoskeletal Disorders

• Ruptures of the shoulder, hand, Achilles, or other tendons that required surgical repair

Skin and Subcutaneous Tissue Disorders

• Pruritus

Sensory Disorders

• Dysgeusia
• Eye irritation
• Abnormal sensation in eye
• Ocular hypertension
• Increased intraocular pressure (>6mmHg)

Levofloxacin
Central Nervous System Disorders

• Headache

Respiratory Disorders

• Rhinitis
• Laryngeal oedema

Musculoskeletal Disorders

• Ruptures of the shoulder, hand, Achilles, or other tendons that required surgical repair

Immune, Blood and Lymphatic System Disorders

• Anaphylaxis

Sensory Disorders

• Extra-ocular allergic reactions
  - Skin rash
• Ocular burning
• Decreased vision
• Mucous strand
• Lid matting
• Chemosis
• Conjunctival papillary reaction
• Lid oedema
• Ocular discomfort
• Ocular itching
• Ocular pain
• Conjunctival hyperaemia
• Conjunctival follicles
• Ocular dryness
• Lid erythema
• Photophobia

Dexamethasone
Gastrointestinal Disorders

• Nausea

Endocrine and Metabolic Disorders

• Cushing's syndrome
• Adrenal suppression

Skin and Subcutaneous Tissue Disorders

• Face oedema

Immune, Blood and Lymphatic System Disorders

• Allergic and hypersensitivity reactions
• Opportunistic infections

Sensory Disorders

• Increased intraocular pressure
• Eye discomfort
• Eye irritation
• Eye burning
• Stinging eye
• Itching eye
• Blurred vision
• Delayed wound healing
• Posterior capsular cataract
• Glaucoma
• Conjunctivitis
• Mydriasis
• Ptosis
• Corticosteroid-induced uveitis
• Corneal calcifications
• Crystalline keratopathy
• Changes in corneal thickness
• Corneal oedema
• Corneal ulceration
• Corneal perforation
• Abnormal sensation in the eye
• Increased lacrimation
• Asthenopia
• Corneal disorder
• Dry eye
• Eye pain
• Ocular discomfort
• Visual brightness

• Topical steroids
• Topical non-steroidal anti-inflammatory drugs (NSAIDs)
• CYP3A4 inhibitors
• Ritonavir
• Cobicistat

• Intraocular pressure

Specific cases may require

• Slit-lamp biomicroscopy (if infection develops)
• Fluorescein staining (if infection develops)
• Ophthalmic examination (if a patient presents with symptoms such as blurred vision and/or other visual disturbances)

Method of administration

South African recommendations

• Ocular use
• Administer one drop in the affected eye
• Patients should be instructed to wash their hands before use and avoid allowing the tip of the container to come into contact with the eye or surrounding structures as this could cause injury to the eye
• Patients should also be instructed that ocular solutions, if handled improperly, can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions

Recommendations in other jurisdictions

• Ocular use
• One drop should be administered in the lateral canthus while applying pressure at the medial canthus to prevent drainage of the drops. Patients should be instructed to wash their hands before use and avoid allowing the tip of the container to come into contact with the eye or surrounding structures as this could cause injury to the eye
• Patients should also be instructed that ocular solutions, if handled improperly, can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions
• Nasolacrimal occlusion by compression of lacrimal ducts may reduce systemic absorption. In case of concomitant treatment with other eye drops solutions, instillations should be spaced out by 15 minutes

Special warnings and precautions for use

• Levofloxacin/ dexamethasone must not be injected sub-conjunctively. The solution should not be introduced directly into the anterior chamber of the eye
• After cataract surgery patients should not wear contact lenses for the whole duration of therapy with levofloxacin/ dexamethasone (Recommendations in other jurisdictions)

Levofloxacin
Levofloxacin, the active L-isomer of ofloxacin, is a fluoroquinolone antibacterial agent, that inhibits bacterial type II topoisomerases- deoxyribonucleic acid (DNA) gyrase and topoisomerase IV. Levofloxacin preferentially targets DNA gyrase in gram-negative bacteria and topoisomerase IV in gram-positive bacteria.

Spectrum of activity: Against ocular pathogens includes aerobic gram-positive microorganisms (e.g. S. aureus MSSA, S. pyogenes, S. pneumoniae, viridans group streptococci), aerobic gram-negative bacteria (e.g. E. coli, H. influenzae, M. catarrhalis, P. aeruginosa community isolates), other organisms (e.g. Chlamydia trachomatis).

Dexamethasone
Corticosteroids like dexamethasone suppress vascular endothelial cell adhesion molecules, cyclooxygenase I or II, and cytokine expression. This action culminates in a reduced expression of proinflammatory mediators and the suppression of adhesion of circulating leukocytes to the vascular endothelium, thereby preventing their migration into inflamed ocular tissue. Dexamethasone has marked anti-inflammatory activity with reduced mineralocorticoid activity compared with some other steroids and is one of the most potent anti-inflammatory agents.

Levofloxacin/ Dexamethasone

Eye drops (per ml) 5mg/1mg

• Voxidex (Pharmacare Limited) originator