Septopal Mini

Indications : Septopal Mini is indicated in bacteraemia, urinary tract infections, chest infections, severe neonatal infections and other serious systemic infections due to susceptible organisms, in adults and children including neonates.

Consideration should be given to official local guidance on the appropriate use of antibacterial agents.

Gentamicin Sterile Ophthalmic Solution is indicated in the topical treatment of ocular bacterial infections, including conjunctivitis, keratitis, keratoconjunctivitis, corneal ulcers, blepharitis, blepharoconjunctivitis, acute meibomianitis, and dacryocystitis caused by susceptible strains of the following microorganisms:

Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus pneumoniae, Enterobacter aerogenes, Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, Neisseria gonorrhoeae, Pseudomonas aeruginosa, and Serratia marcescens.

Adults:

Systemic infections: if renal function is not impaired, 3-5 mg/kg/day in divided doses according to severity of infection, adjusting according to clinical response and body weight.

Serious infections: if renal function is not impaired, 5mg/kg daily in divided doses at six or eight hourly intervals. The total daily dose may be subsequently increased or decreased as clinically indicated.

Urinary tract infections: as 'systemic infections'. Or, if renal function is not impaired, 160mg once daily may be used.

Paediatric Patients:

The daily dose recommended in children (aged 1 year and above) and adolescents with normal renal function, is 3-6 mg/kg body weight per day as 1 single dose (preferred) or up to 2 single doses.

The daily dose in infants after the first month of life is 4.5-7.5 mg/kg body weight per day as 1 single dose (preferred) or up to 2 single doses.

The daily dose in neonates is 4-7 mg/kg body weight per day. Due to the longer half-life, neonates are given the required daily dose in 1 single dose.

Elderly:

There is some evidence that elderly patients may be more susceptible to aminoglycoside toxicity whether secondary to previous eighth nerve impairment or borderline renal dysfunction.

Accordingly, therapy should be closely monitored by frequent determination of Septopal Mini serum levels, assessment of renal function and signs of toxicity.

Renal impairment:

Septopal Mini is excreted by simple glomerular filtration. In impaired renal function, the recommended daily dose has to be decreased and adjusted to the renal function.

Nomograms are available for the calculation of the dose, which depends on the patient's age, weight, and renal function

The following table may be useful when treating adults.

*60mg if body weight <60kg. Frequency of dosage in hours may also be approximated as serum creatine (mg%) x eight or in SI units, as serum creatine (μmol/l) divided by 11. If these dosage guides are used peak serum levels must be measured. Peak levels of Septopal Mini occur approximately one hour after intramuscular injectable and intravenous injectable. Trough levels are measured just prior to the next injectable. Assay of peak serum levels gives confirmation of adequacy of dosage and also serves to detect levels above 10mg/l, at which the possibility of ototoxicity should be considered. One hour concentrations of Septopal Mini should not exceed 10mg/l (but should reach 4mg/l), while the pre-dose trough concentration should be less than 2mg/l

The recommended dose and precautions for intramuscular and intravenous administration are identical. Septopal Mini when given intravenously should be injected directly into a vein or into the drip set tubing over no less than three minutes. If administered by infusion, this should be over no longer than 20 minutes and in no greater volume of fluid than 100ml.

Monitoring advice:

Serum concentration monitoring of Septopal Mini is recommended, especially in elderly, in newborns and in patients with impaired renal function.

Gentamicin Sterile Ophthalmic Solution: Instill one or two drops into the affected eye every 4 hours. In severe infections, dosage may be increased to as much as two drops once every hour.

Hypersensitivity to Septopal Mini or any of the excipients; myasthenia gravis.

GARAMYCIN Sterile Ophthalmic Solution is contraindicated in patients with known hypersensitivity to any of the components.

In patients with advanced renal impairment or with pre-existing inner ear deafness, Septopal Mini should be used only if its use is considered essential by the physician. The frequency or dose of administration should be reduced in patients with impaired renal function.

Renal impairment

Renal impairment such as restriction of glomerular filtration is observed in approximately 10% of patients treated with Septopal Mini and is usually reversible. The most important risk factors are high total dose, long duration of therapy, raised serum level (high trough level); in addition, other potential risk factors are age, hypovolaemia and shock.

Clinical signs of renal damage are: proteinuria, cylindruria, haematuria, oliguria, raised creatinine and urea concentrations in serum.)

Neuromuscular disorders

Since Septopal Mini has neuromuscular blocking properties, particular caution should be exercised in patients with pre- existing neuromuscular diseases (e.g.)

Neuromuscular blockade and respiratory paralysis have been reported from administration of aminoglycosides to patients who have received curare-type muscle relaxants during anaesthesia.)

Effect on vestibulocochlear nerve

Damage to the vestibulocochlear nerve (eighth cranial nerve), whereby both balance and hearing may be affected, is possible. Vestibular damage is the most common ototoxic reaction. Hearing loss is manifested initially by diminution of high-tone acuity and is usually irreversible. Important risk factors are pre-existing renal impairment or a history of damage to the eighth cranial nerve; in addition, the risk increases in proportion to the level of the total and daily dose or by association with potentially ototoxic substances. Symptoms of ototoxic effects are: dizziness, ringing/roaring in the ears (tinnitus), vertigo and less common hearing loss.

With Septopal Mini the vestibular mechanism may be affected if trough levels of 2 µg/ml are exceeded.)

Antibiotic-associated diarrhoea, pseudomembranous colitis Antibiotic-associated diarrhoea and pseudomembranous colitis have been reported with the use of Septopal Mini. These diagnoses should be considered in any patient who develops diarrhoea during or shortly after treatment. Septopal Mini should be discontinued if severe and/or bloody diarrhoea occurs during treatment and appropriate therapy instituted. Drugs that inhibit peristalsis must not be given.

Pregnancy and lactation

Septopal Mini should be used in pregnancy and during lactation only after careful benefit risk assessment.

Once daily dosing of Septopal Mini in elderly patients:

There is limited experience with once daily dosing of Septopal Mini in elderly patients. Once daily dosing of Septopal Mini may not be suitable and therefore, close monitoring is warranted in these patients.

Excipients

This medicine contains 0,78 mg of sodium per ampoule (less than 23 mg per ampoule), i.e. it is essentially sodium free.

Sodium metabisulphite, one of the excipients of this medicinal product, may rarely cause severe hypersensitivity reactions and bronchospasm.

Cross-allergenicity/-resistance

Cross resistance and hypersensitivity to aminoglycosides may occur.

Monitoring

To avoid adverse events, continuous monitoring (before, during and after treatment) of renal function (serum creatinin, creatinin clearance), control of function of vestibule and cochlea as well as hepatic and laboratory parameters is recommended.

In order to reduce the risk of nephrotoxicity and ototoxicity, the following instructions should be considered:

- Regular assessment of auditory, vestibular and renal function is particularly necessary in patients with additional risk factors. Impaired hepatic function or auditory function, bacteraemia and fever have been reported to increase the risk of ototoxicity. Volume depletion or hypotension and liver disease have been reported as additional risk factors for nephrotoxicity.

- Monitoring of renal function before, during and after treatment.

- Dosage strictly according to creatinine clearance (or serum creatinine concentration). In patients with impaired renal function, the dosage must be adjusted according to renal performance.

- In patients with impaired renal function additionally receiving Septopal Mini locally (inhalation, intratracheal, instillation), the amount of Septopal Mini absorbed after local administration must also be taken into account for dose adjustment of systemic treatment.

- Monitoring of serum Septopal Mini concentrations during therapy in order to avoid that peak levels exceed 10 µg/ml (toxic threshold for the cochleo-vestibular system) with conventional multiple daily dosing or trough levels exceed 2 µg/ml when administrating Septopal Mini twice daily and 1 mg/l for a once daily dosing.

- In patients with pre-existing inner ear damage (hearing impairment or balance function impairment), or where treatment is long-term, additional monitoring of the balance function and hearing is required.

- Prolonged treatment should be avoided. If possible, the duration of therapy should be limited to 7 - 10 days.

- Avoid therapy with aminoglycosides immediately subsequent to previous aminoglycoside treatment; if possible, there should be an interval of 7 - 14 days between treatments.

- If possible, avoid concurrent administration of other potentially ototoxic and nephrotoxic substances. If this is unavoidable, particular careful monitoring of renal function is indicated.

- Ensure adequate hydration and urine production.

WARNINGS

NOT FOR INJECTION INTO THE EYE. Gentamicin Sulfate Ophthalmic Solution is not for injection. It should never be injected subconjunctivally, nor should it be directly introduced into the anterior chamber of the eye.

PRECAUTIONS

General

Prolonged use of topical antibiotics may give rise to overgrowth of nonsusceptible organisms including fungi. Bacterial resistance to gentamicin may also develop. If purulent discharge, inflammation, or pain becomes aggravated, the patient should discontinue use of the medication and consult a physician.

If irritation or hypersensitivity to any component of the drug develops, the patient should discontinue use of this preparation, and appropriate therapy should be instituted.

Information for Patients

To avoid contamination, do not touch tip of container to the eye, eyelid, or any surface.

Carcinogenesis, Mutagenesis, Impairment of Fertility

There are no published carcinogenicity or impairment of fertility studies on gentamicin. Aminoglycoside antibiotics have been found to be nonmutagenic.

Pregnancy

Pregnancy Category C: Gentamicin has been shown to depress body weights, kidney weights, and median glomerular counts in newborn rats when administered systemically to pregnant rats in daily doses approximately 500 times the maximum recommended ophthalmic human dose. There are no adequate and well-controlled studies in pregnant women. Gentamicin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Pediatric Use

Safety and effectiveness in neonates have not been established.

Under certain conditions Septopal Mini shows ototoxic and/or nephrotoxic effects. Renal impairment is commonly observed in patients treated with Septopal Mini and is usually reversible upon withdrawal of the drug. In most cases nephrotoxicity is associated with an excessively high dosage or prolonged treatment, pre-existing renal abnormalities or associated with other substances reported to be nephrotoxic.

The adverse reactions considered at least possibly related to treatment are listed below by body system organ class and absolute frequency. Frequencies are defined as:

very common (>1/10);

common (>1/100 to <1/10);

uncommon (>1/1000 to <1/100);

rare (>1/10 000 to <1/1000);

very rare (<1/10 000),

not known (frequency cannot be estimated from the available data).

¹ Usually in these cases other antibiotics are also involved.

² May occur as hypersensitivity reactions

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 national reporting system, by the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Bacterial and fungal corneal ulcers have developed during treatment with gentamicin ophthalmic preparations.

The most frequently reported adverse reactions are ocular burning and irritation upon drug instillation, nonspecific conjunctivitis, conjunctival epithelial defects, and conjunctival hyperemia.

Other adverse reactions which have occurred rarely are allergic reactions, thrombocytopenic purpura, and hallucinations.

Haemodialysis and peritoneal dialysis will aid removal from the blood but the former is probably more efficient.

Calcium salts given intravenously have been used to counter the neuromuscular blockade caused by Septopal Mini.

No information provided.