Danemox

Danemox Oral Suspension is indicated for the treatment of the following infections in adults and children :

- Acute bacterial sinusitis

- Acute otitis media

- Acute streptococcal tonsillitis and pharyngitis

- Acute exacerbations of chronic bronchitis

- Community acquired pneumonia

- Acute cystitis

- Asymptomatic bacteriuria in pregnancy

- Acute pyelonephritis

- Typhoid and paratyphoid fever

- Dental abscess with spreading cellulitis

- Prosthetic joint infections

- Helicobacter pylori eradication

- Lyme disease

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Danemox Oral Suspension is also indicated for the prophylaxis of endocarditis.

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

Posology

The dose of Danemox Oral Suspension that is selected to treat an individual infection should take into account:

- The expected pathogens and their likely susceptibility to antibacterial agents

- The severity and the site of the infection

- The age, weight and renal function of the patient; as shown below

The duration of therapy should be determined by the type of infection and the response of the patient, and should generally be as short as possible.).

Adults and children > 40kg

Children < 40 kg

Children may be treated with Danemox Capsules, dispersible tablets suspensions or sachets

Danemox Paediatric Suspension is recommended for children under six months of age.

Children weighing 40 kg or more should be prescribed the adult dosage.

Recommended doses:

Elderly

No dose adjustment is considered necessary.

Renal impairment

In patients receiving haemodialysis

Danemox may be removed from the circulation by haemodialysis.

In patients receiving peritoneal dialysis

Danemox maximum 500 mg/day.

Hepatic impairment

Dose with caution and monitor hepatic function at regular intervals.

Method of administration

Danemox Oral Suspension is for oral use.

Absorption of Danemox Oral Suspension is unimpaired by food.

Therapy can be started parenterally according to the dosing recommendations of the intravenous formulation and continued with an oral preparation.

Hypersensitivity reactions

Before initiating therapy with Danemox, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam agents.

Serious and occasionally fatal hypersensitivity reactions (including anaphylactoid and severe cutaneous adverse reactions) have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and in atopic individuals. If an allergic reaction occurs, Danemox therapy must be discontinued and appropriate alternative therapy instituted.

Non-susceptible microorganisms

Danemox is not suitable for the treatment of some types of infection unless the pathogen is already documented and known to be susceptible or there is a very high likelihood that the pathogen would be suitable for treatment with Danemox. This particularly applies when considering the treatment of patients with urinary tract infections and severe infections of the ear, nose and throat.

Convulsions

Convulsions may occur in patients with impaired renal function or in those receiving high doses or in patients with predisposing factors (e.g. history of seizures, treated epilepsy or meningeal disorders.

Renal impairment

In patients with renal impairment the dose should be adjusted accordingly to the degree of impairment.

Skin reactions

The occurrence at the treatment initiation of a feverish generalised erythema associated with pustula may be a symptom of acute generalised exanthemous pustulosis. This reaction requires Danemox discontinuation and contra-indicates any subsequent administration.

Danemox should be avoided if infectious mononucleosis is suspected since the occurrence of a morbilliform rash has been associated with this condition following the use of Danemox.

Jarisch-Herxheimer reaction

The Jarisch-Herxheimer reaction has been seen following Danemox treatment of Lyme disease. It results directly from the bactericidal activity of Danemox on the causative bacteria of Lyme disease, the spirochaete Borrelia burgdorferi. Patients should be reassured that this is a common and usually self-limiting consequence of antibiotic treatment of Lyme disease.

Overgrowth of non-susceptible microorganisms

Prolonged use may also occasionally result in overgrowth of non-susceptible organisms.

Antibiotic-associated colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during, or subsequent to, the administration of any antibiotics. Should antibiotic-associated colitis occur, Danemox should immediately be discontinued, a physician consulted and an appropriate therapy initiated. Anti-peristaltic medicinal products are contra-indicated in this situation.

Prolonged therapy

Periodic assessment of organ system functions; including renal, hepatic and haematopoietic function is advisable during prolonged therapy. Elevated liver enzymes and changes in blood counts have been reported.

Anticoagulants

Prolongation of prothrombin time has been reported rarely in patients receiving Danemox. Appropriate monitoring should be undertaken when anticoagulants are prescribed concomitantly. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation.

Crystalluria

In patients with reduced urine output, crystalluria has been observed very rarely, predominantly with parenteral therapy. During the administration of high doses of Danemox, it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of Danemox crystalluria. In patients with bladder catheters, a regular check of patency should be maintained.

Interference with diagnostic tests

Elevated serum and urinary levels of Danemox are likely to affect certain laboratory tests. Due to the high urinary concentrations of Danemox, false positive readings are common with chemical methods.

It is recommended that when testing for the presence of glucose in urine during Danemox treatment, enzymatic glucose oxidase methods should be used.

The presence of Danemox may distort assay results for oestriol in pregnant women.

Important Information about excipients

This medicinal product contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

This medicinal product contains sodium benzoate (E211) which is a mild irritant to the eyes, skin and mucous membrane. May increase the risk of jaundice in new born babies.

No studies on the effects on the ability to drive and use machines have been performed. However, undesirable effects may occur (e.g. allergic reactions, dizziness, convulsions), which may influence the ability to drive or use machines.

The most commonly reported adverse drug reactions (ADRs) are diarrhoea, nausea and skin rash.

The ADRs derived from clinical studies and post-marketing surveillance with Danemox, presented by MedDRA System Organ Class are listed below.

The following terminologies have been used in order to classify the occurrence of undesirable effects.

Very common (>1/10)

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)

Not known (cannot be estimated from the available data)

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 at www.mhra.gov.uk/yellowcard.

Symptoms and signs of overdose

Gastrointestinal symptoms (such as nausea, vomiting and diarrhoea) and disturbance of the fluid and electrolyte balances may be evident. Danemox crystalluria, in some cases leading to renal failure, has been observed. Convulsions may occur in patients with impaired renal function or in those receiving high doses.

Treatment of intoxication

Gastrointestinal symptoms may be treated symptomatically, with attention to the water/electrolyte balance.

Danemox can be removed from the circulation by haemodialysis.

Pharmacotherapeutic group: penicillins with extended spectrum; ATC code: J01CA04.

Mechanism of action

Danemox is a semisynthetic penicillin (beta-lactam antibiotic) that inhibits one or more enzymes (often referred to as penicillin-binding proteins, PBPs) in the biosynthetic pathway of bacterial peptidoglycan, which is an integral structural component of the bacterial cell wall. Inhibition of peptidoglycan synthesis leads to weakening of the cell wall, which is usually followed by cell lysis and death.

Danemox is susceptible to degradation by beta-lactamases produced by resistant bacteria and therefore the spectrum of activity of Danemox alone does not include organisms which produce these enzymes.

Pharmacokinetic/pharmacodynamic relationship

The time above the minimum inhibitory concentration (T>MIC) is considered to be the major determinant of efficacy for Danemox.

Mechanisms of resistance

The main mechanisms of resistance to Danemox are:

- Inactivation by bacterial beta-lactamases.

- Alteration of PBPs, which reduce the affinity of the antibacterial agent for the target.

Impermeability of bacteria or efflux pump mechanisms may cause or contribute to bacterial resistance, particularly in Gram-negative bacteria.

Breakpoints

MIC breakpoints for Danemox are those of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) version 5.0.

The prevalence of resistance may vary geographically and with time for selected species, and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.

Absorption

Danemox fully dissociates in aqueous solution at physiological pH. It is rapidly and well absorbed by the oral route of administration. Following oral administration, Danemox is approximately 70% bioavailable. The time to peak plasma concentration (T_max) is approximately one hour.

The pharmacokinetic results for a study, in which an Danemox dose of 250 mg three times daily was administered in the fasting state to groups of healthy volunteers are presented below.

In the range of 250 to 3000 mg the bioavailability is linear in proportion to dose (measured as C_max and AUC). The absorption in not influenced by simultaneous food intake.

Haemodialysis can be used for elimination of Danemox.

Distribution

About 18% of total plasma Danemox is bound to protein and the apparent volume of distribution is around 0.3 to 0.4 l/kg.

Following intravenous administration, Danemox has been found in gall bladder, abdominal tissue, skin, fat, muscle tissues, synovial and peritoneal fluids, bile and pus. Danemox does not adequately distribute into the cerebrospinal fluid.

From animal studies there is no evidence for significant tissue retention of drug-derived material. Danemox, like most penicillins, can be detected in breast milk.

Danemox has been shown to cross the placental barrier.

Biotransformation

Danemox is partly excreted in the urine as the inactive penicilloic acid in quantities equivalent to up to 10 to 25% of the initial dose.

Elimination

The major route of elimination for Danemox is via the kidney.

Danemox has a mean elimination half-life of approximately one hour and a mean total clearance of approximately 25 l/hour in healthy subjects. Approximately 60 to 70% of the Danemox is excreted unchanged in urine during the first 6 hours after administration of a single 250 mg or 500 mg dose of Danemox. Various studies have found the urinary excretion to be 50-85% for Danemox over a 24 hour period

Concomitant use of probenecid delays Danemox excretion.

Age

The elimination half-life of Danemox is similar for children aged around 3 months to 2 years and older children and adults. For very young children (including preterm newborns) in the first week of life the interval of administration should not exceed twice daily administration due to immaturity of the renal pathway of elimination. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Gender

Following oral administration of Danemox to healthy males and female subjects, gender has no significant impact on the pharmacokinetics of Danemox.

Renal impairment

The total serum clearance of Danemox decreases proportionately with decreasing renal function.

Hepatic impairment

Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals.

Non-clinical data reveal no special hazard for humans based on studies of safety pharmacology, repeated dose toxicity, genotoxicity and toxicity to reproduction and development.

Carcinogenicity studies have not been conducted with Danemox.

Not applicable.

Check cap seal is intact before use.

Invert and shake bottle to loosen powder.

To prepare add 64ml of potable water and shake until all contents are dispersed

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.