1.
NAME OF THE MEDICINAL PRODUCT
Avopenin 800 mg
Avopenin 1g film-coated tablets
2.
QUALITATIVE AND QUANTITATIVE COMPOSITION
Phenoxymethylpenicillin potassium
800 mg or 1 g
For a full list of excipients, see section 6.1.
3.
PHARMACEUTICAL FORM
Film-coated tablets
800 mg: White to offwhite, capsule-shaped film-coated tablets with a breakscore, embossed
P/0.8.
1 g: White to offwhite, capsule-shaped film-coated tablets with a breakscore, embossed P/1.0.
The score line is only to facilitate breaking for ease of swallowing and not to divide into equal
doses.
4.
CLINICAL PARTICULARS
4.1
Therapeutic indications
Avopenin is indicated for the treatment of the following infections if shown to be or
considered very likely to be caused by bacteria susceptible to phenoxymethylpenicillin:
- pharyngotonsillitis due to beta-haemolytic streptococci
- acute sinusitis
- acute otitis media
- community-acquired pneumonia
- uncomplicated skin and soft tissue infections
- cutaneous Borrelia infections
- tooth abscesses.
Avopenin is indicated in adults, children and adolescents from the age of 12 years (or 40
kg), see section 4.2.
Consideration should be given to official guidance on the appropriate use of antimicrobial
agents.
4.2
Posology and method of administration
Posology
Pharyngotonsillitis, community-aquired pneumonia, uncomplicated skin- and soft tissue
infections
Tablet strength
1g
Dosage
1 tabl 2-3times daily
Acute otitis media, acute sinusitis, tooth abscess
The treatment time for acute otitis media is 5 days, in recurring acute otitis media 10 days,
acute sinusitis and tooth abscess 7 - 10 days.
Tablet strength
800 mg
Dosage
2 tabl 2-3 times daily
Additional antibiotics covering anaerobic bacteria may be necessary in the treatment of tooth
abscesses.
Cutaneous Borrelia infection (Erythema migrans):
1 g 3 times daily for 10 days.
Acrodermatitis
For adults with uncomplicated acrodermatitis the dosage should be 2 g 3 times daily for three
weeks.
General regarding the dosing
PK/PD data indicate that dosing three times daily improves the clinical efficacy and is thus
always recommended in severe infections such as pneumonia and erysipelas and at least in
the initial phase of other infections (see section 5.1).
The tablets should be taken fasting, one hour before or two hours after a meal.
Paediatric population
Avopeniin is indicated in patients from the age of 12 years. There are other strengths and
pharmaceutical forms of phenoxymethylpenicillin available for children below 12 years of
age/below 40 kg
4.3
Contraindications
Hypersensitivity to the active substance or to any of the excipients.
4.4 Special warnings and precautions for use
Cross-allergy exists between penicillins and cephalosporins. Antibiotic-associated colitis and
pseudomembranous colitis have been reported with nearly all antibacterial agents, including
phenoxymethylpenicillin, 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
shortly after treatment.
4.5
Interaction with other medicinal products and other forms of interaction
The following combinations with Avopenin may require dose adjustments: anticonceptional
agents (birth control pills) and methotrexate.
Certain antibiotics may in rare cases decrease the effect of birth control pills through
interference with re-absortion of unconjugated steroid in the intestine. This would decrease
the plasma levels of active steroid, Pregnancies have mainly occurred in women taking
ampicillin, amoxicillin or tetracyclines together with birth control pills.
A serious case of a severe toxic reaction to methotrexate has been described, where the
patient was treated concomitantly with furosemide and penicillin V, organic acids that may
inhibit the tubular secretion of methotrexate. A possible interaction has also been described
after combination of methotrexate and mezlocillin, and a second case after combination of
methotrexate and amoxicillin.
Probenecid delays the renal excretion of penicillin, which may result in higher serum
concentrations of phenoxymethylpenicillin over a longer time.
4.6
Fertility, pregnancy and lactation
Pregnancy
A large amount of data on pregnant women indicate no malformative nor feto/ neonatal
toxicity of phenoxymethylpenicillin.
Avopenin can be used during pregnancy if clinically needed.
Breastfeeding
Phenoxymethylpenicillin /metabolites are excreted in human milk, but at therapeutic doses of
Avopenin no effects on the breastfed newborns/infants are anticipated.
4.7
Effects on ability to drive and use machines
Avopenin has no or negligible influence on the ability to drive and use machines.
4.8
Undesirable effects
Approximately 5% of the treated patients can be expected to experience adverse events.
The most common evens are gastrointestinal events with loose stools.
The following undesirable effects have been observed with the following frequencies: Very
common ≥1/10), common (1/100, <1/10), uncommon (1/1,000, <1/100), rare (1/10,000,
<1/1,000), very rare (<1/10,000),not known (cannot be estimated from the available data).
Blood and lymphatic system
disorders
Uncommon
Eosinophilia.
Gastrointestinal disorders
Common
Loose stools, nausea.
Skin and subcutaneous tissue
disorders
Common
Exanthema.
Uncommon
Urticaria.
Uncommon
Generalised hypersensitivity reaction
with fever and/or joint aches.
Rare
Anaphylactic reaction.
Immune system disorders
Fungal superinfection in the oral cavity and genital region may occur.
4.9
Overdose
Toxicity: Large doses are usually well tolerated. Acute reactions are usually caused by
hypersensitivity. There is a certain risk for hyperkalcaemia with massive overdoses of
penicillin as a potassium salt.
Symptoms: Toxic reactions; nausea, vomiting, electrolyte disturbances, decreased
consciousness, muscle fasciculations, myoclonias, cramping, coma, haemolytic reactions,
renal failure, acidosis.
In exceptional cases anaphylactic shock can occur within 20-40 minutes.
Treatment: If justified, gastric lavage, charcoal. Symptomatic treatment. In severe cases,
haemoperfusion or haemodialysis. Treatment of anaphylactic shock: Epinephrine (adrenaline)
0.1 – 0.5 mg intravenously, hydrocortisone 200 mg intravenously, possibly promethazine 25
mg intravenously, fluid, correction of acidosis.
5.
PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antibacterial betalactams, penicillin, ATC code: J01CE02
Mode of action
Phenoxymethylpenicillin is a betalactam antibiotic that exerts its action by inhibiting bacterial
cell wall synthesis. The effect is bactericidal.
PK/PD relationship
Available pharmacokinetic and pharmacodynamic knowledge shows that for betalactam
antibiotics the efficacy is mainly dependent on the time of free antibiotic concentration above
the minimum inhibitory concentration in serum for the microorganism (T>MIC). Based on
this knowledge, shorter dosing intervals should be considered to achieve maximum clinical
efficacy.
Mechanism(s) of resistance
Resistance may evolve because of bacterial synthesis of a large number of batalactamases that
hydrolyze the penicillin. Several of these are inhibited by clavulanic acid. In addition,
resistance may occur because of production of deviating penicillin binding proteins (PBP).
This resistance is often plasmide mediated.
Cross-resistance occurs within the betalactam group (penicillins and cephalosporins).
Breakpoints (EUCAST)
Organism
Staphylococcus spp.
Streptococcus group A, C and G
only
Streptococcus pneumoniae
Susceptibility Breakpoints (mg/L)
Susceptible
Resistant
≤ 0.12
> 0.12
≤0.25
>0.25
≤ 0.06
Breakpoint values in the table are based on benzylpenicillin breakpoints.
Antibacterial spectrum
Susceptible
Streptococci and pneumococci
Corynebacterium diphteriae
>2
Intermediate
Resistant
Pasteurella multocida
Peptococci
Peptostreptococci
Actinomyces
Fusobacteria
Capnocytophaga canimorsus
Borrelia burgdorferi
Borrelia Vincenti
Haemophilus influenzae
Staphylococci
Enterococci
Moraxella catarrhalis
Gram-negative enterococci
Pseudomonas
Legionella
Bacteroides fragilis
Clostridium difficile
Mycoplasma
Chlamydia
Resistance occurs (1-10%) in pneumococci. Resistance is common (>10%) with Haemophilus
influenzae.
Non-betalactamase producing Haemophilus influenzae is therapeutically reachable with high
dose phenoxymethylpenicillin.
5.2
Pharmacokinetic properties
Phenoxymethylpenicillin potassium is soluble in water and acid-stable, and approximately
50% is absorbed. After single doses of 800 mg, given to fasting adults mean peak serum
concentrations of 10 microg/ml are achieved after 0.5 – 1 hour. Concomitant intake of food
results in a lower degree of absorption and lower peak serum concentration. The biological
half-life in serum is approximately 30 minutes and the protein binding is approximately 80%.
Phenoxymethylpenicillin is mainly excreted in urine, where 30 – 50% of a given dose can be
detected in the active form within 8 hours.
5.3
Preclinical safety data
There are no available pre-clinical data of relevance for the safety assessment that have not
already been considered in this Summary of Product Characteristics.
6.
PHARMACEUTICAL PARTICULARS
6.1
List of excipients
Tablet Core:
Magnesium stearate, povidone.
Film-coating:
Titanium dioxide (E171)
Hypromellose
Macrogol
Avopenin tablets have a saliva resistant coating to preserve the normal flora in the oral cavity
and in the throat.
6.2
Incompatibilities
Not applicable.
6.3
Shelf life
2 years
6.4
Special precautions for storage
Do not store above 30°C.
6.5
Nature and contents of container
Blisters (PVC/PVDC/aluminium):
Tablets 800 mg: 14, 20, 30, 40, 98 x 1 and 100 tablets
Tablets 1 g: 14, 20, 30, 40, 98 x 1 and 100 tablets
Not all pack sizes may be marketed.
6.6
Special precautions for disposal
No special requirements
7.
MARKETING AUTHORISATION HOLDER
Pilum Pharma AB
Box 28
257 21 Rydebäck
Sweden
8.
MARKETING AUTHORISATION NUMBER(S)
To be completed nationally
9.
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
10.
DATE OF REVISION OF THE TEXT
27/6/2012