Erythromycin Stragen 1 g Pulver till infusionsvätska, lösning

Sverige - svenska - Läkemedelsverket (Medical Products Agency)

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Bipacksedel Bipacksedel (PIL)

20-04-2018

Produktens egenskaper Produktens egenskaper (SPC)

20-04-2018

Aktiva substanser:
erytromycinlaktobionat
Tillgänglig från:
Stragen Nordic A/S,
ATC-kod:
J01FA01
INN (International namn):
erythromycin
Dos:
1 g
Läkemedelsform:
Pulver till infusionsvätska, lösning
Sammansättning:
erytromycinlaktobionat 1,49 g Aktiv substans
Receptbelagda typ:
Receptbelagt
Bemyndigande status:
Avregistrerad
Godkännandenummer:
52094
Tillstånd datum:
2015-12-10

Dokument på andra språk

Bipacksedel Bipacksedel - engelska

12-03-2018

Produktens egenskaper Produktens egenskaper - engelska

12-03-2018

Offentlig bedömningsrapport Offentlig bedömningsrapport - engelska

10-12-2015

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Package leaflet: Information for the patient

Erythromycin Stragen 1 g powder for solution for infusion

erythromycin

Read all of this leaflet carefully before you start using this medicine because it contains

important information for you.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor or nurse.

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects

not listed in this leaflet. See section 4.

What is in this leaflet

What Erythromycin Stragen is and what it is used for

What you need to know before you use Erythromycin Stragen

How to use Erythromycin Stragen

Possible side effects

How to store Erythromycin Stragen

Contents of the pack and other information

1.

What Erythromycin Stragen is and what it is used for

Erythromycin Stragen is a powder for solution for infusion. Erythromycin lactobionate, the active

substance of this medicine, belongs to the group of antibacterial substances for systemic use (suitable

for intravenous injection).

Erythromycin Stragen disrupts the production of proteins by bacteria, and thereby prevents the bacteria

from multiplying.

Erythromycin Stragen is used primarily for various bacterial infections of the airways such as

pneumonia, whooping cough and diphtheria. Erythromycin Stragen is also used for vaginal infections

and for eye inflammation and pneumonia in new-born infants caused by

Chlamydia

bacteria.

Erythromycin Stragen is also used in the treatment of pneumonia, infections of the skin and soft

tissues in people who are intolerant to penicillin or where penicillin is unsuitable for some other

reason.

2.

What you need to know before you use Erythromycin Stragen

Do not use Erythromycin Stragen:

if you are allergic to erythromycin;

if you are allergic to any other of antibiotics from the same group such as clarithomycin or

azithromycin;

if you have certain heart disorders (long QT syndrome, or acquired QT prolongation).

if you are taking any medicines containing:

astemizole (a medicine for allergies),

cisapride (a medicine for gastrointestinal disorders),

disopyramide (a medicine for heart problems),

ergotamine (a medicine to prevent migraine),

dihydroergotamine (a medicine for low blood pressure),

pimozide (a medicine used for mental illness),

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terfenadine or so-called statins such as simvastatin, atorvastatin and lovastatin

(medicines for treating high blood fat levels).

Warnings and precautions

Talk to your doctor or nurse before using Erythromycin Stragen:

if you have impaired liver function (problems with the way your liver works) or heart

problems.

in case of long-term or severe diarrhoea. Diarrhoea caused by bacteria may occur during and

following treatment with Erythromycin Stragen (see section 4).

if you suffer from

myasthenia gravis

(a chronic, autoimmune disease, manifested by muscle

fatigue), as the symptoms may become worse,

if you are breast-feeding and the child vomits or becomes irritable when being fed.

If you have severe impaired renal function. Temporary hearing loss may occur during

treatment.

Contact your doctor immediately if you get any of the following symptoms (which indicate

angioedema):

swelling of the face, tongue or throat,

difficulty swallowing,

hives and breathing difficulties.

Other medicines and Erythromycin Stragen

Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines.

The section "Do not use Erythromycin Stragen" above lists medicines that must not be taken together

with Erythromycin Stragen.

Erythromycin Stragen can affect or can be affected by certain medicines that contain the following

active ingredients:

fluconazole, ketoconazole and itraconazole (used for fungal infections),

protease inhibitors (used in case of HIV infection),

clarithromycin, rifampicin (used for bacterial infections),

digoxin, quinidine (used for heart problems),

cilostazol (used for intermittent claudication, which is muscle pain in the leg),

warfarin, acenocoumarol (blood-thinning medicines),

fexofenadine (used to prevent allergies),

valproic acid, carbamazepine, phenobarbital or phenytoin (used for epilepsy),

theophylline (used for asthma and other respiratory problems),

ciclosporin, tacrolimus (used following organ transplantation),

bromocriptine (used for Parkinson's disease),

zopiclone, triazolam, alprazolam, clozapine, midazolam, hexobarbitone, buspirone (used for

anxiety, agitation and sleeping disorders),

alfentanil (to prevent pain during surgery),

cimetidine, omeprazole (used to treat acid reflux and stomach ulcers),

colchicine (used for joint pain),

methylprednisolone (used to suppress the body's immune system for example in case of allergy

and inflammation),

St. John's wort (a natural remedy used to treat depression),

verapamil (used in case of heart disease, for example, to prevent high blood pressure),

vinblastine (used for certain types of cancer),

sildenafil (used for erectile dysfunction),

tyrosine kinase inhibitors (e.g. imatinib) used against some specific forms of cancer,

tolterodine (treatment for urinary incontinence).

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask

your doctor for advice before using this medicine.

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Pregnancy

Treatment with Erythromycin Stragen should be given

only

if absolutely necessary and only after

evaluation by a doctor that the benefits outweigh the potential risks.

Breast-feeding

Erythromycin passes into human milk. Your doctor will decide if you should be administered this

medicine, only after making sure that the benefits outweigh the potential risks.

Driving and using machines

No effects on the ability to drive or use machines have been observed.

3.

How to use Erythromycin Stragen

Erythromycin Stragen is given to you by a doctor or a nurse as an infusion directly into your blood.

The doctor decides the dose, which will be set specifically for you. The dosage depends on the type

and severity of the infection.

Adults and children over 12 years old or weighing more than 40 kg

The recommended dosage

is 15-20 mg/kg/day. If necessary, the dose may be increased to 4 grams per

day. Erythromycin Stragen can be given as divided doses every 6 or 8 hours, or as a continuous

intravenous infusion.

Use in children over 1 month to 12 years old or weighing up to 40 kg

The usual dose is 15 - 20 mg/kg of body weight divided over 3 - 4 single doses. The doctor will

calculate the exact dose your child will receive taking into account his/her body weight.

Use in term newborn infants (birth to 1 month)

The usual dose is 10-15 mg/kg divided over 3 single doses. Your doctor will calculate the exact dose

your child will receive taking into account his/her body weight.

Use in patients with renal impairment

Your doctor will avoid giving you additional dose if you have regular dialysis.

If you have any further questions on the use of this medicine, ask your doctor or nurse

.

4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Contact a doctor immediately if you experience a serious skin reaction: a red, scaly rash with bumps

under the skin and blisters (exanthematous pustulosis). The frequency of this side effect is not known

(cannot be estimated from the available data).

Common (may affect up to 1 in 10 people)

heart rhythm disorders (arrhythmia),

upset stomach (in the form of nausea, stomach-ache and diarrhoea); contact your doctor in case

of long-term or severe diarrhoea,

skin rash,

swelling and pain at the infusions site.

Uncommon (may affect up to 1 in 100 people)

hives.

Rare (may affect up to 1 in 1,000 people)

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allergic reaction (anaphylaxis),

temporary hearing loss (primarily in patients with impaired renal function or at high doses),

elevated liver counts, blockage of the bile duct (cholestasis), inflammation of the liver

(hepatitis).

Not known (frequency cannot be estimated from the available data)

feeling ill,

stomach pain,

inflamed pancreas (pancreatitis),

vomiting,

tinnitus (ringing in the ears),

deafness,

chest pain,

heart rhythm disorders,

palpitations,

prolonged QTc interval (seen on an ECG),

fever,

loss of appetite,

confusion,

cramps,

dizziness,

hallucinations (seeing or hearing things that are not there),

inflammation of the kidneys (a condition called interstitial nephritis),

low blood pressure,

swelling of the face, lips, tongue or throat, sometimes with shortness of breath or problems

swallowing, so-called angioedema,

itching, changes in the skin and mucous membranes (at times severe),

severe widespread skin damage (peeling),

increased number of white blood cells in the blood (eosinophilia),

some forms of liver inflammation (cholestatic and hepatocellular hepatitis),

jaundice (yellowing of the skin or whites of the eyes caused by liver or blood problems),

reduced liver function,

enlargement of the liver,

liver failure.

Fungal overgrowth in the mouth and vagina may occur.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side

effects not listed in this leaflet.

You can also report side effects directly via the national reporting

system. By reporting side effects you can help provide more information on the safety on this

medicine.

5.

How to store Erythromycin Stragen

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton after “EXP:” The expiry

date refers to the last day of that month.

Unopened: This product does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to

throw away medicines you no longer use. These measures will help protect the environment.

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6.

Contents of the pack and other information

What Erythromycin Stragen contains

The active substance is erythromycin. 1 vial contains erythromycin lactobionate equivalent to

1 g erythromycin.

- The other ingredients are: none

What Erythromycin Stragen looks like and contents of the pack

Erythromycin Stragen is available as a powder for solution for infusion. The powder is white to

slightly yellow.

The powder is supplied as a single dose vial packed in a carton box.

Each carton box contains 1 vial or 10 vials.

Marketing Authorisation Holder

<[To be completed nationally]>

Manufacturer

<[To be completed nationally]>

This leaflet was last revised in 2018-03-12

-----------------------------------------------------------------------------------------------------------------

The following information is for healthcare professionals only:

The full information can be found in the Summary of Product Characteristics for Erythromycin

Stragen.

Method of administration

Because rapid infusion is closely associated with arrhythmias or hypotension it is recommended that

Erythromycin Stragen solution for infusion should be administered slowly. This should be particularly

noted in patients with risk factors or previous signs of arrhythmias.

A low infusion rate is also recommended for patients with heart disease and for premature babies.

a) Intermittent infusion: max. 5 ml/min for 20–60 minutes

b) Continuous infusion: infusion for up to 24 hours.

Erythromycin Stragen must not be administered as a bolus injection.

Preparation for administration

1. Preparation of base solution:

A 5% base solution (50 mg erythromycin/ml) is prepared by dissolving the powder in the vial (1 g

erythromycin) in 20 ml water for solution for infusion. The base solution must be diluted further

before administration.

2. Dilution of base solution

a) Solution for infusion for intermittent infusion:

20 ml base solution is further diluted by adding to 200

250 ml of a suitable solution for infusion (see

below).

b) Solution for infusion for continuous infusion:

20 ml base solution is further diluted by adding to 500 ml or 1000 ml of a suitable solution for infusion

(see below).

Solution for infusion suitable for dilution of base solution:

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- 0.9% (9 mg/ml) sodium chloride solution for injection

- Glucose 5%

- Hartman’s solution.

Solutions containing glucose must first have sodium bicarbonate added as a buffer to assure neutrality.

Ensure that the finished solution for infusion is free from particles before administration.

Special precautions for storage

After reconstitution:

After reconstitution, chemical and physical in-use stability in water for injection has been

demonstrated for 24 hours when stored at room temperature and for 14 days when stored in a

refrigerator at 2-8° C.

After reconstitution and dilution:

After reconstitution and dilution, chemical and physical in-use stability has been demonstrated for 24

hours at room temperature when the solution is diluted in 0.9% (9 mg/ml) sodium chloride solution for

injection or Glucose 5% and for 12 hours at room temperature when the solution is diluted in

Hartman’s solution.

From a microbiological point of view, once opened, the product should be used immediately.

If not used immediately, in-use storage times and conditions prior to use are the responsibility of the

user and would normally not be longer than 24 hours at 2-8°C, unless reconstitution has taken place in

controlled and validated aseptic conditions

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SUMMARY OF PRODUCT CHARACTERISTICS

1.

NAME OF MEDICINAL PRODUCT

Erythromycin Stragen 1 g powder for solution for infusion

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

1 vial contains erythromycin lactobionate equivalent to 1g erythromycin.

3.

PHARMACEUTICAL FORM

Powder for solution for infusion

White to slightly yellow powder.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Pneumonia caused by

Legionella

Mycoplasma pneumoniae

Chlamydia psittaci

(ornithosis) or

Chlamydia pneumoniae

(TWAR). Pertussis. Diphtheria. Urogenital infections caused by

Chlamydia

trachomatis

. Conjunctivitis and pneumonia in newborns caused by

Chlamydia trachomatis

Given the following indications, Erythromycin Stragen should be reserved for patients who are

hypersensitive to penicillin or where penicillin is unsuitable for other reasons: nosocomial pneumonia;

skin and soft tissue infections.

4.2

Posology and method of administration

Posology

Adults and children over 12years old or weighing more than 40 kg

20 mg/kg/day. Where necessary the dose may be increased to 4 g/day. May be given in divided

doses every 6 or 8 hours (intermittent intravenous infusion) or as a continuous intravenous infusion.

Use in children up to 12 years old or weighing up to 40 kg

1 month to up to 12 years old:

The daily dose for infants and children up to 12 years old for most infections is 15-20 mg of

erythromycin/kg of body weight divided over 3-4 single doses. This dose may be doubled depending

on the indication.

Use in term newborn infants (birth to 1 month)

10-15 mg/kg/day divided over 3 singles doses.

Elderly:

No special dose recommendations.

Method of administration

Because rapid infusion is closely associated with arrhythmias or hypotension it is recommended that

Erythromycin Stragen should be administered slowly. This should be particularly noted in patients

with risk factors or previous signs of arrhythmias.

A low infusion rate is also recommended for patients with heart disease and for premature babies.

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a) Intermittent infusion:

The prepared solution for infusion is infused slowly and intravenously (max. 5 ml/min for 20–60

minutes) to prevent local irritation.

b) Continuous infusion:

The prepared solution for infusion is administered as a continuous intravenous infusion for up to 24

hours.

Erythromycin Stragen

must not be administered as a bolus injection.

For instructions on preparation of the medicinal product before administration, see section 6.6.

4.3

Contraindications

Hypersensitivity to the active substance or to other macrolides.

Simultaneous medication with astemizole, cisapride, disopyramide, ergot alkaloids (such as

ergotamine and dihydroergotamine), pimozide or terfenadine (see section 4.5).

Erythromycin Stragen must not be used together with simvastatin, atorvastatin and lovastatin.

Treatment with these medicines should be interrupted during treatment with Erythromycin Stragen

(see section 4.5).

Erythromycin Stragen

is contra-indicated for patients with congenital long QT syndrome or where

long QT syndrome is present in the family (unless excluded by ECG) and for patients with known

acquired QT prolongation.

4.4

Special warnings and precautions for use

Because erythromycin is primarily excreted via the liver, the exposure to erythromycin and the risk for

adverse effects may increase in patients with impaired hepatic function. Therefore, caution should be

exercised when administering erythromycin to patients with impaired hepatic function.

The low proportion of renal excretion indicates that plasma exposure to erythromycin is not altered in

patients with impaired renal function. However, ototoxicity has been reported in patients with severe

renal impairment and erythromycin should therefore be used with caution in these patients.

Erythromycin is not removed by haemodialysis or peritoneal dialysis. For patients who have regular

dialysis, an additional dose is therefore not recommended.

There are reports suggesting that erythromycin can aggravate the symptoms in Myasthenia gravis

patients.

Close monitoring of patients with heart disease and premature babies.

Diarrhoea/pseudomembranous colitis caused by

Clostridium difficile

(CDAD) may arise from the use

of almost all antibacterial agents, including erythromycin, and may range in severity from mild

diarrhoea to fatal colitis (see section 4.8). Patients with diarrhoea should therefore be carefully

monitored for CDAD. Thorough medical anamnesis is necessary because CDAD has been reported to

appear several weeks after administration of antibacterial agents. If CDAD is suspected or confirmed,

any ongoing treatment with erythromycin should be stopped if possible.

Depending on the risk of increased QT, Erythromycin Stragen and other macrolides should be used

with care on patients with coronary disease, a history of ventricular arrhythmias, uncorrected

hypokalaemia and/or hypomagnesaemia, bradychardia (<50 bpm), or patients being treated with both

Erythromycin Stragen and QT-prolonging medicines or strong CYP3A4 inhibitors (see section 4.5).

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Erythromycin Stragen should not be used during and for two weeks after treatment with CYP3A4

inducers (such as rifampicin, phenytoin, carbamazepine, phenobarbital, St John’s wort). Simultaneous

treatment with these medicines may result in sub-therapeutic levels of erythromycin and carry the risk

of treatment failing (see section 4.5).

Erythromycin Stragen is an inhibitor of CYP3A4 and should only be used in specific situations where

other medicines metabolised by CYP3A4 are being used (see sections 4.3 and 4.5).

There have been reports of cases of infantile hypertrophic pyloric stenosis (IHPS) occurring in infants

following erythromycin therapy (see section 4.8). In a cohort of 157 newborns given erythromycin for

pertussis prophylaxis, seven neonates (5%) developed symptoms of non-bilious vomiting or irritability

during feeding and were subsequently diagnosed with IHPS which required surgical pyloromyotomy.

The benefits of erythromycin therapy need to be weighed against the potential risk of developing

IHPS. Parents should be advised to contact their GP in the event of vomiting or irritability during

feeding.

As with other macrolides, rare serious allergic reactions, including acute generalised exanthematous

pustulosis (AGEP) have been reported. If an allergic reaction occurs, the drug should be discontinued

and appropriate therapy should be instituted. Physicians should be aware that reappearance of the

allergic symptoms may occur when symptomatic therapy is discontinued.

4.5

Interaction with other medicinal products and other forms of interaction

Effect of Erythromycin Stragen on other medicines:

Erythromycin is a moderate inhibitor of CYP3A4 and an inhibitor of the transport protein P-

glycoprotein. The degree of inhibition with different CYP3A4 substrates is difficult to predict.

Erythromycin Stragen should therefore not be used during treatment with medicines which are

CYP3A4 substrates unless plasma concentrations of the CYP3A4 substrate, the effect or side-effects

can be closely monitored. It may be necessary to reduce the dosage of other medicines that are

metabolised by CYP3A4 and care should be taken when combining them with erythromycin (e.g.

acenocoumarol, alfentanil, bromocriptine, cilostazol, ciclosporin, hexobarbitone, colchicine,

methylprednisolone, midazolam, omeprazole, tacrolimus, valproic acid, vinblastine, buspirone and

antimycolytics such as fluconazole, ketoconazole and itraconazole). Alternatively, treatment with

CYP3A4 substrate should be suspended during treatment with Erythromycin Stragen (e.g.,

simvastatin, atorvastatin and lovastatin; see section 4.3).

Medicines that may prolong the QT interval

Erythromycin affects the metabolism of terfenadine, astemizole, pimozide and tolterodine when they

are taken at the same time. Rare cases of serious, potentially life-threatening cardiovascular events

including heart stoppage, torsade de pointes and other ventricular arrhythmias have been observed, so

simultaneous use of these medicines is contra-indicated (see sections 4.3 and 4.8).

Elevated levels of cisapride have been reported in patients also being treated with erythromycin. This

may result in a prolonged QT interval and heart arrhythmia, including ventricular tachycardia,

ventricular fibrillation and torsade de pointes. Similar symptoms have been seen in patients taking

disopyramide and erythromycin at the same time and may be expected in patients taking astemizole

and pimozide. Concomitant administration of astemizole, cisapride, disopyramide and pimozide is

contra-indicated (see section 4.3).

Erythromycin may inhibit the metabolism of quinidine, with a 40% increase in Cmax in healthy trial

subjects. There are occasional case reports of increased plasma concentrations and torsades de pointes.

During treatment with erythromycin, the serum levels of quinidine should be monitored.

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Caution is advised when Erythromycin Stragen

is given to patients who are being treated with other

medicines that may prolong the QT interval (see 4.4).

Sildenafil

Data indicate that erythromycin inhibits the metabolism of sildenafil. An initial dose of 25 mg

sildenafil should be considered.

Benzodiazepines

Erythromycin has been reported to reduce the clearance of triazolam, alprazolam, clozapine and

related benzodiazepines and hence to increase the pharmacological effect of these benzodiazepines. In

healthy trial subjects previously treated with erythromycin, there is more rapid absorption of zopiclone

resulting in higher plasma concentrations and a more pronounced hypnotic effect compared to

controls.

Theophylline

Simultaneous medication with erythromycin and high doses of theophylline may cause theophylline

levels in plasma to increase, with potential theophylline toxicity, probably because of inhibited

metabolism. In the case of combination therapy, theophylline levels in plasma should be monitored to

ensure that no toxic concentrations develop (dosage reduction). The erythromycin concentration in

serum may decrease when oral erythromycin is administered at the same time as theophylline. This

reduction could result in sub-therapeutic erythromycin concentrations.

Warfarin

Erythromycin may inhibit the metabolism of warfarin, resulting in enhanced anticoagulant effects.

Fexofenadine

When erythromycin and fexofenadine are administered together, the plasma concentration of

fexofenadine increases two- to three-fold, probably because of increased absorption.

Statins

Erythromycin inhibits the metabolism of several HMG-CoA reductase inhibitors and produces

increased plasma concentrations of these medicines. Erythromycin also increases the plasma

concentration of simvastatin acid (5-fold). Rhabdomyolosis, which is associated with increased plasma

concentrations, has occurred in rare cases of treatment with clarithromycin together with lovastatin or

simvastatin. Erythromycin Stragen should not be used at the same time as simvastatin, atorvastatin and

lovastatin. Treatment with these medicines should be interrupted during treatment with Erythromycin

Stragen.

Ergot alkaloids (e.g. ergotamine and dihydroergotamine)

There are reported cases of clinical ergotism, characterised by vasospasm and ischaemia of the central

nervous system, because of increased serum levels of ergot alkaloids in the case of simultaneous

treatment with macrolide antibiotics. This combination is contra-indicated; see section 4.3.

Digoxin

Simultaneous use of erythromycin and digoxin may produce increased plasma concentrations of

digoxin. Monitoring of the serum levels should be considered when administering and withdrawing

erythromycin. It may be necessary to adjust the dose.

Calcium channel blockers

Hypotension, bradyarrhythmias and lactic acidosis have been observed in patients who were also

taking verapamil, a calcium channel blocker.

Tyrosine kinase inhibitors

Concomitant medication with tyrosine kinase inhibitors (e.g. Imatinib) carries an increased risk of

undesirable effects on the tyrosine kinase inhibitor by decreasing its metabolism.

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Effects of other medicines on the pharmacokinetics of erythromycin:

Erythromycin is metabolised by the enzyme CYP3A4. Strong inhibitors of this enzyme (e.g.

clarithromycin, itroconazole, ketoconazole) may therefore inhibit the metabolism of erythromycin,

resulting in increased plasma concentrations. Depending on the risk of increased QT, Erythromycin

Stragen should be used with care (see section 4.4).

Medicines that induce CYP3A4 (such as rifampicin, phenytoin, carbamazepine, phenobarbital, St

John’s wort) may induce the metabolism of erythromycin. This can result in sub-therapeutic levels of

erythromycin and reduced effect. The induction gradually decreases over two weeks after the end of

treatment with CYP3A4 inducers. Erythromycin Stragen should not be used during and for two weeks

after treatment with CYP3A4-inducers (see section 4.4).

Cimetidine may inhibit the metabolism of erythromycin, resulting in increased plasma concentrations.

When erythromycin and protease inhibitors are administered together, inhibition of erythromycin

metabolism has been observed.

4.6

Pregnancy and lactation

Pregnancy:

Erythromycin has been reported to cross the placental barrier in humans, but foetal plasma

levels are generally low. Epidemiological studies suggest an increased risk of cardiovascular

malformations after exposure to macrolide antibiotics during early pregnancy (based mainly on data

for erythromycin). Reproduction toxicological animal studies on erythromycin are insufficient, but in

studies of other macrolides that are potent hERG channel blockers like erythromycin, embryo death

and malformations have been produced (including cardiovascular defects and cleft palate).

Mechanistic studies show that substances which are potent blockers of the hERG channel cause

cardiovascular defects and embryo death by producing arrhythmia in the embryo. Erythromycin

should not be used by women who are pregnant or planning to become pregnant unless absolutely

necessary.

Breastfeeding:

Erythromycin is not recommended for nursing mothers unless the expected benefits

outweigh the potential risks. In lactating women, erythromycin is excreted into human breast milk and

can increase the risk for adverse effects in the infant. The benefits and risks of use during lactation

must be carefully considered.

4.

Effects on ability to drive and use machines

No effects observed.

4.8

Undesirable effects

The most common undesirable effect is phlebitis and pain at the infusion site, which is estimated to

occur in approx. 10% of patients.

Cardiac disorders

Common (≥1/100 to <1/10)

Not known (cannot be estimated from the

available data)

Arrhythmia.

QTc interval prolongation, torsades de pointes,

palpitations, heart rhythm perturbations including

ventricular tachyarrhythmias.

Ear and labyrinth disorders

Rare (≥1/10,000 to <1/1,000)

Reversible hearing loss (mainly in patients with

renal insufficiency or high doses).

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Not known (cannot be estimated from the

available data)

Deafness, tinnitus.

Gastrointestinal disorders

Common (≥1/100 to <1/10)

Not known (cannot be estimated from the

available data)

Stomach-ache, nausea, diarrhoea.

Discomfort in the upper abdomen, vomiting,

pancreatitis, anorexia, infantile hypertrophic

pyloric stenosis, pseudomembranous colitis (see

section 4.4).

Skin and subcutaneous tissue disorders

Common (≥1/100 to <1/10)

Uncommon (≥1/1,000 to <1/100)

Not known (cannot be estimated from the

available data)

Rash.

Urticaria.

Itching, exanthema, angioedema, Stevens-

Johnson syndrome, toxic epidermal necrolysis,

erythema multiforme, acute generalised

exanthematous pustulosis (AGEP).

General disorders and administration site

conditions

Common (≥1/100 to <1/10)

Phlebitis and pain at the infusion site.

Immune system disorders

Rare (≥1/10,000 to <1/1,000)

Not known (cannot be estimated from the

available data)

Anaphylaxis

Allergic reactions

Hepatobiliary disorders

Rare (≥1/10,000 to <1/1,000)

Not known (cannot be estimated from the

available data)

Elevated liver enzyme values, bilirubin increase,

intrahepatic cholestasis, hepatitis.

Cholestatic hepatitis, jaundice, hepatic

dysfunction, hepatomegaly, liver failure,

hepatocellular hepatitis (see section 4.4).

Blood and lymphatic system disorders

Not known (cannot be estimated from the

available data)

Eosinophilia

General disorders and administration site

conditions

Not known (cannot be estimated from the

available data)

Chest pain, fever, general discomfort.

Nervous system disorders

Not known (cannot

be estimated from the available data)

Confusion, cramps, dizziness.

Psychiatric disorders

Not known (cannot be estimated from the

available data)

Hallucinations

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Renal and urinary disorders

Not known (cannot be estimated from the

available data)

Interstitial nephritis

Vascular disorders

Not known (cannot be estimated from the

available data)

Hypotension

Local irritation at the infusion site may occur, but can be prevented to some extent by slow

administration.

Fungal infestation of the oral cavity and lower abdomen may occur.

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

listed in Appendix V.

4.9

Overdose

Toxicity:

Low acute toxicity. 3 g to a 3-year-old who got active charcoal and 3.5 g to a 7-year-old who

presented no symptoms.

Symptom:

Nausea, vomiting, diarrhoea. Reversible hearing loss, possible

hallucinations. Possible pancreatitis. Allergic reactions and liver damage may occur.

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Antibacterial substance for systemic use, ATC code: J01FA01.

Erythromycin Stragen solution for infusion contains erythromycin lactobionate. Erythromycin

lactobionate is a water-soluble salt of erythromycin suitable for intravenous injection. The effect is

mainly bacteriostatic and is produced by binding to the bacterial ribosomes, inhibiting their protein

synthesis.

Antibacterial spectrum

Sensitive

Streptococci and pneumococci

Staphylococcus aureus

coagulase-negative staphylococci

Arcanobacterium haemolyticum

Corynebacterium diphteriae

Moraxella catarrhalis

Bordetella pertussis

Legionella pneumophila

Campylobacter

Chlamydia trachomatis, pneumoniae

psittaci

Mycoplasma pneumoniae

Ureaplasma urealyticum

Clostridium perfringens

Intermediate

Haemophilus influenzae

parainfluenzae

Resistant

Enterococci

Pasteurella multocida

Gram-negative intestinal bacteria

Pseudomonas

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Clostridium difficile

Anaerobic gram-negative rods

Mycoplasma hominis

Resistance is found (1

10%) in beta-haemolytic streptococci, pneumococci and

Staphylococcus

aureus

and is common (>10%) in coagulase-negative staphylococci.

Cross-resistance occurs between all macrolides and azithromycin. Some cross-resistance between

macrolides and clindamycin.

Erythromycin resistance in streptococci and pneumococci is common in some parts of the rest of

Europe.

The resistance situation varies geographically and details of the local resistance conditions should be

obtained from a local microbiological laboratory.

5.2

Pharmacokinetic properties

Distribution

The serum concentrations attained vary according to the dose and rate of administration. As a guide,

we may say that after injection of 500 mg over 30 minutes, a serum concentration of

10 micrograms/ml or more may be expected. Erythromycin is distributed to a great extent to other

tissues. There are varying figures for plasma protein binding, but it is usually put at 60

80%.

Particularly high concentrations are obtained, depending on the excretion conditions, in the liver and

bile. On the other hand, not much erythromycin passes through the blood-brain barrier. Erythromycin

crosses the placental barrier, the transplacental transfers has been estimated to approximately 10%.

Elimination

With normal hepatic function, erythromycin is concentrated in the liver and excreted mainly via bile

and faeces, which means that the anaerobic intestinal flora may be affected. Erythromycin is also

partially metabolised by CYP3A4 to its N-demethylated metabolite. From 12% to 15% of

intravenously administered erythromycin is excreted in active form in the urine.

The elimination half-life in patients with normal renal function is 1.5 to 3.0 hours. In patients with

severe renal impairment the half-life may be prolonged to between 4 and 7 hours.

5.3

Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety

pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential.

Reproduction toxicological animal studies on erythromycin are insufficient. In studies of other

macrolides that are potent hERG channel blockers like erythromycin, embryo death and

malformations have been produced (including cardiovascular defects and cleft palate). Mechanistic

studies show that substances which are potent blockers of the hERG channel cause cardiovascular

defects and embryo death by producing arrhythmia in the embryo.

6.

PHARMACEUTICAL PROPERTIES

6.1

List of excipients

None.

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6.2

Incompatibilities

In the absence of compatibility studies, Erythromycin Stragen must not be mixed with other medicinal

products except those mentioned in section 6.6.

The stability of erythromycin is affected by the pH of the infusion solution. It should not be added to

solutions with a pH under 5, but should then be injected, e.g. into a side branch at the infusion site.

6.3

Shelf life

Unopened

: 3 years.

After reconstitution

After reconstitution, chemical and physical in-use stability in water for injection has been

demonstrated for 24 hours when stored at room temperature and for 14 days when stored in a

refrigerator at 2-8° C.

After reconstitution and dilution:

After reconstitution and dilution, chemical and physical in-use stability has been demonstrated for 24

hours at room temperature when the solution is diluted in 0.9% (9 mg/ml) sodium chloride solution for

injection or Glucose 5% and for 12 hours at room temperature when the solution is diluted in

Hartman’s solution.

From a microbiological point of view, once opened, the product should be used immediately.

If not used immediately, in-use storage times and conditions prior to use are the responsibility of the

user and would normally not be longer than 24 hours at 2-8°C, unless reconstitution has taken place in

controlled and validated aseptic conditions

6.4

Special precautions for storage

This medicinal product does not require any special storage conditions.

For storage conditions of the reconstituted/diluted medicinal product, see section 6.3.

6.5

Nature and contents of container

Glass vial type I with rubber closure type I.

1 x 1 g powder for solution for infusion

10 x 1 g powder for solution for infusion

Not all pack sizes may be marketed.

6.6

Special precautions for disposal and other handling

Preparation of 1 g of powder for solution for infusion

1.

Preparation of base

solution:

A 5% base solution (50 mg erythromycin/ml) is prepared by dissolving the powder in the vial (1 g

erythromycin) in 20 ml water for solution for infusion. The base solution must be diluted further

before administration.

2.

Dilution of base

solution

a) Solution for infusion for intermittent infusion:

20 ml base solution is further diluted by adding to 200

250 ml of a suitable solution for infusion (see

below).

b) Solution for infusion for continuous infusion:

20 ml base solution is further diluted by adding to 500 ml or 1000 ml of a suitable solution for infusion

(see below).

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Solution for infusion suitable for dilution of base solution:

- 0.9% (9 mg/ml) sodium chloride solution for injection

-Glucose 5%

-Hartman’s solution.

Solutions containing glucose must first have sodium bicarbonate added as a buffer to assure neutrality.

Ensure that the finished solution for infusion is free from particles before administration.

7.

MARKETING AUTHORISATION HOLDER

<[To be completed nationally]>

8.

MARKETING AUTHORISATION NUMBER(S)

<[To be completed nationally]>

9.

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

<[To be completed nationally]>

10.

DATE OF REVISION OF THE TEXT

2018-03-12

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