Package Leaflet: Information for the User

Eritromicina Panpharma 1 g, powder for solution for infusion EFG

Erythromycin (in the form of erythromycin lactobionate)

Read this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or nurse.
• This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or nurse, even if they are not listed in this leaflet. See section 4.

The name of this medicine is “Eritromicina Panpharma 1 g, powder for solution for infusion EFG”, but in this leaflet we will refer to it as « Eritromicina Panpharma ».

Eritromicina Panpharma is an antibiotic that contains erythromycin (in the form of erythromycin lactobionate), which belongs to the group of antibiotics known as "macrolides," and acts by preventing the growth and multiplication of bacteria.

Eritromicina Panpharma is indicated for the treatment of severe bacterial infections in adult and pediatric patients, when oral administration of erythromycin is not possible or sufficient, or in patients who require higher concentrations of erythromycin due to the severity of the infection, or when patients are allergic or hypersensitive to beta-lactam antibiotics (a class of antibiotics) or when these antibiotics are not suitable for other reasons.

When your doctor has controlled the acute phase of the infection, they will replace intravenous erythromycin administration with an oral pharmaceutical form.

Eritromicina Panpharma is indicated for the treatment of infections, such as:

• Respiratory tract infections: pneumonia, diphtheria.
• Ear infections.
• Eye infections (conjunctivitis).
• Skin and soft tissue infections (such as muscles, blood vessels, tendons, fat).
• Gastrointestinal infections.
• Urinary and reproductive organ infections.
• Lymphogranuloma venereum (a sexually transmitted disease).

No use Eritromicina Panpharma:

• if you are allergic to erythromycin or any of the other ingredients in this medication (listed in section 6).
• if you are allergic (or hypersensitive) to other macrolide antibiotics.
• if you are taking any of the following medications:
• • Astemizol, terfenadine (medications used for the treatment of allergic reactions).
  • Disopiramida (an antiarrhythmic used in the treatment of ventricular tachycardia).
  • Cisaprida (used to treat gastroesophageal reflux disease).
  • Pimocida (used in the treatment of psychiatric disorders).
  • Ergotamina or dihidroergotamina (for migraine).
  • Lovastatina, simvastatina, and atorvastatina (medications to lower blood cholesterol).
  • Class Ia and III antiarrhythmics (used to treat ventricular arrhythmias, to prevent paroxysmal atrial fibrillation, to treat Wolff-Parkinson-White syndrome, ventricular tachycardia, atrial fibrillation, and atrial flutter).
  • Neuroleptics (used to treat psychosis [including delusions, hallucinations, or thought disorders]).
  • Tricyclic and tetracyclic antidepressants (used in the treatment of depression).
  • Fluoroquinolones (antibiotics used to treat certain infections).
  • Trioxide of arsenic (used to treat cancer).
  • Metadona (used to treat opioid dependence, such as heroin addiction).
  • Budipina (an antiparkinsonian).
  • Antifungals and antimalarials.
• if you have liver problems. This is because erythromycin is primarily excreted through the liver (see section 3 "How to use Eritromicina Panpharma").
• if you have any heart problems.
• if you have any electrolyte imbalance (for example: potassium or magnesium deficiency).

Advertencias and precautions

Consult your doctor, pharmacist, or nurse before starting to use Eritromicina Panpharma:

• If you have any heart problems, there may be problems with your heartbeat, such as a prolongation of the "QT interval" or "ventricular arrhythmia," so you should consult your doctor, pharmacist, or nurse before using Eritromicina Panpharma.
• Severe allergic reactions may occur. Do not use Eritromicina Panpharma if you are allergic or hypersensitive to erythromycin or other medications in the macrolide antibiotic group. Consult your doctor, pharmacist, or nurse before using Eritromicina Panpharma.
• If you have myasthenia gravis, erythromycin may worsen symptoms, which could lead to severe respiratory problems.
• If you are elderly, as you have a higher risk of developing kidney disease. Your doctor will adjust the dose and take into account your renal function (see section 3 "How to use Eritromicina Panpharma").

Generally, it is not recommended to use erythromycin in combination with:

• Alfuzosina (used to treat benign prostatic hyperplasia).
• Buspirona (used in the treatment of generalized anxiety disorders).
• Ciclosporina and tacrolimús (used in organ transplantation to prevent rejection).
• Colchicina (used in the treatment of gout).
• Ebastina (an antihistamine).
• Tolterodina (used in the treatment of urinary incontinence).
• Triazolam (used as a sedative to treat severe insomnia).

This medication will be administered continuously or slowly to avoid pain.

Neonates and children

Contact your doctor immediately if your child vomits (explosive non-bilious vomiting) or has problems eating during treatment with this medication. Your doctor will decide on your child's dose (see section 3 "How to use Eritromicina Panpharma").

Use of Eritromicina Panpharma with other medications

If you need to undergo a urine test, inform your doctor that you are using erythromycin, as it may alter the results of some tests.

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

It is not recommended to administer erythromycin simultaneously with:

• Warfarina and derivatives (anticoagulants).
• Zopiclona (to induce sleep).
• Teofilina (to facilitate breathing).
• Sildenafilo (used in the treatment of erectile dysfunction and pulmonary hypertension).
• Some cytostatics and vinblastina (used to treat cancer).
• Digoxina (used in the treatment of heart problems).
• Carbamacepina (used in the treatment of epilepsy and neuropathic pain).
• Alfentanilo (an anesthetic).
• Bromocriptina (used in Parkinson's disease and hyperprolactinemia).
• Cilostazol (used in the treatment of intermittent claudication).
• Metilprednisolona (a corticosteroid used for its anti-inflammatory effects).
• Midazolam (used to induce anesthesia or treat moderate insomnia).
• Omeprazol (used to reduce gastric acid secretion).
• Valproato (an anticonvulsant and mood stabilizer).
• Cimetidina (inhibits acid production in the stomach).
• Rifampicina (an antibiotic).
• Fenitoína (used as an anticonvulsant).
• Fenobarbital (an anticonvulsant).
• Benzodiacepinas (anxiolytics, anticonvulsants, muscle relaxants, sedatives, etc.).
• Fexofenadina (used to treat allergic reactions).
• Hipérico (Hypericum perforatum) (a medicinal herb used to treat moderate depression).

Pregnancy and lactation

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor before using this medication.

Erythromycin has been reported to cross the placenta and reach the fetus.

Erythromycin is excreted in breast milk.

It should be decided whether to interrupt breastfeeding or interrupt treatment after considering the benefits of breastfeeding for the child and the benefits of treatment for the mother.

Driving and operating machinery

The appearance of adverse effects of Eritromicina Panpharma may affect your ability to drive and operate machinery.

Experience to date indicates that the effect of erythromycin on your ability to concentrate and react is insignificant.

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again. This medication will always be administered by a doctor or healthcare professional intravenously (in a vein) for 60 minutes.

Use in adults and in children over 12 years old or weighing over 40 kg

The recommended dose is 1-2 g per day, which is equivalent to 25 mg/kg/day in divided doses (usually 3-4 doses).

This dose may be increased to 4 g per day in the case of a very severe infection.

It is essential to complete the full treatment. Do not stop receiving your infusion treatment before time, even if you feel better.

Use in children between 1 month and 12 years old or weighing ≤ 40 kg

The recommended dose is 15-20 mg/kg of body weight, divided into 3-4 doses.

Your doctor will calculate the exact dose your child should receive, based on their body weight.

Newborns at term (from birth to 1 month of age)

The recommended dose is 10-15 mg/kg, divided into 3 doses.

Your doctor will calculate the exact dose your child should receive, based on their body weight.

Use in patients with severe kidney disease

Your doctor will calculate the exact dose, based on their renal function.

Use in elderly patients

Your doctor will carefully decide your dose and take into account your renal and hepatic function, as you have a higher risk of developing kidney disease.

If you use more Eritromicina Panpharma than you should

If you consider that you or your child have been administered a higher amount of this medication, contact your doctor. Symptoms of overdose include ototoxicity (ear damage), hearing loss, intense nausea, vomiting, and diarrhea.

If you forgot to take Eritromicina Panpharma

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone 915 620 420, indicating the medication and the amount ingested.

If you believe you have missed a dose of this medication, contact your doctor or any other healthcare professional immediately.

If you interrupt the treatment with Eritromicina Panpharma

Do not stop using this medication until your doctor tells you to.

If you have any other doubts about the use of this medication, ask your doctor, pharmacist, or nurse.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

If you experience an allergic reaction, it may appear as a rash and swelling of certain parts of the body, such as the face and neck, accompanied by difficulty breathing.In this case, you must stop using this medicine and seek immediate attention at the emergency service.

Consult a doctor as soon as possible if you experience a severe skin reaction: a red, scaly rash with bumps under the skin and blisters (pustular exanthema). The frequency of this side effect is considered unknown (cannot be estimated from available data).

The most common side effects are anorexia (loss of appetite), nausea, vomiting, abdominal pain, nausea, flatulence, discomfort, cramps, soft stools, or diarrhea.

The following side effects have been reported:

Rare(may affect up to 1 in 100 people)

• Fungal infections (candidiasis) of the mouth, accompanied by white patches
• Vaginal inflammation
• Itching of the vulva in women
• Allergic reactions
• Widespread skin rash (urticaria)
• Itchy skin
• Redness of the skin, accompanied by increased blood flow (hyperemia)
• Alteration of liver and bile duct function, detected by blood tests
• Pain or irritation at the injection site
• Swelling and redness of a vein, which will be extremely sensitive to the touch

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

• Swelling of certain parts of the body, such as the face and neck (allergic edema or anaphylaxis)
• Loss of appetite (anorexia)
• Upper abdominal pain radiating to the back, accompanied by nausea, vomiting, diarrhea, and loss of appetite (pancreatitis)
• Itching accompanied by yellow skin discoloration (jaundice), pale stools (cholestasis and cholestatic jaundice)
• Swollen joints
• Fever
• Abdominal pain
• Rashes
• Severe inflammation of the colon, accompanied by intense diarrhea

Very rare(may affect up to 1 in 10,000 people)

• Unmasking or worsening of a rare disease, associated with muscle weakness (myasthenia gravis)
• Tinnitus in the ears (tinnitus) and hearing loss, usually temporary
• Inability of the liver to perform its normal function
• Inability of the kidneys to perform their normal function
• Severe skin reactions (Stevens-Johnson syndrome and erythema multiforme)
• Peeling of the skin (toxic epidermal necrolysis)

Unknown frequency(cannot be estimated from available data):

• Chest pain, general discomfort
• Irregular heartbeat, strong or rapid heartbeats
• Thoracic discomfort, difficulty breathing, abnormal breathing, rapid and superficial breathing, chest pain in the upper back
• Shortness of breath (including asthma-like symptoms)
• Visual disturbances, including double vision and blurred vision
• Psychological disturbances (such as mood changes and altered sense of reality)
• Confusion, hallucinations
• Dizziness, drowsiness, vertigo
• Seizures, convulsions
• Low blood pressure (hypotension)
• Blood disorders affecting blood cells, usually detected by blood tests
• Headaches

Other side effects in newborns and children

Vomiting (non-bilious explosive vomiting) or eating problems and loss of appetite (infantile hypertrophic pyloric stenosis)

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Usewww.notificaram.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the vial and the box after CAD. The expiration date is the last day of the month indicated.

After reconstitution:

The diluted solutions must be used immediately.

Do not freeze the reconstituted solution.

Reconstituted solution: Physical-chemical stability has been demonstrated for use during 24 hours in the refrigerator (2-8°C).

Diluted solution: Physical-chemical stability has been demonstrated for use during 24 hours in the refrigerator (2-8°C).

From a microbiological point of view, the product must be used immediately.

If not used immediately, the time and conservation conditions prior to use are the responsibility of the user and should not exceed 24 hours in the refrigerator, unless reconstitution or dilution were performed under controlled and validated sterile conditions.

Medications should not be disposed of through drains or in the trash. Dispose of the containers and medications you no longer need at the SIGRE point of the pharmacy or at any other medication waste collection system. If in doubt, ask your pharmacist how to dispose of the containers and medications you no longer need. In this way, you will help protect the environment.

Composition of Erythromycin Panpharma

• The active ingredient is erythromycin lactobionate.

Each vial contains 1 gram of erythromycin.

This medicine does not contain any other component.

Appearance of the product and contents of the package

Before reconstitution, Erythromycin Panpharma is a hygroscopic powder for solution for infusion, of color from white to light yellow, contained in a glass vial. After reconstitution, the solution is transparent and colorless.

Erythromycin Panpharma is marketed in packages of 1, 10 or 25 glass vials. Some package sizes may only be marketed.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

PANPHARMA

Z.I. DU CLAIRAY

35133 LUITRE

FRANCE

Responsible for manufacturing:

PANPHARMA

10 RUE DU CHÊNOT

PARC D’ACTIVITÉ DU CHÊNOT

56380 BEIGNON

FRANCE

or

PANPHARMA

Z.I du Clairay - Fougeres - F-35133 – France

For further information about this medicine, please contact the local representative of the marketing authorization holder:

Pharmavic Ibérica S.L.,

C/Compositor Lehmberg Ruiz, 6

Edificio Ibiza, Office 7

29007 Málaga, Spain

This medicine is authorized in the member states of the European Economic Area with the following names:

Last review date of this leaflet: July 2020

For detailed and updated information about this medicine, please visit the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

This information is intended solely for healthcare professionals:

If you want more information about resistance data, please consult the erythromycin or Erythromycin Panpharma technical data sheet.

Dosage

Use in adults and children over 12 years or weighing over 40 kg

The recommended dose is 1-2 g per day, equivalent to 25 mg/kg/day in divided doses (usually 3-4 doses).

Severe infections

In the case ofsevere infections, the dosage regimen may be increased to 4 g per day, equivalent to 50 mg/kg/day.

The maximum daily dose is 4 g.

Use in children under 12 years or weighing ≤40 kg

1 month to 12 years: The daily dose for infants and children up to 12 years of age to treat most infections is 15-20 mg of erythromycin per kg of body weight, divided into 3-4 doses. This dose may be doubled depending on the indication.

Newborns (from birth to 1 month of age)

10-15 mg/kg/day, divided into 3 doses.

Renal or hepatic impairment

Patients with liver impairment:

When liver function is normal, erythromycin is concentrated in the liver and excreted in the bile. Although the effect of liver impairment on erythromycin excretion and its half-life in this population of patients is unknown, caution should be exercised when administering the antibiotic in these cases, especially in patients with acute liver failure and receiving high doses of erythromycin. In this case, serum concentrations should be monitored and the dose reduced.

Patients with renal impairment:

The low percentage of renal excretion would indicate that no modification of the dosage regimen is necessary in patients with mild to moderate renal impairment (creatinine clearance greater than 10 ml/min).

However, cases of toxicity have been reported in patients with moderate to severe renal impairment, and in these cases, dose adjustment is recommended.

• The administration of doses ≥4 g/day may increase the risk of erythromycin-induced hearing loss in elderly patients, especially in those with renal or hepatic impairment.
• In the case of moderate to severe renal impairment (creatinine serum levels of 2.0 mg/dl, renal failure accompanied by anuria), the maximum daily dose for adolescents over 14 years and adults (with a weight of over 50 kg) is 2 g of erythromycin per day.
• In the case of patients with severe renal impairment (creatinine clearance less than 10 ml/min), the erythromycin dose should be reduced to 50-75% of the usual dose, with administration according to the usual treatment regimen. The maximum daily dose should not exceed 2 g.

Erythromycin is not eliminated by hemodialysis or peritoneal dialysis. Therefore, in patients who undergo dialysis regularly, no additional dose is recommended.

Elderly population

The adult dose should be administered with caution. Elderly patients, particularly those with impaired renal or hepatic function, may be at higher risk of developing erythromycin-induced hearing loss if they receive doses of erythromycin of 4 g/day or higher.

Administration

Precautions to be taken before handling or administering the medicine

To consult the reconstitution instructions of the medicine before administration, see section 6.6.

Erythromycin can be administered by continuous or intermittent intravenous infusion.

The infusion should be administered over a period of 60 minutes, as a rapid infusion may cause local irritation and prolongation of the QT interval, arrhythmias, or hypotension. In patients with risk factors or a history of arrhythmias, the infusion should be administered over a longer period.

To prepare intravenous solutions for intermittent infusion, a minimum of 200 ml of diluent should be used to minimize the appearance of venous irritation.

The concentration of erythromycin should not exceed 5 mg per milliliter, and a concentration of erythromycin of 1 mg/ml (solution 0.1%) is recommended.

Erythromycin should only be administered intravenously. Intrarterial injection is absolutely contraindicated, as it may cause angiospasm accompanied by ischemia. Intramuscular administration and intravenous bolus injection are also contraindicated.

Intravenous treatment should be replaced by oral administration after 2-7 days. Once symptoms have disappeared, treatment with erythromycin should be continued for another 2-3 days to be fully effective.

Warnings and precautions

Newborns and children

If your child vomits or appears irritable related to meals, contact your doctor immediately, as there is a risk of hypertrophic pyloric stenosis (HPS), which causes severe non-bilious explosive vomiting. If the potential benefits of this medicine are not greater than the potential risks, it should not be administered to children.

Reconstitution

Each vial is intended for single use.

Two steps are required: reconstitutionanddilution.

1. Reconstitution:do not use a 0.9% sodium chloride solution in this step.
   1. To ensure proper dissolution, gently shake the vial to eliminate the powder content before reconstitution.
   2. Prepare an initial solution, corresponding to 50mg/ml of a base of erythromycin, by adding 20ml of injectable water to the contents of the Erythromycin Panpharma vial. When you add the solvent, ensure that it comes into contact with the entire wall of the vial (e.g., by holding the vial horizontally).
   3. Shake vigorously until it is completely dissolved. The dissolution may be difficult to obtain and takes a few minutes.

The reconstituted solution can be stored in the refrigerator for 24hours.

1. Dilution

Only a 0.9% sodium chloride solution or a 5% glucose solution should be used.

- In the case of intermittent infusion: the solution is prepared by mixing the contents of the reconstituted Erythromycin Panpharma vial (20ml) with 200ml or 500ml of one of the dilution solutions, obtaining a final concentration of the diluted solution of 5mg/ml or 2mg/ml, respectively.

- In the case of continuous infusion: the solution is prepared by mixing the contents of the reconstituted Erythromycin Panpharma vial (20ml) with 500ml or 1000ml of one of the dilution solutions, obtaining a final concentration of the diluted solution of 2mg/ml or 1mg/ml, respectively.

The diluted solution can be stored in the refrigerator for 24 hours. The diluted solution should be administered without adding any other substance.

In the case of pediatric patients, the amount of the initial solution to be diluted and the infusion volume should be adjusted according to the chosen dosage regimen based on the child's weight.

After reconstitution

The diluted solutions should be used immediately.

The elimination of unused medication and all materials that have come into contact with it should be carried out in accordance with local regulations.

Incompatibilities

This medicine should not be mixed with other medications, except those used in reconstitution.

The erythromycin lactobionate solution should not be mixed with β-lactam antibiotics, aminoglycosides, tetracyclines, chloramphenicol, colistin, aminophylline, barbiturates, phenytoin, heparin, phenothiazine, riboflavin (vitamin B2), vitamin B6, and vitamin C. Therefore, intravenous administration of erythromycin should not be mixed with the listed medications in an intravenous infusion solution.

The addition of other solutions that alter the pH interval of 6-8 reduces the stability of erythromycin lactobionate.

Warning:Do not use sodium chloride solutions or other solutions containing inorganic salts to prepare the initial solution (see section «Reconstitution»), as they may cause precipitation.