AZACTAM 1g POWDER FOR INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Azactam 1g Powder for Solution for Injection

Aztreonam

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 pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

1. What is Azactam and what is it used for
2. What you need to know before you use Azactam
3. How to use Azactam
4. Possible side effects
5. Storage of Azactam

1. Contents of the pack and other information

1. What is Azactam and what is it used for

Azactam is an antibiotic belonging to the monobactam group.

Antibiotics are used to treat bacterial infections and are not effective against viral infections such as the flu or the common cold.

It is essential that you follow the instructions regarding dosage, administration interval, and treatment duration as indicated by your doctor.

Do not store or reuse this medication. If you have any leftover antibiotic after completing treatment, return it to the pharmacy for proper disposal. Do not throw away medications via wastewater or trash.

It is indicated for the treatment of urinary tract infections, lower respiratory tract infections, skin and soft tissue infections, bone and joint infections, abdominal infections, gynecological infections, some sexually transmitted infections (gonorrhea), and sepsis.

2. What you need to know before you use Azactam

Do not use Azactam

If you are allergic (hypersensitive) to aztreonam or any of the other components of this medication (listed in section 6).

Warnings and precautions

If you are allergic to penicillins, cephalosporins, and/or carbapenems, you should only use Azactam with extreme caution, in case the expected benefit justifies the risk of a potential severe allergic reaction. In case you notice the appearance of any allergic reaction, you must discontinue treatment with Azactam and consult your doctor, as certain measures may be necessary.

You must inform your doctor if you have kidney or liver function impairment, as you will need adequate monitoring during treatment. If Azactam is administered to elderly patients, who often have renal impairment, your doctor will perform the necessary studies to determine the appropriate dose.

You must inform your doctor if you experience significant changes in your blood or skin during treatment with Azactam, as it may be necessary to interrupt treatment.

In some rare cases, seizures have been reported during treatment with aztreonam, which usually reverse during treatment. If you experience seizures during treatment with aztreonam, consult your doctor.

If you experience diarrhea during treatment or up to two months after, you should also inform your doctor, who will take the necessary measures.

If you are taking oral anticoagulants, inform your doctor, as some adjustments in the dose of oral anticoagulants may be necessary. Some cases of increased activity of oral anticoagulants have been reported in patients treated with antibiotics. In relation to this, factors such as the presence of inflammation or severe infection, age, and the patient's general condition seem to be risk factors.

If you are using an aminoglycoside antibiotic during treatment with this medication, your doctor will monitor your kidney function due to the potential toxicity of these antibiotics to the kidneys and ears.

The use of beta-lactam antibiotics, such as this medication, may lead to a risk of encephalopathy that can cause confusion, loss of consciousness, epilepsy, and movement disorders, especially in patients with renal insufficiency and in case of overdose (see sections 3 and 4).

Treatment with Azactam may interfere with some analytical determinations (increase in transaminases in blood and false positives for glucose in urine), as well as obtaining positive results in a direct or indirect Coombs test (blood test used to detect some types of diseases based on the detection of antibody presence).

Children and adolescents

The efficacy and safety of Azactam have not been established in newborns under 1 week of age.

Other medications and Azactam

Use of Azactam with other medications

Tell your doctor or pharmacist if you are using, have recently used, or may need to use any other medication.

Especially, you must inform your doctor if you are being treated with other antibiotics(used to treat infections) or oral anticoagulants.

Your doctor should perform adequate monitoring when administering anticoagulants concomitantly. Adjustments in the dose of oral anticoagulants may be necessary to maintain the appropriate coagulation level.

If you use an aminoglycoside antibiotic during treatment with Azactam, your doctor will monitor your kidney function due to the potential toxicity of these antibiotics to the kidneys and ears.

Some antibiotics (such as cefoxitin and imipenem) counteract the effect of many beta-lactam antibiotics, including aztreonam, in the treatment of some bacteria.

Tell your doctor if you are taking probenecid (used to treat gout) or furosemide (a diuretic used to treat hypertension) at the same time, as concomitant administration with these medications may result in increased aztreonam serum levels.

Pregnancy, breastfeeding, and fertility

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

Azactam should not be administered during pregnancy, unless the expected benefit justifies the potential risk.

Aztreonam is excreted in very small amounts in human milk; consequently, temporary interruption of breastfeeding during treatment with this medication should be considered.

Driving and using machines

Do not drive or operate tools or machines because this medication can have a significant influence on the ability to drive vehicles and use machinery, particularly due to the possible appearance of encephalopathies (which can cause confusion, seizures, or abnormal movements) (see sections 3 - If you use more Azactam than you should and 4).

Azactam contains arginine.

Studies conducted in low-birth-weight infants have shown that arginine administered with this medication can lead to increases in insulin, indirect bilirubin, and arginine in serum.

The consequences of this component in newborns treated with aztreonam have not been established with certainty. Therefore, the use in newborns should be carefully evaluated.

3. How to use Azactam

Follow your doctor's instructions for administration of this medication exactly. If in doubt, consult your doctor or pharmacist again.

Azactam is administered by intramuscular injection and by intravenous route. For preparation instructions, see section 6, below.

Intravenous administration is recommended in patients who require single doses greater than 1 g or in those who have septicemia, localized parenchymal abscesses (e.g., intra-abdominal abscesses), peritonitis, and other severe or life-threatening systemic infections. Due to the severe nature of infections caused by Pseudomonas aeruginosa, in systemic infections produced by this microorganism, a dose of 2 g every 6 or 8 hours is recommended, at least at the start of treatment.

Your doctor will indicate the duration of your treatment. Do not discontinue treatment without consulting your doctor first.

Your doctor will determine the appropriate dose and frequency of Azactam based on the severity of the infection you are suffering from.

In adults, the usual dosage guidelines are:

• The maximum recommended dose in adults is 8 g per day.

A single dose of 1 g administered intramuscularly is effective in the treatment of uncomplicated acute gonorrhea and uncomplicated acute cystitis.

If you have renal insufficiency or are an elderly patient, your doctor will adjust the dose based on the creatinine clearance value.

In patients with transient or persistent renal insufficiency, after a normal initial dose, the maintenance dose of Azactam should be reduced by half in patients with an estimated creatinine clearance between 10 and 30 ml/min/1.73 m2.

In patients with severe renal insufficiency, with creatinine clearance values less than 10 ml/min/1.73 m2 (e.g., patients undergoing hemodialysis), normal initial doses should be given. Maintenance doses should be one-fourth of the initial dose, administered at fixed intervals of 6, 8, or 12 hours. In severe or life-threatening infections, in addition to the maintenance doses indicated, one-eighth of the initial dose should be given after each hemodialysis session.

If you have chronic liver disease with cirrhosis, your doctor may recommend a dose reduction of 20-25%, especially in cases of alcoholic cirrhosis and when renal function is also impaired.

Use in children

In children, the usual dosage is 30 mg/kg every 6 to 8 hours in patients over 1 week of age. To treat severe infections in patients 2 years of age or older, a dose of 50 mg/kg every 6 to 8 hours is recommended. The recommended dose for all pediatric patients in the treatment of infections caused by P. aeruginosais 50 mg/kg every 6 to 8 hours. The maximum daily dose should not exceed the maximum recommended dose for adults.

If you think the action of Azactam is too strong or too weak, tell your doctor or pharmacist.

If you use more Azactam than you should

In case of receiving more doses of Azactam than prescribed, and although it is unlikely that you will suffer from severe poisoning, go to the doctor as soon as possible or contact the Emergency Service of the nearest Hospital. If necessary, aztreonam can be eliminated from the serum by hemodialysis and/or peritoneal dialysis.

Overdose of this medication can cause encephalopathy, which can lead to confusion, loss of consciousness, epilepsy, and movement disorders.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

If you forget to use Azactam

Do not administer a double dose to make up for forgotten doses.

Consult your doctor. The doctor will determine the actions to be taken.

If you have any further questions about the use of this product, ask your doctor or pharmacist.

4. Possible side effects

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

Side effects are classified according to their frequency of occurrence as: very common (affect more than 1 in 10 people), common (may affect up to 1 in 10 people), uncommon (may affect up to 1 in 100 people), rare (may affect up to 1 in 1,000 people), very rare (may affect up to 1 in 10,000 people), and frequency not known (cannot be estimated from the available data).

Uncommon: increased creatinine in blood.

Rare: vaginal infection, vaginal candidiasis (fungal infection), increased or decreased platelet and white blood cell count, decreased red blood cell count, increased blood coagulation time, positive Coombs test, seizures, paresthesia (tingling), dizziness, headache, confusion, insomnia, double vision, vertigo, ringing in the ears, decreased blood pressure, hemorrhage, dyspnea (difficulty breathing), sneezing, nasal congestion, wheezing, gastrointestinal hemorrhage, pseudomembranous colitis (inflammation of the colon with diarrhea), bad breath, hepatitis (inflammation of the liver), jaundice (yellowing of the skin and mucous membranes), muscle pain, breast tenderness, fever, malaise, fatigue, chest pain, changes in the electrocardiogram.

Frequency not known: anaphylactic reactions (severe allergic reactions), dysgeusia (alteration of taste), encephalopathy (which can cause confusion, loss of consciousness, epilepsy, and movement disorders), phlebitis (inflammation of the veins), thrombophlebitis (formation of blood clots), hot flashes, bronchospasm (sudden difficulty breathing), abdominal pain, mouth sores, nausea, vomiting, diarrhea, increased liver enzymes, and increased alkaline phosphatase (analytical alterations indicating liver damage), toxic epidermal necrolysis (appearance of blisters and skin peeling), angioedema (allergic reaction), erythema multiforme (redness in patches or diffuse redness of the skin), skin infection and peeling, hyperhidrosis (excessive sweating), petechiae (spots on the skin), purpura (brown spots on the skin), urticaria (skin lesion with itching), rash, pruritus (itching), discomfort at the injection site.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible side effects not listed in this leaflet. You can also report them directly through the Spanish Medicines Monitoring System: www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medication.

5. Storage of Azactam

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

Before opening the vial: Store in the original packaging. Do not store above 25 ºC.

Do not use this medication after the expiration date stated on the packaging.

After the first opening/reconstitution with the corresponding diluent, the solution must be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user.

Medicines should not be disposed of via wastewater or trash. Place the packaging and any unused medications in the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and any unused medications. This will help protect the environment.

6. Container Content and Additional Information

Azactam Composition

• The active ingredient is aztreonam. Each vial of powder contains 1g of aztreonam.
• The other component (excipient) of the powder vial is arginine.

Product Appearance and Container Content

1 Glass vial, Type III, with a capacity of 15 ml containing the active ingredient and excipient, with a 20 mm gray chlorobutyl rubber stopper and sealed with a seal.

Additional Information:Aztreonam is not compatible with sodium nafcillin, cefradine, and metronidazole

Marketing Authorization Holder and Manufacturer

MARKETING AUTHORIZATION HOLDER

Galenicum Derma, S.L.U.

N-1 Highway, Km 36

285750 San Agustín del Guadalix (Madrid)

Spain

MANUFACTURER

CATALENT ANAGNI S.R.L.

Loc.Fontana del Ceraso snc

Strada Provinciale 12 Casilina N. 41

03012 ANAGNI (FR)

Italy

Swords Laboratories Unlimited Company T/A Bristol-Myers

Squibb Pharmaceutical Operations,

External Manufacturing Plaza 254

Blanchardstown Corporate Park 2,

Dublin 15, D15 T867,

Ireland

Date of the Last Revision of the Prospectus: October 2021

Other Sources of Information

Detailed information about this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.

This information is intended only for healthcare professionals

Once the vial is opened, the product must be used immediately. The vials must be visually inspected before administering their contents to detect the presence of particles or discoloration.

Depending on the concentration of aztreonam and the solvent used, the resulting solution will be a colorless or pale yellowish solution, which may develop a slightly pink tint with rest (without altering the potency).

Each gram of reconstituted Azactam with 3 ml of the suitable diluent (see preparation of solutions and diluents accepted for each administration route, as indicated below) provides 1 gram of Azactam in a total volume of approximately 4 ml.

The pH of the solutions varies between 4.5 and 7.5 depending on the type and amount of solvent used.

Intramuscular Administration

The content of a vial (1 g of aztreonam) of Azactam must be reconstituted with at least 3 ml of one of the following solvents:

Water for injectable preparations

Water for injectable preparations (bacteriostatic with benzyl alcohol or methyl-propylparabens)

Sodium chloride 0.9%

Sodium chloride 0.9% (bacteriostatic with benzyl alcohol).

Solvents containing benzyl alcohol are not suitable for use in newborns.

After adding the diluent aseptically to the vial, the content must be shaken immediately and vigorously until a completely transparent solution is obtained. The solution is for single use. Discard the remaining solution.

The dose should be administered by deep intramuscular injection into one of the large muscle masses (such as the upper outer quadrant of the gluteal region or the lateral part of the thigh). Aztreonam is well tolerated and should not be mixed with any local anesthetic.

Intravenous Administration

Intravenous Bolus Injection:

The selected dose of Azactam must be prepared with 6 ml to 10 ml of water for injectable preparations as a diluent. After adding the diluent aseptically to the vial, the content must be shaken immediately and vigorously until a completely transparent solution is obtained. The solution is for single use. Discard the remaining solution.

The solution should be injected slowly over a period of 3 to 5 minutes directly into the vein or through a suitable administration equipment.

Infusion:

Each gram of aztreonam should be dissolved initially in a minimum of 3 ml of water for injectable preparations as a diluent. After adding the diluent aseptically to the vial, the content must be shaken immediately and vigorously until a completely transparent solution is obtained. Subsequent dilutions to achieve a final concentration that does not exceed 2% p/v, i.e., at least 50 ml of solution per gram of aztreonam, can be obtained with one of the following intravenous infusion solutions:

Sodium chloride 0.9% for injectable preparations

Ringer's solution for injectable preparations

Lactated Ringer's solution for injectable preparations

Glucose and sodium chloride solution for injectable preparations.

Sodium lactate solution for injectable preparations (M/6 sodium lactate)

Mannitol 5% or 10% for injectable preparations

Lactated Ringer's and glucose 5% or 10%

The solution is for single use. Discard the remaining solution.

Alternatively, the content of a 100 ml vial should be reconstituted to a final concentration that does not exceed 2% p/v (at least 50 ml of solution per gram of aztreonam) with any of the above-mentioned infusion solutions that is suitable. These solutions can be frozen immediately.

The administration rate of this medication during infusion should be over a period of 20 to 60 minutes.

When using a Y-equipment, attention should be paid to the calculated volume of the aztreonam solution necessary to ensure that the total dose of aztreonam has been injected. A volume control administration equipment can be used to incorporate the initial aztreonam solution into the infusion solution of the compatible medication being administered; in this case, the final dilution of aztreonam should provide a concentration that does not exceed 2% p/v.

If a common tube is used intermittently for both aztreonam and another medication with which aztreonam is not pharmaceutically compatible, it will be necessary to flush the tube with one of the suitable infusion solutions compatible with both medications before and after administering the aztreonam solution. In no case will simultaneous administration be performed.

Frozen aztreonam solutions should be stored at -20°C and should be thawed at controlled room temperature or in a refrigerator overnight. Thawed solutions at controlled temperature and under refrigeration should be used within 24 and 72 hours, respectively, after removal from the freezer. The solution cannot be refrozen.

Azactam solutions should be used immediately after preparation.

Administration with Other Antibiotics

Intravenous administration of AZACTAM solutions that do not exceed 2% p/v diluted with sodium chloride 0.9% or glucose 5% for injectable preparations, to which generally used clinical concentrations of clindamycin phosphate, gentamicin sulfate, tobramycin sulfate, sodium cefazolin, sodium ampicillin have been added, should be used immediately after preparation.

Aztreonam-cloxacillin sodium and aztreonam-vancomycin hydrochloride mixtures in Dianeal 137 (peritoneal dialysis solution) with glucose 4.25% should also be used immediately after preparation.

Mixing with other medications or mixing the above-mentioned medications at concentrations different from those specified above is not recommended, as compatibility data are not available.