Package Insert: Information for the User

Azactam 1g Powder for Injection

Aztreonam

Read this package insert carefully before starting to use this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed for you and should not be given to others, even if they have the same symptoms, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

6. Contents of the Container and Additional Information

Azactam is an antibiotic belonging to the monobactam group.

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.

Do not use Azactam

If you are allergic (hypersensitive) to aztreonam or to 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, if the expected benefit justifies the risk of a possible severe allergic reaction. If you notice the appearance of any allergic reaction, you must suspend treatment with Azactam and consult your doctor, as it may be necessary to take certain measures.

You must inform your doctor if you have any kidney or liver function impairment, as you will need to be closely monitored during treatment. If Azactam is administered to elderly patients, who often have kidney impairment, your doctor will perform the necessary tests to determine the appropriate dose.

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

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

If you experience diarrhea during treatment or within two months after treatment, you must inform your doctor, who will take the necessary measures.

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

If you are taking this medication and also using an aminoglycoside antibiotic, your doctor will monitor your kidney function, due to the possible toxicity of these antibiotics in the kidneys and ears.

The use of beta-lactam antibiotics, such as this medication, may increase the risk of encephalopathy, which can lead to confusion, loss of consciousness, epilepsy, and movement disorders, especially in patients with kidney impairment and in cases of overdose (see sections 3 and 4).

Treatment with Azactam may interfere with some laboratory tests (elevated blood transaminases and false-positive urine glucose), as well as obtaining positive results in a direct or indirect Coombs test (blood test used to detect certain diseases by detecting the presence of antibodies).

Children and adolescents

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

Other medications and Azactam

Use of Azactam with other medications

Inform your doctor or pharmacist if you are using, have used recently, 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 monitor you closely when anticoagulants are administered concomitantly. It may be necessary to adjust the dose of oral anticoagulants to maintain the appropriate level of coagulation.

If you are taking Azactam and also using an aminoglycoside antibiotic, your doctor will monitor your kidney function, due to the possible toxicity of these antibiotics in 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.

Inform your doctor if you are taking probenecid (used to treat gout) or furosemide (diuretic used to treat hypertension) at the same time, as concurrent administration with these medications may cause an increase in aztreonam serum levels.

Pregnancy, lactation, and fertility

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

Azactamshould not be administered during pregnancy, unless the expected benefit justifies the possible risk.

Aztreonam is excreted in very small amounts in human milk; therefore, it is recommended to temporarily discontinue breastfeeding during treatment with this medication.

Driving and operating machinery

Do not drive or operate tools or machinery because this medication may have a significant impact on your ability to drive vehicles and use machinery, particularly due to the possible occurrence of encephalopathies (which may cause confusion, seizures, or abnormal movements) (see sections 3-If you take 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 may lead to increases in insulin, indirect bilirubin, and serum arginine.

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

Follow exactly the administration instructions of this medication as indicated by your doctor.In case of doubt,consult your doctor or pharmacist again.

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

The intravenous route is recommended for patients who require unit doses greater than 1 g or those suffering from bacterial sepsis, localized parenchymal abscesses (e.g., intra-abdominal abscesses), peritonitis, and other severe systemic infections or life-threatening infections. Due to the grave nature of infections caused byPseudomonas aeruginosa,in systemic infections produced by this microorganism, a dose of 2 g every 6 or 8 hours is recommended, at least at the beginning 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.

For adults, the usual dosing 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 acute gonorrhea and 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 to half in patients with an estimated creatinine clearance of 10-30 ml/min/1.73 m2.

In patients with severe renal insufficiency, with creatinine clearance values less than 10ml/min/1.73m2(e.g., those undergoing hemodialysis), initial normal doses should be given. Maintenance doses should be one-quarter 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.

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

Use in children

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

If you estimate that the action of Azactam is too strong or too weak, inform your doctor or pharmacist.

If you take more Azactam than you should

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

Overdose of this medication may cause encephalopathy, which may cause 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 forgot to use Azactam

You should not administer a double dose to compensate for the missed doses.

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

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

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

Side effects are classified according to their frequency of occurrence: 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 1000 people), very rare (may affect up to 1 in 10,000 people) and unknown frequency (cannot be estimated from available data).

Uncommon: increased creatinine in the blood.

Rare: vaginal infection, vaginal candidiasis (fungal infection), increased or decreased platelet and white blood cell count, decreased red blood cell count, prolonged blood clotting time, positive Coombs test, seizures, paresthesia (tingling), dizziness, headache, confusion, insomnia, double vision,vertigo, sensation of ringing in the ears,hypotension, 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 (yellow discoloration of the skin and mucous membranes), muscle pain, breast tenderness, fever, discomfort, fatigue, chest pain, change in electrocardiogram.

Unknown frequency: anaphylactic reactions (severe allergic reactions), dysgeusia (alteration of taste), encephalopathy (which may include confusion, loss of consciousness, epilepsy, and movement disorders), phlebitis (inflammation of 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 of the skin), skin infection and peeling, hyperhidrosis (sweating), petechiae (skin spots), purpura (brown skin lesions), urticaria (skin lesion with itching), rash, pruritus (itching), discomfort at the injection site.

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 throughSpanish System for Pharmacovigilance of Medicines for Human Use:www.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.

Before opening the vial: Store in the original packaging. Do not store at a temperature above 25 °C.

Do not use this medication after the expiration date that appears 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 previous use conditions are the responsibility of the user.

Medications should not be disposed of through drains or in the trash. Deposit the containers and unused medications at the SIGRE collection pointat the pharmacy.In case of doubt, ask your pharmacist how to dispose of the containers and unused medications. This will help protect the environment.

Composition of Azactam

-The active ingredient is aztreonam. Each vial of powder contains 1g of aztreonam.

-The other component (excipient) of the vial of powder is arginine.

Appearance of the product and contents of the package

1 Glass vial, Type III, 15 ml capacity containing the active ingredient and excipient, with a 20 mm grey chlorobutyl rubber stopper and sealed with a tamper-evident band.

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

Marketing authorization holder and manufacturer responsible.

MARKETING AUTHORIZATION HOLDER

Bristol-Myers Squibb S.A.

C/Quintanadueñas, 6

28050 Madrid.

MANUFACTURER RESPONSIBLE

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,

Republic of Ireland

Last review date of the leaflet: October 2021

Other sources of information

The detailed information on this medicine is available on 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

Once the vial is opened, the product must be used immediately. Vials should 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 pinkish tint (does not affect potency) with standing.

Each gram of Azactam reconstituted with 3 ml of the appropriate diluent (see preparation of solutions and accepted diluents for each route of administration, 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 contents of a vial (1 g of aztreonam) of Azactam must be reconstituted with at least 3 ml of the following diluents:

Water for injection preparations

Water for injection preparations (bacteriostatic with benzyl alcohol or methylparaben)

Sodium chloride 0.9% solution

Sodium chloride 0.9% solution (bacteriostatic with benzyl alcohol)

The diluents containing benzyl alcohol are not suitable for use in newborns.

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

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

Intravenous administration

Bolus intravenous injection:

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

The solution must be injected slowly over a period of3 to5 minutes directly into the vein, or through an appropriate administration device.

Perfusion:

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

Sodium chloride 0.9% solution for injection preparations

Ringer solution for injection preparations

Lactate Ringer solution for injection preparations

Glucose and sodium lactate solution for injection preparations.

Sodium lactate solution (M/6 sodium lactate)

Manitol 5% or 10% solution for injection preparations

Lactate Ringer and glucose 5% or 10%

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

Alternatively, the contents of a 100 ml vial must be reconstituted to a final concentration not exceeding 2% p/v (at least 50 ml of solution per gram of aztreonam) with any of the above-mentioned infusion solutions that are suitable. These solutions may be frozen immediately.

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

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

If a common tube is used intermittently for both aztreonam and another medication that is not pharmacologically compatible with aztreonam, it will be necessary to rinse the tube with one of the above-mentioned infusion solutions that are compatible with both medications before and after administering the aztreonam solution. In no case should simultaneous administration be performed.Under no circumstances should simultaneous administration be performed.

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

The Azactam solutions must be used immediately after preparation.

Administration with other antibiotics

The intravenous administration of Azactam solutions that do not exceed 2% p/v diluted with sodium chloride 0.9% or glucose 5% solution for injection preparations, to which generally used concentrations in clinical practice of phosphate clindamicina, gentamicin sulfate, tobramycin sulfate, cefazolin sodium, ampicillin sodium have been added, must be used immediately after preparation.

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

It is not recommended to mix with other medications, or to mix the above-mentioned medications at different concentrations, as there is no compatibility data available.