BENZETACIL 1,200,000 IU Powder and Solvent for Injectable Suspension

2. What you need to know before you use BENZETACIL 1,200,000 UI

Do not use BENZETACIL 1,200,000 UI

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

If you are allergic (hypersensitive) to penicillins, cephalosporins, or soy.

If you have ever had an allergic reaction while taking an antibiotic or other medications. This may include a skin rash or swelling of the face or neck.

Warnings and precautions

Consult your doctor or pharmacist before starting to use BENZETACIL 1,200,000 UI:

-if you have ever had an allergic reaction to other antibiotics such as penicillin or other beta-lactam antibiotics,

-if you have kidney problems (your doctor may need to adjust the dose of this medication),

-if you have liver problems,

-if you are on a low-sodium diet.

BENZETACIL 1,200,000 UI should not be used in tissues with poor blood flow.

In case of allergic symptoms (e.g., skin rash, itching, shortness of breath), consult your doctor immediately.

A hypersensitivity test should be performed if possible before treatment. If an allergic reaction occurs, your doctor will discontinue your treatment and, if necessary, initiate appropriate treatment.

If you are allergic to cephalosporins. In patients hypersensitive to cephalosporins, the possibility of cross-allergic reactions should be considered.

If you are asthmatic or allergic to hay fever, inform your doctor. Severe immediate allergic reactions are possible when the treatment is administered for the first time. In some cases, you may need to be monitored for at least half an hour after administration of the medication in case of acute allergic reaction. In case of allergy, the doctor will take the necessary measures. Treatment with BENZETACIL 1,200,000 UI should be discontinued immediately.

When treating syphilis, a reaction of the body to bacterial toxins may occur, which can last for several days (Jarisch-Herxheimer reaction, see section 4). The symptoms are sudden fever (sometimes with chills), paleness, followed by redness of the skin, headache, muscle and joint pain, or fatigue. Your doctor will initiate appropriate treatment to suppress or alleviate a Jarisch-Herxheimer reaction.

If you have renal and/or severe hepatic insufficiency, the dose should be adjusted. For long-term treatment (more than 5 days), your doctor may schedule blood count checks and tests to evaluate the functioning of your kidneys.

Like other antibiotics, treatment with BENZETACIL 1,200,000 UI may lead to the proliferation of non-sensitive germs. Contact your doctor if you have a fungal infection.

If you have ulcerative colitis, Crohn's disease, or pseudomembranous colitis (persistent and/or severe diarrhea during or after administration of this medication), you should undergo rigorous clinical monitoring, with periodic analytical tests.

During treatment with antibiotics, including BENZETACIL 1,200,000 UI, diarrhea may occur even several weeks after the end of your treatment. In case of severe or persistent diarrhea, or if you notice that your stools contain blood or mucus, inform your doctor immediately to stop treatment. Do not take medications intended to block or delay intestinal transit.

Other medications and BENZETACIL 1,200,000 UI

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medications.

Consult your doctor if you are taking any of the following medications:

• Allopurinol and Probenecid (medications for gout or gouty arthritis)
• Methotrexate (medication used in chemotherapy)
• Other antibiotics
• Anticoagulants (medications to thin the blood)

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medications.

Using BENZETACIL 1,200,000 UI with food and drinks

Treatment with BENZETACIL is not affected if it is administered together with food.

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.

BENZETACIL 1,200,000 UI should not be used during pregnancy unless the clinical situation of the woman requires treatment with benzathine benzylpenicillin.

Small amounts of benzylpenicillin pass into breast milk. Although no side effects have been reported in breastfed infants to date, the possibility of sensitization or interference with the intestinal flora should be considered. In case of diarrhea, candidiasis, or skin rash in the child, consult your doctor immediately. Breastfeeding can be resumed 24 hours after the end of treatment.

Driving and using machines

There is no evidence of effects on the ability to drive vehicles or use machinery.

BENZETACIL 1,200,000 UI contains Sodium

This medication contains less than 1 mmol of sodium (23 mg) per vial; this is, essentially, "sodium-free".

BENZETACIL 1,200,000 UI contains Soy Lecithin

This medication contains 10.25 mg of soy lecithin per vial. It should not be used in case of peanut or soy allergy.

3. How to use BENZETACIL 1,200,000 UI

Follow your doctor's instructions for administering this medication exactly.

In case of doubt, consult your doctor or pharmacist again.

In principle, BENZETACIL 1,200,000 UI is administered by a healthcare professional.

The recommended dose is:

General treatment:

Adults and adolescents: 1,200,000 IU once a week.

Children over 30 kg in weight: 1,200,000 IU once a week.

Children under 30 kg in weight: 600,000 IU once a week.

Treatment duration: a single dose.

Syphilis treatment:

• Primary and secondary:

Adults and adolescents: 2,400,000 IU administered in a single dose.

Children: 50,000 IU/kg of body weight, not exceeding 2,400,000 IU.

If clinical symptoms return or laboratory results remain positive, treatment should be repeated.

Treatment duration: a single dose.

• Latent syphilis:

Adults and adolescents: 2,400,000 IU once a week.

Children: 50,000 IU/kg of body weight, not exceeding 2,400,000 IU.

Treatment duration: 3 weeks

• Congenital syphilis: without neurological involvement

• Newborns and infants: 1 x 50,000 IU/kg of body weight

Treatment duration: a single dose

Treatment of tropical infectious skin diseases (yaws, pinta):

Adults and adolescents: 1,200,000 IU in a single dose.

Children over 30 kg in weight: 1,200,000 IU in a single dose.

Children under 30 kg in weight: 600,000 IU in a single dose.

Treatment duration: a single dose.

Prophylaxis of rheumatic fever, post-streptococcal glomerulonephritis, and erysipelas:

Adults and adolescents: 1,200,000 IU every 3-4 weeks.

Children over 30 kg in weight: 1,200,000 IU every 3-4 weeks.

Children under 30 kg in weight: 600,000 IU every 3-4 weeks.

Treatment duration:

1. Without cardiac involvement: at least 5 years, or until 21 years of age.
2. Temporary cardiac involvement: at least 10 years, or until 21 years of age.
3. Persistent cardiac involvement: at least 10 years or until 40 years of age; sometimes lifelong treatment is necessary.

Patients with renal insufficiency and/or hepatic insufficiency

The dose and dosing interval will be determined by your doctor. Depending on the degree of kidney and/or liver function, your doctor may consider adjusting the dose.

Method of administration

BENZETACIL 1,200,000 UI is administered exclusively by deep intramuscular injection.

The injection should not be administered in tissues with poor blood flow.

In case of repeated intramuscular application, the injection site should be changed.

Severe local reactions may occur during intramuscular administration, especially in small children. For this reason, other treatments, such as a different formulation of penicillin, may be used whenever possible.

To consult the instructions for reconstitution of the medication before administration, see the "Preparation Instructions" section at the end of the package leaflet.

If you use more BENZETACIL 1,200,000 UI than you should

At extremely high doses, penicillins can cause neuromuscular excitability or epileptiform convulsions.

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 used.

If you forget to use BENZETACIL 1,200,000 UI

Do not use a double dose to make up for forgotten doses. Use the forgotten dose as soon as possible and then follow the usual schedule.

If you interrupt treatment with BENZETACIL 1,200,000 UI

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

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone gets them.

The side effects of this medication are generally transient and mild. In most cases, the side effects are of allergic origin and manifest dermatologically. The toxicological profile of this drug is similar to that of the rest of the penicillins, although allergic manifestations are somewhat more frequent, especially by parenteral route.

Severe allergic reactions (anaphylactic or angioedema reactions) may occur as:

• skin rash or itching
• difficulty breathing or chest tightness
• swelling of the eyelids, face, or lips
• swelling or redness of the tongue
• fever
• joint pain
• inflamed lymph nodes

In case of an allergic reaction, the administration will be discontinued, and antihistamines (anti-allergic) and/or corticosteroids (anti-inflammatory) will be instituted.

The side effects listed below are classified according to their frequency and the classification by organs and systems. The frequency categories are defined by the following convention:

Very common (affects more than 1 in 10 patients);

Common (affects up to 1 in 100 patients);

Uncommon (affects up to 1 in 1,000 patients);

Rare (affects 1 to 10 in 10,000 patients);

Very rare (affects less than 1 in 10,000 patients);

Frequency not known (cannot be estimated from the available data).

Infections and infestations:

Common: fungal infection (candidiasis).

Blood and lymphatic system disorders:

Very rare: alteration of blood cells (eosinophilia, neutropenia, leucopenia, agranulocytosis, granulocytopenia, pancytopenia) and coagulation disorders.

Frequency not known: Prolongation of bleeding time and prothrombin time. Hemolytic anemia (reduced red blood cell levels in blood), thrombocytopenia (reduced platelet levels in blood).

Gastrointestinal disorders:

Common: Nausea.

Uncommon: inflammation of the oral mucosa (stomatitis) and inflammation of the tongue (glossitis), vomiting.

Rare: pseudomembranous colitis (colon inflammation), diarrhea.

Immune system disorders:

Rare: allergic reactions: urticaria (hives), angioedema (swelling), skin reactions (erythema multiforme, exfoliative dermatitis), fever, joint pain, anaphylactic shock with collapse, and anaphylactoid reactions (asthma, hemorrhagic skin lesion called purpura, gastrointestinal discomfort).

Frequency not known: serum sickness. When treating syphilis, a reaction called Jarisch-Herxheimer may occur, due to the destruction of bacteria, characterized by fever, chills, general and focal symptoms. Para-allergic reactions may occur in patients with skin mycosis (fungal skin infection). Angioedema (swelling of the skin, mucosa, and subcutaneous tissue, usually localized on the face, mouth, or tongue).

Nervous system disorders:

Rare: neuropathy (nerve damage).

Frequency not known:

Encephalopathy with insomnia, confusion, hallucinations, convulsions, and epileptic status, myoclonus (muscle contraction), and more rarely, aseptic meningitis and benign intracranial hypertension. Metabolic encephalopathy (neurological disorders with convulsions and loss of consciousness).

Hepatic disorders:

Frequency not known: liver inflammation (hepatitis), bile flow disorder (cholestasis).

Skin and subcutaneous tissue disorders:

Common: rashes, exanthems (red rash on the skin), pruritus (itching).

Frequency not known: AGEP - Acute Generalized Exanthematous Pustulosis with symptoms such as severe skin reactions to medications with or without skin redness, fever, pustules, maculopapular rash (flat, red area on the skin), morbilliform rash (rash that looks like measles), itching, erythema (inflammatory redness of the skin).

Renal and urinary disorders:

Rare: kidney disease (nephropathy), kidney inflammation (interstitial nephritis), albuminuria, cylindruria (proteins excreted in urine), and hematuria (blood in urine). Oliguria (decreased urine production) and anuria (no urine excretion) may occur at high doses and usually disappear within 48 hours of ending treatment.

General disorders and administration site conditions:

Common: pain and/or infiltrates at the injection site.

Investigations:

Common: modifications of certain tests and investigations such as:

• Positive direct Coombs test.

False positives in the determination of protein in the urine using precipitation techniques (Folin-Ciocalteu-Lowry and biuret methods)

• False positives in amino acid tests.
• Simulation of albuminemia in the determination of albumin by electrophoretic methods.
• Non-enzymatic tests for detecting false-positive glucose in urine and urobilinogen.
• High levels when determining keto-steroids in the urine (Zimmermann reaction)

Reporting of suspected adverse reactions:

It is important to report any suspected adverse reactions to the medication after its authorization. This allows for continuous monitoring of the benefit-risk balance of the medication. Healthcare professionals are invited to report any suspected adverse reactions through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es.

5. Storage of BENZETACIL 1,200,000 UI

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

The powder for injectable suspension (vial) should be stored in a dry place.

Reconstituted vial: The reconstituted product should be used immediately for intramuscular administration.

Do not use this medication after the expiration date stated on the packaging after "EXP". The expiration date is the last day of the month indicated.

Medications should not be disposed of through wastewater or household waste. Deposit the packaging and medications you no longer need in the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

6. Container Contents and Additional Information

Composition ofBENZETACIL 1,200,000 UI

Vial:

• The active ingredient is Benzathine Benzylpenicillin (Penicillin G benzathine). Each vial contains 1,200,000 UI of Benzathine Benzylpenicillin.
• The other components (excipients) are: Tween 80, lecithin, sodium citrate (E-331).

Ampoule: water for injectable preparations

Once the vial is reconstituted with 4 ml of water, the final volume is 4.8 ml, containing 1,200,000 UI of Benzathine Benzylpenicillin.

There are 300,000 UI of benzathine benzylpenicillin in 1.2 ml of suspension.

Appearance of the Product and Container Contents

BENZETACIL 1,200,000 UI is presented in unitary containers: 1 vial and 1 ampoule, and in clinical containers: 100 vials and 100 ampoules.

Marketing Authorization Holder and Manufacturer:

Marketing Authorization Holder:

Laboratorio Reig Jofré, S.A.

Gran Capitán, 10

08970 San Joan Despí (Barcelona)

Manufacturer:

Laboratorio Reig Jofré, S.A.

Jarama, 111 - Industrial Estate

45007 Toledo

Date of the Last Revision of this Prospectus:October 2021.

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

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This information is intended solely for doctors or healthcare professionals:

Medication:BENZETACIL 1,200,000 UI powder and solvent for injectable suspension

Method of Administration:

BENZETACIL 1,200,000 UI is administered exclusively by deep intramuscular injection in the upper outer quadrant of the buttock or in the ventro-gluteal area of Hochstetter, with the needle pointing towards the iliac crest or according to the Hochstetter method. The puncture should be as perpendicular as possible with respect to the skin surface, and the injection as far as possible from the main vessels. In case of repeated doses, change the injection site.

In children, the recommended injection site is in the mid-lateral muscle of the thigh (quadriceps femoris). Injection into the deltoid muscle is only recommended if the muscle mass is adequate. In this case, attention should be paid to the radial nerve.

In infants and young children, the peripheral area of the upper outer quadrant of the gluteal region should only be used as an injection site in exceptional cases, to avoid damage to the sciatic nerve.

Before injection, intravascular administration should be excluded by aspiration. In case of repeated doses, change the injection site.

For depot preparations, although it is recommended not to administer more than 5 ml per injection site as a tolerance limit, the entire vial can be administered in the same place. In case of excessive pain, the volume can be divided into two injection sites.

The injection should be administered as slowly as possible and only with low pressure.

Avoid pressing and/or rubbing after injection.

Preparation Instructions:

For the injection of BENZETACIL, a long needle with a caliber of 0.9 mm should be used. Prepare the suspension aseptically by injecting the 4 ml of water for injectable preparations from the ampoule provided in the container into the vial.

Shake until a homogeneous suspension is obtained. Aspirate the contents of the vial with the syringe.

1.2 ml of BENZETACIL 1,200,000 UI suspension for injection contains 300,000 UI of benzathine benzylpenicillin after reconstitution with the 4 ml of water from the ampoule.

For injection, insert the needle deeply into the buttock, place the syringe, and aspirate by pulling the plunger of the syringe, checking that no blood comes out to ensure that the needle is not in the lumen of a blood vessel. Apply as soon as possible to avoid crystallization within the injection needle, which may cause the patient greater pain.

For single use. Discard unused suspension.