Label:Information for the User

Soltrim 160 mg/800 mg Powder and Injectable Solution

Trimethoprim/Sulfamethoxazole (Lisinato)

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

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

Soltrim is a medication that contains two antibiotics (trimethoprim and a sulfonamide called sulfamethoxazole) that belongs to a group of medications calledcombinations of sulfonamides and trimethoprim, which act against a wide variety of microorganisms that cause infections.

Soltrim is indicated for adults and children aged 2 months and older for the treatment of the following infections:

• Treatment of pneumonia caused byPneumocystis jiroveci (P. carinii)
• Treatment of nocardiosis (lung infection caused byNocardiaspp.)

Soltrim may also be useful in the treatment of:

• Toxoplasmosis.
• Listeriosis (infection caused by a bacterium).
• Infections caused by the bacteriumStaphylococcus aureusresistant to methicillin (MRSA).

Do not use Soltrim

• If you are allergic to sulfonamides, trimethoprim, co-trimoxazole, or any of the other components of this medication (listed in section 6).
• In children under 2 months.
• If you have a blood disorder called megaloblastic anemia due to folate deficiency.
• If you have severe liver disease.
• If you have severe kidney disease.
• If you have or are at risk of developing a metabolic disorder called acute porphyria, which is a deficiency of substances that synthesize a component of the blood.
• If you are pregnant or breastfeeding.

You must stop taking this medication immediately if you experience skin rash, sore throat, fever, joint pain, cough, difficulty breathing, paleness, purpura (purple spots on the skin), jaundice (yellow discoloration of the skin and mucous membranes), or severe blood abnormalities for the first time.

These signs may be indicators of the onset of severe adverse reactions.

With the use of Soltrim, skin rashes that can be life-threatening have been described (Stevens-Johnson syndrome, toxic epidermal necrolysis, generalized acute exanthematous pustulosis, and drug reaction with eosinophilia and systemic symptoms). You must suspend treatment if you experience circular, red spots or patches on the skin, often with a central blister. Other signs that may appear are mouth, throat, nose, genital, and conjunctivitis (swollen and red eyes).

These life-threatening skin rashes often occur with flu-like symptoms. The rash may progress to generalized blistering or skin peeling.

The highest risk period for severe skin reactions is during the first weeks of treatment.

If you have developed Stevens-Johnson syndrome, toxic epidermal necrolysis, generalized acute exanthematous pustulosis, or drug reaction with eosinophilia and systemic symptoms with the use of Soltrim, do not use this medication again at any time.

If you develop skin rashes or these symptoms, stop using Soltrim, and immediately consult a doctor and inform them that you are using this medication.

Warnings and Precautions

Consult your doctor or pharmacist before starting to use Soltrim.

• If you have kidney problems.
• If you are in situations that predispose to folate deficiency (advanced age, chronic alcoholism, rheumatoid arthritis, treatment with seizure-preventing medications, malabsorption syndrome, and states of malnutrition) or have congenital deficiency of the glucose-6-phosphate dehydrogenase enzyme.
• If you are an elderly patient, especially if you have liver or kidney problems, or are taking other medications, as the risk of adverse effects is higher.
• If you have severe allergies or bronchial asthma.
• If you have acquired immunodeficiency syndrome (AIDS).
• If you are at risk of developing hyperkalemia (elevated potassium levels in the blood) and hyponatremia (decreased sodium levels in the blood).
• If you are taking a diet rich in potassium or other medications that may increase potassium levels in the blood.
• If you have hypoalbuminemia (decreased albumin levels in the blood), as the risk of urate crystals in the urine is higher.

Your doctor may request that you undergo blood tests and may recommend taking folate supplements during prolonged treatments.

If you experience an unexpected worsening of cough and shortness of breath, inform your doctor immediately.

Lymphohistiocytosis

Rare cases of excessive immune reactions due to unregulated activation of white blood cells have been reported, which can be potentially fatal if not diagnosed and treated promptly. If you experience multiple symptoms such as fever, lymph node swelling, feeling weak, dizziness, shortness of breath, bruises, or skin rash with or without a slight delay, contact your doctor immediately.

If local irritation and inflammation occur after administration of Soltrim, treatment should be suspended and restarted at another site.

Soltrim, like most antibiotics, can cause pseudomembranous colitis (inflammation of the large intestine that causes diarrhea and abdominal pain) by the microorganism Clostridium difficile. If you experience diarrhea, you should consult your doctor to rule out this diagnosis.

Consult your doctor if you have experienced or have any of the above situations.

Other Medications and Soltrim

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication, including those purchased without a prescription, vaccines, and herbal remedies.

Soltrim may interact with:

• Immunosuppressive medications, used to reduce the body's defense mechanism (cyclosporine, pyrimethamine, methotrexate, mercaptopurine, or azathioprine), increasing their toxicity.
• Hypoglycemic agents, used to regulate blood sugar levels.
• Diuretics, used to promote the elimination of fluids, increasing the risk of hyperkalemia (elevated potassium levels in the blood).
• Local anesthetics.
• Potassium aminobenzoate, used to treat certain diseases in which the skin becomes less flexible.
• Angiotensin-converting enzyme inhibitors, used to reduce blood pressure.
• Antipsychotics (such as chlorpromazine or haloperidol).
• Antidepressants (such as imipramine).
• Antifungals (such as ketoconazole).
• Antibiotics (such as erythromycin).
• Antihistamines (such as terfenadine or astemizol).

Soltrim may increase the concentrations and potentiate the effect of:

• Antiviral medications, used in the treatment of viral infections (zidovudine, zalcitabine, lamivudine, and amantadine).
• Immunosuppressive medications, used to reduce the body's defense mechanism (tacrolimus).
• Oral anticoagulants, used to prevent blood coagulation (warfarin).
• Antiarrhythmic medications, used to regulate heart rhythm (procainamide and digoxin).
• Antiepileptic medications, used to prevent seizures (phenytoin).
• Antibiotics, used to treat infections (rifampicin and dapsone).
• Methotrexate.

Use of Soltrim with Food, Drinks, and Alcohol

Alcohol consumption should be avoided during treatment with Soltrim.

Precautions should be taken in patients with potassium-rich diets.

Pregnancy, Breastfeeding, and Fertility

This medication should not be taken during pregnancy or lactation.

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medication. Your doctor will evaluate the benefit-risk balance of the treatment.

Driving and Operating Machines

No effects on driving and operating machines have been described.

Soltrim contains benzyl alcohol and sodium metabisulfite

This medication contains 200 mg of benzyl alcohol in each dose unit. Benzyl alcohol may cause allergic reactions. Consult your doctor or pharmacist if you are pregnant or breastfeeding. This is because large amounts of benzyl alcohol can accumulate in your body and cause adverse effects (metabolic acidosis). Consult your doctor or pharmacist if you have liver or kidney disease. This is because large amounts of benzyl alcohol can accumulate in your body and cause adverse effects (metabolic acidosis).

Benzyl alcohol has been associated with the risk of severe adverse effects, including respiratory problems ("breathing difficulty") in children. Do not administer this medication to your newborn (up to 4 weeks old) unless your doctor recommends it. This medication should not be used for more than a week in children under 3 years old unless your doctor or pharmacist advises it.

This medication may cause severe allergic reactions and bronchospasm (sudden feeling of suffocation) due to the presence of sodium metabisulfite.

Soltrim will be prepared and administered by trained healthcare personnel.

Before administration, the vial with lyophilized powder (containing sulfamethoxazole) must be reconstituted with the ampule of solution (containing trimethoprim) and will be administered by intravenous infusion after prior dilution over a period of between one and one and a half hours.

Soltrim parenteral administration should only be performed in patients who cannot take medication orally or when it is necessary to quickly achieve high serum concentrations.

Follow exactly the administration instructions of the medication contained in this leaflet or those indicated by your doctor, pharmacist, or nurse. In case of doubt, ask your doctor, pharmacist, or nurse.

Use in adults and children over 12 years

Depending on the severity of the infection, doses may range from 160 – 320 mg of trimethoprim and 800 – 1,600 mg of sulfamethoxazole (1 vial + 1 ampule or 2 vials + 2 ampules) administered two to four times a day, that is, every 6-12 hours.

Children between 2 months and 12 years

The average dose based on weight is as follows: 3.2 mg of trimethoprim and 16 mg of sulfamethoxazole per kilogram of body weight administered every 12 hours (which corresponds to 0.12 ml/kg every 12 hours).

The recommended doses regardless of body weight are:

Children from6 to12 years

The usual dose is half a vial (80 mg of trimethoprim and 400 mg of sulfamethoxazole) every 12 hours.

Children from 6 months to 5 years

The usual dose is a quarter of a vial (40 mg of trimethoprim and 200 mg of sulfamethoxazole) every 12 hours.

Children from 2 to 5 months

The usual dose is 0.75 ml (20 mg of trimethoprim and 100 mg of sulfamethoxazole) every 12 hours.

Elderly patients

The usual dose is the same as in adults. In case of kidney impairment, the dose will be adjusted according to the functioning of the same.

Patients with kidney impairment

In case of kidney impairment, your doctor will decide if it is necessary to reduce the usual dose based on the creatinine clearance (indicator of kidney function).

Pneumocystis jiroveci pneumonia

In children over 2 months and adults, the recommended intravenous dose is 15–20 mg of trimethoprim/kg/day and 75–100 mg of sulfamethoxazole/kg/day. The daily dose should be divided into 3–4 equal doses administered by intravenous infusion, until oral treatment is established.

The treatment should be prolonged for a total treatment period of at least 2 weeks, with a recommended period of 21 days.

Nocardiosis

The recommended intravenous dose is 15 mg/kg/day of trimethoprim and 75 mg/kg/day of sulfamethoxazole, in 2-4 doses over 3-4 weeks. Then reduce the dose to 10 mg/kg/day of trimethoprim / 50 mg/kg/day of sulfamethoxazole in 2-4 doses, for a period of 3 to 6 months.

Toxoplasmosis

The recommended dose in adults by intravenous route is 10 mg/kg/day of trimethoprim and 50 mg/kg/day of sulfamethoxazole every 12 hours, for 30 days.

Listeriosis

The recommended dose in adults by intravenous route is 10-20 mg/kg/day of trimethoprim and 50-100 mg/kg/day of sulfamethoxazole, in 2-4 doses for at least 2 weeks.

The recommended dose in children by intravenous route is 10-12 mg/kg/day of trimethoprim and 50-60 mg/kg/day of sulfamethoxazole, in 4 doses for a period of between 14 and 21 days.

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) such as osteomyelitis and septic arthritis or skin and soft tissue infections.

- osteomyelitis: the dose in adults is 3.5- 4 mg/kg/dose every 8-12 hours. There is not enough evidence to recommend a pediatric dosage.

- purulent cellulitis: the dose in adults is between 160 mg of trimethoprim/ 800 mg of sulfamethoxazole every 12 hours and 320/1,600 mg every 12 hours. The pediatric dose is 4-6 mg/kg/dose of trimethoprim and 20-30 mg/kg /dose every 12 hours.

- septic arthritis: the dose in adults is 3.4-4 mg/kg/dose every 8-12 hours. There is not enough evidence to recommend a pediatric dosage.

- skin and soft tissue infections: the dose in adults is 160/800 mg every 12 hours.

If you use more Soltrim than you should

Consult your doctor or pharmacist immediately, go to an emergency service or call the Toxicological Information Service, telephone 915.620.420.

The symptoms of overdose include loss of appetite, vomiting, nausea, dizziness, colic, headache, drowsiness, unconsciousness, depression, confusion, and bone marrow depression.

The treatment should be interrupted. If the diuresis is low, the administration of liquids is recommended. This medication is dialyzable by hemodialysis but peritoneal dialysis is not effective.

Calcium folinate administered at doses of 3 to 6 mg by intramuscular route for 5-7 days is an effective antidote against the adverse reactions caused by trimethoprim. There is no antidote for sulfamethoxazole overdose.

If you forget to use Soltrim

Do not use a double dose to compensate for the missed doses.

If you interrupt the treatment with Soltrim

Do not stop using your medication or reduce the dose without consulting your doctor.

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

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

With Soltrim treatment, skin reactions such as generalized exfoliative dermatitis (widespread peeling), rash, itching, purpura (small skin spots); fever, liver changes (elevated liver enzymes or transaminases, hepatitis (liver inflammation)), kidney changes (elevated creatinine in blood, tubulointerstitial nephritis, crystal formation in urine), hyperkalemia (elevated potassium levels in blood), hyponatremia (decreased sodium levels in blood) and hypoglycemia (decreased blood sugar levels) may occur.

Unknown frequency, purple-colored, elevated, and painful lesions may appear on the extremities and sometimes on the face and neck, with fever (Sweet syndrome). Unknown frequency, cases of acute generalized pustular psoriasis (PEGA) and cases of drug reaction with eosinophilia and systemic symptoms, also known as DRESS (see section 2), have also been described.

More serious side effects such as blood changes (neutropenia or agranulocytosis (decreased or absent granulocytes in blood), aplastic anemia, bone marrow insufficiency, leukopenia (decreased white blood cells in blood), thrombocytopenia (decreased platelet count in blood)), severe liver changes (hepatic necrosis) and allergic reactions may occur.

Very rarely, life-threatening skin reactions may appear (Stevens-Johnson syndrome, which presents with red blisters, erosion, and bleeding skin crusts or Toxic Epidermal Necrolysis, which presents with peeling and blisters on the skin's surface) (see section 2).

Antibiotic treatment, including Soltrim, may alter the colon's flora due to the overgrowth of a bacteria called Clostridium difficile, leading to intestinal symptoms (whose severity may range from mild diarrhea to life-threatening colitis). If you experience intense and prolonged diarrhea, even if it appears two months after Soltrim administration, you should consult your doctor.

Special populations

Patients with glucose-6-phosphate dehydrogenase enzyme deficiency:A hemolytic reaction (destruction of red blood cells) may occur, which often depends on the dose.

Older patients: The most common side effects are severe skin reactions or those related to bone marrow function, such as a decrease in platelet count in blood (with or without the appearance of red spots on the skin). An increased incidence of decreased platelet count has been described in patients treated with diuretics (mainly thiazides) at the same time.

Patients infected with HIV: The most serious side effects that occur more frequently include neutropenia (decreased white blood cell count), intense redness of the skin with peeling in layers or scales (exfoliative dermatitis), appearance of blisters on the skin and mucous membranes, and may be life-threatening (Toxic Epidermal Necrolysis).

Patients with AIDS:Experience skin and bone marrow reactions more frequently than the general population. They may experience leukopenia (decreased white blood cell count), thrombocytopenia (decreased platelet count), skin rash (exanthema), and elevated liver enzymes (indicators of liver function) and creatinine (renal function indicator), usually around the 7th to 14th day of treatment; they may also experience elevated potassium levels in blood (hyperkalemia) and decreased sodium levels in blood (hyponatremia).

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es.

By reporting adverse 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 reconstitution:

No special storage conditions are required.

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

After reconstitution:

Once the powder has been reconstituted with the solution, the medication must be used within 24 hours. This solution must be stored at room temperature.

To be administered by intravenous infusion, Soltrim must be mixed extemporaneously at a ratio of 1 ml of the reconstituted vial with the ampule of solution for 50 ml of infusion solution, see the section with information for healthcare professionals at the end of the prospectus.

Once prepared, the solution must be used within the next 6 hours. This solution can be stored at room temperature.

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. If in doubt, ask your pharmacist how to dispose of the containers and medications you no longer need. By doing so, you will help protect the environment.

Composition of Soltrim

• The active principles of Soltrim are trimethoprim and sulfamethoxazole.
• Each ampoule of solution contains 160 mg of trimethoprim and each vial with lyophilized powder contains 800 mg of sulfamethoxazole.

• The other components present in the ampoule are: benzyl alcohol (200 mg), glycerol formaldehyde, formaldehyde, sodium metabisulfite, hydrochloric acid (to adjust pH) and water for injectable preparations.

Appearance of the product and contents of the package

Lyophilized powder and injectable solution.

The powder contained in the vial is white in color. The solution contained in the ampoule is transparent and colorless.

Both components must be mixed before administration. The total volume of the reconstituted injectable solution is 6 ml. The appearance of this reconstituted solution is transparent and slightly yellowish.

Each package of Soltrim contains:

• 5 glass ampoules containing 5 ml of trimethoprim solution
• 5 glass vials containing lyophilized powder of sulfamethoxazole

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Almirall, S.A. General Mitre, 151 08022 – Barcelona (Spain)

Responsible for manufacturing

Famar Health Care Services Madrid, S.A.U. Avda. Leganés, 62 28923 Alcorcón – Madrid (Spain).

and/or

Industrias Farmacéuticas Almirall, S.A.

Ctra. de Martorell, 41-61 (Sant Andreu de la Barca (Barcelona)) - 08740 - Spain

Last review date of this leaflet: June 2020

The detailed information of this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es.

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This information is intended solely for doctors or healthcare professionals:

Intravenous perfusion

Soltrim should not be injected directly into a vein.

Instructions for diluting the medication before administration by intravenous perfusion:

Soltrim should be mixed extemporaneously at a ratio of 1 ml of the reconstituted vial with the ampoule solution (containing trimethoprim) per 50 ml of solution, resulting in the following:

• ½ reconstituted vial of Soltrim per 125 ml of solution to be infused.
• 1 reconstituted vial of Soltrim per 250 ml of solution to be infused.
• 2 reconstituted vials of Soltrim per 500 ml of solution to be infused.

The solutions to be used may be the following:

• Ringer's solution
• Physiological saline solution (0.9% sodium chloride)
• Glucose-saline solution (sodium chloride 0.18% + glucose 4%)
• Glucose solution 5% or 10%
• Levulose solution 10%
• Sodium bicarbonate solution 1.6 M

Do not use solutions of sodium lactate 1/6 Molar, glucose 15% or high molecular weight solutions such as dextran.

If once prepared the solution is observed to be turbid or precipitates after agitation, the solution should be discarded and a new one prepared.

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