Daptomycin Hikma 350 mg powder for injection and for infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Daptomicina Hikma 350 mg powder for solution for injection and infusion EFG

Read all of this leaflet carefully before you start using 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, ask your doctor or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of this leaflet

1. What Daptomicina Hikma is and what it is used for
2. What you need to know before receiving Daptomicina Hikma
3. How Daptomicina Hikma is administered
4. Possible side effects
5. How to store Daptomicina Hikma
6. Contents of the pack and other information

1. What Daptomicina Hikma is and what it is used for

The active substance of Daptomicina Hikma 350 mg powder for solution for injection and for infusion EFG is daptomycin. Daptomycin is an antibacterial agent capable of inhibiting the growth of certain bacteria.

Daptomicina Hikma is used in adults and in children and adolescents (aged between 1 and 17 years) to treat skin and soft tissue infections. It is also used to treat bloodstream infections when associated with a skin infection.

Daptomycin Hikma is also used in adults to treat infections in the tissues lining the inside of the heart (including the heart valves), caused by a type of bacteria called Staphylococcus aureus. It is also used to treat bloodstream infections caused by the same type of bacteria when associated with a heart infection.

Depending on the type of infection(s) you have, your doctor may also prescribe other antibacterial agents while you are receiving daptomycin treatment.

2. What you need to know before receiving Daptomicina Hikma

Do not receive Daptomicina Hikma

If you are allergic to daptomycin or to sodium hydroxide or to any of the other ingredients of this medicine (listed in section 6).

If this applies to you, inform your doctor or nurse. If you think you may be allergic, consult your doctor or nurse.

Warnings and precautions

Talk to your doctor or nurse before receiving daptomycin:

• If you have or have previously had kidney problems. Your doctor may need to adjust the dose of daptomycin (see section 3 of this leaflet).
• Occasionally, patients receiving daptomycin may develop increased sensitivity, pain, or muscle weakness (see section 4 of this leaflet for more information). Inform your doctor if this occurs. Your doctor will ensure that you have a blood test and will advise you whether or not it is advisable to continue using daptomycin. Symptoms usually resolve within a few days after stopping treatment with daptomycin.
• If you have ever had, after taking daptomycin, a severe skin rash or skin peeling, blisters and/or mouth sores, or serious kidney problems.
• If you have significant overweight, there is a possibility that your blood levels of daptomycin may be higher than those found in individuals of average weight, and therefore you may require closer monitoring for adverse effects.

If any of the above situations apply to you, inform your doctor or nurse before receiving daptomycin.

Tell your doctor or nurse immediately if you develop any of the following symptoms:

• Severe and serious allergic reactions have been observed in patients treated with almost all antibacterial agents, including daptomycin. Symptoms may include wheezing, difficulty breathing, swelling of the face, neck, and throat, skin rash and hives, or fever.
• Serious skin diseases have been reported with the use of daptomycin. Symptoms associated with these skin conditions may include:
  • onset or worsening of fever,
  • raised or fluid-filled red spots on the skin, which may start in the armpits or areas of the chest or groin and may spread over a large area of the body,
  • blisters or sores in the mouth or genital area.
• Serious kidney problems have been reported with the use of daptomycin. Symptoms may include fever and rash.
• Any type of tingling or numbness in the hands or feet, loss of sensation, or unusual movement difficulties. If this occurs, inform your doctor, who will decide whether treatment should continue.
• Diarrhea, especially if you notice blood or mucus in the stool or if the diarrhea becomes severe or prolonged.
• Onset or worsening of fever, cough, or difficulty breathing. These may be signs of a rare but serious lung function deterioration known as eosinophilic pneumonia. Your doctor will check your lung condition and decide whether or not to continue treatment with daptomycin.

Daptomycin may interfere with laboratory tests measuring your blood's clotting ability. Results may falsely suggest impaired clotting, even though no actual problem exists. Therefore, it is important that your doctor is aware that you are receiving daptomycin. Inform your doctor that you are being treated with daptomycin.

Your doctor will perform blood tests to monitor your muscle health before starting treatment and regularly during treatment with daptomycin.

Children and adolescents

Daptomycin must not be given to children under one year of age, as animal studies have shown that this age group may experience severe adverse effects.

Use in elderly patients

Patients over 65 years of age may receive the same dose as other adults, provided their kidneys are functioning properly.

Other medicines and Daptomicina Hikma

Inform your doctor or nurse if you are taking, have recently taken, or might need to take any other medicines.

It is particularly important that you mention the following:

• Medications called statins or fibrates (used to lower cholesterol) or cyclosporine (a medicine used in transplant patients to prevent organ rejection or for other conditions, e.g., rheumatoid arthritis or atopic dermatitis). The risk of muscle-related adverse effects may increase if you take any of these medicines (and others that may affect muscles) during treatment with daptomycin. Your doctor may decide not to administer daptomycin or to temporarily discontinue treatment with the other medicine.
• Pain-relieving medicines called non-steroidal anti-inflammatory drugs (NSAIDs) or COX-2 inhibitors (e.g., celecoxib). These may interfere with the kidney elimination of daptomycin.
• Oral anticoagulants (e.g., warfarin), which are medicines that prevent blood clotting. Your doctor may need to monitor your blood clotting times.

Pregnancy and breastfeeding

Daptomycin is generally not given to pregnant women. If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

You must not breastfeed while receiving daptomycin, as it may pass into breast milk and harm the baby.

Driving and using machines

Daptomycin has no known effects on the ability to drive or use machines.

Daptomicina Hikma contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose; this is essentially “sodium-free”.

3. How Daptomycin Hikma is administered

Daptomycin will normally be administered to you by your doctor or nurse.

Adults (18 years of age and older)

The dose will depend on your body weight and the type of infection being treated. The usual dose for adults is 4 mg per kg of body weight once daily for skin infections, or 6 mg per kg of body weight once daily for heart infection or bloodstream infection associated with skin or heart infection. In adult patients, this dose is administered directly into the bloodstream (into a vein), either as an infusion lasting approximately 30 minutes or as an injection lasting approximately 2 minutes. The same dose is recommended for people aged 65 years and older, provided their kidneys are functioning properly.

If your kidneys are not functioning well, you may receive daptomycin less frequently, e.g., once every other day. If you are undergoing dialysis and your next dose of daptomycin is due on a dialysis day, you will normally receive daptomycin after the dialysis session.

Children and adolescents (from 1 to 17 years of age)

The recommended doses in children and adolescents (from 1 to 17 years of age) will depend on the patient's age and the type of infection being treated. This dose is administered directly into the bloodstream (into a vein) as an infusion lasting approximately 30–60 minutes.

A full course of treatment for skin infections usually lasts between 1 and 2 weeks. Your doctor will decide the duration of your treatment for bloodstream or heart infections and for skin infections.

Detailed instructions for use and handling are provided at the end of the leaflet.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

The following are the most serious adverse effects:

Serious adverse effects with unknown frequency (cannot be estimated from available data)

Cases of hypersensitivity reactions (severe allergic reactions including anaphylaxis and angioedema) have been reported during administration of daptomycin. These severe allergic reactions require immediate medical attention. Inform your doctor or nurse immediately if you experience any of the following symptoms:

• Chest pain or tightness,
• Rash or hives, sometimes affecting the mouth and genitals,
• Swelling around the throat,
• Rapid or weak pulse,
• Wheezing,
• Fever,
• Chills or shivering,
• Flushing,
• Dizziness,
• Fainting,
• Metallic taste.

Consult your doctor immediately if you experience muscle pain, tenderness, or weakness of unknown origin. Muscle problems may be serious, including muscle breakdown (rhabdomyolysis), which may lead to kidney damage.

• Other adverse effects reported with the use of daptomycin include: A rare but potentially serious lung disorder called eosinophilic pneumonia, mostly after more than 2 weeks of treatment. Symptoms may include difficulty breathing, new or worsening cough, or new or worsening fever.
• Serious skin disorders. Symptoms may include:
  • new or worsening fever,
  • raised red spots or fluid-filled lesions on the skin, which may start in the armpits or on the chest or groin and may spread over a large area of the body,
  • blisters or sores in the mouth or genitals.
• A serious kidney problem. Symptoms may include fever and rash.

If you experience these symptoms, inform your doctor or nurse immediately. Your doctor will perform additional tests to establish a diagnosis.

The following are the most frequently reported adverse effects:

Frequent adverse effects (may affect up to 1 in 10 patients)

• Fungal infections, such as thrush,
• Urinary tract infection,
• Decrease in the number of red blood cells (anaemia),
• Dizziness, anxiety, difficulty sleeping,
• Headache,
• Fever, weakness (asthenia),
• High or low blood pressure,
• Constipation, abdominal pain,
• Diarrhoea, discomfort (nausea or vomiting),
• Flatulence,
• Abdominal swelling or bloating,
• Skin rash or itching,
• Pain, itching, or redness at the infusion site,
• Pain in arms or legs,
• Elevated levels of liver enzymes or creatine phosphokinase (CPK) in blood tests.

The following are other adverse effects that may occur after treatment with daptomycin:

Uncommon adverse effects (may affect up to 1 in 100 patients)

• Blood disorders (e.g. increased number of platelets, which may increase the tendency to form blood clots, or increased number of certain types of white blood cells),
• Decreased appetite,
• Tingling or numbness in the hands or feet, disturbances in taste sensation,
• Tremors,
• Changes in heart rhythm, flushing,
• Indigestion (dyspepsia), inflammation of the tongue,
• Itchy rash,
• Muscle pain, cramps or weakness, muscle inflammation (myositis), joint pain,
• Kidney problems,
• Inflammation and irritation of the vagina,
• Generalised pain or weakness, tiredness (fatigue),
• Elevated blood sugar, serum creatinine, myoglobin or lactate dehydrogenase (LDH) levels, prolonged blood clotting time, or electrolyte imbalance in blood tests,
• Itchy eyes.

Rare adverse effects (may affect up to 1 in 1,000 patients)

• Yellowing of the skin and eyes (jaundice),
  • Prolonged prothrombin time.

Frequency not known (cannot be estimated from available data)

Antibiotic-associated colitis, including pseudomembranous colitis (severe or persistent diarrhoea containing blood and/or mucus, associated with abdominal pain or fever), bruising more easily, bleeding gums or nosebleeds.

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor, pharmacist, or nurse, even if it is a possible adverse reaction not listed in this leaflet. You may also report them directly through the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. Storage of Daptomicina Hikma

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the carton and label after EXP. The expiry date refers to the last day of the month indicated.
• Store in a refrigerator (between 2 °C and 8 °C).

After reconstitution:

The physical and chemical stability during use of the reconstituted solution in the vial has been demonstrated for 12 hours at 25 °C and up to a maximum of 48 hours at 2 °C – 8 °C.

After dilution:

The physical and chemical stability of the diluted solution in infusion bags has been established for 12 hours at 25 °C or 24 hours at 2 °C – 8 °C.

For intravenous infusion over 30 minutes, the total storage time (reconstituted solution in the vial and diluted solution in infusion bags; see section 6) at 25 °C must not exceed 12 hours (or 24 hours at 2 °C – 8 °C).

For intravenous injection over 2 minutes, the storage time of the reconstituted solution in the vial (see section 6) at 25 °C must not exceed 12 hours (or 48 hours at 2 °C – 8 °C).

However, from a microbiological standpoint, the product should be used immediately. This product does not contain any preservative or bacteriostatic agent. If not used immediately, storage times in use are the responsibility of the user and normally should not exceed 24 hours at 2 °C–8 °C, unless reconstitution/dilution has been carried out under controlled and validated aseptic conditions.

Do not use Daptomicina Hikma if you notice any change in the appearance of the product (signs of moisture or presence of particles with a different colour in the powder, or presence of particles, turbidity or precipitate upon reconstitution of the solution).

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

Composition of Daptomycin Hikma

• The active substance is daptomycin. One vial of powder contains 350 mg of daptomycin. One ml contains 50 mg of daptomycin after reconstitution with 7 ml of sodium chloride 9 mg/ml (0.9%) injection solution.
• The other component is sodium hydroxide (for pH adjustment).

Appearance of the product and contents of the container

Daptomycin Hikma for injection and infusion solution is presented as a pale yellow to light brown powder or cake in a glass vial. It is mixed with a solvent to form an injectable and infusion solution prior to administration.

Daptomycin Hikma is available in pack sizes containing 1 vial or 5 vials.

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Hikma Farmacêutica (Portugal) S.A.

Estrada do Rio da Mó, 8, 8A and 8B, Fervença

2705-906 Terrugem SNT

Portugal

Manufacturer responsible

Medichem, S.A.

Narcis Monturiol 41A

08970 Sant Joan Despí (Barcelona)

Spain

Or

Hikma Italia S.p.A.

Viale Certosa, 10

27100 Pavia

Italy

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

Hikma España, S.L.U.

Calle Anabel Segura nº11, Edificio A, planta 1ª, oficina 2

28108 - Alcobendas, Madrid

Spain

This medicinal product is authorized in the European Economic Area member states under the following names:

Date of the most recent review of this leaflet: December 2023.

Other sources of information

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

The following information is intended exclusively for healthcare professionals

Important: Consult the Summary of Product Characteristics before prescribing this medicinal product.

Instructions for use and handling

In adults, daptomycin may be administered intravenously either as a 30-minute infusion or as a 2-minute injection. Unlike adults, daptomycin must not be administered as a 2-minute injection in pediatric patients. Pediatric patients aged 7 to 17 years should receive daptomycin via a 30-minute infusion. Pediatric patients under 7 years of age receiving a dose of 9–12 mg/kg should receive daptomycin over 60 minutes. Preparation of the infusion solution requires an additional dilution step, as detailed below:

Daptomycin Hikma administered as intravenous infusion over 30 or 60 minutes

Reconstitution of the lyophilisate with 7 ml of sodium chloride 9 mg/ml (0.9%) injection solution yields a daptomycin concentration of 50 mg/ml for infusion.

The lyophilisate takes approximately 15 minutes to dissolve. The fully reconstituted product will appear clear and may contain a few small bubbles or foam around the edge of the vial.

To prepare daptomycin for intravenous infusion, follow the instructions below:

An aseptic technique must be used when reconstituting or diluting the daptomycin lyophilisate.

For reconstitution:

1. Remove the flip-off polypropylene cap to expose the central portion of the rubber stopper. Clean the top of the rubber stopper with an alcohol swab or other antiseptic solution and allow it to dry. After cleaning, do not touch the rubber stopper or allow it to come into contact with any other surface. Draw 7 ml of sodium chloride 9 mg/ml (0.9%) injection solution into a syringe using a sterile 21-gauge or smaller transfer needle or a needle-free device, then slowly inject it into the vial through the center of the rubber stopper, directing the needle toward the vial wall.
2. Gently rotate the vial to ensure complete wetting of the product, then allow it to stand for 10 minutes.
3. Finally, gently rotate or agitate the vial for a few minutes until a clear reconstituted solution is obtained. Avoid vigorous shaking or agitation to prevent foam formation.
4. Carefully inspect the reconstituted solution before use to ensure the product is fully dissolved and to verify the absence of suspended particles. The color of the reconstituted daptomycin solution may range from pale yellow to light brown.
5. The reconstituted solution must then be diluted with sodium chloride 9 mg/ml (0.9%) (typical volume 50 ml).

For dilution:

1. Slowly withdraw the appropriate reconstituted liquid (50 mg daptomycin/ml) from the vial using a new sterile 21-gauge or smaller needle, inverting the vial to allow the solution to drain toward the stopper. With a syringe, insert the needle into the inverted vial. While keeping the vial inverted, place the needle tip at the bottom of the solution in the vial and withdraw the solution into the syringe. Before removing the needle from the vial, pull the plunger to the end of the syringe barrel to withdraw all solution from the inverted vial.
2. Expel air, large bubbles, and any excess solution to obtain the required dose.
3. Transfer the required reconstituted dose into 50 ml of sodium chloride 9 mg/ml (0.9%).
4. The reconstituted and diluted solution must be administered intravenously over 30 or 60 minutes.

Daptomycin is neither physically nor chemically compatible with glucose-containing solutions. The following substances have been shown to be compatible when added to daptomycin-containing infusion solutions: aztreonam, ceftazidime, ceftriaxone, gentamicin, fluconazole, levofloxacin, dopamine, heparin, and lidocaine.

The total storage time (reconstituted solution in vial and diluted solution in infusion bag) at 25 °C must not exceed 12 hours (24 hours under refrigeration).

The stability of the diluted solution in infusion bags is 12 hours at 25 °C or 24 hours if refrigerated at 2 °C – 8 °C.

Daptomycin Hikma administered as a 2-minute intravenous injection (for adult patients only)

Water must not be used for reconstitution of daptomycin for intravenous injection. Daptomycin must only be reconstituted with sodium chloride 9 mg/ml (0.9%).

Reconstituting the lyophilisate with 7 ml of sodium chloride 9 mg/ml (0.9%) injection solution yields a concentration of 50 mg/ml of daptomycin for injection.

The lyophilisate takes approximately 15 minutes to dissolve. The fully reconstituted product will appear clear and may contain a few small bubbles or foam around the edge of the vial.

To prepare daptomycin for intravenous injection, follow the instructions below:

An aseptic technique must be used at all times when reconstituting the daptomycin lyophilisate.

1. Remove the polypropylene flip-off cap to expose the central portion of the rubber stopper. Clean the top of the rubber stopper with an alcohol swab or other antiseptic solution and allow it to dry. After cleaning, do not touch the rubber stopper or allow it to come into contact with any other surface. Draw 7 ml of sodium chloride 9 mg/ml (0.9%) injection solution into a syringe using a sterile 21-gauge or smaller transfer needle or a needle-free device, then slowly inject it into the vial through the center of the rubber stopper, directing the needle toward the vial wall.
2. Gently rotate the vial to ensure complete wetting of the product, then allow it to stand for 10 minutes.
3. Finally, gently rotate or agitate the vial for a few minutes until a clear reconstituted solution is obtained. Avoid vigorous shaking or agitation to prevent foam formation.
4. Carefully inspect the reconstituted solution before use to ensure the product is fully dissolved and to verify the absence of suspended particles. The color of the reconstituted daptomycin solution may range from pale yellow to light brown.
5. Slowly withdraw the reconstituted liquid (50 mg daptomycin/ml) from the vial using a sterile 21-gauge or smaller needle.
6. Invert the vial to allow the solution to drain toward the stopper. Using a new syringe, insert the needle into the inverted vial. While keeping the vial inverted, place the needle tip at the bottom of the solution in the vial and withdraw the solution into the syringe. Before removing the needle from the vial, pull the plunger to the end of the syringe barrel to withdraw all solution from the inverted vial.
7. Replace the needle with a new one for intravenous injection.
8. Expel air, large bubbles, and any excess solution to obtain the required dose.
9. The reconstituted and diluted solution must then be administered intravenously slowly over 2 minutes.

Chemical and physical stability of the reconstituted solution in the vial has been demonstrated for 12 hours at 25 °C and up to 48 hours under refrigeration (2 °C – 8 °C).

However, from a microbiological standpoint, the product should be used immediately. If not used immediately, in-use storage times are the responsibility of the user and normally should not exceed 24 hours at 2 °C – 8 °C, unless reconstitution/dilution has been carried out under controlled and validated aseptic conditions.

This medicinal product must not be mixed with other medicinal products except those mentioned above.

Daptomycin Hikma vials are for single use only. Any unused portion remaining in the vial must be discarded.