LINEZOLID HIKMA 2 mg/ml SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the Patient

Linezolid Hikma 2 mg/ml Solution for Infusion EFG

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, pharmacist, or nurse.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

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

Linezolid is an antibiotic of the oxazolidinone group that works by preventing the growth of certain bacteria (germs) that cause infections. It is used to treat pneumonia and some skin or subcutaneous tissue infections. Your doctor will decide if Linezolid is suitable to treat your infection.

2. What you need to know before you use Linezolid Hikma

Do not use Linezolid Hikma:

• if you are allergic to linezolid or any of the other ingredients of this medicine (listed in section 6).
• if you are taking or have taken in the last 2 weeks certain medicines called monoamine oxidase inhibitors (MAOIs such as phenelzine, isocarboxazid, selegiline, moclobemide). These medicines are used to treat depression or Parkinson's disease.
• if you are breast-feeding. Linezolid passes into breast milk and may affect the baby.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting treatment with Linezolid.

Linezolid may not be suitable for you if you answer yesto any of the following questions. In this case, tell your doctor, as he/she will need to monitor your general health and blood pressure before and during treatment or may decide that another treatment is better for you.

Ask your doctor if you are not sure if any of these categories apply to your case.

• Do you have high blood pressure, are you taking or not taking medicines to treat it?
• Have you been diagnosed with hyperthyroidism?
• Do you have a tumor of the adrenal glands (pheochromocytoma) or carcinoid syndrome (caused by tumors in the hormonal system that cause symptoms such as diarrhea, skin flushing, wheezing when breathing)?
• Do you suffer from bipolar disorder, schizophrenic disorder, mental confusion, or other mental problems?
• Do you take opioids?

The use of certain medicines, including antidepressants and opioids, with Linezolid may cause serotonin syndrome, a potentially life-threatening condition (see section 2 "Using Linezolid Hikma with other medicines" and section 4).

Be careful with Linezolid Hikma

Tell your doctor before using this medicine if:

• You bruise easily and bleed,
• You have anemia (low red blood cell count),
• You are prone to infections,
• You have a history of seizures,
• You have liver or kidney problems, especially if you are on dialysis,
• You have diarrhea.

Tell your doctor immediately if during treatment you experience:

• Vision problems such as blurred vision, changes in color vision, difficulty seeing clearly, or if you notice that your field of vision is reduced.
• Numbness or tingling in your arms or legs or a sensation of tingling or burning in your arms or legs.
• Diarrhea may occur while you are taking or after taking antibiotics, including linezolid. If diarrhea becomes severe, lasts a long time, or if you notice that your stools contain blood or mucus, you should stop taking Linezolid immediately and consult your doctor. In this situation, you should not take medicines that stop or reduce bowel movements.
• Repeated nausea or vomiting, abdominal pain, or rapid breathing.

Using Linezolid Hikma with other medicines

Occasionally, Linezolid may interact with certain medicines and produce side effects such as changes in blood pressure, body temperature, or heart rate.

Tell your doctor or pharmacist if you are taking, have recently taken, or may need to take any other medicine.

Tell your doctor if you are taking or have taken in the last 2 weeksthe following medicines, as you should notuse Linezolid if you are still taking them or if you have taken them recently (see also section 2 above "Do not use Linezolid Hikma").

• monoamine oxidase inhibitors (MAOIs, such as phenelzine, isocarboxazid, selegiline, moclobemide). These medicines can be used to treat depression or Parkinson's disease.

Also, tell your doctor if you are taking the following medicines. Your doctor may decide to treat you with Linezolid, but will need to assess your general health and blood pressure before and during treatment. In other cases, your doctor may decide that another treatment is better for you.

• Cold remedies that contain pseudoephedrine or phenylpropanolamine.
• Certain asthma medicines such as salbutamol, terbutaline, fenoterol.
• Certain antidepressants called tricyclics or SSRIs (selective serotonin reuptake inhibitors). There are many medicines of this type, including amitriptyline, citalopram, clomipramine, dosulepin, doxepin, fluoxetine, fluvoxamine, imipramine, lofepramine, paroxetine, sertraline, or certain medicines used to treat opioid dependence, such as buprenorphine. These medicines can interact with linezolid and you may experience symptoms such as muscle contraction, agitation, hallucinations, coma, excessive sweating, tremors, excessive reflexes, increased muscle tension, body temperature above 38°C. Contact your doctor if you experience these symptoms.
• Migraine medicines such as sumatriptan or zolmitriptan.
• Medicines for treating severe allergic reactions such as adrenaline (epinephrine).
• Medicines that increase blood pressure, such as noradrenaline (norepinephrine), dopamine, and dobutamine.
• Medicines used to treat moderate or severe pain, opioids such as pethidine.
• Medicines used to treat anxiety disorders, such as buspirone.
• Medicines that prevent blood clotting, such as warfarin.
• An antibiotic called rifampicin.

Using Linezolid Hikma with food, drinks, and alcohol

• You can use Linezolid before, during, or after meals.
• Avoid eating excessive amounts of cheese, yeast extracts, or soybean extracts (e.g., soy sauce) and alcoholic beverages, especially draft beer and wine. The reason is that this medicine may react with a substance called tyramine that is naturally present in some foods. This interaction can cause an increase in your blood pressure.
• If you develop a throbbing headache after eating or drinking, tell your doctor or pharmacist or nurse immediately.

Pregnancy, breast-feeding, and fertility

The effect of Linezolid on pregnant women is unknown. Therefore, pregnant women should not use this medicine unless advised by their doctor. If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

You should not breast-feed while being treated with Linezolid, as this medicine passes into breast milk and may affect your baby.

Driving and using machines

Linezolid may cause dizziness or vision problems. If this happens, do not drive or use machines. Remember that if you do not feel well, your ability to drive or use machines may be affected.

Linezolid Hikma contains Glucose

This medicine contains 45.7 mg/ml (13.7 g/300 ml) of glucose. Patients with diabetes mellitus should be aware of this.

Linezolid Hikma contains Sodium

This medicine contains 114 mg of sodium (main component of cooking/table salt) in each bag. This is equivalent to 5.7% of the maximum recommended daily intake of sodium for an adult.

3. How to use Linezolid Hikma

Adults

Follow exactly the instructions for administration of the medicine contained in this leaflet or as indicated by your doctor, pharmacist, or nurse. If you are unsure, ask your doctor, pharmacist, or nurse.

This medicine will be administered to you by a doctor or other healthcare professional through a drip (by infusion into a vein). The recommended dose for adults (18 years and older) is 300 ml (600 mg of linezolid) twice a day administered directly into the bloodstream (intravenously) through a drip over a period of 30 to 120 minutes.

If you are on a dialysis program, you will be given Linezolid after each session.

A treatment cycle usually lasts 10-14 days, but may be extended up to 28 days. The safety and efficacy of this medicine have not been established for treatment periods longer than 28 days. Your doctor will decide the duration of your treatment.

While you are being treated with Linezolid, your doctor will perform regular blood tests to monitor your blood count.

If you are being treated with Linezolid for more than 28 days, your doctor will need to monitor your vision.

Use in children and adolescents

Linezolid is not normally used in children or adolescents (under 18 years).

If you use more Linezolid Hikma than you should

If you think you may have been given more Linezolid than you should, tell your doctor or nurse.

In case of overdose or accidental ingestion, consult your doctor or call the Toxicology Information Service, telephone 91 562 04 20, indicating the medicine and the amount received.

If you miss a dose of Linezolid Hikma

Since this medicine is administered under close supervision, it is very unlikely that a dose will be missed. If you think a dose of your treatment has been missed, tell your doctor or nurse. Do not take a double dose to make up for missed doses.

4. Possible side effects

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

Tell your doctor, nurse, or pharmacist immediatelyif you notice any of the following side effects while being treated with Linezolid:

The serious side effects (with frequency in parentheses) of Linezolid are:

• Severe skin reactions (uncommon), swelling, particularly around the face and neck (uncommon), wheezing and/or difficulty breathing (rare). This may be a sign of an allergic reaction and may require discontinuation of treatment with Linezolid. Skin reactions such as purpuric elevated lesions due to inflammation of blood vessels (rare), painful, red, and scaly skin (dermatitis) (uncommon), skin rash (common), itching (common).
• Vision problems (uncommon) such as blurred vision, changes in color perception (not known), difficulty seeing clearly (not known), or if you notice that your field of vision is reduced (rare).
• Severe diarrhea that contains blood and/or mucus (antibiotic-associated colitis including pseudomembranous colitis), which in rare circumstances may lead to life-threatening complications (uncommon).
• Repeated nausea or vomiting, abdominal pain, or rapid breathing (rare),
• There have been reports of seizures or convulsions (uncommon) in patients treated with this medicine.
• Serotonin syndrome (not known): You should tell your doctor if you experience agitation, confusion, delirium, rigidity, tremors, uncoordination, convulsions, rapid heartbeat, serious breathing problems, and diarrhea (suggestive of serotonin syndrome) while taking antidepressants known as SSRIs or opioids (see section 2).
• Bleeding or unexplained bruising, which may be due to an alteration in the number of certain blood cells that can affect blood clotting or cause anemia (common).
• Changes in the number of blood cells that can affect the ability to fight infections (uncommon). Some signs of infection include: fever (common), sore throat (uncommon), mouth ulcers (uncommon), and fatigue (uncommon).
• Pancreatitis (uncommon).
• Seizures (uncommon).
• Transient ischemic attacks (temporary alteration of blood flow to the brain that causes short-term symptoms such as vision loss, weakness in arms and legs, difficulty speaking, and loss of consciousness) (uncommon).
• "Ringing" in the ears (tinnitus) (uncommon).

There have been reports of numbness, tingling, or blurred vision in patients who have taken this medicine for more than 28 days. If you experience difficulties with your vision, consult your doctor as soon as possible.

Other side effects include:

Common (may affect up to 1 in 10 patients):

• Fungal infections, especially "thrush" in the vagina or mouth.
• Headache.
• Metallic taste.
• Diarrhea, vomiting, nausea.
• Alteration of some blood test results, including protein, salt, or enzyme tests that measure liver, kidney, or blood sugar function.
• Difficulty sleeping.
• Increased blood pressure.
• Anemia (reduced red blood cell count).
• Dizziness.
• Abdominal pain, localized or generalized.
• Constipation.
• Indigestion.
• Localized pain.
• Reduced platelet count.

Uncommon (may affect up to 1 in 100 patients):

• Vaginal or genital inflammation in women.
• Feeling of tingling or numbness.
• Swelling, discomfort, color changes of the tongue.
• Dry mouth.
• Pain at the infusion site (drip) or around it.
• Venous inflammation (including the site where the drip is placed for infusion).
• Need to urinate more frequently.
• Chills.
• Feeling of thirst.
• Increased sweating.
• Hyponatremia (low sodium levels in the blood).
• Kidney failure.
• Abdominal swelling.
• Pain at the injection site.
• Increased creatinine.
• Stomach pain.
• Changes in heart rate (e.g., increased heart rate).
• Low blood count.
• Weakness and/or sensory changes.

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

• Change in tooth color, which disappears with professional dental cleaning procedures.

Other side effects have also been reported (frequency not known: cannot be estimated from available data)

• Alopecia (hair loss).

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 side effects directly through the Spanish Pharmacovigilance System for Human Use Website: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Linezolid Hikma

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

Store in the original packaging until use to protect from light. Do not use this medicine after the expiry date stated on the packaging, bag, and outer packaging, after EXP. The expiry date is the last day of the month indicated.

Hospital staff will ensure that Linezolid Hikma solution for infusion is not used after the expiry date printed on the bag and that it is administered immediately after breaking the seal. They will also visually inspect the solution before use and will only use it if it is a clear solution without particles. They will also ensure that the solution is stored correctly in its box and aluminum wrapping to protect it from light and to keep it out of the sight and reach of children until use.

After opening:

From a microbiological point of view, unless the opening method excludes the risk of microbial contamination, the product should be used immediately. If not, the in-use storage times and conditions are the responsibility of the user.

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

6. Container Content and Additional Information

Composition of Linezolid Hikma

• The active ingredient is linezolid. Each ml of solution contains 2 mg of linezolid. Each 300 ml infusion bag contains 600 mg of linezolid.
• The other components are glucose monohydrate, sodium citrate, anhydrous citric acid, hydrochloric acid or sodium hydroxide for pH adjustment, and water for injectable preparations. See section 2 "Linezolid contains glucose and sodium"

Appearance of the Product and Container Content

Linezolid Hikma is a transparent solution presented in individual infusion bags containing 300 ml of solution. The bags are presented in packs of 10 bags.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Hikma Farmacêutica (Portugal), S.A.

Estrada do Rio da Mó n.º 8, 8A e 8B, Fervença

2705-906 Terrugem SNT

Portugal

Manufacturer

Hikma Farmacêutica (Portugal), S.A.

Estrada do Rio da Mó n.º 8, 8A e 8B, Fervença

2705-906 Terrugem SNT

Portugal

You can request more information about this medicine by contacting 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 medicine is authorized in the Member States of the European Economic Area under the following names:

Austria Linezolid Hikma 2 mg/ml Infusionslösung

Germany Linezolid Hikma 2 mg/ml Infusionslösung

Spain Linezolid Hikma 2 mg/ml solution for infusion EFG

France LINEZOLIDE HIKMA 2 mg/mL, solution for infusion

Italy Linezolid Hikma

Portugal Linezolid Hikma

Date of the last revision of this leaflet:July 2024

Other sources of information

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

Thisinformation is intended only for healthcare professionals:

Linezolid Hikma 2 mg/ml solution for infusion EFG

IMPORTANT: Consult the technical data sheet before prescribing.

Posology and Method of Administration

Treatment with linezolid should only be started in the hospital setting and after evaluation by a specialist doctor, such as a microbiologist or an infectious disease specialist.

Patients who start treatment with the parenteral formulation may switch to any of the oral formulations when clinically indicated. In this case, no dose adjustment is required, as the oral bioavailability of linezolid is approximately 100%.

The infusion solution should be administered over a period of 30 to 120 minutes.

The recommended dose of linezolid should be administered intravenously twice a day.

Duration and recommended dosing for treatment in adults:

The duration of treatment depends on the microorganism, the site of infection, the severity, and the patient's clinical response.

The recommendations on the duration of treatment indicated below reflect those used in clinical trials. For some types of infection, it may be convenient to prescribe shorter treatments, although this has not been evaluated in clinical trials.

The maximum duration of treatment is 28 days. The safety and efficacy of linezolid when administered for periods longer than 28 days have not been established.

For infections associated with concomitant bacteremia, it is not necessary to increase the recommended dose or duration of treatment.

The recommended posology for the infusion solution is as follows:

Pediatric population:There are insufficient data on the pharmacokinetics, safety, and efficacy of linezolid in children and adolescents (< 18 years) to establish dosage recommendations. Therefore, until more data are available, the use of linezolid is not recommended in this age group.

Elderly patients:No dose adjustment is required.

Renal insufficiency:No dose adjustment is required.

Severe renal insufficiency (i.e., CLCR < 30 ml/min):No dose adjustment is required in these patients. Since the clinical relevance of exposure to high concentrations (up to 10 times) of the two main metabolites of linezolid is unknown, this medicine will be used with special caution in patients with severe renal insufficiency and will only be administered if the expected benefit outweighs the possible risk.

Since approximately 30% of the linezolid dose is eliminated during 3 hours of hemodialysis, Linezolid Hikma will be administered after dialysis in patients receiving such treatment. The main metabolites of linezolid are partially eliminated by hemodialysis, but the concentrations of these metabolites are considerably higher after dialysis than those observed in patients with normal renal function or mild to moderate renal insufficiency. Therefore, linezolid will be used with special caution in patients with severe renal insufficiency undergoing dialysis and only if the expected benefit outweighs the possible risk.

So far, there is no experience with the administration of linezolid to patients undergoing continuous ambulatory peritoneal dialysis (CAPD) or alternative treatments for renal insufficiency (other than hemodialysis).

Hepatic insufficiency:Patients with mild to moderate hepatic insufficiency (Class A or B on the Child-Pugh scale): No dose adjustment is required.

Severe hepatic insufficiency (Class C on the Child-Pugh scale):Since linezolid is metabolized through a non-enzymatic process, it is not expected that impaired liver function will significantly alter its metabolism, and therefore, no dose adjustment is recommended. However, there are insufficient clinical data, and it is recommended to use linezolid in these patients only if the expected benefit outweighs the theoretical risk.

Overdose

No specific antidote is known. No cases of overdose have been reported. However, the following information may be useful: Supportive treatment is recommended, along with maintenance of glomerular filtration. Approximately 30% of a linezolid dose is eliminated during 3 hours of hemodialysis, but there are no data available on the elimination of linezolid by peritoneal dialysis or hemoperfusion.

Instructions for Use and Handling

For single use only. Remove the packaging only when ready to use, then check for minor leaks by firmly squeezing the bag. If leaks are found, it should not be used because it may have lost sterility. The solution should be visually inspected before use, and only transparent and particle-free solutions should be used. Do not use these bags in serial connections. Discard any remaining solution. Any unused medicinal product or waste material must be disposed of in accordance with local regulations. Do not reconnect partially used bags.

Linezolid Hikma infusion solution is compatible with the following solutions: 5% glucose for intravenous infusion, 0.9% sodium chloride for intravenous infusion, lactated Ringer's injection solution (Hartmann's solution).

Incompatibilities

No additives should be added to this solution. If linezolid is administered with other medicines simultaneously, each one should be administered separately according to its instructions for use. Similarly, if the same intravenous route is to be used for the sequential infusion of several medicines, it should be flushed before and after the administration of linezolid with a compatible infusion solution.

It is known that Linezolid Hikma infusion solution is not physically compatible with the following compounds: amphotericin B, chlorpromazine hydrochloride, diazepam, pentamidine isethionate, erythromycin lactobionate, sodium phenytoin, and sulfamethoxazole/trimethoprim. Additionally, it is not chemically compatible with sodium ceftriaxone.

Shelf Life

Before opening: 24 months.

After opening: From a microbiological point of view, unless the opening method excludes the risk of microbial contamination, the product should be used immediately. If not used immediately, the in-use storage times and conditions are the responsibility of the user.

Special Precautions for Storage

Store in the original packaging (overbag and carton) until ready for use to protect from light.