Linezolid Hikma

Package leaflet: Information for the user

Linezolid Hikma 2 mg/ml infusion solution

Linezolid
Generic medicine
Read this entire leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, including those not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

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

Linezolid Hikma is an antibiotic belonging to the oxazolidinone group that works by inhibiting the growth of certain bacteria causing infections. It is used to treat pneumonia and certain skin or soft tissue infections. Your doctor will decide whether Linezolid Hikma is suitable for treating your infection.

2. What you need to know before taking Linezolid Hikma

Do not use Linezolid Hikma

• if you are allergic to linezolid or to any of the other ingredients of this medicine (listed in section 6)
• if you are taking or have taken within the last 2 weeks any medicines known as Monoamine Oxidase Inhibitors (MAOIs: for example phenelzine, isocarbazide, selegiline, moclobemide). These medicines may be used to treat depression or Parkinson's disease;
• if you are breastfeeding, as Linezolid Hikma passes into breast milk and could affect your baby.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Linezolid Hikma.
Linezolid Hikma may not be suitable for you if the answer to any of the following questions is yes.
In this case, inform your doctor, who may need to monitor your general health and blood pressure before and during treatment, or who may decide that another treatment would be more appropriate for you.
If you are unsure whether these conditions apply to you, ask your doctor.

• Do you have high blood pressure, whether or not you are taking medicines for it?
• Have you been diagnosed with an overactive thyroid?
• Do you have a tumour of the adrenal glands (pheochromocytoma) or carcinoid syndrome (caused by tumours of the hormonal system with symptoms such as diarrhoea, skin flushing, wheezing)?
• Do you suffer from manic depression, schizoaffective disorder, mental confusion, or other mental health problems?
• Are you taking opioids? Using certain medicines, including antidepressants and opioids, together with Linezolid Hikma can lead to serotonin syndrome, a potentially life-threatening condition (see section 2 “Other medicines and Linezolid Hikma” and section 4).

Take special care with Linezolid Hikma
Inform your doctor before being treated with this medicine if:

• you bruise easily or bleed easily;
• you are anaemic (have low levels of red blood cells in your blood);
• you tend to develop infections;
• you have a history of seizures;
• you have liver or kidney problems, especially if you are on dialysis;
• you have diarrhoea.

Immediately inform your doctor if during treatment you experience:

• vision problems such as blurred vision, changes in colour vision, difficulty seeing details, or narrowing of your visual field;
• loss of sensation in arms or legs, or tingling or prickling sensations in arms or legs;
• diarrhoea during or after taking antibiotics, including Linezolid Hikma. If this becomes severe or persistent, or if you notice blood or mucus in your stools, stop taking Linezolid Hikma immediately and consult your doctor. In this case, do not take medicines that block or slow down intestinal movement;
• recurrent nausea or vomiting, abdominal pain, or rapid breathing.

Other medicines and Linezolid Hikma
There is a risk that Linezolid Hikma may interact with certain other medicines, causing unwanted effects such as changes in blood pressure, body temperature, or heart rate.
Inform your doctor if you are taking or have recently taken any other medicines.
Inform your doctor if you are taking or have taken any of the following medicines within the last 2 weeks, as Linezolid Hikma must not be taken if you are already taking these medicines or have recently taken them.
(See also section 2 above “Do not take Linezolid Hikma”).

• Monoamine oxidase inhibitors (MAOIs, for example phenelzine, isocarbazide, selegiline, moclobemide). These medicines may be used to treat depression or Parkinson's disease. Also inform your doctor if you are taking the following medicines. Your doctor may still decide to prescribe Linezolid Hikma, but will need to monitor your general health and blood pressure before and during treatment. In other cases, your doctor may decide that another treatment would be more suitable for you.
• Decongestants for colds or flu containing pseudoephedrine or phenylpropanolamine.
• Certain medicines used to treat asthma such as salbutamol, terbutaline, fenoterol;
• Certain antidepressants known as tricyclics or SSRIs (selective serotonin reuptake inhibitors). There are many of these, 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 may interact with Linezolid Hikma and symptoms such as involuntary rhythmic muscle contractions, including muscles controlling eye movement, agitation, hallucinations, coma, excessive sweating, tremor, exaggerated reflexes, increased muscle tension, and body temperature above 38°C may occur. Contact your doctor if you experience such symptoms.
• Medicines used to treat migraine such as sumatriptan and zolmitriptan.
• Medicines used to treat severe and sudden allergic reactions such as adrenaline (epinephrine).
• Medicines that increase blood pressure, such as noradrenaline (norepinephrine), dopamine, and dobutamine.
• Opioids, such as pethidine, used to treat moderate to severe pain.
• Medicines used to treat anxiety disorders, such as buspirone.
• Medicines that inhibit blood clotting such as warfarin.
• An antibiotic called rifampicin.

Linezolid Hikma with food, drinks and alcohol

• You may take Linezolid Hikma before, during or after a meal.
• Avoid eating large amounts of aged cheese, yeast extracts or soybean extracts (e.g. soy sauce), and avoid drinking alcohol, especially draught beer and wine. This is because Linezolid Hikma may react with a substance called tyramine, which is naturally present in certain foods. This interaction may increase blood pressure.
• If you develop a pulsating headache after eating or drinking, inform your doctor, pharmacist, or nurse immediately.

Pregnancy, breastfeeding and fertility
The effect of Linezolid Hikma in pregnant women is unknown. Therefore, it should not be taken during pregnancy unless advised by your doctor. If you are pregnant, suspect you may be pregnant, are breastfeeding, or planning to become pregnant, consult your doctor or pharmacist before taking this medicine.
You must not breastfeed while taking Linezolid Hikma, as the medicine passes into breast milk and may affect your baby.
Driving and using machines
Linezolid Hikma may cause dizziness or vision problems. If this occurs, do not drive or operate machinery. Remember that if you do not feel well, your ability to drive or operate machinery may be impaired.
Linezolid Hikma contains
Glucose
This medicine contains 45.7 mg of glucose (i.e. 13.7 g/300 ml). This should be taken into account in patients with diabetes mellitus.
Sodium
This medicine contains 114 mg of sodium (the main component of table salt) in each bag. This is equivalent to 5.7% of the maximum daily recommended dietary intake for an adult.

3. How to take Linezolid Hikma

Adults
Always use this medicine exactly as described in this leaflet or as told by your doctor, pharmacist, or nurse.
If you have any doubts, consult your doctor, pharmacist, or nurse.
This medicine will be administered to you by intravenous infusion (via a drip into a vein) by a doctor or healthcare professional.
The recommended dose for adults (from 18 years of age) is 300 ml (600 mg of linezolid) twice daily, given directly into the bloodstream (intravenously) by infusion over a period of 30 to 120 minutes.
If you are undergoing renal dialysis, Linezolid Hikma will be administered to you after the dialysis session.
A treatment course usually lasts from 10 to 14 days, but may extend up to 28 days. The safety and efficacy of this medicine have not been established for periods longer than 28 days.
Your doctor will decide how long your treatment should continue.
During treatment with Linezolid Hikma, your doctor will regularly perform blood tests to monitor your blood cell counts.
Your doctor will monitor your vision if your treatment with Linezolid Hikma lasts longer than 28 days.

Use in children and adolescents
Linezolid Hikma is normally not used to treat children and adolescents (under 18 years of age).

If you take more Linezolid Hikma than you should
If you think you have been given too much Linezolid Hikma, inform your doctor or nurse immediately.

If you forget to use Linezolid Hikma
Since this medicine will be administered under strict medical supervision, it is very unlikely that you will miss a dose.
If you think you have missed a dose of treatment, inform your doctor or nurse immediately.
Do not take a double dose to make up for a forgotten dose.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Immediately inform your doctor, nurse or pharmacist if you experience any of these
side effects during treatment with Linezolid Hikma.
The serious (with frequency in brackets) side effects of Linezolid Hikma are:

• Severe skin reactions (uncommon), swelling, particularly around the face and neck (uncommon), wheezing and/or difficulty breathing (rare). This could be a sign of an allergic reaction and you may need to stop using Linezolid Hikma. Skin reactions such as a raised purple rash due to inflammation of blood vessels (rare), red, irritated skin and peeling (dermatitis) (uncommon), rash (common), itching (common).
• Vision problems (uncommon) such as blurred vision, changes in colour vision (not known), difficulty seeing details (not known), or narrowing of the visual field (rare).
• Severe diarrhoea containing blood and/or mucus (antibiotic-associated colitis including pseudomembranous colitis), which in rare cases may progress to life-threatening complications (uncommon).
• Recurrent nausea or vomiting, abdominal pain or rapid breathing (rare).
• Seizures or convulsions (uncommon) have been reported with linezolid.
• Serotonin syndrome (not known): you must inform your doctor if you experience agitation, confusion, delirium, stiffness, tremor, lack of coordination, convulsions, rapid heartbeat, severe breathing problems and diarrhoea (which may indicate serotonin syndrome) while taking antidepressants known as SSRIs or opioids (see section 2).
• Unexplained bleeding or bruising, which may be due to changes in the number of certain blood cells that can affect blood clotting or lead to anaemia (common).
• Changes in the number of certain 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).
• Inflammation of the pancreas (uncommon).
• Convulsions (uncommon).
• Transient ischaemic attacks (temporary disturbance in blood flow to the brain causing short-term symptoms such as loss of vision, weakness in arms and legs, speech disturbances and loss of consciousness) (uncommon).
• Ringing in the ears (tinnitus) (uncommon). Numbness, tingling or blurred vision have been reported in patients treated with Linezolid for more than 28 days. If you have difficulty with your vision, you should consult your doctor as soon as possible.

Other side effects include:
Common (may affect up to 1 in 10 people):

• fungal infections, especially vaginal or oral “thrush”
• headache
• metallic taste in the mouth
• diarrhoea, nausea or vomiting
• changes in certain blood test results, including those measuring proteins, salts or enzymes used to assess kidney or liver function, or blood sugar levels
• difficulty falling asleep
• increased blood pressure
• anaemia (low level of red blood cells in the blood)
• dizziness
• localized or general abdominal pain
• constipation
• indigestion
• localized pain
• reduced platelet count

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

• inflammation of the vagina or other genital area disorders in women
• tingling or numbness sensation
• swollen, painful or discoloured tongue
• dry mouth
• pain at the site where the infusion (drip) is administered and in the surrounding area
• inflammation of veins (including at the site where the infusion (drip) was administered)
• need to urinate more frequently
• chills
• thirst
• increased sweating
• hyponatraemia (low sodium levels in the blood)
• kidney failure
• abdominal swelling
• injection site pain
• increased creatinine
• stomach ache
• changes in heart rate (e.g. increased rate)
• decreased blood cell count
• weakness and/or sensory changes

Rare (may affect up to 1 in 1,000 people):

• superficial tooth discoloration, which can be removed by dental cleaning (manual removal).

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

• alopecia (hair loss)

Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse.
You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Linezolid Hikma

Keep this medicine out of the sight and reach of children.
Store in the original packaging (wrapper and carton) until the time of use to protect it from light.
Do not use this medicine after the expiry date stated on the carton, bag, and foil after "Exp". The expiry date refers to the last day of that month.
Hospital staff will ensure that Linezolid Hikma is not used after the expiry date printed on the bag after "Exp" and that it is administered immediately after breaking the seal.
Staff will also visually inspect the solution before use and will use only a clear solution free from visible particles. They will also check that the solution is properly stored in its carton and aluminium foil wrapper to protect the product from light and that it is kept out of the sight and reach of children until required.

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

Do not dispose of medicines via wastewater or household waste.
Ask your pharmacist how to dispose of medicines you no longer use. These measures will help protect the environment.

6. Package contents and other information

What Linezolid Hikma contains

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

Description of the appearance of Linezolid Hikma and contents of the pack
Linezolid Hikma is presented as a clear solution in a 300 ml infusion bag.
The bags are supplied in cartons containing 10 bags.
Marketing Authorisation Holder and Manufacturer
Hikma Farmacêutica (Portugal), S.A.
Estrada do Rio da Mó, nº8, 8A, 8B
Fervença
2705-906 Terrugem SNT
Portugal
This medicinal product is authorised in the Member States of the European Economic Area with the
following names:
Austria: Linezolid Hikma 2 mg/ml Infusionslösung
France: Linezolid Hikma 2 mg/mL solution for infusion
Germany: Linezolid Hikma 2 mg/ml Infusionslösung
Italy: Linezolid Hikma
Portugal: Linezolida Hikma
Spain: Linezolid Hikma 2 mg/ml solution for infusion EFG

The following information is intended for medical or healthcare professionals only:
Linezolid Hikma 2 mg/ml solution for infusion
Linezolid
IMPORTANT: Refer to the Summary of Product Characteristics before prescribing.
Dosage and method of administration
Treatment with linezolid should only be initiated in a hospital setting and after consultation with a qualified specialist such as a microbiologist or an infectious disease specialist.
Patients starting treatment with the parenteral formulation may subsequently switch to oral formulations if clinically appropriate. In such cases, no dosage adjustment is required, as the oral bioavailability of linezolid is approximately 100%.
The infusion solution must be administered over a period of 30 to 120 minutes.
The recommended dosage of linezolid must be administered intravenously (i.v.) twice daily.
Recommended dosage and duration of treatment in adults:
The duration of treatment depends on the pathogen, the site and severity of the infection, and the patient's clinical response.
The following recommendations on treatment duration reflect those used in clinical trials. Shorter treatment regimens may be suitable for certain types of infection but have not been evaluated in clinical trials.
The maximum duration of treatment is 28 days. The safety and efficacy of linezolid administered for periods longer than 28 days have not been established.
No dose increase or extension of treatment duration is required for infections associated with concomitant bacteraemia.
The recommended dosage for the infusion solution is as follows:

Paediatric 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 further data become available, the use of linezolid in this age group is not recommended.

Elderly patients: No dose adjustment is required.

Severe renal impairment (i.e. CrCl <30 ml/min): No dose adjustment is required. Due to the unknown clinical significance of increased exposure (up to 10-fold) to the two primary metabolites of linezolid in patients with severe renal impairment, linezolid should be used with particular caution in these patients and only when the expected benefit outweighs the theoretical risk.

Since approximately 30% of a dose of linezolid is removed during 3 hours of haemodialysis, Linezolid Hikma should be administered after dialysis in patients undergoing this treatment. The primary metabolites of linezolid are partially removed by haemodialysis, but concentrations of these metabolites remain considerably higher after dialysis than those observed in patients with normal renal function or mild to moderate renal impairment. Therefore, linezolid should be used with particular caution in patients with severe renal impairment undergoing dialysis and only if the expected benefit outweighs the theoretical risk.

To date, there is no experience with administration of linezolid in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) or other alternative treatments for renal failure (other than haemodialysis).

Hepatic impairment: Patients with mild to moderate hepatic impairment (Child-Pugh class A or B): No dose adjustment is required.

Severe hepatic impairment (Child-Pugh class C): Since linezolid is metabolized via a non-enzymatic process, impaired hepatic function is not expected to significantly alter its metabolism, and therefore dose adjustment is not recommended. However, clinical data are limited and it is recommended that linezolid be used in such patients only when the expected benefit outweighs the theoretical risk.

Overdose

There is no known specific antidote. Cases of overdose have not been reported. However, the following information may still be useful: supportive treatment together with maintenance of glomerular filtration is recommended. Approximately 30% of a dose of linezolid is removed during 3 hours of haemodialysis, but there are no data available on the elimination of linezolid by peritoneal dialysis or haemoperfusion.

Instructions for use and handling

For single use only. Remove the outer wrapper immediately before use and check for any signs of leakage by firmly squeezing the bag. Do not use if leakage is observed, as sterility may be compromised. The solution should be inspected visually prior to use; only clear solutions without particulate matter should be used. Do not use these bags in series connections. Any unused solution must be discarded. Any unused medicinal product or waste material must be disposed of in accordance with local requirements.
Do not reconnect partially used bags.
Linezolid Hikma infusion solution is compatible with the following solutions: 5% glucose intravenous infusion, 0.9% sodium chloride intravenous infusion, Ringer-lactate injectable solution (Hartmann's injectable solution).
Incompatibilities
No additives should be introduced into this solution. If linezolid is to be administered concomitantly with other medicinal products, each should be administered separately according to its own instructions for use. Similarly, if the same intravenous line is used for sequential infusion of multiple drugs, the line must be flushed before and after administration of linezolid with a compatible infusion solution.
Linezolid Hikma infusion solution is known to be physically incompatible with the following compounds: amphotericin B, chlorpromazine hydrochloride, diazepam, pentamidine isethionate, erythromycin lactobionate, sodium phenytoin, and sulfamethoxazole/trimethoprim. In addition, it is chemically incompatible with ceftriaxone sodium.
Shelf life
Before opening: 24 months
After opening: From a microbiological standpoint, unless the method of opening excludes the risk of microbial contamination, the product should be used immediately. If not used immediately, the times and conditions of storage during use are the responsibility of the user.
Special precautions for storage
Store in the original packaging (wrapper and carton) until time of use to protect from light.