LINEZAN® 600 mq/300 ml solution for infusion
LINEZAN®
International non-patented name: Linezolid
Composition
Active substance: 1 ml of solution contains 2 mg of linezolid.
Excipients: sodium citrate dihydrate, anhydrous citric acid, glucose monohydrate, hydrochloric acid or sodium hydroxide, water for injection.
Description
It is a transparent, colorless, homogeneous solution. After a certain time, it is allowed to change the color of the solution to yellow.
Pharmacotherapeutic group
Other antibacterial medicines:
ATC : J01XX08.
Pharmacological properties
Pharmacodynamics
Mechanism of action Linezolid is a synthetic antibacterial substance belonging to a new class of antimicrobial drugs – the class of oxazolidinones, which shows clinical activity against aerobic gram-positive bacteria. Linezolid is also active in vitro against some anaerobic bacteria. Linezolid selectively inhibits the synthesis of bacterial proteins by a unique mechanism of action; therefore, cross-resistance of linezolid with other groups of antibiotics is not expected. In particular, it binds to the bacterial ribosomal site (23S of the 50S subunit) and prevents the initiation of the formation of the 70S functional complex, an important component of the translation process. Susceptibility: the results of the time/destruction curve study show that linezolid has a bacteriostatic effect on enterococci and staphylococci. It has been established that linezolid has a bactericidal effect on most strains of streptococci. Linezolid has both in vitro and clinical activity against the following microorganisms: Sensitive aerobic gram-positive bacteria: – Enterococcus faecium* – Enterococcus faecalis -Staphylococcus aureus* – Coagulation negative Staphylococci -Streptococcus agalactiae* -Streptococcus pneumoniae* -Streptococcus pyogenes* -Group C Streptococci -Group G Streptococci Sensitive anaerobic gram-positive bacteria: – Clostridium perfringens – Peptostreptococcus anaerobius – Peptostreptococcus strains Resistant bacteria: -Haemophilus influenzae – Moraxella catarrhalis – Neisseria strains -Enterobacteriaceae -Pseudomonas strains *Clinical efficacy has been demonstrated for susceptible isolates in clinically indicated trials.
Pharmacokinetics
Absorption Linezolid is rapidly and widely absorbed after oral administration. The maximum plasma concentration occurs in 1-2 hours and the bioavailability of linezolid is approximately 100%. Therefore, linezolid can be used both orally and intravenously without any dose adjustment. Distribution Human and animal studies show that linezolid is readily distributed in highly perfused tissues. Linezolid is 31% bound to plasma proteins and is dose-independent. The volume of distribution in healthy adults is about 40-50 liters in the steady state. Biotransformation Linezolid is primarily metabolized by oxidation of the morpholine ring. This mainly leads to the formation of two inactive open-chain carboxylic acid derivatives; aminoethoxyacetic acid metabolite (A) and hydroxyethyl glycine metabolite (B). Elimination Non-renal clearance accounts for approximately 65% of the total clearance of linezolid. At steady state, approximately 30% of each dose is excreted in the urine as linezolid, 40% as metabolite B, and 10% as metabolite A. Renal clearance of linezolid is low (approximately 40 ml/min) and is due to tubular reabsorption. Linearity/ non-linearity As the dose of linezolid increases, a low level of non-linearity in clearance is expected. This situation is thought to be due to lower renal and extrarenal clearance of linezolid at higher doses. However, the difference in clearance is small and does not manifest itself in the half-life. Average pharmacokinetic parameters of linezolid after single or multiple oral and intravenous doses are given in the table below.
Pharmacokinetics in special patient groups Elderly patients No significant difference in the pharmacokinetics of Linezolid is observed in elderly patients (65 years and older). Therefore, there is no need to adjust the dose in elderly patients. Children The dosage of LINEZAN in pediatric patients is determined according to their age and body weight (see: “Usage and dosage). Women There is no need to adjust the dose in women. Kidney failure No dose adjustment is required (see “Pharmacokinetics”, “Special warnings and precautions”). Severe renal failure (creatinine clearance < 30 ml/min): No dose adjustment is required. Since the clinical significance of the higher exposure (up to 10-fold) of the two primary metabolites is unknown, linezolid should be used with extreme caution in patients with severe renal impairment and only if the expected benefit outweighs the theoretical risk. Since approximately 30% of the dose of LINEZAN is excreted from the body during the first 3 hours of hemodialysis, LINEZAN should be used after dialysis in patients receiving dialysis. Although the primary metabolites are removed to some extent by hemodialysis, plasma concentrations of these metabolites are significantly higher than in patients with normal renal function or mild or moderate renal impairment. Therefore, LINEZAN can be used in patients with severe renal failure and receiving hemodialysis only if the expected benefit outweighs the theoretical risk. Until now, there is no information on the use of LINEZAN in patients receiving ineffective ambulatory peritoneal dialysis or in patients receiving any other alternative treatment of renal failure. Liver failure The pharmacokinetics of linezolid are unchanged in patients with mild-to-moderate hepatic impairment (Child-Pugh Class A or B). Based on available data, no dose adjustment is recommended in patients with mild-to-moderate hepatic impairment..
Instructions for use
LINEZAN is used to treat pneumonia or certain infections of the skin or under the skin is used for Nosocomial pneumonia: Infections caused by Staphylococcus aureus (methicillin-resistant and methicillin-susceptible strains) or Streptococcus pneumoniae (including multidrug-resistant strains). Community-acquired pneumonia: Infections caused by Streptococcus pneumoniae (including multidrug-resistant strains) or Staphylococcus aureus (only methicillin-susceptible strains). Complicated skin and soft tissue infections (diabetic foot lesions without accompanying osteomyelitis): Staphylococcus aureus (methicillin-resistant and methicillin-susceptible strains) Infections caused by Streptococcus pyogenes or Streptococcus agalactiae.
Contraindications
Allergy (hypersensitivity) to the active substance or any of the excipients (see “Ingredients”). If you are taking a medicine from the group of monoamine oxidase inhibitors (for example, phenelzine, isocarboxazid, selegiline, moclobemide) or if you have taken it up to two weeks ago. These drugs may be used to treat depression or Parkinson’s disease. If any of these conditions exist, the use of LINEZAN solution may not be suitable for you. If you suspect that these conditions apply to you, consult a doctor. If you have high blood pressure, whether or not you are taking medication for it, If you have been diagnosed with hyperthyroidism Adrenal gland tumor (phaeochromocytoma) or hormonal system tumor-related symptoms such as diarrhea, skin redness, wheezing (carcinoid syndrome), If you have bipolar depression, schizoaffective disorder, anxiety or other mental problems If any of the medicines listed below are used Cold and flu medicines or nasal decongestants (decongestants) containing pseudoephedrine or phenylpropanolamine Medicines used to treat asthma, such as salbutamol, terbutaline, and fenoterol Antidepressants such as amitriptyline, cipramil, clomipramine, dosulepin, doxepin, fluoxetine, fluvoxamine, imipramine, lofepramine, paroxetine, sertraline, known as tricyclic antidepressants or selective serotonin reuptake inhibitors; Medicines used to treat migraines, such as sumatriptan and zolmitriptan Medicines used to treat sudden and severe allergic reactions, such as adrenaline (epinephrine). Medicines that raise blood pressure, such as noradrenaline (norepinephrine), dopamine, and dobutamine Acute pain relievers such as pethidine Medicines used to treat anxiety disorders, such as buspirone
Special instructions and precaution
Before using LINEZAN, inform your doctor about the following cases: If you have bleeding or bleed easily Anemia Susceptibility to infections The presence of seizures in the anamnesis If you have liver or kidney problems, especially if you are on dialysis Diarrhea. If you experience any of the following symptoms during treatment, inform your doctor immediately: Vision problems, such as blurred vision, changes in color vision, difficulty seeing details, visual field disturbances. Treatment may be discontinued if there is diarrhea, especially bloody diarrhea. This can be inflammation of the intestine that occurs after treatment with antibiotics. Recurrent nausea and vomiting, abdominal pain, or hyperventilation. Even if these symptoms are in the past, please tell your doctor if they apply to you. Important information about some ingredients in LINEZAN: Each vial of this medicine contains 13.6 g of glucose. This should be considered in patients with diabetes. Each vial of this medicine contains 38.48 mg of sodium. This should be considered in patients on a controlled sodium diet.
Interaction with other medicines
Sometimes LINEZAN interacts with certain medications. VEMEZOLID may cause side effects such as changes in blood pressure, body temperature, heart rate. Tell your doctor if any of the medicines listed below are being used or have been used in the past two weeks. Do not use LINEZAN if you are currently taking the following medicines or will take them in the near future. Medicines belonging to the group of monoamine oxidase inhibitors (eg, phenelzine, isocarboxazid, selegiline, moclobemide) used to treat depression or Parkinson’s disease. Also, consult your doctor if you are taking any of the medications listed below. A doctor may decide to treat with LINEZAN, but general health and blood pressure should be checked before and during treatment. In other cases, the doctor may decide on another treatment method that is more beneficial for the patient. Cold and flu medications containing pseudoephedrine or phenylpropanolamine, or medications used to relieve nasal congestion. Medicines used to treat asthma such as salbutamol, terbutaline, fenoterol. Antidepressants such as amitriptyline, cipramil, clomipramine, dosulepin, doxepin, fluoxetine, fluvoxamine, imipramine, lofepramine, paroxetine, sertraline, also known as tricyclic antidepressants or selective serotonin reuptake inhibitors. Medicines used to treat migraines, such as sumatriptan and zolmitriptan. Medicines used to treat sudden and severe allergic reactions, such as adrenaline (epinephrine). Medicines that raise blood pressure, such as noradrenaline (norepinephrine), dopamine, and dobutamine. Acute pain relievers such as pethidine. Medicines used to treat anxiety disorders, such as buspirone. Medicines that prevent blood clotting, such as warfarin. Rifampicin-an antibiotic. Tell your doctor or pharmacist if you are taking or have recently taken any other prescription or over-the-counter medicines.
Use during pregnancy and lactation
Consult a doctor or pharmacist before using the medicine! The effect of LINEZAN in pregnant women has not been determined. Therefore, do not use the drug during pregnancy without consulting a doctor. Tell your doctor if you are pregnant or planning to become pregnant. If you feel that you are pregnant during the treatment period, inform the doctor immediately! Lactation Consult a doctor or pharmacist before using the medicine! It is not known whether LINEZAN passes into breast milk. When deciding whether to continue/discontinue treatment or discontinue breast-feeding during lactation, your doctor will consider the benefit to the mother of treatment with LINEZAN and the benefit of breast-feeding to the nursing child.
Effects on the ability to drive vehicles and other potentially dangerous mechanisms
LINEZAN may cause dizziness. If such situations occur, do not use LINEZAN, as it may adversely affect the ability to drive vehicles and other potentially dangerous machinery.
Method of use and dosage
The drug is injected intravenously. The dose will be determined by the doctor depending on the disease. This medicine will be administered as an intravenous infusion by a doctor or medical staff. For adults (18 years and older), 300 ml (600 mg linezolid) of the solution will be injected directly into the blood (intravenously) over 30 minutes to 120 minutes twice a day. The course of treatment is usually 10-14 days, but can be extended up to 28 days. Safety and efficacy of the drug after 28 days of treatment have not been established. Your doctor will decide on the duration of treatment. While taking LINEZAN, the doctor will perform regular blood tests to monitor blood parameters. Use in children LINEZAN is usually not used in the treatment of children and adolescents (under 18 years old). Special cases Kidney failure The doctor does not make special adjustments to the dosage for people with kidney failure. If kidney failure has developed or the patient is on dialysis, the doctor will decide whether to use the drug. Dialysis patients should be prescribed the drug after dialysis. Liver failure The doctor does not make special adjustments to the dosage for people with liver failure. Depending on the degree of liver failure, the doctor will decide whether to use this medicine or not. Use of LINEZAN with food and drinks: LINEZAN can be used before food intake, during food intake or after food intake. Avoid overripe cheese, yeast extracts, or soybean extracts, such as soy sauce, and alcoholic beverages, especially draft beer and wine.
If a throbbing headache develops after eating or drinking, consult a doctor or pharmacist immediately. If the use of the dose is forgotten Missing a dose is less likely, as the infusion of LINEZAN is carried out under the strict supervision of a doctor or nurse. However, if you think you have missed a therapeutic dose, tell your doctor or nurse right away. Effects that can be observed after the end of treatment with LINEZAN Consult a doctor about the use of the drug.
Side effects
As with all drugs, LINEZAN drug can cause side effects in patients with high sensitivity to its components. If any side effects occur during treatment with LINEZAN, tell your doctor, nurse or pharmacist immediately. Skin reactions such as red sores and crusting (dermatitis), rash, itching or swelling, especially around the face and neck. This can be a cause of an allergic reaction and it is necessary to stop using LINEZAN. Blurry vision, changes in color vision, difficulty seeing details, vision problems. If you have diarrhea, especially bloody diarrhea, treatment may need to be stopped. This can be inflammation of the intestine that can occur after treatment with antibiotics. Recurrent nausea and vomiting, abdominal pain and hyperventilation. People who have been prescribed linezolid for more than 28 days have been reported to experience symptoms such as numbness, tingling, or blurred vision. If you experience vision problems, you should consult a doctor as soon as possible. Other side effects Side effects are listed according to the categories below. Very common: may affect at least 1 in 10 patients. Common: may affect up to 1 in 10 but more than 1 in 100 patients. Uncommon: may affect up to 1 in 100 but more than 1 in 1000 patients. Rare: May affect up to 1 in 1,000 patients. Very rare: may occur in less than 1 in 10,000 patients. Not known: it is not possible to determine the frequency of occurrence based on the available data. Often: Fungal infections, especially vaginal infections and oral thrush. Headache. Insomnia. Dizziness. Increased blood pressure. Indigestion, abdominal pain, constipation. Metallic taste in the mouth.
Fever, pain. Redness of the skin, rash. Diarrhea, nausea and vomiting. A change in the results of certain blood tests, including measurements of kidney or liver function or blood sugar levels. Unexplained bleeding and bruising caused by changes in the number of certain cells in the blood, which can affect clotting or cause anemia. Sometimes Inflammation in the vagina or genital area in women. A change in the number of certain cells in the blood that fight infection. Cramping, sometimes a tingling sensation or numbness. Hyponatremia. Blurry vision. “Ringing” in the ears (tinnitus). Arrhythmia (tachycardia). Inflammation in the veins, transient ischemic attacks (transient disruption of blood flow to the brain; causes reduced vision, weakness in the legs and arms, impaired speech and fogging of consciousness). Dryness or sores in the mouth, swelling, sores, discoloration of the tongue. Pain around the vein. Inflammation of the veins (including the site of infusion by drip method). More frequent urination. Chills, pain at the injection site. Feeling tired and thirsty. Pancreatitis, gastritis, flatulence, watery stools. Increased sweating, urticaria, dermatitis. Renal failure, polyuria. Changes in the level of proteins, salts or enzymes in the blood, which are indicators of kidney and liver functions. A decrease in blood cells that fight infections. The side effects listed below have been observed to a lesser extent. Myelosuppression. Serotonin syndrome (rapid heartbeat, agitation, abnormal sweating, hallucinations, involuntary tremors, and chills). Peripheral neuropathy. Lactoacidosis (symptoms include repeated nausea and vomiting, abdominal pain, hyperventilation). Anaphylaxis. Serious skin diseases, alopecia. Antibiotic-related colitis, including pseudomembranous colitis. Pancytopenia. Optic neuropathy, optic neuritis, loss of vision, decreased visual acuity, change in color vision.
Overdose
If you think an overdose of LINEZAN infusion has been given, tell your doctor or nurse immediately.
Packing form
300 ml (600 mg linezolid) solution in a polypropylene vial closed with a bromobutyl stopper and secured with a white flip-off cap. 1 (2, 5, 10, 20) vials are packed in a cardboard box with the corresponding number of leaflets.
Store condition
It should be stored at room temperature below 25 C, in the original packaging, in a dry place and out of the reach of children. The vial should be used immediately after opening. After opening, any unused solution should be discarded. LINEZAN solution for infusion may turn yellow over time, but this does not affect the quality of the medicine.
Shelf life
The shelf life is indicated on the packaging
By prescription
Manufacturer
ANFARM HELLAS S.A.
61st km NAT. RD. Athens-Lamia Schimatari Viotias 32009, Greece.