Active substanceMeropenemMeropenem
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  • Dosage form: & nbsppowder for solution for intravenous administration
    Composition:

    In 1 bottle in mg contains:

    Active substance:

    Dosage 0.5 g

    Dosage 1 g

    meropenem trihydrate

    570.0 mg

    1140.0 mg

    is equivalent to meropenem

    Excipient:

    500.0 mg

    1000.0 mg

    sodium carbonate

    104.0 mg

    208.0 mg

    in terms of sodium

    45.1 mg

    90.2 mg

    Total weight of the contents of the bottle

    674.0 mg

    1348.0 mg

    Description:

    From white to light yellow color powder.

    Pharmacotherapeutic group:Antibiotic carbapenem
    ATX: & nbsp

    J.01.D.H.02   Meropenem

    J.01.D.H   Carbapenems

    Pharmacodynamics:

    Meropenem is an antibiotic of the carbapenem class, intended for parenteral use, relatively resistant to human dehydropeptidase-1 (DHP-1), does not require additional administration of DHP-1 inhibitor.

    Meropenem has a bactericidal effect due to the effect on the synthesis of the bacterial cell wall.The high bactericidal activity of meropenem against a wide range of aerobic and anaerobic bacteria is due to the high capacity of meropenem penetrate through the bacterial cell wall, a high level of stability to the majority of beta-lactamases and significant affinity for various penicillin-binding proteins (PSBs). The minimum bactericidal concentrations (MBCs) are usually the same as the minimum inhibitory concentrations (MICs). For 76% of the tested bacterial species, the MBC / MIC ratio was 2 or less. Tests in vitro show that meropenem acts synergistically with various antibiotics. In the tests in vitro and in vivo shown, that meropenem has a post-antibiotic effect.

    Microorganisms may possess one or more of the listed mechanisms of resistance to meropenem: a violation of the permeability of the cell wall of Gram-negative bacteria due to a violation of the synthesis of porins; decrease in affinity for the target PSB; activation of efflux mechanisms; production of beta-l actam az. under the action of which hydrolysis of carbapenems takes place.

    The only recommendedthe criteria for sensitivity to meropenem are based on the pharmacokinetics of the drug and on the correlation of clinical and microbiological data - the diameter of the zone and MICs, determined for the respective pathogens.

    Category of the pathogen

    Diameter of the zone (mm)

    Sensitive

    ≥14

    Intermediate

    From 12 to 13

    Resistant

    11

    The following table shows the threshold values ​​of MIC of meropenem in the European Union (EU) for various bacterial pathogens in clinical settings:

    Pathogens

    Sensitivity

    Resistance

    (mg / L)

    (mg / L)

    Enterobacteriaceae

    ≤2

    >8

    Pseudomonas

    ≤2

    >8

    Acinetobacter

    ≤2

    >8

    Streptococcus groups A, B,

    C, G

    ≤2

    >2

    Streptococcus pneumoniae1

    ≤2

    >2

    Other streptococci

    2

    2

    Enterococcus5

    -

    -

    Staphylococcus2

    Depends on the availability of sensitivity to

    methicillin

    Haemophilus influenzae1, Moraxella catarrhalis

    ≤2

    >2

    Neisseria meningitides2,3

    ≤0,25

    >0,25

    Gram-positive anaerobes

    ≤2

    >8

    Gram-negative anaerobes

    ≤2

    >8

    Nonspecific thresholds4

    ≤2

    >8

    1 - The sensitivity threshold for Streptococcus pneumoniae and Haemophilus influenzae in meningitis is 0.25 mg / L.

    2 - Strains for which MICs are above the sensitivity threshold are rare or not currently detectable. If such a strain is detected, the MIC test is repeated, when the result is confirmed, the strain is sent to a reference laboratory, and the strain is considered resistant until a confirmed clinical effect is obtained with respect to it.

    3 - Values ​​used only for meningitis.

    4 - For all other pathogens, according to pharmacokinetic and pharmacodynamic data, without taking into account the specific distribution of MIC specific pathogens.

    5 - The sensitivity test is not recommended, since this agent is not an optimal target for meropenem.

    Pathogens, sensitive to meropenem:

    Gram-positive aerobes:

    Enterococcus faecalis1,

    Staphylococcus aureus (methicillin-sensitive)2,

    Staphylococcus spp. (methicillin-sensitive), including Staphylococcus epidermidis; Streptococcus agalactiae (group B),

    Group Streptococcus milleri (S. anginosus, S. constellatus, S. intermedius),

    Streptococcus pneumoniae.

    Streptococcus pyogenes (Group A).

    Gram-negative aerobes:

    Citrobacter freundii,

    Citrobacter koseri,

    Enterobacter aerogenes,

    Enterobacter cloacae,

    Escherichia coli,

    Haemophilus influenzae,

    Klebsiella oxytoca,

    Klebsiella pneumoniae,

    Morganella morganii,

    Neisseria meningitidis,

    Proteus mirabilis,

    Proteus vulgaris,

    Serratia marcescens.

    Gram-positive anaerobes:

    Clostridium perfringens.

    Peptoniphilus asaccharolyticus,

    Peptostreptococcus spp. (including P. micros, P. anaerobius. P. magnus).

    Gram-negative anaerobes:

    Bacteroides caccae,

    Bacteroides fragilis,

    Prevotella bivia,

    Prevotella disiens

    Pathogens for which the problem of acquired resistance is relevant:

    Gram-positive aerobes:

    Enterococcus faecium1

    Gram-negative aerobes:

    Acinetobacter spp.,

    Burkholderia cepacia,

    Pseudomonas aeruginosa.

    Pathogens with natural resistance:

    Stenotrophomonas maltophilia.

    Legionella spp.

    Other pathogens:

    Chlamydophila pneumoniae,

    Chlamydophila psittaci,

    Coxiella burnettii,

    Mycoplasma pneumoniae.

    1 - pathogens with intermediate sensitivity;

    2 - all methicillin-resistant staphylococcus are resistant to meropenem.

    Pharmacokinetics:

    With a single intravenous (IV) administration within 30 minutes, the maximum concentration in the plasma (FROMmax) is 11 μg / ml for a dose of 250 mg, 23 μg / ml for a dose of 500 mg and 49 μg / ml for a dose of 1 g.

    However, with respect to Cmax and the area under the pharmacokinetic curve "concentration-time" (AUC) There is no absolute pharmacokinetic proportional dependence on the administered dose. There was a decrease in plasma clearance from 287 to 205 ml / min with increasing doses from 250 mg to 2 g.

    With iv bolus administration for 5 minutes, the dose of 500 mg Cmax is 52 μg / ml; The dose of 1 g is 112 μg / ml.

    6 hours after IV administration of 500 mg of the drug, the concentration of meropenem in the blood plasma is reduced to 1 μg / ml and lower.

    Extended (up to 3 hours) infusion of carbapenems can lead to optimization of their pharmacokinetic and pharmacodynamic parameters.

    With a standard 30-minute infusion of two doses of 500 and 2000 mg every 8 hours in healthy volunteers, the value of% T> MIC (the ratio between the period of time when the drug concentration exceeds MIC and the dosing interval: MIC = 4 μg / ml) was 30% and 58%. When volunteers were given the same doses by a 3-hour infusion every 8 hours, the% T> MIC index increased to 43% and 73%, respectively, for 500 and 2000 mg.With an intravenous bolus dose of 1000 mg for 10 min, the average plasma concentration in healthy volunteers exceeded the MIC of 4 μg / ml for 42% of the dosing interval, compared to 59% with a 3-hour infusion of 1000 mg.

    Meropenem penetrates well into most tissues and body fluids, incl. in the cerebrospinal fluid (CSF) of patients with bacterial meningitis, reaching concentrations exceeding those required for the suppression of most bacteria. Binding to plasma proteins is approximately 2%. Exposed to a slight metabolism in the liver with the formation of a single inactive metabolite. The half-life (T1/2) in patients with normal renal function approximately 1 hour, in children under 2 years - 1.5-2.3 hours. In the dose range of 10-40 mg / kg in adults and children, a linear dependence of pharmacokinetic parameters is observed.

    Do not cumulate.

    It is excreted by the kidneys - 70% unchanged for 12 hours. The concentration of meropenem in the urine, exceeding 10 μg / ml, is maintained for 5 hours after the administration of 500 mg.

    Renal insufficiency

    Studies of pharmacokinetics in patients with renal insufficiency showed that the clearance of meropenem correlates with creatinine clearance.Such patients need dose adjustment.

    The study of pharmacodynamics in elderly people revealed a decrease in the clearance of meropenem, which correlated with the age-related decrease in creatinine clearance. Meropenem is derived in hemodialysis with a clearance of about 4 times the clearance of meropenem in patients with anuria.

    Liver failure

    Studies of pharmacokinetics in patients with liver disease have shown that these pathological changes do not affect the pharmacokinetics of meropenem.

    Indications:

    Infectious-inflammatory diseases in children (over 3 months old) and adults caused by one or several susceptible to meropenem pathogens:

    - pneumonia, including nosocomial pneumonia;

    - urinary tract infection;

    - infection of the abdominal cavity;

    - Infectious-inflammatory diseases of the pelvic organs, such as endometritis;

    - infection of the skin and its structures;

    - meningitis;

    - septicemia.

    Empirical therapy of adult patients with a presumed infection with symptoms of febrile neutropenia in monotherapy or in combination with antiviral or antifungal agents.

    The effectiveness of the drug Merexide is proven both in monotherapy mode and in combination with other antimicrobial agents in the treatment of polymicrobial infections.

    Contraindications:

    Hypersensitivity to meropenem or other drugs of the carbapenem group in the anamnesis.

    Severe hypersensitivity (anaphylactic reactions, severe skin reactions) to any antibacterial agent having a beta-lactam structure (ie to penicillins or cephalosporins). Children up to 3 months.

    Carefully:

    With simultaneous application with potentially nephrotoxic drugs, with diseases of the gastrointestinal tract (including colitis).

    Pregnancy and lactation:

    Pregnancy

    The safety of the use of meropenem in women during pregnancy has not been studied. Studies in animals have not shown any adverse effects on the developing fetus.

    The drug should not be used during pregnancy, except when the potential benefit of its use for the mother exceeds the possible risk to the fetus. In each case, the drug should be administered under strict medical supervision.

    Breastfeeding period

    Data were obtained on the isolation of meropenem with breast milk. Meropenem should not be used during breastfeeding, except in cases where the potential advantage for the mother from the use of the drug exceeds the possible risk to the child. Having evaluated the advantage for the mother, a decision should be made to stop breastfeeding or to cancel the drug.

    Dosing and Administration:

    The dose and duration of therapy should be determined depending on the type and severity of the infection and the condition of the patient.

    The following daily doses are recommended:

    Adults

    500 mg intravenously every 8 hours in the treatment of pneumonia, urinary tract infections, gynecological infections such as endometritis, skin infections and skin structures.

    1 g intravenously every 8 hours in the treatment of nosocomial pneumonia, peritonitis, suspected bacterial infection in patients with symptoms of neutropenia, and septicemia.

    In the treatment of meningitis, the recommended dose is 2 g every 8 hours.

    The safety of taking a dose of 2 g in the form of a bolus injection has not been sufficiently studied.

    Special categories of patients

    Patients with impaired renal function

    In patients with creatinine clearance less than 51 mL / min, the dose should be reduced as follows:

    Creatinine clearance

    Dose

    Frequency is entered and si

    26-50 ml / min

    500 mg - 1.0 g - 2.0 g

    every 12 hours

    10-25 ml / min

    250 - 500 mg - 1.0 g

    every 12 hours

    <10 ml / min

    250 - 500 mg - 1.0 g

    every 24 hours

    Meropenem is excreted in hemodialysis and hemofiltration. If prolonged treatment is required, it is recommended to administer a dose (determined according to the type and severity of the infection) at the end of hemodialysis to restore the effective concentration in the blood plasma.

    At present, there is no data on the experience of using the drug for administration to patients on peritoneal dialysis.

    Patients with impaired hepatic function

    Patients with hepatic insufficiency do not need a dose adjustment.

    Elderly patients

    In elderly patients with normal renal function or creatinine clearance greater than 50 mL / min, dose adjustment is not required.

    Children

    For children aged 3 months to 12 years, the recommended dose for intravenous administration is 10-20 mg / kg every 8 hours, depending on the type and severity of the infection, the sensitivity of the pathogen and the patient's condition.For children weighing more than 50 kg, dosages should be used for adults. With meningitis, the recommended dose is 40 mg / kg every 8 hours. The safety of administering a dose of 40 mg / kg in the form of a bolus injection has not been adequately studied. Experience with the drug in children with impaired liver and kidney function is absent.

    Preparation of solutions and method of administration

    Meropenem for intravenous use may be given as an intravenous bolus injection, or as an intravenous infusion.

    To prepare a solution for intravenous bolus injections, the drug should be dissolved with sterile water for injection (5 ml per 250 mg), with a solution concentration of 50 mg / ml (injected for at least 5 minutes). The resulting solution remains stable for 3 hours at a temperature of up to 25 ° C and for 16 hours when stored in a refrigerator (2-8 ° C).

    To prepare a solution for intravenous infusions, the drug should be dissolved with 0.9% sodium chloride solution or 5% dextrose solution, with the concentration of the solution should be from 1 to 20 mg / ml (injected for 15-30 minutes). The resulting solution remains stable for 3 hours at a temperature of up to 25 ° C and for 24 hours when stored in a refrigerator (2-8 ° C), if 0.9% sodium chloride solution was used for its preparation.A solution prepared using a 5% dextrose solution should be used immediately.

    The possibility of using meropenem in the regime of prolonged infusion (up to 3 hours) is based on pharmacokinetic and pharmacodynamic parameters (see the section "Pharmacokinetics"). To date, clinical data and safety data supporting this regimen are limited.

    The drug solution should not be frozen.

    The prepared solution is recommended to be administered immediately after preparation (from the microbiological point of view), if the conditions for the preparation of the solution do not exclude the possibility of microbiological contamination.

    Side effects:

    The frequency of adverse reactions listed below was determined according to the following criteria: Very often (not less than 1/10), often (more than 1/100, less than 1/10); sometimes (more than 1/1000, less than 1/100); rarely (more than 1/10000, less than 1/1000); very rarely (less than 1/10000), including individual messages.

    From the digestive system: often: nausea, vomiting, diarrhea, increased activity of "liver" transaminases, alkaline phosphatase, lactate dehydrogenase and serum bilirubin concentration. Infrequent: constipation **, cholestatic hepatitis **.Very rarely: pseudomembranous colitis.

    Allergic reactions: infrequently: itching of the skin, skin rash, hives. Very rarely: erythema multiforme, Stephen-Johnson syndrome, toxic epidermal necrolysis.

    From the nervous system: infrequently: headache, paresthesia, fainting**, hallucinations **, depression **, anxiety **, increased excitability **, insomnia **. Rarely: convulsions.

    From the laboratory indicators: often: thrombocytosis. Infrequently: eosinophilia, thrombocytopenia. Rarely: leukopenia, neutropenia, agronolocytosis. Rarely: hemolytic anemia.

    From the immune system: very rarely: angioedema, manifestations of anaphylaxis.

    From the side of the cardiovascular system: infrequently: heart failure **, cardiac arrest **, tachycardia **, bradycardia **, myocardial infarction **, decreased or increased blood pressure **, thromboembolism of the branches of the pulmonary artery **.

    From the urinary system: infrequently: increasing the concentration of creatinine in the blood, increasing the concentration of urea in the blood.

    Other: infrequently: dyspnea **, often: local reactions - inflammation, thrombophlebitis, pain at the injection site, rarely - vaginal candidiasis and candidiasis of the oral mucosa.

    * - cases of positive direct or indirect Coombs test were reported, as well as cases of partial thromboplastin time reduction.

    ** - the cause-and-effect relationship with taking meropenem is not established.

    Overdose:Accidental overdose is possible during treatment, especially in patients with impaired renal function. Treatment in case of an overdose should be symptomatic. When hemodialysis occurs, rapid elimination of the drug.
    Interaction:

    Probenecid competes with meropenem for active tubular secretion, inhibiting renal excretion and causing an increase in the half-life and concentration of meropenem in plasma. Since the efficacy and duration of action of meropenem administered without probenecid is adequate, a compatible administration of probenecid with meropenem is not recommended. The possible effect of meropenem on the degree of association of other drugs with plasma proteins or metabolism has not been studied. The association of meropenem with plasma proteins is low (about 2%), so interaction with other drugs based on the mechanism of displacement from plasma protein binding is not expected.The combined use of carbapenems and valproic acid preparations led to a decrease in the concentration of valproic acid in blood plasma by 60-100% after 2 days of therapy. Due to the rapid and significant decrease in the concentration of valproic acid, the combined use of meropenem and valproic acid preparations is not recommended.

    There are no specific data on possible drug interactions (with the exception of probenecid).

    The use of meropenem during the administration of other drugs was not accompanied by the development of unfavorable pharmacological interactions.

    Repeatedly reported cases of increased anticoagulant effect in the joint use of indirect anticoagulants (for example, warfarin) and antibacterial drugs. The risk of enhancing the anticoagulant effect may depend on the nature of the infection, the age and general condition of the patient, so it is difficult to assess the effect of the antibacterial drug on increasing the international normalized ratio (INR). With the simultaneous use of an antibacterial drug and an indirect anticoagulant, and for some time after its termination, frequent monitoring of INR is recommended.

    Special instructions:

    Experience in pediatric practice in patients with neutropenia or primary or secondary immunodeficiency is not present.

    As with the use of other antibiotics in the use of meropenem in monotherapy in patients in critical condition with an identified lower respiratory tract infection caused by Pseudomonas aeruginosa, or if suspected, regular testing of sensitivity is recommended.

    In rare cases, with the use of Merexide, as with almost all antibiotics, there is a development of pseudomembranous colitis, which can vary in severity from lungs to life-threatening forms. It is important to remember the possibility of developing pseudomembranous colitis when diarrhea occurs when the drug Merexide is used. With the development of pseudomembranous colitis, Mereside should be discontinued. Contraindicated use of drugs that inhibit intestinal peristalsis.

    Against the background of the use of carbapenems, including meropenem, infrequent reports of seizures occurred. Caution should be exercised when using the drug Merexide in patients with a reduced threshold of convulsive readiness.There are clinical and laboratory signs of cross-allergic reactions between other carbapenems and beta-lactam antibiotics, penicillins and cephalosporins. There are rare reports of cases of hypersensitivity reactions (including fatal outcome) with the use of meropenem, as well as other beta-lactam antibiotics (see the "Side effect" section). Before starting therapy with meropenem, the patient should be thoroughly questioned, paying special attention to the history of hypersensitivity reactions to beta-lactam antibiotics. Mereside should be used with caution in patients with a history of hypersensitivity reactions to beta-lactam antibiotics (ie, penicillins and cephalosporins). If there was an allergic reaction to meropenem, it is necessary to stop the introduction of the drug and take appropriate measures.

    The use of Merexide in patients with liver disease should be carried out under close monitoring of the activity of "liver" transaminases and bilirubin concentrations. As with other antibiotics, excessive growth of insensitive microorganisms is possible, and therefore, constant monitoring of the patient is necessary.The prevalence of acquired antibiotic resistance of various pathogens may vary depending on the region and time, it is desirable to have up-to-date information on the resistance of common pathogens in a particular region, especially when treating severe infections. In case the resistance is such that the efficacy of the drug against at least some infections becomes questionable, an expert should be consulted. It is not recommended joint use of the drug Merexide and valproic acid because of a possible decrease in the concentration of valproic acid in the blood serum. In some patients, a concentration below the therapeutic level can be achieved (see "Interaction with other drugs"). The use of the drug for infections caused by methicillin-resistant staphylococcus is not recommended.

    Effect on the ability to drive transp. cf. and fur:

    There have been no studies of the effect of meropenem on the ability to drive a car and other equipment. Nevertheless, it should be taken into account that with the use of the drug Merexide, headache, paresthesia and convulsions can be observed.

    Form release / dosage:Powder for the preparation of a solution for intravenous administration of 500 mg and 1000 mg.
    Packaging:

    500 mg (15 ml bottle) or 1000 mg (20 ml bottle) of meropenem into a transparent glass bottle sealed with a rubber stopper, crimped with an aluminum cap covered with a protective plastic lid.

    Solvent: Water for Injection (RU No. LP-002377 dated February 18, 2014), 5.0 or 10.0 ml per ampoule of colorless neutral glass of hydrolytic class I or low density polyethylene with a fault line.

    Dosage 0.5 g:

    1 bottle with a preparation and 1 ampoule of a solvent 10.0 ml or 2 ampoules of 5.0 ml or without a solvent together with instruction for use in a cardboard box or 1 bottle with a preparation and 1 ampoule of a solvent 10.0 ml or 2 ampoules per 5.0 ml or without solvent on a plastic pallet along with instructions for use in a cardboard box.

    Dosage 1 g:

    1 bottle with a preparation and 2 ampoules of a solvent of 10.0 ml or 4 ampoules of a solvent of 5.0 ml or without a solvent together with instructions for use in a cardboard box or 1 bottle with a preparation and 2 ampoules of a solvent of 10.0 ml or 4 ampoules of solvent, 5.0 ml, or without solvent on a plastic pallet, together with instructions for use in a cardboard pack.

    For hospitals:

    Dosage 0.5 g:

    10, 25, 48 or 100 vials without a solvent, or together with 10, 25, 48 or 100 ampoules of a solvent of 10.0 ml, or 20, 50, 96 or 200 ampoules of a solvent of 5.0 ml and the appropriate number of instructions for use in a cardboard box or 10, 25, 48 or 100 vials without a solvent or together with 10, 25, 48 or 100 ampoules of a solvent of 10.0 ml, or 20, 50, 96 or 200 ampoules of a solvent of 5.0 ml per plastic pallets and a corresponding number of instructions for use in a cardboard box.

    Dosage 1 g:

    10, 25, 48 or 100 vials without a solvent or together with 20, 50, 96 or 200 ampoules of a solvent of 10.0 ml, or 40, 100, 192 or 400 ampoules of a solvent of 5.0 ml and the appropriate number of instructions for use in a cardboard box or 10, 25, 48 or 100 vials without a solvent or together with 20, 50, 96 or 200 ampoules of a solvent of 10.0 ml, or 40, 100, 192 or 400 ampoules of a solvent of 5.0 ml per plastic pallets and a corresponding number of instructions for use in a cardboard box.

    Storage conditions:

    In the dark place at a temperature of no higher than 30 ° C.

    Keep out of the reach of children.

    Shelf life:

    3 years.

    Do not use after expiry date.

    Terms of leave from pharmacies:On prescription
    Registration number:LSR-008460/10
    Date of registration:19.08.2010 / 17.03.2017
    Expiration Date:Unlimited
    The owner of the registration certificate:JODAS EKSPOIM, LLC JODAS EKSPOIM, LLC Russia
    Manufacturer: & nbsp
    Representation: & nbspJodas Expoim, Open CompanyJodas Expoim, Open Company
    Information update date: & nbsp29.04.2018
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