Doriprex - Instructions For Use, Price, Reviews, Analogues

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Doriprex

Doriprex: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. For violations of liver function
13. 13. Use in the elderly
14. 14. Drug interactions
15. 15. Analogs
16. 16. Terms and conditions of storage
17. 17. Terms of dispensing from pharmacies
18. 18. Reviews
19. 19. Price in pharmacies

Latin name: Doriprex

ATX code: J01DH04

Active ingredient: Doripenem (Doripenem)

Manufacturer: SHIONOGI & Co. Ltd. (Japan)

Description and photo update: 2018-11-05

Prices in pharmacies: from 26,000 rubles.

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Doriprex is a synthetic drug of the class of β-lactam antibiotics carbapenems with a broad spectrum of action.

Release form and composition

Doriprex dosage form - powder for solution for infusion: white, almost white or slightly yellowish crystalline powder; the reconstituted solution is a homogeneous suspension from white to almost white color, freely passing through a needle No. 0840 into a syringe (500 mg of powder in vials made of transparent colorless glass with a capacity of 20 ml, sealed with an elastomer stopper with an aluminum cap, equipped with a protective plastic cap; pack of cardboard 1 or 10 bottles).

1 bottle with the drug contains the active ingredient: doripenem - 500 mg (in the form of doripenem monohydrate - 521.4 mg).

Pharmacological properties

Pharmacodynamics

Doripenem is structurally similar to other β-lactam antibiotics and in vitro has a pronounced activity against aerobic and anaerobic bacteria, both gram-positive and gram-negative. It is 2–4 times more active than meropenem and imipenem in relation to Pseudomonas aeruginosa (Pseudomonas aeruginosa).

Mechanism of action: the bactericidal effect of doripenem is to disrupt the biosynthesis of the bacterial cell wall by inactivating many important penicillin-binding proteins (PSP), which subsequently leads to the death of bacteria. Doripenem has the highest affinity for the PSB of Staphylococcus aureus (Staphylococcus aureus). In E. coli (Escherichia coli) and Pseudomonas aeruginosa cells, doripenem strongly binds to PSB, which is involved in maintaining the configuration of the bacterial cell. In experiments in vitro, it turned out that doripenem weakly inhibits the action of other antibiotics, as well as other antibiotics slightly inhibit its action. There is evidence of additive activity or weak synergism of doripenem with levofloxacin and amikacin against Pseudomonas aeruginosa, as well as with vancomycin, linezolid,levofloxacin and daptomycin against gram-positive bacteria.

Mechanisms of resistance: bacterial resistance to doripenem includes its inactivation by enzymes capable of hydrolyzing carbapenems, as well as acquired or mutant PSBs; a decrease in the permeability of the outer membrane and an active exit from bacterial cells. Doripenem is resistant to hydrolysis by most β-lactamases (including penicillinases and cephalosporinases) produced by gram-positive and gram-negative bacteria. The only exceptions are relatively rare β-lactamases. The prevalence of certain species with acquired resistance may vary at different times and in different geographic regions, therefore information on the structure of local resistance is very useful, especially in the treatment of severe infections.

Commonly sensitive to doripenem types of microorganisms:

• gram-positive aerobes: Staphylococcus aureus (methicillin-sensitive strains), Enterococcus faecalis, Staphylococcus epidermidis (methicillin-sensitive strains), Staphylococcus saprophyticus, Staphylococcus haemolyticillin (methicillin-sensitive strains) Streptococcus constellatus, Streptococcus intermedius, Streptococcus pneumoniae (including strains resistant to penicillin or ceftriaxone), Streptococcus viridans (including moderately sensitive and penicillin-resistant strains), Streptococcus pyogenes;
• gram-negative aerobes: Citrobacter diversus, Acinetobacter calcoaceticus, Acinetobacter baumannii, Enterobacter aerogenes, Aeromonas hydrophila, Citrobacter freundii (including strains insensitive to ceftazidime), Enterobacter cloacae (including ceptamophilus insensitive) including β-lactamase-producing strains, or ampicillin-resistant strains that do not produce β-lactamases), Escherichia coli (including levofloxacin-resistant strains and extended spectrum β-lactamase producing strains), Klebsiella pneumoniae * (in t including producing extended-spectrum β-lactamases - Extended-Spectrum Beta-Lactamase or ESBL strains), Morganella morganii, Klebsiella oxytoca, Proteus mirabilis (including ESBL-producing strains), Providencia stuartii, Providencia rettgeri, Proteus vulgarisPseudomonas aeruginosa * (including strains resistant to ceftazidime), Serratia marcescens (including strains insensitive to ceftazidime), species of the genus Shigella and Salmonella;
• anaerobes: Bilophila wadsworthia, Bacteroides caccae, Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Peptostreptococcus, Peptostreptococcus.

* - types of microorganisms for which the activity of doripenem has been determined in clinical studies.

Doripenem-resistant types of microorganisms:

• gram-positive aerobes: methicillin-resistant Staphylococcus species; Enterococcus faecium;
• gram-negative aerobes: Stenotrophomonas maltophila;
• species with acquired resistance: Burkholderia cepacia may have induced resistance.

Pharmacokinetics

Average concentration in plasma of doripenem depending on dose and duration of infusion parameters change in time for ¹ / ₂ /1/2/3/4/6 hours:

• 1-hour intravenous infusion at a dose of 500 mg: 20.2 / 20.9 / 6.13 / 2.69 / 1.41 / 0.45 mg / L;
• 4-hour intravenous infusion at a dose of 500 mg: 4.01 / 5.70 / 7.26 / 8.12 / 8.53 / 1.43 mg / L;
• 4-hour intravenous infusion at a dose of 1000 mg: 7.80 / 11.6 / 15.1 / 16.9 / 18.3 / 2.98 mg / L.

The maximum concentration of doripenem in plasma (Cmax) and the area under the concentration-time curve (AUC) change linearly when the drug is taken in a dose range of 500-1000 mg with an intravenous infusion duration of 1 or 4 hours and doses of 500-2000 mg with an intravenous infusion duration 1 hour.

With normal renal function, signs of accumulation of doripenem are not observed after intravenous infusions of 500–1000 mg every 8 hours, for a course of 7–10 days.

Pharmacokinetic characteristics of doripenem:

• distribution: the average degree of binding to plasma proteins - 8.1% (regardless of plasma concentration); volume of distribution ~ 16.8 l (close in value to the volume of extracellular fluid ~ 18.2 l); there is good permeability to a number of biological fluids and tissues (for example, retroperitoneal fluid and urine, tissues of the prostate gland, uterus, gallbladder), doripenem reaches concentrations there that exceed the minimum inhibitory concentration (MIC);
• metabolism: doripenem is biotransformed mainly under the action of dehydropeptidase-I into a microbiologically inactive metabolite. In experimental studies in vitro, biotransformation of doripenem was recorded with the participation of isoenzymes of the CYP450 system, other enzymes, both in the presence and in the absence of nicotinamide adenine dinucleotide phosphate (NADP);
• Excretion: elimination of doripenem occurs mainly by the kidneys in an unchanged form; for young healthy adults, the average half-life (T ¹ / ₂) ~ 1 h; plasma clearance ~ 15.9 l / h; average renal clearance ~ 10.3 l / h (the value of this indicator, in combination with a significant decrease in the excretion of doripenem simultaneously with probenecid, indicates that doripenem undergoes both glomerular filtration and renal secretion); when receiving one dose of 500 mg in young healthy adults, 71% of the dose was excreted in the urine unchanged; 15% - in the form of an open ring metabolite; less than 1% was found in feces.

Pharmacokinetic features of certain groups of patients:

• renal failure: administration of a single dose of 500 mg doripenem increased AUC as follows: mild renal failure with creatinine clearance (CC) 51–79 ml / min - 1.6 times, moderate renal failure CC 31–50 ml / min - 2, 8 times, severe renal failure CC 80 ml / min; with moderate and severe renal impairment, the dose of doripenem should be reduced;
• liver dysfunction: there is currently no data on the pharmacokinetics of doripenem in patients with hepatic insufficiency; metabolism in the liver is practically not exposed to doripenem, which suggests the absence of the effect of liver function on its pharmacokinetics;
• old age: AUC of doripenem in the elderly was increased by 49% compared with the value for young healthy adults, mainly due to age-related changes in CC; with normally functioning kidneys, elderly patients do not need to reduce the dose of doripenem;
• sex differentiation: AUC of doripenem in women is 13% higher than in men; women and men are advised to administer the same dose of the drug;
• racial differentiation: when using doripenem among various racial groups, there was no significant discrepancy in its clearance, therefore, dose adjustment is not required.

Indications for use

• nosocomial pneumonia, including those associated with mechanical ventilation (artificial lung ventilation);
• complicated infections of the urinary system, including pyelonephritis (complicated / uncomplicated) and with concomitant bacteremia;
• complicated intra-abdominal infections.

Contraindications

• children and adolescents up to 18 years old;
• period of breastfeeding;
• increased individual sensitivity to doripenem, other antibiotics from the carbapenem group and to β-lactam antibiotics.

Instructions for the use of Doriprex: method and dosage

Doriprex is given as an intravenous infusion.

Recommended dosage:

• nosocomial pneumonia, including those associated with mechanical ventilation: every 8 hours, 500 mg, duration of infusion 1 or 4 hours ¹; course duration - 7-14 days ²;
• complicated infections of the urinary system, including pyelonephritis: every 8 hours, 500 mg, duration of infusion 1 hour; course duration - 10 days ^{2, 3};
• complicated intra-abdominal infections: every 8 hours, 500 mg, duration of infusion 1 hour; course duration - 5-14 days ^{2, 3}.

¹ - the recommended duration of infusion for nosocomial pneumonia - 1 hour; if there is a risk of infection with microorganisms less sensitive to the antibiotic, Doriprex should be administered within 4 hours.

² - the total duration of therapy includes a possible transition to taking the appropriate oral drugs after 3-day (minimum) parenteral administration of Doriprex, which caused clinical improvement (in the case of switching to oral dosage forms, a wide spectrum of action of penicillins in combination with clavulanic acid, fluoroquinolones, and also antibiotics of any other pharmacotherapeutic group).

³ - for infections complicated by bacteremia, the duration of treatment can be increased to 14 days.

Preparation of solution for infusion at a dose of 500 mg:

1. 10 ml of sterile water for injection or physiological solution (0.9% NaCl solution) is injected into a vial with a powder.
2. Check the suspension visually for the presence of visible foreign particles (for direct administration, the prepared suspension is not used).
3. Using a syringe and a needle, the suspension is added to a bag for infusion solutions containing 100 ml of 5% glucose solution or 0.9% NaCl solution and gently stirred until completely dissolved.

To prepare a drug in a dose of 250 mg for administration to patients with moderate or severe impairment of renal function, 55 ml of the solution is taken from the infusion bag with a prepared dose of 500 ml and disposed of, the remaining volume of the solution contains 250 mg of doripenem.

The prepared suspension before its dilution in the infusion solution may be stored in a bottle for no more than 1 hour.

Stability time (shelf life) of the prepared Doriprex solution, depending on the diluent and storage conditions:

• 0.9% NaCl solution (saline): at room temperature - 12 hours; at a temperature of 2–8 ° C (in the refrigerator) - 72 hours;
• 5% glucose solution: at room temperature - 4 hours; at a temperature of 2-8 ° C (in the refrigerator) - 24 hours.

Once removed from the refrigerator, the infusion solution should be administered within the allowed storage time at room temperature. In total, the time for storing the solution in the refrigerator, warming it to room temperature and administering it to the patient in total should not exceed the permissible storage time of the prepared drug in the refrigerator.

The introduction of Doriprex with 5% glucose solution should not last more than 1 hour.

Doriprex solution should be transparent, from colorless to slightly yellowish, differences in color do not affect the quality of the product. Before the introduction, the infusion solution is checked visually for the absence of mechanical impurities and, if the latter are found, discarded.

Unused solution and other waste remaining after the infusion should be disposed of in accordance with the rules.

Side effects

• nervous system: very often - headache; frequency unknown - seizures;
• cardiovascular system: often - phlebitis;
• gastrointestinal tract (GIT): often - nausea, diarrhea;
• skin and subcutaneous tissue: often - itching, rash;
• hypersensitivity reactions: infrequently - anaphylactic reactions;
• hepatobiliary system: often - increased activity of liver enzymes;
• other reactions: often - candidiasis of the oral mucosa and vaginal candidiasis.

In the post-registration period, the following undesirable effects were observed:

• circulatory and lymphatic systems: infrequently - neutropenia, thrombocytopenia;
• hypersensitivity reactions: very rarely - Lyell's syndrome, Stevens-Johnson syndrome.

Doctors voluntarily reported seizures without indicating the number of patients receiving Doriprex, and therefore it is impossible to establish their relative frequency.

Overdose

With intravenous drip of doripenem at a dose of 2 g every 8 hours for 10-14 days, there were cases of papulo-erythematous rash, which disappeared 10 days after stopping therapy.

In case of an overdose, the administration of Doriprex must be stopped and maintenance treatment carried out until it is completely eliminated from the body by the kidneys. Therapy of the condition is symptomatic, it consists in monitoring the clinical condition of the patient and monitoring the main physiological indicators. Doripenem is excreted from the body through hemodialysis or long-term renal replacement therapy, but there is currently no sufficient information on the effectiveness of these methods.

special instructions

Serious (even fatal) anaphylactic reactions can occur in patients receiving β-lactam antibiotics. Before starting therapy, the patient's history should be carefully collected, especially information about hypersensitivity reactions to β-lactam antibiotics and other carbapenems. If an allergic reaction to doripenem occurs, Doriprex is immediately discontinued and appropriate therapeutic measures are taken. Anaphylactic shock requires emergency treatment, including the administration of epinephrine (pressor amines) and glucocorticosteroids, as well as oxygen therapy, intravenous fluids, antihistamines, and airway maintenance.

It has been reported about episodes of the development of seizures during therapy with carbapenems, including doripenem. In clinical studies, seizures were more often observed in patients with underlying diseases of the central nervous system (stroke or a history of seizures), renal failure, and also with the introduction of high doses of> 500 mg.

Clostridium difficile-induced pseudomembranous colitis can occur with virtually all antibiotics, ranging from mild to life-threatening. That is why, in case of diarrhea, you should immediately consult a doctor.

Long-term treatment with Doriprex must be avoided to prevent excessive reproduction of pathological microorganisms resistant to it.

Before starting treatment, it is recommended to undergo a bacteriological study with the selection of appropriate samples for the isolation of pathogens, their identification and determination of sensitivity to doripenem. In the absence of such a possibility, the empirical choice of drugs is carried out on the basis of local epidemiological data and the structure of the sensitivity of microorganisms at the local level.

Patients on long-term renal replacement therapy require careful monitoring of side effects.

Influence on the ability to drive vehicles and complex mechanisms

Studies on the effect of doripenem on concentration and the speed of psychomotor reactions have not been conducted, but given the presence of side effects from the nervous system and the safety profile of Doriprex, attention should be paid to the possibility of the drug's influence on these functions.

Application during pregnancy and lactation

There are limited data on clinical observations of the use of doripenem during pregnancy, therefore, it is not possible to determine the likely threat to the fetus. In this connection, Doriprex during pregnancy is used only if the intended benefit to the mother exceeds the potential risk to the fetus.

If the use of Doriprex is necessary during lactation, breastfeeding should be interrupted during therapy.

Pediatric use

Doriprex is contraindicated for use in children and adolescents under the age of 18.

With impaired renal function

Doriprex dose adjustment depending on renal function:

• CC> 50 ml / min: dose adjustment is not required;
• CC 30-50 ml / min (moderate renal impairment): 250 mg every 8 hours;
• CC from 10-30 ml / min (severe renal impairment): 250 mg every 12 hours.

For violations of liver function

Doriprex dose adjustment is not required for patients with impaired liver function.

Use in the elderly

Elderly patients with age-appropriate renal function do not require dose adjustment of Doriprex.

Drug interactions

• probenecid: competes with doripenem for secretion by the renal tubules, reducing renal clearance doripenem, increasing the AUC by 75%, while T ¹ / ₂ at 53%; their simultaneous use is not recommended;
• drugs metabolized by isoenzymes of the cytochrome P450 system: doripenem does not inhibit the main isoenzymes, therefore, most likely, it does not interact with these drugs; data from in vitro studies confirm that it does not have the ability to induce enzyme activity;
• valproic acid or sodium valproate: doripenem is able to reduce their plasma concentration to a subtherapeutic level, with unchanged pharmacokinetics of doripenem itself; simultaneous use is carried out while monitoring the concentration of valproic acid or sodium valproate with consideration of the possibility of prescribing another treatment.

According to the instructions, Doriprex should not be mixed with other drugs except sterile water for injection, physiological solution (0.9% NaCl solution) or 5% glucose solution.

Analogs

There is no information on Doriprex analogues for the active substance.

Terms and conditions of storage

Store in original packaging, out of light, at a temperature not exceeding 15-30 ° C. Keep out of the reach of children.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Doriprex

The few reviews about Doriprex are positive; in a single case, an increase in appetite was reported immediately after the infusion.

The price of Doriprex in pharmacies

The approximate price of Doriprex in pharmacies ranges from 13 thousand rubles. up to 44 thousand rubles. and above for a package of 10 bottles of 500 mg of the drug.

Doriprex: prices in online pharmacies

Drug name Price Pharmacy

Doriprex 500 mg powder for solution for infusion 20 ml 10 pcs. RUB 26,000 Buy

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!