primaxin

同

imipenem-cilastatin

WordNet

1. trade name for a parenteral antibiotic

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/06/05 17:59:27」(JST)

wiki en

[Wiki en表示]

Imipenem/cilastatin

Combination of
Imipenem	Carbapenem antibiotic
Cilastatin	Dehydropeptidase inhibitor
Clinical data
MedlinePlus	a605011
Pregnancy cat.	C (US)
Legal status	POM (UK) ℞-only (US)
Routes	Intravenous, intramuscular
Identifiers
CAS number	92309-29-0 Y
ATC code	J01DH51
PubChem	CID 11954222
ChemSpider	21106325 Y
ChEMBL	CHEMBL296854 Y
Y (what is this?)  (verify)

Imipenem/cilastatin (marketed as Primaxin in the USA, and as Cilasafe in India) is an antibiotic useful for the treatment of a number of bacterial infections. It is a broad spectrum beta-lactam containing equal quantities of imipenem and cilastatin. It is related to the penicillin/cephalosporin family of antibiotics but is classified as belonging to the carbapenem class.

It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.

Medical uses

Primaxin is indicated in: lower respiratory tract infections (IV, IM), urinary tract infections (IV), intra-abdominal infections (IV, IM), gynecologic infections (IV, IM), bacterial septicemia (IV), bone and joint infections (IV), skin and skin structure infections (IV, IM), endocarditis (IV) and polymicrobic infections (IV).

Precautions

Patients who are allergic to penicillin, cephalosporins and related drugs should tell their doctor. It is important tell your doctor or pharmacist your medical history, especially of: brain disorders (e.g., seizures, head injury, tumor), kidney disease, liver disease, stomach/intestinal diseases (e.g., colitis).

Hepatotoxicity

In large clinical trials, imipenem was associated with transient and asymptomatic elevations in serum aminotransferase levels in approximately 6% of patients given the drug for 5 to 14 days. More serious hepatic injury from imipenem/cilastatin is rare, but jaundice and liver test abnormalities have been reported in 0.1% of patients in prospective trials of the agent. Several instances of cholestatic jaundice arising during or shortly after therapy have been reported with imipenem-cilastatin and other carbapenems. The latency to onset has been within 1 to 3 weeks and the pattern of enzyme elevations is usually cholestatic. Immunoallergic features can occur but autoantibodies are rare. The course is usually self-limiting, but at least one case of vanishing bile duct syndrome related to the carbapenems has been reported. Imipenem and other carbapenems have not been linked to cases of acute liver failure.

Mechanism of liver injury

The cause of the mild, transient serum enzyme elevations during imipenem-cilastatin therapy is not known. The cholestatic hepatitis attributed to imipenem-cilastin and the carbapenems is probably immunoallergic and resembles the rare clinically apparent liver injury that has been linked to penicillins and cephalosporins.

Outcome and management

The liver injury due to the carbapenems is usually mild and self-limited. Rarely, the carbapenems can cause a clinically apparent acute cholestatic hepatitis that is usually self-limiting and not requiring therapy or intervention. In patients with vanishing bile duct syndrome, corticosteroids are often used but have not been shown to be beneficial and are best avoided. Some patients may benefit from symptomatic therapy of the pruritus associated with cholestasis using antihistamines, ursodiol or cholestyramine. There is little information on possible cross-sensitivity to liver injury among the different betalactam antibiotics, but patients with clinically apparent liver injury due to imipenem should probably avoid the other carbapenems.

Side effects

Common side effects for both forms are:

• Upset stomach
• Vomiting
• Stomach pain

Major side effects requiring medical attention:

• Diarrhea
• Rash
• Fever
• Facial swelling
• Difficulty breathing
• Unusual bleeding
• Seizures

This medicine is passed through breast milk so its usage during pregnancy or breast feeding should only be done when clearly needed. Primaxin is cleared from the body via the kidneys so it is important to tell your doctor about any other drugs you take that are also cleared through the kidneys (such as other antibiotics), especially for older patients as kidney function declines with age.

Interactions

• valproic acid (Depakene, Stavzor)
• ganciclovir (Cytovene)
• probenecid (Benemid)
• penicillin antibiotics such as amoxicillin (Amoxil, Augmentin), ampicillin (Omnipen, Principen), dicloxacillin (Dycill, Dynapen), oxacillin (Bactocill), or penicillin (Beepen-VK, Ledercillin VK, Pen-V, Pen-Vee K, Pfizerpen, V-Cillin K, Veetids, and others); or
• cephalosporin antibiotics such as cefaclor (Ceclor), cefuroxime (Ceftin), cefadroxil (Duricef), cephalexin (Keflex), and others.

Mechanism of action

Imipenem/cilastatin has the ability to kill a wide variety of bacteria. Imipenem is the active antibiotic agent and works by interfering with their ability to form cell walls, and therefore the bacteria break up and die.

Imipenem is rapidly degraded by the renal enzyme dehydropeptidase if administered alone (making it less effective); the metabolites can cause kidney damage. Imipenem is a broad spectrum betalactam antibiotic which is used for severe bacterial infections caused by susceptible organisms. Because imipenem is rapidly inactivated by renal dehydropeptidase I, it is given in combination with cilastatin, a DHP-I inhibitor which increases half-life and tissue penetration of imipenem. Imipenem/cilastatin, like other carbapenems, binds to bacterial penicillin binding proteins and interferes with bacterial cell wall integrity and synthesis. It is a broad spectrum antibiotic with activity against many aerobic and anaerobic gram-positive and gram-negative organisms, including Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, viridans group streptococci, Enterococcus faecalis, Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Bacteroides fragilis and Peptostreptococcus species. Imipenem/cilastatin was approved for use in the United States in 1985. Imipenem/cilastatin is indicated for the treatment of severe or complicated skin, tissue, joint, respiratory tract, intra-abdominal, urinary tract and urogenital infections, But not meningitis (as it doesn't pass through the blood brain barrier), endocarditis and sepsis due to susceptible organisms. Its use is generally restricted to severe infections largely in hospitalized patients. The recommended dosage is 250 mg to 1 gram given intravenously every 6 to 8 hours or in intramuscular doses of no more than 1.5 gm daily, usually for 5 to 14 days. It is commercially available as Primaxin as 250 mg or 500 mg infusion bottles for IV use or 500 mg or 750 mg vials of lyophilized powder for im injection. The most common side effects of imipenem are diarrhea, nausea, vomiting, skin rash, pruritus (itch) and injection site reactions.

Pharmacology

Mechanism of action

Imipenem inhibits bacterial cell-wall synthesis by binding to penicillin-binding proteins; cilastatin prevents renal metabolism of imipenem

Absorption

Bioavailability (IM): Imipenem, 60–75%; cilastatin, 95–100%

Distribution

Distributed rapidly and widely to most tissues and fluids, including sputum, pleural fluid, peritoneal fluid, interstitial fluid, bile, aqueous humor, reproductive organs, and bone; highest concentrations in pleural fluid, interstitial fluid, peritoneal fluid, and reproductive organs; low concentrations in CSF; crosses placenta; enters breast milk

Protein binding

Imipenem, 13–21%; cilastatin, 40%

Metabolism

Imipenem is metabolized in the kidney by dehydropeptidase 1; activity is blocked by cilastatin

Elimination

Half-life (both drugs): 60 min; prolonged with renal impairment Excretion (both drugs): Urine (~70% as unchanged drug)

Availability and description

Primaxin IV is a combination of imipenem, cilastatin sodium and sodium bicarbonate which is added as a buffer. Primaxin IM lacks the sodium bicarbonate buffer.

Marketing

Imipenem/cilastatin is marketed by Merck & Co. under the trade names Primaxin, Tienam and Zienam whereas in India it is marketed as ICL (by Zuventus Healthcare Ltd). The combination is also marketed by Ranbaxy Laboratories & BIOCON in India under the brand name Cilanem and IMICELUM respectively, as well as by New Medicon Pharma under the brand name Tinaxin and Lupin as Lupinem. It's also available under the brand name of Cilapen by Bosch Pharmaceuticals in Pakistan in 250mg and 500mg strengths and is now the largest selling generic in the country. It is also marketed by Highnoon Laboratories Ltd. in Pakistan under the trade name Prepenem. Prepenem was launched by Highnoon in May 2007 and was the first generic brand after the research brand Tienam.

References

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 成人における確定診断を得られていない低血圧やショックの評価および初期アプローチ evaluation of and initial approach to the adult patient with undifferentiated hypotension and shock
• 2. β-ラクタマーゼ阻害剤、カルバペネム系、およびモノバクタム系抗菌薬の併用 combination beta lactamase inhibitors carbapenems and monobactams
• 3. 基質特異性拡張型β-ラクタマーゼ extended spectrum beta lactamases
• 4. βラクタム系抗生物質の長期注入投与 prolonged infusions of beta lactam antibiotics
• 5. ペニシリン-アレルギー患者：セフェム系、カルバペネム系、およびモノバクタム系の使用 penicillin allergic patients use of cephalosporins carbapenems and monobactams

English Journal

• The role of CXCL10 in the pathogenesis of experimental septic shock.

• Herzig DS, Luan L, Bohannon JK, Toliver-Kinsky TE, Guo Y, Sherwood ER.
• Critical care (London, England).Crit Care.2014 Jun 2;18(3):R113. doi: 10.1186/cc13902.
• INTRODUCTION: The chemokine CXCL10 is produced during infection and inflammation to activate the chemokine receptor CXCR3, an important regulator of lymphocyte trafficking and activation. The goal of this study was to assess the contributions of CXCL10 to the pathogenesis of experimental septic shoc
• PMID 24890566

• Discovery of MK-7655, a β-lactamase inhibitor for combination with Primaxin®.

• Blizzard TA1, Chen H2, Kim S2, Wu J2, Bodner R2, Gude C2, Imbriglio J2, Young K3, Park YW3, Ogawa A3, Raghoobar S3, Hairston N3, Painter RE3, Wisniewski D3, Scapin G2, Fitzgerald P2, Sharma N2, Lu J2, Ha S2, Hermes J3, Hammond ML4.
• Bioorganic & medicinal chemistry letters.Bioorg Med Chem Lett.2014 Feb 1;24(3):780-5. doi: 10.1016/j.bmcl.2013.12.101. Epub 2014 Jan 3.
• β-Lactamase inhibitors with a bicyclic urea core and a variety of heterocyclic side chains were prepared and evaluated as potential partners for combination with imipenem to overcome class A and C β-lactamase mediated antibiotic resistance. The piperidine analog 3 (MK-7655) inhibited both class A
• PMID 24433862

• Systematic review and meta-analysis of antimicrobial treatment effect estimation in complicated urinary tract infection.

• Singh KP1, Li G, Mitrani-Gold FS, Kurtinecz M, Wetherington J, Tomayko JF, Mundy LM.
• Antimicrobial agents and chemotherapy.Antimicrob Agents Chemother.2013 Nov;57(11):5284-90. doi: 10.1128/AAC.01257-13. Epub 2013 Aug 12.
• Noninferiority trial design and analyses are commonly used to establish the effectiveness of a new antimicrobial drug for treatment of serious infections such as complicated urinary tract infection (cUTI). A systematic review and meta-analysis were conducted to estimate the treatment effects of thre
• PMID 23939900

Related Links

• Primaxin IM (Imipenem and Cilastatin) Drug Information ...

What are the possible side effects of imipenem and cilastatin (Primaxin IM, Primaxin IV)? Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue ...

• Proposed Prescribing Informtion PRIMAXIN IV

1 PRIMAXIN® I.V. (IMIPENEM AND CILASTATIN FOR INJECTION) To reduce the development of drugresistant bacteria and maintain the effectiveness of PRIMAXIN-® I.V. and other antibacterial drugs, PRIMAXIN I.V. should be used ...

Related Pictures