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Revision as of 10:07, 19 January 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers from ChemSpider, CommonChemistry and FDA for the Chem/Drugbox validation project - Updated: ChEMBL.← Previous edit		Latest revision as of 23:08, 27 October 2024 edit undo2601:642:c303:f370:d0eb:3fda:e1ac:58f2 (talk) Redlink fix
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			{{short description|Combination antibiotic medication}}
	{{drugbox
			{{Drugbox
	| verifiedrevid = 400115046
			| verifiedrevid = 408760159
	| type = combo
			| image = Imipenem + cilastatin.svg
	| component1 = Imipenem
	| class1 = ] ]
			<!--Combo data-->
	| component2 = Cilastatin
			| type = combo
	| class2 = Dehydropeptidase inhibitor
			| component1 = Imipenem
	| image =
			| class1 = ] ]
			| component2 = Cilastatin
			| class2 = Dehydropeptidase inhibitor
			<!--Clinical data-->
			| tradename = Primaxin, Tienam, Cilasafe, others
			| Drugs.com = {{drugs.com|monograph|imipenem-and-cilastatin}}
			| MedlinePlus = a605011
			| pregnancy_AU =
			| pregnancy_US = C
			| pregnancy_category =
			| legal_AU = <!-- VI, VII, VIII -->
			| legal_UK = POM
			| legal_US = Rx-only
			| legal_status =
			| routes_of_administration = ], ]
			<!--Identifiers-->
			| CAS_number_Ref = {{cascite|correct|CAS}}
			| CAS_number = 64221-86-9
			| CAS_number2_Ref = {{cascite|correct|CAS}}
			| CAS_number2 = 82009-34-5
			| UNII_Ref = {{fdacite|correct|FDA}}
			| UNII = Q20IM7HE75
			| UNII2_Ref = {{fdacite|correct|FDA}}
			| UNII2 =141A6AMN38
			| ATC_prefix = J01
			| ATC_suffix = DH51
			| PubChem = 11954222
			| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
			| DrugBank =
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}		| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| ChemSpiderID = 21106325		| ChemSpiderID = 21106325
			| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| N)CSCCCC\C=C(/NC(=O)1CC1(C)C)C(O)=O
	|| ChEMBL = 296854		| ChEMBL = 296854
	| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
			<!--Chemical data-->
	| StdInChIKey = DAYDLKPFBFPKHL-KJWPAVRRSA-N
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 1S/C16H26N2O5S.C12H17N3O4S.H2O/c1-16(2)8-10(16)13(19)18-12(15(22)23)6-4-3-5-7-24-9-11(17)14(20)21;1-6(16)9-7-4-8(20-3-2-14-5-13)10(12(18)19)15(7)11(9)17;/h6,10-11H,3-5,7-9,17H2,1-2H3,(H,18,19)(H,20,21)(H,22,23);5-7,9,16H,2-4H2,1H3,(H2,13,14)(H,18,19);1H2/b12-6-;;/t10-,11+;6-,7-,9-;/m11./s1
	| smiles = O.O(C)2C(=O)N1C(=C(/C12)SCCNC=N)\C(O)=O.OC(=O)(N)CSCCCC\C=C(/NC(=O)1CC1(C)C)C(O)=O
	| CAS_number = 92309-29-0
	| ATC_prefix = J01
	| ATC_suffix = DH51
	| PubChem = 11954222
	| DrugBank =
	| pregnancy_AU =
	| pregnancy_US = C
	| pregnancy_category=
	| legal_AU = <!-- VI, VII, VIII -->
	| legal_UK = POM
	| legal_US = Rx-only
	| legal_status =
	| routes_of_administration = Intravenous, intramuscular
	}}		}}
			<!-- Definition and medical uses -->
	'''Imipenem/cilastatin''' (Primaxin) is a broad spectrum ] ] containing equal quantities of ] and ]. It is related to the penicillin/cephalosporin family of antibiotics but is classified as belonging to the ] class.
			'''Imipenem/cilastatin''', sold under the brand name '''Primaxin''' among others, is an ] useful for the treatment of a number of ].<ref name=AHFS2016/> It is made from a combination of ] and ].<ref name=AHFS2016/> Specifically it is used for ], ], ], ], ], and ].<ref name=AHFS2016/> It is given by ] or ].<ref name=AHFS2016>{{cite web|title=Imipenem and Cilastatin|url=https://www.drugs.com/monograph/imipenem-and-cilastatin.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161220230449/https://www.drugs.com/monograph/imipenem-and-cilastatin.html|archive-date=20 December 2016}}</ref>
			<!-- Side effects and mechanism -->
	==Mechanism==
			Common side effects include nausea, ], and pain at the site of injection.<ref name=AHFS2016/> Other side effects may include ] and ] including ].<ref name=AHFS2016/> It is unclear if use during pregnancy is safe for the baby.<ref>{{cite web|title=Cilastatin / imipenem Use During Pregnancy {{!}} Drugs.com|url=https://www.drugs.com/pregnancy/cilastatin-imipenem.html|website=www.drugs.com|access-date=10 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161220230318/https://www.drugs.com/pregnancy/cilastatin-imipenem.html|archive-date=20 December 2016}}</ref> Imipenem is in the ] family of medications and works by interfering with the bacteria's ].<ref name=AHFS2016/> Cilastatin blocks the activity of ] which prevents the breakdown of imipenem.<ref name=AHFS2016/>
	It has the ability to kill a wide variety of bacteria. It works by interfering with their ability to form cell walls, and therefore the bacteria break up and die.
			<!-- History and culture -->
	* Doripenem, the active cardiac agent, is rapidly degraded by the ] enzyme ] if administered alone (making it less effective); the metabolites can cause kidney damage.
			Imipenem/cilastatin was first sold in 1987.<ref>{{cite book|title=Oxford Handbook of Infectious Diseases and Microbiology|date=2009|publisher=OUP Oxford|isbn=9780191039621|page=56|url=https://books.google.com/books?id=5W-WBQAAQBAJ&pg=PT56|url-status=live|archive-url=https://web.archive.org/web/20151124232554/https://books.google.ca/books?id=5W-WBQAAQBAJ&pg=PT56|archive-date=2015-11-24}}</ref> It is on the ].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref>
	* Administration. , Food and Drug Administration. Oct 2006.</ref> It may be less likely to cause an allergic reaction in people who have had an allergic reaction to a penicillin in the past. It is particularly effective against '']'' species.
	==Marketing==		==Medical uses==
			Imipenem/cilastatin is used for ], ], intra-abdominal infections, gynecologic infections, bacterial ], bone and joint infections, skin and skin structure infections, ] and polymicrobic infections.<ref name="RxList"/><ref name="RxList2"/>
	Imipenem/cilastatin is marketed by ] under the trade names '''Primaxin''' , '''Tienam''' and '''Zienam'''. The combination is also marketed by ] in India under the brand name '''Cilanem''' and by Nucleus as '''Thilia'''. Imipenem/cilastatin is 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'''.
			It is a broad-spectrum ] containing equal quantities of ] and ].<ref name="RxList"/>
			==Side effects==
			Common side effects for both forms are:<ref name="Medline"/>
			* Upset stomach
			* Vomiting
			* Stomach pain
			Major side effects requiring medical attention:<ref name="Medline"/>
			* Diarrhea
			* Rash
			* Fever
			* Facial swelling
			* Difficulty breathing
			* Unusual bleeding
			* Seizures
			This medicine is passed through breast milk, so its use during pregnancy or breastfeeding should only be done when clearly needed.<ref name="RxList2"/> Primaxin is cleared from the body by the kidneys, so it is important to tell one's doctor about any other drugs being taken that are also cleared through the kidneys (such as other antibiotics), especially for older patients, as kidney function declines with age.<ref name="RxList"/><ref name="RxList2"/>
			Patients who are allergic to penicillin, cephalosporins, and related drugs may react to imipenem.<ref name="Medline">{{cite web|url=https://www.nlm.nih.gov/medlineplus/druginfo/meds/a686013.html|title=Imipenem and Cilastatin Sodium Injection|website=Medline Plus|access-date=January 25, 2013|url-status=live|archive-url=https://web.archive.org/web/20130123133525/http://www.nlm.nih.gov/medlineplus/druginfo/meds/a686013.html|archive-date=January 23, 2013}}</ref>
			It is important tell one's doctor or pharmacist one's medical history, especially of brain disorders (e.g., seizures, head injury, tumor), kidney disease, liver disease, and stomach/intestinal diseases (e.g., ]).<ref name="RxList">{{cite web|url=http://www.rxlist.com/primaxin-iv-drug.htm|title=Primaxin I.V.|website=RxList|access-date=January 25, 2013|url-status=live|archive-url=https://web.archive.org/web/20130127031822/http://www.rxlist.com/primaxin-iv-drug.htm|archive-date=January 27, 2013}}</ref>
			=== Hepatotoxicity ===
			In large clinical trials, imipenem was associated with transient and asymptomatic elevations in serum ] levels in about 6% of patients given the drug for five 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 one to three 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.{{cn|date=March 2023}}
			=== 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-cilastatin and the carbapenems is probably immunoallergic and resembles the rare, clinically apparent liver injury that has been linked to penicillins and cephalosporins.{{cn|date=March 2023}}
			=== 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, ] 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. Little information is available 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.{{cn|date=March 2023}}
			==Interactions==
			* ] (Depakene, Stavzor)<ref name="RxList3"/>
			* ] (Cytovene)<ref name="RxList3"/>
			* ] (Benemid)<ref name="RxList3"/>
			* penicillin antibiotics such as ] (Amoxil, Augmentin), ] (Omnipen, Principen), ] (Dycill, Dynapen), ] (Bactocill), or ] (Beepen-VK, Ledercillin VK, Pen-V, Pen-Vee K, Pfizerpen, V-Cillin K, Veetids, and others);<ref name="RxList3"/> or
			* cephalosporin antibiotics such as ] (Ceclor), ] (Ceftin), ] (Duricef), ] (Keflex), and others.<ref name="RxList3">{{cite web|url=http://www.rxlist.com/primaxin-im-drug/patient-avoid-while-taking.htm|title=Primaxin IM-Missed dose|website=RxList|access-date=January 25, 2013|url-status=live|archive-url=https://web.archive.org/web/20131230022521/http://www.rxlist.com/primaxin-im-drug/patient-avoid-while-taking.htm|archive-date=December 30, 2013}}</ref>
			==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, so the bacteria break up and die.
			Imipenem is rapidly degraded by the ] enzyme ] if administered alone (making it less effective); the metabolites can cause kidney damage.<ref>{{cite web |url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050587s065,050630s028lbl.pdf |title=Archived copy |access-date=2009-10-23 |url-status=live |archive-url=https://web.archive.org/web/20121016180424/http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050587s065,050630s028lbl.pdf |archive-date=2012-10-16 }}</ref>
			Imipenem is a broad-spectrum betalactam antibiotic 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 has activity against many aerobic and anaerobic Gram-positive and Gram-negative organisms, including ''Staphylococcus aureus, Streptococcus pyogenes, S. agalactiae, S. 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 does not 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&nbsp;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 five 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, ], 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.
			=== Bioavailability ===
			Intramuscular injection:
			* imipenem: 60–75%
			* cilastatin: 95–100%
			=== Distribution ===
			The drug is 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 occur in pleural fluid, interstitial fluid, peritoneal fluid, and reproductive organs; low concentrations occur in CSF; it crosses the placenta, and 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 ] is a combination of imipenem, cilastatin sodium, and ] which is added as a buffer.<ref name="RxList"/>
			Primaxin ] lacks the sodium bicarbonate buffer.<ref name="RxList2">{{cite web|url=http://www.rxlist.com/primaxin-im-drug.htm|title=Primaxin IM|website=RxList|access-date=January 25, 2013|url-status=live|archive-url=https://web.archive.org/web/20130127031955/http://www.rxlist.com/primaxin-im-drug.htm|archive-date=January 27, 2013}}</ref>
			==See also==
			* ]
	==References==		==References==
	{{reflist}}		{{reflist}}
			==External links==
			* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/imipenem%20%252F%20cilastatin | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Cilastatin mixture with Imipenem }}
	{{Cell wall disruptive antibiotics}}		{{Cell wall disruptive antibiotics}}
			{{portal bar|Medicine}}
			{{DEFAULTSORT:Imipenem Cilastatin}}
	]
			]
	]
			]
			]
			]
			]
			]