DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/16305999http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021304s008,022257s003lbl.pdfhttps://www.ncbi.nlm.nih.gov/pubmed/2177317 | https://www.ncbi.nlm.nih.gov/pubmed/3265058 | https://adisinsight.springer.com/drugs/800001059http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/019661s030lbl.pdfCurator's Comment: description was created based on several sources, including:
https://www.drugs.com/monograph/valganciclovir-hydrochloride.html | http://www.rxlist.com/valcyte-drug/indications-dosage.htm
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16305999http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021304s008,022257s003lbl.pdfhttps://www.ncbi.nlm.nih.gov/pubmed/2177317 | https://www.ncbi.nlm.nih.gov/pubmed/3265058 | https://adisinsight.springer.com/drugs/800001059http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/019661s030lbl.pdf
Curator's Comment: description was created based on several sources, including:
https://www.drugs.com/monograph/valganciclovir-hydrochloride.html | http://www.rxlist.com/valcyte-drug/indications-dosage.htm
Ganciclovir is a synthetic acyclic nucleoside analogue of 2'-deoxyguanosine active against cytomegalovirus. Ganciclovir has been shown to be active against cytomegalovirus (CMV) and herpes simplex virus (HSV) in humans. To achieve anti-CMV activity, ganciclovir is phosphorylated first to the monophosphate form by a CMV-encoded (UL97 gene) protein kinase homologue, then to the di- and triphosphate forms by cellular kinases. Ganciclovir triphosphate concentrations may be 100-fold greater in CMV-infected than in uninfected cells, indicating preferential phosphorylation in infected cells. Ganciclovir triphosphate, once formed, persists for days in the CMV-infected cell. Ganciclovir triphosphate is believed to inhibit viral DNA synthesis by (1) competitive inhibition of viral DNA polymerases; and (2) incorporation into viral DNA, resulting in eventual termination of viral DNA elongation. Ganciclovir is indicated for the treatment of CMV retinitis in immunocompromised patients, including patients with acquired immunodeficiency syndrome (AIDS) and for the treatment of acute herpetic keratitis.
Originator
Sources: https://worldwide.espacenet.com/publicationDetails/biblio?II=0&ND=3&adjacent=true&locale=en_EP&FT=D&date=19960131&CC=EP&NR=0694547A2&KC=A2http://shodhganga.inflibnet.ac.in/bitstream/10603/2450/15/15_chapter%204.pdf
Curator's Comment: The first synthesis of ganciclovir was reported by Julien Verheyden and John Martin at Syntex Research in California in 1980 and is marketed as sodium salt (Ganciclovir sodium) under the trade names Cytovene and Cymevene.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: P08546 Gene ID: NA Gene Symbol: UL54 Target Organism: Human cytomegalovirus (strain AD169) (HHV-5) (Human herpesvirus 5) |
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Target ID: CHEMBL3414 |
0.08 µM [EC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | ZIRGAN Approved UseZIRGAN is a topical ophthalmic antiviral that is indicated for the treatment of acute herpetic keratitis (dendritic ulcers). Launch Date1995 |
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Primary | CYTOVENE Approved UseCYTOVENE-IV is indicated for the treatment of CMV retinitis in immunocompromised patients, including patients with acquired immunodeficiency syndrome (AIDS). CYTOVENE-IV is also indicated for the prevention of CMV disease in transplant recipients at risk for CMV disease. Launch Date1994 |
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Primary | VALCYTE Approved UseVALCYTE is indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS) Launch Date2001 |
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Primary | VALCYTE Approved UseVALCYTE is indicated for the prevention of CMV disease in kidney, heart, and kidney-pancreas transplant patients at high risk Launch Date2001 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
4.8 mg/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/10747829 |
1 g 3 times / day multiple, oral dose: 1 g route of administration: Oral experiment type: MULTIPLE co-administered: |
GANCICLOVIR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
13.3 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16737936 |
5 mg/kg single, intravenous dose: 5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
GANCICLOVIR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
35.4 mg × h/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/10747829 |
1 g 3 times / day multiple, oral dose: 1 g route of administration: Oral experiment type: MULTIPLE co-administered: |
GANCICLOVIR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
53.8 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16737936 |
5 mg/kg single, intravenous dose: 5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
GANCICLOVIR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5.2 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16737936 |
5 mg/kg single, intravenous dose: 5 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered: |
GANCICLOVIR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
1000 mg 6 times / day multiple, oral Highest studied dose Dose: 1000 mg, 6 times / day Route: oral Route: multiple Dose: 1000 mg, 6 times / day Sources: |
unhealthy, 37.4 n = 19 Health Status: unhealthy Condition: AIDS Age Group: 37.4 Population Size: 19 Sources: |
|
2000 mg 3 times / day multiple, oral Highest studied dose Dose: 2000 mg, 3 times / day Route: oral Route: multiple Dose: 2000 mg, 3 times / day Sources: |
unhealthy, 38.6 n = 50 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: 38.6 Population Size: 50 Sources: |
Other AEs: Neutropenia, Thrombocytopenia... Other AEs: Neutropenia (18%) Sources: Thrombocytopenia (4%) Anemia (severe, 4%) Renal impairment (4%) |
50 mg/kg 3 times / day multiple, oral Highest studied dose Dose: 50 mg/kg, 3 times / day Route: oral Route: multiple Dose: 50 mg/kg, 3 times / day Sources: |
unhealthy, 7.4 years (range: 0.5-16.9 years) n = 36 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: 7.4 years (range: 0.5-16.9 years) Population Size: 36 Sources: |
Other AEs: Neutropenia... |
5 mg/kg 1 times / day multiple, intravenous Recommended Dose: 5 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 5 mg/kg, 1 times / day Sources: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Other AEs: Fever, Infection... Other AEs: Fever (48%) Sources: Infection (13%) Chills (10%) Sepsis (15%) Diarrhea (44%) Anorexia (14%) Vomiting (13%) Leukopenia (41%) Anemia (25%) Thrombocytopenia (6%) Neuropathy (9%) Sweating (12%) Pruritus (5%) Catheter infection (9%) Catheter sepsis (8%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Neutropenia | 18% | 2000 mg 3 times / day multiple, oral Highest studied dose Dose: 2000 mg, 3 times / day Route: oral Route: multiple Dose: 2000 mg, 3 times / day Sources: |
unhealthy, 38.6 n = 50 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: 38.6 Population Size: 50 Sources: |
Renal impairment | 4% | 2000 mg 3 times / day multiple, oral Highest studied dose Dose: 2000 mg, 3 times / day Route: oral Route: multiple Dose: 2000 mg, 3 times / day Sources: |
unhealthy, 38.6 n = 50 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: 38.6 Population Size: 50 Sources: |
Thrombocytopenia | 4% | 2000 mg 3 times / day multiple, oral Highest studied dose Dose: 2000 mg, 3 times / day Route: oral Route: multiple Dose: 2000 mg, 3 times / day Sources: |
unhealthy, 38.6 n = 50 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: 38.6 Population Size: 50 Sources: |
Anemia | severe, 4% | 2000 mg 3 times / day multiple, oral Highest studied dose Dose: 2000 mg, 3 times / day Route: oral Route: multiple Dose: 2000 mg, 3 times / day Sources: |
unhealthy, 38.6 n = 50 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: 38.6 Population Size: 50 Sources: |
Neutropenia | 22% | 50 mg/kg 3 times / day multiple, oral Highest studied dose Dose: 50 mg/kg, 3 times / day Route: oral Route: multiple Dose: 50 mg/kg, 3 times / day Sources: |
unhealthy, 7.4 years (range: 0.5-16.9 years) n = 36 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: 7.4 years (range: 0.5-16.9 years) Population Size: 36 Sources: |
Chills | 10% | 5 mg/kg 1 times / day multiple, intravenous Recommended Dose: 5 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 5 mg/kg, 1 times / day Sources: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Sweating | 12% | 5 mg/kg 1 times / day multiple, intravenous Recommended Dose: 5 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 5 mg/kg, 1 times / day Sources: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Infection | 13% | 5 mg/kg 1 times / day multiple, intravenous Recommended Dose: 5 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 5 mg/kg, 1 times / day Sources: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Vomiting | 13% | 5 mg/kg 1 times / day multiple, intravenous Recommended Dose: 5 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 5 mg/kg, 1 times / day Sources: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Anorexia | 14% | 5 mg/kg 1 times / day multiple, intravenous Recommended Dose: 5 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 5 mg/kg, 1 times / day Sources: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Sepsis | 15% | 5 mg/kg 1 times / day multiple, intravenous Recommended Dose: 5 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 5 mg/kg, 1 times / day Sources: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Anemia | 25% | 5 mg/kg 1 times / day multiple, intravenous Recommended Dose: 5 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 5 mg/kg, 1 times / day Sources: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Leukopenia | 41% | 5 mg/kg 1 times / day multiple, intravenous Recommended Dose: 5 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 5 mg/kg, 1 times / day Sources: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Diarrhea | 44% | 5 mg/kg 1 times / day multiple, intravenous Recommended Dose: 5 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 5 mg/kg, 1 times / day Sources: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Fever | 48% | 5 mg/kg 1 times / day multiple, intravenous Recommended Dose: 5 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 5 mg/kg, 1 times / day Sources: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Pruritus | 5% | 5 mg/kg 1 times / day multiple, intravenous Recommended Dose: 5 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 5 mg/kg, 1 times / day Sources: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Thrombocytopenia | 6% | 5 mg/kg 1 times / day multiple, intravenous Recommended Dose: 5 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 5 mg/kg, 1 times / day Sources: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Catheter sepsis | 8% | 5 mg/kg 1 times / day multiple, intravenous Recommended Dose: 5 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 5 mg/kg, 1 times / day Sources: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Catheter infection | 9% | 5 mg/kg 1 times / day multiple, intravenous Recommended Dose: 5 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 5 mg/kg, 1 times / day Sources: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Neuropathy | 9% | 5 mg/kg 1 times / day multiple, intravenous Recommended Dose: 5 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 5 mg/kg, 1 times / day Sources: |
unhealthy, adult n = 179 Health Status: unhealthy Condition: CMV retinitis in HIV infection Age Group: adult Sex: M+F Population Size: 179 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/22777050/ |
PubMed
Title | Date | PubMed |
---|---|---|
Oral ganciclovir and pharmacokinetics of valganciclovir in liver transplant recipients. | 1999 |
|
Prophylaxis against herpesvirus infections in transplant recipients. | 2001 |
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Recent advances in imaging endogenous or transferred gene expression utilizing radionuclide technologies in living subjects: applications to breast cancer. | 2001 |
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Suicide gene therapy for human oral squamous cell carcinoma cell lines with adeno-associated virus vector. | 2001 Apr |
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Intravitreal pharmacokinetics and retinal concentrations of ganciclovir and foscarnet after intravitreal administration in rabbits. | 2001 Apr |
|
Cytological monitoring of peripheral blood, bronchoalveolar lavage fluid, and transbronchial biopsy specimens during acute rejection and cytomegalovirus infection in lung and heart--lung allograft recipients. | 2001 Apr |
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Suspension of anticytomegalovirus maintenance therapy following immune recovery due to highly active antiretroviral therapy. | 2001 Apr |
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Risk for cytomegalovirus disease in patients receiving polymerase chain reaction-based preemptive antiviral therapy after allogeneic stem cell transplantation depends on transplantation modality. | 2001 Apr 1 |
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Protection from lethal murine graft-versus-host disease without compromise of alloengraftment using transgenic donor T cells expressing a thymidine kinase suicide gene. | 2001 Apr 15 |
|
A time to live, a time to die. | 2001 Apr 15 |
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Adenoviral-mediated gene therapy for thyroid carcinoma using thymidine kinase controlled by thyroglobulin promoter demonstrates high specificity and low toxicity. | 2001 Feb |
|
[Cytomegalovirus rhombencephalomyelitis in an immunocompetent subject]. | 2001 Feb |
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Gamma-rays enhance rAAV-mediated transgene expression and cytocidal effect of AAV-HSVtk/ganciclovir on cancer cells. | 2001 Feb |
|
Human prostate carcinoma cells as targets for herpes simplex virus thymidine kinase-mediated suicide gene therapy. | 2001 Feb |
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Immune-dependent distant bystander effect after adenovirus-mediated suicide gene transfer in a rat model of liver colorectal metastasis. | 2001 Feb |
|
Effect of the complexation with cyclodextrins on the in vitro antiviral activity of ganciclovir against human cytomegalovirus. | 2001 Feb |
|
Genetic risks of antiviral nucleoside analogues--a survey. | 2001 Feb |
|
Conditional abatement of tissue fibrosis using nucleoside analogs to selectively corrupt DNA replication in transgenic fibroblasts. | 2001 Feb |
|
Failure of cidofovir to reduce CMV-antigenemia in a child transplanted from a matched unrelated donor. | 2001 Feb |
|
Stimulation of intercellular communication of poor-communicating cells by gap-junction-competent cells enhances the HSV-TK/GCV bystander effect in vitro. | 2001 Feb 15 |
|
Ovarian epithelial cell lineage-specific gene expression using the promoter of a retrovirus-like element. | 2001 Feb 15 |
|
Coexpression of the partial androgen receptor enhances the efficacy of prostate-specific antigen promoter-driven suicide gene therapy for prostate cancer cells at low testosterone concentrations. | 2001 Feb 15 |
|
A tightly regulated immortalized human fetal hepatocyte cell line to develop a bioartificial liver. | 2001 Feb-Mar |
|
Meta-analysis of prophylaxis of CMV disease in solid organ transplantation: is Ganciclovir a superior agent to Acyclovir? | 2001 Feb-Mar |
|
Preemptive ganciclovir for CMV viremia in liver transplantation. | 2001 Feb-Mar |
|
Prophylactic antiviral therapy in CMV high-risk liver transplant recipients. | 2001 Feb-Mar |
|
Is preemptive therapy for CMV infection following liver transplantation superior to symptom-triggered treatment? | 2001 Feb-Mar |
|
Cytomegalovirus infection-enhanced chronic rejection in the rat is prevented by antiviral prophylaxis. | 2001 Feb-Mar |
|
Ganciclovir prophylaxis for cytomegalovirus infection in simultaneous kidney-pancreas transplant recipients receiving tacrolimus, mycophenolate mofetil, and prednisone. | 2001 Feb-Mar |
|
CMV in kidney transplants in the tacrolimus-mycophenolate era. | 2001 Feb-Mar |
|
Rat glioma cell death induced by cationic liposome-mediated transfer of the herpes simplex virus thymidine kinase gene followed by ganciclovir treatment. | 2001 Jan |
|
Targeting the replication of adenovirus to p53-defective thyroid carcinoma with a p53-regulated Cre/loxP system. | 2001 Jan |
|
Toxic megacolon: remember cytomegalovirus. | 2001 Mar |
|
Cytomegalovirus colitis complicating ulcerative colitis in the steroid-naive patient. | 2001 Mar |
|
Prevalence of cytomegalovirus infection in severe refractory ulcerative and Crohn's colitis. | 2001 Mar |
|
Characterization of the cyclooxygenase-2 promoter in an adenoviral vector and its application for the mitigation of toxicity in suicide gene therapy of gastrointestinal cancers. | 2001 Mar |
|
The real danger of lamivudine-resistant hepatitis B virus infection in the immunocompromised host. | 2001 Mar |
|
High-dose intravitreal ganciclovir and foscarnet for cytomegalovirus retinitis. | 2001 Mar |
|
Frosted branch angiitis in a child with HIV infection. | 2001 Mar |
|
New developments in the management of cytomegalovirus infection and disease after renal transplantation. | 2001 Mar |
|
Protease pretreatment increases the efficacy of adenovirus-mediated gene therapy for the treatment of an experimental glioblastoma model. | 2001 Mar 1 |
|
Expression of herpes simplex virus-thymidine kinase gene controlled by a promoter region of the midkine gene confers selective cytotoxicity to ganciclovir in human carcinoma cells. | 2001 Mar 1 |
|
Preevaluation of clinical trial data: the case of preemptive cytomegalovirus therapy in patients with human immunodeficiency virus. | 2001 Mar 1 |
|
Preemptive therapy versus universal prophylaxis with ganciclovir for cytomegalovirus in solid organ transplant recipients. | 2001 Mar 1 |
|
Adenovirus-mediated gene therapy specific for small cell lung cancer cells using a Myc-Max binding motif. | 2001 Mar 15 |
|
Prophylaxis for CMV should not now replace pre-emptive therapy in solid organ transplantation. | 2001 Mar-Apr |
|
Reactivity of valganciclovir in aqueous solution. | 2005 Oct |
|
The Role of Antiviral Prophylaxis for the Prevention of Epstein-Barr Virus-Associated Posttransplant Lymphoproliferative Disease in Solid Organ Transplant Recipients: A Systematic Review. | 2017 Mar |
|
A 42-Year-Old Woman With Anemia, Shock, and Ischemic Stroke After Lung Transplantation. | 2017 Mar |
|
Top 1% of Inpatients Administered Antimicrobial Agents Comprising 50% of Expenditures: A Descriptive Study and Opportunities for Stewardship Intervention. | 2017 Mar |
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N0000175461
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C1556
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J05AB14
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N0000175459
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N0000175459
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NBK548760
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N0000020060
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675818
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N0000175459
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C281
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WHO-VATC |
QJ05AB14
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63635
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All of the following components must be present:
ACTIVE MOIETY
SALT/SOLVATE (PARENT)
SUBSTANCE RECORD