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 |
|
Psychotic symptoms and confusion associated with intravenous ganciclovir in a heart transplant recipient. | 2000 Apr |
|
A novel peptide aldehyde with activity against human cytomegalovirus in two different in vivo models. | 2000 Jan |
|
In vitro activities of methylenecyclopropane analogues of nucleosides and their phosphoralaninate prodrugs against cytomegalovirus and other herpesvirus infections. | 2000 Jun |
|
Prophylaxis against herpesvirus infections in transplant recipients. | 2001 |
|
Pharmacokinetics of the ganciclovir implant in the silicone-filled eye. | 2001 |
|
Suicide gene therapy for human oral squamous cell carcinoma cell lines with adeno-associated virus vector. | 2001 Apr |
|
Intravitreal pharmacokinetics and retinal concentrations of ganciclovir and foscarnet after intravitreal administration in rabbits. | 2001 Apr |
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Suspension of anticytomegalovirus maintenance therapy following immune recovery due to highly active antiretroviral therapy. | 2001 Apr |
|
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 |
|
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 |
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[Cytomegalovirus rhombencephalomyelitis in an immunocompetent subject]. | 2001 Feb |
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Human prostate carcinoma cells as targets for herpes simplex virus thymidine kinase-mediated suicide gene therapy. | 2001 Feb |
|
Immune-dependent distant bystander effect after adenovirus-mediated suicide gene transfer in a rat model of liver colorectal metastasis. | 2001 Feb |
|
Genetic risks of antiviral nucleoside analogues--a survey. | 2001 Feb |
|
Failure of cidofovir to reduce CMV-antigenemia in a child transplanted from a matched unrelated donor. | 2001 Feb |
|
Mutation of Gln125 to Asn selectively abolishes the thymidylate kinase activity of herpes simplex virus type 1 thymidine kinase. | 2001 Feb |
|
Construction of gene therapy vectors targeting thyroid cells: enhancement of activity and specificity with histone deacetylase inhibitors and agents modulating the cyclic adenosine 3',5'-monophosphate pathway and demonstration of activity in follicular and anaplastic thyroid carcinoma cells. | 2001 Feb |
|
Selective killing of human immunodeficiency virus-infected cells by targeted gene transfer and inducible gene expression using a recombinant human immunodeficiency virus vector. | 2001 Feb 10 |
|
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 |
|
Rising pp65 antigenemia during preemptive anticytomegalovirus therapy after allogeneic hematopoietic stem cell transplantation: risk factors, correlation with DNA load, and outcomes. | 2001 Feb 15 |
|
A tightly regulated immortalized human fetal hepatocyte cell line to develop a bioartificial liver. | 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 |
|
Imaging in vivo herpes simplex virus thymidine kinase gene transfer to tumour-bearing rodents using positron emission tomography and. | 2001 Jan |
|
[Gene therapy for colorectal cancer]. | 2001 Jan |
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[Perspectives on postgenome medicine: Gene therapy for brain tumors]. | 2001 Jan |
|
Management of complications associated with totally implantable ports in patients with AIDS. | 2001 Jan |
|
Cytomegalovirus hemorrhagic gastritis. | 2001 Jan |
|
Cytomegalovirus infection and non-neutropenic fever after autologous stem cell transplantation: high rates of reactivation in patients with multiple myeloma and lymphoma. | 2001 Jan |
|
Isolation and analysis of an aciclovir-resistant murine cytomegalovirus mutant. | 2001 Jan |
|
Disseminated cytomegalovirus disease in hosts without acquired immunodeficiency syndrome and without an organ transplant. | 2001 Jan 15 |
|
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 |
|
High-dose intravitreal ganciclovir and foscarnet for cytomegalovirus retinitis. | 2001 Mar |
|
Frosted branch angiitis in a child with HIV infection. | 2001 Mar |
|
Gene therapy for hepatocellular carcinoma using two recombinant adenovirus vectors with alpha-fetoprotein promoter and Cre/lox P system. | 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 |
|
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 |
|
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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N0000175459
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FDA ORPHAN DRUG |
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N0000175459
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LIVERTOX |
NBK548760
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N0000020060
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N0000175459
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C281
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WHO-VATC |
QJ05AB14
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C121677
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C2629
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63635
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All of the following components must be present:
ACTIVE MOIETY
SALT/SOLVATE (PARENT)
SUBSTANCE RECORD