Drug/Small Molecule:
rofecoxib

PharmGKB contains no dosing guidelines for this drug/small molecule. To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.

PharmGKB has no annotated drug labels with pharmacogenomic information for this drug/small molecule. If you know of a drug label with PGx, send us a message.

PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

Gene ? Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
rs20417 -899G>C, 186650321C>G, 38138963C>G, 4239G>C, COX-2 G-765C, PTGS2:-765G>C
C > G
5' Flanking
No VIP available No Clinical Annotations available VA
rs3842787 -248C>T, -249C>T, -278C>T, 125133507C>T, 130C>T, 356C>T, 50C>T, 5279C>T, 54298039C>T, C>T, PTGS1: P17L, Pro17Leu
C > T
5' UTR
Pro17Leu
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • MK 966
  • MK 996
  • rofecoxib
Trade Names
  • Vioxx
Brand Mixture Names

PharmGKB Accession Id:
PA451268

Description

On September 30, 2004, Merck voluntarily withdrew rofecoxib from the market because of concerns about increased risk of heart attack and stroke associated with long-term, high-dosage use.

Source: Drug Bank

Indication

For the treatment of osteoarthritis, rheumatoid arthritis, acute pain in adults, and primary dysmenorrhea, as well as acute treatment of migraine attacks with or without auras.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

The anti-inflammatory, analgesic, and antipyretic effects of NSAIDs appear to result from the inhibition of prostaglandin synthesis. Although the exact mechanism of action has not been determined, these effects appear to be mediated through the inhibition of the COX-2 isoenzyme at the sites of inflammation with subsequent reduction in the synthesis of certain prostaglandins from their arachidonic acid precursors. Rofecoxib selectively inhibits the cyclooxygenase-2 (COX-2) enzyme, which is important for the mediation of inflammation and pain. Unlike non-selective NSAIDs, rofecoxib does not inhibit platelet aggregation. It also has little to no affinity for COX-1.

Source: Drug Bank

Pharmacology

Rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is classified as a nonsteroidal anti-inflammatory drug (NSAID). Unlike celecoxib, rofecoxib lacks a sulfonamide chain and does not require CYP450 enzymes for metabolism. Like other NSAIDs, rofecoxib exhibits anti-inflammatory, analgesic, and antipyretic activity. NSAIDs appear to inhibit prostaglandin synthesis via the inhibition of cyclooxygenase (COX), which are responsible for catalyzing the formation of prostaglandins in the arachidonic acid pathyway. There are at least two isoenzymes, COX-1 and COX-2, that have been identified. Although the exact mechanisms have not been clearly established, NSAIDs exert their anti-inflammatory, analgesic, and antipyretic primarily through the inhibition of COX-2. The inhibition of COX-1 is principally responsible for the negative effects on the GI mucosa. As rofecoxib is selective for COX-2, it may be potentially associated with a decreased risk of certain adverse events, but more data is needed to fully evaulate the drug.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic. Metabolism of rofecoxib is primarily mediated through reduction by cytosolic enzymes. The principal metabolic products are the cis-dihydro and trans-dihydro derivatives of rofecoxib, which account for nearly 56% of recovered radioactivity in the urine. An additional 8.8% of the dose was recovered as the glucuronide of the hydroxy derivative, a product of oxidative metabolism. The biotransformation of rofecoxib and this metabolite is reversible in humans to a limited extent (< 5%). These metabolites are inactive as COX-1 or COX-2 inhibitors. Cytochrome P450 plays a minor role in metabolism of rofecoxib.

Source: Drug Bank

Protein Binding

87%

Source: Drug Bank

Absorption

The mean oral bioavailability of rofecoxib at therapeutically recommended doses of 12.5, 25, and 50 mg is approximately 93%.

Source: Drug Bank

Half-Life

17 hours

Source: Drug Bank

Toxicity

No overdoses of rofecoxib were reported during clinical trials. Administration of single doses of rofecoxib 1000 mg to 6 healthy volunteers and multiple doses of 250 mg/day for 14 days to 75 healthy volunteers did not result in serious toxicity.

Source: Drug Bank

Chemical Properties

Chemical Formula

C17H14O4S

Source: Drug Bank

Isomeric SMILES

CS(=O)(=O)c1ccc(cc1)C2=C(C(=O)OC2)c3ccccc3

Source: OpenEye

Canonical SMILES

CS(=O)(=O)C1=CC=C(C=C1)C1=C(C(=O)OC1)C1=CC=CC=C1

Source: Drug Bank

Average Molecular Weight

314.356

Source: Drug Bank

Monoisotopic Molecular Weight

314.061279626

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

EvidenceGene
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
PTGS1
PTGS2

Drug Targets

Gene Description
ELN (source: Drug Bank)
PTGS1 (source: Drug Bank)
PTGS2 (source: Drug Bank)

Drug Interactions

Drug Description
rofecoxib Rofecoxib increases the effect and toxicity of theophylline (source: Drug Bank)
rofecoxib The COX-2 inhibitor increases serum levels of lithium (source: Drug Bank)
rofecoxib The COX-2 inhibitor increases serum levels of lithium (source: Drug Bank)
rofecoxib Rofecoxib increases the levels of methotrexate (source: Drug Bank)
rofecoxib Rofecoxib increases the levels of methotrexate (source: Drug Bank)
rofecoxib Rofecoxib increases the effect and toxicity of theophylline (source: Drug Bank)
rofecoxib Decreased levels/effect of the NSAID (source: Drug Bank)
rofecoxib Rofecoxib increases the effect and toxicity of theophylline (source: Drug Bank)
rofecoxib Rofecoxib increases the effect and toxicity of theophylline (source: Drug Bank)

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to rofecoxib: 13

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics of drugs withdrawn from the market. Pharmacogenomics. 2012. Zhang Wei, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
PharmGKB summary: very important pharmacogene information for PTGS2. Pharmacogenetics and genomics. 2010. Thorn Caroline F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
COX inhibitors downregulate PDE4D expression in a clinical model of inflammatory pain. Clinical pharmacology and therapeutics. 2008. Wang X-M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Modeling and simulation to support dose selection and clinical development of SC-75416, a selective COX-2 inhibitor for the treatment of acute and chronic pain. Clinical pharmacology and therapeutics. 2008. Kowalski K G, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Acceleration of cardiovascular disease by a dysfunctional prostacyclin receptor mutation: potential implications for cyclooxygenase-2 inhibition. Circulation research. 2008. Arehart Eric, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pyrosequencing of polymorphisms in the COX-2 gene (PTGS2) with reported clinical relevance. Pharmacogenomics. 2007. Skarke Carsten, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Genetically mediated interindividual variation in analgesic responses to cyclooxygenase inhibitory drugs. Clinical pharmacology and therapeutics. 2006. Lee Yun-Sil, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Marked interindividual variability in the response to selective inhibitors of cyclooxygenase-2. Gastroenterology. 2006. Fries Susanne, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. The New England journal of medicine. 2005. Bresalier Robert S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Relationship between COX-2 specific inhibitors and hypertension. Hypertension. 2004. Solomon Daniel H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
COX-2 inhibition and cancer: experimental findings and clinical correlates. The West Virginia medical journal. 2004. Roberts Elizabeth Gail, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Involvement of human UGT2B7 and 2B15 in rofecoxib metabolism. Drug metabolism and disposition: the biological fate of chemicals. 2003. Zhang Ji Y, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
COX-2-selective inhibitors in the treatment of arthritis. Cleveland Clinic journal of medicine. 2002. Schnitzer Thomas J, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00533
ChEBI:
8887
KEGG Compound:
C07590
KEGG Drug:
D00568
PubChem Compound:
5090
PubChem Substance:
207247
46504787
Drugs Product Database (DPD):
2241109
BindingDB:
22369
ChemSpider:
4911

Clinical Trials

These are trials that mention rofecoxib and are related to either pharmacogenetics or pharmacogenomics.

Common Searches

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.