Gene:

CYP2C19

cytochrome P450, family 2, subfamily C, polypeptide 19

Guidelines regarding the use of pharmacogenomic tests in dosing for clopidogrel have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).

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Excerpt from the clopidogrel dosing guidelines:

The table below summaries the therapeutic CPIC guidelines for clopidogrel based on CYP2C19 phenotype for patients with acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI) initiating antiplatelet therapy. These guidelines have been limited to the CYP2C19*2 allele (rs4244285). At the time of writing these guidelines, only the CYP2C19*2 allele has been adequately studied with respect to clinical outcomes on clopidogrel; other variants are too rare, have not been studied, or have resulted in inconclusive findings. In addition to the CYP2C19*2 allele, many clinical genotyping platforms include other variant alleles (*3-*8, *17) that may alter the interpretation of a patient's predicted metabolizer phenotype. For some rare genotype combinations (e.g.*2/*17) metabolic phenotypes are difficult to predict.

Clopidogrel therapy based on CYP2C19 phenotype for ACS/PCI patients initiating antiplatelet therapy:

¹ The CYP2C19*17 allele (rs12248560) may be associated with increased risk of bleeding (see article for reference).

An important caveat for all genotyping tests is that the "wild-type" (*1) status is reported if all other alleles that are measured are absent. Some genotype tests do not interrogate the rare loss of function alleles and therefore, if present, they may be erroneously reported as "wild type". Furthermore, in human DNA, it is always possible that a new, previously undiscovered (and therefore un-interrogated) site of variation may confer altered enzyme function in an individual, and thus lead to the rare possibility of a loss-of-function allele being erroneously called as "wild-type" (*1). The guidelines do not focus on demographic and other clinical variables, such as adherence to therapy, age, diabetes mellitus, obesity, smoking, and concomitant use of other drugs that may influence clopidogrel efficacy and clinical decision making; see article.

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for citalopram based on CYP2C19 genotype. They conclude to monitor plasma concentration and titrate dose to a maximum of 150% in response to efficacy and adverse drug event or select alternative drug (e.g. fluoxetine, paroxetine) for the CYP2C19 UM phenotype.

• *See Methods or PMID: 18253145 for definition of "good quality."
• Please see attached PDF for detailed information about the evaluated studies: Citalopram CYP2C19

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for clopidogrel based on the CYP2C19 genotype. For the CYP2C19 PM and IM phenotype they conclude an increased risk for reduced response to clopidogrel and recommend to consider an alternative drug. Prasugrel is not or to a much smaller extent metabolized by CYP2C19 but is associated with an increased bleeding risk compared to clopidogrel.

• *See Methods or PMID: 18253145 for definition of "good quality."
• #wherever one or more of the "good quality" criteria was missing, the quality of the study was considered to be "moderate"

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for escitalopram based on the CYP2C19 genotype. They conclude to monitor plasma concentration and titrate dose to a maximum of 150% in response to efficacy and adverse drug event or select alternative drug (e.g. fluoxetine, paroxetine) for the CYP2C19 UM phenotype.

• *See Methods or PMID: 18253145 for definition of "good quality."
• Please see attached PDF for detailed information about the evaluated studies: Escitalopram CYP2C19

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for esomeprazole based on CYP2C19 genotype. For the CYP2C19 UM phenotype, they conclude to be extra alert to insufficient response and recommend to consider dose increase by 50-100%.

• *See Methods or PMID: 18253145 for definition of "good quality."

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for imipramine based on CYP2C19 genotype.

• #See Methods or PMID: 18253145 for definition of "moderate" quality.
• Please see attached PDF for detailed information about the evaluated studies: Imipramine CYP2C19

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for lansoprazole based on CYP2C19 genotype. For the CYP2C19 UM phenotype, they conclude to be extra alert to insufficient response and recommend to consider dose increase by 200%.

• *See Methods or PMID: 18253145 for definition of "good quality."

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for moclobemide based on CYP2C19 genotype. They conclude that there are no recommendations at this time.

• #See Methods or PMID: 18253145 for definition of "moderate" quality.

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for omeprazole based on CYP2C19 genotype. For the CYP2C19 UM phenotype, they conclude to be extra alert to insufficient response and recommend to consider dose increase by 100-200%.

• * and # See Methods or PMID: 18253145 for definition of "good" and "moderate" quality.
• Please see attached PDF for detailed information about the evaluated studies: Omeprazole CYP2C19

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for pantoprazole based on CYP2C19 genotype. For the CYP2C19 UM phenotype, they conclude to be extra alert to insufficient response and recommend to consider dose increase by 400%.

• #See Methods or PMID: 18253145 for definition of "moderate" quality.

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for rabeprazole based on CYP2C19 genotype. They conclude that there are no recommendations at this time.

• *See Methods or PMID: 18253145 for definition of "good quality."

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for sertraline based on CYP2C19 genotype.

• *See Methods or PMID: 18253145 for definition of "moderate" quality.
• Please see attached PDF for detailed information about the evaluated studies: Sertraline CYP2C19

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for voriconazole based on CYP2C19 genotype. They conclude to monitor serum concentration for patients carrying the CYP2C19 PM or IM phenotype.

• *See Methods or PMID: 18253145 for definition of "moderate" quality.

The FDA recommends, but does not require, genetic testing prior to initiating or reinitiating treatment with Carisoprodol.

Excerpt from the Carisoprodol drug label:
"Patients with Reduced CYP2C19 Activity: Carisoprodol should be used with caution in patients with reduced CYP2C19 activity. Published studies indicate that patients who are poor CYP2C19 metabolizers have a 4-fold increase in exposure to carisoprodol, and concomitant 50% reduced exposure to meprobamate compared to normal CYP2C19 metabolizers. The prevalence of poor metabolizers in Caucasians and African Americans is approximately 3-5% and in Asians is approximately 15-20%."

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Carisoprodol drug label PDF.

The FDA recommends, but does not require, genetic testing prior to initiating or reinitiating treatment with Clobazam.

PGx information can be found in the Clinical Pharmacology, Dosage and Administration and Use in Specific Populations label sections.

Excerpts from the clobazam (ONFI) label:

Concentrations of clobazam's active metabolite, N-desmethylclobazam, are higher in CYP2C19 poor metabolizers than in extensive
metabolizers. For this reason, the initial dose in patients known to be CYP2C19 poor metabolizers should be 5 mg/day. These patients
should be titrated initially to 10-20 mg/day, and may be titrated further to a maximum daily dose of 40 mg if tolerated

The major metabolic pathway of clobazam involves N-demethylation, primarily by CYP3A4 and to a lesser extent by CYP2C19 and CYP2B6. N-desmethylclobazam, an active metabolite, is the major circulating metabolite in humans, and at therapeutic doses,
plasma concentrations are 3-5 times higher than those of the parent compound.

In CYP2C19 poor metabolizers, levels of N-desmethylclobazam were 5-fold higher in plasma and 2-to 3-fold higher in the urine than in CYP2C19 extensive metabolizers.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the clobazam (ONFI) drug label.

The clopidogrel label highlights the pharmacogenetics of this drug.

Excerpt from the clopidogrel drug label:

The effectiveness of Plavix is dependent on its activation to an active metabolite by the cytochrome P450 (CYP) system, principally CYP2C19 [see Warnings and Precautions (5.1)]. Plavix at recommended doses forms less of that metabolite and has a smaller effect on platelet function in patients who are CYP2C19 poor metabolizers. Poor metabolizers with acute coronary syndrome or undergoing percutaneous coronary intervention treated with Plavix at recommended doses exhibit higher cardiovascular event rates than do patients with normal CYP2C19 function. Tests are available to identify a patient's CYP2C19 genotype; these tests can be used as an aid in determining therapeutic strategy [see Clinical Pharmacology (12.5)]. Consider alternate treatment or treatment strategies in patients identified as CYP2C19 poor metabolizers [see Dosage and Administration (2.3)].

Twenty-one studies involving 4,520 subjects have shown that CYP2C19*2, CYP2C19*3, and other CYP2C19 loss-of-function alleles are associated with diminished antiplatelet responses to treatment with clopidogrel. CYP2C19 participates in the formation of both the active metabolite of clopidogrel and the 2-oxo-clopidogrel intermediate metabolite. Individuals with CYP2C19 loss-of-function alleles have reduced exposure to the active metabolite of clopidogrel, leading to less platelet inhibition or higher residual platelet reactivity. Key publications on pharmacogenetic studies of response to clopidogrel include: [Article:19106083, 19106084, 19108880, 19193675@PubMed].

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the clopidogrel drug label, updated 3/2010.

Diazepam is used mainly for treatment of anxiety and anxiety disorders and also for treatment of other issues including seizures, muscle spasms and irritable bowel syndrome. CYP2C19 is involved in its metabolism.

Excerpts from the Diazepam drug label:

"Diazepam is N-demethylated by CYP3A4 and 2C19 to the active metabolite N-desmethyldiazepam, and is hydroxylated by CYP3A4 to the active metabolite temazepam."

"There is a potentially relevant interaction between diazepam and compounds which inhibit certain hepatic enzymes (particularly
cytochrome P450 3A and 2C19."

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Diazepam drug label.

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

Esomeprazole is a proton pump inhibitor and entantiomer of omeprazole. It is metabolized in the liver by CYP2C19 and CYP3A4 (see Proton Pump Inhibitor Pathway).

The FDA recommends, but does not require, genetic testing prior to initiating or reinitiating treatment with esomeprazole.

Excerpt from the esomeprazole (Nexium) drug label:
"Esomeprazole may potentially interfere with CYP 2C19, the major esomeprazole metabolizing enzyme. Coadministration of esomeprazole 30 mg and diazepam, a CYP 2C19 substrate, resulted in a 45% decrease in clearance of diazepam. Concomitant administration of esomeprazole and a combined inhibitor of CYP 2C19 and CYP 3A4, such as voriconazole, may result in more than doubling of the esomeprazole exposure. Dose adjustment of esomeprazole is not normally required."

"CYP 2C19 isoenzyme exhibits polymorphism in the metabolism of esomeprazole, since some 3% of Caucasians and 15 to 20% of Asians lack CYP 2C19 and are termed Poor Metabolizers. At steady state, the ratio of AUC in Poor Metabolizers to AUC in the rest of the population (Extensive Metabolizers) is approximately 2."

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the esomeprazole (Nexium) drug label.

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

The FDA recommends, but does not require, genetic testing prior to initiating or reinitiating treatment with dexlansoprazole. Dexlansoprazole is the R-enantiomer of lansoprazole (a racemic mixture of the R- and S-enantiomers).

Excerpts from the dexlansoprazole (Dexilant) label:

"Dexlansoprazole is extensively metabolized in the liver by oxidation, reduction, and subsequent formation of sulfate, glucuronide and glutathione conjugates to inactive metabolites. Oxidative metabolites are formed by the cytochrome P450 (CYP) enzyme system including hydroxylation mainly by CYP2C19, and oxidation to the sulfone by CYP3A4."

"In male Japanese subjects who received a single dose of DEXILANT 30 mg or 60 mg (N=2 to 6 subjects/group), mean dexlansoprazole Cmax and AUC values were up to 2 times higher in intermediate compared to extensive metabolizers; in poor metabolizers, mean Cmax was up to 4 times higher and mean AUC was up to 12 times higher compared to extensive metabolizers. Though such study was not conducted in Caucasians and African Americans, it is expected dexlansoprazole exposure in these races will be affected by CYP2C19 phenotypes as well."

"Concomitant administration of dexlansoprazole and tacrolimus may increase whole blood levels of tacrolimus, especially in transplant patients who are intermediate or poor metabolizers of CYP2C19."

PGx information can be found in the Clinical Pharmacology and Drug Interactions label sections.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the dexlansoprazole (Dexilant) drug label.

The FDA recommends, but does not require, genetic testing prior to initiating or reinitiating treatment with Omeprazole.

PGx information can be found in the Dosage and Administration, Warnings and Precautions and Drug Interactions label sections.

Excerpts from the omeprazole (Prilosec) label:

Omeprazole is an inhibitor of CYP2C19 enzyme.

Avoid concomitant use of clopidogrel and omeprazole. Co-administration of clopidogrel with 80 mg omeprazole, a proton pump
inhibitor that is an inhibitor of CYP2C19, reduces the pharmacological activity of clopidogrel if given concomitantly or if given 12
hours apart

In pharmacokinetic studies of single 20 mg omeprazole doses, an increase in AUC of approximately four-fold was noted in Asian
subjects compared with Caucasians. Dose reduction, particularly where maintenance of healing of erosive esophagitis is indicated, for
Asian subjects should be considered.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the omeprazole (Prilosec) drug label.

The FDA recommends, but does not require, genetic testing prior to initiating or reinitiating treatment with Pantoprazole.

PGx information can be found in the Clinical Pharmacology, Drug Interactions and Special Populations label sections.

Excerpts from the pantoprazole (Protonix) label:

Pantoprazole is metabolized mainly by CYP2C19 and to minor extents by CYPs 3A4, 2D6, and 2C9. In in vivo drug-drug interaction studies with CYP2C19 substrates (diazepam (also a CYP3A4 substrate) and phenytoin (also a CYP3A4 inducer) and clopidogrel), nifedipine, midazolam, and clarithromycin (CYP3A4 substrates), metoprolol (a CYP2D6 substrate), diclofenac, naproxen and piroxicam (CYP2C9 substrates), and theophylline (a CYP1A2 substrate) in healthy subjects, the pharmacokinetics of pantoprazole were not significantly altered.

For adult patients who are CYP2C19 poor metabolizers, no dosage adjustment is needed.
Similar to adults, pediatric patients who have the poor metabolizer genotype of CYP2C19 (CYP2C19 *2/*2) exhibited greater than a 6-fold increase in AUC compared to pediatric extensive (CYP2C19 *1/*1) and intermediate (CYP2C19 *1/*x) metabolizers. Poor metabolizers exhibited approximately 10-fold lower apparent oral clearance compared to extensive metabolizers. For known pediatric poor metabolizers, a dose reduction should be considered.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the pantoprazole (Protonix) drug label.

The FDA recommends, but does not require, genetic testing prior to initiating or reinitiating treatment with Prasugrel.

PGx information can be found in the Use in Specific Populations, Clinical Pharmacology and Clinical Studies label sections.

Excerpts from the prasugrel (Effient) label:

In healthy subjects, patients with stable atherosclerosis, and patients with ACS receiving prasugrel, there was no relevant effect
of genetic variation in CYP2B6, CYP2C9, CYP2C19, or CYP3A5 on the pharmacokinetics of prasugrel's active metabolite or its
inhibition of platelet aggregation.

12.5 Pharmacogenomics
There is no relevant effect of genetic variation in CYP2B6, CYP2C9, CYP2C19, or CYP3A5 on the pharmacokinetics of prasugrel's
active metabolite or its inhibition of platelet aggregation.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the prasugrel (Effient) drug label.

Rabeprazole is a proton-pump inhibitor used for treatment of Erosive or Ulcerative Gastroesophageal Reflux Disease (GERD). CYP2C19 poor metabolizer genotypes may have lower suppression of gastric acid as compared to more extensive metabolizers.

Excerpts from the rabeprazole drug label:

"In a clinical study in Japan evaluating rabeprazole in patients categorized by CYP2C19 genotype (n=6 per genotype category), gastric acid suppression was higher in poor metabolizers as compared to extensive metabolizers. This could be due to higher rabeprazole plasma levels in poor metabolizers."

"CYP2C19 exhibits a known genetic polymorphism due to its deficiency in some sub-populations (e.g. 3 to 5% of Caucasians and 17 to 20% of Asians). Rabeprazole metabolism is slow in these sub-populations, therefore, they are referred to as poor metabolizers of the drug."

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Rabeprazole drug label.

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

Voriconazole is an antifungal used to treat serious infections of Aspergillus fumigatu, Candida, Scedosporium, Fusarium and other species. Voriconazole is metabolized in the liver by CYP2C19, CYP2C9 and CYP3A4. It also influences expression of metabolizing enzymes and interacts with several other drugs.

The FDA recommends, but does not require, genetic testing prior to initiating or reinitiating treatment with Voriconazole.

Excerpt from the Voriconazole (VFEND) drug label:
"Inhibitors and inducers of CYP3A4, CYP2C9, and CYP2C19 may alter VFEND concentrations. Adjust the VFEND dose and monitor for adverse events or lack of efficacy."

"VFEND may increase the concentrations and activity of drugs that are CYP3A4, CYP2C9 and CYP2C19 substrates. Reduce doses of and monitor for lack of efficacy or adverse events associated with drugs that are substrates of these enzymes."

"In vivo studies indicated that CYP2C19 is significantly involved in the metabolism of voriconazole. This enzyme exhibits genetic polymorphism. For example, 1520% of Asian populations may be expected to be poor metabolizers. For Caucasians and Blacks, the prevalence of poor metabolizers is 35%. Studies conducted in Caucasian and Japanese healthy subjects have shown that poor metabolizers have, on average, 4-fold higher voriconazole exposure (AUCt) than their homozygous extensive metabolizer counterparts. Subjects who are heterozygous extensive metabolizers have, on average, 2-fold higher voriconazole exposure than their homozygous extensive metabolizer counterparts."

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Voriconazole drug label.

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

The FDA recommends, but does not require, genetic testing prior to initiating or reinitiating treatment with Citalopram.

PGx information can be found in the Drug Interactions and Warnings label sections.

Excerpts from the citalopram (Celexa) label:

CYP3A4 and 2C19 Inhibitors - In vitro studies indicated that CYP3A4 and 2C19 are the primary enzymes involved in the metabolism
of citalopram. However, coadministration of citalopram (40 mg) and ketoconazole (200 mg), a potent inhibitor of CYP3A4, did not
significantly affect the pharmacokinetics of citalopram. Because citalopram is metabolized by multiple enzyme systems, inhibition of
a single enzyme may not appreciably decrease citalopram clearance.

In vitro studies suggest that citalopram is a relatively weak inhibitor of CYP2D6. Coadministration of Celexa (40 mg/day for 10 days) with the TCA imipramine (single dose of 100 mg), a substrate for
CYP2D6, did not significantly affect the plasma concentrations of imipramine or citalopram. However, the concentration of the
imipramine metabolite desipramine was increased by approximately 50%. The clinical significance of the desipramine change is
unknown. Nevertheless, caution is indicated in the coadministration of TCAs with Celexa.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the citalopram (Celexa) drug label.

Drospirenone and ethinyl estradiol (Yasmin) is a combined oral contraceptive drug.

The FDA recommends, but does not require, genetic testing prior to initiating or reinitiating treatment with drospirenone and ethinyl estradiol.

Excerpt from the drospirenone and ethinyl estradiol (Yasmin) drug label:
"In in vitro studies DRSP did not affect turnover of model substrates of CYP1A2 and CYP2D6, but had an inhibitory influence on the turnover of model substrates of CYP1A1, CYP2C9, CYP2C19 and CYP3A4 with CYP2C19 being the most sensitive enzyme."

"The potential effect of DRSP on CYP2C19 activity was investigated in a clinical pharmacokinetic study using omeprazole as a marker substrate. In the study with 24 postmenopausal women including 12 women with homozygous (wild type) CYP2C19 genotype and 12 women with heterozygous CYP2C19 genotype the daily oral administration of 3 mg DRSP for 14 days did not affect the oral clearance of omeprazole (40 mg, single oral dose). Based on the available results of in vivo and in vitro studies it can be concluded that, at clinical dose level, DRSP shows little propensity to interact to a significant extent with cytochrome P450 enzymes."

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Drospirenone and ethinyl estradiol (Yasmin) drug label.

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

The FDA recommends, but does not require, genetic testing prior to initiating or reinitiating treatment with Modafinil.

PGx information can be found in the Drug Interactions label section.

Excerpts from the modafinil label:

Potential Interactions with Drugs That Inhibit, Induce, or are Metabolized by Cytochrome P-450 Isoenzymes and Other Hepatic Enzymes
In in vitro studies using primary human hepatocyte cultures, modafinil was shown to slightly induce CYP1A2, CYP2B6 and CYP3A4 in a concentration-dependent manner. Although induction results based on in vitro experiments are not necessarily predictive of response in vivo, caution needs to be exercised when modafinil is coadministered with drugs that depend on these three enzymes for their clearance. Specifically, lower blood levels of such drugs could result (See Other Drugs, Cyclosporine above).
The exposure of human hepatocytes to modafinil in vitro produced an apparent concentration-related suppression of expression of CYP2C9 activity suggesting that there is a potential for a metabolic interaction between modafinil and the substrates of this enzyme
(e.g., S-warfarin and phenytoin). In a subsequent clinical study in healthy volunteers, chronic modafinil treatment did not show a significant effect on the single-dose pharmacokinetics of warfarin when compared to placebo (See Other Drugs, Warfarin above).

In vitro studies using human liver microsomes showed that modafinil reversibly inhibited CYP2C19 at pharmacologically relevant concentrations of modafinil. CYP2C19 is also reversibly inhibited, with similar potency, by a circulating metabolite, modafinil sulfone. Although the maximum plasma concentrations of modafinil sulfone are much lower than those of parent modafinil, the combined effect of both compounds could produce sustained partial inhibition of the enzyme. Drugs that are largely eliminated via CYP2C19 metabolism, such as diazepam, propranolol, phenytoin (also via CYP2C9) or S-mephenytoin may have prolonged elimination upon coadministration with modafinil and may require dosage reduction and monitoring for toxicity.

Tricyclic antidepressants - CYP2C19 also provides an ancillary pathway for the metabolism of certain tricyclic antidepressants (e.g., clomipramine and desipramine) that are primarily metabolized by CYP2D6. In tricyclic-treated patients deficient in CYP2D6 (i.e., those who are poor metabolizers of debrisoquine; 7-10% of the Caucasian population; similar or lower in other populations), the amount of metabolism by CYP2C19 may be substantially increased. Modafinil may cause elevation of the levels of the tricyclics in this subset of patients. Physicians should be aware that a reduction in the dose of tricyclic agents might be needed in these patients.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the modafinil drug label.

Nelfinavir is a protease inhibitor which is used in combination with other medications to treat human immunodeficiency virus (HIV) infection by slowing the spread of the infection within the body. It is metabolized by cytochrome P-450 enzymes, mainly CYP3A and CYP2C19.

Excerpts from the Nelfinavir drug label:

"Nelfinavir is an inhibitor of the CYP3A enzyme. Coadministration of VIRACEPT and drugs primarily metabolized by CYP3A may result in increased plasma concentrations of the other drug that could prolong its therapeutic and adverse effects."

"Nelfinavir is metabolized by CYP3A and CYP2C19. Coadministration of VIRACEPT and drugs that induce CYP3A or CYP2C19 may decrease nelfinavir plasma concentrations and reduce its therapeutic effect. Coadministration of VIRACEPT and drugs that inhibit CYP3A or CYP2C19 may increase nelfinavir plasma concentrations."

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Nelfinavir drug label.

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

The FDA recommends, but does not require, genetic testing prior to initiating or reinitiating treatment with Fluvoxamine.

PGx information can be found in the Drug Interactions label section.

Excerpts from the fluvoxamine label:

Based on a finding of substantial interactions of fluvoxamine with certain of these drugs (see later parts of this section and also WARNINGS for details) and limited in vitro data for the 3A4 isozyme, it appears that fluvoxamine inhibits the following isozymes
that are known to be involved in the metabolism of the listed drugs:
1A2, 2C9, 3A4, 2C19, Warfarin, Alprazolam, Omeprazole, Theophylline, Propranolol, Tizanidine. In vitro data suggest that fluvoxamine is a relatively weak inhibitor of the 2D6 isozyme.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the fluvoxamine drug label.