Gene:
ABCB1
ATP-binding cassette, sub-family B (MDR/TAP), member 1

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

PharmGKB annotates drug labels containing pharmacogenetic information approved by the US Food and Drug Administration (FDA), European Medicines Agency (EMA), the Pharmaceuticals and Medical Devices Agency, Japan (PMDA), and Health Canada (Santé Canada) (HCSC). PharmGKB annotations provide a brief summary of the PGx in the label, an excerpt from the label and a downloadable highlighted label PDF file. A list of genes and phenotypes found within the label is mapped to label section headers and listed at the end of each annotation. PharmGKB also attempts to interpret the level of action implied in each label with the "PGx Level" tag.

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last updated 09/15/2014

1. EMA Label for aliskiren and ABCB1

Informative PGx

Summary

The EMA European Public Assessment Report (EPAR) for aliskiren (Rasilez HCT) does not contain pharmacogenetic information. It contains information regarding the role of ABCB1 (P-gp, MDR1) in intestinal absorption and biliary secretion of aliskiren, and concomitant use of aliskiren with potent P-gp inhibitors is contraindicated.

Annotation

The EMA-approved drug aliskiren is tagged with P-gp (encoded by the ABCB1 gene) in Article:24433361.

Excerpt from the aliskiren (Rasilez HCT) EPAR:

P-glycoprotein interactions: MDR1/Mdr1a/1b (P-gp) was found to be the major efflux system involved in intestinal absorption and biliary excretion of aliskiren in preclinical studies. Rifampicin, which is an inducer of P-gp, reduced aliskiren bioavailability by approximately 50% in a clinical study. Other inducers of P-gp (St. John’s wort) might decrease the bioavailability of aliskiren. Although this has not been investigated for aliskiren, it is known that P-gp also controls tissue uptake of a variety of substrates and P-gp inhibitors can increase the tissue-to-plasma concentration ratios. Therefore, P-gp inhibitors may increase tissue levels more than plasma levels. The potential for drug interactions at the P-gp site will likely depend on the degree of inhibition of this transporter.

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

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

Genes and/or phenotypes found in this label

  • ABCB1
    • metabolism/PK, Contraindications section, Drug interactions section, Warnings and precautions section
    • source: European Medicines Agency

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 table.

Clinical Annotation for rs2032583 (ABCB1), amitriptyline, antidepressants, citalopram, fluvoxamine, paroxetine, sertraline, venlafaxine, Depression, Depressive Disorder and Depressive Disorder, Major (level 3 Efficacy)

Level of Evidence
Level 3
Type
Efficacy
Genes
ABCB1
Phenotypes
Depression, Depressive Disorder, Depressive Disorder, Major
OMB Race
White
Race Notes
One study in mostly German patients, the other unknown race.

To see the rest of this clinical annotation please register or sign in.

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.

? = Mouse-over for quick help

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 on the appropriate tab.

Links in the "Drugs" column lead to PharmGKB Drug Pages.

List of all variant annotations for ABCB1

Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available CA VA *1 N/A N/A N/A
No VIP available CA VA *2 (PMID: 11503014) N/A N/A N/A
No VIP available No VIP available VA *2 (PMID: 12893986) N/A N/A N/A
No VIP available CA VA
rs10248420 182579T>C, 2481+788T>C, 25197829A>G, 87164986A>G
A > G
Intronic
No VIP available CA VA
rs10267099 -330-48366C>T, 123-1378G>A, 25311603G>A, 68805C>T, 87278760G>A
G > A
Intronic
No VIP available CA VA
rs10276036 1000-44G>A, 167367G>A, 25213041C>T, 87180198C>T, ABCB1: IVS9 ¿44a>G
C > T
Intronic
No VIP available CA VA
rs10280101 193980T>G, 25186428A>C, 2686-3393T>G, 87153585A>C
A > C
Intronic
rs1045642 208920T>A, 208920T>C, 25171488A>G, 25171488A>T, 3435T>A, 3435T>C, 87138645A>G, 87138645A>T, ABCB1*6, ABCB1: 3435C>T, ABCB1: C3435T, ABCB1: c.3435C>T, ABCB1:3435C>T, Ile1145=, Ile1145Ile, MDR1 3435C>T, MDR1 C3435T, PGP C3435T, c.3435C>T, mRNA 3853C>T
A > T
A > G
Synonymous
Ile1145Ile
rs1128503 1236T>C, 167964T>C, 87179601A>G, 87550285A>G, ABCB1 1236C>T, ABCB1*8, ABCB1: c.1236T>C, ABCB1:1236C>T, ABCB1:1236T>C, Gly412=, Gly412Gly, mRNA 1654T>C, p.Gly412Gly
A > G
Synonymous
Gly412Gly
No VIP available No Clinical Annotations available VA
rs1186745 213618G>T, 25166790C>A, 3637-182G>T, 87133947C>A
C > A
Intronic
No VIP available No Clinical Annotations available VA
rs1186746 213572A>G, 25166836T>C, 3637-228A>G, 87133993T>C
T > C
Intronic
No VIP available CA VA
rs11983225 186045A>G, 2482-707A>G, 25194363T>C, 87161520T>C
T > C
Intronic
No VIP available CA VA
rs12720067 178209G>A, 2320-695G>A, 25202199C>T, 87169356C>T
C > T
Intronic
No VIP available CA VA
rs17160359 25379662G>T, 458+6848G>T, 509+6848G>T, 746C>A, 87346819G>T
G > T
Intronic
No VIP available CA VA
rs1922242 173898T>A, 2065-76T>A, 25206510A>T, 87173667A>T
A > T
Intronic
rs2032582 186947T>A, 186947T>G, 2677A, 2677G, 2677T, 2677T>A, 2677T>G, 3095G>T/A, 87160618A>C, 87160618A>T, 87531302A>C, 87531302A>T, 893 Ala, 893 Ser, 893 Thr, ABCB1*7, ABCB1: 2677G>T/A, ABCB1: 2677T/A>G, ABCB1: A893S, ABCB1: G2677T/A, ABCB1: c.2677G>T/A, ABCB1:2677G>A/T, ABCB1:2677G>T/A, ABCB1:A893T, Ala893Ser/Thr, MDR1, MDR1 G2677T/A, Ser893Ala, Ser893Thr, mRNA 3095G>T/A, p.Ala893Ser/Thr
A > T
A > C
Missense
Ser893Ala
Ser893Thr
No VIP available CA VA
rs2032583 187004T>C, 25193404A>G, 2685+49T>C, 87160561A>G
A > G
Intronic
No VIP available No Clinical Annotations available VA
rs2032588 1350+44C>T, 168122C>T, 25212286G>A, 87179443G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs2229107 208906T>A, 25171502A>T, 3421T>A, 87138659A>T, ABCB: S1141T, Ser1141Thr
A > T
Missense
Ser1141Thr
No VIP available CA VA
rs2229109 1199G>A, 1199G>T, 167756G>A, 167756G>T, 25212652C>A, 25212652C>T, 87179809C>A, 87179809C>T, ABCB1: c.1199G>A, Ser400Asn, Ser400Ile, mRNA 1617G>A, p.Ser400Asn
C > T
C > A
Missense
Ser400Ile
Ser400Asn
No VIP available CA VA
rs2235015 148001G>T, 25232407C>A, 287-25G>T, 87199564C>A
C > A
Intronic
No VIP available CA VA
rs2235040 181815G>A, 2481+24G>A, 25198593C>T, 87165750C>T
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs2235047 209033T>G, 25171375A>C, 3489+59T>G, 87138532A>C
A > C
Intronic
No VIP available No Clinical Annotations available VA
rs2235048 209054C>T, 25171354G>A, 3489+80C>T, 87138511G>A
G > A
Intronic
No VIP available CA VA
rs2235067 197643G>A, 25182765C>T, 2786+170G>A, 87149922C>T
C > T
Intronic
No VIP available CA VA
rs28401781 199237G>A, 25181171C>T, 2927+314G>A, 87148328C>T
C > T
Intronic
No VIP available CA VA
rs3213619 -129T>C, 117372T>C, 25263036A>G, 87230193A>G, ABCB1:T-129C
A > G
5' UTR
No VIP available No Clinical Annotations available VA
rs3747802 -440T>C, 25375429A>G, 458+2615A>G, 4979T>C, 509+2615A>G, 87342586A>G
A > G
5' UTR
No VIP available CA VA
rs3789243 117+4196T>C, 126679T>C, 25253729A>G, 87220886A>G
A > G
Intronic
No VIP available CA VA
rs3842 *193A>G, 214199A>G, 24997271T>C, 87504050T>C
T > C
Not Available
No VIP available CA VA
rs4148737 176413A>G, 2212-372A>G, 25203995T>C, 87171152T>C
T > C
Intronic
No VIP available CA VA
rs4148739 186516A>G, 2482-236A>G, 25193892T>C, 87161049T>C
T > C
Intronic
No VIP available CA VA
rs4148740 195462T>C, 25184946A>G, 2686-1911T>C, 87152103A>G
A > G
Intronic
No VIP available CA VA
rs4728709 -330-3208C>T, 113963C>T, 25266445G>A, 87233602G>A
G > A
Intronic
No VIP available CA VA
rs72552784 201651G>A, 25178757C>T, 2995G>A, 87145914C>T, ABCB1: c.2995G>A, Ala999Thr, mRNA 3413G>A, p.Ala999Thr
C > T
Missense
Ala999Thr
No VIP available CA VA
rs7787082 190514C>T, 25189894G>A, 2685+3559C>T, 87157051G>A
G > A
Intronic
No VIP available CA VA
rs9282564 118125A>G, 25262283T>C, 61A>G, 87229440T>C, ABCB1: c.61A>G, Asn21Asp, mRNA 479A>G, p.Asn21Asp
T > C
Missense
Asn21Asp
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Alternate Names:  CLCS; PGY1; multidrug resistance protein 1
Alternate Symbols:  ABC20; CD243; GP170; MDR1; P-gp
PharmGKB Accession Id: PA267

Details

Cytogenetic Location: chr7 : q21.12 - q21.12
GP mRNA Boundary: chr7 : 87133179 - 87342639
GP Gene Boundary: chr7 : 87130179 - 87352639
Strand: minus

Visualization

UCSC has a Genome Browser that you can use to view PharmGKB annotations for this gene in context with many other sources of information.

View on UCSC Browser
The mRNA boundaries are calculated using the gene's default feature set from NCBI, mapped onto the UCSC Golden Path. PharmGKB sets gene boundaries by expanding the mRNA boundaries by no less than 10,000 bases upstream (5') and 3,000 bases downstream (3') to allow for potential regulatory regions.

ABCB1 Description
ABCB1 (MDR1) is one of many ubiquitous adenosine triphosphate (ATP)-binding cassette (ABC) genes present in all kingdoms of life that is responsible for cellular homeostasis [Articles:15052411, 9099718, 7765321]. ABC genes encode transporter and channel proteins possessing multiple membrane-spanning domains that form a pore, and intracellular nucleotide-binding domains for ATP-dependent translocation of substrates or ions across the cell membrane [Articles:15052411, 12045106, 10331089]. Although bacterial ABC proteins function as both importers and exporters [Article:14630327], all eukaryotic ABC proteins are efflux pumps [Articles:15052411, 11907151]. ABCB1 is one of forty-nine putative members in the superfamily of human ABC transporters [Articles:1869973, 18154452] within sub-family B (MDR/TAP), which is one of seven phylogenetically distinct sub-families [Article:12045106] with overlapping substrate specificity [Article:18668431] (see Wageningen University website: www.nutrigene.4t.com/humanabc.htm).

Molecular and protein structure
ABCB1 was first cloned by Riordan and colleagues in 1985 [Article:2863759]. The gene lies less than 25 kilobases (kb) from ABCB4 on chromosome 7q21.12 (UCSC Genome Browser, March 2006 Assembly (hg18)). Analysis of human cell lines, liver tissue, and lymphocytes consistently show ABCB1 to contain 29 exons in a genomic region spanning 209.6 kb [Article:16146331] (Entrez GeneID: 5243, GenBank accession NT_007933). The two most 5' exons are untranslated. Two primary transcriptional start regions exist: a proximal promoter in exon 1 and intron 1 for constitutive expression, and a cryptic distal promoter that is active in drug-selected cell lines and cancer patient samples for overexpression of the protein product. The ABCB1 promoter region contains a few low-frequency polymorphisms and is relatively invariant compared to other genes in the genome [Article:16608921].

The messenger RNA (mRNA) is 4872 base pairs in length, including the 5' untranslated region (UTR) (RefSeq accession NM_000927.3), which gives rise to a protein that is 1280 amino acids in length, named P-glycoprotein (P-gp) [Article:16146331]. The secondary structure of P-gp reveals two homologous halves to the protein, each containing six transmembrane domains and a nucleotide-binding domain (see image per Fung et al. [Article:19285158] as adapted from Ambudkar et al. [Article:10331089]). The existence and number of putative splice variants is undetermined [Article:16146331]. Alternative transcripts for ABCB1 have been predicted from sequence alignments with human complementary DNA (cDNA) (see ABCB1 in AceView), protein sequences, and expressed sequence tags [Article:[16708052]. P-gp is post-translationally modified by phosphorylation and N-glycosylation. Differential phosphorylation of P-gp by kinases have been shown to influence P-gp activity [Articles:10790147, 16309179].

A number of mechanistic observations have been made from low-resolution crystal structures for P-gp in bacteria [Article:12777401] and Chinese hamster ovary cells [Article:9099718], and from a high-resolution structure of the mouse homolog with 87% sequence identity to humans (see Protein Data Bank accession 3G60, 3G5U, and 3G61) [Article:19325113]. The twelve transmembrane helices form a toroidal protein with an aqueous pore (see image from Higgins et al. [Article:9099718]). Two nucleotide-binding domains for the protein lie in the cytoplasm. The pore is lined with hydrophobic and aromatic amino acids at the extracellular-facing half of the pore, while the cytosolic-facing portion of the pore contains polar, charged residues [Article:19325113]. Structural analysis reveals two openings in the protein that open into the lipid bilayer and permit extraction of substrates directly from the membrane upon the passive diffusion of substrates into the cell (see image from Aller et al. [Article:19325113]) [Articles:9099718, 12777401]. Several highly conserved residues within the pore are able to recognize a diverse range of substrates. The protein exhibits high conformational flexibility to allow for structural rearrangements in binding and effluxing substrates [Article:19325113]. Substrate-bound images reveal the capacity to distinguish stereoisomers and simultaneously bind multiple substrates at overlapping binding sites. The ability to bind substrates in close proximity to one another provides a mechanistic rationale for observed functional interactions between co-administered substrates (e.g. allosteric, competitive and non-competitive inhibition, and cooperativity) [Articles:9300798, 18668431, 19325102].

Tissue distribution and function
P-gp is expressed in a polarized manner in the plasma membrane of cells in barrier and elimination organs, where it has protective and excretory function [Article:11913728]. It plays an important role in the first-pass elimination of orally administered drugs to limit their bioavailability by effluxing them at the lumen-facing epithelia of the small intestine and colon, and the bile-facing canaliculi of the liver. It eliminates substrates from the systemic circulation at the urine-facing side of the brush border membrane of proximal tubules in the kidney, and again via biliary excretion. It restricts permeability of drugs into 'sanctuary' organs from the apical or serosal side of blood-tissue barriers (e.g. blood-brain, blood-cerebral spinal fluid, blood-placenta, blood-testis barriers) [Article:15276711]. P-gp expression in the adrenal cortex is thought to play a role in hormone transport and homeostasis, and glucorcorticoid resistance [Articles:12844331, 10331089]. In lymphocytes and other immunological and blood components P-gp putatively plays a role in viral resistance and in trafficking cytokines and enveloped viruses [Articles:10331089, 8765502, 10698966]. P-gp is also thought to be important for steroid partitioning and lipid homeostasis in the periphery and central nervous system [Articles:12379510, 19285054, 12844331]. Intracellular P-gp has been detected in the endoplasmic reticulum, vesicles, and the nuclear envelope, and has been associated with cell trafficking machinery with unknown function [Article:18560012]. Relevant to the clinical challenge of multi-drug resistance, P-gp is overexpressed in numerous tissues transformed by cancer.

Physiological role
P-gp was discovered in 1970 by Biedler and colleagues who observed the phenomenon of multi-drug resistance (MDR) conferred by a cell surface protein in mammalian cell lines. This membrane protein conferred up to a 2500-fold increase in drug resistance to actinomycin D and cross-resistance to a single exposure of mithramycin, vinblastine, vincristine, puromycin, daunomycin, demecolcine, and mitomycin C [Article:5533992]. The 170 kilo Dalton (kD) phospho-glycoprotein, or 'permeability' glycoprotein, was identified as the cause for reduced cellular drug exposure [Article:990323] by its active extrusion of drugs from the cell [Articles:1203765, 2900833]. The physiological impact of this multi-drug efflux pump was appreciated in 1994 by Schinkel and colleagues who observed a 100-fold increase in the brain penetration of antiparasitic medication, ivermectin, in genetically engineered mice lacking abcb1 [Article:7910522]. Animals naturally deficient for abcb1 were also found to exhibit neurological and fetal drug toxicity due to a breach in the blood-brain and blood-placenta barriers where P-gp is normally active [Articles:9299600, 19171022]. A 4-base pair deletion (ABCB1-1 Delta) was subsequently identified as the cause of the non-functioning allele in dogs [Article:19171022], which led to proposed dosing changes in veterinary medicine [Articles:9934933, 19411645]. In humans, spontaneous deletion of ABCB1 has not been described, but a nonfunctional variant was found in two heterozygous individuals in which a single nucleotide polymorphism (SNP), T3587G, results in an isoleucine to serine change at residue 1196 in the second ATP-binding domain of P-gp [Article:16648557]. However, in one heterozygous subject tested, the SNP was not shown to affect the clearance of the P-gp substrate, SN-38, after parenteral irinotecan administration [Articles:16648557, 14646693]. The frequency of the 3587 G allele was 1:300 in a Japanese population, thus homozygotes with two copies of the non-functioning 1196Ser allele would be very rare (1:100,000).

Numerous common coding variants in ABCB1 have been studied for their potential influence on P-gp expression, function, and disease risk. Genetic associations with molecular or clinical phenotypes have largely been inconsistent [Articles:12406646, 14749689, 16969364]. As a result, no adjustments in drug dosing have been recommended for individuals carrying sequence variants of ABCB1 in humans, and replication studies are needed to understand the influence of ABCB1 genetics on disease susceptibility. Current clinical considerations for P-gp are therefore related to its important role in (1) multi-drug resistance, and (2) drug-drug interactions, derived primarily from its broad substrate specificity and variable intrinsic and drug-induced expression [Article:17933685].

Compounds that interact with P-gp
P-gp recognizes and effluxes a multitude of structurally and biochemically unrelated substrates (cyclic, linear, basic, uncharged, zwitterionic, negatively charged, hydrophobic, aromatic, non-aromatic, amphipathic), from 250 to 4,000 molecular weight ISBN: [9780123695208], [Articles:18560012, 15072439], sufficiently indeterminate to predict in drug design [Article:11907151]. Substrates include xenobiotics, endogenous compounds (e.g. peptides (including beta-amyloids), steroid hormones, lipids, phospholipids, cholesterol, and cytokines) [Article:9300798], pharmaceuticals [Article:16454744], neutraceuticals (e.g. St. John's wort), dietary compounds (e.g. grapefruit juice, green tea) ISBN: [9781588293138, [Article:15072439] , and other compounds, which may also modulate P-gp activity [Article:19545213]. P-gp compounds can act as substrates, inhibitors, inducers, and repressors; and citations refer to P-gp compounds as being in more than one category, depending upon the circumstance [Article:18668431]. Modulation of ABCB1 gene expression and/or P-gp activity by various mechanisms consequently influences P-gp-mediated drug disposition.

Repressors of P-gp, including certain antineoplastic agents that act at nuclear receptors [Article:17048260], or endotoxin [Article:14709616], cobalamin [Article:17982279], and atorvastatin [Articles:18156365, 19543298], potentiate the action of substrates; while rifampin (rifampicin) [Article:10411543] and cell stress signals induce P-gp-mediated drug resistance [Articles:17982279, 18156365, 18560012]. Another mechanism for P-gp-related pharmacoresistance to cytotoxic agents is hypothesized to relate to the cell stress signals they induce [Articles:18699730, 19638996]. Upregulation of ABCB1 gene expression can occur at gene promoter sequences via transactivation [Articles:15072439, 18668431, 19460946], for example, by the pregnane X receptor (NR1I2, PXR) gene in response to substrates that may have overlapping specificity for P-gp [Article:18560012]; or induction can occur independent of nuclear receptors [Article:15258100]. Alternatively, epigenetic inactivation of P-gp can occur by DNA methylation at specific nucleotide sequences within the promoter sequence, called CpG islands, as has been observed in some cancer tissues [Article:15326379]; or downregulation of P-gp can also occur by mechanisms other than by DNA methylation, for example, in response to cobalamin, a vitamin B-12 derivative [Article:17982279].

Drug interactions
Many studies have characterized the interactions between P-gp compounds, since concomitant administration can substantially alter the pharmacokinetics of the compounds involved [Article:17933685]. Research has focused on both the deleterious and beneficial effects of interactions between P-gp compounds: (1) interactions that potentially affect drug safety and efficacy [Article:9300798], and (2) interactions exploited to optimize drug delivery.

Drug safety and efficacy are major health concerns, particulary for drugs with a narrow therapeutic index and/or large clinical effect [Article:17168768]. A number of drug interactions of clinical relevance are cited as warnings in the drug labels. For example, the drug label for the contraceptive, Trinessa (Watson Pharma, Inc.), warns against potential drug inefficacy when coadministered with compounds that induce P-gp (e.g. rifampin, St. John's wort, protease inhibitors, carbamazepine, and barbiturates). The drug label for the antidiarrheal, loperamide (Imodium, McNeil Consumer Healthcare), warns against neurotoxic side effects when coadministered with P-gp inhibitors (e.g. quinidine, ritonavir) since this gut-targeted optiate relies upon P-gp to prohibit intestinal absorption and entry into the central nervous system [Article:19372478].

Interactions between compounds are substrate-specific, concentration-dependent [Article:9300798], and tissue-specific [Article:16537797]. For example, unlike the drug-potentiating interaction between quinine [Articles:11014404, 14583678] or ritonavir [Article:16304151] on loperamide, the potent P-gp inhibitor, tariquidar, does not produce the same analgesic effects, despite its efficient inhibition of P-gp in lymphocytes. This is presumably due to tissue-specific factors [Article:16537797]. Concentration is another important determinant of drug interactions. For example, at the therapeutic concentration for the beta blocker and P-gp substrate, propranolol (Innopran Xl, Reliant Pharmaceuticals, Inc.), propranolol disposition is not affected by modulation of P-gp by other compounds. Other influences include key pharmacokinetic genes that affect the disposition of substrates for P-gp. For example, P-gp and cytochrome P450 3A4 metabolizing enzyme (CYP3A4) overlap in tissue distribution and specificity for a substantial number of substrates, inducers, and inhibitors [Articles:7619215, 15276711]. Furthermore, genes responsible for the disposition of a drug can act synergistically [Article:16435171]. Marchetti et al. cite clinically relevant drug interactions influenced by the interplay of ABCB1 with other genes in the disposition of P-gp compounds, such as paclitaxel and cyclosporine A (CsA) (via CYP3A4 inhibition), digoxin and rifampin (via CYP3A4 induction), and topotecan and elacridar (via ABCG2 inhibition) [Article:17766652].

Multi-drug resistance
Drug resistance by multiple mechanisms [Articles:2892943, 12712010, 15641020, 16454744, 18699730] accounts for more than 90% treatment failure in metastatic cancer [Articles:15641020, 18286284]. Multi-drug resistance from intrinsic (drug-naive) and acquired (drug-induced) over-expression of P-gp [Article:2892943] is a notable impediment to brain-targeted therapies (e.g. antiepileptics, neuro-antiretrovirals) and chemotherapies ISBN: [9781402059636], [Articles:16011870, 11907151, 17048260, 18627414]. P-gp expression predicts between 30 to 40% of treatment failure in epilepsy [Articles:10331089, 15072439, 18199522] and is correlated with drug non-response in acute myeloid leukemia [Article:18056183], childhood neuroblastoma [Article:1682809] and sarcoma [Article:1968964], and other cancers [Article:8504063]. The relationship between P-gp expression with non-response to chemotherapy and drug-induced upregulation of P-gp according to tumor type is nicely reviewed by Takara et al. [Article:16454744].

Known interactions between substrates and modulators of P-gp have been exploited in drug development and treatment protocols to overcome low drug delivery. Inhibitors of P-gp, such as formulary excipients (e.g. tocopherol (vitamin E preparation, TPGS 1000) and Cremophor EL) [Articles:8118035, 9520143, 17367162] and approved drugs, are clinically used to enhance the delivery of P-gp substrates. Verapamil and cyclosporine A (CsA) are examples of the first-generation of 'P-gp reversal agents' [Article:16454744] used in combination with antineoplastic agents, such as doxorubicin, vincristine, and paclitaxel to enhance bioavailability [Articles:1676918, 8725386, 12454106, 16969354, 18510173]. However, dose-limiting toxicity of early reversal agents and formulary excipients has led to the development of second-generation antagonists of P-gp, such as valspodar (PSC833), with ten-fold greater potency for P-gp and less side effects [Articles:19949935, 1346494, 12712010].

Substrate interactions with other pharmacokinetic genes affecting the absorption, distribution, metabolism, elimination (ADME) of drugs play a significant role in the effectiveness of P-gp reversal agents. Substrate specificity for multiple ADME genes can be advantageous or disadvantageous in adjunct therapy. For example, the mechanism by which both cyclosporine A and valspodar enhance the bioavailability of paclitaxel is owed in part to their inhibition of CYP3A4 [Articles:9698296, 10589748], ABCC2 [Article:17062689], and other elimination-pathway genes (e.g. CYP2J2) [Article:19923256] for paclitaxel. On the other hand, non-specific inhibition of multiple elimination-pathway genes involved in drug clearance can lead to side effects associated with the prolonged half life of the primary drug. As more is known about the gene expression profile of specific pathological conditions, P-gp reversal agent use can be optimized. For example, where redundant drug resistance mechanisms are operant, as with ABCB1, ABCC1 (MRP1), and ABCG2 (BCRP) in acute myeloid leukemia [Articles:14617793, 18699730], inhibition of multiple drug resistance genes can be beneficial. Characterization of the genes responsible for pharmacoresistance in a particular disease or disease stage is used to inform drug treatment. Also, third-generation P-gp reversal agents (e.g. tariquidar (XR9576), zosuquidar (LY335979), laniquidar (R101933), and OC144-093 (ONT093)) with greater specificity for P-gp and less affinity for other ADME genes, have been developed [Articles:10975553, 12712010]. A number of the newer-generation P-gp reversal agents (e.g. tariquidar, valspodar (PSC833), zosuquidar, OC144-093, elacridar (GF120918, GG918), and CBT-1) have shown promise in in vitro and early trials for treatment of epilepsy and cancer [Articles:12712010, 18234154, 15565444, 18234154, 18627414].

P-gp-guided therapy
Techniques to characterize the mechanisms of drug resistance that are operant in individual patients inform treatment with P-gp antagonists as adjuncts in the appropriate case. Single photon emission computed tomography (SPECT) analysis of the P-gp substrate, Tc-99m sestamibi, is used to probe P-gp-positive cells as a way to predict pharmacoresistance to antiepileptics [Article:18627414] and antitumor drugs [Articles:9815718, 19390941]. This technique is shown to be a cost-effective method for pre-selecting responders to lung cancer treatment [Article:19223414]. Tc-99m sestamibi is also used to monitor the efficacy of P-gp reversal agents in sensitizing pharmacoresistant cells to P-gp substrates [Article:15269145]. A phase I clinical trial using vinblastine plus valspodar reversal agent, and Tc-99m sestamibi imaging to monitor the sensitization of P-gp-positive cells, showed increased Tc-99m sestamibi retention in tumor cells of metastatic renal carcinoma patients (and thus presumably, cytotoxic agent, vinblastine) [Article:9815718]. Tariquidar/taxane/anthracycline polytherapy guided by serial Tc-99m sestamibi tumor scans was tried in a phase II clinical trial for breast cancer with acquired pharmacoresistance (Clinical trial ID: NCT00048633 at http://clinicaltrials.gov). Results to date show that cancers exhibiting de novo pharmacoresistance (drug naive), such as leukemias, myeloma, lymphomas, and breast and ovarian cancers, are the most amenable to P-gp modulation with reversal agents as adjunct therapy.

Genetic associations
Disease-causing mutations in fourteen of the ABC superfamily members have been described, as in CFTR (ABCC7) for cystic fibrosis, ABCA4 for macular degeneration, ABCC2 and ABCB11 for biliary dysfunction, and ABCA1, ABCG5, ABCG8, and ABCD1 for fatty acid/lipid disorders [Article:12045106]. A large corpus of literature about sequence variations for ABCB1 exists, however there is no clear consensus regarding the contribution of ABCB1 variation to disease risk [Articles:16969364, 17661727, 18370231]; and despite evidence for inter-individual variability in ABCB1 expression and P-gp function [Articles:7473127, 14965248, 19285158], the genetic contribution is unclear [Article:16969364]. A great number of studies has been carried out to establish the role of ABCB1 genetics in various phenotypes such as P-gp expression, function, drug response, and disease susceptibility with little consensus. Most genotype-phenotype associations are not substantiated by study replication, meaningful sample size, and appropriate multitesting correction. See helpful reviews [Articles:12505329, 12406646, 14749689, 15212152], including a detailed summary by Leschziner et al. of the discordant literature regarding genetic association of ABCB1 SNPs and haplotypes with P-gp expression, activity, drug response, and disease risk [Article:16969364].

Despite much work to ascertain the genetic contribution of ABCB1 on drug disposition and disease susceptibility, the accumulation of studies to date are unclear. Until data is amassed to form a consensus about the role of genetics in P-gp-related phenotypes, the primary clinical focus on P-gp relates to its role in (1) multi-drug resistance, and (2) drug-drug interactions [Article:17933685].

ABCB1 variants
As of April 30, 2009 for build 130 of the Single Nucleotide Polymorphism database (dbSNP), there are 1279 SNPs in the ABCB1 gene region, 62 of which are coding (22 synonymous, 41 non-synonymous, and 1 in the start codon). The number and frequency of SNPs observed varies by ethnicity. Excluding SNPs below 5% allele frequency, there are approximately 124 SNPs observed in Caucasians, 134 in African Americans, 153 in Chinese, and 166 in Japanese (see ABCB1 in HapMap at www.hapmap.org). Additional information is available at the University of California, San Francisco Pharmacogenetics of Membrane Transporters Database (see ABCB1 at http://pharmacogenetics.ucsf.edu).

About 2.6 times fewer (n = 4) SNPs occur in the transmembrane domains compared to the intracellular and extracellular regions of the protein. None of the three prime untranslated region (3'UTR) SNPs are reported to alter mRNA stability [Article:19285158]. The three most common SNPs in the protein coding region are rs1128503 (1236T>C, Gly412Gly), rs2032582 (2677T>G/A, Ser893Ala/Thr), and rs1045642 (3435T>C, Ile1145Ile) [Article:16141795], according to build 130 of (dbSNP). These three SNPs have been the focus of many pharmacokinetic and disease association studies with controversial results [Article:16969364]. Other less frequent variants include -129C>T (5'-UTR), 61A>G (Asn21Asp), and 1199G>A (Ser400Asn), which have been studied in vivo and in vitro. (See coding SNP locations on the secondary structure of P-gp per Fung et al. [Article:19285158] as adapted from Ambudkar et al. [Article:10331089].)

ABCB1 haplotypes
Closely positioned sequence variants tend not to segregate independently with each generation due to linkage disequilibrium (LD). As a result, multiple variant alleles are inherited together on the same physical chromatid in a particular pattern. That is to say that for linked variant alleles, the occurance of one variant allele informs the valence other alleles with a certain level of predictability. For example, alleles from the three most common coding SNPs at nucleotides 1236, 2677, and 3435, are in high LD [Article:16708052] and are observed most frequently as the 893Ala-containing CGC haplotype and 893Ser-containing TTT haplotype in most ethnic groups [Articles:11503014, 12172212, 12893986, 14976162]. Other observed haplotypes extend beyond the exonic region of ABCB1 [Article:16255080]. Leschziner et al. observed LD extending 75 kilobases, linking 3' variant alleles of ABCB1 to coding variant alleles of the adjacent ABC transporter gene, ABCB4 [Article:16708052].

Haplotype structure relates to the location of recombination hot spots and ancestry-specific patterns of LD [Articles:16255080, 18288195]. Tang et al. observed ethnic-specific LD blocks at the ABCB1 locus that are 80, 60, and 40 kilobase in length and distinguish Chinese, Malay, and Indian populations, respectively [Article:12172212]. Similarly, comparison of the mutation rate between Beninese Africans (1 variant per 224 basepairs) and American Africans (1 variant per 172 bp) reflects admixture in the U.S. cohort that differentiates the ABCB1 haplotype structure in these populations [Article:15692830]. Accordingly, haplotype frequencies differ by ethnic group. For example, the 893Ser-containing TTT haplotype occurs relatively infrequently in African Americans compared to Caucasians [Articles:11503014, 12893986] and Asians [Article:12172212].

A haplotype by definition is not bound by a gene region, but gene-specific haplotypes can acquire allelic designations in the literature. Sequence analysis of ABCB1 in different ethnic groups has been performed [Articles:11503014, 12172212, 12893986, 14646693, 15692830, 16708052, 17187507] and led to the designation of "star alleles" [Articles:14646693, 11503014, 12893986], as explained by Robarge et al. [Article:17700589]. Briefly, the designation of ABCB1 star alleles follows rules established by the Cytochrome P450 Allele Nomenclature Committee and others for naming haplotypes observed for cytochrome P450 (CYP450), uridinediphosphate-glucuronosyltransferase (UGT), N-acetyltransferase (NAT), and aldehyde dehydrogenase (ALDH) [Articles:10862518, 17700589] genes. Star alleles are defined relative to an arbitrarily established reference sequence, denoted *1. ABCB1*1 contains 1236C, 2677G (893Ala), and 3435C. Many star allele designations for ABCB1 are currently not harmonization in the literature. To illustrate, ABCB1*2, as defined by Kim et al., harbors three coding variants, namely 1236T, 2677T (893Ser), and 3435T [Article:11503014]; while ABCB1*2, as defined by Kroetz et al., contains 3435T (and is reference for 1236C and 2677G (893Ala)) [Article:12893986]. ABCB1*13 per Kroetz et al. (1236T, 2677T (893Ser), 3435T, and 3 intronic SNPs) [Article:12893986] is most similar to ABCB1*2 defined by Kim et al. [Article:11503014] as they are indistinguishable in terms of the coding region and amino acid sequence.

To investigate the regulatory impact of promoter variants on functional phenotypes, haplotype analysis of the promoter region has also been performed [Articles:15280437, 16907707, 16608921, 19072639]. Wang et al. observed a haplotype formed from eight low-frequency variants (<5% minor allele frequency) in the promoter region that accounted for 85% of all haplotypes observed in five ethnic groups [Article:16608921]. They functionally characterized promoter haplotypes observed in Chinese, Malays, Indians, European Americans, and African Americans using an in vitro reporter assay and found significant ethnic-specific differences in promoter activity, although activity differed by the cell line used in the assay (presumably due to cell-specific regulatory factors). Other work has been done to understand the relationship between regulatory and coding variants for ABCB1 and their potential association with endophenotypes. Takane et al. showed that variation in promoter haplotype activity was independent of variation at the synonymous 3435 SNP, and the methylation status of the proximal promoter did not correlate with ABCB1 mRNA expression [Article:15280437]. Jiang et al. found an association between the promoter methylation status and variation in coding SNPs for ABCB1. They showed that lower promoter methylation was associated with the 3435 TT and 893Ala-containing 2677 genotypes, while the 893Ser-containing TTT (1236, 2677, 3435) haplotype was associated with higher methylation [Article:19072639]. More research is needed to elucidate the functional relevance of regulatory variants for ABCB1 and their potential value to predicting P-gp-related phenotypes.

The vast majority of haplotype studies for ABCB1 do not take into account all segregating sites that are used to distinguish ABCB1 star alleles, but interrogate a select few variants. The variant alleles of the three most common coding SNPs, at nucleotides 1236 (rs1128503), 2677 (rs2032582), and 3435 (rs1045642), are in high linkage disequilibrium [Article:16708052]. Genotyping these three common ABCB1 coding SNPs captures a large portion of observed population haplotypes [Articles:11503014, 12893986, 19072639]. The linked variant alleles for 1236-2677-3435 are observed most frequently as the 893Ala-containing CGC haplotype and the 893Ser-containing TTT haplotype in most ethnic groups [Articles:11503014, 12172212, 12893986].

ABCB1 star alleles
ABCB1 star allele designations are currently not harmonized in the literature, and thus are specific to the citation referenced.
ABCB1*1 contains 1236C, 2677G (893Ala), 3435C, as named by Kim et al. 2001 [Article:11503014].
ABCB1*2 contains 1236T, 2677T (893Ser), 3435T, as named by Kim et al. 2001 [Article:11503014] and 1236C, 2677G (893Ala), 3435T, as named by Kroetz et al. 2003 [Article:[12893986].
ABCB1*13 contains 1236T, 2677T (893Ser), 3435T, and three intronic SNPs, as named by Kroetz et al. 2003 [Article:12893986].

Citation Very important pharmacogene summary: ABCB1 (MDR1, P-glycoprotein). Pharmacogenetics and genomics. 2011. Hodges Laura M, Markova Svetlana M, Chinn Leslie W, Gow Jason M, Kroetz Deanna L, Klein Teri E, Altman Russ B. PubMed
History

Submitted by Chinn LW, Gow JM (PMT)

Updated by Hodges LM (PharmGKB), Markova SM, Chinn LW, Gow JM, Kroetz DL (PMT)

Variant Summaries rs1045642, rs1128503, rs2032582
Haplotype Summaries ABCB1*1, ABCB1*2 per Kim et al. 2001 [PMID: 11503014], ABCB1*2 per Kroetz et al. 2003 [PMID: 12893986], ABCB1*13 per Kroetz et al. 2003 [PMID: 12893986]
Drugs
Drug Substrate (77)
Actinomycines, aldosterone, amitriptyline, amprenavir, atorvastatin, bromperidol, calcein, carbamazepine, Celiprolol, chlorpromazine, cimetidine, citalopram, clopidogrel, colchicine, corticosteroids, cyclosporine, daunorubicin, dexamethasone, digoxin, diltiazem, docetaxel, domperidone, doxorubicin, doxycycline, erythromycin, etoposide, fexofenadine, gramicidin d, grapefruit juice, imatinib, indinavir, irinotecan, itraconazole, ivermectin, ketoconazole, lamotrigine, lansoprazole, levetiracetam, levofloxacin, loperamide, losartan, lovastatin, melphalan, methylprednisolone, mitomycin, mitoxantrone, morphine, nelfinavir, omeprazole, paclitaxel, pantoprazole, pentazocine, phenobarbital, Phenothiazine derivatives, phenothiazines with aliphatic side-chain, phenytoin, pravastatin, propranolol, quinidine, ranitidine, rifampin, ritonavir, saquinavir, simvastatin, sirolimus, sparfloxacin, tacrolimus, talinolol, teniposide, terfenadine, tetracycline, topotecan, Valspodar, vecuronium, verapamil, vinblastine, vincristine
Drug Inhibitor (68)
amiodarone, amitriptyline, astemizole, atorvastatin, bepridil, Biricodar, bromocriptine, carvedilol, chlorpromazine, clarithromycin, Cremophor EL, curcumin, cyanocobalamin, cyclosporine, desipramine, diltiazem, dipyridamole, disulfiram, Elacridar, erlotinib, erythromycin, felodipine, fluoxetine, flupenthixol, fluphenazine, gefitinib, haloperidol, hydrocortisone, hydroxocobalamin, indinavir, itraconazole, ketoconazole, lansoprazole, maprotiline, mefloquine, midazolam, mifepristone, nelfinavir, nicardipine, nitrendipine, OC144-093, omeprazole, pantoprazole, paroxetine, pentazocine, progesterone, propafenone, quinidine, quinine, R101933, reserpine, ritonavir, saquinavir, sertraline, simvastatin, sirolimus, spironolactone, tacrolimus, tamoxifen, Tariquidar, tetrabenazine, valinomycin, Valspodar, verapamil, vinblastine, vitamin e, XR9051, Zosuquidar
Pathways

Haplotype Overview

Haplotypes are derived from [Article:11503014] and [Article:12893986].

Source: PharmGKB

All alleles in the download file are on the positive chromosomal strand. PharmGKB considers the first haplotype listed in each table as the reference haplotype for that set.

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Atorvastatin/Lovastatin/Simvastatin Pathway, Pharmacokinetics
    Drug-specific representation of the candidate genes involved in transport, metabolism and clearance.
  1. Carbamazepine Pathway, Pharmacokinetics
    Stylized liver cell depicting candidate genes involved in the pharmacokinetics of carbamazepine.
  1. Citalopram Pathway, Pharmacokinetics
    Pharmacokinetics of the selective serotonin reuptake inhibitor citalopram.
  1. Clopidogrel Pathway, Pharmacokinetics
    Clopidogrel metabolism.
  1. Codeine and Morphine Pathway, Pharmacokinetics
    Representation of the candidate genes involved in metabolism of codeine and morphine.
  1. Doxorubicin Pathway (Cancer Cell), Pharmacodynamics
    Representation of the candidate genes involved in the action of doxorubicin in a stylized cancer cell.
  1. Doxorubicin Pathway, Pharmacokinetics
    Diagrammatic representation of the transport and metabolism of doxorubicin.
  1. Erlotinib Pathway, Pharmacokinetics
    Model human liver cell showing genes involved in the transportation and metabolism of Erlotinib.
  1. Etoposide Pathway, Pharmacokinetics/Pharmacodynamics
    Etoposide cellular disposition and effects.
  1. Gefitinib Pathway, Pharmacokinetics
    Representation of the candidate genes involved in the transportation and metabolism of gefitinib.
  1. Irinotecan Pathway, Pharmacodynamics
    Model non-tissue specific cancer cell displaying genes which may be involved in the irinotecan pathway.
  1. Irinotecan Pathway, Pharmacokinetics
    Model human liver cell showing blood, bile and intestinal compartments, indicating tissue specific involvement of genes in the irinotecan pathway.
  1. Lamivudine Pathway, Pharmacokinetics/Pharmacodynamics
    Representation of candidate genes involved in the metabolism of lamivudine and its mechanism of antiviral action.
  1. Methotrexate Pathway (Brain Cell), Pharmacokinetics
    Representation of transport and exchange of methotrexate in the brain.
  1. Methotrexate Pathway, Pharmacokinetics
    Diagramatic representation of uptake, transport and elimination of methotrexate.
  1. Paroxetine Pathway, Pharmacokinetics
    Genes involved in the metabolism of paroxetine and in the mechanism of action.
  1. Pravastatin Pathway, Pharmacokinetics
    Drug-specific representation of the candidate genes involved in transport, metabolism and clearance.
  1. Proton Pump Inhibitor Pathway, Pharmacokinetics
    Omeprazole metabolism in the liver.
  1. Statin Pathway - Generalized, Pharmacokinetics
    Representation of the superset of all genes involved in the transport, metabolism and clearance of statin class drugs.
  1. Statin Pathway, Pharmacodynamics
    Genes involved in mediating statin effects on hepatic cholesterol metabolism and consequent effects on plasma lipoprotein transport.
  1. Tacrolimus/Cyclosporine Pathway, Pharmacokinetics
    Schematic representation of tacrolimus and cyclosporine metabolism
  1. Taxane Pathway, Pharmacokinetics
    Representation of the genes involved in the metabolism and transport of paclitaxel and docetaxel, and the downstream effects of the drugs.
  1. Vinka Alkaloid Pathway, Pharmacokinetics
    Representation of the genes involved in the metabolism, transport, and downstream effects of the vinca alkaloid vincristine.
  1. Warfarin Pathway, Pharmacokinetics
    Representation of the candidate genes involved in transport, metabolism and clearance of warfarin.
  1. Zidovudine Pathway, Pharmacokinetics/Pharmacodynamics
    Representation of candidate genes involved in the metabolism of zidovudine and its mechanism of antiviral action.

External Pathways

Links to non-PharmGKB pathways.

  1. HIF-1-alpha transcription factor network - (Pathway Interaction Database NCI-Nature Curated)
  2. hypoxia and p53 in the cardiovascular system - (BioCarta via Pathway Interaction Database)
  3. multi-drug resistance factors - (BioCarta via Pathway Interaction Database)

Curated Information ?

Evidence Gene
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NR1I2
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
SLCO1B1

Curated Information ?

Evidence Drug
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abacavir
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abatacept
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acamprosate
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acenocoumarol
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acetaminophen
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acetazolamide
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aciclovir
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adalimumab
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afatinib
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agomelatine
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aldosterone
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
alfentanil
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
aliskiren
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alitretinoin
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amiodarone
amitriptyline
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
amlodipine
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amprenavir
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anakinra
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anastrozole
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aripiprazole
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arsenic trioxide
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arsenite
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asparaginase
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aspirin
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astemizole
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
atazanavir
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
atenolol
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atomoxetine
atorvastatin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
atrasentan
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
auranofin
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axitinib
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azathioprine
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AZD1152
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azithromycin
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bepridil
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bevacizumab
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bilirubin
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Biricodar
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
bisantrene
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bleomycin
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
boceprevir
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
bosentan
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
bosutinib
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
bromocriptine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
bromperidol
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budesonide
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buprenorphine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
bupropion
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
cabazitaxel
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
caffeine
calcein
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
capecitabine
carbamazepine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
carbamazepine 10,11-epoxide
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
carboplatin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
carisoprodol
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
carmustine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
carvedilol
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
caspofungin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
celecoxib
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Celiprolol
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
cephalexin
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ceritinib
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cerivastatin
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certolizumab pegol
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cetuximab
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cevimeline
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chlorambucil
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chloroquine
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chlorpromazine
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cimetidine
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ciprofloxacin
cisplatin
citalopram
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
cladribine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
clarithromycin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
clobazam
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
clofarabine
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
clomipramine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
clonazepam
clopidogrel
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
clotrimazole
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
clozapine
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
codeine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
colchicine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Cremophor EL
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
crizotinib
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
curcumin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
cyanocobalamin
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
cyclophosphamide
cyclosporine
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
cytarabine
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
dabrafenib
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
dactinomycin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
danazol
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
dapsone
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
daptomycin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
darunavir
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
dasatinib
daunorubicin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
decitabine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
desipramine
dexamethasone
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
dexrazoxane
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
dextromethorphan
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
diazepam
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
dicloxacillin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
didanosine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
diflomotecan
digoxin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
diltiazem
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
diphenhydramine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
dipyridamole
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
disulfiram
docetaxel
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
domperidone
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
donepezil
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
doxepin
doxorubicin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
doxycycline
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
edoxaban
efavirenz
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Elacridar
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
eliglustat
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
elvitegravir
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
emtricitabine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
enalapril
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
enoxacin
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
epirubicin
erlotinib
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
erythromycin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
escitalopram
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
eslicarbazepine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
esomeprazole
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
estradiol
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
estrone
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
etanercept
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ethambutol
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ethanol
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ethosuximide
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ethotoin
etoposide
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
exemestane
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ezetimibe
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
felodipine
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
fentanyl
fexofenadine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
floxuridine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
fluconazole
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
fludarabine
fluorouracil
fluoxetine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
flupenthixol
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
fluphenazine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
flurbiprofen
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
flutamide
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
fluticasone propionate
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
fluvastatin
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
fluvoxamine
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
folic acid
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
forskolin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
fulvestrant
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
furosemide
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
gabapentin
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
galantamine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ganciclovir
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
gatifloxacin
gefitinib
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
gemcitabine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
gemfibrozil
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
glatiramer acetate
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
glibenclamide
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
gramicidin d
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
granisetron
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
grapefruit juice
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
haloperidol
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
heroin
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
homoharringtonine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
hydralazine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
hydrochlorothiazide
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
hydrocortisone
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
hydroxocobalamin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
hydroxychloroquine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
hydroxyurea
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ibutilide
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
idarubicin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ifosfamide
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
iloperidone
imatinib
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
imipramine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
indacaterol
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
indinavir
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
infliximab
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
insulin lyspro recombinant
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
insulin recombinant
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
insulin, porcine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
insulin-aspart
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
insulin-detemir
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
insulin-glargine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
insulin-glulisine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
insulin-lispro
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
interferon beta-1a
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
interferon beta-1b
irinotecan
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
isoniazid
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
itraconazole
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ivacaftor
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
ivermectin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
ketoconazole
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
labetalol
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
lactulose
No Dosing Guideline available No Drug Label available CA VA No VIP available PW
lamivudine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
lamotrigine
lansoprazole
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
lapatinib
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
leflunomide
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
lenalidomide
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
letrozole
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
leucovorin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
levetiracetam
levofloxacin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
levothyroxine
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
liothyronine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
lisinopril
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
lithium
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
lomefloxacin
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
lomitapide
loperamide
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
lopinavir
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
losartan
lovastatin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
maprotiline
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
maraviroc
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
mefloquine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
melphalan
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
mercaptopurine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
metformin
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
methadone
methotrexate
methylprednisolone
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
metoprolol
midazolam
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
mifepristone
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
minoxidil
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
mitomycin
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
mitotane
mitoxantrone
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
modafinil
morphine
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
mycophenolate mofetil
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
mycophenolic acid
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
naltrexone
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
natalizumab
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
nefazodone
nelfinavir
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
nevirapine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
niacin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
nicardipine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
nicotine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
nifedipine
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
nilotinib
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
nitrazepam
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
nitrendipine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
norfloxacin
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
nortriptyline
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
OC144-093
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
olanzapine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
olmesartan
omeprazole
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
ondansetron
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
oseltamivir
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ouabain
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
oxaliplatin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
oxcarbazepine
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
oxycodone
paclitaxel
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
panitumumab
pantoprazole
paroxetine
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
pazopanib
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
peginterferon alfa-2b
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
penicillin g
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
pentazocine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
perphenazine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
pertuzumab
phenobarbital
phenytoin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
pimozide
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
pitavastatin
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
platinum
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ponatinib
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
posaconazole
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
prasugrel
pravastatin
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
prazosin
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
prednisolone
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
prednisone
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
primaquine
probenecid
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
procainamide
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
progesterone
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
promazine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
propafenone
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
propranolol
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
pyrazinamide
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
pyrimethamine
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
quetiapine
quinidine
quinine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
R101933
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
raltegravir
ranitidine
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ranolazine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
repaglinide
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
reserpine
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
rhodamine 123
rifampin
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
risperidone
ritonavir
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
rituximab
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
rocuronium
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
rosiglitazone
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
rosuvastatin
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ruxolitinib
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
salbutamol
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
saquinavir
sertraline
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
silibinin
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
simeprevir
simvastatin
sirolimus
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
sitagliptin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
SJG-136
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available PW
SN-38
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
sofosbuvir
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
sorafenib
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
sparfloxacin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
spironolactone
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
st. john's wort
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
stavudine
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
sulfamethoxazole
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
sulfasalazine
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
sunitinib
tacrolimus
talinolol
tamoxifen
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Tariquidar
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
telaprevir
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
telithromycin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
telmisartan
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
temozolomide
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
teniposide
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
tenofovir
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
terbinafine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
terfenadine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
testosterone
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
tetrabenazine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
tetracycline
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
thalidomide
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
thioguanine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
thioridazine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
thyroxine
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ticagrelor
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ticlopidine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
timolol
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
tipifarnib
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
tipranavir
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
tocilizumab
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
topiramate
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
topotecan
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
toremifene
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
trabectedin
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
tramadol
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
trastuzumab
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
tretinoin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
trichostatin A
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
trimethoprim
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
trimipramine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
troglitazone
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
valaciclovir
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
valinomycin
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
valproic acid
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
valsartan
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Valspodar
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
varenicline
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
vasopressin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
vecuronium
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
vemurafenib
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
venlafaxine
verapamil
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
vigabatrin
vinblastine
vincristine
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
vindesine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
vitamin e
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
voriconazole
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available PW
warfarin
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
XR9051
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
yohimbine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
zalcitabine
No Dosing Guideline available No Drug Label available CA VA No VIP available PW
zidovudine
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
zonisamide
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Zosuquidar

Curated Information ?

Evidence Disease
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Acquired Immunodeficiency Syndrome
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
acute cellular rejection
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Acute coronary syndrome
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Adenocarcinoma
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Adrenocortical Carcinoma
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Alcoholism
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Alzheimer Disease
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Anemia
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Anemia, Sickle Cell
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Angina Pectoris
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Arrhythmias, Cardiac
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Arthritis, Rheumatoid
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Atrial Fibrillation
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Autism Spectrum Disorder
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Autistic Disorder
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
bioavailability
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Bipolar Disorder
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Blood Coagulation Disorders
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Body Weight Changes
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Brain Neoplasms
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Breast Neoplasms
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Burkitt Lymphoma
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Carcinoma, Non-Small-Cell Lung
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Carcinoma, Renal Cell
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Carcinoma, Transitional Cell
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Cardiomyopathies
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
cardiotoxicity
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Carotid Artery Diseases
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Cholelithiasis
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Cholestasis
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Colitis, Ulcerative
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Colonic Neoplasms
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Colorectal Neoplasms
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Coronary Artery Disease
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Coronary Disease
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
creatine kinase
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Crohn Disease
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Cystic Fibrosis
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Death, Sudden, Cardiac
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Dementia
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Depression
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Depressive Disorder
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Depressive Disorder, Major
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Diabetes Mellitus, Type 2
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Diarrhea
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Drug Hypersensitivity
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Drug interaction with drug
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Drug Resistance
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Drug Toxicity
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
drug-induced liver injury
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Dyslipidaemia
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
electrocardiogram qt prolonged
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Epilepsies, Partial
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Epilepsy
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Epilepsy, Generalized
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Epilepsy, Temporal Lobe
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Esophageal Neoplasms
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
event-free survival
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Exanthema
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Fractures, Bone
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Gastroesophageal Reflux
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Gastrointestinal Stromal Tumors
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
gastrointestinal toxicity
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Gilbert's syndrome
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Gingival Hyperplasia
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
glomerular disease
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
glomerular filtration rate
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available