Drug Class
hormonal contraceptives for systemic use

last updated 02/07/2014

1. DPWG Guideline for hormonal contraceptives for systemic use and F5

Summary

In individuals who carry the Factor V Leiden allele and have a family history of thrombotic events, estrogen-containing oral contraceptives should be avoided and alternative forms of contraception used.

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for hormonal contraceptives for systemic use based on Factor V Leiden (FVL, or F5) genotype [Article:21412232]. They suggest that in individuals who carry the Factor V Leiden allele and have a family history of thrombotic events, estrogen-containing oral contraceptives should be avoided and alternative forms of contraception used.

Phenotype (Genotype) Therapeutic Dose Recommendation Level of Evidence Clinical Relevance
F5 homozygous rs6025 TT Positive (family) history of thrombotic events: avoid estrogen-containing oral contraceptives and select alternative (e.g., copper intrauterine device, progestin-only contraceptive). Negative (family) history of thrombotic events: avoid additional risk factors (e.g., obesity, smoking). Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Clinical effect (S): long-standing discomfort (> 168 hr), permanent symptom or invalidating injury e.g. failure of prophylaxis of atrial fibrillation; venous thromboembolism; decreased effect of clopidogrel on inhibition of platelet aggregation; ADE resulting from increased bioavailability of phenytoin; INR > 6.0; neutropenia 0.5-1.0x10 9/l; leucopenia 1.0-2.0x10 9/l; thrombocytopenia 25-50x10 9/l; severe diarrhea
F5 heterozygous rs6025 CT Positive (family) history of thrombotic events: avoid estrogen-containing oral contraceptives and select alternative (e.g., copper intrauterine device, progestin-only contraceptive). Negative (family) history of thrombotic events: avoid additional risk factors (e.g., obesity, smoking). Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Clinical effect (S): long-standing discomfort (> 168 hr), permanent symptom or invalidating injury e.g. failure of prophylaxis of atrial fibrillation; venous thromboembolism; decreased effect of clopidogrel on inhibition of platelet aggregation; ADE resulting from increased bioavailability of phenytoin; INR > 6.0; neutropenia 0.5-1.0x10 9/l; leucopenia 1.0-2.0x10 9/l; thrombocytopenia 25-50x10 9/l; severe diarrhea
  • *See Methods or PMID: 18253145 for definition of "good" and "moderate" quality.
  • S: statistically significant difference.

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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Annotated Labels

  1. FDA Label for norepinephrine
  2. EMA Label for ethinyl estradiol,norelgestromin and F5
  3. HCSC Label for ethinyl estradiol,norelgestromin and F2,F5,MTHFR,PROC,PROS1,SERPINC1


last updated 05/08/2014

2. EMA Label for ethinyl estradiol,norelgestromin and F5

Genetic testing required

Summary

The EMA European Public Assessment Report (EPAR) for norelgestromin and ethinyl estradiol (Evra) contains information regarding its contraindication in women with known predisposition to venous thromboembolism (including Factor V Leiden, rs6025).

There's more of this label. Read more.


last updated 06/08/2015

3. HCSC Label for ethinyl estradiol,norelgestromin and F2,F5,MTHFR,PROC,PROS1,SERPINC1

Actionable PGx

Summary

The product monograph for norelgestromin and ethinyl estradiol (EVRA) states that the drug is contraindicated in women with Factor V Leiden mutation, antithrombin-III-deficiency, protein C deficiency, protein S deficiency, hyperhomocysteinaemia due to mutations in the MTHFR gene and prothrombin mutation G20210A (among other contraindications), due to the risk for arterial or venous thrombosis.

There's more of this label. Read more.


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

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

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

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

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

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

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

List of all variant annotations for hormonal contraceptives for systemic use

Gene ? Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available CA VA
rs1799963 *97G>A, 25313G>A, 46701055G>A, 46761055G>A
G > A
3' UTR
No VIP available No Clinical Annotations available VA
rs1801133 11210333G>A, 11796321G>A, 14783C>T, 419C>T, 665C>T, 677C>T, 788C>T, A222V, Ala140Val, Ala222Val, Ala263Val, C677T, MTHFR: c.677C>T, MTHFR:667C>T, p.A222V
G > A
Not Available
Ala140Val
rs6025 1601G>A, 1601G>G, 169519049T>C, 169519049T>T, 21007691T>C, 21007691T>T, 41721G>A, 41721G>G, Arg534=, Arg534Gln, F5:Factor V Leiden
T > C
Missense
Arg534Gln
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Generic Names
Trade Names
Brand Mixture Names

PharmGKB Accession Id

PA452637

Other Vocabularies

Drugs And Small Molecules

The following have been classified under this therapeutic category:

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

Curated Information ?

No related drugs are available.

Curated Information ?

Publications related to hormonal contraceptives for systemic use: 8

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics: From Bench to Byte- An Update of Guidelines. Clinical pharmacology and therapeutics. 2011. Swen J J, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Oral contraceptive use, thrombophilia and their interaction in young women with ischemic stroke. Haematologica. 2006. Martinelli Ida, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Prothrombotic conditions, oral contraceptives, and the risk of ischemic stroke. Journal of thrombosis and haemostasis : JTH. 2005. Slooter A J C, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Venous thromboembolic disease in users of low-estrogen combined estrogen-progestin oral contraceptives. Contraception. 2004. Sidney Stephen, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Venous thromboembolism in young women; role of thrombophilic mutations and oral contraceptive use. European heart journal. 2002. Legnani C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Interaction between the G20210A mutation of the prothrombin gene and oral contraceptive use in deep vein thrombosis. Arteriosclerosis, thrombosis, and vascular biology. 1999. Martinelli I, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Oral contraceptives enhance the risk of clinical manifestation of venous thrombosis at a young age in females homozygous for factor V Leiden. British journal of haematology. 1996. Rintelen C, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation. Lancet. 1994. Vandenbroucke J P, et al. PubMed

Clinical Trials

These are trials that mention hormonal contraceptives for systemic use and are related to either pharmacogenetics or pharmacogenomics.

No trials found.

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