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Treatment Guidelines

TEST MATERIAL ONLY - PLEASE DO NOT USE THIS CONTENT TO INFORM TREATMENT

  • Guidelines, Overview 
  • Detailed Result Guidelines 
  • Contraindications 
  • Warnings 

    GUIDELINES, OVERVIEW
    In 2011, the Clinical Pharmacogenetics Implementation Consortium (CPIC) of the National Institutes of Health's Pharmacogenomics Research Network issued a series of guidelines related to thiopurine methyltransferase (TPMT) and its implications for thiopurines. Guidelines are peer-reviewed, updated, evidence-based, and freely-accessible. They are intended to facilitate translation of pharmacogenomic knowledge from bench to bedside.
    In 2013, the guidelines were updated and are reproduced below.

    The most common TPMT-azathioprine results are listed immediately below. Each result pair is hyperlinked, with more detailed information listed in Detailed Result Guidelines  below.

    Result in EMR Phenotype Recommended
    Dosing
    Pharmacologic
    Implications
    Classification
    *1/*1 
    *1/*24 
    Homozygous wild-type or normal, high activity 1) Start with normal starting dose (e.g., 75 mg/m2/d or 1.5 mg/kg/d).
    2) Adjust doses of MP (and of any other myelosuppressive therapy) without any special emphasis on MP compared to other agents.
    3) Allow 2 weeks to reach steady state after each
    dose adjustment.
    Lower concentrations of TGN metabolites, higher
    methylTIMP, this is the “normal” pattern
    Strong
    *1/*3A (probable) 
    *1/*8 (possible) 
    *1/*3C 
    *1/*2 
    *1/*3B 
    *1/*4 
    Heterozygote or intermediate activity 1) Start with reduced doses (start at 30–70% of full dose: e.g., at 50 mg/m2/d or 0.75 mg/kg/d).
    2) Adjust doses of MP based on degree of myelosuppression and disease-specific guidelines.
    3) Allow 2–4 weeks to reach steady state after each dose adjustment.
    4) In those who require a dosage reduction based on myelosuppression:
     - The median dose may be ~40% lower (44 mg/m2) than that tolerated in wild-type patients (75 mg/m2).
    5) In setting of myelosuppression, and depending on other therapy:
     - Emphasis should be on reducing MP over other agents.
    Moderate to high concentrations of TGN
    metabolites; low concentrations of methylTIMP
    Strong
    *2/*3A 
    *2/*3C 
    *3A/*3B 
    *3A/*3C 
    *2/*2 
    *3A/*3A 
    *3B*3B 
    *3C/*3C 
    *2/*3B 
    *2/*4 
    *3A/*4 
    *3B/*3C 
    *3B/*4 
    *3C/*3C 
    *4/*4 
    Homozygous variant, mutant, low, or deficient
    activity
    1) For malignancy:
     - Reduce daily dose by 10-fold
     - Reduce frequency to thrice weekly instead of daily (e.g., 10 mg/m2/d given just 3 days/week).

     - Adjust doses of MP based on degree of myelosuppression and disease-specific guidelines.
     - Allow 4–6 weeks to reach steady state after each dose adjustment.
     - In setting of myelosuppression, emphasis should be on reducing MP over other agents.
    2) For nonmalignant conditions:
     - Consider alternative nonthiopurine immunosuppressant therapy.
    Extremely high concentrations of TGN metabolites; fatal toxicity possible without dose decrease; no methylTIMP metabolites Strong
    *1/*3D 
    *3D/*3D 
    *3D/*8 
    *3D/*24 
    *8/*8 
    *8/*24
    *24/*24 
    Indeterminate None Indeterminate N/A

    DETAILED RESULT GUIDELINES

    TEST MATERIAL ONLY - PLEASE DO NOT USE THIS CONTENT TO INFORM TREATMENT

    Result Phenotype EMR Entry Details
    *1/*1 Normal (high) activity None •This result signifies that this patient has two copies of a wild-type (high activity) allele. This patient is predicted to have normal (high) TPMT activity, consistent with approximately 90% of the population. •The expected phenotype suggests that there is no reason to selectively adjust the dose of thiopurines (6-mercaptopurine, 6-thioguanine or azathioprine). Initiate with the normal starting dose for 6-mercaptopurine (e.g., 75 mg/m2/day), azathioprine (e.g., 2-3 mg/kg/day), or thioguanine. If myelosuppression occurs consult the treatment protocol for dosing adjustments. No special emphasis should be placed upon thiopurines when compared to other agents if dose adjustments are necessary due to myelosuppression. Allow 2 weeks to reach steady state after each dose adjustment.
    *1/*24 Normal (high) activity None This result signifies that this patient has two copies of a wild-type (high activity) allele.• This patient is predicted to have normal (high) TPMT activity, consistent with approximately 90% of the population. •The expected phenotype suggests that there is no reason to selectively adjust the dose of thiopurines (6-mercaptopurine, 6-thioguanine or azathioprine). Initiate with the normal starting dose for 6-mercaptopurine (e.g., 75 mg/m2/day), azathioprine (e.g., 2-3 mg/kg/day), or thioguanine. If myelosuppression occurs consult the treatment protocol for dosing adjustments. No special emphasis should be placed upon thiopurines when compared to other agents if dose adjustments are necessary due to myelosuppression. Allow 2 weeks to reach steady state after each dose adjustment.
    *1/*3A Intermediate Activity - Probable TPMT - Intermediate Activity This result signifies that the patient is heterozygous for a wild-type (*1, high activity) and non-functional (*3A, low activity) allele. However, there is a small chance (< 1 in 100,000) that this patient’s diplotype is instead a compound heterozygote (*3B/*3C) which would indicate the patient has two copies of a non-functional allele, and would therefore have low or absent TPMT activity. In either circumstance the patient is at risk for myelosuppression when receiving thiopurines (6-mercaptopurine, 6-thioguanine or azathioprine), and thus reduced starting doses may be needed. A TPMT phenotype test could distinguish intermediate from low/absent TPMT activity.• Based on the diplotype of *1/*3A this patient will most likely display intermediate TPMT activity. •The following recommendations are based on the assumption that the *1/*3A diplotype is correct; if it is suspected that the diplotype could be *3B/*3C, consult with a clinical pharmacist for information on ordering a TPMT phenotype test, as dosage recommendations are different. For 6-mercaptopurine and azathioprine, consider starting at 30-70% of normal dose; e.g., a normal dose of 6-mercaptopurine (75 mg/m2/day) should be reduced to 20-50 mg/m2/day; a normal dose of azathioprine (2-3 mg/kg/day) should be reduced to 0.6 - 2.0 mg/kg/day. For thioguanine reduce the normal dose by 30-50%. Titrate thiopurine doses based on myelosuppression. In the setting of myelosuppression, and depending on other therapy, emphasis should be on reducing thiopurine doses over other agents. Allow 2-4 weeks to reach steady-state after each dosage adjustment. For drug monitoring, consider obtaining a thiopurine metabolite plasma concentration.
    *1/*3C Intermediate Activity TPMT - Intermediate Activity •This result signifies that this patient has one copy of a wild-type (high activity) allele and one copy of a non-functional (low activity) allele.• This patient is predicted to have intermediate TPMT activity. The patient is at risk for myelosuppression with normal doses of drugs in the thiopurine class (6-mercaptopurine, 6-thioguanine or azathioprine), and thus reduced starting doses may be needed. Some experts recommend lower doses of thiopurines in heterozygotes because these patients may be at a higher risk of thiopurine-related late secondary cancers.• For 6-mercaptopurine and azathioprine, consider starting at 30-70% of the normal dose. For example, a normal dose of 6-mercaptopurine (e.g., 75 mg/m2/day) should be reduced to 20-50 mg/m2/day. A normal dose of azathioprine (e.g., 2-3 mg/kg/day) should be reduced to 0.6 - 2.0 mg/kg/day. For thioguanine reduce the normal dose by 30-50%. Titrate thiopurine doses based on myelosuppression. In the setting of myelosuppression, and depending on other therapy, emphasis should be on reducing thiopurine doses over other agents. Allow 2-4 weeks to reach steady-state after each dosage adjustment. For drug monitoring, consider obtaining a thiopurine metabolite plasma concentration.
    *1/*8 Possible Intermediate Activity TPMT - Possible Intermediate Activity •This result signifies that the patient has one copy of a wild-type (high activity) allele and one copy of an uncharacterized allele. Because this patient carries an uncharacterized allele in combination with a wild-type allele, the patient may have normal (high) TPMT activity or intermediate TMPT activity. The patient MAY be at risk for myelosuppression with normal doses of drugs in the thiopurine class (6-mercaptopurine, 6-thioguanine or azathioprine), and thus reduced starting doses may be needed. •For 6-mercaptopurine and azathioprine, consider starting at 30-70% of the normal dose. For example, a normal dose of 6-mercaptopurine (e.g., 75 mg/m2/day) should be reduced to 20-50 mg/m2/day. A normal dose of azathioprine (e.g., 2-3 mg/kg/day) should be reduced to 0.6 - 2.0 mg/kg/day. For thioguanine reduce the normal dose by 30-50%. Titrate thiopurine doses based on myelosuppression. In the setting of myelosuppression, and depending on other therapy, emphasis should be on reducing thiopurine doses over other agents. Allow 2-4 weeks to reach steady-state after each dosage adjustment. For drug monitoring, consider obtaining a thiopurine metabolite plasma concentration.
    *1/*2 Intermediate Activity TPMT - Intermediate Activity •This result signifies that this patient has one copy of a wild-type (high activity) allele and one copy of a non-functional (low activity) allele.• This patient is predicted to have intermediate TPMT activity. The patient is at risk for myelosuppression with normal doses of drugs in the thiopurine class (6-mercaptopurine, 6-thioguanine or azathioprine), and thus reduced starting doses may be needed. Some experts recommend lower doses of thiopurines in heterozygotes because these patients may be at a higher risk of thiopurine-related late secondary cancers.• For 6-mercaptopurine and azathioprine, consider starting at 30-70% of the normal dose. For example, a normal dose of 6-mercaptopurine (e.g., 75 mg/m2/day) should be reduced to 20-50 mg/m2/day. A normal dose of azathioprine (e.g., 2-3 mg/kg/day) should be reduced to 0.6 - 2.0 mg/kg/day. For thioguanine reduce the normal dose by 30-50%. Titrate thiopurine doses based on myelosuppression. In the setting of myelosuppression, and depending on other therapy, emphasis should be on reducing thiopurine doses over other agents. Allow 2-4 weeks to reach steady-state after each dosage adjustment. For drug monitoring, consider obtaining a thiopurine metabolite plasma concentration.
    *1/*3B Intermediate Activity TPMT - Intermediate Activity This result signifies that this patient has one copy of a wild-type (high activity) allele and one copy of a non-functional (low activity) allele.• This patient is predicted to have intermediate TPMT activity. The patient is at risk for myelosuppression with normal doses of drugs in the thiopurine class (6-mercaptopurine, 6-thioguanine or azathioprine), and thus reduced starting doses may be needed. Some experts recommend lower doses of thiopurines in heterozygotes because these patients may be at a higher risk of thiopurine-related late secondary cancers.• For 6-mercaptopurine and azathioprine, consider starting at 30-70% of the normal dose. For example, a normal dose of 6-mercaptopurine (e.g., 75 mg/m2/day) should be reduced to 20-50 mg/m2/day. A normal dose of azathioprine (e.g., 2-3 mg/kg/day) should be reduced to 0.6 - 2.0 mg/kg/day. For thioguanine reduce the normal dose by 30-50%. Titrate thiopurine doses based on myelosuppression. In the setting of myelosuppression, and depending on other therapy, emphasis should be on reducing thiopurine doses over other agents. Allow 2-4 weeks to reach steady-state after each dosage adjustment. For drug monitoring, consider obtaining a thiopurine metabolite plasma concentration.
    *1/*4 Intermediate Activity TPMT - Intermediate Activity This result signifies that this patient has one copy of a wild-type (high activity) allele and one copy of a non-functional (low activity) allele.• This patient is predicted to have intermediate TPMT activity. The patient is at risk for myelosuppression with normal doses of drugs in the thiopurine class (6-mercaptopurine, 6-thioguanine or azathioprine), and thus reduced starting doses may be needed. Some experts recommend lower doses of thiopurines in heterozygotes because these patients may be at a higher risk of thiopurine-related late secondary cancers.• For 6-mercaptopurine and azathioprine, consider starting at 30-70% of the normal dose. For example, a normal dose of 6-mercaptopurine (e.g., 75 mg/m2/day) should be reduced to 20-50 mg/m2/day. A normal dose of azathioprine (e.g., 2-3 mg/kg/day) should be reduced to 0.6 - 2.0 mg/kg/day. For thioguanine reduce the normal dose by 30-50%. Titrate thiopurine doses based on myelosuppression. In the setting of myelosuppression, and depending on other therapy, emphasis should be on reducing thiopurine doses over other agents. Allow 2-4 weeks to reach steady-state after each dosage adjustment. For drug monitoring, consider obtaining a thiopurine metabolite plasma concentration.
    *2/*3A Low or Absent Activity TPMT - Low or Absent Activity This result signifies that this patient has two copies of a non-functional (low activity) allele.• This patient is predicted to have low or absent TPMT activity. The patient is at a high risk for life-threatening myelosuppression with normal doses of drugs in the thiopurine class (6-mercaptopurine, 6-thioguanine or azathioprine), and should receive greatly reduced doses of these drugs.• For malignancy, reduce dose and frequency of 6-mercaptopurine or 6-thioguanine drastically. Consider reducing the normal dose for 6-mercaptopurine and 6-thioguanine by 10-fold and administer thrice weekly; e.g., a normal dose of 6-mercaptopurine (75 mg/m2/day) should be reduced to 10 mg/m2/day administered 3 days per week. Azathioprine should be avoided, or if azathioprine is given, reduce the dose by 10-fold and administer thrice weekly instead of daily. Titrate thiopurine doses based on myelosuppression. In the setting of myelosuppression emphasis should be on reducing thiopurine doses over other agents. Allow 4-6 weeks to reach steady-state after each dosage adjustment. For drug monitoring, consider obtaining thiopurine metabolite plasma concentrations. For a nonmalignant condition, consider alternative non-thiopurine immunosuppressant therapy.
    *2/*3C Low or Absent Activity TPMT - Low or Absent Activity This result signifies that this patient has two copies of a non-functional (low activity) allele.• This patient is predicted to have low or absent TPMT activity. The patient is at a high risk for life-threatening myelosuppression with normal doses of drugs in the thiopurine class (6-mercaptopurine, 6-thioguanine or azathioprine), and should receive greatly reduced doses of these drugs.• For malignancy, reduce dose and frequency of 6-mercaptopurine or 6-thioguanine drastically. Consider reducing the normal dose for 6-mercaptopurine and 6-thioguanine by 10-fold and administer thrice weekly; e.g., a normal dose of 6-mercaptopurine (75 mg/m2/day) should be reduced to 10 mg/m2/day administered 3 days per week. Azathioprine should be avoided, or if azathioprine is given, reduce the dose by 10-fold and administer thrice weekly instead of daily. Titrate thiopurine doses based on myelosuppression. In the setting of myelosuppression emphasis should be on reducing thiopurine doses over other agents. Allow 4-6 weeks to reach steady-state after each dosage adjustment. For drug monitoring, consider obtaining thiopurine metabolite plasma concentrations. For a nonmalignant condition, consider alternative non-thiopurine immunosuppressant therapy.
    *3A/*3B Low or Absent Activity TPMT - Low or Absent Activity This result signifies that this patient has two copies of a non-functional (low activity) allele.• This patient is predicted to have low or absent TPMT activity. The patient is at a high risk for life-threatening myelosuppression with normal doses of drugs in the thiopurine class (6-mercaptopurine, 6-thioguanine or azathioprine), and should receive greatly reduced doses of these drugs.• For malignancy, reduce dose and frequency of 6-mercaptopurine or 6-thioguanine drastically. Consider reducing the normal dose for 6-mercaptopurine and 6-thioguanine by 10-fold and administer thrice weekly; e.g., a normal dose of 6-mercaptopurine (75 mg/m2/day) should be reduced to 10 mg/m2/day administered 3 days per week. Azathioprine should be avoided, or if azathioprine is given, reduce the dose by 10-fold and administer thrice weekly instead of daily. Titrate thiopurine doses based on myelosuppression. In the setting of myelosuppression emphasis should be on reducing thiopurine doses over other agents. Allow 4-6 weeks to reach steady-state after each dosage adjustment. For drug monitoring, consider obtaining thiopurine metabolite plasma concentrations. For a nonmalignant condition, consider alternative non-thiopurine immunosuppressant therapy.
    *3A/*3C Low or Absent Activity TPMT - Low or Absent Activity •This result signifies that this patient has two copies of a non-functional (low activity) allele.• This patient is predicted to have low or absent TPMT activity. The patient is at a high risk for life-threatening myelosuppression with normal doses of drugs in the thiopurine class (6-mercaptopurine, 6-thioguanine or azathioprine), and should receive greatly reduced doses of these drugs.• For malignancy, reduce dose and frequency of 6-mercaptopurine or 6-thioguanine drastically. Consider reducing the normal dose for 6-mercaptopurine and 6-thioguanine by 10-fold and administer thrice weekly; e.g., a normal dose of 6-mercaptopurine (75 mg/m2/day) should be reduced to 10 mg/m2/day administered 3 days per week. Azathioprine should be avoided, or if azathioprine is given, reduce the dose by 10-fold and administer thrice weekly instead of daily. Titrate thiopurine doses based on myelosuppression. In the setting of myelosuppression emphasis should be on reducing thiopurine doses over other agents. Allow 4-6 weeks to reach steady-state after each dosage adjustment. For drug monitoring, consider obtaining thiopurine metabolite plasma concentrations. For a nonmalignant condition, consider alternative non-thiopurine immunosuppressant therapy.
    *2/*2 Low or Absent Activity TPMT - Low or Absent Activity •This result signifies that this patient has two copies of a non-functional (low activity) allele.• This patient is predicted to have low or absent TPMT activity. The patient is at a high risk for life-threatening myelosuppression with normal doses of drugs in the thiopurine class (6-mercaptopurine, 6-thioguanine or azathioprine), and should receive greatly reduced doses of these drugs.• For malignancy, reduce dose and frequency of 6-mercaptopurine or 6-thioguanine drastically. Consider reducing the normal dose for 6-mercaptopurine and 6-thioguanine by 10-fold and administer thrice weekly; e.g., a normal dose of 6-mercaptopurine (75 mg/m2/day) should be reduced to 10 mg/m2/day administered 3 days per week. Azathioprine should be avoided, or if azathioprine is given, reduce the dose by 10-fold and administer thrice weekly instead of daily. Titrate thiopurine doses based on myelosuppression. In the setting of myelosuppression emphasis should be on reducing thiopurine doses over other agents. Allow 4-6 weeks to reach steady-state after each dosage adjustment. For drug monitoring, consider obtaining thiopurine metabolite plasma concentrations. For a nonmalignant condition, consider alternative non-thiopurine immunosuppressant therapy.
    *3A/*3A Low or Absent Activity TPMT - Low or Absent Activity This result signifies that this patient has two copies of a non-functional (low activity) allele.• This patient is predicted to have low or absent TPMT activity. The patient is at a high risk for life-threatening myelosuppression with normal doses of drugs in the thiopurine class (6-mercaptopurine, 6-thioguanine or azathioprine), and should receive greatly reduced doses of these drugs.• For malignancy, reduce dose and frequency of 6-mercaptopurine or 6-thioguanine drastically. Consider reducing the normal dose for 6-mercaptopurine and 6-thioguanine by 10-fold and administer thrice weekly; e.g., a normal dose of 6-mercaptopurine (75 mg/m2/day) should be reduced to 10 mg/m2/day administered 3 days per week. Azathioprine should be avoided, or if azathioprine is given, reduce the dose by 10-fold and administer thrice weekly instead of daily. Titrate thiopurine doses based on myelosuppression. In the setting of myelosuppression emphasis should be on reducing thiopurine doses over other agents. Allow 4-6 weeks to reach steady-state after each dosage adjustment. For drug monitoring, consider obtaining thiopurine metabolite plasma concentrations. For a nonmalignant condition, consider alternative non-thiopurine immunosuppressant therapy.
    *3B/*3B Low or Absent Activity TPMT - Low or Absent Activity This result signifies that this patient has two copies of a non-functional (low activity) allele.• This patient is predicted to have low or absent TPMT activity. The patient is at a high risk for life-threatening myelosuppression with normal doses of drugs in the thiopurine class (6-mercaptopurine, 6-thioguanine or azathioprine), and should receive greatly reduced doses of these drugs.• For malignancy, reduce dose and frequency of 6-mercaptopurine or 6-thioguanine drastically. Consider reducing the normal dose for 6-mercaptopurine and 6-thioguanine by 10-fold and administer thrice weekly; e.g., a normal dose of 6-mercaptopurine (75 mg/m2/day) should be reduced to 10 mg/m2/day administered 3 days per week. Azathioprine should be avoided, or if azathioprine is given, reduce the dose by 10-fold and administer thrice weekly instead of daily. Titrate thiopurine doses based on myelosuppression. In the setting of myelosuppression emphasis should be on reducing thiopurine doses over other agents. Allow 4-6 weeks to reach steady-state after each dosage adjustment. For drug monitoring, consider obtaining thiopurine metabolite plasma concentrations. For a nonmalignant condition, consider alternative non-thiopurine immunosuppressant therapy.
    *3C/*3C Low or Absent Activity TPMT - Low or Absent Activity This result signifies that this patient has two copies of a non-functional (low activity) allele.• This patient is predicted to have low or absent TPMT activity. The patient is at a high risk for life-threatening myelosuppression with normal doses of drugs in the thiopurine class (6-mercaptopurine, 6-thioguanine or azathioprine), and should receive greatly reduced doses of these drugs.• For malignancy, reduce dose and frequency of 6-mercaptopurine or 6-thioguanine drastically. Consider reducing the normal dose for 6-mercaptopurine and 6-thioguanine by 10-fold and administer thrice weekly; e.g., a normal dose of 6-mercaptopurine (75 mg/m2/day) should be reduced to 10 mg/m2/day administered 3 days per week. Azathioprine should be avoided, or if azathioprine is given, reduce the dose by 10-fold and administer thrice weekly instead of daily. Titrate thiopurine doses based on myelosuppression. In the setting of myelosuppression emphasis should be on reducing thiopurine doses over other agents. Allow 4-6 weeks to reach steady-state after each dosage adjustment. For drug monitoring, consider obtaining thiopurine metabolite plasma concentrations. For a nonmalignant condition, consider alternative non-thiopurine immunosuppressant therapy.
    *2/*3B Low or Absent Activity TPMT - Low or Absent Activity •This result signifies that this patient has two copies of a non-functional (low activity) allele.• This patient is predicted to have low or absent TPMT activity. The patient is at a high risk for life-threatening myelosuppression with normal doses of drugs in the thiopurine class (6-mercaptopurine, 6-thioguanine or azathioprine), and should receive greatly reduced doses of these drugs.• For malignancy, reduce dose and frequency of 6-mercaptopurine or 6-thioguanine drastically. Consider reducing the normal dose for 6-mercaptopurine and 6-thioguanine by 10-fold and administer thrice weekly; e.g., a normal dose of 6-mercaptopurine (75 mg/m2/day) should be reduced to 10 mg/m2/day administered 3 days per week. Azathioprine should be avoided, or if azathioprine is given, reduce the dose by 10-fold and administer thrice weekly instead of daily. Titrate thiopurine doses based on myelosuppression. In the setting of myelosuppression emphasis should be on reducing thiopurine doses over other agents. Allow 4-6 weeks to reach steady-state after each dosage adjustment. For drug monitoring, consider obtaining thiopurine metabolite plasma concentrations. For a nonmalignant condition, consider alternative non-thiopurine immunosuppressant therapy.
    *2/*4 Low or Absent Activity TPMT - Low or Absent Activity This result signifies that this patient has two copies of a non-functional (low activity) allele.• This patient is predicted to have low or absent TPMT activity. The patient is at a high risk for life-threatening myelosuppression with normal doses of drugs in the thiopurine class (6-mercaptopurine, 6-thioguanine or azathioprine), and should receive greatly reduced doses of these drugs.• For malignancy, reduce dose and frequency of 6-mercaptopurine or 6-thioguanine drastically. Consider reducing the normal dose for 6-mercaptopurine and 6-thioguanine by 10-fold and administer thrice weekly; e.g., a normal dose of 6-mercaptopurine (75 mg/m2/day) should be reduced to 10 mg/m2/day administered 3 days per week. Azathioprine should be avoided, or if azathioprine is given, reduce the dose by 10-fold and administer thrice weekly instead of daily. Titrate thiopurine doses based on myelosuppression. In the setting of myelosuppression emphasis should be on reducing thiopurine doses over other agents. Allow 4-6 weeks to reach steady-state after each dosage adjustment. For drug monitoring, consider obtaining thiopurine metabolite plasma concentrations. For a nonmalignant condition, consider alternative non-thiopurine immunosuppressant therapy.
    *3A/*4 Low or Absent Activity TPMT - Low or Absent Activity •This result signifies that this patient has two copies of a non-functional (low activity) allele.• This patient is predicted to have low or absent TPMT activity. The patient is at a high risk for life-threatening myelosuppression with normal doses of drugs in the thiopurine class (6-mercaptopurine, 6-thioguanine or azathioprine), and should receive greatly reduced doses of these drugs.• For malignancy, reduce dose and frequency of 6-mercaptopurine or 6-thioguanine drastically. Consider reducing the normal dose for 6-mercaptopurine and 6-thioguanine by 10-fold and administer thrice weekly; e.g., a normal dose of 6-mercaptopurine (75 mg/m2/day) should be reduced to 10 mg/m2/day administered 3 days per week. Azathioprine should be avoided, or if azathioprine is given, reduce the dose by 10-fold and administer thrice weekly instead of daily. Titrate thiopurine doses based on myelosuppression. In the setting of myelosuppression emphasis should be on reducing thiopurine doses over other agents. Allow 4-6 weeks to reach steady-state after each dosage adjustment. For drug monitoring, consider obtaining thiopurine metabolite plasma concentrations. For a nonmalignant condition, consider alternative non-thiopurine immunosuppressant therapy.
    *3B/*3C Low or Absent Activity TPMT - Low or Absent Activity This result signifies that this patient has two copies of a non-functional (low activity) allele.• This patient is predicted to have low or absent TPMT activity. The patient is at a high risk for life-threatening myelosuppression with normal doses of drugs in the thiopurine class (6-mercaptopurine, 6-thioguanine or azathioprine), and should receive greatly reduced doses of these drugs.• For malignancy, reduce dose and frequency of 6-mercaptopurine or 6-thioguanine drastically. Consider reducing the normal dose for 6-mercaptopurine and 6-thioguanine by 10-fold and administer thrice weekly; e.g., a normal dose of 6-mercaptopurine (75 mg/m2/day) should be reduced to 10 mg/m2/day administered 3 days per week. Azathioprine should be avoided, or if azathioprine is given, reduce the dose by 10-fold and administer thrice weekly instead of daily. Titrate thiopurine doses based on myelosuppression. In the setting of myelosuppression emphasis should be on reducing thiopurine doses over other agents. Allow 4-6 weeks to reach steady-state after each dosage adjustment. For drug monitoring, consider obtaining thiopurine metabolite plasma concentrations. For a nonmalignant condition, consider alternative non-thiopurine immunosuppressant therapy.
    *3B/*4 Low or Absent Activity TPMT - Low or Absent Activity •This result signifies that this patient has two copies of a non-functional (low activity) allele.• This patient is predicted to have low or absent TPMT activity. The patient is at a high risk for life-threatening myelosuppression with normal doses of drugs in the thiopurine class (6-mercaptopurine, 6-thioguanine or azathioprine), and should receive greatly reduced doses of these drugs.• For malignancy, reduce dose and frequency of 6-mercaptopurine or 6-thioguanine drastically. Consider reducing the normal dose for 6-mercaptopurine and 6-thioguanine by 10-fold and administer thrice weekly; e.g., a normal dose of 6-mercaptopurine (75 mg/m2/day) should be reduced to 10 mg/m2/day administered 3 days per week. Azathioprine should be avoided, or if azathioprine is given, reduce the dose by 10-fold and administer thrice weekly instead of daily. Titrate thiopurine doses based on myelosuppression. In the setting of myelosuppression emphasis should be on reducing thiopurine doses over other agents. Allow 4-6 weeks to reach steady-state after each dosage adjustment. For drug monitoring, consider obtaining thiopurine metabolite plasma concentrations. For a nonmalignant condition, consider alternative non-thiopurine immunosuppressant therapy.
    *3C/*4 Low or Absent Activity TPMT - Low or Absent Activity •This result signifies that this patient has two copies of a non-functional (low activity) allele.• This patient is predicted to have low or absent TPMT activity. The patient is at a high risk for life-threatening myelosuppression with normal doses of drugs in the thiopurine class (6-mercaptopurine, 6-thioguanine or azathioprine), and should receive greatly reduced doses of these drugs.• For malignancy, reduce dose and frequency of 6-mercaptopurine or 6-thioguanine drastically. Consider reducing the normal dose for 6-mercaptopurine and 6-thioguanine by 10-fold and administer thrice weekly; e.g., a normal dose of 6-mercaptopurine (75 mg/m2/day) should be reduced to 10 mg/m2/day administered 3 days per week. Azathioprine should be avoided, or if azathioprine is given, reduce the dose by 10-fold and administer thrice weekly instead of daily. Titrate thiopurine doses based on myelosuppression. In the setting of myelosuppression emphasis should be on reducing thiopurine doses over other agents. Allow 4-6 weeks to reach steady-state after each dosage adjustment. For drug monitoring, consider obtaining thiopurine metabolite plasma concentrations. For a nonmalignant condition, consider alternative non-thiopurine immunosuppressant therapy.
    *4/*4 Low or Absent Activity TPMT - Low or Absent Activity •This result signifies that this patient has two copies of a non-functional (low activity) allele.• This patient is predicted to have low or absent TPMT activity. The patient is at a high risk for life-threatening myelosuppression with normal doses of drugs in the thiopurine class (6-mercaptopurine, 6-thioguanine or azathioprine), and should receive greatly reduced doses of these drugs.• For malignancy, reduce dose and frequency of 6-mercaptopurine or 6-thioguanine drastically. Consider reducing the normal dose for 6-mercaptopurine and 6-thioguanine by 10-fold and administer thrice weekly; e.g., a normal dose of 6-mercaptopurine (75 mg/m2/day) should be reduced to 10 mg/m2/day administered 3 days per week. Azathioprine should be avoided, or if azathioprine is given, reduce the dose by 10-fold and administer thrice weekly instead of daily. Titrate thiopurine doses based on myelosuppression. In the setting of myelosuppression emphasis should be on reducing thiopurine doses over other agents. Allow 4-6 weeks to reach steady-state after each dosage adjustment. For drug monitoring, consider obtaining thiopurine metabolite plasma concentrations. For a nonmalignant condition, consider alternative non-thiopurine immunosuppressant therapy.
    *1/*3D Indeterminate None •The expected phenotype for this patient cannot be determined based upon the TPMT diplotype result. Please consult with a clinical pharmacist for further information, and the possibility of ordering a TPMT phenotype test.
    *3D/*3D Indeterminate None •The expected phenotype for this patient cannot be determined based upon the TPMT diplotype result. Please consult with a clinical pharmacist for further information, and the possibility of ordering a TPMT phenotype test.
    *3D/*8 Indeterminate None The expected phenotype for this patient cannot be determined based upon the TPMT diplotype result. Please consult with a clinical pharmacist for further information, and the possibility of ordering a TPMT phenotype test.
    *3D/*24 Indeterminate None The expected phenotype for this patient cannot be determined based upon the TPMT diplotype result. Please consult with a clinical pharmacist for further information, and the possibility of ordering a TPMT phenotype test.
    *8/*8 Indeterminate None The expected phenotype for this patient cannot be determined based upon the TPMT diplotype result. Please consult with a clinical pharmacist for further information, and the possibility of ordering a TPMT phenotype test.
    *8/*24 Indeterminate None The expected phenotype for this patient cannot be determined based upon the TPMT diplotype result. Please consult with a clinical pharmacist for further information, and the possibility of ordering a TPMT phenotype test.
    *24/*24 Indeterminate None The expected phenotype for this patient cannot be determined based upon the TPMT diplotype result. Please consult with a clinical pharmacist for further information, and the possibility of ordering a TPMT phenotype test.

    CONTRAINDICATIONS
    Reproduced from the NIH-supported DailyMed website. Based on labeling most recently submitted to FDA. Update recency is listed in the About tab.

    Azathioprine should not be given to patients who have shown hypersensitivity to the drug. Azathioprine should not be used for treating rheumatoid arthritis in pregnant women. Patients with rheumatoid arthritis previously treated with alkylating agents (cyclophosphamide, chlorambucil, melphalan, or others) may have a prohibitive risk of neoplasia if treated with azathioprine.

    WARNINGS
    Reproduced from the NIH-supported DailyMed website. Based on labeling most recently submitted to FDA. Update recency is listed in the About tab.

    Severe leukopenia, thrombocytopenia, macrocyticanemia, and/or pancytopenia may occur in patients being treated with azathioprine. Severe bone marrow suppression may also occur. Patients with intermediate thiopurine S-methyl transferase (TPMT) activity may be at an increased risk of myelotoxicity if receiving conventional doses of azathioprine. Patients with low or absent TPMT activity are at an increased risk of developing severe, life-threatening myelotoxicity if receiving conventional doses of azathioprine. TPMT genotyping or phenotyping can help identify patients who are at an increased risk for developing azathioprine toxicity.

    Hematologic toxicities are dose related and may be more severe in renal transplant patients whose homograft is undergoing rejection. It is suggested that patients on azathioprine have complete blood counts, including platelet counts, weekly during the fi rst month, twice monthly for the second and third months of treatment, then monthly or more frequently if dosage alterations or other therapy changes are necessary. Delayed hematologic suppression may occur. Prompt reduction in dosage or temporary withdrawal of the drug may be necessary if there is a rapid fall in, or persistently low leukocyte count, or other evidence of bone marrow depression. Leukopenia does not correlate with therapeutic effect; therefore, the dose should not be increased intentionally to lower the white blood cell count.

    Serious infections are a constant hazard for patients receiving chronic immunosuppression, especially for homograft recipients. Fungal, viral, bacterial, and protozoal infections may be fatal and should be treated vigorously. Reduction of azathioprine dosage and/or use of other drugs should be considered.

    Azathioprine is mutagenic in animals and humans, carcinogenic in animals, and may increase the patient’s risk of neoplasia. Renal transplant patients are known to have an increased risk of malignancy, predominantly skin cancer and reticulum cell or lymphomatous tumors. The risk of post-transplant lymphomas may be increased in patients who receive aggressive treatment with immunosuppressive drugs. The degree of immunosuppression is determined, not only by the immunosuppressive regimen, but also by a number of other patient factors. The number of immunosuppressive agents may not necessarily increase the risk of post-transplant lymphomas. However, transplant patients who receive multiple immunosuppressive agents may be at risk for over-immunosuppression; therefore, immunosuppressive drug therapy should be maintained at the lowest effective levels. Information is available on the spontaneous neoplasia risk in rheumatoid arthritis, and on neoplasia following immunosuppressive therapy of other autoimmune diseases. It has not been possible to define the precise risk of neoplasia due to azathioprine. The data suggest the risk may be elevated in patients with rheumatoid arthritis, though lower than for renal transplant patients. However, acute myelogenous leukemia as well as solid tumors have been reported in patients with rheumatoid arthritis who have received azathioprine.

    Azathioprine has been reported to cause temporary depression in spermatogenesis and reduction in sperm viability and sperm count in mice at doses 10 times the human therapeutic dose;10 a reduced percentage of fertile matings occurred when animals received 5 mg/kg.

  • Overview

    TEST MATERIAL ONLY - PLEASE DO NOT USE THIS CONTENT TO INFORM TREATMENT

    Azathioprine is an immunosuppressive pro-drug. [Image:Wikicommons].

    What is Azathioprine?

  • Azathioprine is an immunosuppressive pro-drug. It is converted into 6-mercaptopurine in the body where it blocks purine metabolism and DNA synthesis.
  • Thiopurines are widely-used in managing acute lymphoblastic leukemia, which is the most common childhood malignancy, and are also frequently used as chronic immunosuppressive therapy after organ transplantation, in inflammatory bowel disease, and other immune conditions.
  • As well as azathioprine (Aza), mercaptopurine (MP) and thioguanine (TG) are similar pro-drugs that are inactivated by TPMT). All three yield the same active thioguanine nucleotide (TGN) metabolites.

    What is being tested?

  • S-methyltransferase (TPMT) is an enzyme involved in the metabolism of purine analogs such as azathioprine, 6-mercaptopurine and thioguanine, drugs that are used as chemotherapeutic and immunosuppressant agents.
  • TPMT methylates mercaptopurine (MP) and thioguanine, resulting in an inverse relationship between TPMT activity and concentrations of active thioguanine nucleotide (TGN) metabolites. Individuals that inherit two inactive TPMT alleles (0.3% of the population - though range is 1 in 178 to 1 in 3,736) are homozygous deficient and experience severe myelosuppression.
  • A high proportion of individuals that are heterozygous for inactive TPMT alleles (~8-10% of the population) experience moderate to severe myelosuppression.
  • Individuals that are homozygous for wild-type TPMT alleles have lower levels of TGN metabolites and therefore have a lower risk of myelosuppression.

    Recommendations

  • FDA: Due to the potential cytotoxicity and narrow therapeutic index of thiopurines, the FDA recommends TPMT testing prior to treatment.

  • The Clinical Pharmacogenetics Implementation Consortium (CPIC): CPIC updated its Guidelines for Thiopurine Methyltransferase Genotype and Thiopurine Dosing in 2013. The guidelines specifically address pediatric cohorts, and much of the evidence used to support the original dosing recommendation were generated from studies in children. CPIC recommends that guidelines "can be used in both the adult and pediatric populations", and dosing recommendations are presented in units of mg/m2 and mg/kg.

    How will this affect patient healthcare?

  • The Treatment Guidelines tab includes a list of guidelines based on patients' genotype.

  • PGx Studies

    TEST MATERIAL ONLY - PLEASE DO NOT USE THIS CONTENT TO INFORM TREATMENT

    Recommendations are based on two papers from the Clinical Pharmacogenetics Implementation Consortium from 2013 (updated) and 2011 (original). Both are available through open access:
    Clinical Pharmacogenetics Implementation Consortium Guidelines for Thiopurine Methyltransferase Genotype and Thiopurine Dosing: 2013 Update.
    MV Relling et al, 2013. Clinical Pharmacology & Therapeutics.

    CPIC: Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network (original 2011 guidelines - subscription NOT required).
    MV Relling & TE Klein, 2011. Clinical Pharmacology & Therapeutics.

    In addition, the following table is reproduced from Relling et al. (2013) based on PubMed (1966 - 10/2012) and MEDLINE (1950-10/2012) review using the following keyword search criteria:
    ((TPMT) OR (thiopurine methyltransferase) OR thiopurine S-methyltransferase) AND (thiopurine OR mercaptopurine OR thioguanine OR azathioprine).

    Model Major Findings Refs (links below) Level of Evidence
    In vitro MP’s catabolism to methylmercaptopurine absent in human erythrocytes, lymphocytes, liver, and kidneys from TPMT homozygous deficient individuals 1-4 High
    In vitro TG’s catabolism to methylthioguanine 5 High
    In vitro Mechanisms of functional inactivation for TPMT *2, *3A, *3B, *3C, *4 demonstrated by expression of specific variant alleles 6-8 High
    In vitro Heterologous expression of TPMT catabolizes mercaptopurine to methylmercaptopurine, thioguanine to methylthioguanine, and TIMP to methylTIMP 9, 10 High
    In vitro TPMT deficiency could lead to chronic exposure to thiopurine and could be linked to development of brain cancer (astrocytomas). 11 Low
    TPMT knock-out mice have more morbidity and mortality from thioguanine and mercaptopurine than wild type mice; heterozygotes were at intermediate risk. 12 High
    Clinical TPMT wild-type patients with ALL have higher risk of relapse than those with at least one variant TPMT allele, particularly in regimens that are primarily antimetabolite-based; wild-type patients with IBD have higher risk of treatment failure 13-16 High
    Clinical TPMT homozygous deficient individuals have life-threatening toxicity (myelosuppression) from normal doses of MP, TG, and azathioprine; toxicity can be minimized with substantially decreased doses 17-31 High
    Clinical Increased risk of myelosuppression in TPMT heterozygotes receiving normal doses of MP 13, 17, 20, 22, 32-34 High
    Clinical Increased risk of leukopenia in TPMT heterozygotes and homozygotes receiving thiopurines for treatment of chronic inflammatory diseases. 35 High
    Clinical Compared with intermediate or normal TPMT activity, low TPMT enzyme activity significantly associated with myelotoxicity and leukopenia. 35 High
    Clinical Higher level of residual leukemia in TPMT wild-type patients than in heterozygous/homozygous deficient patients with ALL after 10 days of fixed-dose TG but not in absence of thiopurines 36 High
    Clinical No change in relapse risk for heterozygous patients with ALL who receive MP doses adjusted downward for TPMT defective patients 37, 38 Moderate
    Clinical No increase in acute toxicity in heterozygous compared to homozygous wild-type patients with ALL who received MP doses adjusted downward for TPMT defective patients 33, 39, 40 High
    Clinical Increased risk of secondary leukemia in those with low TPMT activity and in those with high thiopurine active metabolites when dosed independently of TPMT status 41-45 Moderate
    Clinical TPMT genotyping is useful in predicting myelosuppression and likelihood of clinical response to AZA/6-MP in IBD 23-26, 46-52 Moderate
    Clinical TPMT genotyping is useful in predicting myelosuppression and likelihood of clinical response to AZA in CD 22, 49, 53-55 Moderate
    Clinical TPMT genotype-based dosing reduced toxicity while maintaining drug efficacy in trial of AZA for moderate-severe atopic eczema 56 Moderate
    Clinical TPMT genotyping is useful in predicting myelosuppression from AZA in RA 57-60 Moderate
    Clinical TPMT genotyping is useful in predicting myelosuppression from AZA in transplant recipients 27-29, 61, 62 High
    Clinical No change in clinical outcome for IBD patients who receive AZA based on TPMT activity or TG concentration 63 Moderate
    Clinical Increased risk of hepatotoxicity to MP in ALL patients with TPMT wild-type genotype and with higher MP metabolite (6-MMPN) 64 Moderate

    Patient FAQs

    TEST MATERIAL ONLY - PLEASE DO NOT USE THIS CONTENT TO INFORM TREATMENT

    Elsewhere on MyResults.org, we have compiled a list of resources to help patients understand Pharmacogenomics and Azathiopurine, as well as a range of videos, recommended websites, and other patient-friendly content. Immediately below, we have reproduced relevant sections addressing common questions your patients may have.
    Should your patient need to discuss genetic testing and/or results in more detail, the National Society of Genetic Counselors has developed a directory to help locate nearby genetic counseling services.

    OVERVIEW
  • What is Azathioprine? 
  • What is being tested? 
  • How will this affect my healthcare? 

    BACKGROUND
  • Why test for genetic interactions with azathioprine? 
  • How will this affect my treatment? 

    GENETIC TEST
  • What is the test? 
  • What will the test result mean? 
  • How is the test being performed? 
  • Will it hurt? 
  • Is it safe? 
  • How long will I have to wait for results? 
  • Is this a standard test? 
  • What type of test is this? 
  • Will I need to have this test done more than once? 

    TREATMENT
  • How will this test affect my treatment? 
  • How will this result be used? 
  • Will I be referred to a specialist? 
  • Is there anything else I should know? 

    PRIVACY & SHARING
  • Should I tell other healthcare providers about my test result? 
  • Who will see my test results? 
  • Should I tell other healthcare providers about my test result? 
  • Should my other family members be tested to see how they might respond to thiopurines? 
  • Will this affect my health insurance? 
  • Who can I contact if they have any more questions? 
  • Is it there a risk to my privacy? 

    RISKS
  • What should I do if I have concerns about genetic test results? 
  • Is there a reason why I may be a specific risk?  
  • Are there any implications for having children? 
  • If I am found to have a specific gene variant, am I at increased risk? 
  • Can I expect to experience emotional consequences related to my test result? 
  • Can I expect to experience social consequences related to my test result? 
  • Can I expect to experience an increase in anxiety? 
  • Are there any implications in terms of discrimination arising from the test result?  
  • If I am found to be at increased risk for responding poorly to azathioprine, are there similar health implications for my family? 
  • Are there likely to be emotional consequences relevant to azathioprine for my family? 

    OVERVIEW
    What is Azathioprine?
    Azathioprine is part of a group of drugs called thiopurines. These drugs that are widely used to treat leukemias and autoimmune disorders such as inflammatory bowel disease (Crohn's disease and ulcerative colitis) and arthritis. They are also used as immunosuppressants after organ transplantation.
    As well as azathioprine the most common thiopurine drugs are mercaptopurine and thioguanine.

    What is being tested?
    A gene called TPMT (thiopurine S-methyltransferase) is involved in metabolizing azathioprine. Certain individuals have a genetic difference in a gene called TPMT, which means their body has problems processing the azathioprine. For these people, the drug can accumulate in the body, and become toxic.
    Genetic testing allows us to identify these people prior to treatment, and therefore avoid this potentially negative reaction.

    How will this affect my healthcare?
    If testing shows that you may have a negative reaction to thiopurines such as azathioprine, you may be prescribed a different medication by your doctor.

    If you have any questions about your test results or the medications you are on, please talk with your doctor.

    You should follow your doctor's instructions on taking any medication. Do not change your medications on your own before speaking with your doctor.

    Why test for genetic interactions with azathioprine?
    By performing a test on your DNA, we may be able to anticipate how you will respond to thiopurines and to adjust your treatment accordingly.

    How will this affect my treatment?
    If genetic testing does indicate that you may not respond optimally to treatment with azathioprine, your doctor will likely change your prescription.

    Can taking azathioprine cause any problems?
    For the majority of people taking azathioprine will not cause any problems. However, in a small proportion of people, a change in medication may be recommended to prevent potentially toxic effects. These effects can include bleeding, sores, fever, red spots on the skin, yellowing eyes/skin, discolored urine and stool, bloody urine and stool.

    Are any other complications associated with thiopurines?
    Other complications include diarrhea, nausea, loss of appetite, tiredness, vomiting, loss of appetite, skin rash, pain, and hair loss.

    Who is affected?Approximately 8% of people may have a genetic difference that affects how they metabolize azathioprine. Less than 1% of people may have a variant in the TPMT that may seriously affect their health if taking azathioprine.

    Do different populations respond differently to azathioprine?
    Genetic differences in azathioprine response are found in all populations.

    Do reactions to azathioprine and other drugs run in my family?
    We (typically) inherit two gene copies from each parent. If you have a genetic difference that affects how you respond to azathioprine, it is likely to have been inherited from one or both of your parents, and it is possible you will pass this to your children. However, this is not always the case, and a large variety of inheritance scenarios are possible. If you are concerned about this, we strongly advise you to discuss with your doctor or healthcare provider.

    Is there a difference between being a carrier and being predisposed to a particular drug response?
    You may carry a genetic a difference that does not affect how you respond to azathioprine, but may affect how your children might respond. A full discussion of the relevant scenarios/implications are beyond the scope of this site, however, and we recommend you discuss with your doctor or healthcare provider if this is a concern.

    Why do genetic differences make people respond to azathioprine differently?
    Azathioprine interacts with the TPMTgene in our body. Certain differences in the TPMT gene will make some people use azathioprine differently. For these people, the genetic difference means that taking azathioprine can be toxic and should be avoided.

    GENETIC TEST

    What is the test?
    People react differently to medicine and some of those different reactions can be related to their genes. People with certain differences in their genes might not respond to particular medications as well as other people. The gene involved in how people use azathioprine is called, TPMT. This test will look for some of the genetic differences in the TPMTgene that can make people respond negatively to azathioprine.

    What will the test result mean?
    This test will tell your doctor whether you are likely to respond poorly to treatment with azathioprine, in which case an alternative course of medication will be recommended.

    How is the test being performed?
    Testing is performed on your DNA, usually extracted from a blood sample. For many patients, your hospital or treatment center may already have some of your DNA stored in a biobank. You may be asked for an additional sample or be asked to give us permission to do testing on the existing samples.

    Will it hurt?
    For some patients, we may need an additional blood sample. Taking blood may cause some pain, bleeding or bruising at the spot where the needle enters your body. Rarely, taking blood may cause fainting or infection.

    Is it safe?
    There is a risk that you may experience pain or bleeding if you need to give an additional blood sample. Risks concerning privacy are discussed under Privacy & Sharing.

    How long will I have to wait for results?
    Unfortunately, we cannot give an accurate estimate for the time you will have to wait for results - this will depend on the resources available at the center where you receive treatment.

    Is this a standard test?
    Although increasingly more common, this test is not yet standard, and is typically offered as part of a research study.

    What type of test is this?
    Is this test intended to confirm a diagnosis? No
    Is this test intended to predict a family history of disease? No
    Is this test intended to check if I am a carrier for a particular disease? No
    Is this test intended to screen for genetic disorders? No
    Is this test intended to screen for disorders related to pregnancy? No
    Is this test intended to screen for disorders related to newborns? No

    Will I need to have this test done more than once?
    No, you should not need to have this test done more than once. You will need to keep track of your testing result in order to share with all of your doctors, including those you see at other medical care centers.

    TREATMENT

    How will this test affect my treatment?

    For most people tested, it is likely that your treatment options will stay the same and that you will begin treatment with azathioprine using standard doses. If this is not the case, your doctor will either change your recommended dose or recommend a new treatment.

    How will this result be used?

    The result will be put into your medical record for your doctor to use when deciding about prescribing you azathioprine. Your doctor may:

  • Do other tests to see how you might respond to azathioprine
  • Do nothing and continue with your planned course of treatment
  • Change your dosage of azathioprine
  • Give you another medication that is not azathioprine to treat your condition
  • You should follow your doctor's instructions when taking any medication. Do not change your medications on your own before speaking with your doctor.

    Will I be referred to a specialist?
    It is unlikely that you will be referred to a specialist, but you may request an appointment with a genetic counselor.

    Is there anything else I should know?
    You should follow your doctor's instructions when taking any medication. Do not change your medications on your own before speaking with your doctor.

    PRIVACY & SHARING

    Should I tell other healthcare providers about my test result?
    If your doctor who prescribes medication for you doesn't already know about your test result, we do recommend that you share this information with him/her. However, what you decide to do with your results is up to you.

    Who will see my test results?
    People who have access to your medical record will be able to see your genetic test result. This may include health professionals such as doctors, nurses, pharmacists, and genetic counselors. However, health professionals from other centers or hospitals will likely not have access to your results.

    Should I tell other healthcare providers about my test result?
    If your doctor who prescribes medication for you doesn't already know about your test result, you should share this information with him/her.

    Should my other family members be tested to see how they might respond to thiopurines?
    You may want to share your test results with your family, since they might have the same genetic variant as you.

    Will this affect my health insurance?
    No, your health insurance will not be affected by this azathioprine test result.

    Who can I contact if they have any more questions?
    You can contact your local center, where you received the test.

    Is it there a risk to my privacy?
    Research that uses information from medical records and that involves genetic testing can affect your privacy. Your participation in this research will be held strictly confidential, and only coded numbers will be used to identify specimens and research records. While it is impossible to absolutely guarantee that information in our secure system will never be known by others, we are taking every possible precaution to see that this does not happen.

    RISKS

    What should I do if I have concerns about genetic test results?
    If you are concerned about genetic test results you have received, you should discuss your concerns with your doctor. Your doctor should be able to explain results to you, and may recommend you to a genetic counselor or another doctor that can further help you understand your results.

    Is there a reason why I may be a specific risk?
    Testing is recommended for all individuals undergoing or considering undergoing treatment with azathioprine.

    Are there any implications for having children?
    No.

    If I am found to have a specific gene variant, am I at increased risk?
    For some individuals, there gene test result may indicate that they are at an increased risk of responding poorly to azathioprine. Testing is done to help guide your doctor chose the best treatment for you.

    Can I expect to experience emotional consequences related to my test result?
    A range of reactions are possible and normal. Some patients may experience anxiety or other negative reactions related to their use/potential use of azathioprine. If this is the case, please discuss with your doctor, who can address your concerns and refer you another health professional if required.

    Can I expect to experience social consequences related to my test result?
    We do not anticipate any social consequences related to use/potential use of azathioprine. As always however, if you do experience any negative social reactions, please discuss with your doctor who can address your concerns.

    Can I expect to experience an increase in anxiety?
    Many individual experience increased anxiety related to genetic testing. Again, please discuss with your doctor if this is the case.

    Are there any implications in terms of discrimination arising from the test result?
    Health insurance companies are prevented by law from discriminating against you based on your genetic test results. However, the same law does not apply to long-term disability insurance or to life insurance.

    If I am found to be at increased risk for responding poorly to azathioprine, are there similar health implications for my family?
    If results indicate that you may respond poorly to azathioprine, your family may be more likely to have a similar response should azathioprine ever be considered an option for them. As such, you may want to discuss your results with your family.

    Are there likely to be emotional consequences relevant to azathioprine for my family?
    Similar to patients, family members may experience a range of reactions, which is normal. We recommend that if you discuss any questions or problems with your healthcare provider.

    About

    TEST MATERIAL ONLY - PLEASE DO NOT USE THIS CONTENT TO INFORM TREATMENT

    When was this content last updated?
    July 08, 2014.

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