For U.S. Healthcare Professionals Only

Patient Information

What is PURIXAN^®?

PURIXAN is a prescription medicine used along with other medicines to treat people with acute lymphoblastic leukemia (ALL).

What should I tell my healthcare provider before taking PURIXAN?

Before you take PURIXAN, tell your healthcare provider about all of your medical conditions, including if you:

have kidney or liver problems.
have a condition where your body produces too little of the enzyme thiopurine methyltransferase (TPMT) or the enzyme nucleotide diphosphatase (NUDT15).
have recently received or plan to receive a vaccine.
are pregnant or plan to become pregnant. PURIXAN can harm your unborn baby.

If you are a female who is able to become pregnant:

- Your healthcare provider will do a pregnancy test before you start treatment with PURIXAN.
- Use an effective method of birth control (contraception) during treatment with PURIXAN and for 6 months after your last dose. Talk with your healthcare provider about birth control methods you can use during this time.
- Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with PURIXAN.

If you are a male with a female partner who is able to become pregnant:

- Use effective birth control (contraception) during treatment with PURIXAN and for 3 months after your last dose.
- Tell your healthcare provider right away if your female partner becomes pregnant or thinks she is pregnant during your treatment with PURIXAN.

are breastfeeding or plan to breastfeed. Do not breastfeed during treatment with PURIXAN and for at least 1 week after your last dose.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How should I take PURIXAN?

See the detailed “Instructions for Use” that comes with PURIXAN for information about the right way to measure and take a dose of PURIXAN.
Take PURIXAN exactly as your healthcare provider tells you. Do not stop taking PURIXAN or change your dose without talking to your healthcare provider.
Take PURIXAN by mouth 1 time each day.
If PURIXAN comes into contact with skin, eyes, or clothes?

Remove contaminated clothing.
Wash skin or eyes immediately with water.
Contact with skin or eyes can cause hypersensitive reactions resulting in rash, redness, itching and inflammation. If symptoms appear seek medical attention.

During treatment with PURIXAN, your healthcare provider will do blood tests regularly to check your blood cell counts and liver function. Your healthcare provider may change your dose if you have side effects.
If you miss a dose of PURIXAN, call your healthcare provider for advice.
If you take too much PURIXAN, call your healthcare provider or go to the nearest emergency room right away.

What should I avoid while taking PURIXAN?

PURIXAN can make your skin more sensitive to sunlight. Protect yourself from sunlight during treatment with PURIXAN.

What are the possible side effects of PURIXAN?

PURIXAN can cause serious side effects, including:

Decreased blood cell counts are common with PURIXAN, but can also be severe. PURIXAN affects your bone marrow and can cause decreased white blood cells, red blood cells, and platelets. Decreased blood cell counts can make you more likely to develop infections, bleeding, or anemia. If you take certain medicines during treatment with PURIXAN, it could make the effects on your bone marrow worse. Tell your healthcare provider if you develop any of the following symptoms during treatment with PURIXAN:

fever
sore throat
cuts or wounds that are red, or swollen, or are draining
any bleeding
tiredness or weakness
shortness of breath

Liver problems. Increases in liver function test results are common with PURIXAN, but you can also develop severe liver problems with PURIXAN that can lead to death. Your healthcare provider may tell you to stop taking PURIXAN if you develop liver problems. Tell your healthcare provider right away if you develop any of the following symptoms of a liver problem during treatment with PURIXAN:

decreased appetite
diarrhea
nausea or vomiting
yellowing of your skin or the whites of your eyes
a build-up of fluid in your stomach-area (ascites)

Possible increased risk of other cancers. Talk with your healthcare provider about your risk of other cancers if you take PURIXAN.

Less common side effects of PURIXAN include: loss of appetite, nausea, vomiting, diarrhea, generally do not feel well and rash.
Low blood sugar (hypoglycemia) can happen, especially in children under six years of age.
Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of PURIXAN.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store PURIXAN?

PURIXAN comes in a bottle with a child-resistant cap.
Store PURIXAN between 59ºF to 77ºF (15ºC to 25ºC), in a dry place. Do not store above 25°C.
Store the oral dispensing syringe in a clean place, with the medicine.
PURIXAN oral suspension should be used within 8 weeks after opening the bottle. Dispose of (throw away) any unused medicine after 8 weeks.
Do not use after the expiry date which is stated on the carton and the bottle after ‘EXP’.
Keep the bottle tightly closed to prevent spoilage of the medicine and reduce the risk of accidental spillage.
Keep PURIXAN out of the reach of children, preferably in a locked cupboard. If a child accidentally takes PURIXAN, it could cause death.

How should I dispose of PURIXAN?

This medicine should not be disposed of in wastewater or household waste. Ask your pharmacist how to dispose of (throw away) PURIXAN that is no longer needed.

General information about the safe and effective use of PURIXAN.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use PURIXAN for a condition for which it was not prescribed. Do not give PURIXAN to other people, even if they have the same symptoms you have. It could harm them. You can ask your healthcare provider or pharmacist for information about PURIXAN that is written for health professionals.

What are the ingredients in PURIXAN?

Active ingredient: mercaptopurine
Inactive ingredients: xanthan gum, aspartame, concentrated raspberry juice, sucrose, ethyl parahydroxybenzoate sodium, methyl parahydroxybenzoate sodium, potassium sorbate, sodium hydroxide and purified water.

Manufactured by: Nova Laboratories Ltd, Leicester, LE18 4YL, United Kingdom
Manufactured for: Rare Disease Therapeutics, Inc., 2550 Meridian Blvd. Suite 150, Franklin, TN 37067
For more information, go to www.purixan-us.com.
This Patient Information has been approved by the U.S. Food and Drug Administration
D001354/1

INDICATION
PURIXAN^® is indicated for the treatment of patients with acute lymphoblastic leukemia (ALL) as part of a combination chemotherapy maintenance regimen.

IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
None.

WARNINGS AND PRECAUTIONS
Myelosuppression
The most consistent, dose-related adverse reaction of PURIXAN is myelosuppression, manifested by anemia, leukopenia, thrombocytopenia, or any combination of these. Monitor CBC and adjust the dosage of PURIXAN for excessive myelosuppression.

Consider testing for thiopurine S-methyltransferase (TPMT) or nucleotide diphosphatase (NUDT15) deficiency in patients with severe myelosuppression or repeated episodes of myelosuppression. TPMT genotyping or phenotyping (red blood cell TPMT activity) and NUDT15 genotyping can identify patients who have reduced activity of these enzymes. Patients with homozygous TPMT or NUDT15 deficiency may require a dose reduction.

Myelosuppression can be exacerbated by coadministration with allopurinol, aminosalicylates or other products that cause myelosuppression. Reduce the dosage of PURIXAN when coadministered with allopurinol.

Hepatotoxicity
Mercaptopurine is hepatotoxic. There are reports of deaths attributed to hepatic necrosis associated with the administration of mercaptopurine. Hepatic injury can occur with any dosage but seems to occur with greater frequency when the recommended dosage is exceeded. In some patients, jaundice has cleared following withdrawal of mercaptopurine and reappeared with rechallenge.

Monitor serum transaminase levels, alkaline phosphatase, and bilirubin levels at weekly intervals when first beginning therapy and at monthly intervals thereafter. Monitor liver tests more frequently in patients who are receiving PURIXAN with other hepatotoxic drugs or with known pre-existing liver disease. Withhold PURIXAN at onset of hepatotoxicity.

Immunosuppression
Mercaptopurine is immunosuppressive and may impair the immune response to infectious agents or vaccines. Due to the immunosuppression associated with maintenance chemotherapy for ALL, response to all vaccines may be diminished and there is a risk of infection with live virus vaccines. Consult immunization guidelines for immunocompromised patients.

Treatment Related Malignancies
Patients receiving immunosuppressive therapy, including mercaptopurine, are at an increased risk of developing lymphoproliferative disorders and other malignancies, notably skin cancers (melanoma and non-melanoma), sarcomas (Kaposi's and non-Kaposi's) and uterine cervical cancer in situ. The increased risk appears to be related to the degree and duration of immunosuppression. It has been reported that discontinuation of immunosuppression may provide partial regression of the lymphoproliferative disorder.

A treatment regimen containing multiple immunosuppressants (including thiopurines) should therefore be used with caution as this could lead to lymphoproliferative disorders, some with reported fatalities. A combination of multiple immunosuppressants, given concomitantly increases the risk of Epstein-Barr virus (EBV)-associated lymphoproliferative disorders.

Macrophage Activation Syndrome
Macrophage activation syndrome (MAS) (hemophagocytic lymphohistiocytosis) is a known, life-threatening disorder that may develop in patients with autoimmune conditions, in particular with inflammatory bowel disease (IBD), and there could potentially be an increased susceptibility for developing the condition with the use of mercaptopurine (an unapproved use). If MAS occurs, or is suspected, discontinue PURIXAN. Monitor for and promptly treat infections such as EBV and cytomegalovirus (CMV), as these are known triggers for MAS.

Embryo-Fetal Toxicity
PURIXAN can cause fetal harm when administered to a pregnant woman. An increased incidence of miscarriage has been reported in women who received mercaptopurine in the first trimester of pregnancy. Adverse embryo-fetal findings, including miscarriage and stillbirth, have been reported in women who received mercaptopurine after the first trimester of pregnancy. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with PURIXAN and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with PURIXAN and for 3 months after the last dose.

ADVERSE REACTIONS
Based on multicenter cooperative group ALL trials, the most common adverse reaction occurring in > 20% of patients was myelosuppression, including anemia, neutropenia, lymphopenia and thrombocytopenia. Adverse reactions occurring in 5% to 20% of patients included anorexia, nausea, vomiting, diarrhea, malaise, and rash. Adverse reactions occurring in 5% to 20% of patients included anorexia, nausea, vomiting, diarrhea, malaise, and rash. Adverse reactions occurring in < 5% of patients included urticaria, hyperuricemia, oral lesions, elevated transaminases, hyperbilirubinemia, hyperpigmentation, infections, and pancreatitis. Oral lesions resemble thrush rather than antifolic ulcerations. Delayed or late toxicities include hepatic fibrosis, hyperbilirubinemia, alopecia, pulmonary fibrosis, oligospermia and secondary malignancies.

USE IN SPECIFIC POPULATIONS

Lactation: Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with PURIXAN and for 1 week after the last dose.
Pediatric Use: Symptomatic hypoglycemia has been reported in pediatric patients with ALL receiving mercaptopurine. Reported cases were in pediatrics less than 6 years or with a low body mass index.
Renal Impairment: Use the lowest recommended starting dosage for PURIXAN or increase the dosing interval to every 36 to 48 hours in patients with renal impairment (CLcr less than 50 mL/min). Adjust the dose to maintain absolute neutrophil count (ANC) at a desirable level and for adverse reactions.
Hepatic Impairment: Use the lowest recommended starting dosage for PURIXAN in patients with hepatic impairment. Adjust the dose to maintain absolute neutrophil count (ANC) at a desirable level and for adverse reactions.

OVERDOSAGE
Signs and symptoms of mercaptopurine overdosage may be immediate (anorexia, nausea, vomiting, and diarrhea) or delayed (myelosuppression, liver dysfunction, and gastroenteritis). Dialysis cannot be expected to clear mercaptopurine. Hemodialysis is thought to be of marginal use due to the rapid intracellular incorporation of mercaptopurine into active metabolites with long persistence.

Withhold PURIXAN immediately if severe or life-threatening adverse reactions occur during treatment. If a patient is seen immediately following an accidental overdosage, it may be useful to induce emesis.

Please see complete Prescribing Information and Patient Information at www.purixan-us.com/pi.

To report SUSPECTED ADVERSE REACTIONS, contact Rare Disease Therapeutics, Inc., at 1-844-472-7389 or by email at safety@raretx.com or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

PUR-ISIF-003

2250 Meridian Blvd. Suite 150
Franklin, TN 37067

* Images on this website are for illustrative purposes only and do not depict actual patients.