For U.S. Healthcare Professionals Only

Instructions for Use

PURIXAN^® (pure-ee-zan)

(mercaptopurine) oral suspension 20 mg/mL

Review these Instructions for Use before you start taking PURIXAN, and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

Important information about measuring PURIXAN oral suspension

Always use the oral dispensing syringe provided with your PURIXAN oral suspension to make sure you measure the right amount.
You will be provided:
- 1 bottle of PURIXAN oral suspension
- 1 bottle adapter
- 2 oral dispensing syringes (one 1 mL and one 5 mL)

If you did not receive an oral dispensing syringe with your PURIXAN oral suspension, ask your pharmacist to give you one.

You will need disposable gloves.

Important Information You Need to Know Before Administering PURIXAN:

Wash your hands well with soap and water before and after administering a dose.
Put on disposable gloves before handling PURIXAN.
Shake the bottle vigorously for at least 30 seconds to make sure that the medicine is well mixed (See Figure A).
Remove the child-resistant bottle cap (See Figure B).
Push the ribbed end of the bottle adapter into the neck of the bottle until it is firmly in place. The bottom edge of the adapter should fully contact the top rim of the bottle (See Figure C). Do not remove the adapter from the bottle after it is inserted.

Figure A

Figure B

Figure C

Preparing a dose of PURIXAN:

Hold the bottle upright. Remove the bottle cap by turning in the direction of the arrow (See Figure B).
Push the tip of the oral dispensing syringe into the hole in the bottle adapter (See Figure D and Figure E).
Turn the bottle upside down (See Figure F).
Pull back slowly on the plunger of the oral dispensing syringe to withdraw the prescribed dose of PURIXAN. Pull the plunger back to the mL mark on the syringe that corresponds to the dose prescribed (Figure F). If you are not sure about how much medicine to draw into the oral dispensing syringe, always ask your doctor, pharmacist or nurse for advice.
Leave the oral dispensing syringe in the bottle adapter and turn the bottle right-side up. Place the bottle onto a flat surface. Hold the oral dispensing syringe by the barrel and carefully remove it from the adapter. Do not hold the oral dispensing syringe by the plunger, because the plunger may come out.
Place the tip of the oral dispensing syringe in your mouth and aim the tip toward the inside of your cheek.
Gently squirt the PURIXAN oral suspension into your mouth by pushing on the plunger until the oral dispensing syringe is empty. Swallow the medicine.

Do not forcefully push on the plunger.
Do not squirt the medicine to the back of your mouth or throat. This may cause you to choke.

Remove the oral dispensing syringe from your mouth.
Swallow the dose of oral suspension then drink some water, making sure no medicine is left in your mouth.
Put the cap back on the bottle with the adapter left in place. Close the cap tightly.
Wash the oral dispensing syringe with warm soapy water and rinse well. Hold the oral dispensing syringe under water and move the plunger up and down several times to make sure the inside of the oral dispensing syringe is clean. Let the oral dispensing syringe dry completely before you use it again for dosing. Do not throw away the oral dispensing syringe after use.

Figure D

Figure E

Figure F

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.

Storing PURIXAN

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 oral suspension and all medicines out of the reach of children, preferably in a locked cupboard. If a child accidentally takes PURIXAN, it could cause death. Ask your pharmacist how to dispose of (throw away) PURIXAN that is no longer needed.

Disposing of PURIXAN

Ask your pharmacist how to dispose of PURIXAN that is expired or no longer required. Medicines should not be disposed of via wastewater or household waste.

Clean Up Spillage of PURIXAN

Use appropriate personal protective equipment (disposable gloves and eye protection). Mop up and contain spill material in a compatible container. Wash your hands thoroughly afterwards.

PURIXAN Contact with Skin, Eyes, or Clothes

Remove and launder 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.

Manufactured by:
Nova Laboratories, Ltd
Leicester LE18 4YL United Kingdom
Manufactured for:
Rare Disease Therapeutics, Inc.
2550 Meridian Blvd., Suite 150
Franklin, TN 37067
Part Number: D001356/1
This “Instructions for Use” has been approved by the U.S. Food and Drug Administration
Revised: April 2020

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.