Purinethol

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Mercaptopurine suspension can be kept at room temperature for up to 6 weeks after the bottle is opened for the first time. Then, dispose of any suspension that is left over after 6 weeks.

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

• Gate Pharmaceuticals

• Teva Select Brands

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if mercaptopurine crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using mercaptopurine.

Take mercaptopurine exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The mercaptopurine dose your doctor recommends will be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• whether or not you have a genetic deficiency of the TPMT enzyme
• your liver function
• your kidney function
• your age

The recommended dose range for mercaptopurine is 1.5 to 2.5 mg/kg/day once daily.

Mercaptopurine is a cancer medication that interferes with the growth and spread of cancer cells in the body.

Mercaptopurine is used to treat certain types of leukemia. Mercaptopurine is sometimes given with other cancer medications.

Mercaptopurine may also be used for purposes not listed in this medication guide.

Antineoplastic and immunosuppressive agent; purine antagonist.a 103

Absorption

Bioavailability

Absorption from GI tract is variable and incomplete; about 50% of an oral dose is absorbed.103 a

Maximum serum concentrations are reached within 2 hours.a

Distribution

Extent

Distributed throughout total body water.a

Only negligible concentrations attained in CSF.a 103

Not known whether mercaptopurine is distributed into milk.a 103

Plasma Protein Binding

Approximately 19% following IV doses >5–10 mg/kg.103

Elimination

Metabolism

Rapidly and extensively metabolized in the liver by oxidation via xanthine oxidase to 6-thiouric acid.a Also, undergoes thiol methylation via the enzyme TPMT to form the inactive metabolite methyl-6-MP.103

Elimination Route

Excreted principally in urine (about 46%) as unchanged drug and metabolites within 24 hours.103

Half-life

Following IV administration: 21 minutes in pediatric patients and 47 minutes in adults.103 a

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of mercaptopurine in the pediatric population. Safety and efficacy have not been established. The oral liquid may cause hypoglycemia (low blood sugar) in children younger than 6 years of age or with a low body mass index.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of mercaptopurine in the elderly. However, elderly patients are more likely to have age-related kidney or liver problems, which may require caution and an adjustment in the dose for patients receiving mercaptopurine.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Febuxostat
• Measles Virus Vaccine, Live
• Mumps Virus Vaccine, Live
• Rotavirus Vaccine, Live
• Rubella Virus Vaccine, Live
• Varicella Virus Vaccine

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Adenovirus Vaccine
• Alacepril
• Alfalfa
• Allopurinol
• Azathioprine
• Bacillus of Calmette and Guerin Vaccine, Live
• Benazepril
• Black Cohosh
• Captopril
• Cholera Vaccine, Live
• Cilazapril
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Enalaprilat
• Enalapril Maleate
• Fosinopril
• Influenza Virus Vaccine, Live
• Lisinopril
• Mesalamine
• Moexipril
• Mycophenolic Acid
• Olsalazine
• Oxypurinol
• Pentopril
• Perindopril
• Poliovirus Vaccine, Live
• Quinapril
• Ramipril
• Ribavirin
• Smallpox Vaccine
• Spirapril
• Sulfamethoxazole
• Sulfasalazine
• Trandolapril
• Trimethoprim
• Typhoid Vaccine
• Warfarin
• Yellow Fever Vaccine
• Zofenopril

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acenocoumarol
• Cyclosporine
• Methotrexate
• Phenprocoumon

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Anemia or
• Blood or bone marrow problems or
• Bowel problems (eg, nausea, vomiting, diarrhea) or
• Gout or
• Leukopenia (low white blood cells) or
• Liver disease or
• Thrombocytopenia (low platelets in the blood)—Use with caution. May make these conditions worse.

• Autoimmune disease (eg, inflammatory bowel disease) or
• Virus infection (eg, Epstein-Barr, cytomegalovirus)—Use with caution. May cause side effects to become worse.

• Infection—May decrease your body's ability to fight infection.

• Kidney disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

• It is used to treat a type of leukemia.
• It may be given to you for other reasons. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Loose stools (diarrhea).
• Not hungry.
• Upset stomach or throwing up.
• Feeling tired or weak.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

The principal and potentially serious toxic effects of Purinethol are bone marrow toxicity and hepatotoxicity (see WARNINGS and PRECAUTIONS).

Hematologic

The most frequent adverse reaction to Purinethol is myelosuppression. The induction of complete remission of acute lymphatic leukemia frequently is associated with marrow hypoplasia. Patients without TPMT enzyme activity (homozygous-deficient) are particularly susceptible to hematologic toxicity, and some patients with low or intermediate TPMT enzyme activity are more susceptible to hematologic toxicity than patients with normal TPMT activity (see WARNINGS, Bone Marrow Toxicity), although the latter can also experience severe toxicity. Maintenance of remission generally involves multiple-drug regimens whose component agents cause myelosuppression. Anemia, leukopenia, and thrombocytopenia are frequently observed. Dosages and also schedules are adjusted to prevent life-threatening cytopenias.

Renal

Hyperuricemia and/or hyperuricosuria may occur in patients receiving Purinethol as a consequence of rapid cell lysis accompanying the antineoplastic effect. Renal adverse effects can be minimized by increased hydration, urine alkalinization, and the prophylactic administration of a xanthine oxidase inhibitor such as allopurinol. The dosage of Purinethol should be reduced to one third to one quarter of the usual dose if allopurinol is given concurrently.

Gastrointestinal

Intestinal ulceration has been reported. Nausea, vomiting, and anorexia are uncommon during initial administration, but may increase with continued administration. Mild diarrhea and sprue-like symptoms have been noted occasionally, but it is difficult at present to attribute these to the medication. Oral lesions are rarely seen, and when they occur they resemble thrush rather than antifolic ulcerations.

Miscellaneous

The administration of Purinethol has been associated with skin rashes and hyperpigmentation. Alopecia has been reported.

Drug fever has been very rarely reported with Purinethol. Before attributing fever to Purinethol, every attempt should be made to exclude more common causes of pyrexia, such as sepsis, in patients with acute leukemia.

Oligospermia has been reported.

Purinethol Tablets 50 mg 60s Label Text

NDC 57844-522-06

Purinethol®
(mercaptopurine)
Each scored tablet contains:
50 mg

Rx only

60 Tablets

TEVA

Applies to mercaptopurine: oral suspension, oral tablet

Along with its needed effects, mercaptopurine (the active ingredient contained in Purinethol) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking mercaptopurine:

• Black, tarry stools
• clay colored stools
• cough or hoarseness
• dark urine
• decreased appetite
• fever or chills
• headache
• loss of appetite
• lower back or side pain
• nausea, vomiting
• painful or difficult urination
• pinpoint red spots on the skin
• rash, itchy skin
• stomach pain or tenderness
• swelling of the feet or lower legs
• unusual bleeding or bruising
• unusual tiredness or weakness
• yellow eyes or skin

• Bleeding gums
• chest pain
• joint pain
• pale skin
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• swollen glands
• trouble with breathing upon exertion

• Constipation
• diarrhea
• heartburn
• indigestion
• joint pain, stiffness, or swelling
• stomach cramping or burning
• vomiting of blood or material that looks like coffee grounds

Some side effects of mercaptopurine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Darkening of the skin
• headache

• Hair loss or thinning of the hair
• low sperm count