Succimer

Frequency Not Defined

Nausea/vomiting

Diarrhea

Abd gas/pain

Transient LFTs incr (AST, AP)

Rash

Pruritus

Sore throat

Rhinorrhea

Drowsiness

Paresthesia

Thrombocytosis

Eosinophilia

Possible decr renal function

Fever

Mechanism of Action

2 sulfhydryl groups capable of complexing to lead making it water soluble

Pharmacokinetics

Rapid but incomplete

Protein binding: Highly bound to albumin

Excretion: Feces (39%), urine (9%)

Time to peak: 1-2 hr (serum)

Half-life elimination: 2 days

Metabolism: Metabolized extensively to succimer cysteine sulfides

Clinical experience with CHEMET has been limited. Consequently, the full spectrum and incidence of adverse reactions including the possibility of hypersensitivity or idiosyncratic reactions have not been determined. The most common events attributable to succimer, i.e., gastrointestinal symptoms or increases in serum transaminases, have been observed in about 10% of patients (see PRECAUTIONS). Rashes, some necessitating discontinuation of therapy, have been reported in about 4% of patients. If rash occurs, other causes (e.g. measles) should be considered before ascribing the reaction to succimer. Rechallenge with succimer may be considered if lead levels are high enough to warrant retreatment. One allergic mucocutaneous reaction has been reported on repeated administration of the drug (see PRECAUTIONS). Mild to moderate neutropenia has been observed in some patients receiving succimer (see WARNINGS). Table I presents adverse events reported with the administration of succimer for the treatment of lead and other heavy metal intoxication.

TABLE I : INCIDENCE OF ADVERSE EVENTS IN DOMESTIC STUDIES REGARDLESS OF ATTRIBUTION OR SUCCIMER DOSAGE

To report SUSPECTED ADVERSE REACTIONS, contact Recordati Rare Diseases Inc. at 1-888-755-8344 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Succimer is a chelating (KEE-late-ing) agent that is used to remove a heavy metal (such as lead) from the body. Succimer binds to lead in the blood and allows it to be passed out in the urine.

Succimer is used to treat lead poisoning.

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

You should not use succimer if you are allergic to it.

To make sure succimer is safe for you, tell your doctor if you have:

• kidney disease;

• liver disease; or

• if you have been treated with dimercaprol or edetate calcium disodium in the past month.

It is not known whether succimer will harm an unborn baby. Tell your doctor if you are pregnant.

It is not known whether succimer passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

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.

• Importance of identifying source of lead poisoning and then removing patient from that source.1 2 Importance of patient residing in an environment free of lead both during and after therapy.1 2

• For patients unable to swallow capsules, contents of capsules may be sprinkled on soft food just before administration or placed on a spoon for administration and taken with fruit juice.a

• Importance of maintaining adequate fluid intake.a

• Importance of informing clinicians if rash or infection occurs.a

• Importance of completing full course of therapy.a

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.a

• Importance of keeping succimer out of reach of children.a

• Importance of informing patients of other important precautionary information.a (See Cautions.)

In the U.S.

• Chemet

Available Dosage Forms:

• Capsule

Therapeutic Class: Heavy Metal Chelator

Succimer is used in the treatment of acute lead poisoning to remove excess lead from the body, especially in small children.

Succimer combines with lead in the blood stream. The combination of lead and succimer is then removed from the body by the kidneys. By removing the excess lead, the medicine lessens damage to various organs and tissues of the body.

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:

• Upset stomach or throwing up.
• Metallic taste.
• Loose stools (diarrhea).
• Not hungry.
• Feeling sleepy.
• Dizziness.
• Lower back or side pain.
• Stomach cramps.
• Belly pain.
• Headache.
• Flu-like signs.
• Feeling tired or weak.
• Signs of a common cold.

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.

Lead poisoning: For the treatment of high blood lead levels in children, the CDC recommends chelation treatment when blood lead levels are >45 mcg/dL (CDC, 2002). Children with blood lead levels >70 mcg/dL or symptomatic lead poisoning should be treated with parenteral agents (AAP, 2005).

Oral: 10 mg/kg/dose (or 350 mg/m2/dose) every 8 hours for 5 days followed by 10 mg/kg/dose (or 350 mg/m2/dose) every 12 hours for 14 days. Maximum: 500 mg/dose.

Note: Treatment courses may be repeated, but 2-week intervals between courses is generally recommended.

Adverse events were observed in animal reproduction studies.

Lead poisoning: Lead is known to cross the placenta in amounts related to maternal plasma levels. Prenatal lead exposure may be associated with adverse events such as spontaneous abortion, preterm delivery, decreased birth weight, and impaired neurodevelopment. Some adverse outcomes may occur with maternal blood lead levels <10 mcg/dL. In addition, pregnant women exposed to lead may have an increased risk of gestational hypertension. Consider chelation therapy in pregnant women with confirmed blood lead levels ≥45 mcg/dL (pregnant women with blood lead levels ≥70 mcg/dL should be considered for chelation regardless of trimester); consultation with experts in lead poisoning and high-risk pregnancy is recommended. Encephalopathic pregnant women should be chelated regardless of trimester (CDC, 2010).

Mild to moderate neutropenia has been reported in some patients receiving succimer. While a causal relationship to succimer has not been absolutely established, neutropenia has been reported with other drugs in the same chemical class. A complete blood count with white blood cell differential and direct platelet counts should be obtained prior to and weekly during succimer therapy. Succimer should either be withheld or discontinued if the absolute neutrophil count (ANC) is below 1200/mcL, and the patient followed closely to document recovery of the ANC to above 1500/mcL or to the patient's baseline neutrophil count. In patients who develop neutropenia, there is limited experience with reexposure. Such patients should be rechallenged only if the benefit of succimer therapy clearly outweighs the potential risk of another episode of neutropenia and then only with careful patient monitoring. Patients should be instructed to promptly report any signs of infection. If infection is suspected, the above laboratory tests should be conducted promptly.

Since the extent of clinical experience with succimer is limited, patients should be carefully observed during treatment.

Elevated blood lead levels and associated symptoms may rapidly return following discontinuation of succimer because of redistribution of lead from bone stores to soft tissues and blood. After therapy, patients should be monitored for rebound of blood lead levels with at least once- weekly laboratory measurements until stable. Nonetheless, the severity of lead intoxication (as measured by the initial blood lead level and the rate and degree of rebound of blood lead) should be used as a guide for more frequent blood lead monitoring.

Patients should be adequately hydrated during treatment with succimer.

Caution should be exercised in patients with compromised renal function.

Mild, transient elevations of serum transaminases have been observed in some patients during treatment with succimer therapy. Serum transaminases should be monitored prior to and at least weekly during therapy. Patients with a history of liver disease should be monitored closely.

Clinical experience with repeated courses of succimer therapy is limited. The safety of uninterrupted dosing lasting longer than three weeks has not been established and is not recommended.

The possibility of allergic or other mucocutaneous reactions to succimer should be considered, particularly upon readministration (as well as during initial courses). Patients requiring repeated courses of succimer should be monitored during each course.