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Succimer

Medically reviewed on March 25, 2018

Pronunciation

(SUKS si mer)

Index Terms

  • DMSA

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Chemet: 100 mg

Brand Names: U.S.

  • Chemet

Pharmacologic Category

  • Antidote

Pharmacology

Succimer is an analog of dimercaprol. It forms water soluble chelates with heavy metals which are subsequently excreted renally. Succimer binds heavy metals; however, the chemical form of these chelates is not known.

Absorption

Rapid but incomplete

Distribution

Primarily extracellular (Aposhian 1992)

Metabolism

Rapidly and extensively to mixed succimer cysteine disulfides

Excretion

Urine (~25%) with peak urinary excretion between 2 to 4 hours (90% as mixed succimer-cysteine disulfide conjugates, 10% as unchanged drug); feces (as unabsorbed drug)

Time to Peak

Serum: ~1 to 2 hours

Half-Life Elimination

~3 hours (Aposhian 1992)

Protein Binding

>95% primarily to albumin (Aposhian 1992)

Use: Labeled Indications

Treatment of lead poisoning in children with serum lead levels >45 mcg/dL

Off Label Uses

Lead poisoning (adults)

Clinical experience suggests the utility of succimer in the treatment of symptomatic lead poisoning in adult patients [Kosnett 2007]. Additional data are necessary to further define the role of succimer in the treatment of this condition.

Mercury poisoning

Clinical experience suggests the utility of succimer in the treatment of organic and inorganic mercury poisoning [Andersen 1999], [ATSDR [Mercury] 2014b], [Drasch 2007], [Kosnett 2013]; succimer is designated an orphan drug by the US Food and Drug Administration (FDA) for this purpose. Additional data are necessary to further define the role of succimer in the treatment of this condition.

Arsenic poisoning

Clinical experience suggests the utility of succimer in the treatment of arsenic poisoning [Andersen 1999], [ATSDR [Arsenic and Inorganic Arsenic Compounds] 2014a], [Kosnett 2013]. Additional data are necessary to further define the role of succimer in the treatment of this condition.

Contraindications

Hypersensitivity to succimer or any component of the formulation

Dosing: Adult

Lead poisoning (off-label use) (Kosnett 2007), arsenic poisoning (off-label use) (Kosnett 2013), mercury poisoning (off-label use) (Kosnett 2013): For the treatment of high blood lead levels in adults, chelation therapy is recommended with blood lead levels >50 mcg/dL and significant symptoms; chelation therapy may also be indicated with blood lead levels ≥100 mcg/dL and/or symptoms. Consultation with a clinical or medical toxicologist or poison control center is highly recommended in patients who are being considered for chelation therapy.

Oral: Consider using labeled dose for children: 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 a 2-week interval between courses is generally recommended because lead reequilibrates between the extravascular storage sites (eg, bone) and the vascular compartment.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Lead poisoning, arsenic poisoning (off-label use) (Kosnett 2013), mercury poisoning (off-label use) (Kosnett 2013): 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). Consultation with a clinical or medical toxicologist or poison control center is highly recommended in patients who are being considered for chelation therapy.

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 a 2-week interval between courses is generally recommended because lead reequilibrates between the extravascular storage sites (eg, bone) and the vascular compartment.

Dosing: Renal Impairment

No dosage adjustment provided in the manufacturer’s labeling; use with caution. Succimer is dialyzable; however, the lead chelates are not.

Dosing: Hepatic Impairment

No dosage adjustment provided in the manufacturer’s labeling; has not been studied. More frequent monitoring of serum transaminases may be required in patients with a history of liver disease due to the risk of transient increases.

Dosing: Adjustment for Toxicity

ANC <1200 mm3: The manufacturer recommends withholding treatment; treatment may be cautiously resumed when ANC returns to baseline or >1500/mm3. Consultation with a medical toxicologist to determine the risk versus benefit of withholding treatment is recommended.

Administration

If unable to swallow whole, capsule may be separated and contents sprinkled on a small amount of soft food, or the contents placed on a spoon and administered followed by fruit drink.

Storage

Store between 15°C to 25°C (59°F to 77°F); avoid excessive heat.

Drug Interactions

There are no known significant interactions.

Test Interactions

False-positive ketones (U) using nitroprusside methods, falsely decreased serum CPK; falsely decreased uric acid measurement

Adverse Reactions

>10%:

Central nervous system: Metallic taste

Gastrointestinal: Decreased appetite, diarrhea, hemorrhoids, loose stools, nausea, vomiting

1% to 10%:

Cardiovascular: Cardiac arrhythmia (adults: 2%)

Central nervous system: Chills, dizziness, drowsiness, fatigue, flank pain, headache, neuropathy, paresthesia

Dermatologic: Skin rash (including herpetic lesion, mucocutaneous eruptions, papular rash), pruritus

Endocrine & metabolic: Increased serum cholesterol

Gastrointestinal: Abdominal cramps, mucositis, sore throat

Genitourinary: Decreased urine output (adults), difficulty in micturition (adults), proteinuria (adults)

Hematologic & oncologic: Change in platelet count (increase), eosinophilia

Hepatic: Increased serum alkaline phosphatase, increased serum ALT, increased serum AST

Infection: Candidiasis, common cold

Neuromuscular & skeletal: Back pain, knee pain (adults), leg pain (adults), rib pain

Ophthalmic: Cloudy vision (cloudy film in eye), watery eyes

Otic: Blocked ear, otitis media

Respiratory: Cough, flu-like symptoms, nasal congestion, rhinorrhea

Miscellaneous: Fever

<1%, postmarketing, and/or case reports: Hypersensitivity reaction (especially with retreatment), neutropenia (causal relationship not established)

Warnings/Precautions

Concerns related to adverse effects:

• Hematologic effects: Mild-to-moderate neutropenia has been reported; evaluate CBC with differential at baseline, weekly during treatment, and immediately upon the development of any sign of infection. The manufacturer recommends withholding treatment for ANC <1200/mm3; treatment may be cautiously resumed when ANC returns to baseline or >1500/mm3. Consultation with a medical toxicologist to determine the risk versus benefit of withholding treatment is recommended.

• Hepatic effects: Transient elevations in serum transaminases have been reported. Evaluate serum transaminases at baseline and weekly during treatment; more frequent monitoring may be required in patients with a history of liver disease.

• Hypersensitivity reactions: Monitor for the development of allergic or other mucocutaneous reactions. A reversible mucocutaneous vesicular eruption of the oral mucosa, external urethral meatus, or perianal area has been reported (rarely).

Disease-related concerns:

• Encephalopathy: Succimer does not cross blood-brain barrier and should not be used to treat encephalopathy associated with lead toxicity.

• Lead poisoning: Investigate, identify, and remove sources of lead exposure prior to treatment; do not permit patients to re-enter the contaminated environment until lead abatement has been completed. Primary care providers should consult experts in chemotherapy of heavy metal toxicity before using chelation drug therapy. Succimer is not used to prevent lead poisoning. A rebound rise in serum lead levels may occur after treatment as lead is released from storage sites into blood. The severity of rebound may guide the frequency of future monitoring and the need for additional chelation therapy.

• Renal impairment: Use with caution in patients with renal impairment. Succimer is dialyzable; however, the lead chelates are not.

Other warnings/precautions:

• Hydration: Adequate hydration should be maintained during therapy.

Monitoring Parameters

Blood lead levels (baseline and 7 to 21 days after completing chelation therapy); serum aminotransferase (baseline and weekly during treatment; may require more frequent monitoring in patients with a history of liver disease), CBC with differential and platelets (baseline, and weekly during treatment); hemoglobin or hematocrit, iron status, free erythrocyte protoporphyrin or zinc protoporphyrin; neurodevelopmental changes

Pregnancy Risk Factor

C

Pregnancy Considerations

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).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, vomiting, metallic taste, lower back pain, side pain, abdominal cramps, abdominal pain, headache, flu-like signs, loss of strength and energy, common cold symptoms, diarrhea, lack of appetite, fatigue, or dizziness. Have patient report immediately to prescriber signs of infection, rectal irritation, ear pain, or burning or numbness feeling (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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