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Succimer


General


Pronunciation

(SUKS si mer)


Brand Names: U.S.

  • Chemet

Indications


Use: Labeled Indications

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


Contraindications


Hypersensitivity to succimer or any component of the formulation


Dosing and Administration


Dosing: Adult

Lead poisoning (off-label use; Kosnett, 2007): 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.

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 2-week intervals between courses is generally recommended.


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

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.


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.


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.


Dosage Forms/Strengths


Dosage Forms

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

Capsule, Oral:

Chemet: 100 mg


Drug Interactions

There are no known significant interactions.


Monitoring Parameters

Blood lead levels (baseline and 7-21 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


Lab Test Interferences


Test Interactions

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


Adverse Reactions


>10%: Gastrointestinal: Appetite decreased, diarrhea, hemorrhoid symptoms, metallic taste, loose stools, nausea, vomiting

1% to 10%:

Cardiovascular: Arrhythmia (adults 2%)

Central nervous system: Chills, dizziness, drowsiness, fatigue, fever, headache, sleepiness

Dermatologic: Rash (including papular rash, herpetic rash and mucocutaneous eruptions); pruritus

Endocrine & metabolic: Cholesterol increased

Gastrointestinal: Abdominal cramps, mucosal irritation, sore throat

Genitourinary: Proteinuria (adults), urine output decreased (adults), voiding difficulty (adults)

Hematologic & oncologic: Eosinophilia, increased platelet count

Hepatic: Alkaline phosphatase increased, ALT increased, AST increased

Infection: Common cold

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

Ocular: Cloudy film in eye, watery eyes

Otic: Otitis media, plugged ears

Respiratory: Cough, nasal congestion, rhinorrhea

Miscellaneous: Flu-like syndrome, moniliasis

<1% (Limited to important or life-threatening): Allergic reactions (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.


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).


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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 2-4 hours (90% as mixed succimer-cysteine disulfide conjugates, 10% as unchanged drug); feces (as unabsorbed drug)


Time to Peak

Serum: ~1-2 hours


Half-Life Elimination

~3 hours (Aposhian, 1992)


Protein Binding

>95% primarily to albumin (Aposhian, 1992)


Patient and Family Education


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, diarrhea, lack of appetite, fatigue, or dizziness. Have patient report immediately to prescriber signs of infection 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.

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