Succimer

FDA Drug Information • Also known as: Chemet, Nephroscan

Brand Names: Chemet, Nephroscan
Dosage Form: POWDER
Product Type: BULK INGREDIENT

Description

11 DESCRIPTION CHEMET (succimer) is an orally active, lead chelating agent. The chemical name for succimer is meso 2, 3-dimercaptosuccinic acid (DMSA). Its empirical formula is C 4 H 6 O 4 S 2 and molecular weight is 182.2. The meso -structural formula is: Succimer is a white crystalline powder with an unpleasant, characteristic mercaptan odor and taste. Each CHEMET opaque white capsule for oral administration contains medicated beads with 100 mg of succimer and the following inactive ingredients: povidone, sodium starch glycolate, and sugar spheres. The capsule shell contains benzyl alcohol, butylparaben, edetate calcium disodium, gelatin, methylparaben, propylparaben, sodium lauryl sulfate, sodium propionate, titanium dioxide, and is imprinted with edible black ink. Chemical Structure

What Is Succimer Used For?

1 INDICATIONS AND USAGE CHEMET is indicated for the treatment of lead poisoning in pediatric patients aged 1 year and older with blood lead levels above 45 mcg/dL. CHEMET is a lead chelator indicated for the treatment of lead poisoning in pediatric patients aged 1 year and older with blood lead levels above 45 mcg/dL. ( 1 ) Limitations of Use CHEMET is not indicated for prophylaxis of lead poisoning in a lead-containing environment. ( 1 ) CHEMET does not cross the blood-brain barrier and is not indicated to treat encephalopathy associated with lead toxicity. ( 1 ) Limitations of Use CHEMET is not indicated for prophylaxis of lead poisoning in a lead-containing environment. CHEMET does not cross the blood-brain barrier and is not indicated to treat encephalopathy associated with lead toxicity.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION See Full Prescribing Information for important pretreatment evaluations. ( 2.1 ) Ensure patients receiving CHEMET are adequately hydrated. ( 2.3 ) Administer CHEMET capsules whole when possible. ( 2.3 ) Pediatric patients who cannot swallow whole capsules: Sprinkle contents of capsule in food (or on a spoon followed by a drink). ( 2.3 ) Recommended Dosage: 10 mg/kg or 350 mg/m 2 orally every 8 hours for five days followed by 10 mg/kg or 350 mg/m 2 orally every 12 hours for an additional 14 days. ( 2.2 ) 2.1 Important Pretreatment Evaluations Identify the source of lead in the pediatric patient's environment and eliminate the source prior to beginning treatment with CHEMET. Assess the following before initiating treatment with CHEMET: Blood lead concentration Complete blood count (CBC) with differential and platelets [see Dosage and Administration (2.2) , Warnings and Precautions (5.2) ] Ensure absolute neutrophil count (ANC) > 1500/mcL [see Dosage and Administration (2.2) ] Transaminases (AST/ALT) [see Warnings and Precautions (5.3) and Use in Specific Populations (8.6) ] Renal function with blood urea nitrogen (BUN), creatinine, urinary protein [see Use in Specific Populations (8.5) ] . Patients who have previously received Edetate calcium disodium (CaNa 2 EDTA) with or without dimercaprol may receive CHEMET for subsequent treatment after an interval of four weeks. 2.2 Recommended Dosage The recommended dosage of CHEMET for pediatric patients with lead poisoning is 10 mg/kg or 350 mg/m 2 orally every 8 hours for five days followed by 10 mg/kg or 350 mg/m 2 orally every 12 hours for an additional 14 days [see Table 1 CHEMET Pediatric Dosing Chart ]. Initiation of therapy at higher doses is not recommended. The total treatment course consists of 19 days. After discontinuation of CHEMET, elevated blood levels and associated symptoms may return rapidly because of redistribution of lead from bone stores to soft tissues and blood. Assess blood lead concentration after the completion of a 19 day course and every week until stable. Repeated courses may be administered after two weeks off treatment if blood lead concentrations remain elevated. A minimum of two weeks between treatment courses is recommended unless blood lead concentrations indicate the need for more prompt treatment. Table 1. CHEMET Pediatric Dosing Chart Weight in Kilograms (kg) Dose (mg) Number of Capsules 8 to15 kg 100 mg 1 16 to 23 kg 200 mg 2 24 to 34 kg 300 mg 3 35 to 44 kg 400 mg 4 >45 kg 500 mg 5 The safety of uninterrupted dosing longer than 3 weeks has not been established and is not recommended. Dosage Modifications for Neutropenia Monitor CBCs weekly. If the absolute neutrophil count (ANC) is <1200/mcL interrupt CHEMET. Resume CHEMET when ANC has recovered to >1500/mcL (or the patient's baseline count). Immediately discontinue CHEMET for signs/symptoms of infection. Only rechallenge patients who developed neutropenia with CHEMET therapy if the...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity and Dermatologic Reactions [see Warnings and Precautions (5.1) ] Neutropenia [see Warnings and Precautions (5.2) ] Hepatic Toxicity [see Warnings and Precautions (5.3) ] Most common adverse reactions (incidence ≥ 10%) in Pediatric patients: Digestive (nausea, vomiting, diarrhea, appetite loss, hemorrhoidal symptoms, metallic taste in mouth). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Recordati Rare Diseases Inc. at 1-888-575-8344 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Table 2 presents the adverse reactions associated with Chemet in pediatric patients. Table 2 Incidence of Adverse Reactions Associated with Chemet in Pediatric Patients Body System: Adverse Reactions Pediatric Patients (n=191) Digestive Nausea, vomiting, diarrhea, appetite loss, hemorrhoidal symptoms, metallic taste in mouth 12% Body as a Whole Back pain, abdominal cramps, stomach pains, head pain, rib pain, chills, flank pain, fever, flu-like symptoms, heavy head/tired, head cold, headache, moniliasis. 5% Metabolic Elevated ALT or AST, alkaline phosphatase, serum cholesterol. 4% Respiratory Sore throat, rhinorrhea, nasal congestion, cough. 4% Skin Papular rash, herpetic rash, rash, mucocutaneous eruptions, pruritis. 3% Nervous Drowsiness, dizziness, sensorimotor neuropathy, sleepiness, paresthesia. 1% Special Senses Cloudy film in eye, ears plugged, otitis media, eyes watery. 1% Heme/Lymphatic Neutropenia, increased platelet count, eosinophilia 1%

Drug Interactions

7 DRUG INTERACTIONS CHEMET may interfere with serum and urinary laboratory test. ( 7.1 ) 7.1 Laboratory Test Interference CHEMET may interfere with serum and urinary laboratory tests. In vitro studies have shown CHEMET to cause false positive results for ketones in urine using nitroprusside reagents and falsely decreased measurements of serum uric acid and creatinine phosphokinase (CPK). 7.2 Use with Other Chelation Therapies Concomitant administration of CHEMET with other chelation therapy, such as CaNa 2 EDTA is not recommended.

Contraindications

4 CONTRAINDICATIONS CHEMET is contraindicated in patients with a history of hypersensitivity reaction to succimer. Reactions have included mucocutaneous vesicular eruptions, urticaria, and angioedema [see Warnings and Precautions (5.1) ] . Patients with a history of hypersensitivity reaction to succimer. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary There are no studies with the use of CHEMET in pregnant women to inform drug-associated risks. Administration of CHEMET to pregnant mice during organogenesis at dose exposure of 11-times the human exposure at the maximum recommended human dose (MRHD) of 700 mg based on body surface area (BSA) resulted in maternal toxicity and mortality and impaired reflex development in offspring (see Animal Data ) . There are adverse effects on maternal and fetal outcomes associated with lead poisoning in pregnancy (see Clinical Considerations ) . CHEMET should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. However, the background risk in the U.S general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Lead exposure in pregnancy may increase the risk of gestational hypertension. Lead crosses the placenta in amounts related to maternal plasma levels. Prenatal lead exposure may be associated with spontaneous abortion, preterm delivery, decreased birth weight, and impaired neurodevelopment. Data Animal Data In embryo-fetal developmental studies, pregnant mice received subcutaneous succimer during the period of organogenesis at doses up to 1640 mg/kg/day (11-times the MRHD based on BSA) which resulted in both maternal and fetal toxicity. In a developmental study in rats, dosing with succimer during the period of organogenesis resulted in maternal toxicity and deaths at the dose of 720 mg/kg/day (10-times the MRHD based on BSA) or more. The dose of 510 mg/kg/day (7-times the MRHD based on BSA) was the highest tolerable dose in pregnant rats. Impaired development of...

Overdosage

10 OVERDOSAGE Doses of 2300 mg/kg in the rat and 2400 mg/kg in the mouse produced ataxia, convulsions, labored respiration and frequently death. Limited data indicate that CHEMET is dialyzable. In case of acute overdosage, consider use of induction of vomiting or gastric lavage followed by administration of an activated charcoal slurry and appropriate supportive therapy.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Capsules: 100 mg of CHEMET (succimer), imprinted black with "CHEMET 100", in a bottle of 100 (NDC 55292-201-11). Store between 15°C and 25°C and avoid excessive heat. Dispense in tight, light-resistant container.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.