Lampit Drug Information

LAMPIT is indicated in pediatric patients (birth to less than 18 years of age and weighing at least 2.5 kg) for the treatment of Chagas disease (American Trypanosomiasis) caused by Trypanosoma cruzi.

Important Administration Instructions • LAMPIT (30 mg and 120 mg) tablets are for oral use and must be taken with food. • LAMPIT tablets are dosed by body weight of the patient. • LAMPIT (30 mg and 120 mg) tablets are functionally scored tablets which can be split into one-half (15 mg and 60 mg respectively) at the scored lines by hand. Do not break LAMPIT tablets mechanically with a tablet splitting device. • LAMPIT 30 mg and 120 mg tablets can be made into a slurry as an alternative method of administration for patients who cannot swallow the tablets. • Discontinue consumption of alcohol during treatment with LAMPIT. • Complete the full course of treatment to prevent recurrence of the infection. • If a dose is missed, take the missed dose as soon as possible together with food. However, if it is within 3 hours of the next scheduled dose, skip the missed dose and continue treatment as prescribed.

Do not take a double dose to make up for a missed dose.

Recommended Dosage in Pediatric Patients • Administer LAMPIT (30 mg and 120 mg) tablets orally three times a day with food. • Total daily recommended dosages of LAMPIT are based on the body weight of the patient (see Table 1 ). • Adjust LAMPIT dosage accordingly if body weight decreases during treatment. • The recommended duration of treatment with LAMPIT is 60 days. Table 1: Total Daily Recommended Dosages of LAMPIT Based on Body Weight a Term newborn with body weight of greater than or equal to 2.5 kg Table 2: Individual Dosages Based on Body Weight in Pediatric Patients (Birth a to Less than 18 years of age) a Term newborn with body weight of greater than or equal to 2.5 kg

Pregnancy Testing Prior to Initiating LAMPIT Obtain a pregnancy test in females of reproductive potential prior to initiating treatment with LAMPIT.

Instructions for Splitting LAMPIT Tablets

A functional score line is used to divide the tablet by hand as follows: • To split LAMPIT tablet, place the tablet on a flat surface with the score line facing up. • With the tablet resting on the flat surface, apply enough downward pressure with the index finger centered on the top of the tablet to break it along the score line.

Preparation of a Slurry of LAMPIT as an Alternate Method of Administration For patients who are unable to swallow whole or half tablets, LAMPIT tablet can be dispersed in water and administered as outlined below. • Place approximately 2.5 mL of water into a spoon. • Place the prescribed dose into the water. • Allow the tablet(s) to disintegrate (typically less than 30 seconds). • A slurry (liquid suspension) is formed. • Take the slurry immediately with food.

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. The safety data described below reflect exposure to LAMPIT in one prospective, randomized, double-blind trial (Trial 1). 330 pediatric patients with serologic evidence of T. cruzi infection and without Chagas disease-related cardiac or gastrointestinal symptoms were randomly assigned in a 2:1 fashion to a 60-day (n=219) or a 30-day (n=111) LAMPIT treatment regimen and were followed up for one year after end of treatment. LAMPIT was administered three times a day with food using a body weight-based dosing.

The median treatment duration was 61 days for subjects in the 60-day regimen. The majority (86.7%) of the study population was ≥2 to <18 years of age at randomization. Adverse reactions were reported for 213 of 330 (64.5%) patients.

The proportion of patients with adverse reactions was higher in the 60-day regimen (67.1%) compared with the 30-day regimen (59.5%). Most patients with adverse reactions had mild (76.5%) or moderate (22.0%) reactions. Adverse reactions occurring in ≥1% of LAMPIT-treated patients are shown in Table 3.

Table 3 Adverse Reactions Reported in (≥1%) Pediatric Patients with Chagas Disease in Trial 1 Treated with LAMPIT for 60 days a Abdominal pain includes abdominal pain and abdominal pain upper b Rash includes rash, rash macular, rash maculo-papular, rash morbilliform, and rash papular. Other adverse reactions occurring in 0.1% to less than 1% of patients treated with LAMPIT for 60 days included asthenia, vertigo, arthralgia, myalgia, paresthesia, tremor, irritability, anxiety, pruritus, fatigue, somnolence, seizure, syncope, neutropenia, leukopenia.

Postmarketing Experience

The following safety data were derived during postmarketing surveillance of nifurtimox from outside the United States, including literature data for all age groups (pediatric and adult populations). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Table 4: Postmarketing Adverse Reactions Reported in Pediatric and Adult Populations Treated with Nifurtimox

Concomitant use of LAMPIT with alcohol may increase the incidence and severity of undesirable effects similar to other nitrofurans and nitroheterocyclic compounds. LAMPIT is contraindicated in patients who consume alcohol during treatment.

Pregnancy Risk Summary Based on animal studies, LAMPIT may cause fetal harm when administered to a pregnant woman. Published postmarketing reports on nifurtimox use during pregnancy are insufficient to inform a drug-associated risk of birth defects and miscarriage. There are risks to the fetus associated with Chagas disease ( see Clinical Considerations).

Nifurtimox administered orally to pregnant rats, and rabbits during organogenesis was associated with reduced maternal body weights in rats, and abortions, reduced maternal weight gain, and reduced numbers of live fetuses in rabbits when nifurtimox was administered orally during organogenesis at doses approximately equal to the MRHD in rats and 2-times the MRHD in rabbits. An increased incidence of a fetal skeletal malformation (fusion of caudal vertebral bodies) occurred in rabbits at nifurtimox doses approximately 0.2 times the MRHD. In a pre-postnatal study, maternal body weights and fetal body weights of first-generation offspring were reduced at doses approximately equal to or 0.5 times the MRHD, respectively, and several male offspring in the nifurtimox treatment groups exhibited slightly small testes at doses ≥0.2 times the MRHD ( see Data).

Advise pregnant women of the potential risk to a fetus. There is a pregnancy safety study for LAMPIT. If LAMPIT is administered during pregnancy, or if a patient becomes pregnant while receiving LAMPIT or within six months following the last dose of LAMPIT, healthcare providers should report LAMPIT exposure by calling 1-888-842-2937.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively.

Clinical Considerations Disease-associated Maternal and/or Embryo/Fetal Risk Published data from case-control and observational studies on chronic Chagas disease during pregnancy are inconsistent in their findings. Some studies showed an increased risk of pregnancy loss, prematurity and neonatal mortality in pregnant women who have chronic Chagas disease while other studies did not demonstrate these findings. Chronic Chagas disease is usually not immediately life-threatening.

Since pregnancy findings are inconsistent, treatment of chronic Chagas disease during pregnancy is not recommended due to risk of embryo-fetal toxicity from LAMPIT. Acute symptomatic Chagas disease is rare in pregnant women; however, symptoms may be serious or life-threatening. If a pregnant woman presents with acute symptomatic Chagas disease, the risks versus benefits of treatment with LAMPIT to the mother and the fetus should be evaluated on a case-by-case basis.

Maternal body weights, body weight gain, and food consumption were reduced in the 60 mg/kg/day dose group. Treatment with nifurtimox did not produce fetal toxicity and no nifurtimox-related fetal malformations were observed. No maternal toxicity was observed at 30 mg/kg/day nifurtimox (approximately 0.5 times the MRHD based on body surface area comparison) and no adverse fetal effects were observed at 60 mg/kg/day nifurtimox (approximately equivalent to the MRHD based on body surface area comparison).

The mean number of live fetuses/litter and the percent of live fetuses per total implantations per group were significantly lower in the mid- and high-dose groups compared to the control group. Nifurtimox administration was associated with increased fetal and litter incidences of a skeletal malformation (fusion of caudal vertebral bodies) in fetuses in the low-dose group receiving 5 mg/kg/day (approximately equivalent to 0.2-times the MRHD based on body surface area comparison). No maternal toxicity was observed at 15 mg/kg/day which is approximately equivalent to 0.5 times the MRHD based on body surface area comparison.

In a pre-postnatal study, pregnant female rats were orally administered 15, 30, and 60 mg/kg/day nifurtimox during organogenesis and lactation. Maternal findings included reduced maternal body weights in high-dose dams during gestation and to a lesser degree during lactation. In first-generation offspring, body weights were significantly reduced in males and females in the high-dose group during the lactation and post-lactation periods.

Physical development, neurological function, and reproduction of first-generation offspring were not substantially changed in the nifurtimox treatment groups, but 5–20% of male offspring in all the nifurtimox treatment groups exhibited slightly small testes. No adverse maternal effects or fetal effects on first-generation female offspring occurred at 30 mg/kg/day, and no adverse fetal effects on the development of male offspring occurred at 15 mg/kg/day (respectively approximately 0.5- and 0.2-times the MRHD based on body surface area comparison).

Pediatric Use The safety and effectiveness of LAMPIT have been established for the treatment of Chagas disease (American Trypanosomiasis) caused by Trypanosoma cruzi in pediatric patients from birth to less than 18 years of age weighing at least 2.5 kg. The efficacy of LAMPIT was demonstrated in pediatric patients 0 to 4 years of age in Trial 1 based on seroconversion to negative on lysate ELISA, recombinant ELISA and IHA at 4 years post-treatment compared to untreated patients. The efficacy of LAMPIT in pediatric patients 5 to <18 years of age was extrapolated from efficacy established in the younger pediatric population.

Supportive evidence of efficacy was provided by seroconversion to negative on the F29 ELISA. The safety and effectiveness of LAMPIT has not been established in pediatric patients weighing less than 2.5 kg.

• LAMPIT tablets are contraindicated in:
• Patients with known hypersensitivity to nifurtimox or any of the excipients in LAMPIT.
• Patients who consume alcohol during treatment
• Alcohol consumption during treatment.