32/20. Nifurtimox- (LAMPY)- (Aug 2020)- Chagas Disease -Pediatric drug
Drug Name:32/20. Nifurtimox- (LAMPY)- (Aug 2020)- Chagas Disease -Pediatric drug
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
DRUG INTERACTIONS-
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
Indication:
U.S. FDA APPROVED DRUGS DURING 2020
Sr.No- 32
Adverse Reaction:
Contra-Indications:
Patient Information:
PATIENT COUNSELING INFORMATION
Advise patients to read the FDA-approved patient labeling (Patient Information and Instructions for Use).
Embryo Fetal Toxicity • Advise pregnant women and females of reproductive potential of the potential risk of LAMPIT to a fetus and to inform their healthcare provider of a known or suspected pregnancy.
• Advise females of reproductive potential to use effective contraception while taking LAMPIT and for 6 months after the last dose
• Advise male patients with female partners of reproductive potential to use condoms during treatment with LAMPIT and for 3 months after the final dose of LAMPIT
Lactation- Advise nursing mothers to monitor infants exposed to LAMPIT through breast milk for vomiting, rash, decreased appetite, fever, and irritability
Infertility - Advise males of reproductive potential that LAMPIT may impair fertility
Worsening of Neurological and Psychiatric Conditions- Advise patients with a history of brain injury, seizures, psychiatric disease, serious behavioral alterations or if neurological and/or psychiatric drug reactions occur, that LAMPIT tablets should be administered only under close medical supervisio
Hypersensitivity- Inform patients that hypersensitivity could be a reaction caused by LAMPIT or an immune response triggered by Chagas disease during treatment.
Hypersensitivity reactions could include hypotension, angioedema (including laryngeal or facial edema), dyspnea, pruritus, rash or other severe skin reactions
Alcohol Consumption- Advise patients to discontinue alcohol use during treatment with LAMPIT. LAMPIT is contraindicated in patients who consume alcohol during treatment.
Decreased Appetite and Weight Loss- Inform patients that LAMPIT can cause decreased appetite and weight loss. Body weight should be checked every 14 days, as the dosage may have to be adjusted
Porphyria - Advise patients with porphyria that treatment with nitrofuran derivatives, such as LAMPIT, may precipitate acute attacks of porphyria.
Administer LAMPIT tablets under close medical supervision in patients with porphyria.
Important Administration Instructions- Advise patients to take LAMPIT with food. Advise patients not to break LAMPIT tablets mechanically with a tablet splitting device .
For patients who cannot swallow tablets, LAMPIT can be dispersed in water and administered as a slurry, taken with food.
Ability to Operate Vehicles or Machinery- Inform patients that if muscle weakness or tremors occur during treatment with LAMPIT they should not drive, cycle or use any tools or machines
Manufactured for: Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ 07981 USA © 2020 Bayer HealthCare Pharmaceuticals Inc. For more information, call Bayer HealthCare Pharmaceuticals Inc. at Bayer at 1-888-842-2937 or go to www.LAMPIT.com
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
.1 Mechanism of Action
Nifurtimox is an antiprotozoal drug
2. Pharmacodynamics- Nifurtimox exposure-response relationships and the time course of pharmacodynamics response are unknown.
Cardiac Electrophysiology - At the recommended dose, nifurtimox treatment does not result in large mean increases (>20 ms) in the QTc interval.
3. Pharmacokinetics- Absorption- The mean (%CV) nifurtimox AUC estimates ranged between 1676-2670 µg·h/L (19–32%) and Cmax estimates ranged between 425-568 µg/L (26–50%) following administration of single dose 120 mg nifurtimox with food in adult Chagas patients.
No clinically significant differences in nifurtimox AUC or Cmax at the 120 mg dose were observed when using two tablet strengths (30 and 120 mg) or administered as whole or dissolved tablets under fed conditions.
The median time to reach maximum concentration (Tmax) of nifurtimox under fed conditions was 4 hours (range: 2 to 8 hours).
Effect of Food- Following administration of a single oral dose of 120 mg LAMPIT in adult Chagas patients, nifurtimox Cmax increased 68%, AUC increased 71%, and Tmax increased by 1 hour with a high-fat meal (800–1000 calorie, approximately 60% fat) compared to fasted conditions.
Distribution- Nifurtimox passes the blood brain barrier as well as the placental barrier. The plasma proteins binding of nifurtimox is 42%.
Elimination- The mean (%CV) estimates for elimination half-life of nifurtimox ranged between 2.4–3.6 hours (12–37%).
Metabolism- Metabolism of nifurtimox is primarily mediated via nitroreductases.
Exploratory investigations identified two major pharmacologically inactive metabolites (M-4, M-6) and several other minor metabolites in pooled human plasma. M-4 is a rearranged cysteine conjugate of nifurtimox with a half-life of approximately 28 hours, and M-6 is postulated to be formed by hydrolytic cleavage of the hydrazone moiety with a half-life of approximately 10 hours.
Excretion- Following administration of nifurtimox under fed and fasted conditions, approximately 44% and 27% of the dose was recovered in urine mainly as metabolites, respectively. Biliary and fecal elimination of nifurtimox and its metabolites has not been evaluated.
Specific Populations- The effect of renal or hepatic impairment on the pharmacokinetics of nifurtimox is unknown. Blood concentrations of nifurtimox increased in patients with ESRD.
Drug Interaction Studies- Clinical Studies- No clinical studies evaluating the drug interaction potential of nifurtimox have been conducted.
In Vitro Studies Cytochrome P450 Enzymes (CYPs): Nifurtimox is not a substrate of CYPs. Nifurtimox and its metabolites (M-4 or M-6) are not inhibitors or inducers of CYPs.
Transporter Systems: Nifurtimox is not a substrate or inhibitor of P-glycoprotein (P-gp) or breast cancer resistant protein (BCRP), and is not an inhibitor of organic anion transporting polypeptide (OATPs), multidrug and toxin extrusion (MATE) proteins (MATE1/MATE2-K), organic anion transporter 1/3 (OAT1/OAT3), or organic cation transporter 2 (OCT2).
Major metabolites- (M-4 or M-6) of nifurtimox are not inhibitors of P-gp, BCRP, OATPs, MATE1, MATE2K, OAT1, OAT3, or OCT2 at clinically relevant concentrations.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. 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.
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.
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 2 to 4% and 15 to 20%, respectively.
2. Lactation Risk Summary
Published literature demonstrates that nifurtimox is present in human breast milk with an estimated infant daily dose of less than 15% of the recommended daily dose for pediatric patients with Chagas disease.
There were no reports of adverse effects on the small number of infants who were breastfed by mothers taking nifurtimox. There is no information on the effects of nifurtimox on milk production.
Monitor infants exposed to LAMPIT through breast milk for vomiting, rash, decreased appetite, pyrexia and irritability.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for LAMPIT and any potential adverse effects on the breastfed infant from LAMPIT or from the underlying maternal condition.
3. Females and Males of Reproductive Potential- Pregnancy Testing- Pregnancy testing is recommended for females of reproductive potential prior to initiating treatment with LAMPIT.
Contraception- Females- LAMPIT may cause fetal harm when administered to a pregnant woman.
Advise females of reproductive potential to use effective contraception during treatment with LAMPIT and for 6 months after the final dose.
Males- Due to the potential for genotoxicity, advise male patients with female partners of reproductive potential to use condoms during treatment and for 3 months after the final dose of LAMPIT.
Infertility- Males- Based on findings in rodents, LAMPIT may impair fertility in males of reproductive potential. These effects on fertility were not reversible in 75% of the animals at 11 weeks after dosing
4. 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 safety and effectiveness of LAMPIT has not been established in pediatric patients weighing less than 2.5 kg.
5. Renal Impairment- The effect of renal impairment on the pharmacokinetics of nifurtimox is unknown
Published literature suggests that blood concentrations of nifurtimox were increased in patients with End Stage Renal Disease (ESRD) requiring hemodialysis
Administer LAMPIT under close medical supervision.
6. Hepatic Impairment- The effect of hepatic impairment on the pharmacokinetics of nifurtimox is unknown. Administer LAMPIT under close medical supervision.
