Paromomycin

Paromomycin is an Antibacterial Agent belonging to Aminoglycoside antibiotic

Paromomycin can be used in the treatment of Intestinal Amebiasis, Hepatic coma.

Paromomycin is Poorly absorbed from the GI tract and get excreted Via faeces (approx 100% of the dose, as unchanged drug); via urine (approx 0.1%).

The common side effects associated with Paromomycin include Abdominal cramps, diarrhea, heartburn, nausea, vomiting.

Paromomycin is available in the form of oral solid.

The molecule is available in India, USA, Germany, Japan.

Paromomycin inhibits protein synthesis by binding to 16S ribosomal RNA. Bacterial proteins are synthesized by ribosomal RNA complexes which are composed of 2 subunits, a large subunit (50s) and small (30s) subunit, which forms a 70s ribosomal subunit. tRNA binds to the top of this ribosomal structure. Paramomycin binds to the A site, which causes defective polypeptide chains to be produced. Continuous production of defective proteins eventually leads to bacterial death. (Tmax of Paromomycin was Within 1 to 2 hours.

Paromomycin is available in Capsule.

Oral: Administer higher doses preferably at late afternoon or as bedtime doses to minimize daytime sedation.

Paromomycin is available in Capsule.

Oral: Administer higher doses preferably at late afternoon or as bedtime doses to minimize daytime sedation.

Paromomycin acts directly on ameba and has antibacterial activity against normal and pathogenic organisms in the GI tract and interferes with bacterial protein synthesis by binding to 30S ribosomal subunits. Paromomycin is to be used in intestinal amoebiasis, hepatic coma, cryptosporiodosis and Associated diarrhea in HIV patients.

Paromomycin is approved for use in the following clinical indications

• Intestinal amebiasis: Treatment of acute and chronic intestinal amebiasis (not effective for extraintestinal amebiasis).
• Hepatic coma: Management (adjunctive) of hepatic coma.
• Although not approved there have been certain off labelled uses documented for Paromomycin which include:

Cryptosporidiosis-associated diarrhea in patients with HIV; Dientamoeba fragilis infection; Trichomoniasis, refractory or resistant infection.

Hepatic coma: Oral: 4 g daily in divided doses (at regular intervals) for 5 to 6 days.

Intestinal amebiasis: Oral: 25 to 35 mg/kg/day in 3 divided doses for 5 to 10 days.

Cryptosporidiosis-associated diarrhea in patients with HIV (off-label use): Oral: 500 mg 4 times daily for 14 to 21 days (must be used in conjunction with optimized antiretroviral therapy, electrolyte replacement, symptomatic treatment, and rehydration)

Dientamoeba fragilis (off-label use): Oral: 25 to 35 mg/kg/day in 3 divided doses for 7 days

Trichomoniasis, refractory or resistant infection (off-label use):

Note: For patients with infection refractory to multiple prior regimens

Intravaginal: 4 g (equivalent to 250 mg paromomycin) of an extemporaneously compounded 6.25% cream once daily at bedtime in combination with oral tinidazole for 14 days.

(The dosage and duration of treatment should be as per the clinical judgement of the treating physician).

250 mg

Capsule

• Dose Adjustment in Pediatric Patient:

Cryptosporidiosis, immunocompromised or nutritionally deficient patients (alternative therapy): Limited data available:

Infants, Children, and Adolescents: Oral: 25 to 35 mg/kg/day in 2 to 4 divided doses for 14 days as monotherapy or in combination with azithromycin; longer durations (>14 days) may be needed in solid organ transplant recipients. Note: Usual adult dose: 500 mg 4 times daily.

HIV-infected: Adolescents: Oral: 500 mg 4 times daily for 14 to 21 days in combination with optimized antiretroviral therapy, symptomatic treatment, rehydration, and electrolyte replacement . Note: Efficacy data variable; paromomycin is not recommended for infants or children with HIV based on insufficient data

Cutaneous Leishmaniasis, simple cutaneous: Limited data available :

Note: Topical preparations are not commercially available in the US; extemporaneous preparations may be available from compounding pharmacies. Formulations are not equivalent and should not be substituted for each other; efficacy is dependent upon formulation/compounding vehicle used .

Ointment, paromomycin 15% with methylbenzethonium chloride (MBCL) 12%: Children and Adolescents: Topical: Apply ointment twice daily for 10 days, rest for 10 days (do not apply), then repeat twice daily application for 10 days.

Cream, paromomycin 15% with gentamicin 0.5% : Children and Adolescents: Topical: Apply cream once daily for 20 days.

Dientamoeba fragilis infection: Limited data available: Infants, Children, and Adolescents: Oral: 25 to 35 mg/kg/day in divided doses 3 times daily for 7 days.

Giardiasis (alternative therapy): Limited data available: Infants, Children, and Adolescents: Oral: 25 to 30 mg/kg/day in divided doses 3 times daily for 5 to 10 days; maximum daily dose: 1,500 mg/day.

Intestinal amebiasis (Entamoeba histolytica): Infants, Children, and Adolescents: Oral: 25 to 35 mg/kg/day in divided doses 3 times daily for 5 to 10 days; usual duration 7 days.

Bioavailability may be increased with food.

The dietary restriction should be individualized as per patient requirements.

Hypersensitivity to paromomycin or any component of the formulation; intestinal obstruction

Documentation of allergenic cross-reactivity for aminoglycosides is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

The treating physician must closely monitor the patient and keep pharmacovigilance as follows

Concerns related to adverse effects:

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Renal impairment: Use with caution in patients with renal impairment.

• Ulcerative bowel lesions: Use with caution in patients with ulcerative bowel lesions; may lead to renal toxicity due to inadvertent absorption.

Other warnings/precautions:

• Appropriate use: Use in the absence of proven (or strongly suspected) susceptible infection is unlikely to provide benefit and may increase the risk for drug-resistance.

May enhance the sedative effect of alcohol.

When used orally, paromomycin is poorly absorbed. According to the available data, paromomycin may be used in nursing women if both the mother's and the infant's renal function is normal.

Bioavailability may be increased with food.

The adverse reactions related to Paromomycin can be categorized as

• Common

Ototoxicity, Anorexia, Nausea, Vomiting, Epigastric Burning and Pain, Increased GI Motility, Abdominal Cramps, Diarrhea.

• Less Common

Pruritus Ani, Hypocholesterolemia, Malabsorption of Xylose and Sucrose, Abnormal Fat Metabolism, Headache

• Rare

Pseudomembranous Colitis, Nephrotoxicity, Neuromuscular Blockade.

The common side of Paromomycin include the following:

Ototoxicity, Anorexia, Nausea, Vomiting, Epigastric Burning and Pain, Increased GI Motility, Abdominal Cramps, Diarrhea.

Pharmacodynamics

Paromomycin inhibits protein synthesis by binding to 16S ribosomal RNA. Bacterial proteins are synthesized by ribosomal RNA complexes which are composed of 2 subunits, a large subunit (50s) and small (30s) subunit, which forms a 70s ribosomal subunit. tRNA binds to the top of this ribosomal structure. Paramomycin binds to the A site, which causes defective polypeptide chains to be produced. Continuous production of defective proteins eventually leads to bacterial death.

Pharmacokinetics

Absorption Poorly absorbed from the GI tract.

Excretion: Via faeces (approx 100% of the dose, as unchanged drug); via urine (approx 0.1%).

1. https://www.uptodate.com/contents/Paromomycin -drug-information?search=Paromomycin &source=panel_search_result&selectedTitle=1~148&usage_type=panel&kp_tab=drug_general&display_rank=1#F23890541
2. https://www.mims.com/india/drug/info/Paromomycin ?type=full
3. https://www.ncbi.nlm.nih.gov/books/NBK537225/
4. https://go.drugbank.com/drugs/DB00321
5. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/071297s030lbl.pdf