Paromomycin

Overview

Paromomycin is an antimicrobial used to treat a number of parasitic infections including amebiasis, giardiasis, leishmaniasis, and tapeworm infection. It is a first-line treatment for amebiasis or giardiasis during pregnancy. Otherwise, it is generally a second line treatment option. It is taken by mouth, applied to the skin, or by injection into a muscle.[1] WP

Common side effects when taken by mouth include loss of appetite, vomiting, abdominal pain, and diarrhea. When applied to the skin side effects include itchiness, redness, and blisters. When given by injection there may be fever, liver problems, or hearing loss. Use during breastfeeding appears to be safe. Paromomycin is in the aminoglycoside family of medications and causes microbe death by stopping the creation of bacterial proteins.[1][2] WP

Paromomycin was discovered in the 1950s from a type of streptomyces and came into medical use in 1960. It is on the World Health Organization's List of Essential Medicines. Paromomycin is available as a generic medication.[2–6] WP

Uses, dosage and effects

Medical uses

It is an antimicrobial used to treat intestinal parasitic infections such as cryptosporidiosis and amoebiasis, and other diseases such as leishmaniasis. Paromomycin was demonstrated to be effective against cutaneous leishmaniasis in clinical studies in the USSR in the 1960s, and in trials with visceral leishmaniasis in the early 1990s.[7–10] WP

The route of administration is intramuscular injection and capsule. Paromomycin topical cream with or without gentamicin is an effective treatment for ulcerative cutaneous leishmaniasis, according to the results of a phase-3, randomized, double-blind, parallel group–controlled trial.[11] WP

Pregnancy and breastfeeding

The medication is poorly absorbed. The effect it may have on the baby is still unknown.[12][13] WP

There is limited data regarding the safety of taking paromomycin while breastfeeding but because the drug is poorly absorbed minimal amounts of drug will be secreted in breastmilk.[14] WP

HIV/aids

There is limited evidence that paromomycin can be used in persons coinfected with HIV and Cryptosporidium. A few small trials have shown a reduction in oocyst shedding after treatment with paromomycin.[15] WP

Risks and side effects

Adverse effects

The most common adverse effects associated with paromomycin sulfate are abdominal cramps, diarrhea, heartburn, nausea, and vomiting. Long-term use of paromomycin increases the risk for bacterial or fungal infection. Signs of overgrowth include white patches in the oral cavities. Other less common adverse events include myasthenia gravis, kidney damage, enterocolitis, malabsorption syndrome, eosinophilia, headache, hearing loss, ringing in the ear, itching, severe dizziness, and pancreatitis.[16] WP

Interactions

Interactions

Paromomycin belongs to the aminoglycoside drug class and therefore are toxic to the kidneys and to ears. These toxicities are additive and are more likely to occur when used with other drugs that cause ear and kidney toxicity. Concurrent use of foscarnet increases the risk of kidney toxicity. Concurrent use of colistimethate and paromomycin can cause a dangerous slowing of breathing known as respiratory depression, and should be done with extreme caution if necessary. When used with systemic antibiotics such as paromomycin, the cholera vaccine can cause an immune response. Use with strong diuretics, which can also harm hearing, should be avoided. Paromomycin may have dangerous reactions when used with the paralytic succinylcholine by increasing its neuromuscular effects.[15][17][18][19] WP

There are no known food or drink interactions with paromomycin.[17] WP

Pharmacology

Mechanism

Paromomycin is a protein synthesis inhibitor in nonresistant cells by binding to 16S ribosomal RNA. This broad-spectrum antibiotic soluble in water, is very similar in action to neomycin. Antimicrobial activity of paromomycin against Escherichia coli and Staphylococcus aureus has been shown. Paromomycin works as an antibiotic by increasing the error rate in ribosomal translation. Paromomycin binds to an RNA loop, where residues A1492 and A1493 are usually stacked, and expels these two residues. These two residues are involved in detection of correct Watson-Crick pairing between the codon and anti codon. When correct interactions are achieved, the binding provides energy to expel the two residues. Paromomycin binding provides enough energy for residue expulsion and thus results in the ribosome incorporating the incorrect amino acid into the nascent peptide chain. Recent real-time measurements of aminoglycoside effects on protein synthesis in live E. coli cells found that paromomycin's interference with protein synthesis is not only due to the misreading of mRNA but also due to a significant reduction in the overall protein elongation rate, suggesting a more comprehensive inhibition of protein synthesis.[20–23] WP

Absorption

GI absorption is poor. Any obstructions or factors which impair GI motility may increase the absorption of the drug from the digestive tract. In addition, any structural damage, such as lesions or ulcerations, will tend to increase drug absorption.[24] WP

For intramuscular (IM) injection, the absorption is rapid. Paromomycin will reach peak plasma concentration within one hour following IM injection. The in-vitro and in-vivo activities parallel those of neomycin.[1][25] WP⚠ A word may be missing here. It reads this way in the source too.

Elimination

Almost 100% of the oral dose is eliminated unchanged via feces. Any absorbed drug will be excreted in urine.[26] WP

History

History

Paromomycin was discovered in the 1950s amongst the secondary metabolites of a variety of Streptomyces then known as Streptomyces krestomuceticus, now known as Streptomyces rimosus. It came into medical use in 1960.[2][3] WP

Chemistry

Formula

C23H47N5O18S PC

Formula (Wikipedia infobox)

C23H45N5O14 WP⚠ Wikipedia and PubChem give different formulas. Both are shown as each source has it.

CAS number

1263-89-4 PC

Molar mass (g/mol)

713.7 PC

IUPAC name (computed by PubChem)

(2S,3S,4R,5R,6R)-5-amino-2-(aminomethyl)-6-[(2R,3S,4R,5S)-5-[(1R,2R,3S,5R,6S)-3,5-diamino-2-[(2S,3R,4R,5S,6R)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]oxyoxane-3,4-diol;sulfuric acid PC

SMILES

C1[C@H]([C@@H]([C@H]([C@@H]([C@H]1N)O[C@@H]2[C@@H]([C@H]([C@@H]([C@H](O2)CO)O)O)N)O[C@H]3[C@@H]([C@@H]([C@H](O3)CO)O[C@@H]4[C@@H]([C@H]([C@@H]([C@@H](O4)CN)O)O)N)O)O)N.OS(=O)(=O)O PC

InChIKey

LJRDOKAZOAKLDU-UDXJMMFXSA-N PC

PubChem CID

441375

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Other Paromomycin Sulfate
2. Journal / agency Davidson RN, den Boer M, Ritmeijer K. Paromomycin. Transactions of the Royal Society of Tropical Medicine and Hygiene. July 2009. doi:10.1016/j.trstmh.2008.09.008 · PMID 18947845
3. Other Pharmaceutical Manufacturing Encyclopedia. 2013
4. Other Organization WH. World Health Organization model list of essential medicines: 21st list 2019. 2019
5. Other Organization WH. World Health Organization model list of essential medicines: 22nd list (2021). 2021
6. Other Hamilton R. Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. 2015
7. Other Martindale: The Complete Drug Reference. 2002
8. Other DorlandsDict six/000078796 paromomycin
9. Journal / agency Sundar S, Jha TK, Thakur CP, Sinha PK, Bhattacharya SK. Injectable paromomycin for Visceral leishmaniasis in India. The New England Journal of Medicine. June 2007. doi:10.1056/NEJMoa066536 · PMID 17582067
10. Journal / agency Neal RA, Murphy AG, Olliaro P, Croft SL. Aminosidine ointments for the treatment of experimental cutaneous leishmaniasis. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1994. doi:10.1016/0035-9203(94)90307-7 · PMID 8036682
11. Journal / agency Ben Salah A, Ben Messaoud N, Guedri E, Zaatour A, Ben Alaya N, Bettaieb J, Gharbi A, Belhadj Hamida N, Boukthir A, Chlif S, Abdelhamid K, El Ahmadi Z, Louzir H, Mokni M, Morizot G, Buffet P, Smith PL, Kopydlowski KM, Kreishman-Deitrick M, Smith KS, Nielsen CJ, Ullman DR, Norwood JA, Thorne GD, McCarthy WF, Adams RC, Rice RM, Tang D, Berman J, Ransom J, Magill AJ, Grogl M. Topical paromomycin with or without gentamicin for cutaneous leishmaniasis. The New England Journal of Medicine. February 2013. doi:10.1056/NEJMoa1202657 · PMID 23388004
12. Other Sweet RL, Gibbs RS. Infectious Diseases of the Female Genital Tract. 2009
13. Other Handbook of Antimicrobial Therapy. 2015
14. Other Paromomycin Use During Pregnancy
15. Other Bennett JE, Blaser MJ, Dolin R. Mandell, Douglas, and Bennett's principles and practice of infectious diseases. 2015
16. Other paromomycin oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD
17. Other Micromedex
18. Other Kucers' the use of antibiotics a clinical review of antibacterial, antifungal, antiparasitic and antiviral drugs. 2012
19. Other Aschenbrenner DS. Drug therapy in nursing. 2008
20. Journal / agency Vicens Q, Westhof E. Crystal structure of paromomycin docked into the eubacterial ribosomal decoding A site. Structure. August 2001. doi:10.1016/S0969-2126(01)00629-3 · PMID 11587639
21. Other Paromomycin. 2010-01-12
22. Other Voet D, Voet JG. Biochemistry. 2011
23. Journal / agency Aguirre Rivera J, Larsson J, Volkov IL, Seefeldt AC, Sanyal S, Johansson M. Real-time measurements of aminoglycoside effects on protein synthesis in live cells. Proceedings of the National Academy of Sciences of the United States of America. March 2021. doi:10.1073/pnas.2013315118 · PMID 33619089 · PMC7936356
24. Other Paromomycin sulfate capsules, USP prescribing information. March 1997
25. Harm reduction site Paromomycin. 2016-08-17
26. Journal / agency Iwaki S, Honke K, Nishida N, Taniguchi N. The absorption, excretion and influence on bowel flora of oral paromomycin sulfate (author's transl). The Japanese Journal of Antibiotics. July 1981. PMID 7321186

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.