Paromomycin is an antimicrobial used to treat a number of parasitic infections including amebiasis, giardiasis, leishmaniasis, and tapeworm infection.[3] It is a first-line treatment for amebiasis or giardiasis during pregnancy.[3] Otherwise, it is generally a second line treatment option.[3] It is taken by mouth, applied to the skin, or by injection into a muscle.[3]

Paromomycin
Clinical data
Trade namesCatenulin, Aminosidine, Humatin, others[1]
Other namesmonomycin, aminosidine[2]
AHFS/Drugs.comMonograph
MedlinePlusa601098
License data
Pregnancy
category
  • C
Routes of
administration
By mouth, intramuscular, topical[3]
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityPoorly absorbed in the GI tract
MetabolismNot available
ExcretionFecal
Identifiers
  • (2R,3S,4R,5R,6S)-5-amino-6-[(1R,2S,3S,4R,6S)-
    4,6-diamino-2-[(2S,3R,4R,5R)-4-[(2R,3R,4R,5R,6S)-
    3-amino-6-(aminomethyl)-4,5-dihydroxy-oxan-2-yl]
    oxy-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-
    3-hydroxy-cyclohexyl]oxy-2-(hydroxymethyl)oxane-3,4-diol
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.028.567 Edit this at Wikidata
Chemical and physical data
FormulaC23H47N5O18S
Molar mass713.71 g·mol−1
3D model (JSmol)
  • O=S(=O)(O)O.O([C@H]3[C@H](O[C@@H]2O[C@H](CO)[C@@H](O[C@H]1O[C@@H](CN)[C@@H](O)[C@H](O)[C@H]1N)[C@H]2O)[C@@H](O)[C@H](N)C[C@@H]3N)[C@H]4O[C@@H]([C@@H](O)[C@H](O)[C@H]4N)CO
  • InChI=1S/C23H45N5O14.H2O4S/c24-2-7-13(32)15(34)10(27)21(37-7)41-19-9(4-30)39-23(17(19)36)42-20-12(31)5(25)1-6(26)18(20)40-22-11(28)16(35)14(33)8(3-29)38-22;1-5(2,3)4/h5-23,29-36H,1-4,24-28H2;(H2,1,2,3,4)/t5-,6+,7+,8-,9-,10-,11-,12+,13-,14-,15-,16-,17-,18-,19-,20-,21-,22-,23+;/m1./s1 checkY
  • Key:LJRDOKAZOAKLDU-UDXJMMFXSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Common side effects when taken by mouth include loss of appetite, vomiting, abdominal pain, and diarrhea.[3] When applied to the skin side effects include itchiness, redness, and blisters.[3] When given by injection there may be fever, liver problems, or hearing loss.[3] Use during breastfeeding appears to be safe.[4] Paromomycin is in the aminoglycoside family of medications and causes microbe death by stopping the creation of bacterial proteins.[3]

Paromomycin was discovered in the 1950s from a type of streptomyces and came into medical use in 1960.[1][4] It is on the World Health Organization's List of Essential Medicines.[5][6] Paromomycin is available as a generic medication.[7]

Medical uses

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It is an antimicrobial used to treat intestinal parasitic infections such as cryptosporidiosis[8] and amoebiasis,[9] and other diseases such as leishmaniasis.[10] 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.[2]

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]

Pregnancy and breastfeeding

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

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]

HIV/AIDS

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

Adverse effects

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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]

Interactions

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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.[15] Concurrent use of foscarnet increases the risk of kidney toxicity.[17] 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.[17] When used with systemic antibiotics such as paromomycin, the cholera vaccine can cause an immune response.[17] Use with strong diuretics, which can also harm hearing, should be avoided.[18] Paromomycin may have dangerous reactions when used with the paralytic succinylcholine by increasing its neuromuscular effects.[19]

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

Mechanism

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Paromomycin is a protein synthesis inhibitor in nonresistant cells by binding to 16S ribosomal RNA.[20] 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.[21] Paromomycin works as an antibiotic by increasing the error rate in ribosomal translation. Paromomycin binds to a 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.[22] 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.[23]

Pharmacokinetics

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Absorption

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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]

For intramuscular (IM) injection, the absorption is rapid. Paromomycin will reach peak plasma concentration within one hour following IM injection.[3] The in-vitro and in-vivo activities parallel those of neomycin.[25]

Elimination

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

History

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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.[1][4]

References

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  1. ^ a b c "Paromomycin". Pharmaceutical Manufacturing Encyclopedia (3rd ed.). Elsevier. 2013. p. 21p. ISBN 978-0-8155-1856-3. Archived from the original on 20 December 2016.
  2. ^ a b Neal RA, Murphy AG, Olliaro P, Croft SL (1994). "Aminosidine ointments for the treatment of experimental cutaneous leishmaniasis". Transactions of the Royal Society of Tropical Medicine and Hygiene. 88 (2): 223–225. doi:10.1016/0035-9203(94)90307-7. PMID 8036682.
  3. ^ a b c d e f g h i j "Paromomycin Sulfate". The American Society of Health-System Pharmacists. Archived from the original on 17 November 2016. Retrieved 3 December 2016.
  4. ^ a b c Davidson RN, den Boer M, Ritmeijer K (July 2009). "Paromomycin". Transactions of the Royal Society of Tropical Medicine and Hygiene. 103 (7): 653–660. doi:10.1016/j.trstmh.2008.09.008. PMID 18947845.
  5. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  6. ^ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
  7. ^ Hamilton R (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 54. ISBN 978-1-284-05756-0.
  8. ^ Sweetman S, ed. (2002). Martindale: The Complete Drug Reference (33rd ed.). London: Pharmaceutical Press. ISBN 978-0-85369-499-1.
  9. ^ "paromomycin" at Dorland's Medical Dictionary
  10. ^ Sundar S, Jha TK, Thakur CP, Sinha PK, Bhattacharya SK (June 2007). "Injectable paromomycin for Visceral leishmaniasis in India". The New England Journal of Medicine. 356 (25): 2571–2581. doi:10.1056/NEJMoa066536. PMID 17582067.
  11. ^ Ben Salah A, Ben Messaoud N, Guedri E, Zaatour A, Ben Alaya N, Bettaieb J, et al. (February 2013). "Topical paromomycin with or without gentamicin for cutaneous leishmaniasis". The New England Journal of Medicine. 368 (6): 524–532. doi:10.1056/NEJMoa1202657. PMID 23388004.
  12. ^ Sweet RL, Gibbs RS (2009). "Parasitic Disease in Pregnancy". Infectious Diseases of the Female Genital Tract. Lippincott Williams & Wilkins. p. 364. ISBN 978-0-7817-7815-2. Archived from the original on 7 November 2016.
  13. ^ Abramowicz M, ed. (2015). Handbook of Antimicrobial Therapy. New Rochelle, New York: The Medical Letter. p. 468. ISBN 978-0-9815278-8-8.
  14. ^ "Paromomycin Use During Pregnancy". Drugs.com. Archived from the original on 10 November 2016. Retrieved 10 November 2016.
  15. ^ a b Bennett JE, Blaser MJ, Dolin R (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases (Eighth ed.). Philadelphia, PA: Saunders. ISBN 978-1-4557-4801-3.
  16. ^ "paromomycin oral : Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD". WebMD. Archived from the original on 10 November 2016. Retrieved 10 November 2016.
  17. ^ a b c d "Micromedex".
  18. ^ Grayson ML, ed. (2012). "Agents Active Against Intestinal and Intra-Abdominal Protozoa: Paromomycin". Kucers' the use of antibiotics a clinical review of antibacterial, antifungal, antiparasitic and antiviral drugs (6th ed.). Boca Raton, FL: CRC Press. p. 2144. ISBN 978-1-4441-4752-0. Archived from the original on 8 September 2017.
  19. ^ Aschenbrenner DS (2008). Drug therapy in nursing. US: Wolters Kluwer Health. ISBN 978-1-60547-270-6.
  20. ^ Vicens Q, Westhof E (August 2001). "Crystal structure of paromomycin docked into the eubacterial ribosomal decoding A site". Structure. 9 (8): 647–658. doi:10.1016/S0969-2126(01)00629-3. PMID 11587639.
  21. ^ "Paromomycin" (PDF). Toku-E. 12 January 2010. Archived from the original (PDF) on 26 April 2014. Retrieved 11 June 2012.
  22. ^ Voet D, Voet JG (2011). "Ribosomes". Biochemistry (4th ed.). New York: John Wiley & Sons Inc. p. 1397. ISBN 978-0-470-57095-1.
  23. ^ Aguirre Rivera J, Larsson J, Volkov IL, Seefeldt AC, Sanyal S, Johansson M (March 2021). "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. 118 (9). Bibcode:2021PNAS..11813315A. doi:10.1073/pnas.2013315118. PMC 7936356. PMID 33619089.
  24. ^ Paromomycin sulfate capsules, USP prescribing information (Report). Detroit, MI: Caraco Pharmaceutical Laboratories. March 1997.
  25. ^ "Paromomycin". DrugBank. 17 August 2016. Archived from the original on 10 November 2016.
  26. ^ Iwaki S, Honke K, Nishida N, Taniguchi N (July 1981). "[The absorption, excretion and influence on bowel flora of oral paromomycin sulfate (author's transl)]". The Japanese Journal of Antibiotics (in Japanese). 34 (7): 1078–81. PMID 7321186.
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