Paromomycin
Regulatory sources consulted
Approved indications
- Treatment of acute and chronic non-invasive intestinal amoebiasis in children and adults.
- Treatment and prophylaxis of portosystemic encephalopathy in adults.
Contraindications
Absolute
- Hypersensitivity to paromomycin, other aminoglycosides or excipients; constipation, paralytic ileus or intestinal obstruction; prior vestibular or cochlear injury; myasthenia gravis; pregnancy and breastfeeding.
Clinical warnings
- Major warning · Although oral absorption is usually minimal, ulcerative gastrointestinal lesions may increase it and raise nephrotoxicity and ototoxicity risk; monitor renal and auditory function. — AEMPS CIMA, Humatin, ficha técnica 36795, sección 4.4
- Major warning · Aminoglycosides may cause neuromuscular blockade; use with caution in muscular disorders and with neuromuscular blockers or anaesthetics. — AEMPS CIMA, Humatin, ficha técnica 36795, sección 4.4
Drug interactions
- ModerateMethotrexate
Mechanism: Paromomycin may significantly reduce methotrexate absorption.
Recommendation: Avoid or closely monitor methotrexate efficacy.
https://cima.aemps.es/cima/dochtml/ft/36795/FT_36795.html
- HighNephrotoxic or ototoxic medicines
Mechanism: Additive nephrotoxicity and ototoxicity may occur.
Recommendation: Avoid concomitant use where possible; monitor renal and auditory function if unavoidable.
https://cima.aemps.es/cima/dochtml/ft/36795/FT_36795.html
- HighNeuromuscular blockers and anaesthetics
Mechanism: Aminoglycosides can potentiate neuromuscular blockade.
Recommendation: Avoid or use with close respiratory and neuromuscular monitoring.
https://cima.aemps.es/cima/dochtml/ft/36795/FT_36795.html
Adverse events
Common (≥1%)
Soft stools · Diarrhoea · Nausea · Abdominal pain
Rare but serious
Nephrotoxicity · Ototoxicity · Neuromuscular blockade · Pancreatitis
Pregnancy and lactation
Do not use during pregnancy or breastfeeding. Aminoglycosides cross the placenta and embryotoxicity or teratogenicity cannot be excluded; there are no milk-excretion data for paromomycin.
Recent literature (PubMed)
Amoebiasis, caused by Entamoeba histolytica, remains a major public health issue, particularly in developing countries with poor sanitation. It is also a significant challenge among those who travel to endemic areas, causing, in many cases, so-called traveler diarrhea. Approximately 10 percent of the global population is estimated to be affected by this parasitic infection. The primary route of transmission is the consumption of food or water contaminated with E. histolytica cysts. While most infected individuals may remain asymptomatic, some develop severe complications, including hemorrhagic colitis, liver abscesses, and, in extreme cases, colonic perforation. It has been estimated that amoebiasis is responsible for nearly 100,000 deaths annually. Standard treatment for amoebic colitis involves a combination of luminal agents (such as paromomycin, diloxanide furoate, and diiodohydroxyquin) and tissue amoebicides (including metronidazole and tinidazole). Although these treatments are effective, new therapeutic options to improve patient outcomes are needed. One promising avenue for drug discovery is the β-carbonic anhydrase enzyme (EhiCA) of E. histolytica, which has emerged as a potential target for novel antiamoebic therapies. EhiCA was recently produced as a recombinant protein and has been used in kinetic and inhibition studies with various sulfonamides and anions, with promising results.
Over the past 20 years, significant progress has been made in anti-leishmanial therapy. Three new drugs/formulations are available for the treatment of various forms of leishmaniasis, namely oral miltefosine, paromomycin and liposomal amphotericin B. However, these advances in drug development have added considerable complexity for clinicians including toxicity, emergence of resistance and decreased sensitivity of available drugs. The development of newer drugs with less toxicity and more efficacy is urgently needed. This review comprehensively examines the latest developments and current status of antileishmanial drugs for the treatment of leishmaniasis across the world. Several new investigational drugs that showed anti-leishmanial activity under in vitro or in vivo conditions and either underwent the phase-I/II clinical trials or are on the verge of entering the trials were reviewed. We also delve into the challenges of drug resistance and discuss the emergence of new and effective antileishmanial compounds. The available treatments for leishmaniasis are limited in number, toxic, expensive, and demand extensive healthcare resources. Every available antileishmanial drug is associated with several disadvantages, such as drug resistance and toxicity or high cost. Miltefosine is potentially teratogenic. New antileishmanial drugs/treatment modalities are sorely needed for expanding future treatment options.
Despite their clinical importance, saving numerous human lifes, over- and mis-uses of antibiotics have created a strong selective pressure on bacteria, which induces the emergence of (multi)resistant strains. Antibioresistance is becoming so pregnant that since 2017, WHO lists bacteria threatening most human health (AWaRe, ESKAPE lists), and those for which new antibiotics are urgently needed. Since the century turn, this context is leading to a burst in the chemical synthesis of new antibiotics, mostly derived from natural antibiotics. Among them, aminoglycosides, and especially the neomycin family, exhibit broad spectrum of activity and remain clinically useful drugs. Therefore, numerous endeavours have been undertaken to modify aminoglycosides with the aim of overcoming bacterial resistances. After having replaced antibiotic discovery into an historical perspective, briefly surveyed the aminoglycoside mode of action and the associated resistance mechanisms, this review emphasized the chemical syntheses performed on the neomycin family and the corresponding structure activity relationships in order to reveal the really efficient modifications able to convert neomycin and its analogues into future drugs. This review would help researchers to strategically design novel aminoglycoside derivatives for the development of clinically viable drug candidates.
Dientamoeba fragilis is a protozoan of the gastrointestinal tract, very prevalent in our environment and responsible for diverse clinical symptoms mainly abdominal pain, diarrhoea and eosinophilia, although some infected patients are asymptomatic. Since the first description just a century ago, there are many unanswered questions: its different morphologies and the role of each of them, its actual prevalence, the mode of transmission, its pathogenicity, or the treatment of choice, continue to be source of controversy. Risk factors associated with infection by D. fragilis are: contact with children, residence in a rural area, and co-infection by Enterobius vermicularis. New molecular diagnostic techniques in the form of commercial multi-diagnostic panels are now considered first choice techniques. Paromomycin show higher cure rates, than metronidazole.