Paromomycin Sulfate

(rINNM)
Synonyms: Aminosidin Sulphate; Aminosidine Sulphate; Catenulin Sulphate; Crestomycin Sulphate; Estomycin Sulphate; Hydroxymycin Sulphate; Monomycin A Sulphate; Neomycin E Sulphate; Paromomycin Sulphate ni Sulfas; Paucimycin Sulphate; Sulfato de paromomicina. O-2,6Diamino-2,6-dideoxyosyl-(1→5)O-[2-amino-2-deoxy2-deoxystreptamine sulphate.
Cyrillic synonym: Паромомицина Сульфат.

💊 Chemical information

Chemical formula: C23H45N5O14,xH2SO4.
CAS — 59-04-1 (paromomycin); 7542-37-2 (paromomycin); 1263-89-4 (paromomycin sulfate).
ATC — A07AA06.
ATC Vet — QA07AA06.

Pharmacopoeias.

In Chin., Int., It., and US.

USP 31

(Paromomycin Sulfate). The sulfate salt of an antibiotic substance produced by the growth of Streptomyces rimosus var. paromomycinus, or a mixture of two or more such salts. A creamy-white to light yellow, odourless or practically odourless, very hygroscopic powder. It loses not more than 5% of its weight on drying. Very soluble in water; insoluble in alcohol, in chloroform, and in ether. pH of a 3% solution in water is between 5.0 and 7.5. Store in airtight containers.

💊 Adverse Effects, Treatment, and Precautions

As for Neomycin.

Effects on the pancreas.

Pancreatitis was associated with use of paromomycin during treatment of cryptosporidiosis in a patient with HIV infection.1
1. Tan WW, et al. Paromomycin-associated pancreatitis in HIV-related cryptosporidiosis. Ann Pharmacother 1995; 29: 22–4.

💊 Interactions

As for Neomycin.

💊 Antimicrobial Action

Paromomycin is active against various protozoa including Leishmania spp., Entamoeba histolytica, and Cryptosporidium spp. In addition, it has an antibacterial spectrum similar to that of neomycin. There is cross-resistance between paromomycin and kanamycin, framycetin, neomycin, and streptomycin. Paromomycin also has anthelmintic properties against tapeworms.

Antimycobacterial activity.

References.
1. Kanyok TP, et al. Activity of aminosidine (paromomycin) for Mycobacterium tuberculosis and Mycobacterium avium. J Antimicrob Chemother 1994; 33: 323–7
2. Piersimoni C, et al. Bacteriostatic and bactericidal activities of paromomycin against Mycobacterium avium complex isolates. J Antimicrob Chemother 1994; 34: 421–4
3. Kanyok TP, et al. In vivo activity of paromomycin against susceptible and multidrug-resistant Mycobacterium tuberculosis and M. avium complex strains. Antimicrob Agents Chemother 1994; 38: 170–3.

💊 Pharmacokinetics

Paromomycin is poorly absorbed from the gastrointestinal tract and most of the dose is eliminated unchanged in the faeces.

Parenteral administration.

References.
1. Kanyok TP, et al. Pharmacokinetics of intramuscularly administered aminosidine in healthy subjects. Antimicrob Agents Chemother 1997; 41: 982–6.

💊 Uses and Administration

Paromomycin is an aminoglycoside antibiotic that has been given orally in the treatment of intestinal protozoal infections, including amoebiasis, cryptosporidiosis, and giardiasis. It has also been tried parenterally for visceral, and topically for cutaneous, leishmaniasis. For details of these infections and their treatment, see under Choice of Antiprotozoal. It has been used in the treatment of tapeworm infection, but it is not the treatment of choice. Like neomycin, it has been used in the suppression of intestinal flora both pre-operatively and in the management of hepatic encephalopathy. Paromomycin is given as the sulfate although doses are expressed in terms of the base. In intestinal amoebiasis, the dose for both adults and children is the equivalent of paromomycin 25 to 35 mg/kg daily in 3 divided oral doses with meals for 5 to 10 days. Similar doses have been tried in cryptosporidiosis. In taeniasis and other tapeworm infections, a dose of 4 g is given orally as a single dose or in divided doses over the course of one hour. For hepatic coma, 4 g is given daily in divided oral doses at regular intervals for 5 to 6 days.

Leishmaniasis.

Topical treatment with paromomycin 15% plus methylbenzethonium chloride 5 or 12% has produced promising results1-3 in cutaneous leishmaniasis; paromomycin 12 to 15% with urea 10% was better tolerated.4 However, benefit has not been seen in all studies.5,6 Treatment with topical paromomycin plus systemic meglumine antimonate was initially promising in patients with New World cutaneous leishmaniasis;7however, a subsequent study8 found no clear advantage over treatment with meglumine antimonate alone. Good responses to parenteral paromomycin 14 mg/kg daily, with sodium stibogluconate 10 mg/kg daily, in cases of diffuse cutaneous leishmaniasis have also been reported.9 Paromomycin has also been used intramuscularly, either alone10or with sodium stibogluconate,11 in the treatment of visceral leishmaniasis in an area of India with increasing resistance to pentavalent antimony compounds. The authors of one study10found paromomycin 16 or 20 mg/kg daily for 21 days to be significantly more effective than sodium stibogluconate 20 mg/kg daily for 30 days and suggested that paromomycin be considered as first-line treatment for visceral leishmaniasis in this region. Oral paromomycin plus intravenous pentamidine was reported to be effective in the treatment of amphotericin-resistant visceral leishmaniasis in an HIV-infected patient.12
1. El-On J, et al. Topical treatment of Old World cutaneous leishmaniasis caused by Leishmania major: a double-blind control study. J Am Acad Dermatol 1992; 27: 227–31
2. Krause G, Kroeger A. Topical treatment of American cutaneous leishmaniasis with paromomycin and methylbenzethonium chloride: a clinical study under field conditions in Ecuador. Trans R Soc Trop Med Hyg 1994; 88: 92–4
3. Arana BA, et al. Randomized, controlled, double-blind trial of topical treatment of cutaneous leishmaniasis with paromomycin plus methylbenzethonium chloride ointment in Guatemala. Am J Trop Med Hyg 2001; 65: 466–70
4. Bryceson ADM, et al. Treatment of Old World cutaneous leishmaniasis with aminosidine ointment: results of an open study in London. Trans R Soc Trop Med Hyg 1994; 88: 226–8
5. Ben Salah A, et al. A randomized, placebo-controlled trial in Tunisia treating cutaneous leishmaniasis with paromomycin ointment. Am J Trop Med Hyg 1995; 53: 162–6
6. Asilian A, et al. A randomized, placebo-controlled trial of a two week regimen of aminosidine (paromomycin) ointment for treatment of cutaneous leishmaniasis in Iran. Am J Trop Med Hyg 1995; 53: 648–51
7. Soto J, et al. Successful treatment of New World cutaneous leishmaniasis with a combination of topical paromomycin/methylbenzethonium chloride and injectable meglumine antimonate. Clin Infect Dis 1995; 20: 47–51
8. Soto J, et al. Topical paromomycin/methylbenzethonium chloride plus parenteral meglumine antimonate as treatment for American cutaneous leishmaniasis: controlled study. Clin Infect Dis 1998; 26: 56–8
9. Teklemariam S, et al. Aminosidine and its combination with sodium stibogluconate in the treatment of diffuse cutaneous leishmaniasis caused by Leishmania aethiopica. Trans R Soc Trop Med Hyg 1994; 88: 334–9
10. Jha TK, et al. Randomised controlled trial of aminosidine (paromomycin) v sodium stibogluconate for treating visceral leishmaniasis in North Bihar, India. BMJ 1998; 316: 1200–5
11. Thakur CP, et al. A prospective randomized, comparative, openlabel trial of the safety and efficacy of paromomycin (aminosidine) plus sodium stibogluconate versus sodium stibogluconate alone for the treatment of visceral leishmaniasis. Trans R Soc Trop Med Hyg 2000; 94: 429–31
12. Manfredi R, et al. Diffuse cutaneous dissemination of visceral leishmaniasis during human immunodeficiency virus (HIV) infection, despite negligible immunodeficiency: repeated failure of liposomal amphotericin B administration, followed by successful long-term pentamidine and paromomycin administration. Int J Antimicrob Agents 2008; 31: 590–2.

Tr i ch o mo n i as i s.

Local application of a paromomycin cream has been tried in a small number of patients with metronidazoleresistant vaginal trichomoniasis with moderate success.1
1. Nyirjesy P, et al. Difficult-to-treat trichomoniasis: results with paromomycin cream. Clin Infect Dis 1998; 26: 986–8.

💊 Preparations

USP 31: Paromomycin Sulfate Capsules; Paromomycin Sulfate Syrup.

Proprietary Preparations

Austria: Humatin; Belg.: Gabbroral; Canad.: Humatin; Ger.: Humatin; Indon.: Gabbryl; Ital.: Gabbroral; Humatin; Kaman; Spain: Humatin; Switz.: Humatin; USA: Humatin. Multi-ingredient: Israel: Leshcutan.
Published December 14, 2018.