Pentavalent Antimonials Combined with Other Therapeutic Alternatives for the Treatment of Cutaneous and Mucocutaneous Leishmaniasis: A Systematic Review

Table 3

Description of adverse effects of combinations for the treatment of tegumentary leishmaniasis.

Treatment	Side effects	Study source
MA + IM	Localized pruritus, erythema and edema (77%); arthralgia, myalgia, flu-like symptoms (86%); and elevated liver enzyme levels (64%).	Arevalo et al., 2007
	Moderate pruritus and burning sensation (7.1%).	Firooz et al., 2006
	Edema (35%); itching (10%); burning (15%); pain (5%); erythema (55%).	Miranda-Verastegui et al., 2005
MA + PE	Nausea (27.3%); arthralgias (9.1%); dizziness, abdominal pain, and diarrhea (9.1%).	Machado et al., 2007
	Vomiting (2.4%); Diarrhea (1.2%); Nausea (8.6%); Headache (11%); Asthenia (3.7%); Anorexia (3.7%); Epigastralgia (3.7%); Pain (2.4%); Dizziness (2.4%); Fever (7.4%); Arthralgia (8.6%); Myalgia (13.5%)	Brito et al., 2017
MA + cryotherapy	No adverse effects were observed	Farajzadeh et al., 2015
MA + (LEISH-F1 + MPL-SE)	Local: induration (44.4 – 77.8%); erythema (11.1 – 100%); tenderness (33.3-44.4%).; Systemic: headache (0-22.2%); pyrexia (0-22.2%).; MA-related AEs (22.2 – 88.9%).	Nascimento et al., 2010
MA + GM-CSF	No adverse effects were observed	Almeida et al., 2005
MA + OM	NR	Nilforoushzadeh et al., 2008
il MA + silver PD	Itching and burning (35.3%); edema (33.3%).	Khatami et al., 2013
il MA + topical honey	Dermatitis to honey (3%).	Nilforoushzadeh et al., 2007
il MA + cryotherapy	Hyper pigmentation+trivial scar (18.7%); atrophic scar (7.5%); hypo pigmentation+trivial scar (18.8%).	Meymandi et al., 2011
SSG + (LEISH-F1 + MPL-SE)	Local: induration (41.7 – 75.0%); erythema (50.0 – 100.0%); tenderness (66.7 – 91.7%).; Systemic: anorexia (0 – 8.3%); fatigue (0 – 8.3%); malaise (25.0%); myalgia (0 – 8.3%); headache (33.3 – 50.0%).; SSG-related (100%).	Llanos Cuentas et al., 2010
SSG + IM	Swelling (30%); itching (25%); pain (12.5%); erythema (32.5%).	Miranda-Verastegui et al., 2009
il SSG + im SSG	im SSG: Pain at the injection site (100%).; il SSG: Pain and swelling at the intralesional injection site (100%).	El-Sayed & Anwar, 2010
il SSG + KE	KE: No.; il SSG: Pain and swelling at the intralesional injection site (100%).	El-Sayed & Anwar, 2010
il SSG + cryotherapy	Secondary infection (31%); lymphatic involvement (48.8%); pain at the injection site	Van Thiel et al., 2010

NR, not reported; G1, Group 1; G2, Group 2; G3, Group 3. MA, meglumine antimoniate; PE, pentoxifylline; GM-CSF, granulocyte macrophage colony-stimulating factor; IM, imiquimod; il SSG, intralesional sodium stibugluconate; im SSG, intramuscular sodium stibugluconate; KE, ketoconazole; il MA (intralesional meglumine antimoniate); non-silver PD, non-silver containing polyester dressing; silver PD, silver containing polyester dressing; SSG, sodium stibugluconate; LEISH-F1, lyophilized LEISH-F1 protein; MPL-SE, adjuvant; OM, omeprazole; AEs, adverse events.