Table 5. Serious and/or Common Adverse Reactions Associated with Systemically Administered Drugs Used to Treat or Prevent Opportunistic Infections

Actualizado 25/09/2023 - 12:00 Reviewed Lun, 25/09/2023 - 12:00

Tables

Table 5. Serious and/or Common Adverse Reactions Associated with Systemically Administered Drugs Used to Treat or Prevent Opportunistic Infections

This table should not be considered a comprehensive list of all possible adverse reactions to each medication. For additional information, clinicians should consult other appropriate resources, such as the U.S. Food and Drug Administration prescribing information. For persons of childbearing potential, please refer to Table 7. Summary of Pre-Clinical and Human Data on, and Indications for, Opportunistic Infection Drugs During Pregnancy for information regarding adverse effect potential of these medications during pregnancy.

Drug(s)	Adverse Reactions
Acyclovir	Crystalluria and nephrotoxicity secondary to obstructive urolithiasis, particularly after rapid high-dose IV infusion. Risk is increased with dehydration or pre-existing renal impairment. Administer IV fluid hydration to reduce the risk for nephrotoxicity. Neurotoxicity with high doses (agitation, confusion, hallucination, seizure, coma), especially in patients with renal impairment and/or older patients Thrombophlebitis at peripheral IV infusion site Nausea, vomiting, and headache
Adefovir	Nephrotoxicity, especially in patients with underlying renal insufficiency, predisposing comorbidities, or taking concomitant nephrotoxic drugs Nausea and asthenia
Albendazole	Hepatotoxicity Reversible alopecia Nausea, vomiting, headache, and dizziness Bone marrow suppression (i.e., pancytopenia, aplastic anemia, agranulocytosis, and leukopenia) (rare) Patients with liver disease, including hepatic echinococcosis, appear to be at higher risk.
Amikacin	Nephrotoxicity Administer IV fluid hydration to reduce the risk for nephrotoxicity. Ototoxicity, both hearing loss and vestibular toxicity, are possible. Neuromuscular blockade, especially with myasthenia or Parkinson’s disease and rapid infusion of large doses (rare)
Amphotericin B Deoxycholate and Lipid Formulations	Nephrotoxicity (lower incidence with liposomal formulations) Administer IV fluid hydration to reduce the risk for nephrotoxicity. Hypokalemia, hypomagnesemia, and hypocalcemia Infusion-related reactions, including fever, chills, rigors, flank or back pain, and hypotension (lower incidence with liposomal formulations) Thrombophlebitis Transaminase and bilirubin elevations Headache, nausea, vomiting, and diarrhea Heart failure (rarely reported) Anemia (rare)
Anidulafungin	Refer to the row on Echinocandins.
Artemether/Lumefantrine	QTc prolongation Fever, chills, fatigue, arthralgia, and myalgia Headache, dizziness, asthenia, and insomnia Nausea, vomiting, diarrhea, abdominal pain, and anorexia Rash and pruritus Delayed hemolytic anemia (rare)
Artesunate	Acute renal failure requiring dialysis Hemoglobinuria and jaundice Post-treatment hemolysis that may require transfusion QTc prolongation and bradycardia Hypersensitivity reactions (anaphylaxis) Dizziness, nausea, and vomiting
Atovaquone	Hepatotoxicity Rash, nausea, vomiting, and diarrhea Fever, headache, and insomnia
Atovaquone/Proguanil	Abdominal pain, nausea, vomiting, anorexia, diarrhea, headache, asthenia, dizziness, and rash Reversible transaminase elevations
Azithromycin	Ototoxicity with prolonged use Hepatotoxicity Hypersensitivity reactions Nausea, vomiting, diarrhea, and abdominal pain QTc prolongation
Benznidazole	Photosensitivity and hypersensitivity reactions (including allergic dermatitis, TEN, and DRESS) Paresthesia and peripheral neuropathy, headache, and insomnia Bone marrow suppression Embryo-fetal toxicity Nausea, vomiting, abdominal pain, anorexia, and weight loss
Bedaquiline	QTc prolongation Hepatotoxicity Nausea, vomiting, anorexia, diarrhea, elevated amylase, arthralgia, headache, and skin rash
Bezlotoxumab	Exacerbation of congestive heart failure Nausea, pyrexia, and headache
Brincidofovir	Elevations in hepatic transaminases and bilirubin Nausea, vomiting, and diarrhea Embryo-fetal toxicity, male infertility
Caspofungin	Refer to the row on Echinocandins.
Chloroquine and Hydroxychloroquine	Auditory and visual disturbances, including blurry vision. Retinal toxicity may occur with long-term use. QTc prolongation Cardiomyopathy Bone marrow suppression and hemolysis Neuropsychiatric changes, including extrapyramidal reactions, suicidal behavior, and convulsive seizures Hypersensitivity reactions (including TEN, SJS, and EM) Severe hypoglycemia which may require adjustment of antidiabetic medications Photosensitivity, pruritus, skin pigmentation, and exacerbation of psoriasis Headache, nausea, vomiting, diarrhea, anorexia, abdominal pain, and hepatitis Neuromyopathy (may occur with long-term use)(rare)
Cidofovir	Nephrotoxicity, proteinuria, azotemia, proximal tubular dysfunction (normoglycemic glycosuria, hypophosphatemia), and metabolic acidosis (including Fanconi’s syndrome) Administer IV fluid hydration and oral probenecid to reduce the risk for nephrotoxicity. Neutropenia and anemia Ocular hypotony and anterior uveitis/iritis Possibly carcinogenic and teratogenic; may cause hypospermia Gastrointestinal intolerance and diarrhea Asthenia, fever, headache, and alopecia Side effects most likely related to co-administration with probenecid are rash, nausea, vomiting, anorexia, and gout exacerbation.
Ciprofloxacin	Refer to the row on Fluoroquinolones.
Clarithromycin	Hepatotoxicity Ototoxicity, including reversible hearing loss and tinnitus, with high doses or prolonged use QTc prolongation Increased risk of cardiac complications or death in patients with heart disease Diarrhea Headache, nausea, vomiting, diarrhea, abdominal cramps, and dysgeusia
Clindamycin	Diarrhea, including C. difficile–associated diarrhea and colitis Metallic taste (with IV infusion), thrombophlebitis, and arrhythmia with rapid IV infusion Hypersensitivity reactions (including SJS and TEN) Nausea, vomiting, abdominal pain, and abnormal liver function tests
Clotrimazole (Troche)	Nausea, vomiting, anorexia, and metallic taste
Cycloserine	Neuropsychiatric toxicities, including convulsions, psychosis, somnolence, confusion, inability to concentrate, hyperreflexia, headache, tremor, vertigo, paresis, dysarthria, depression (with suicidal ideation), peripheral neuropathy, and seizures (particularly with higher doses and in patients with history of chronic alcoholism) Administer with pyridoxine. Hypersensitivity reactions (including SJS), allergic dermatitis, and rash
Dapsone	Methemoglobinemia, hemolytic anemia, neutropenia, and agranulocytosis Do not use in patients with moderate to severe G6PD deficiency. Sulfone syndrome (fever, exfoliative dermatitis, lymphadenopathy, hepatic necrosis, and hemolysis) Phototoxicity and severe cutaneous reactions (including SJS and TEN) Drug-induced lupus erythematosus Hepatotoxicity and nephrotic syndrome Peripheral neuropathy Nausea and anorexia
Doxycycline	Pill-induced esophagitis/esophageal ulceration Intracranial hypertension Photosensitivity and skin hyperpigmentation Thrombophlebitis (with IV infusion) Nausea and vomiting
Echinocandins (Anidulafungin, Caspofungin, Micafungin)	Histamine-related infusion reactions (flushing, rash, pruritus, hypotension, and dyspnea) and thrombophlebitis Hypersensitivity reactions (including anaphylaxis and anaphylactoid reaction) Abnormal liver enzymes and hepatotoxicity Hypokalemia Embryo-fetal toxicity Diarrhea, nausea, vomiting, fever, and headache Hemolysis (micafungin) (rare)
Emtricitabine	Headache, nausea, and diarrhea Skin hyperpigmentation and rash (palms and soles)
Entecavir	Headache, fatigue, dizziness, and nausea
Ethambutol	Optic neuritis (dose- and duration-dependent) and peripheral neuropathy Headache, nausea, vomiting, anorexia, abdominal pain, and hyperuricemia/gout flare
Ethionamide	Postural hypotension, hepatotoxicity, hypothyroidism (with or without goiter), and hypoglycemia Dizziness, drowsiness, confusion, clumsiness, visual disturbances, and depression Administer with pyridoxine. Dose-dependent gastrointestinal side effects, including nausea, vomiting, anorexia, diarrhea, abdominal pain, and metallic taste Photosensitivity and severe cutaneous reactions (including SJS, TEN, and DRESS) Gynecomastia, acne, hair loss, and impotence
Famciclovir	Nephrotoxicity (in patients with underlying renal disease) Headache, nausea, vomiting, and diarrhea
Fidaxomicin	Nausea, vomiting, and abdominal pain
Flucytosine	Concentration-dependent (>100 mcg/mL) bone marrow suppression (anemia, neutropenia, agranulocytosis, and thrombocytopenia) Hepatotoxicity Diarrhea, nausea, vomiting, and headache Rash, pruritus, and photosensitivity
Fluconazole	Hepatotoxicity, nausea, vomiting, diarrhea, and abdominal pain QTc prolongation Reversible alopecia (with doses ≥400 mg/day for >2 months)
Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin)	Restlessness, insomnia, nightmares, confusion, anxiety, paranoia, tremors, seizure, hallucinations, depression, suicidal thoughts, and attempted and completed suicide Tendonitis and tendon rupture (associated with age over 60, concurrent corticosteroids, diabetes, and kidney, heart, and lung transplant) Diarrhea including C. difficile–associated diarrhea and colitis QTc prolongation Photosensitivity/phototoxicity Anemia, thrombocytopenia, and leukopenia Arthralgia and myalgia Peripheral neuropathy and retinal detachment Hyper- and hypoglycemia, including hypoglycemic coma Nausea, diarrhea, bloating, headache, dizziness, and malaise Vasculitis Aortic dissection (rare) Transaminase elevations and interstitial nephritis (rare) Severe cutaneous reactions (including SJS and TEN) (rare)
Foscarnet	Nephrotoxicity and electrolyte imbalances (e.g., hypocalcemia, hypomagnesemia, hypophosphatemia, hyperphosphatemia, hypokalemia) Administer IV fluid hydration to reduce the risk for nephrotoxicity. Paresthesia and seizure (associated with electrolyte imbalances) Anemia Nausea, vomiting, anorexia, and headache Genital ulceration Thrombophlebitis
Ganciclovir	Neutropenia, thrombocytopenia, anemia, and pancytopenia Carcinogenic and teratogenic potential and impaired fertility Nephrotoxicity Neuropathy Thrombophlebitis
Glecaprevir/Pibrentasvir	Risk of hepatitis B virus reactivation Hepatic decompensation/failure in patients with advanced liver disease Mild headache, fatigue, nausea, and diarrhea Altered glucose tolerance in diabetic patients
Interferon-Alfa and Peginterferon-Alfa	Neuropsychiatric effects (e.g., depression, suicidal ideation) Neutropenia, anemia, and thrombocytopenia Flu-like syndrome (e.g., fever, headache, fatigue, myalgia) Hepatitis exacerbations, thyroid dysfunction, and alopecia Nausea, anorexia, diarrhea, and weight loss Development or exacerbation of autoimmune diseases and ocular effects (e.g., retinal hemorrhage, retinal artery or vein obstructions, and cotton wool spots) Ischemic and hemorrhagic cerebrovascular events, cardiovascular and pulmonary effects, hyper- and hypoglycemia, diabetes, severe infection, and colitis Hypersensitivity reactions
Isavuconazonium (Isavuconazole)	Hepatotoxicity and cholelithiasis Infusion-related reactions (hypotension, dyspnea, chills, dizziness, paresthesia, and hypoesthesia) Hypersensitivity reactions (including SJS) Embryo-fetal toxicity Shortening of QT interval Nausea, vomiting, diarrhea, headache, hypokalemia, dyspnea, and cough
Isoniazid	Hepatotoxicity and asymptomatic elevation in aminotransferase enzymes Peripheral neuropathy, paresthesia, seizures, and optic neuritis Administer with pyridoxine Nausea, diarrhea, and flushing Arthralgia and lupus-like syndrome Psychosis (rare) Hypersensitivity reactions (including TEN and DRESS) (rare)
Itraconazole	Congestive heart failure, edema, and hypokalemia QTc prolongation Hepatotoxicity Hearing loss Neuropathy Gynecomastia Nausea, vomiting, diarrhea, and abdominal pain
Lamivudine	Nausea and vomiting
Levofloxacin	Refer to the row on Fluoroquinolones.
Linezolid	Anemia, neutropenia, and thrombocytopenia (especially with treatment lasting longer than 2–4 weeks and renal insufficiency) Peripheral neuropathy and optic neuritis with long-term therapy Nausea, vomiting, diarrhea, and headache Serotonin syndrome (rare) Seizure (in patients with a history of seizure or with risk factors for seizure) (rare) Lactic acidosis, hypoglycemia, and hyponatremia (rare)
Mefloquine	Depression, psychosis, anxiety, agitation, dizziness, headache, insomnia, and abnormal dreams QTc prolongation and arrhythmias (extrasystole and sinus bradycardia) Agranulocytosis and aplastic anemia Nausea, vomiting, diarrhea, and epigastric pain
Micafungin	Refer to the row on Echinocandins.
Miconazole Buccal Tablets	Dysgeusia, diarrhea, nausea, vomiting, upper abdominal pain, and headache Local reactions (e.g., oral discomfort, burning, pain, tongue/mouth ulceration, gingival pruritus, swelling, and dry mouth) Hypersensitivity reaction (may occur in patients with known hypersensitivity reaction to milk product concentrate)
Miltefosine	Nephrotoxicity and elevated transaminases and bilirubin Retinal degeneration Leukocytosis and thrombocytopenia Embryo-fetal toxicity and impaired fertility, scrotal pain, and impaired ejaculation Nausea, vomiting, diarrhea, anorexia, headache, and motion sickness Severe cutaneous reactions (including SJS)
Moxifloxacin	Refer to the row on Fluoroquinolones.
Nifurtimox	Patients with a history of brain injury, seizures, psychiatric disease, and serious behavioral alterations may experience worsening of their conditions. Vomiting, abdominal pain, headache, decreased appetite, weight loss, nausea, pyrexia, rash, polyneuropathy, insomnia, dizziness, and vertigo Carcinogenic and teratogenic potential and impaired fertility Hypersensitivity reactions with hypotension, angioedema, dyspnea, pruritus, rash or other severe skin reactions
Nitazoxanide	Nausea, vomiting, diarrhea, abdominal pain, headache, and chromaturia
Nystatin (Oral Preparations)	Unpleasant taste, nausea, vomiting, anorexia, and diarrhea
Paromomycin	Nausea, vomiting, abdominal cramps, anorexia, rash, and headache Nephrotoxicity (rare) Inflammatory bowel disease and renal insufficiency may increase risk.
Penicillin G	All Penicillin G Preparations Hypersensitivity (immediate or delayed reactions, including anaphylaxis), bone marrow suppression, nausea, vomiting, diarrhea, and drug fever Jarisch-Herxheimer reaction when used for syphilis (occurs most frequently in persons with early syphilis, high non-treponemal antibody titers, and prior penicillin treatment) Benzathine Penicillin G IM injection-site reactions (pain and erythema), procaine neuropsychiatric reactions (with high dose), and neurovascular damage (due to inadvertent intravascular instead of IM injection) Aqueous Crystalline Penicillin G (IV) Thrombophlebitis Neurotoxicity at high doses—especially in patients with renal dysfunction—and hyperkalemia or hypernatremia at high doses (depending on formulation)
Pentamidine	Nephrotoxicity, infusion-related hypotension, and thrombophlebitis QTc prolongation, arrhythmias (including Torsades de pointes), and electrolyte abnormalities Hypoglycemia, hyperglycemia, and diabetes mellitus Hepatotoxicity and GI intolerance Leukopenia and thrombocytopenia Embryotoxic Rash Pancreatitis (rare) Aerosolized Therapy Bronchospasm, cough, dyspnea, tachypnea, and metallic taste
Posaconazole	Hepatotoxicity, QTc prolongation, and hypokalemia Pseudohyperaldosteronism (hypokalemia and hypertension) Nausea, vomiting, diarrhea, abdominal pain, and headache IV Infusion Thrombophlebitis, accumulation, and worsening renal function with IV formulation (especially in patients with eGFR <50 mL/min per package labeling, but observational studies with IV voriconazole suggest that this may not be a concern)
Primaquine	Methemoglobinemia, hemolytic anemia (use with caution in patients with mild-moderate G6PD deficiency; do not use if severe G6PD deficiency), leukopenia, and neutropenia QTc prolongation Abdominal cramps, nausea, vomiting, and dizziness
Pyrazinamide	Hepatotoxicity Polyarthralgia and myalgia Hyperuricemia/gout flare Thrombocytopenia and sideroblastic anemia Nausea, vomiting, flushing, rash, and photosensitivity
Pyrimethamine	Neutropenia, thrombocytopenia, and megaloblastic anemia Administer with leucovorin. Anorexia, vomiting, and rash
Quinine	QTc prolongation and cardiac arrythmias Cinchonism (tinnitus, vertigo, and blurred vision) Hemolytic anemia (especially in patients with G6PD deficiency), thrombocytopenia, and agranulocytosis Vision abnormalities (e.g., photophobia, altered color perception, and blindness) Hypersensitivity reactions (including SJS and TEN) Hypoglycemia Headache, nausea, vomiting, and diarrhea
Rifabutin	Uveitis (concentration-dependent) Neutropenia and thrombocytopenia Arthralgia Hepatotoxicity Rash Nausea, vomiting, abdominal pain, diarrhea, and anorexia Red-orange discoloration of body fluids
Rifampin	Hepatotoxicity (cholestatic hepatitis) Thrombocytopenia and hemolytic anemia Renal failure Hypersensitivity reactions with flu-like syndrome Interstitial pulmonary disease Nausea, vomiting, anorexia, abdominal pain, flatulence, diarrhea, headache, confusion, and flushing, rash Red-orange discoloration of body fluids
Rifapentine	Hepatotoxicity Anemia, neutropenia, and lymphopenia Hypersensitivity reactions Arthralgia Rash and pruritis Nausea, vomiting, diarrhea, and anorexia Red-orange discoloration of body fluids
Sofosbuvir/Velpatasvir	Risk of hepatitis B virus reactivation Headache, fatigue, and anemia (associated with ribavirin co-administration) Altered glucose tolerance in diabetic patients
Streptomycin	Neurotoxicity including irreversible ototoxicity (both hearing loss and vestibular toxicity) Nephrotoxicity Neuromuscular blockade and respiratory paralysis (associated with rapid infusion of large aminoglycoside doses)
Sulfadiazine	Severe cutaneous reactions (including SJS, EM, and TEN) and photosensitivity Anemia, neutropenia, agranulocytosis, and thrombocytopenia Crystalluria (nephrolithiasis, urolithiasis) and nephrotoxicity Hepatotoxicity Drug fever Peripheral neuritis, tinnitus, vertigo, and insomnia Nausea, vomiting, and headache
Tafenoquine	Decreased hemoglobin and methemoglobinemia and hemolytic anemia Do not use in patients with G6PD deficiency; may cause harm to fetuses and breastfeeding infants who are G6PD deficient. Psychiatric adverse reactions (in patients with history of psychiatric illness) Hypersensitivity reactions (angioedema and urticaria) Visual disturbances Dizziness, nausea, vomiting, and headache
Tecovirimat	Headache, nausea, abdominal pain, and vomiting IV formulation Infusion site pain, swelling, erythema, and extravasation Contains hydroxypropyl-β-cyclodextrin, which may accumulate in patients with renal impairment and has the potential to cause renal toxicity
Tenofovir disoproxil fumarate	Renal insufficiency and Fanconi syndrome (proximal renal tubulopathy with hypophosphatemia, hypouricemia, proteinuria, and normoglycemic glycosuria) Decrease in bone mineral density Nausea and vomiting
Tenofovir alafenamide	Headache, abdominal pain, fatigue, and nausea Lower incidence of renal or bone toxicities than with tenofovir disoproxil fumarate
Trimethoprim-Sulfamethoxazole	Cutaneous reactions (in some cases SJS, EM, and TEN) and photosensitivity Anemia, neutropenia, agranulocytosis, and thrombocytopenia Hepatotoxicity Dose-dependent increase in serum creatinine (without change in GFR), interstitial nephritis, crystalluria (in patients with inadequate hydration), and hyperkalemia (with high-dose TMP) Hypoglycemia and hyponatremia Drug fever Nausea and vomiting Aseptic meningitis and pancreatitis (rare)
Valacyclovir	Neurotoxicity (e.g., agitation, confusion, hallucination, seizure, coma) with high doses, especially in patients with renal impairment Nephrotoxicity Nausea, vomiting, abdominal pain, and headache
Valganciclovir	Bone marrow suppression Confusion, pyrexia, and tremor Nephrotoxicity Carcinogenic and teratogenic potential and impaired fertility Nausea, vomiting, and diarrhea
Voriconazole	Visual disturbances (e.g., abnormal vision, color vision change, and/or photophobia) Optic neuritis (associated with >28 days treatment) Headache, delirium, hallucination, peripheral neuropathy (rare), and encephalopathy (associated with trough >5.5 mcg/mL) Hepatotoxicity QTc prolongation Photosensitivity Voriconazole-associated cutaneous squamous cell carcinoma (with long-term use) Fever, nausea, vomiting, chills, tachycardia, and peripheral edema Embryo-fetal toxicity Nail changes and alopecia (with long-term use) SBECD accumulation with IV formulation and worsening renal function (especially in patients with eGFR <50 mL/min per package labeling, but observational studies suggest that this may not be a concern)
Key: DRESS = drug reaction with eosinophilia and systemic symptoms; eGFR = estimated glomerular filtration rate; EM = erythema multiforme; G6PD = glucose-6-phosphate dehydrogenase; GFR = glomerular filtration rate; GI = gastrointestinal; IM = intramuscular; IV = intravenous; QTc = QT corrected for heart rate; SBECD = sulfobutylether cyclodextrin; SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis; TMP = trimethoprim

Tables

Table 5. Serious and/or Common Adverse Reactions Associated with Systemically Administered Drugs Used to Treat or Prevent Opportunistic Infections

Drug(s)	Adverse Reactions
Acyclovir	Crystalluria and nephrotoxicity secondary to obstructive urolithiasis, particularly after rapid high-dose IV infusion. Risk is increased with dehydration or pre-existing renal impairment. Administer IV fluid hydration to reduce the risk for nephrotoxicity. Neurotoxicity with high doses (agitation, confusion, hallucination, seizure, coma), especially in patients with renal impairment and/or older patients Thrombophlebitis at peripheral IV infusion site Nausea, vomiting, and headache
Adefovir	Nephrotoxicity, especially in patients with underlying renal insufficiency, predisposing comorbidities, or taking concomitant nephrotoxic drugs Nausea and asthenia
Albendazole	Hepatotoxicity Reversible alopecia Nausea, vomiting, headache, and dizziness Bone marrow suppression (i.e., pancytopenia, aplastic anemia, agranulocytosis, and leukopenia) (rare) Patients with liver disease, including hepatic echinococcosis, appear to be at higher risk.
Amikacin	Nephrotoxicity Administer IV fluid hydration to reduce the risk for nephrotoxicity. Ototoxicity, both hearing loss and vestibular toxicity, are possible. Neuromuscular blockade, especially with myasthenia or Parkinson’s disease and rapid infusion of large doses (rare)
Amphotericin B Deoxycholate and Lipid Formulations	Nephrotoxicity (lower incidence with liposomal formulations) Administer IV fluid hydration to reduce the risk for nephrotoxicity. Hypokalemia, hypomagnesemia, and hypocalcemia Infusion-related reactions, including fever, chills, rigors, flank or back pain, and hypotension (lower incidence with liposomal formulations) Thrombophlebitis Transaminase and bilirubin elevations Headache, nausea, vomiting, and diarrhea Heart failure (rarely reported) Anemia (rare)
Anidulafungin	Refer to the row on Echinocandins.
Artemether/Lumefantrine	QTc prolongation Fever, chills, fatigue, arthralgia, and myalgia Headache, dizziness, asthenia, and insomnia Nausea, vomiting, diarrhea, abdominal pain, and anorexia Rash and pruritus Delayed hemolytic anemia (rare)
Artesunate	Acute renal failure requiring dialysis Hemoglobinuria and jaundice Post-treatment hemolysis that may require transfusion QTc prolongation and bradycardia Hypersensitivity reactions (anaphylaxis) Dizziness, nausea, and vomiting
Atovaquone	Hepatotoxicity Rash, nausea, vomiting, and diarrhea Fever, headache, and insomnia
Atovaquone/Proguanil	Abdominal pain, nausea, vomiting, anorexia, diarrhea, headache, asthenia, dizziness, and rash Reversible transaminase elevations
Azithromycin	Ototoxicity with prolonged use Hepatotoxicity Hypersensitivity reactions Nausea, vomiting, diarrhea, and abdominal pain QTc prolongation
Benznidazole	Photosensitivity and hypersensitivity reactions (including allergic dermatitis, TEN, and DRESS) Paresthesia and peripheral neuropathy, headache, and insomnia Bone marrow suppression Embryo-fetal toxicity Nausea, vomiting, abdominal pain, anorexia, and weight loss
Bedaquiline	QTc prolongation Hepatotoxicity Nausea, vomiting, anorexia, diarrhea, elevated amylase, arthralgia, headache, and skin rash
Bezlotoxumab	Exacerbation of congestive heart failure Nausea, pyrexia, and headache
Brincidofovir	Elevations in hepatic transaminases and bilirubin Nausea, vomiting, and diarrhea Embryo-fetal toxicity, male infertility
Caspofungin	Refer to the row on Echinocandins.
Chloroquine and Hydroxychloroquine	Auditory and visual disturbances, including blurry vision. Retinal toxicity may occur with long-term use. QTc prolongation Cardiomyopathy Bone marrow suppression and hemolysis Neuropsychiatric changes, including extrapyramidal reactions, suicidal behavior, and convulsive seizures Hypersensitivity reactions (including TEN, SJS, and EM) Severe hypoglycemia which may require adjustment of antidiabetic medications Photosensitivity, pruritus, skin pigmentation, and exacerbation of psoriasis Headache, nausea, vomiting, diarrhea, anorexia, abdominal pain, and hepatitis Neuromyopathy (may occur with long-term use)(rare)
Cidofovir	Nephrotoxicity, proteinuria, azotemia, proximal tubular dysfunction (normoglycemic glycosuria, hypophosphatemia), and metabolic acidosis (including Fanconi’s syndrome) Administer IV fluid hydration and oral probenecid to reduce the risk for nephrotoxicity. Neutropenia and anemia Ocular hypotony and anterior uveitis/iritis Possibly carcinogenic and teratogenic; may cause hypospermia Gastrointestinal intolerance and diarrhea Asthenia, fever, headache, and alopecia Side effects most likely related to co-administration with probenecid are rash, nausea, vomiting, anorexia, and gout exacerbation.
Ciprofloxacin	Refer to the row on Fluoroquinolones.
Clarithromycin	Hepatotoxicity Ototoxicity, including reversible hearing loss and tinnitus, with high doses or prolonged use QTc prolongation Increased risk of cardiac complications or death in patients with heart disease Diarrhea Headache, nausea, vomiting, diarrhea, abdominal cramps, and dysgeusia
Clindamycin	Diarrhea, including C. difficile–associated diarrhea and colitis Metallic taste (with IV infusion), thrombophlebitis, and arrhythmia with rapid IV infusion Hypersensitivity reactions (including SJS and TEN) Nausea, vomiting, abdominal pain, and abnormal liver function tests
Clotrimazole (Troche)	Nausea, vomiting, anorexia, and metallic taste
Cycloserine	Neuropsychiatric toxicities, including convulsions, psychosis, somnolence, confusion, inability to concentrate, hyperreflexia, headache, tremor, vertigo, paresis, dysarthria, depression (with suicidal ideation), peripheral neuropathy, and seizures (particularly with higher doses and in patients with history of chronic alcoholism) Administer with pyridoxine. Hypersensitivity reactions (including SJS), allergic dermatitis, and rash
Dapsone	Methemoglobinemia, hemolytic anemia, neutropenia, and agranulocytosis Do not use in patients with moderate to severe G6PD deficiency. Sulfone syndrome (fever, exfoliative dermatitis, lymphadenopathy, hepatic necrosis, and hemolysis) Phototoxicity and severe cutaneous reactions (including SJS and TEN) Drug-induced lupus erythematosus Hepatotoxicity and nephrotic syndrome Peripheral neuropathy Nausea and anorexia
Doxycycline	Pill-induced esophagitis/esophageal ulceration Intracranial hypertension Photosensitivity and skin hyperpigmentation Thrombophlebitis (with IV infusion) Nausea and vomiting
Echinocandins (Anidulafungin, Caspofungin, Micafungin)	Histamine-related infusion reactions (flushing, rash, pruritus, hypotension, and dyspnea) and thrombophlebitis Hypersensitivity reactions (including anaphylaxis and anaphylactoid reaction) Abnormal liver enzymes and hepatotoxicity Hypokalemia Embryo-fetal toxicity Diarrhea, nausea, vomiting, fever, and headache Hemolysis (micafungin) (rare)
Emtricitabine	Headache, nausea, and diarrhea Skin hyperpigmentation and rash (palms and soles)
Entecavir	Headache, fatigue, dizziness, and nausea
Ethambutol	Optic neuritis (dose- and duration-dependent) and peripheral neuropathy Headache, nausea, vomiting, anorexia, abdominal pain, and hyperuricemia/gout flare
Ethionamide	Postural hypotension, hepatotoxicity, hypothyroidism (with or without goiter), and hypoglycemia Dizziness, drowsiness, confusion, clumsiness, visual disturbances, and depression Administer with pyridoxine. Dose-dependent gastrointestinal side effects, including nausea, vomiting, anorexia, diarrhea, abdominal pain, and metallic taste Photosensitivity and severe cutaneous reactions (including SJS, TEN, and DRESS) Gynecomastia, acne, hair loss, and impotence
Famciclovir	Nephrotoxicity (in patients with underlying renal disease) Headache, nausea, vomiting, and diarrhea
Fidaxomicin	Nausea, vomiting, and abdominal pain
Flucytosine	Concentration-dependent (>100 mcg/mL) bone marrow suppression (anemia, neutropenia, agranulocytosis, and thrombocytopenia) Hepatotoxicity Diarrhea, nausea, vomiting, and headache Rash, pruritus, and photosensitivity
Fluconazole	Hepatotoxicity, nausea, vomiting, diarrhea, and abdominal pain QTc prolongation Reversible alopecia (with doses ≥400 mg/day for >2 months)
Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin)	Restlessness, insomnia, nightmares, confusion, anxiety, paranoia, tremors, seizure, hallucinations, depression, suicidal thoughts, and attempted and completed suicide Tendonitis and tendon rupture (associated with age over 60, concurrent corticosteroids, diabetes, and kidney, heart, and lung transplant) Diarrhea including C. difficile–associated diarrhea and colitis QTc prolongation Photosensitivity/phototoxicity Anemia, thrombocytopenia, and leukopenia Arthralgia and myalgia Peripheral neuropathy and retinal detachment Hyper- and hypoglycemia, including hypoglycemic coma Nausea, diarrhea, bloating, headache, dizziness, and malaise Vasculitis Aortic dissection (rare) Transaminase elevations and interstitial nephritis (rare) Severe cutaneous reactions (including SJS and TEN) (rare)
Foscarnet	Nephrotoxicity and electrolyte imbalances (e.g., hypocalcemia, hypomagnesemia, hypophosphatemia, hyperphosphatemia, hypokalemia) Administer IV fluid hydration to reduce the risk for nephrotoxicity. Paresthesia and seizure (associated with electrolyte imbalances) Anemia Nausea, vomiting, anorexia, and headache Genital ulceration Thrombophlebitis
Ganciclovir	Neutropenia, thrombocytopenia, anemia, and pancytopenia Carcinogenic and teratogenic potential and impaired fertility Nephrotoxicity Neuropathy Thrombophlebitis
Glecaprevir/Pibrentasvir	Risk of hepatitis B virus reactivation Hepatic decompensation/failure in patients with advanced liver disease Mild headache, fatigue, nausea, and diarrhea Altered glucose tolerance in diabetic patients
Interferon-Alfa and Peginterferon-Alfa	Neuropsychiatric effects (e.g., depression, suicidal ideation) Neutropenia, anemia, and thrombocytopenia Flu-like syndrome (e.g., fever, headache, fatigue, myalgia) Hepatitis exacerbations, thyroid dysfunction, and alopecia Nausea, anorexia, diarrhea, and weight loss Development or exacerbation of autoimmune diseases and ocular effects (e.g., retinal hemorrhage, retinal artery or vein obstructions, and cotton wool spots) Ischemic and hemorrhagic cerebrovascular events, cardiovascular and pulmonary effects, hyper- and hypoglycemia, diabetes, severe infection, and colitis Hypersensitivity reactions
Isavuconazonium (Isavuconazole)	Hepatotoxicity and cholelithiasis Infusion-related reactions (hypotension, dyspnea, chills, dizziness, paresthesia, and hypoesthesia) Hypersensitivity reactions (including SJS) Embryo-fetal toxicity Shortening of QT interval Nausea, vomiting, diarrhea, headache, hypokalemia, dyspnea, and cough
Isoniazid	Hepatotoxicity and asymptomatic elevation in aminotransferase enzymes Peripheral neuropathy, paresthesia, seizures, and optic neuritis Administer with pyridoxine Nausea, diarrhea, and flushing Arthralgia and lupus-like syndrome Psychosis (rare) Hypersensitivity reactions (including TEN and DRESS) (rare)
Itraconazole	Congestive heart failure, edema, and hypokalemia QTc prolongation Hepatotoxicity Hearing loss Neuropathy Gynecomastia Nausea, vomiting, diarrhea, and abdominal pain
Lamivudine	Nausea and vomiting
Levofloxacin	Refer to the row on Fluoroquinolones.
Linezolid	Anemia, neutropenia, and thrombocytopenia (especially with treatment lasting longer than 2–4 weeks and renal insufficiency) Peripheral neuropathy and optic neuritis with long-term therapy Nausea, vomiting, diarrhea, and headache Serotonin syndrome (rare) Seizure (in patients with a history of seizure or with risk factors for seizure) (rare) Lactic acidosis, hypoglycemia, and hyponatremia (rare)
Mefloquine	Depression, psychosis, anxiety, agitation, dizziness, headache, insomnia, and abnormal dreams QTc prolongation and arrhythmias (extrasystole and sinus bradycardia) Agranulocytosis and aplastic anemia Nausea, vomiting, diarrhea, and epigastric pain
Micafungin	Refer to the row on Echinocandins.
Miconazole Buccal Tablets	Dysgeusia, diarrhea, nausea, vomiting, upper abdominal pain, and headache Local reactions (e.g., oral discomfort, burning, pain, tongue/mouth ulceration, gingival pruritus, swelling, and dry mouth) Hypersensitivity reaction (may occur in patients with known hypersensitivity reaction to milk product concentrate)
Miltefosine	Nephrotoxicity and elevated transaminases and bilirubin Retinal degeneration Leukocytosis and thrombocytopenia Embryo-fetal toxicity and impaired fertility, scrotal pain, and impaired ejaculation Nausea, vomiting, diarrhea, anorexia, headache, and motion sickness Severe cutaneous reactions (including SJS)
Moxifloxacin	Refer to the row on Fluoroquinolones.
Nifurtimox	Patients with a history of brain injury, seizures, psychiatric disease, and serious behavioral alterations may experience worsening of their conditions. Vomiting, abdominal pain, headache, decreased appetite, weight loss, nausea, pyrexia, rash, polyneuropathy, insomnia, dizziness, and vertigo Carcinogenic and teratogenic potential and impaired fertility Hypersensitivity reactions with hypotension, angioedema, dyspnea, pruritus, rash or other severe skin reactions
Nitazoxanide	Nausea, vomiting, diarrhea, abdominal pain, headache, and chromaturia
Nystatin (Oral Preparations)	Unpleasant taste, nausea, vomiting, anorexia, and diarrhea
Paromomycin	Nausea, vomiting, abdominal cramps, anorexia, rash, and headache Nephrotoxicity (rare) Inflammatory bowel disease and renal insufficiency may increase risk.
Penicillin G	All Penicillin G Preparations Hypersensitivity (immediate or delayed reactions, including anaphylaxis), bone marrow suppression, nausea, vomiting, diarrhea, and drug fever Jarisch-Herxheimer reaction when used for syphilis (occurs most frequently in persons with early syphilis, high non-treponemal antibody titers, and prior penicillin treatment) Benzathine Penicillin G IM injection-site reactions (pain and erythema), procaine neuropsychiatric reactions (with high dose), and neurovascular damage (due to inadvertent intravascular instead of IM injection) Aqueous Crystalline Penicillin G (IV) Thrombophlebitis Neurotoxicity at high doses—especially in patients with renal dysfunction—and hyperkalemia or hypernatremia at high doses (depending on formulation)
Pentamidine	Nephrotoxicity, infusion-related hypotension, and thrombophlebitis QTc prolongation, arrhythmias (including Torsades de pointes), and electrolyte abnormalities Hypoglycemia, hyperglycemia, and diabetes mellitus Hepatotoxicity and GI intolerance Leukopenia and thrombocytopenia Embryotoxic Rash Pancreatitis (rare) Aerosolized Therapy Bronchospasm, cough, dyspnea, tachypnea, and metallic taste
Posaconazole	Hepatotoxicity, QTc prolongation, and hypokalemia Pseudohyperaldosteronism (hypokalemia and hypertension) Nausea, vomiting, diarrhea, abdominal pain, and headache IV Infusion Thrombophlebitis, accumulation, and worsening renal function with IV formulation (especially in patients with eGFR <50 mL/min per package labeling, but observational studies with IV voriconazole suggest that this may not be a concern)
Primaquine	Methemoglobinemia, hemolytic anemia (use with caution in patients with mild-moderate G6PD deficiency; do not use if severe G6PD deficiency), leukopenia, and neutropenia QTc prolongation Abdominal cramps, nausea, vomiting, and dizziness
Pyrazinamide	Hepatotoxicity Polyarthralgia and myalgia Hyperuricemia/gout flare Thrombocytopenia and sideroblastic anemia Nausea, vomiting, flushing, rash, and photosensitivity
Pyrimethamine	Neutropenia, thrombocytopenia, and megaloblastic anemia Administer with leucovorin. Anorexia, vomiting, and rash
Quinine	QTc prolongation and cardiac arrythmias Cinchonism (tinnitus, vertigo, and blurred vision) Hemolytic anemia (especially in patients with G6PD deficiency), thrombocytopenia, and agranulocytosis Vision abnormalities (e.g., photophobia, altered color perception, and blindness) Hypersensitivity reactions (including SJS and TEN) Hypoglycemia Headache, nausea, vomiting, and diarrhea
Rifabutin	Uveitis (concentration-dependent) Neutropenia and thrombocytopenia Arthralgia Hepatotoxicity Rash Nausea, vomiting, abdominal pain, diarrhea, and anorexia Red-orange discoloration of body fluids
Rifampin	Hepatotoxicity (cholestatic hepatitis) Thrombocytopenia and hemolytic anemia Renal failure Hypersensitivity reactions with flu-like syndrome Interstitial pulmonary disease Nausea, vomiting, anorexia, abdominal pain, flatulence, diarrhea, headache, confusion, and flushing, rash Red-orange discoloration of body fluids
Rifapentine	Hepatotoxicity Anemia, neutropenia, and lymphopenia Hypersensitivity reactions Arthralgia Rash and pruritis Nausea, vomiting, diarrhea, and anorexia Red-orange discoloration of body fluids
Sofosbuvir/Velpatasvir	Risk of hepatitis B virus reactivation Headache, fatigue, and anemia (associated with ribavirin co-administration) Altered glucose tolerance in diabetic patients
Streptomycin	Neurotoxicity including irreversible ototoxicity (both hearing loss and vestibular toxicity) Nephrotoxicity Neuromuscular blockade and respiratory paralysis (associated with rapid infusion of large aminoglycoside doses)
Sulfadiazine	Severe cutaneous reactions (including SJS, EM, and TEN) and photosensitivity Anemia, neutropenia, agranulocytosis, and thrombocytopenia Crystalluria (nephrolithiasis, urolithiasis) and nephrotoxicity Hepatotoxicity Drug fever Peripheral neuritis, tinnitus, vertigo, and insomnia Nausea, vomiting, and headache
Tafenoquine	Decreased hemoglobin and methemoglobinemia and hemolytic anemia Do not use in patients with G6PD deficiency; may cause harm to fetuses and breastfeeding infants who are G6PD deficient. Psychiatric adverse reactions (in patients with history of psychiatric illness) Hypersensitivity reactions (angioedema and urticaria) Visual disturbances Dizziness, nausea, vomiting, and headache
Tecovirimat	Headache, nausea, abdominal pain, and vomiting IV formulation Infusion site pain, swelling, erythema, and extravasation Contains hydroxypropyl-β-cyclodextrin, which may accumulate in patients with renal impairment and has the potential to cause renal toxicity
Tenofovir disoproxil fumarate	Renal insufficiency and Fanconi syndrome (proximal renal tubulopathy with hypophosphatemia, hypouricemia, proteinuria, and normoglycemic glycosuria) Decrease in bone mineral density Nausea and vomiting
Tenofovir alafenamide	Headache, abdominal pain, fatigue, and nausea Lower incidence of renal or bone toxicities than with tenofovir disoproxil fumarate
Trimethoprim-Sulfamethoxazole	Cutaneous reactions (in some cases SJS, EM, and TEN) and photosensitivity Anemia, neutropenia, agranulocytosis, and thrombocytopenia Hepatotoxicity Dose-dependent increase in serum creatinine (without change in GFR), interstitial nephritis, crystalluria (in patients with inadequate hydration), and hyperkalemia (with high-dose TMP) Hypoglycemia and hyponatremia Drug fever Nausea and vomiting Aseptic meningitis and pancreatitis (rare)
Valacyclovir	Neurotoxicity (e.g., agitation, confusion, hallucination, seizure, coma) with high doses, especially in patients with renal impairment Nephrotoxicity Nausea, vomiting, abdominal pain, and headache
Valganciclovir	Bone marrow suppression Confusion, pyrexia, and tremor Nephrotoxicity Carcinogenic and teratogenic potential and impaired fertility Nausea, vomiting, and diarrhea
Voriconazole	Visual disturbances (e.g., abnormal vision, color vision change, and/or photophobia) Optic neuritis (associated with >28 days treatment) Headache, delirium, hallucination, peripheral neuropathy (rare), and encephalopathy (associated with trough >5.5 mcg/mL) Hepatotoxicity QTc prolongation Photosensitivity Voriconazole-associated cutaneous squamous cell carcinoma (with long-term use) Fever, nausea, vomiting, chills, tachycardia, and peripheral edema Embryo-fetal toxicity Nail changes and alopecia (with long-term use) SBECD accumulation with IV formulation and worsening renal function (especially in patients with eGFR <50 mL/min per package labeling, but observational studies suggest that this may not be a concern)
Key: DRESS = drug reaction with eosinophilia and systemic symptoms; eGFR = estimated glomerular filtration rate; EM = erythema multiforme; G6PD = glucose-6-phosphate dehydrogenase; GFR = glomerular filtration rate; GI = gastrointestinal; IM = intramuscular; IV = intravenous; QTc = QT corrected for heart rate; SBECD = sulfobutylether cyclodextrin; SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis; TMP = trimethoprim

Download Guidelines

Section Only PDF (165.97 KB)
Full Guideline PDF (5.8 MB)
Tables Only PDF (1006.96 KB)

Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV

Tables

Table 5. Serious and/or Common Adverse Reactions Associated with Systemically Administered Drugs Used to Treat or Prevent Opportunistic Infections

Tables

Table 5. Serious and/or Common Adverse Reactions Associated with Systemically Administered Drugs Used to Treat or Prevent Opportunistic Infections

Download Guidelines

Related Content