Table 9.

Adverse drug reactions of NTM therapy and monitoring guidance [201], [202].

Drug	Adverse drug reactions	Laboratory/Clinical monitoring
Amikacin (parenteral)	Kidney toxicity, electrolyte abnormalities (K, Mg, Ca), vestibular, toxicity, hearing loss	Clinical: consider audiometry, balance assessments Laboratory: BMP w/SCr, BUN, K (2x/weekly), TDM for durations >1 week
Amikacin (inhalation)	Sore mouth/throat, bronchospasm, cough, wheezing/SOB, dysphonia Rare: kidney/vestibular/auditory toxicity	Clinical: pre-/post administration respiratory status Laboratory: SCr (monthly), serum trough level (to confirm lack of systemic accumulation) after 1 week of therapy
Amoxicillin- Clavulanate	Abdominal discomfort, diarrhea, nausea, vomiting Rare: hypersensitvity, rash	Clinical: GI effects Laboratory: CBC w/differential, ALT and SCr (1 month, 3 months, then annually)
Azithromycin	GI (abdominal pain, nausea, vomiting, diarrhea, dyspepsia), headache, visual disturbance Rare: hearing loss, QT prolongation	Clinical: consider audiometry, GI effects, consider ECGc Laboratory: CBC w/differential , ALT, SCr (1 month, 3 months, then annually)
Bedaquiline Fumarate	Nausea, arthralgia, headache, chest pain, QT prolongation, hepatotoxicity	Clinical: ECG (baseline, 2 weeks, 12 weeks, and 24 weeks) Laboratory: serum Ca, Mag, and K (baseline); liver function tests: AST, ALT, bilirubins, alk phos (baseline, then monthly)
Cefoxitin	Injection site reactions, hypotension, transaminitis, leukopenia, thrombocytopenia Rare: aplastic anemia	Clinical: rash and hypersensitivity symptoms Laboratory: CBC w/differential, ALT, and BMP w/SCr, BUN, K (weekly)
Ciprofloxacin	GI (abdominal pain, nausea, vomiting, diarrhea, dyspepsia), hypoglycemia, CNS effects (agitation, nervousness, disorientation, memory impairment), rash Rare: peripheral neuropathy, tendon rupture, QT prolongation	Clinical: consider ECG, signs of hypoglycemia/ CNS effects Laboratory: CBC w/differential, ALT, and SCr (1 month, 3 months, then annually)
Clarithromycin	GI (taste disturbance, abdominal pain, nausea, vomiting, diarrhea, dyspepsia) Rare: hearing loss, QT prolongation, hepatotoxicity	Clinical: consider audiometry, GI effects, consider ECGc, Monitor DDI Laboratory: CBC w/differential , ALT, SCr (1 month, 3 months, then annually)
Clofazimine	Orange/red discoloration of body fluids/feces, skin manifestations (hyperpigmentation ichythosis, xeroderma ,pruritis, phototoxicity, rash), GI disturbance (nausea, vomiting, diarrhea, anorexia, abdominal pain) Rare: QT prolongation, hepatitis, depression due to skin discoloration	Clinical: ECG (baseline, 2 weeks, 12 weeks, and 24 weeks), GI adverse effects, psychological disturbances (depression/anxiety) related to skin effects Laboratory: liver function tests: AST, ALT, bilirubins, alk phos (baseline, then monthly)
Doxycycline	GI effects (nausea, vomitting, diarrea, dysphagia), photosensitivity, rash Rare: esophageal ulceration, benign intracranial hypertension, hepatitis	Clinical: photosensitivity, esophageal discomfort Laboratory: CBC w/differential, ALT, and SCr (1 month, 3 months, then annually)
Ethambutol	optic neuritis, GI effects (nausea/vomitting) Rare: peripheral neuropathy	Clinical: monthly visual acuity assessment and red-green color-discrimination assessment (Ishihara), fundoscopic exam (baseline and every 3 months) Laboratory: Scr (baseline and monthly)
Ethionamide	GI (nausea, vomiting, anorexia, taste disturbance, diarrhea), endocrine (gynecomastia, hair loss, acne, impotence, menstrual irregularity, reversible hypothyroidism), hepatotoxicity, neurotoxicity (peripheral neuropathy, optic neuritis, depression, and psychosis)	Clinical: GI, endocrine, and psychiatric symptoms Laboratory: creatinine and LFTs: AST/ALT, alk phos, bilirubins (baseline and monthly), TSH (baseline and every 3 months)
Imipenem/Cilastin	GI effects (nausea, vomiting, diarrea), rash Rare: seizure, cytopenias	Clinical: GI effects and rash Laboratory: CBC w/differential, ALT, and BMP w/SCr, BUN, K (weekly)
Isoniazid	Peripheral neuropathy, asymptomatic transaminase elevations, hepatitis Rare: rash, hypersensitivity reactions	Clinical: clinical signs of hepatotoxicity (nausea, abdominal pain, jaundice) and neuropathy Laboratory: LFTs: AST/ALT, alk phos, bilirubins (baseline and monthly) if underlying liver compromise or concomitant hepatotoxic drugs
Levofloxacin	GI (nausea, diarrhea) hypoglycemia, CNS effects (dizziness, agitation, nervousness, disorientation, memory impairment, insomnia) Rare: peripheral neuropathy, tendon rupture, QT prolongation	Clinical: Consider ECG, signs of hypoglycemia/CNS effects Laboratory: CBC w/differential, ALT, and SCr (1 month, 3 months, then annually)
Linezolid	GI effects (nausea, vomiting, diarrhea), headache, hematologic myelosuppression (thrombocytopenia, leukopenia, anemia) Rare: lactic acidosis, peripheral neuropathy, seizure, optic neuropathy	Clinical: GI effects, clinical thrombocytopenia (unusual bleeding, bruising) and peripheral neuropathy Laboratory: CBC w/differential (weekly × 4 weeks, then bi-weekly), LFTs: AST/ALT, alk phos, bilirubins (baseline and monthly)
Minocycline	GI effects (nausea, vomiting, diarrea), skin effects (rash, photosensitivity, skin pigmentation), dizziness, headache	Clinical: cutaneous, neurologic, and GI effects Laboratory: CBC w/differential, ALT, and SCr (1 month, 3 months, then annually)
Moxifloxacin	GI (nausea, diarrhea) hypoglycemia, CNS effects (dizziness, agitation, nervousness, disorientation, memory impairment, insomnia) Rare: peripheral neuropathy, tendon rupture, QT prolongation	Clinical: consider ECG, signs of hypoglycemia/CNS effects Laboratory: CBC w/differential, ALT, and SCr (1 month, 3 months, then annually)
Rifabutin	Discoloration (orange/red) of body fluids, cutaneous effects (pruritus, rash), GI effects (nausea, vomitting), hepatitis, anterior uveítis, hematologic toxicity (leukopenia, neutropenia), arthralgias/myalgias	Clinical: Monitor DDI, GI/ cutaneous effects Laboratory: CBC w/differential, ALT, and SCr (1 month then every 3 months)
Rifampin	Discoloration (orange/red) of body fluids, cutaneous effects (pruritus, rash), GI effects (nausea, vomitting), hepatitis, hematologic toxicity (leukopenia, hemolytic anemia) Rare: flu-like syndrome	Clinical: Monitor DDI, GI/ cutaneous effects Laboratory: CBC w/differential, ALT, and SCr (1 month then every 3 months)
Streptomycin	Kidney toxicity, electrolyte abnormalities (K, Mg, Ca), vestibular, toxicity, hearing loss	Clinical: consider audiometry, balance assessments Laboratory: BMP w/SCr, BUN, K (2x/weekly), TDMb for durations >1 week
Tigecycline	GI effects (nausea, vomiting, diarrea, anorexia, dyspepsia), dizziness, rash	Clinical: nausea/vomitting, dizziness Laboratory: BMP w/SCr, BUN, K; LFTs: AST/ALT, alk phos, bilirubins; CBC w/differential (weekly)
Tobramycin	Kidney toxicity, electrolyte abnormalities (K, Mg, Ca), vestibular, toxicity, hearing loss	Clinical: consider audiometry, balance assessments Laboratory: BMP w/SCr, BUN, K (2x/weekly), TDM for durations >1 week
Trimethoprim/Sulfamethoxazole	GI effects (nausea, vomiting, diarrea), cutaneous effects (pruritus, rash),	Clinical: nausea/vomiting and rash Laboratory: CBC w/differential, ALT, and SCr (1 month, 3 months, then annually)

Abbreviations: Alk Phos – alkaline phosphatase, ALT – alanine aminotransferase, AST – aspartate aminotransferase, BMP – basic metabolic panel, BUN – blood urea nitrogen, Ca – calcium, CBC – complete blood count, CNS – central nervous system, DDI – drug drug interaction, ECG – electrocardiogram, GI – gastrointestinal, K – potassium, Mag – magnesium, SCr – serum creatinine, SOB – shortness of breath, TDM – therapeutic drug monitoring, TSH – thyroid stimulating hormone.