Table 2.
World Health Organization classification (Groups A-C) of second-line antituberculosis drugs, important adverse effects, monitoring and cerebrospinal fluid penetration [17]
| Drug group and drug name | Important adverse effects | Adverse effect monitoring | Cerebrospinal fluid (CSF) penetration |
|---|---|---|---|
| Group A drugsa | |||
| Levofloxacin (Lfx) | Sleep disturbance, GI disturbance, arthralgia/ arthritis, raised intracranial pressure | Clinically | Good |
| Moxifloxacin (Mfx) | As for levofloxacin, plus QT-interval prolongation | Clinically; monthly ECG if given with other QT-prolonging drugs | Good |
| Bedaquiline (Bdq) | Headache, nausea, liver dysfunction, QT-interval prolongation | Clinically; monthly ECG if given with other QT-prolonging drugs | Does enter CSF – unbound fraction important |
| Linezolid (Lzd) | Diarrhea, nausea, headache, myelosuppression, peripheral neuropathy, optic neuritis, lactic acidosis and pancreatitis | Clinically; baseline 2-weekly FBC & differential WCC for first month, then monthly; visual acuity testing when possible | Good |
| Group B drugs | |||
| Clofazimine (Cfz) | Skin discoloration, ichthyosis, abdominal pain, QTc prolongation | Clinically; monthly ECG if given with other QT-prolonging drugs | Poor |
|
Cycloserine (Cs) /Terizidone (Trd) |
Neurological and psychological effects | Clinically | Good |
| Group C drugs | |||
| Ethambutol (E) | Optic neuritis | Clinically | Very poor |
| Delamanid (Dlm) | Nausea, vomiting, dizziness, paresthesia, anxiety, hallucinations, QTc prolongation | Clinically; monthly ECG if given with other QT-prolonging drugs | Likely enters CSF and good penetration in brain tissue |
| Pyrazinamide (Z) | Arthritis/arthralgia, hepatitis, skin rashes | Clinically; liver function tests if any vomiting or abdominal complaints | Good |
| Amikacin (Am)b (Kanamycin and capreomycin same dose) |
Ototoxicity (irreversible), nephrotoxicity Use NOT recommended in children |
Monthly audiology and renal function testing, if no other options for treatment | Poor; moderate in acute inflammatory stage |
| Ethionamide (Eto) / Prothionamide (Pto) | GI disturbance, metallic taste, hypothyroidism | Clinically; thyroid function testing at least two-monthly | Good |
| Meropenem (Mpm) | GI intolerance, hypersensitivity reactions, seizures, liver and renal dysfunction | Clinically; liver and renal function testing | Good |
| Amoxicillin-clavulanate (Amx-Clv) |
Only to be used with a carbapenem GI intolerance, hypersensitivity reactions |
Clinically | Poor |
| Para-aminosalicylic acid (PAS) | GI intolerance, hypothyroidism, hepatitis | Clinically; thyroid function testing at least two-monthly | Moderate to poor. Use as single daily dose for better CSF penetration |
| Isoniazid high-dose (Hhd) | Hepatitis, peripheral neuropathy | Clinically; liver function tests if any vomiting or abdominal complaints | Good |
CSF Cerebrospinal fluid, ECG Electrocardiogram, FBC Full blood count, GI Gastrointestinal, WCC White cell count
aWHO Group A drugs are considered highly effective and strongly recommended for inclusion in all regimens unless contra-indicated [18]
bCan be given with lidocaine to reduce pain of intramuscular injections [13]