TABLE 2.
Reported cough cases after administration of some antibiotic inhalation products in clinical studies
Drug | Formulation | Dose | Regimen | Delivery platform | Subjects | Reported coughs | Reference |
---|---|---|---|---|---|---|---|
Tobramycin | Powder | 112 mg (4 capsules) | Twice daily | T‐326 dry powder inhaler | Cystic fibrosis |
• 48% (powder) • 31% (solution) • Higher cough incidents in all age groups receiving powder |
(Geller et al., 2014; Konstan et al., 2011) |
Solution | 300 mg in 5‐ml saline | Twice daily | PARI LC PLUS® air jet nebuliser | ||||
Tobramycin | Powder | 112 mg (4 capsules) | Twice daily | T‐326 dry powder inhaler | Cystic fibrosis |
• 20% (powder) • 0% (solution) • Increased cough incident with increased powder dose |
(Geller, Konstan, Smith, Noonberg, & Conrad, 2007) |
Solution | 300 mg in 5‐ml saline | Twice daily | PARI LC PLUS air jet nebuliser | ||||
Tobramycin | Solution | 300 mg in 5‐ml saline | Twice daily for 28 days | PARI LC PLUS air jet nebuliser | Bronchiectasis |
• 41% (tobramycin solution) • 24% (placebo) |
(Barker et al., 2000) |
Placebo (1.25 mg of quinine sulfate in saline) | |||||||
Tobramycin (radiolabelled) | Solution | 300 mg in 5‐ml saline | Single dose | eFlow rapid or PARI LC PLUS air jet nebuliser | Cystic fibrosis |
• 50% (eFlow rapid) • 17% (PARI LC PLUS) |
(Lenney, Edenborough, Kho, & Kovarik, 2011) |
Tobramycin | Solution | 300 mg in 5‐ml saline | Twice daily, 14‐day on/off cycle; 3 cycles | PARI LC PLUS air jet nebuliser | Severe bronchiectasis | • 44% (27%: thought to be treatment related) | (Scheinberg & Shore, 2005) |
Tobramycin | Solution | 300 mg in 5‐ml saline | Twice daily, 28‐day on/off cycle; 1 + 6 cycles | PARI LC PLUS air jet nebuliser | Cystic fibrosis |
• 6.4% (300 mg per 4 ml) • 6.0% (300 mg per 5 ml) |
(Mazurek et al., 2014) |
300 mg in 4‐ml saline | |||||||
Tobramycin | Solution | 300 mg in 5‐ml saline | Phase 1: twice daily for 14 days + once a day on Day 15 using one type of nebuliser | eFlow rapid or PARI LC PLUS air jet nebuliser | Cystic fibrosis |
• 12% (eFlow) • 0% (PARI LC PLUS) |
(Hubert et al., 2009) |
Phase 2: twice daily for 14 days + once a day on Day 15 using other type of nebuliser | |||||||
Tobramycin | Powder | 112 mg (4 × 28‐mg capsules) |
Group A Phase 1: tobramycin solution, twice daily for 28‐day on/off Phase 2: tobramycin powder, twice daily for 28‐day on/off |
T‐326 dry powder inhaler or patients' personal nebuliser | Cystic fibrosis |
• Group A: not reported • Group B: comparable • Group C: post‐inhalation rates reduced from 55% during Phase 1 down to 37% in Phase 2 |
(Greenwood et al., 2017) |
Solution | 300 mg in 3‐ml saline |
Group B Phase 1: colistin solution, twice daily for 56 days Phase 2: tobramycin powder, twice daily for 28‐day on/off |
|||||
Colistimethate sodium | Solution | 1 or 2 million units |
Group C Phases 1 and 2: tobramycin powder, twice daily for 28‐day on/off |
||||
Tobramycin | Powder | 112 mg (4 × 28‐mg capsules) | Twice daily, 28‐day on/off cycle; 3 cycles | T‐326 dry powder inhaler | Cystic fibrosis |
Cycle 1 • 13% (tobramycin powder) • 27% (placebo) Cycles 2 and 3 • 26% (tobramycin powder) • 24% (placebo) |
(Konstan, Geller, et al., 2011) |
Placebo: 112 mg of excipients | Cycle 1: tobramycin powder or placebo | ||||||
Cycles 2 and 3: open‐label tobramycin powder | |||||||
Colistin | Powder | 25 mg | A single dose at each visit | In‐house built dry powder inhaler or Ventstream® jet nebuliser | Cystic fibrosis |
• Moderate to severe (powder) • No coughs reported (solution) |
(Le Brun et al., 2002) |
Solution | 160 mg in 6‐ml saline | ||||||
Colistin sulfometate | Solution | 160 mg in 6‐ml saline | A single dose | Ventstream® jet nebuliser | Cystic fibrosis |
• Severe cough (solistin sulfate) • No coughs reported (colistin sulfometate) |
(Westerman, Le Brun, Touw, Frijlink, & Heijerman, 2004) |
Colistin sulfate | 100 mg in 6‐ml saline | ||||||
Both contained an equivalent amount of colistin (67 mg in 6 ml) | |||||||
Colistimethate sodium | Powder | 125 mg | Twice daily, 24 weeks | Turbospin dry powder inhaler or PARI LC PLUS air jet nebuliser | Cystic fibrosis |
• 75% (colistimethate sodium powder) • 43% (tobramycin solution) |
(Schuster, Haliburn, Doring, & Goldman, 2013) |
Tobramycin | Solution | 300 mg in 5‐ml saline | Twice daily, three 28‐day courses |