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. 2020 Aug 7;177(18):4096–4112. doi: 10.1111/bph.15197

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