Table 3.
Dose‐Finding Postmarketing Studies (Alimentary Tract and Metabolism)
| Disease | Drug (Registered Dose) | Studied Doses Postmarketing | References |
|---|---|---|---|
| Fabry | Fabrazyme (1 mg/kg EOW) | 0.2 mg/kg EOW | Vedder et al, 20075 |
| 0.5 mg/kg EOW, 0.3 mg/kg EOW (due to shortage) | Ghali et al, 20126 | ||
| 0.3–0.5 mg/kg (due to shortage) | Lenders et al, 20167Weidemann et al, 20148 | ||
| 0.3 mg/kg | Lubanda et al, 20099 | ||
| Fabry | Replagal (0.2 mg/kg EOW) | 0.1, 0.2, or 0.4 mg/kg weekly; 0.2 mg/kg EOW, 0.4 mg/kg EOW | Clarke et al, 200710 |
| 0.2 mg/kg weekly | Schiffmann et al, 201511 | ||
| Gaucher | Zavesca (100 mg TID) | None | |
| MPS 1 | Aldurazyme (100 U/kg EOW = 0.58 mg/kg) | 1.2 mg/kg EOW | Horovitz et al, 201612 |
| NAGS deficiency | Start: Carbaglu (100 mg/[kg·d] up to 250 mg/kg if necessary, then 10‐100 mg/[kg·d]) | None | |
| Organic acidurias | Start: Carbaglu (100 mg/[kg·d] up to 250 mg/kg if necessary, then individually adjusted.) | None | |
| Wilson disease | Wilzin (50 mg TID) | 50 mg BID (in pregnant woman) | Masciullo et al, 201113 |
| Hereditary tyrosinemia type 1 | Orfadin (1 mg/[kg·d] divided into 2 doses) | Single daily dose | Schlune et al, 201214 |
| 0.55 to 0.65 mg/[kg·d] | El‐Karaksy et al, 201015 | ||
| 0.55 mg/[kg·d] | D'Eufemia et al, 201116 | ||
| Niemann‐Pick C | Zavesca (200 mg TID) | None | |
| MPS 6 | Naglazyme (1 mg/[kg·wk]) | None | |
| Pompe | Myozyme (20 mg/kg EOW) | 40 mg/[kg·wk] | Van Gelder et al, 201617 |
| 20 mg/[kg·wk] or 40 mg/kg EOW | Case et al, 201518 | ||
| MPS 2 | Elaprase (0.5 mg/[kg·wk]) | None | |
| Homocystinuria | Cystadane (100 mg/[kg·d] given in 2 doses daily) | None | |
| PKU | Kuvan (start: 10 mg/[kg·d], adjusted to 5–20 mg/[kg·d]) | Pediatric patients: 5 or 20 mg/[kg·d] | Qi et al, 201519 |
| Gaucher | Vpriv (60 U/kg EOW) | Starting dose: 60 U/kg per infusion EOW. Between 15 and 18 mo of cumulative treatment, patients were eligible for stepwise dose reduction to 30 U/kg per EOW based on achievement of at least 2 of 4 therapeutic goals | Elstein et al, 201120 |
| Short bowel syndrome | Revestive (0.05 mg/[kg·d]) | None | |
| Errors in bile acid synthesis | Orphacol (5 to 15 mg/[kg·d]) | None | |
| Cystinosis | Procysbi (1.3 g[m2·d]) | None | |
| Errors in bile acid synthesis | Kolbam (10–15 mg/[kg·d]) | None | |
| MPS 4a | Vimizim (2 mg/[kg·wk]) | None | |
| Gaucher | Cerdelga (84 mg BID) (100 mg eliglustat tartrate) | 50 mg BID or 100 mg BID | Charrow et al, 201821 |
| LAL deficiency | Kanuma (<6 mo: 1 mg/[kg·wk]; >6 mo: 1 mg/kg EOW) | Infants <6 mo: 0.35 mg/[kg·wk] with intrapatient dose escalation up to 5 mg/[kg·wk] | Jones et al, 201722 |
| Urea cycle disorders | Ravicti (4.5 mL/[m2·d] to 11.2 mL/[m2·d]) | None | |
| Hypophosphatasia | Strensiq (2 mg/kg 3 times per week or 1 mg/kg 6 times per week) | None | |
| Fabry | Galafold (123 mg EOD) | None |
BID, twice a day; EOD, every other day; EOW, every other week; LAL, lysosomal acid lipase; MPS, mucopolysaccharidosis; NAGS, N‐acetylglutamate synthetase; PKU, phenylketonuria; TID, 3 times daily; U, units.