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. 2022 Jul 2;14(13):2755. doi: 10.3390/nu14132755

Table 4.

Pharmacologic treatment of acute hyperammonaemia.

Drug	First Dose	Maintenance	Considerations
Urea cycle enhancers: useful in cases of hyperammonaemia due to any cause but primary urea cycle deficiencies. Should be always included in cases of unknown aetiology.
N-carbamylglutamate	100 mg/kg	100–250 mg/kg/day in 2–4 doses	Oral (or crushed through feeding tube): tablets.
			Useful in most genetic and non-genetic disorders. Not useful in most known primary urea cycle disorders (only NAGS deficiency).
			Maximum dose not stablished. In adults use weight for lean body mass.
L-Arginine	<20 kg: 250–400 mg/kg	<20 kg: 250 mg/kg/day	Oral: powder, sachets. IV: diluted in 10% glucose solution. Can be administered together with benzoate.
	>20 kg: 250 mg/kg (max 12 g)	>20 kg: 200 mg/kg/day (max 12 g/day)

Urea cycle scavengers: useful in all cases of hyperammonaemia. Should be included in hyperammonaemia due to primary urea cycle disorders or severe cases of unknown aetiology.
Sodium benzoate ± Sodium phenylacetate	<20 kg: 250 mg/kg	<20 kg: 250–500 mg/kg/day	IV: requires central venous access.
	>20 kg: 5.5 g/m² (max 12g)	>20 kg: 5.5 g/m² (max 12g/day)	Diluted in 10% glucose solution and administered over 2 h.
			Attention to the sodium content.
			Precaution in organic acidaemias.
Phenylbutyrate		<20 kg: 250–500 mg/kg/day in 4 doses	Oral: tablet, powder, or solution presentations.
Phenylbutyrate		>20 kg: 9.9–13 g/m²/day in 4 doses	Slow action: not first option in acute hyperammonaemia.
Cofactor therapy: useful if unknown aetiology or an underlying genetic disease is suspected. If known diagnosis, only start those that have been proven effective.
L-Carnitine	50 mg/kg	100 mg/kg/day in 4 doses	Oral: 10 or 30% solutions.
	Maximum dose: 4 g	Maximum dose: 6 g/day	IV: 20% solution.
			Caution in long-chain fatty acid oxidation deficiencies.
Biotin	10 mg	20–40 mg/day	Oral or iv presentations.
Hydroxocobalamin	1 mg	Repeat only depending on diagnosis	IM or IV.
Hydroxocobalamin	1 mg	Repeat only depending on diagnosis	Only one dose required initially.
Therapies aimed to reduce ammonia gut production: proven effective in cases of hepatic encephalopathy and propionic acidaemia. Slow action: not useful as monotherapy and if high ammonia levels.
Osmotic laxatives	Lactulose 15–20 mL every 12 h		Titrate until 2–3 stools/day.
Osmotic laxatives	Polyethylene glycol 1 dose		Titrate until 2–3 stools/day.
Antimicrobial agents	Rifaximin 2–12 years of age (off-label) 20–30 mg/kg/day 2–4 doses >12 years of age 200–400 mg/day 2–4 doses		Use preferably antibiotics with low absorption rates. Other options: metronidazole, ciprofloxacin, doxycycline, etc.