Levocarnitine

US label §DOSAGE AND ADMINISTRATION, adults, verbatim: 'The recommended dosage of levocarnitine is 1 to 3 g/day for a 50 kg subject, which is equivalent to 10 to 30 mL/day of levocarnitine oral solution. Higher doses should be administered only with caution and only where clinical and biochemical considerations make it seem likely that higher doses will be of benefit. Dosage should start at 1 g/day (10 mL/day), and be increased slowly while assessing tolerance and therapeutic response.' Note the dose is expressed FOR A 50 kg SUBJECT — scale by clinical judgement, not by a fixed per-kg rule, because the label gives none for adults. The mL figures belong to the US oral solution, whose strength is pinned by the label's own equivalences (1 g = 10 mL, i.e. 100 mg/mL); the UK product in this bundle is a 30 % solution and therefore a DIFFERENT strength — never carry a mL volume between the two. NO ADULT MAXIMUM is stated, so maxDose is empty; the '3 g/day' ceiling that does appear in the label is stated for infants and children, not adults, and has deliberately not been copied up here. What the UK SPC §4.2 gives is an ORAL maintenance regimen under its heading 'Haemodialysis - maintenance therapy', verbatim: 'If significant clinical benefit has been gained by a first course of intravenous Levocarnitine then maintenance therapy can be considered using 1g per day of Levocarnitine orally. On the day of the dialysis oral Levocarnitine has to be administered at the end of the session.' The IV course it refers to is not dosed anywhere in the bundle, so no IV figure is published. INBORN ERRORS OF METABOLISM — the UK SPC's regimen (up to 200 mg/kg/day orally, up to 400 mg/kg/day or the IV route in acute decompensation) sits under its paediatric heading and is recorded in paedDose, not here.

DELIBERATELY NO SINGLE PER-KG FIGURE. The two labels in this bundle do not agree, and the UK SPC says the dose is disorder-specific. UK SPC §4.2, verbatim: 'The dosage required depends upon the specific inborn error of metabolism concerned and the severity of presentation at the time of treatment. However, the following can be considered as a general guide. An oral dosage of up to 200mg/kg/day in divided doses (2 to 4) is recommended for chronic use in some disorders, with lower doses sufficing in other conditions. If clinical and biochemical symptoms do not improve, the dose may be increased on a short-term basis. Higher doses of up to 400mg/kg/day may be necessary in acute metabolic decompensation or the i.v. route may be required.' US label, verbatim: 'Infants and children: The recommended dosage of levocarnitine is 50 to 100 mg/kg/day which is equivalent to 0.5 mL/kg/day levocarnitine oral solution… Dosage should start at 50 mg/kg/day, and be increased slowly to a maximum of 3 g/day (30 mL/day) while assessing tolerance and therapeutic response.' A calculator fed 50 mg/kg/day would sit fourfold below the UK ceiling for a child in metabolic decompensation, and one fed 200 mg/kg/day would be a ceiling rather than a recommendation — so dosePerKg is null and the prescriber must pick the figure for the specific disorder. CONCENTRATION IS NULL ON PURPOSE: the two products are different strengths — the US oral solution is 100 mg/mL (the label's own equivalences: 1 g = 10 mL, 3 g = 30 mL, 0.5 mL/kg/day = 50 mg/kg/day), while the UK product is a 30 % solution — so no single mg/mL value can serve both and no volume should be auto-calculated. EXCIPIENT WARNINGS for the UK 30 % oral solution (§4.4): it contains sorbitol, and 'Patients with hereditary fructose intolerance (HFI) should not take/be given this medicinal product'; it also 'contains approximately 1.5 mg sodium methyl parahydroxybenzoate per ml', which 'may increase jaundice (yellowing of the skin and eyes) in newborn babies (up to 4 weeks old). May cause allergic reactions (possibly delayed).' Verify the dose for the specific metabolic disorder against a children's formulary and specialist metabolic advice before prescribing.