Specific medicine switches for solid dose and liquid formulations

Recommendation

Re-titrate the dose of captopril when switching between Noyada oral solution and other captopril formulations.

Noyada oral suspension will produce slightly lower peak plasma levels than the same dose in tablet form.

Recommendation

A dose adjustment is not required because the difference in bioavailability is not clinically significant (63% in tablet form and 75% in oral solution).

However, digoxin 62.5 microgram tablets are approximately equivalent to 1mL of digoxin 50 microgram/mL oral solution for ease of administration.

Monitoring

See our guidance on digoxin monitoring.

Recommendation

The MHRA recommends that patients being treated for epilepsy should be maintained on a specific manufacturer’s product of carbamazepine.

Carbamazepine oral suspension will produce higher peak plasma levels than the same dose in the modified-release tablet form. Therefore, the total daily dose is divided into 4 doses for the liquid formulation and 2 doses for modified-release tablets.

Monitoring

See our guidance on carbamazepine monitoring.

Recommendation

Citalopram 10mg tablet is equivalent to 4 drops (8mg) of citalopram 40mg/mL oral solution.

Recommendation

The MHRA provides guidance on switching antiseizure medicines between different manufacturers’ products.

A cautious approach is required when switching between tablet and liquid formulations and when switching between clobazam brands.

The mean peak concentration from a single dose of suspension is higher than that for the tablet. This may lead to an increased risk of respiratory depression and sedation, which may be most noticeable when switching to oral suspension from tablets.

Monitoring

Monitor patients for signs of respiratory depression and sedation.

Recommendation

Lithium prescriptions should specify the brand and formulation. Switching from one brand or formulation of lithium to another requires the same precaution as initiation of treatment.

As most lithium tablets are modified-release, the total daily dose should be administered in divided doses when switching to a liquid preparation.

Lithium carbonate 200mg is approximately equivalent to lithium citrate 509mg.

Lithium carbonate and Priadel liquid (lithium citrate): switching

Lithium carbonate 204mg is equivalent to one 5mL spoonful of Priadel 520mg/5mL liquid (520mg lithium citrate).

Lithium carbonate and Li-Liquid (lithium citrate): switching

There are two strengths of Li-Liquid available. Ensure the necessary precautions are taken when prescribing, dispensing or administering Li-liquid, as selection of the incorrect strength may result in significant dosing errors.

Lithium carbonate 200mg is equivalent to one 5mL spoonful of Li-Liquid 509mg/5mL oral solution (509mg lithium citrate).

Lithium carbonate 400mg is equivalent to one 5mL spoonful of Li-Liquid 1018mg/5mL oral solution (1018mg lithium citrate).

Monitoring

Monitor serum lithium levels before switching and then weekly until re-stabilisation is achieved. Lithium has a narrow therapeutic index and is highly toxic when serum levels rise above the normal threshold. Lithium monitoring (SPS page) provides further detail.

Recommendation

The MHRA recommends that patients being treated for epilepsy should be maintained on a specific manufacturer’s product of phenytoin.

Phenytoin 100mg tablet or capsule (as phenytoin sodium) is approximately equivalent in therapeutic effect to 90mg phenytoin suspension (as phenytoin base). The dose is the same for all phenytoin products when initiating therapy.

Monitoring

Care is needed when switching. Monitor plasma phenytoin concentration.

Recommendation

The MHRA provides guidance on switching antiseizure medicines between different manufacturers’ products.

Sodium valproate: switching

Sodium valproate formulations are interchangeable with other sodium valproate immediate-release, modified-release or liquid formulations. The total daily dose should remain the same.

Valproic acid and sodium valproate: switching

No dose adjustment is required when switching between Convulex (valproic acid) and sodium valproate formulations.

Valproic acid (as valproate semi-sodium) and sodium valproate: switching

A 10% dose increase is recommended when switching from valproic acid (as valproate semi-sodium), such as Depakote, Syonell or Belvo, to sodium valproate.

Available products

Valproate is available in the UK in the following forms:

• sodium valproate
• valproic acid (as valproate semi-sodium)
• valproic acid

Both sodium valproate and valproic acid (valproate semi-sodium) are metabolised to valproic acid, which is responsible for the pharmacological activity of all three preparations.

Licensing varies between the different forms of valproate. If the patient is unable to take solid dose formulations of valproate, the only available liquid preparation is sodium valproate oral solution.

Monitoring

See our guidance on valproic acid and sodium valproate monitoring.

Recommendation

Sodium fusidate 500mg tablet is approximately equivalent to a dose of 15mL (750mg) fusidic acid suspension.

Recommendation

Refer to the individual Summary of Product Characteristics for specific dose regimens according to the indication when switching between solid dose and liquid formulation.

Itraconazole oral solution has a higher bioavailability than the capsules.

Recommendation

Tablets should be used in preference to the suspension as they have a higher bioavailability. Refer to the individual Summary of Product Characteristics for specific dose regimens according to the indication.

Differences in frequency of dosing, administration with food and plasma drug concentration achieved means that posaconazole tablets and oral suspension are not interchangeable.

Recommendation

Switching between oral formulations should only be carried out under specialist advice and supervision.

Oral ciclosporin products should be prescribed and dispensed by brand name only.

Switching between the same brand

No dose adjustments are required when switching formulations within the same brand as they are bioequivalent:

• Neoral capsules and oral solution
• Sandimmun capsules and oral solution
• Capsorin capsules and oral solution

Switching between Sandimmun and Neoral

The same daily dose can be prescribed when switching between Sandimmun and Neoral branded formulations. Switch cautiously with monitoring as these have different bioavailabilities and peak plasma concentrations.

Monitoring

See our guidance on ciclosporin monitoring.

Refer to the Summary of Product Characteristics for information on monitoring requirements for specific switches.

Recommendation

Refer to the individual Summary of Product Characteristics for specific dose regimens.

Mercaptopurine tablets and mercaptopurine 20mg/mL for oral suspension (Xaluprine) are not bioequivalent with respect to peak plasma concentration and there is considerable inter-individual variability.

Monitoring

Monitor haematological function closely when switching. See our guidance on mercaptopurine monitoring.

Recommendation

No dose adjustment is required when switching between mycophenolate mofetil solid dose formulations and mycophenolate mofetil suspension.

Mycophenolate mofetil and mycophenolate sodium: switching

Mycophenolate sodium 720mg administered twice daily (1440mg daily dose) is approximately equivalent to 1g mycophenolate mofetil administered twice daily (2g daily dose) in terms of mycophenolic acid content.

Recommendation

The MHRA recommends that oral tacrolimus should be prescribed and dispensed by brand name only to minimise the risk of inadvertent switching between products, which has been associated with reports of toxicity and graft rejection.

Switching between oral formulations should only be carried out under specialist advice and supervision. Guidance is only available for switching between Prograf capsules and Modigraf granules for oral suspension.

Prograf capsules to Modigraf granules for oral suspension: switching

The total daily dose of tacrolimus should remain the same. Round the dose to the nearest whole sachets (do not give part sachets) and prescribe as two equally-divided doses. If equal doses are not possible, the larger dose should be administered in the morning.

Switching between different immediate- or prolonged-release preparations can cause clinically relevant differences in systemic exposure to tacrolimus.

Monitoring

Specialist supervision and plasma tacrolimus concentration monitoring is required when switching a patient to a different brand of oral tacrolimus as it has a narrow therapeutic index.

Recommendation

Alfacalcidol 500 nanogram capsule is approximately equivalent to 5 drops (0.25mL) of One-Alpha 2 microgram/mL oral drops (100 nanograms per drop).

Recommendation

One drop of Thorens 10,000 international units/mL oral drops, solution contains:

• 200 international units colecalciferol (vitamin D3)
• equivalent to 5 micrograms colecalciferol (vitamin D)