Medicines for Pediatric & Geriatric Patients PDF

# Design and administration of medicines for paediatric and geriatric patients ## Adaptation of existing dosage forms - If a specific paediatric or geriatric product is not available, then the manipulation of existing products, usually tablets or capsules, before administration has to be considere...

# Design and administration of medicines for paediatric and geriatric patients ## Adaptation of existing dosage forms - If a specific paediatric or geriatric product is not available, then the manipulation of existing products, usually tablets or capsules, before administration has to be considered. - The process of tablet crushing or capsule opening and mixing with food or water is a form of unlicensed manufacture (i.e. the procedure has not received approval by the appropriate regulatory authority). - Therefore, it can be authorized only by a prescriber. - While in some situations it may be safe to undertake this practice, there are many tablet and capsule formulations where it would generally be considered unwise to tamper with the product before administration. ## Unlicensed products - When suitable licensed alternative formulations are not available, it might be necessary to prepare, by extemporaneous compounding or by outsourcing ("specials"), unlicensed formulations to ensure that a patient obtains access to a prescribed drug. - The quality of unlicensed products, patient acceptability, shelf life and cost can differ considerably. - It is therefore necessary for pharmacists to have some understanding of the quality of the available products, as frequently there may be a choice available to them. - Pharmacy compounding includes the preparation, mixing, assembling, packaging or labelling of a drug in response to a prescription written by an authorized prescriber. - It remains one of the highest-risk activities performed in pharmacy, as the risks of unlicensed medicines are combined with the inherent risks associated with the compounding of a formulation. - The quality, safety and efficacy of compounded preparations are jeopardized by the lack of standardization of compounding practices, nonharmonization of formulations and paucity of information on stability. - "Specials" have a similar status but are usually made in larger volumes by licensed manufacturers and suitably licensed hospital units (the licence is issued by the appropriate regulatory authority to authorize manufacture, not the product). - These products are not always subjected to full quality assurance test procedures, especially if they are not produced as a batch. - The preparation of the same drug as an unlicensed liquid medicine could range from crushing a tablet in a suspending agent with a 2-week shelf life to a sourced pure drug placed in a carefully formulated base with an extended shelf life. - However, in all cases, bioequivalence of the liquid medicine compared with a tablet or capsule will not have been demonstrated and therefore once a patient has been given and stabilized on a certain unlicensed product, it is preferable to always source the same product for that patient. - The main measure of quality of an unlicensed product is via the certificate with which it is supplied. - A certificate of analysis is supplied when the special has been produced in a batch and the supplier has quality assured the final product by analyzing the ingredients to confirm (quantitatively) the content of the active ingredient and excipients in the final product. - A certificate of conformity basically confirms that in the making of a one-off product, the production formula and process were followed. - Any problems with sourced ingredients will not be identified within such a process, nor will mistakes in production. - Consequently, a certificate of analysis is always preferable to a certificate of conformity. - There might be an appropriate product with a license available in another country, which can be imported, yet remains unlicensed in the country of import. - However, this option is not without logistic issues (product information provided in the local language, recall systems in place, time to obtain it, cost, etc.). - When sourcing and supplying unlicensed medicines, pharmacists need to be aware of their increased legal liability. - Where licensed medicines are used within the terms of their license, liability for any subsequent patient harms reside with the manufacturer. - If, however, a patient is harmed following receipt of an unlicensed medicine, the liability is shared between the prescriber and the supplier, with the actions of both being carefully considered in any subsequent legal action. - While a small number of medicines are licensed for administration via enteral feed tubes, the administration of medicines via enteral tubes usually represents an unlicensed action, as most medicines have not been tested via this route. - The practice of crushing or dispersing tablets, or opening capsules before administration, does not significantly increase the legal liability associated with this activity. ## Dosage form issues ### Immediate-release film-coated tablets Immediate-release film coats are placed on medicines for various reasons: - to mask the taste of the drug - to allow for colour recognition, e.g. to differentiate between different strengths of a product - to prevent contact sensitization when the medicine is being handled - In some cases (when the coat is nonfunctional and is there, for instance, only for colour recognition), damaging the film coat immediately before administration is unlikely to adversely affect patient care. - Removing a taste-masking coating may decrease palatability, whilst film coats which protect against contact sensitization should not be disrupted. - Drugs that have a narrow therapeutic window can switch from being effective to causing adverse events just by small changes to their bioavailability. - Crushing or dispersing digoxin tablets, which have a bioavailability of just less than 70%, could in theory increase the bioavailability to 100% and effectively increase the dose received in the patient by almost 50%. - Where formulations of drugs with a small therapeutic window are manipulated, the clinical effects should be monitored to ensure that toxicity does not ensue. ### Gastro-resistant (enteric) coated tablets Gastro-resistant coats are placed on tablets to: - protect the stomach from the active ingredient within the medicine, e.g. naproxen, aspirin - protect the active ingredient from the hostile environment of the stomach, e.g. omeprazole, lansoprazole - release the active ingredient beyond the stomach, e.g. sulfasalazine for local treatment within the colon. - It is never appropriate to recommend tampering with gastro-resistant coated formulations. ### Modified-release products - Modified-release products are carefully designed to release the drug over an extended period so as to reduce the peak drug concentrations in the blood observed with immediate-release products, and reduce the required frequency of dosing. - Reduction in peak plasma concentrations minimizes side effects, e.g. for nifedipine and theophylline, whereas reducing dosing frequency improves patient adherence. - Where a particular formulation is intended to extend the duration of drug release, a larger dose of the drug is incorporated compared with the dose in an immediate-release product. - Consequently, anything that damages the designed release mechanism (such as crushing tablets) could increase the likelihood of adverse events in the patient resulting from a larger than usual dose dump. - Where dose dumping of this type occurs, elimination of the drug is quicker and thus the patient will experience a period between doses when drug levels are subtherapeutic. - Consequently, tampering with any modified-release product is not recommended, unless the manufacturer clearly indicates that this is allowable. - Modified-release morphine capsules (MXL), for example, contain modified-release pellets which can be safely released from the outer shell of the capsule, providing they are not themselves tampered with or chewed, as this will affect their release properties. ### The practice of tablet splitting - To facilitate administration, sometimes tablets are cut into smaller segments, for instance to achieve a smaller dose for a child. - The limitations described earlier with respect to coated tablets equally apply. - Additionally, it should be checked that if a score line (break-line) is present, it is appropriate and safe (i.e. clearly stated in the SmPC for a particular product) for a part-tablet to be administered. - If this is not the case, the manufacturer should be contacted to confirm content uniformity and stability of tablet segments. The document also includes a diagram that illustrates the theoretical release of drug from an intact modified-release formulation and from a modified-release formulation that has been crushed. The diagram shows the following: - Modified-release formulation swallowed whole - Modified-release formulation crushed prior to administration - Maximum safe concentration - Minimum effective concentration The graph plots the concentration of drug in plasma against time following administration of a single dose.