Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://emc.medicines.org.uk), or the British National Formulary (BNF) (www.bnf.org).

• When nebulized 0.9% saline solution is used to ease cough associated with tenacious secretions [Ahmedzai and Davis, 1997; Twycross and Wilcock, 2001; Twycross et al, 2002]:
• Initially use 2.5 mL to 5 mL four times a day.
• If greater symptomatic relief is required, gradually increase nebulizer use to up to every 2 hours.
• A very small trial (n = 8) found use of nebulized saline for approximately 5 minutes prior to chest physiotherapy in people with bronchiectasis may give more benefit than use of saline alone [Sutton et al, 1988]. Note: availability of physiotherapy in the community may be limited.
• People should be reviewed after 48 hours to check that they are adequately responding and that there are no usability problems [Twycross et al, 2002].

• Instruct people to take steady normal breaths (interspersed with occasional deep ones) and to stop 1 minute after the nebulizer contents start spluttering or after a maximum of 10 minutes [Twycross et al, 2002].
• Advise people of the need to speak to their doctor or nurse if they do not adequately benefit when using the nebulizer [Twycross et al, 2002].
• When using a nebulizer, it is useful to have some tissues to hand as there is the potential to expectorate [Twycross et al, 2002].
• The nebulizer and mask or mouthpiece should be cleaned at least once a day (but preferably after each use) by washing in warm water and detergent, rinsing, and drying. To ensure the equipment is dry, it should be set up and switched on for a few moments. Once a week the compressor should be unplugged and, together with the tubing, should be wiped with a damp cloth [Twycross et al, 2002].

• If the person is already taking a strong opioid such as morphine, do not try a weak opioid such as pholcodine. Instead an 'as required' dose of morphine solution should be used to relieve cough and, if this is beneficial, continue to use in this way, or increase the regular morphine dose [Twycross et al, 2002]. The 'as required' dose is a sixth of the total daily dose of regular morphine.
• Pholcodine Linctus BP 10 mg may be taken three to four times a day for symptomatic relief of unproductive coughs. Sugar-free brands are available where preferred, and for people with diabetes.
• The adverse effects usually associated with opioids (e.g. constipation) are rarely reported, as pholcodine is such a weak opioid. However, it has mild sedative properties and so people should be warned to avoid activities where drowsiness may be detrimental.
• If pholcodine (or codeine) is ineffective, switch to morphine solution 5 mg to 10 mg every 4 hours and 'as required'.

[ABPI Medicines Compendium, 2003; BNF 53, 2007]

• If the person is already taking a strong opioid such as morphine, do not try a weak opioid such as codeine. Instead an 'as required' dose of morphine solution should be used to relieve cough and, if this is beneficial, continue to use in this way, or increase the regular morphine dose [Twycross et al, 2002]. The 'as required' dose is a sixth of the total daily dose of regular morphine.
• Codeine linctus BP 5 mL to 10 mL (15 mg to 30 mg) three to four times a day, or codeine phosphate tablets 30 mg to 60 mg three to four times a day can be taken for symptomatic relief of a dry cough [Twycross et al, 2002; Regnard and Hockley, 2004; BNF 53, 2007]. Doses of codeine 10 mg to 120 mg/day have been found to be effective in relieving the frequency and intensity of cough [Homsi et al, 2001].
• Sugar-free brands of codeine linctus BP are available where preferred, and for people with diabetes.
• Consider using codeine phosphate tablets if a dose requiring a large volume of linctus is required. Codeine phosphate tablets are not licensed for symptomatic relief of a dry or painful cough.
• Codeine has the potential to cause gastrointestinal problems (e.g. constipation), and central nervous system (e.g. sedation) toxicity [Homsi et al, 2001; BNF 53, 2007]. People should be warned to avoid activities where drowsiness may be detrimental.
• If codeine (or pholcodine) is ineffective, switch to morphine solution 5 mg to 10 mg every 4 hours and 'as required'.

• Morphine should be titrated in the same way as for pain relief, and the initial starting dose will depend on the person's previous exposure to opioids. For more information about the use of morphine in pain relief, see the CKS topic on Palliative cancer care - pain.
• For someone not already taking an opioid, a dose of 2.5 mg regularly every 4 hours, and as required, is suitable.
• For someone in whom a weak opioid (e.g. codeine or pholcodine) was ineffective, a dose of 5 mg to 10 mg regularly every 4 hours, and as required, should be used.
• If using 4-hourly morphine:
• After 1–2 days, calculate the total dose given over 24 hours, and use this to recalculate the 4-hourly dose. (The new 4-hourly and 'as required' dose is a sixth of the new total daily dose).
• Repeat this process every 1–2 days until the cough is controlled.
• Once a stable dose has been reached, this can be converted to once- or twice-daily modified-release morphine if preferred.
• For someone already taking a strong opioid such as morphine (for analgesia), do not try a weak opioid such as pholcodine or codeine. Instead, use an 'as required' dose of morphine to relieve cough.
• If an 'as required' dose relieves cough, either increase the regular daily dose by 30–50% every 2–3 days until symptoms are controlled or adverse effects prevent further dose increases, or continue to use additional morphine as required.
• If the total daily dose is increased, the 'as required' dose will also need to be recalculated. If an 'as required' dose of morphine does not relieve cough, there is little point continuing to increase the dose.
• Some people with cough but no pain can benefit from a dose of morphine at bedtime to prevent cough from disturbing sleep.

[Twycross et al, 2002]

• Adverse effects are less serious when morphine is used as a cough suppressant than for analgesia, as doses for cough are generally lower.
• Common adverse effects of morphine (especially in the elderly) include nausea and vomiting, drowsiness, unsteadiness, and constipation:
• An anti-emetic (e.g. haloperidol or metoclopramide) should be prescribed [Twycross et al, 2002]:
• Regularly for the first week to prevent opioid-induced nausea and vomiting if the person has experienced nausea with a weak opioid, or
• On standby, for use on an 'as required' basis for a week, in case the person experiences nausea with morphine but has not previously had nausea with a weak opioid.
• Some drowsiness is common at the start of treatment or after dose increases, and people should be warned to avoid activities where drowsiness may be detrimental [Twycross et al, 2002]. However, in most people any drowsiness resolves within a few days. Persistent sedation can usually be resolved by dose reduction.
• Constipation is an ongoing problem, as tolerance to morphine does not develop:
• Prescribe a regular stimulant laxative (e.g. senna or bisacodyl) with a faecal softener (e.g. docusate or lactulose), or a laxative likely to have both properties (e.g. co-danthramer or co-danthrusate) to prevent opioid-induced constipation. Note: people taking dantron-containing laxatives may experience reddening of the perianal area.
• More occasional adverse effects of strong opioids include dry mouth, sweating, pruritus, hallucinations, myoclonus, and bronchoconstriction [Twycross et al, 2002].

• Carbocisteine and mecysteine hydrochloride are options to reduce the viscosity of the secretions.
• If a palliative care patient does not demonstrate any convincing benefit after a week or two of using a mucolytic, then use of a mucolytic should be discontinued.
• For carbocisteine:
• A starting dose of carbocisteine 750 mg three times a day is recommended.
• Once a satisfactory improvement in sputum viscosity has been achieved, the dose should be reduced to carbocisteine 750 mg twice a day.
• For mecysteine hydrochloride:
• Start with mecysteine 200 mg, four times a day, for 2 days; then 200 mg, three times a day (for up to 6 weeks).
• After 6 weeks use, the dose should be reduced to mecysteine 200 mg twice a day.

[Twycross et al, 2002; ABPI Medicines Compendium, 2006; BNF 53, 2007]

• Carbocisteine and mecysteine may disrupt the gastric mucosal barrier and should therefore be avoided in people with active peptic ulceration [ABPI Medicines Compendium, 2006; BNF 53, 2007].