Indications And Dose
Vertigo, tinnitus and hearing loss associated with Ménière’s disease ▶BY MOUTH ▶Adult: Initially 16 mg 3 times a day, dose preferably taken with food; maintenance 24–48 mg daily
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Drug reference
Vertigo, tinnitus and hearing loss associated with Ménière’s disease ▶BY MOUTH ▶Adult: Initially 16 mg 3 times a day, dose preferably taken with food; maintenance 24–48 mg daily
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Phaeochromocytoma
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Asthma. history of peptic ulcer
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→Appendix 1: betahistine
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▶Common or very common Gastrointestinal discomfort. headache. nausea ▶Frequency not known Allergic dermatitis. vomiting
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Avoid unless clearly necessary—no information available.
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Use only if potential benefit outweighs risk—no information available.
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There can be variation in the licensing of different medicines containing the same drug. Forms available from special-order manufacturers include: oral suspension, oral solution Tablet CAUTIONARY AND ADVISORY LABELS 21 ▶Betahistine dihydrochloride (Non-proprietary) Betahistine dihydrochloride 8 mg Betahistine 8mg tablets | 84 tablet P £10.50 DT = £2.08 | 120 tablet P £3.48 Betahistine dihydrochloride 16 mg Betahistine 16mg tablets | 84 tablet P £17.19 DT = £3.41 ▶Serc (Mylan) Betahistine dihydrochloride 8 mg Serc 8mg tablets | 120 tablet P £9.04 Betahistine dihydrochloride 16 mg Serc 16mg tablets | 84 tablet P £12.65 DT = £3.41 Nervous system Pain Pain, Chronic Overview Pain is described as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Physiologically, it can be described as neuropathic or nociceptive, and classified as either acute or chronic in nature. Nociceptive pain generally responds to treatment with conventional analgesics whereas neuropathic pain responds poorly to conventional analgesics and can be difficult to treat. Chronic pain is defined as pain that has been present for more than 12 weeks; beyond the expected time of wound healing. It is a complex phenomenon and can have a considerable impact on quality of life, resulting in significant suffering and disability. Aims of treatment Treatment aims to reduce the impact of chronic pain on quality of life, mood and function. Management of chronic pain A wide range of both pharmacological and non- pharmacological management strategies are available for chronic pain. For guidance on the management of chronic pain in osteoarthritis, see Osteoarthritis and soft-tissue disorders p. 1152, for musculoskeletal conditions, see Soft- tissue disorders p. 1218, and for neuropathic pain, see Neuropathic pain p. 505. g Consider specialist referral when non-specialist management is failing, the pain is poorly controlled, the patient is experiencing significant distress, and/or where a specialist intervention is being considered. h Non-drug treatment g Exercise and exercise therapies, regardless of their form, are recommended in the management of chronic pain; strategies to improve adherence (such as supervised exercise sessions) should be implemented. Transcutaneous electrical nerve stimulation (either high or low frequency) should be considered for the relief of chronic pain. Referral to a pain management programme and psychologically based interventions such as cognitive behavioural therapy, biofeedback, and progressive relaxation should be considered for patients with chronic pain; brief education should be given to all patients. The use of self-management resources (safe, low- technology, community-based, and affordable programmes) should be considered to complement other therapies in the treatment of chronic pain. For information on self- management resources, see SIGN clinical guideline: Management of chronic pain (see Useful resources). h Drug treatment A variety of analgesics are used in the treatment of chronic pain and can be divided into non-opioid and opioid analgesics. Although developed and validated for cancer pain, the World Health Organisation (WHO) analgesic ladder is widely used to guide the basic treatment of acute and chronic pain; whilst there is little evidence to support its use in chronic pain it may provide an analgesic strategy for non- specialists. The WHO analgesic ladder is available at: www.who.int/cancer/palliative/painladder/en/. Individual responses to analgesia vary considerably, both in terms of efficacy and side effects; even with the same chronic pain syndrome, the underlying pain mechanisms may differ between individuals. This provides challenges with assessment and management in routine clinical Nervous system practice. g If an individual either fails to tolerate, or has an inadequate response to a drug, then it is worthwhile considering a different agent from the same class. Individuals using analgesics to manage chronic pain should be reviewed at least annually, with review frequency increased if there are any changes to their medication, underlying pain syndrome or comorbidities. h For comparative information on analgesic options, see Analgesics below. g Depression is a common comorbidity in those with chronic pain; individuals should be monitored and treated for depression when necessary. Optimising antidepressant therapy should be considered in individuals with moderate depression and chronic pain. h For information on the treatment of depression in adults, see Antidepressant drugs p. 376. Non-opioid analgesics Non-opioid analgesics include paracetamol p. 465 and non- steroidal anti-inflammatory drugs (NSAIDs). For information on the use of NSAIDs, see Non-steroidal anti-inflammatory drugs p. 1193. g Cannabis-based medicinal products (nabilone, dronabinol, delta-9-tetrahydrocannabinol (THC), and combination cannabidiol (CBD) with THC) are not recommended for managing chronic pain. The use of CBD is not recommended unless as part of a clinical trial. If the patient is already using cannabis-based treatment for chronic pain, it may be continued until they and the appropriate clinician deem it suitable to stop. h Topical analgesic preparations may be useful for the management of chronic pain in different disorders. Preparations include capsaicin or lidocaine (see Neuropathic pain p. 505), NSAIDs (see Osteoarthritis and soft-tissue disorders p. 1152), and rubefacients (see Soft-tissue disorders p. 1218). Compound preparations g The use of single-ingredient analgesics is preferred to allow for independent titration of each drug; however, fixed dose combination analgesics (except those with low-dose opioids) may be considered for those with stable chronic pain. h Opioids Opioid analgesics can be divided into those used for mild-to- moderate pain (such as codeine phosphate p. 475) and those used for moderate-to-severe pain (such as morphine p. 484 or oxycodone hydrochloride p. 487). g Opioids should only be considered in carefully selected individuals for the short- to medium-term treatment of chronic non-malignant pain, when other therapies have been insufficient; the benefits should outweigh the risks of serious harms (such as addiction, overdose and death). With continuous longer-term use of opioids, tolerance and dependence compromise both safety and efficacy. Prescribers should have knowledge of opioid pharmacology, and be competent and experienced in the use of strong opioids. When starting treatment with an opioid there should be an agreement between the prescriber and patient about the expected outcomes—with advanced agreement on the reduction and cessation of the opioid if these are not met. Opioids should be reviewed at least annually but more frequently if required; consideration should be given to a gradual reduction of the opioid to the lowest effective dose or complete cessation. Pain specialist advice or review should be sought for individuals taking doses >90 mg/day morphine equivalent. h There is a rationale for switching between opioids if the initial choice is ineffective or if side effects are unacceptable. g Caution should be used with dose comparisons and switching due to limited evidence for the accuracy of dose equivalence tables and considerable variation between individuals. h For more information on opioid dose conversions or equivalents, see Prescribing in palliative care p. 28. Resources for the prescribing of opioids have been produced by the Faculty of Pain Medicine in partnership with Public Health England, and are available at: fpm.ac.uk/opioids- aware. Useful Resources Management of chronic pain. Scottish Intercollegiate Guidelines Network. SIGN guideline 136. August 2019. www.sign.ac.uk/sign-136-management-of-chronic-pain.html Analgesics Pain relief The non-opioid drugs, paracetamol p. 465 and aspirin p. 130 (and other NSAIDs), are particularly suitable for pain in musculoskeletal conditions, whereas the opioid analgesics are more suitable for moderate to severe pain, particularly of visceral origin. Pain in sickle-cell disease The pain of mild sickle-cell crises is managed with paracetamol, a NSAID, codeine phosphate p. 475, or dihydrocodeine tartrate p. 477. Severe crises may require the use of morphine p. 484 or diamorphine hydrochloride p. 477; concomitant use of a NSAID may potentiate analgesia and allow lower doses of the opioid to be used. Pethidine hydrochloride p. 490 should be avoided if possible because accumulation of a neurotoxic metabolite can precipitate seizures; the relatively short half-life of pethidine hydrochloride necessitates frequent injections. Dental and orofacial pain Analgesics should be used judiciously in dental care as a temporary measure until the cause of the pain has been dealt with. Dental pain of inflammatory origin, such as that associated with pulpitis, apical infection, localised osteitis or pericoronitis is usually best managed by treating the infection, providing drainage, restorative procedures, and other local measures. Analgesics provide temporary relief of pain (usually for about 1 to 7 days) until the causative factors have been brought under control. In the case of pulpitis, intra-osseous infection or abscess, reliance on analgesics alone is usually inappropriate. Similarly the pain and discomfort associated with acute problems of the oral mucosa (e.g. acute herpetic gingivostomatitis, erythema multiforme) may be relieved by benzydamine hydrochloride mouthwash or spray p. 1280 until the cause of the mucosal disorder has been dealt with. However, where a patient is febrile, the antipyretic action of paracetamol or ibuprofen p. 1203 is often helpful. The choice of an analgesic for dental purposes should be based on its suitability for the patient. Most dental pain is relieved effectively by non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs that are used for dental pain include ibuprofen, diclofenac sodium p. 1198, and aspirin. Paracetamol has analgesic and antipyretic effects but no anti-inflammatory effect. Opioid analgesics such as dihydrocodeine tartrate act on the central nervous system and are traditionally used for moderate to severe pain. However, opioid analgesics are relatively ineffective in dental pain and their side-effects can be unpleasant. Paracetamol, ibuprofen, or aspirin are adequate for most cases of dental pain and an opioid is rarely required. Combining a non-opioid with an opioid analgesic can provide greater relief of pain than either analgesic given alone. However, this applies only when an adequate dose of each analgesic is used. Most combination analgesic preparations have not been shown to provide greater relief of pain than an adequate dose of the non-opioid component given alone. Moreover, combination preparations have the disadvantage of an increased number of side-effects. Any analgesic given before a dental procedure should have a low risk of increasing postoperative bleeding. In the case of pain after the dental procedure, taking an analgesic before the effect of the local anaesthetic has worn off can improve control. Postoperative analgesia with ibuprofen or aspirin is usually continued for about 24 to 72 hours. Temporomandibular dysfunction can be related to anxiety in some patients who may clench or grind their teeth (bruxism) during the day or night. The muscle spasm (which appears to be the main source of pain) may be treated empirically with an overlay appliance which provides a free sliding occlusion and may also interfere with grinding. In addition, diazepam p. 360, which has muscle relaxant as well as anxiolytic properties, may be helpful but it should only be prescribed on a short-term basis during the acute phase. Analgesics such as aspirin or ibuprofen may also be required. Dysmenorrhoea Use of an oral contraceptive prevents the pain of dysmenorrhoea which is generally associated with ovulatory cycles. If treatment is necessary paracetamol or a NSAID will generally provide adequate relief of pain. The vomiting and severe pain associated with dysmenorrhoea in women with endometriosis may call for an antiemetic (in addition to an analgesic). Antispasmodics (such as alverine citrate p. 93) have been advocated for dysmenorrhoea but the antispasmodic action does not generally provide significant relief. Non-opioid analgesics and compound analgesic preparations Aspirin is indicated for headache, transient musculoskeletal pain, dysmenorrhoea, and pyrexia. In inflammatory conditions, most physicians prefer anti-inflammatory treatment with another NSAID which may be better tolerated and more convenient for the patient. Aspirin is used increasingly for its antiplatelet properties. Aspirin tablets or dispersible aspirin tablets are adequate for most purposes as they act rapidly. Gastric irritation may be a problem; it is minimised by taking the dose after food. Enteric-coated preparations are available, but have a slow onset of action and are therefore unsuitable for single-dose analgesic use (though their prolonged action may be useful for night pain). Aspirin interacts significantly with a number of other drugs and its interaction with warfarin sodium p. 150 is a special hazard. Paracetamol is similar in efficacy to aspirin, but has no demonstrable anti-inflammatory activity; it is less irritant to the stomach and for that reason is now generally preferred to aspirin, particularly in the elderly. Overdosage with paracetamol is particularly dangerous as it may cause hepatic damage which is sometimes not apparent for 4 to 6 days. Nefopam hydrochloride p. 467 may have a place in the relief of persistent pain unresponsive to other non-opioid analgesics. It causes little or no respiratory depression, but sympathomimetic and antimuscarinic side-effects may be troublesome. Non-steroidal anti-inflammatory analgesics (NSAIDs) are particularly useful for the treatment of patients with chronic disease accompanied by pain and inflammation. Some of them are also used in the short-term treatment of mild to moderate pain including transient musculoskeletal pain but paracetamol is now often preferred, particularly in the elderly. They are also suitable for the relief of pain in dysmenorrhoea and to treat pain caused by secondary bone tumours, many of which produce lysis of bone and release prostaglandins. Selective inhibitors of cyclo-oxygenase-2 may be used in preference to non-selective NSAIDs for Nervous system patients at high risk of developing serious gastro-intestinal side-effects. Several NSAIDs are also used for postoperative analgesia. A non-opioid analgesic administered by intrathecal infusion (ziconotide (Prialt ®), available from Eisai) is licensed for the treatment of chronic severe pain; ziconotide can be used by a hospital specialist as an adjunct to opioid analgesics. Compound analgesic preparations Compound analgesic preparations that contain a simple analgesic (such as aspirin p. 130 or paracetamol p. 465) with an opioid component reduce the scope for effective titration of the individual components in the management of pain of varying intensity. Compound analgesic preparations containing paracetamol or aspirin with a low dose of an opioid analgesic (e.g. 8 mg of codeine phosphate p. 475 per compound tablet) are commonly used, but the advantages have not been substantiated. The low dose of the opioid may be enough to cause opioid side-effects (in particular, constipation) and can complicate the treatment of overdosage yet may not provide significant additional relief of pain. A full dose of the opioid component (e.g. 60 mg codeine phosphate) in compound analgesic preparations effectively augments the analgesic activity but is associated with the full range of opioid side-effects (including nausea, vomiting, severe constipation, drowsiness, respiratory depression, and risk of dependence on long-term administration). Important: the elderly are particularly susceptible to opioid side-effects and should receive lower doses. In general, when assessing pain, it is necessary to weigh up carefully whether there is a need for a non-opioid and an opioid analgesic to be taken simultaneously. Caffeine is a weak stimulant that is often included, in small doses, in analgesic preparations. It is claimed that the addition of caffeine may enhance the analgesic effect, but the alerting effect, mild habit-forming effect and possible provocation of headache may not always be desirable. Moreover, in excessive dosage or on withdrawal caffeine may itself induce headache. Co-proxamol tablets (dextropropoxyphene in combination with paracetamol) are no longer licensed because of safety concerns, particularly toxicity in overdose. Co-proxamol tablets [unlicensed] may still be prescribed for patients who find it difficult to change, because alternatives are not effective or suitable. Opioid analgesics and dependence Opioid analgesics are usually used to relieve moderate to severe pain particularly of visceral origin. Repeated administration may cause dependence and tolerance, but this is no deterrent in the control of pain in terminal illness. Regular use of a potent opioid may be appropriate for certain cases of chronic non-malignant pain. For general guidance on the use of opioid analgesics in chronic pain, see Pain, Chronic p. 461. Strong opioids Morphine p. 484 remains the most valuable opioid analgesic for severe pain although it frequently causes nausea and vomiting. It is the standard against which other opioid analgesics are compared. In addition to relief of pain, morphine also confers a state of euphoria and mental detachment. Morphine is the opioid of choice for the oral treatment of severe pain in palliative care. It is given regularly every 4 hours (or every 12 or 24 hours as modified-release preparations). Buprenorphine p. 468 has both opioid agonist and antagonist properties and may precipitate withdrawal symptoms, including pain, in patients dependent on other opioids. It has abuse potential and may itself cause dependence. It has a much longer duration of action than Nervous system morphine and sublingually is an effective analgesic for 6 to 8 hours. Unlike most opioid analgesics, the effects of buprenorphine are only partially reversed by naloxone hydrochloride p. 1440. Dipipanone hydrochloride used alone is less sedating than morphine but the only preparation available contains an antiemetic and is therefore not suitable for regular regimens in palliative care. Diamorphine hydrochloride p. 477 (heroin) is a powerful opioid analgesic. It may cause less nausea and hypotension than morphine. In palliative care the greater solubility of diamorphine hydrochloride allows effective doses to be injected in smaller volumes and this is important in the emaciated patient. Alfentanil p. 1413, fentanyl p. 479 and remifentanil p. 1414 are used by injection for intra-operative analgesia; fentanyl is available in a transdermal drug delivery system as a self-adhesive patch which is changed every 72 hours. Methadone hydrochloride p. 524 is less sedating than morphine and acts for longer periods. In prolonged use, methadone hydrochloride should not be administered more often than twice daily to avoid the risk of accumulation and opioid overdosage. Methadone hydrochloride may be used instead of morphine in the occasional patient who experiences excitation (or exacerbation of pain) with morphine. Oxycodone hydrochloride p. 487 has an efficacy and side- effect profile similar to that of morphine. It is commonly used as a second-line drug if morphine is not tolerated or does not control the pain. Papaveretum is rarely used; morphine is easier to prescribe and less prone to error with regard to the strength and dose. Pentazocine p. 490 has both agonist and antagonist properties and precipitates withdrawal symptoms, including pain in patients dependent on other opioids. By injection it is more potent than dihydrocodeine tartrate p. 477 or codeine phosphate, but hallucinations and thought disturbances may occur. It is not recommended and, in particular, should be avoided after myocardial infarction as it may increase pulmonary and aortic blood pressure as well as cardiac work. Pethidine hydrochloride p. 490 produces prompt but short-lasting analgesia; it is less constipating than morphine, but even in high doses is a less potent analgesic. It is not suitable for severe continuing pain. It is used for analgesia in labour; however, other opioids, such as morphine or diamorphine hydrochloride, are often preferred for obstetric pain. Tapentadol p. 491 produces analgesia by two mechanisms. It is an opioid-receptor agonist and it also inhibits noradrenaline reuptake. Nausea, vomiting, and constipation are less likely to occur with tapentadol than with other strong opioid analgesics. Tramadol hydrochloride p. 491 produces analgesia by two mechanisms: an opioid effect and an enhancement of serotonergic and adrenergic pathways. It has fewer of the typical opioid side-effects (notably, less respiratory depression, less constipation and less addiction potential); psychiatric reactions have been reported. Weak opioids Codeine phosphate can be used for the relief of mild to moderate pain where other painkillers such as paracetamol or ibuprofen p. 1203 have proved ineffective. Dihydrocodeine tartrate has an analgesic efficacy similar to that of codeine phosphate. Higher doses may provide some additional pain relief but this may be at the cost of more nausea and vomiting. Meptazinol p. 484 is claimed to have a low incidence of repiratory depression. It has a reported length of action of 2 to 7 hours with onset within 15 minutes. Postoperative analgesia A combination of opioid and non-opioid analgesics is used to treat postoperative pain. The use of intra-operative opioids affects the prescribing of postoperative analgesics. A postoperative opioid analgesic should be given with care since it may potentiate any residual respiratory depression. Morphine is used most widely. Tramadol hydrochloride is not as effective in severe pain as other opioid analgesics. Buprenorphine p. 468 may antagonise the analgesic effect of previously administered opioids and is generally not recommended. Pethidine hydrochloride p. 490 is generally not recommended for postoperative pain because it is metabolised to norpethidine which may accumulate, particularly in renal impairment; norpethidine stimulates the central nervous system and may cause convulsions. Opioids are also given epidurally [unlicensed route] in the postoperative period but are associated with side-effects such as pruritus, urinary retention, nausea and vomiting; respiratory depression can be delayed, particularly with morphine p. 484. Patient-controlled analgesia (PCA) can be used to relieve postoperative pain—consult individual hospital protocols. Pain management and opioid dependence Although caution is necessary, patients who are dependent on opioids or have a history of drug dependence may be treated with opioid analgesics when there is a clinical need. Treatment with opioid analgesics in this patient group should normally be carried out with the advice of specialists. However, doctors do not require a special licence to prescribe opioid analgesics to patients with opioid dependence for relief of pain due to organic disease or injury. Other drugs used for Pain Dexibuprofen, p. 1196. Diclofenac potassium, p. 1197. Levomepromazine, p. 460. Mefenamic acid, p. 1208 ANAESTHETICS, GENERAL › VOLATILE LIQUID ANAESTHETICS
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Initially 16 mg 3 times a day, dose preferably
First-line fragment. Read the complete Indications and Dose section above.
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