Managing symptoms in advanced liver disease
| Drug | Recommended dose | Notes |
| Pain | ||
| Paracetamol | 2–3 g/24 hours orally (long term) | >50 kg (dry weight) 1 g four times a day orally safe for short periods (<7 days) |
| NSAIDs | Avoid (bleeding risk/renal toxicity) | |
| Tramadol | Avoid (half-life>double, lowers seizure threshold) | |
| Codeine | 15–30 mg orally three times a day (short course only) | Avoid if possible—oral morphine preferable. If unable to use oral morphine monitor closely for constipation and encephalopathy |
| Morphine sulfate | 2.5 mg 4–6 hourly as needed | first choice oral opiate if eGFR>30 Use short acting unless pain and liver function stable Titrate as required Monitor closely for constipation and encephalopathy |
| Hydromorphone | 1.3 mg 8 hourly orally as needed (×10 as potent as oral morphine) | First choice oral opiate for eGFR<30 Increased dose interval Monitor for constipation and encephalopathy |
| Oxycodone | 1.25 mg 6–8 hourly orally as needed (×2 as potent as oral morphine) | Ideally avoid (half-life>triples) Consider if patient not tolerating oral morphine/coexisting renal impairment (eGFR 30–60) Monitor closely for constipation and worsening encephalopathy |
| Buprenorphine transdermal patch | Dose according to oral opioid requirements | Can be used if pain and liver function are stable Monitor closely for constipation and worsening encephalopathy Only initiate on advice of palliative care and/or specialist pain team |
| Gabapentin | 100 mg orally two times and titrate up as normal | Probably safe but can have sedative effect and may exacerbate HE. |
| Pregabalin | 50 mg orally two times and titrate up as normal | Probably safe but can have sedative effect and may exacerbate HE. |
| Amitriptyline | Avoid | |
| Dexamethasone | 4–8 mg orally once | For patients with HCC/liver metastases and capsular pain Give gastric protection Review after 5 days |
| Nefopam | 30–60 mg orally three times a day | An option in patients who do not tolerate other analgesia. Use with caution in decompensated disease, use lowest possible dose and monitor for side effects. Use may be limited by high cost and lack of evidence of effectiveness. |
| Nausea and vomiting | ||
| Metoclopramide | 5 mg orally/intravenous/subcutaneaous three times a day Titrate to max 10 mg three times a day | First-line option if gastrointestinal (GI) cause, acts as prokinetic May increase fluid retention Consider QT interval prolongation |
| Domperidone | 5 mg orally two times a day | Titrate to maximum 10 mg three times a day Alternative first line option, acts as prokinetic Consider QT interval prolongation |
| Haloperidol | 0.5–1 mg orally two times aday | Titrate to maximum 5 mg/24 hours in divided doses First line option if opioid or centrally induced |
| 0.25–0.5 mg subcutaneaous three times a day | ||
| Ondansetron | 4 mg orally/intravenous two times a day Maximum dose 8 mg/24 hours | Second-line option Monitor for constipation |
| Levomepromazine | 3 mg orally nightly Titrate to maximum 12.5 mg two times a day | Second-line option Causes drowsiness and can lower seizure threshold |
| 2.5 mg subcutaneaous three times a day | ||
| Cyclizine | 50 mg orally two times a day | Third-line option Monitor closely for constipation and worsening encephalopathy |
| 25 intravenous/subcutaneaous two time a day | ||
| Depression | ||
| Mirtazapine | Start at 15 mg orally every night Titrate slowly to max dose 30 mg on | Avoid in renal impairment May help stimulate appetite Can have sedating effect—15 mg on dose more sedating than 30 mg on |
| Citalopram | Start at 10 mg orally every morning Titrate slowly to dose 20 mg every morning | Almost double half life Can lower seizure threshold and increase risk of GI bleed. |
| Symptoms specific to liver disease | |||
| Symptom | Drug | Dose | Notes |
| Hepatic encephalopathy | Lactulose | 10–30 mL orally four times a day | Aim 2–3 soft stools/day |
| Phosphate enema | 1 enema PR once/two times | Aim 2–3 soft stools/day can be administered by district nurses regularly/PRN to prevent recurrent hospital admissions/as part of EHCP | |
| Rifaximin | 550 mg orally two times | Second line after lactulose/enemas | |
| Itching | Menthol 1% in aqueous cream | Apply 1–2 times daily | |
| Cholestyramine | 4–8 g orally once | First line for itching due to cholestasis Affects absorption of other medicines: take other meds >1 hour before or 4–6 hours after cholestyramine. | |
| Rifampicin, naltrexone, SSRIs (eg, sertraline) | Rifampicin can cause hepatotoxicity (see table 2) Can all be used second line but should be initiated cautiously with hepatology supervision | ||
| Colesevelam | Off license, limited evidence of effectiveness | ||
| Ascites | See section on ascites | ||
Adapted from British Association for the Study of the Liver clinical guideline: symptom control and end of life care in adults with advanced liver disease.45
eGFR, estimated glomerular filtration rate; EHCP, emergency healthcare plan; HCC, hepatocellular carcinoma; HE, hepatic encephalopathy; NSAIDs, non-steroidal anti-inflammatory drugs; PRN, as required; SSRI, selective serotonin reuptake inhibitor.