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Home , Alcohol tolerance, Chlorphenamine, Clomethiazole, Cyproheptadine, Dosulepin, Felodipine

Guidance on the administration of medicines to inpatients believed to have consumed

Sussex Partnership NHS Trust clinical policy Alcohol, Harmful Substance and Illegal Use by Service Users and Visitors in Inpatient Services and Trust Premises states that ‘any situation where a service user is found to be misusing substances (includes alcohol in excess), whilst in hospital must be treated individually’. ‘Baseline observations of pulse, blood pressure, respiration, levels of consciousness, arousal and pupil size must be taken and recorded. Medical staff and shift coordinator should agree what actions need to be taken and the frequency of physical observation.’ (1)

To help decide whether to administer or omit in a patient who is apparently acutely intoxicated two factors can be taken into account: 1. The Alcometer reading 2. The nature of the medicine to be administered (its potential to interact with alcohol)

This guidance applies to general psychiatry units, (incl. WAA, OPMH and CAMHS), but may not be suitable for application on specialist units caring for patients who are known alcohol abusers or are alcohol dependent.

1. Alcometer Readings

Alcometer Reading Comment / Suggested Course of Action (breath alcohol) Zero Administer all medication due, unless there are other clinical reasons not to do so. 0-0.15mg/L Administer all medication due, unless there are other clinical reasons not to do so. Consider whether prescribed regular / are required if patient is already sedated or asleep. 0.16-0.35mg/L Medication may be given following clinical assessment and (Note - 0.35mg/L is the discussion with a doctor. It is possible that prescribed regular UK drink-drive limit). sedatives / hypnotics may not be required. 0.36-0.8mg/L Medication may only be given following clinical assessment and discussion with a doctor. Above 0.8mg/L No medication to be administered

As the blood (breath) alcohol level declines, it may be appropriate to repeat Alcometer readings and patient observations, and re-consider drug administration when the alcohol level has significantly reduced.

2. Medication to be Administered, and its potential to interact with alcohol. The following table provides a list of medicines that are known to interact with alcohol. A course of action is suggested with every drug that should help decide whether to administer it or not. Please note that the evidence to support this advice is at times limited and that with some medicines further patient-relevant information needs to be taken into account. Please refer the decision to the doctor in charge if unsure.

Drug - Alcohol Interactions or evidence of lack thereof:

Class Example of drug Available information on Suggested course of interaction with alcohol action ACE inhibitors, Lisinopril Enhanced hypotensive effect with Use with caution. Monitor alcohol. patient closely. neurone blockers, Angiotensin-II- antagonists Alpha-blockers Increased levels of indoramin and Use with caution. Monitor alcohol when used concurrently. patient closely. Increased drowsiness and enhanced hypotensive effect. Baratol SPC advises against ingestion of alcohol. Enhanced hypotensive effects. Use with caution. Monitor patient closely. Antibiotics Cephalosporins, No reports of cefadroxil and Cefadroxil and cefalexin safe cefalexin causing this reaction. to administer. Metronidazole, -like effect (see Discuss with doctor to delay possibly tinidazole disulfiram). administration until patient is sober. Co-trimoxazole Disulfiram like effects have been Use with caution reported Anticoagulants Warfarin and Major changes in alcohol Monitor INR phenindione consumption may affect anticoagulant control. No pharmacokinetic interaction. SPC states concurrent use not advisable. However, effect on patient might be minimal. Little evidence published. SPC Use with caution. states that combination not advisable however concedes that clinical studies have not revealed adverse pharmacodynamic interactions. See citalopram. Use with caution. No additional effect of alcohol on SPC states concurrent use drowsiness, sedation or task not advisable. Use with performance tests with fluoxetine 40 caution. mg/day, compared with fluoxetine alone. No significant potentiation of the Use with caution. cognitive effects of 40 g IV alcohol by single and multiple doses of 50 mg fluvoxamine occurred in one study. SPC advises to avoid alcohol. Irreversible MAOI’s: Alcohol may increase central Since alcohol is likely to have , catecholamine synthesis and been ingested in form of , release, and MAOIs may inhibit or , which contain , tyramine and could potentiating alcohol. Phenelzine precipitate a severe SPC contra-indicates, hypertensive crisis: avoid isocarboxazid SPC advises to avoid combination. combination. Drowsiness caused by mianserin As one single missed dose of enhanced significantly by alcohol. mianserin might produce only Significant additive effect on limited harm, probably best to objective psychomotor avoid combination in this performance. situation.

Mirtazapine May increase the CNS As one single missed dose of effect of alcohol. SPC advised to might produce avoid alcohol. only limited harm, probably best to avoid combination. Some degree of potentiation of the Use with great caution. effects of alcohol has been noted. Monitor patient. Case of fatality with a moclobemide overdose, plus half a bottle of whisky. Lack of interaction has been shown. Use with caution. SPC advises against combination. No potentiation of alcohol’s Probably safe to administer. cognitive effects reported. Monitor patient as above. Evidence for lack of interaction. Probably safe to administer. SPC does not recommend Monitor patient. combination, however. Additive sedation has been Use with caution. Monitor reported. patient. , e.g. Enhanced sedation, increased Use with caution. Monitor , impairment of psychomotor patient. , performance. No studies evaluating , respiratory response. Both alcohol and tricyclics lower the seizure threshold; care is needed in patients susceptible to seizures. Concurrent alcohol may increase oral of tricyclics. There appears to be no significant Use with caution. additive effect between alcohol and venlafaxine. No effect on the Use with caution. of vortioxetine or and no significant impairment. SPC advised to avoid alcohol. Antidiabetics Reports of severe hypoglycaemia. Monitor BMs before and after Rarely, slight disulfiram-like reaction administration. Warn patients with , and on glibenclamide and other sulphonylureas. gliclazide of disulfiram-like Increased risk of lactic acidosis with reaction. metformin and alcohol. Metoclopramide can increase rate Give with caution. of alcohol absorption and its blood- level. Increases in effect of alcohol seen. Antiepileptics In general Moderate social drinking (1-2 Use with caution. Monitor drinks/occasion, 3-6 drinks/week) patient. does not change serum levels of , and , but increases levels marginally and levels somewhat. Social drinking (see above) has no effect on the frequency of convulsions. Moderate to heavy amounts at one occasion (3-4 drinks) increase risk of seizures. Alcohol can exaggerate the side effects of antiepileptics.

Carbamazepine No published evidence but additive Use with caution. Monitor sedation would be expected. SPC patient. states that alcohol tolerance may be reduced.

Gabapentin Additive sedation can occur Use with caution No data available. Most frequently Given the indication for reported side effects of levetiracetam () and levetiracetam: dizziness, its central side effects involve somnolence, headache and doctor in decision. postural dizziness. Additive sedation can occur. Use with caution.

Paraldehyde Enhanced sedative effect can be Given the complex situations expected. when is given, refer decision to doctor. Avoid whenever possible. Phenytoin Alcohol intake might affect Use with caution. Remind phenytoin levels. The half-life of doctor to check phenytoin phenytoin can be up to 50% shorter levels regularly. Monitor in an abstaining alcoholic than in a patient as mentioned above. non-drinker. Possible potentiation of sedative Use with caution. effects. No information available (SPC). PIL Given the severity of advises not to drink alcohol. Most indication (epilepsy) and lack commonly reported side effects of of information, refer decision rufinamide that were more frequent to doctor. Monitor patient. than with placebo: somnolence and vomiting. Lack of interaction has been shown. Use with caution. Reports of disulfiram-like reactions. Discuss with doctor benefit The incidence of this reaction vs. risks of administration. appears to be very low and its importance is probably small. Reactions of this kind are usually more unpleasant than serious. All symptoms resolved completely within a few hours (SPC). Possibly enhances effect of alcohol Use with caution. Non-sedating: e.g. Acrivastatine might slow reaction Depending on clinical need , , times with alcohol. , () give with caution. , desloratadine, , and , loratadine and fexofenadine. do not interact with alcohol. Slight additive effect of cetirizine. Sedating: e.g. Significant impairment of Probably best avoided with , psychomotor performance with large amounts of alcohol. , alcohol and chlorphenamine. , ... Reports of abuse of cyclizine with alcohol (dangerous, as effect of cyclizine increases alcohol ). Cyclizine may have additive effects with alcohol. Severely sedating enhances Probably best avoided with eg.diphenhydramine, detrimental effect of alcohol on alcohol. , psychomotor performance. Marked , interaction with hydroxyzine and Benylin, Night Nurse promethazine. Antihypertensive , , Enhanced hypotensive effect with Use with caution. (see also , alcohol. beta-blockers & , channel hydralazine, blockers below) and Antimalarials Mefloquine does not affect blood- Consider giving mefloquine alcohol levels or effect of alcohol on on a day when patient is psychomotor tests. One report of sober (it is given once weekly severe paranoid , for prophylaxis, once only for and suicidal treatment). behaviour. Antimuscarinics Reduction of bioavailablity of Use with caution. alcohol by oral atropine. Marked attention impairment. Glycopyrronium No effect on reaction times and co- Use with caution. ordination. Marked impairment of attention. Hyoscine Increased sedative effect. Use with caution. Hyoscine Does not as readily cross brain- Use with caution. butylbromide blood barrier as hyoscine, and so is expected to be less likely to cause additive effects with alcohol. Antimycobacterials Cycloserine Possible enhancement of effects of Do not use. alcohol. Manufacturer contraindicates its use in due to increased risk of seizures. Slight increase of impairment seen Use with caution. in psychomotor tests. The incidence of severe progressive damage due to isoniazid is said to be higher in those who drink alcohol regularly, and the clinical effects of isoniazid are also said to be reduced by heavy drinking in some patients. Apparently no effect of acute alcohol intake on pharmacokinetics of isoniazid. Antiplatelet Small increase in gastrointestinal Avoid large doses. Small agents blood loss as well as increase in doses (75 mg/day) with haemorrhage (especially in heavy caution if not contraindicated drinkers). Small additive damaging or no increased risk of effect on gastric mucosa. A single bleeding present (e.g. peptic dose of aspirin (1 g or 600 mg) may ulcer, bleeding disorder, raise blood alcohol levels. chronic and gross overuse of salicylates in combination with alcohol). In general Enhanced CNS suppression Do not administer to patients resulting in impaired concentration with , respiratory and coordination, drowsiness and or chest infection lethargy as well as and as accidental alcohol- respiratory depression. overdosage in these patients Drowsiness is significant with the could prove fatal. and . Do not administer in severe EPSEs may also be enhanced as CNS depression. Refer can hepatotoxicity with eg decision to doctor. Omit, if . doctor unavailable. No published evidence that alcohol If is stopped for reduces efficacy. longer than 48 hours, it needs to be titrated again. Single oral doses do not seem to Use with caution. enhance the effects of alcohol on the performance and memory of healthy subjects. No significant difference in Safety and efficacy has not performance or gross motor skills, been evaluated in patients although 2.5 to 10 mg/day intoxicated with alcohol. Use increases sedation. with caution. Clozapine Enhanced central effects. Additive Avoid, if possible. Consider, CNS depression and cognitive and however, that clozapine motor performance interference needs to be retitrated if when used in combination. Possible omitted for 48 hours or risk of circulatory collapse. longer. Concomitant use contraindicated by manufacturer of clozapine. Flupentixol Significant drowsiness with alcohol. Avoid with alcohol. SPC contraindicates concomitant use.

Lurasidone SPC states should be used with Use with caution. caution in combination with other centrally acting medicinal products and alcohol. Enhanced CNS sedation. Raised Use with caution. heart rate and increased postural hypotension have been reported.

Phenotiazines (e.g. Significant drowsiness with alcohol. Since respiratory depression ) might occur, discuss with doctor. As with antipsychotics in general Use with caution. If stopped for longer, consider re- titrating patient. Contraindicated in acute alcohol Do not use. intoxication. Antiretrovirals Abacavir Alcohol increases AUC and half-life Give drug. Use caution in of a single dose of abacavir. The liver disease (chronic increase in exposure to abacavir is ). not considered clinically significant (one of the primary metabolic pathways of abacavir by alcohol dehydrogenase). Other antiretrovirals: One study showed that the amount Use with caution. e.g. , of alcohol use did not affect antiviral saquinavir, nelfinavir, response. Another study suggests , ... that heavy users of alcohol are twice as likely not to achieve a positive virological response. Alcohol consumption can induce CYP3A4 (protease inhibitors and non-nucleosidic reverse transcriptase inhibitors metabolised by it). Anti-worm Levamisole Possible disulfiram-like reaction Use with caution infection medicines Niclosamide May increase levels of niclosamide Use with caution potentially leading to more side- effects Increased sedation but little Use with caution. impairment of psychomotor performance. SPC still recommends avoiding the combination. E.g. phenobarbital Enhanced or prolonged CNS and Use phenobarbital for respiratory depression can occur, epilepsy with great caution. seriously impairing concentration Monitor patient closely, and performance. Lethal dose of respiratory depression barbiturates is up to 50% lower in possible. Do not use other combination with alcohol. barbiturates. Manufacturer of phenobarbital advises not to drink alcohol. Note half-life of phenobarbital: 1.5 to 4.9 days. , Sedative effects caused by Inform doctor. Use with great , benzodiazepines increased by 20- caution after assessing , 30%. Larger quantities of alcohol benefits vs. risks. , may inhibit metabolism. Patient might be unaware of the impairment that occurs. Temazepam, , and , when taken at night with alcohol, can still interact with it the next morning. The effects of lorazepam and possibly chlordiazepoxide may be opposed by alcohol. Possible increased behavioural aggression with and flunitrazepam. Lorazepam SPC states that “use in individuals with a history of alcoholism or drug abuse should be avoided” and does not recommend combination. Beta-blockers Enhanced hypotensive effects Use with caution. Enhanced hypotensive effects Use with caution. Enhanced hypotensive effects. May Use with caution. reduce propranolol levels. Blood pressure lowering effects of Use with caution. sotalol increased by alcohol. Calcium-channel Enhanced hypotensive effect. Use with caution. blockers SPC for Adizem brand warns Do not use Adizem brand at against use of alcohol at the same the same time as alcohol. time as this may increase the Use other brands with release of diltiazem from the caution. Monitor blood modified release preparation. pressure. Felodipine levels doubled by Use with caution. Monitor alcohol in one study. Increased blood pressure. heart-rate and diuresis. Possible lowered blood pressure. Increases in heart rate and Use with caution. Monitor decreases in blood pressure blood pressure. enhanced. Significant increases of nifedipine Use with caution. blood-levels seen, no significant changes in heart-rate and blood pressure, though. No significant interaction with Use with caution. respect to psychomotor response, blood pressure, heart rate. One study found that verapamil Use with caution. raises blood-alcohol levels, and that subjects on combination felt more intoxicated. Another study did not find any significant interaction with respect to pharmacokinetics, blood pressure, heart rate and psychomotor response. Chemotherapeutics Methotrexate Possibly increased hepatotoxicity Discuss discontinuing with alcohol. One manufacturer methotrexate temporarily for contraindicates use of methotrexate psoriasis and rheumatoid in alcoholism. arthritis (given once weekly) with doctor. Procarbazine Flushing reaction on face reported Use with caution. Involve after small amounts of alcohol. doctor in decision. Procarbazine is also a weak MAOI (see there). Enhanced hypotensive effect with Use with caution. alcohol Increased side-effects when Use with caution. agonists combined with alcohol. Drugs for Memantine has no effect on Use with caution. dementia alcohol-induced performance impairment, but may increase some subjective symptoms. H2-receptor , Cimetidine and might Use with caution. blockers , nizatidine, slightly increase alcohol levels. Famotidine could produce hypoglycaemia with alcohol. Ranitidine might increase alcohol levels and worsen hypoglycaemia after alcohol ingestion. Hypnotics hydrate, Additive CNS effects occur. Avoid if used as . cloral betaine , impaired concentration, disulfiram-like effects and profound may also occur. Bioavailability of oral clomethiazole Probably best to avoid increased (inhibition of first-pass combination. metabolism). Reduced effectiveness of melatonin No data on other adverse on sleep; SPC advises against use interactions. Use with caution. of alcohol for this reason. While zaleplon enhances alcohol Given the indication performance impairment, the effect (sleeplessness), probably appears short-lived. safest to avoid combination.

Zolpidem No published information on Combination not interaction available. Risk of recommended. habituation and in alcoholics. There appears to be no significant Given the indication interaction. Additive adverse effect (sleeplessness), probably on driving ability. safest to avoid combination. Illicit substances Decreased ethanol metabolism may Refer to Medicines Code for (See also ) occur with enhanced CNS information on what to do with depression. illicit substances. May produce changes in heart rate Avoid if possible. Refer to and blood pressure, increasing the Medicines Code for risk of cardiovascular toxicity. information on what to do with Enhanced cocaine-induced hepatic illicit substances. and cardiac toxicity Immune and Increased facial flushing / redness Use with caution modulators Pimecrolimus ointment/ cream Lipid lowering Nicotinic acid Concurrent use of nicotinic acid and Use with caution, especially if drugs alcohol may result in an increase in patient has drunk substantial adverse effects such as flushing amounts of alcohol. and pruritus, and possibly liver toxicity. Mood stabilisers No clinically significant adverse Involve doctor in decision. interactions have been reported. Use with caution. Impaired driving skills have been Be aware signs of lithium suggested. Alcohol may produce a toxicity may be mistaken for slight (12%) increase in peak lithium . levels. Muscle relaxants , Possible enhanced sedation. Use with caution. Acute alcohol intoxication combined Avoid combination. with methocarbamol can lead to increased CNS depression. and Glyceryl trinitrate Increased risk of exaggerated Tell patient to sit down before (GTN) hypotension and fainting. administration. Administer nicorandil drug. Tell patient to lie down if feeling faint or dizzy. Monitor closely. NSAIDs E.g. , Increased risk of gastrointestinal Use with caution. naproxen, complications in those combining , ... alcohol with NSAIDs. More than additive risk of NSAIDs in patients with history of alcohol abuse. Phenylbutazone worsens impairment of psychomotor skills (driving) caused by alcohol. Report of acute renal failure with ibuprofen and 375 ml rum.

Opioids Enhanced hypotensive and Probably best avoided if sedative effects when given with patient is heavily intoxicated. alcohol. Delay dose until alcometer reading reduced to below 0.35mg/L. Enhanced hypotensive and Probably best avoided if sedative effects when given with patient is heavily intoxicated. alcohol. Use with care otherwise. Enhanced hypotensive and Avoid combination. sedative effects when given with alcohol. Increased impairment of psychomotor skills. Reduction of lethal dose of dextropropoxyphene by alcohol.

Hydromorphone Increased CNS depression. SPC (of Avoid combination. m/r preparation) contraindicates use with alcohol.

Methadone Increased sedation and respiratory Use with great caution. depression may occur, especially in Involve doctor in decision. overdose, as could hepatotoxicity. Delay dose until alcometer SPC states that should reading reduced to below be used with great caution in acute 0.35mg/L. alcoholism. Enhanced hypotensive and Probably best avoided if sedative effects when given with patient is heavily intoxicated. alcohol. Use with care otherwise. Phosphodiesterase Headache and flushing reported Use with caution. type-5 inhibitors with alcohol. PIL advises against use of large amounts of alcohol. Reports of dizziness and postural Use with caution. hypotension. Additive blood- pressure lowering effects possible. Smoking Increased risk of seizures. Rare Combination should be cessation reports of adverse neuropsychiatric avoided. Do not give to events or reduced alcohol tolerance patients on alcohol in patients drinking alcohol during detoxification. bupropion treatment. SPC contraindicates in patients who, at any time during treatment, is undergoing alcohol withdrawal. Treatment for Alcohol may exacerbate some CNS Discuss need for ADHD effects (Increased drowsiness and administration with doctor. sedation). Avoid where possible. alternative for patients with a history of substance misuse. Dexamphetamine (as methylphenidate above) (as methylphenidate above) Atomoxetine Increased somnolence when taken Use with caution. Alternative together. Dizziness and to in patients with lightheadedness may be increased history of substance misuse. with alcohol. No other specific interactions. Treatment for Enhanced CNS depression can Probably best avoided if narcolepsy with occur. patient is heavily intoxicated. cataplexy Use with great caution otherwise. Treatments to No detectable pharmacokinetic Probably safe to administer. maintain interaction. However, continued alcohol abstinence from use may negate therapeutic alcohol effect of acamprosate. Disulfiram Flushing, sweating, , Avoid combination. hyperventilation, increased pulse, hypotension, nausea and vomiting. Reaction occurs within 5-15 minutes and can be fatal. Interaction can occur with disguised sources of alcohol, e.g. “Listerine” mouthwash, cough mixtures ... Delirium has been reported with combination. Treatment for Increased sedative effect Use with caution opiate withdrawal symptoms

References:

1. Sussex Partnership NHS trust clinical policy. Therapeutic Engagement and Observation Policy and Procedure. May 2017 Sussex Partnership NHS Trust. 1. Bazire S. Psychotropic drug directory 2018. Lloyd-Reinhold Publications. 2. Taylor D, Barnes T, Young A. The Maudsley Prescribing Guidelines. 12th ed. London: Wiley Blackwell 3. Stockley’s Drug Interactions. [Online] London: Pharmaceutical Press. Available from: http://www.medicinescomplete.com. 4. Electronic Medicines Compendium . Available from: http://www.medicines.org.uk. 5. Thomson Reuters Healthcare. DRUGDEX® Evaluations. [Online] 1974-2009 [cited 2009 May] Available from: http://www.thomsonhc.com. 6. Bezchlibnyk-Butler KZ, Jeffries JJ, editors. Clinical handbook of psychotropic drugs. 16th ed. Portland (OR): Hogrefe & Huber Publishers; 2006. 7. BNF 68 March 2019 - September 2020

Approved by the Drugs & Therapeutics Group – April 2012

Reviewed unchanged May 2015

Reviewed minor changes: November 2019

Next review: November 2022