Medication (ILO/IMO Guidelines Appendix D)

Introduction

The risks from medications used by seafarers vary widely as do the benefits in terms of control of disease and symptoms. Both over the counter and prescribed medications include statutory information on their uses and side effects in their packaging or in widely available reference sources held by pharmacists and doctors. This information does not relate directly to work at sea but warnings such as 'do not drive or work with moving machinery' or the red, yellow and green traffic light coding used in some countries to warn of driving risks carry obvious implications for safety critical work at sea.

This guidance relates to decision taking on fitness for work at sea in those who are using medication at the time of examination.

It does not cover:

• Emergency use of medication from a ship's medical chest while at sea, except insofar as prior information on individual risks of adverse effects is available to the medical examiner.
• Occasional use of non-prescription remedies while at sea or on shore. However seafarers should be made aware of the importance of reading warning labels or package inserts and not undertaking safety-critical tasks if the medication may cause drowsiness or visual disturbances.
• Responsibilities for providing and paying for medication.
• Immunisations and prophylaxis against malaria, except insofar as prior information on individual risks of adverse effects is available to the medical examiner.
• Misuse of medication, including taking doses outside the range recommended by the supplier.
• 'Performance foods' and nutrients.

Assessment of medication use and risks

In the course of the medical assessment, information on any medication use, including complementary remedies, should be obtained. Every medication will have a clinical indication for use and fitness must be considered in terms of both the disease and its treatment. Seafarers should be asked about benefits and symptoms arising from their use of medication. If the medication is not familiar to the AD then the product information leaflet or other sources of information on the medication should be reviewed for warnings about side effects.

During the assessment any history of adverse reactions to medication should be obtained. The seafarer should be made aware of the need to inform anyone giving them medication about such reactions. Particular attention needs to be given to risks arising from the medications carried in the ship's medicine chest and to medications used for malaria prophylaxis.

Where a short course of medication is being taken or where the dose of a medication is being adjusted a case by case judgement is needed on whether, either because of the medication or the condition for which it is given, the seafarer should be made temporarily unfit or the issue of a certificate delayed until completion of the course.

Impairment and risks, clinical assessment and decision taking will be considered separately for each type of therapeutic effect or side-effect. Where feasible these are grouped together. Where a particular medication is not covered reference sources and analogy should be used to identify the likely problems.

Many ship operators require crewmembers to declare any medication to the master at embarkation. It is considered to be contraband if not declared. If a seafarer is on medication it is advisable to recommend that they have the information leaflet for the medication available when they board so that decision taking on any adverse effects will be simplified.

Side effects to be considered

• Medications that can impair routine and emergency duties
  Note: - Where the product information leaflet states that the user must not drive or work with moving machinery, this will normally be an indication of unfitness to work at sea.
  - Where the recommendation is that, if there are any subjective adverse effects, the user should not drive or work with moving machinery, an assessment of any effects in relation to the person's duties is required.
  • Central nervous system depressants (Sleeping tablets, antipsychotics, some anti-anxiety and anti-depression treatments, some antihistamines).
  • Agents that increase the risk of sudden incapacitation (insulin, some of the older anti-hypertensives, medications predisposing to seizures).
  • Medications impairing vision (see section 4 on vision).
    
    
• Medications and increased risk to user while at sea
  • Risk of bleeding from injury or spontaneously (warfarin, asprin and some other analgesics).
  • Dangers from cessation of medication use (metabolic replacement hormones including insulin, anti-epileptics, anti-hypertensives, oral anti-diabetics).
  • Antibiotics and other anti-infection agents.
  • Anti-metabolites and cancer treatments.
  • Medications supplied for use at individual discretion (asthma treatments, antibiotics for recurrent infections).
    
    
• Medications that require limitation of period at sea because of surveillance requirements
  • A wide range of agents, such as anti-diabetics, anti-hypertensives, endocrine replacements.

Specific classes of medication

Note: the condition for which the medication is used, as well as the effects of the medication itself, needs to be considered when making an assessment of fitness. This should include any beneficial effects that the medication may have in reducing the impairment or risks from the underlying condition.

1. Narcotic analgesics – impairment of cognition.
   - Opiates including methadone. Unfit for work at sea, other than in non-safety critical duties on vessels within harbour areas. Case by case assessment for opiate antagonists. Possession and use may be prohibited in some countries. Seafarers should be advised to check and to inform the ship's master if they are in any doubt.
   
   
2. Other analgesics – few complications, risks of allergy and of gastrointestinal bleeding with regular use of some products.
   - Normally no restrictions.
   
   
3. Antidepressants – impairment of cognition and drowsiness (tricyclics), impairment of cognition (SSRIs), adverse interactions with other medications and foods (MAOIs).
   - Need to be stabilised on treatment and without apparent adverse effects prior to work at sea. MAOIs not usually acceptable because of interactions.
   
   
4. Benzodiazepines as sedatives, hypnotics and anxiolytics. Long acting preparations cause day-long sedation. Short acting hypnotics are without adverse effects if eight hours sleep taken, unsuitable for shorter periods between watches. Habituation may occur leading to use of increasing doses. Alcohol greatly increases impairing effects.
   - Not generally acceptable for work at sea. Only suitable if stable pattern of use, absence of subjective and objective impairment and regular monitoring of dose and effects.
   
   
5. Anti psychotics and therapy for bipolar disorders. Consider in relation to underlying condition. Not normally acceptable for work at sea. (See 14)
   
   
6. Stimulants other than caffeine. Erratic behaviour.
   - Not generally acceptable. Methylphenidate (Ritalin) is widely used in treatment of attention deficit hyperactivity disorder (ADHD). Both the condition and the side effects and practical consequences of a seafarer holding a stock of this medication need to be considered. Possession and use may be prohibited in some countries. Seafarers should be advised to check and to inform the ship's master if they are in any doubt.
   
   
7. Antihistamines. Used for treatment of allergies, as cough suppressants, as sedatives and as treatments for motion sickness. Many available as non-prescription medicines. All can have sedative effects but many of those used for allergy treatment do not cross the blood brain barrier and only sedate at doses in excess of those recommended.
   - sedating antihistamines are incompatible with most safety critical duties. Regular use is not acceptable at sea. Non-sedating preparations are acceptable provided the user is aware of the dangers of exceeding the recommended dose.
   
   
8. Atropine and hyoscine containing systemic medicines, including motion sickness remedies, and topical eye medications. Paralysis of accommodation in the eye leading to visual impairment occurs.
   - Not acceptable if lookout duties or other safety critical visual tasks. Non absorbable hyoscine salts used in intestinal antispasmodics acceptable.
   
   
9. Antihypertensives. Some of the older medications can lead to postural hypotension, impaired cardiac responses to exercise and to depression. Such effects are not generally found with newer products.
   - May work at sea once stabilised on treatment unless it is one of the medications with the above side effects. If so assess risks in the individual and decide on fitness based on these.
   
   
10. Anticoagulants including warfarin. (See annex to this section for more detailed information on decision taking) Increased risk of bleeding: spontaneous gastrointestinal, cerebral haemorrhage, haemarthrosis, after laceration or contused injury, intracranial bleeds after head injury. Anticoagulants are used to reduce risk after venous thrombosis, in cardiac arrhythmia and after the insertion of artificial heart valves. The use of anticoagulants at the required dose normally carries a risk of bleeding of c 2% per year, in addition to the risk of the underlying condition after such treatment. Because of the practical difficulties of dealing with poorly controlled bleeding at sea they can cause major problems in casualty management.
    
    
11. Medications increasing the risk of seizures. Few medications increase the risk of seizures to a level where it will prevent work at sea. The anti smoking product bupropion increases the risk at doses higher than those used for smoking cessation and carries a small risk at the dose now used. It is best to start treatment at the beginning of a period of leave. It should not be used at sea if there is a history of past seizures or head injury.
    
    
12. Insulin. Hypoglycaemia risk
    
    
13. Oral antidiabetic medications. Hypoglycaemic risk with sulphonyl ureas
    
    
14. Endocrine replacement medications. In addition to insulin therapy replacement hormones may be used for thyroid and adrenal deficiencies as well as for sex hormone replacement. The latter is not relevant to fitness to work at sea. The effects of imbalance of thyroid hormones will be slow to develop but regular surveillance will be needed. The requirements for adrenal hormones will increase if there is intercurrent infection or other stress. Inadequate doses can lead to serious illness.
    - case by case assessment of adrenal insufficiency. Not normally fit for duties other than in near coastal waters.
    
    
15. Therapeutic use of corticosteroids. Short courses of inhaled steroids for asthma treatment are normally free from problems over and above those of underling condition. Continuous use or high dose oral use will increase a range of health risks.
    - self administered inhaled steroids for asthma (see 18). Oral administration for asthma is not compatible with work at sea except for non-safety critical coastal duties.
    
    
16. Antibiotics and other anti infection medications. Range of side effects, commonly gastro intestinal disturbances.
    - For short courses temporarily unfit until any impairing infection resolved. Self administered courses for infection prophylaxis – case by case decision based on underlying conditions and antibiotic used. Prolonged use of antibiotics – case by case decision based on underlying conditions and medication used. Treatment of tuberculosis. Treatment of HIV with retrovirals.
    
    
17. Antimetabolites and anti-cancer medications. These may increase the risk of infection and a range of other complications in addition to those of the underlying condition.
    - Case by case decision, normally will be unfit or require a limited certificate in terms of distance from health care or duties.
    
    
18. Medications requiring regular surveillance of dose, effectiveness or side effects. In all cases the period of service at sea should not be such that surveillance is prevented.
    
    
19. Medications where cessation of treatment can be dangerous. When cessation of medication use could increase the risk of a medical emergency in a seafarer it is essential that sufficient is carried for the duration of the period at sea. In addition the risks from inability to take the medication because of sea sickness or vomiting from other causes need to be considered. If they are such that severe adverse consequences can be anticipated an injectable form of the medication may need to be carried or a restricted certificate issued.
    
    
20. Known adverse effects from a medication in an individual. Information on any known allergies or other severe side effects from medication use in an individual should be recorded and the person advised to tell anyone who treats them. Where these are potentially life threatening or the cause is a medication that could be used in an emergency they may need to be restricted or advised to wear a warning bracelet giving the details.
    
    
21. Self-administered courses of prescription medications. See 15 and 16 above. If such medications are carried then the seafarer should be advised to inform the master or responsible officer in advance of the medication and the indications for use. Self administration of emergency anti-allergy treatments such as the 'epi-pen' for acute allergic reactions needs to be carefully considered. If the reaction is severe and can be reasonably foreseen to be a risk at sea, for instance from a reaction to a widely used food ingredient such as peanuts, then this should limit the fitness of the seafarer as use of self-medication alone may well not be sufficiently effective. However if it is carried, for instance for use in the event of a bee sting, and the event is unlikely at sea it may be considered a useful form of personal risk reduction.

Advice to seafarers

• Be aware of any possible side effects of the medications you use and if they occur inform the officer responsible who can obtain radiomedical or other advice on the action required.
• Always have more than enough of any medication to last a trip (in case of unforeseen delays)
• There will often be a requirement to notify the master of any medications brought on board and a failure to notify may be a breach of your crew agreement, or of a company drug and alcohol policy.
• Ensure that you have arrangements for any required doctor visits and repeat prescriptions organised for your next leave period.

Annex: warfarin and other anticoagulants (Relevant to ILO/IMO Guidelines Appendix E I 00-99, where anticoagulants form part of the treatment)

Introduction

This annex covers the use of warfarin and other anticoagulants and the implications of this for work at sea. It applies to their use after heart valve replacement, myocardial infarction, deep vein thrombosis and pulmonary embolism, and in atrial fibrillation and other arrhythmias. In all of these situations there is a trade off between the risks of embolism and the increased risk of bleeding from anticoagulation.
The clinical criteria for use of anticoagulants are set such that the overall total risk of embolism plus that from bleeding is minimised. For some of the conditions listed such as atrial fibrillation the current criteria in the ILO/IMO Guidelines are inherently more severe because of the bleeding risks from anticoagulants when the overall risk has been minimised by their use than they are when this treatment is not used and the overall risk of incapacitation while at sea is higher.

Antithrombotic drugs (anticoagulants, antiplatelets) and their risks

The antithrombotic drugs commonly used include antiplatelet agents (eg. asprin, clopidogrel), and anticoagulants (eg. warfarin and the newer replacements for warfarin such as dabagatran and rivaroxaban). Their modes of action and metabolism vary and this affects both the pattern of risk and the consequences of any episode of bleeding.

A number of individual risk factors for bleeding have been reliably identified. These include age, use of multiple agents with antithrombotic properties and a history of bleeding or of stroke. These factors form the basis for several well-validated risk scoring systems that are used to take decisions on when to prescribe anticoagulants. These systems have the potential to be used to stratify risk in seafarers. Because seafarers are of normal working age and because of other selection factors applied during medical assessment most will be in groups with a relatively low risk of bleeding from anticoagulation use.

Until recently anticoagulant use has prevented people from working at sea or in other remote locations so there is no direct evidence about risks. Radiomedical data indicates that head injury in the whole current population of seafarers, one of the major risk for serious bleeding when on anticoagulants, is not a common cause of requests for advice. Hence the frequency of such an incident in anyone working at sea who is on anticoagulants can be expected to be low.

The key features of the different medications and their risks have been reviewed in some detail.[7] Most of the data relates to use in those with atrial fibrillation but it is probably reasonable to extend it to all uses. These are:

1. 1. Asprin alone: small (but not negligible) risk of bleeding, limited effectiveness as an anti-embolic medication.
   2. Clopidogrel alone: small (but not negligible) risk of bleeding, limited effectiveness as an anti embolic medication.
   3. Asprin and clopidogrel together: more effective to prevent stroke in atrial fibrillation but with a risk of bleeding comparable to warfarin.
   4. Warfarin: dose requirements vary so INR (International Normalized Ratio) monitoring is essential and a period of stabilisation on the medication is needed. Effective reduction of embolization risk, with appreciable risk of bleeding. Well-defined individual risk factors that can be used to stratify risk. Bleeding risks increase greatly when anticoagulation aims for INR levels above 3, as is the case with artificial heart valve replacements. Effects are reversible in 10-12 hours by administration of vitamin K, or sooner with infusion of clotting factors. The aim of therapy is to keep the INR level within the therapeutic range (INR 2-3) for more than 60-70% of the time. Normally a period of 4-6 weeks is needed at the start of treatment to confirm the stability of control, with at least 3 consecutive readings within the therapeutic range.
   5. Dabagatran and related agents: standard dosages, so no monitoring needed. Reduction in embolic risks similar to (or better than) warfarin. Bleeding risks comparable to warfarin, but with some evidence of a lower risk for some types of serious bleeding. Effects cannot be reversed with an antidote, half-life of dabagatran is c12 hours and so cessation of medication will progressively reduce the excess risk of bleeding.

Because of the relatively lower risk (compared to warfarin, at least in younger patient groups) of bleeding from aspirin or clopidogrel, these do not require medication-related restrictions on duties, although the underlying condition being treated may require this. As aspirin is a widely used OTC (over the counter) medication, often at higher doses than those used for embolic risk reduction, restrictions would be impractical.

For those on warfarin or dabagatran and related agents, their risk may be assessed using the HAS-BLED score.[8] This score is one of several that have been developed to aid risk assessment. It has been validated for atrial fibrillation but there is no reason to expect that it is not also relevant to other indications for anticoagulation.

HAS-BLED Bleeding Risk Score

(INR in 2-3 range or standard dose of dabagatran or equivalent)

H Hypertension (ie. uncontrolled BP, eg. systolic >160 mm Hg) (1 point)
A Abnormal renal and liver function (biochemical evidence) (1 point each)1 or 2
S Stroke (medical history) (1 –point)
B Bleeding tendency or predisposition
(hospitalization or haemoglobin drop >2g/L) (1 point)
L Labile INRs (in therapeutic range <60% of time) (1 point)
E Elderly (eg. >65 years) (1point)
D Drugs(eg. concomitant Asprin, NSAIDs) or alcohol (misuse) (1 point each)

Add up scores.
0 = 1.13 major bleeding risk % p.a.
1 = 1.02  "    "
2 = 1.88  "    "
3 = 3.74  "    "
4 = 8.70  "    "

Thus a score of 2 or less carries a risk less than the 2% p. a. threshold used for other maritime health risks such as cardiac events and seizures.

Assessment of individuals

1. 1. All indications for the use of anticoagulants should be assessed in a similar way, but the risk of the underlying condition and of any other medical conditions will also need to be taken into account.
   2. For those on either just aspirin or clopidogrel no specific restrictions need be applied.
   3. For those on aspirin and clopidogrel together advice should be obtained from the treating physician on the risks of bleeding.
   4. For those on warfarin reliable control within the therapeutic range is needed and the person should be made temporarily unfit until this has been confirmed. Once it is confirmed they may be considered fit for restricted duties as follows provided their HAS-BLED score is between 0 and 2. This is subject to the conditions noted below (5-8).
      May be considered fit for work with low liability of injury in national near coastal waters, once stabilized on anticoagulants with regular monitoring of level of coagulation.
   5. For those on dabagatran and similar agents the HAS-BLED score should be between 0 and 2. They should be restricted as follows. This is subject to the conditions noted below (5,7)
      May be considered fit for work with low liability of injury in national near coastal waters

Explanatory note

1. 1. There are no duties on board that are entirely free from injury risks. Adverse outcomes following head injury are more frequent in those on anticoagulants and so any work where severe impacts to the head are foreseeable is unsuitable, for instance cargo-handling using cranes or work at heights.
   2. National near coastal waters if not locally defined should be taken to be those within helicopter range.
   3. An unrestricted certificate should not be issued, and one with a duration of less than two years would be appropriate if regular surveillance of coagulation control and bleeding incidents is indicated. This is because beyond helicopter range crewmembers are likely to be faced with complex and prolonged medical care requirements until evacuation can be arranged.
   4. Stabilisation should be taken to mean, in the case of warfarin, a period of at least three months with stable dosage and at least 3 consecutive INR levels in the therapeutic range of 2-3.
   5. Higher levels of anticoagulation, as commonly used after heart valve replacements, will normally result in permanent unfitness.

Conditions for certificate issue

1. 1. Compliance with treatment and with any coagulation monitoring requirements should be made a condition of certification and the duration of the certificate may need to be shortened to correspond with clinical surveillance.
   2. Self-monitoring with a personal INR meter is acceptable. The meter should log results obtained or if it does not do so the seafarer should keep a record of the date and value of each reading and make this available at their next medical.
   3. Seafarers on anticoagulants should be given a 'to whom it may concern' letter outlining their condition, its treatment and the risks. In the case of warfarin it should include instructions on the administration of vitamin K. Seafarers should be advised to show it to the captain or responsible officer on embarkation.
   4. For those on warfarin,vitamin K, plus instructions on its use, should be carried either by the seafarer or be available on board the ship.

7. Bleeding risk assessment and management in atrial fibrillation patients: a position document from the European Heart Rhythm Association, endorsed by the European Society of Cardiology. Working Group on Thrombosis. Gregory Y.H. Lip et al. Europace (2011) 13, 723–746

8. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Pisters R et al. Chest 2010;138:1093-1100.