Drugs to Continue vs. Drugs to Stop

Research and writing made possible thanks to the generous sponsorship from Pemason Pharmaceutical Limited – owned by Pharmacists and operated by a team of Pharmacists with a commitment to quality pharmaceuticals & drug information.

Perioperative refers to the period before, during and after surgery. Preoperative refers to the time before surgery. Intraoperative refers to the time during surgery.

Many surgical patients are on regular medications. Some of these drugs can interact with anaesthetics or anaesthesia and/or surgical interventions. As a result, patients may experience complications such as bleeding, ischemia, infection or severe circulatory reactions.

Proper perioperative management helps to prevent or minimize complications, to reduce postoperative pain, and to accelerate recovery. Perioperative pharmacotherapy protocol should include:

• Accurate and complete medication history
• Established protocol for discontinuation and reinstitution of medications during the perioperative period
• Monitoring of relevant parameters to ensure accurate dosing of medications and help minimize adverse effects
• Appropriate management of pain
• Administration of adjunctive medications
• Use of appropriate formulations and alternative products when needed
• Review of discharge medications to ensure discontinuation of surgery-specific drugs (e.g., anticoagulants, analgesics) to avoid polypharmacy

It is extremely important to obtain a complete and accurate list of all the patient’s medications and this should occur at least 2 weeks before surgery. A thorough medication review should include:

• All prescription medications
• All over-the-counter (OTC) agents
• All vitamins & dietary supplements
• All herbal medications
• Substance use including alcohol, nicotine, etc.

Decisions about stopping or continuing medications perioperatively should be based on withdrawal potential, the potential for disease progression if therapy is interrupted, the potential for drug interactions with anaesthesia, and the patient’s short-term quality of life.

In the preoperative period, it is important to avoid the use of medications that may negatively interact with anaesthetic agents and to know whether the drug will negatively affect the procedure.

In the postoperative period, the concern is when to restart these agents in order to avoid the potential for withdrawal, a progression of the underlying disease state, and other adverse events.

KEY POINTS

Common drugs that have been associated with withdrawal symptoms when discontinued preoperatively include selective serotonin reuptake inhibitors (SSRIs), beta-blockers, clonidine, and corticosteroids.

In general, most nonsteroidal anti-inflammatory drugs should be stopped at least 3 days before surgery.

Although ACE inhibitors and angiotensin receptor blockers (ARBs) intensify the hypotensive effects of anaesthesia, it may be prudent to continue them perioperatively unless their only indication is for hypertension and the patient’s blood pressure is well controlled.

Herbal medications should be stopped at least 7 days before surgery, owing to the uncertainty over their actual contents.

Among psychotropics, SSRIs, tricyclic antidepressants, benzodiazepines, and antipsychotics are generally safe to continue perioperatively.

General principles of perioperative medication management

• Continue medications with withdrawal potential or taper where feasible. Substitute intravenous, transdermal, or transmucosal medicines when absorption will be impaired due to loss of gastrointestinal function or restrictions on oral intake.
• Discontinue medications that increase the risk of anaesthetic or surgical complications and are not essential for the short-term quality of life
• Use clinical judgment in other cases i.e., medications that do not meet either of the above principles. Note that:
  • Many other medications are given in the narrow perioperative time window increasing the potential for drug-drug interactions
  • Metabolism and elimination of medications and their metabolites may be altered during the perioperative period.

Medications contributing to the patient’s current state of medical homeostasis should be continued and generally, these include most prescription drugs. These drugs are not without risk and can potentially interact with anaesthesia agents.

Medications that do not contribute to the medical homeostasis of the patient should be discontinued in preparation for surgery (i.e., OTC medications, herbal or dietary supplements). Those that may increase the risk of adverse outcomes perioperatively should generally be discontinued based on pharmacokinetic principles. For example, NSAIDs and other anticoagulants increase bleed risk perioperatively. Some herbal supplements can prolong bleeding time, as well as increase blood pressure. The effects of many herbal supplements are unknown, as the actual composition of each product varies widely. Hormone replacement therapies and some osteoporosis agents may promote clot development perioperatively.

Optimal time frame for discontinuation before surgery depends on the pharmacokinetic profile of the medication, as well as individual patient factors. In general, it takes a drug approximately five half-lives to be completely eliminated from the system.

Quick reference tables

Click the links below to access the PDF Tables

Management of various classes of medications in the perioperative period (Table 1)

• Table 1a: – Perioperative management of cardiovascular medications
• Table 1b: – Perioperative management of gastrointestinal and pulmonary medications
• Table 1c: – Perioperative management of endocrine medications
• Table 1d: – Perioperative management of medications affecting hemostasis
• Table 1e: – Perioperative management of psychotropic medications
• Table 1f: – Perioperative management of rheumatologic medications

Perioperative management of diabetes mellitus (Table 2)

• Table 2: – Perioperative management of diabetes mellitus

Guidelines for perioperative corticosteroid management (Table 3)

• Table 3: – Guidelines for perioperative corticosteroid management

Overview of topical antiseptic used for preoperative skin preparation (Table 4)

• Table 4: – Overview of topical antiseptics used for preoperative skin preparation

Antibiotic selection guide (Table 5)

• Table 5a: – Antimicrobial prophylaxis for gastrointestinal surgery in adults
• Table 5b: – Antimicrobial prophylaxis for genitourinary surgery in adults
• Table 5c: – Antimicrobial prophylaxis for orthopaedic surgery in adults
• Table 5d: – Antimicrobial prophylaxis for gynecologic and obstetric surgery in adults

References:

1. Whinney C. Perioperative medication management: General principles and practical applications. CCJM 2009 Nov. Available from: http://www.ccjm.org/view-pdf.html?file=fileadmin/content_pdf/ccjm/content_68daa88_S126
2. Muluk V, Macpherson DS, Cohn SL, Whinney C.. Perioperative medication management. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2015.
3. Pass SE, Simpson RW. Discontinuation and reinstitution of medications during the perioperative period. Am J Health-Syst Pharm—Vol 61; 2004 May. Available from: http://goo.gl/DMgNgg (login required)
4. Card R, Sawyer M, Degnan B, Harder K, Kemper J, Marshall M, Matteson M, Roemer R, Schuller-Bebus G, Swanson C, Stultz J, Sypura W, Terrell C, Varela N. Perioperative protocol. Health care protocol. Bloomington (MN): Institute for Clinical Systems Improvement (ICSI); 2014 Mar. Available from: http://www.guideline.gov/content.aspx?id=48408

Study finds an association between topical corticosteroid use and new-onset type 2 diabetes

There is a positive and significant association between exposure to topical corticosteroids and new-onset type 2 diabetes (T2D), according to three large pharmaco-epidemiological studies based on data from Denmark and U.K. The findings are published online April 1 2019, in Diabetes Care.

Topical corticosteroids (TCSs) are widely used to treat chronic inflammatory and pruritic skin conditions such as psoriasis and eczema due to their efficacy, moderate costs, and relatively good safety profile. However, TCSs are small molecules that can get absorbed into the skin and ultimately reach the systemic circulation and cause internal exposure. Although TCS package inserts describe hyperglycemia and glycosuria as adverse drug reactions, it is unclear whether their use in real life is also associated with an increased risk of type 2diabetes.

The study was designed to assess whether TCS use in real-world settings is associated with an increased risk for T2D. A total of 115,218 and 54,944 adults were identified as case subjects with new-onset T2D in the Danish and U.K. case-control study, respectively. For the Danish cohort study, 2,689,473 adults were included. The main exposure was TCSs, and the outcome was incident T2D.

The findings showed that TCS use was significantly associated with T2D in the Danish (adjusted odds ratio [OR] 1.35 [95% CI 1.33–1.38]) and U.K. (adjusted OR 1.23 [95% CI 1.19–1.27]) case-control studies. Individuals who were exposed to TCSs had significantly increased risk of incident T2D (adjusted hazard ratio 1.27 [95% CI 1.26–1.29]). Significant dose-response relationships between T2D and increasing potency of TCSs were observed in the two Danish studies.

The authors concluded that clinicians should be cognizant of diabetogenic effects of high-potency topical corticosteroids and consider other treatment options if possible.

Source: Diabetes Care. Abstract/Full Text available here https://doi.org/10.2337/dc18-2158 (Subscription may be required)

Footnote: Below is an excerpt from our earlier publication on “Therapeutic Analysis of Topical Corticosteroids & their Combination Products Available in the Nigerian Market ”

Comparison of topical corticosteroids

Ultra-high and High Potency TCS

Recommended for thick skin areas like Palm and Soles for: Atopic dermatitis (resistant); Discoid lupus; Hyperkeratotic eczema; Lichen planus; Lichen sclerosus (skin); Psoriasis; Severe hand eczema.

High-potency may also be used on the Trunk, Extremities, Scalp & Hairy skin areas for: Scalp dermatitis; Atopic dermatitis; Psoriasis, etc.

They pose the highest risk of systemic side effects. Avoid abrupt discontinuation; continuous daily use >3 weeks, and occlusive dressings.

Monitor for symptoms of adrenal suppression: weakness, weight loss, hypotension, and gastrointestinal distress.

Lower potency agents are preferred for the face, groin, armpits, or skin folds due to susceptibility to local side effects and systemic absorption

Ultra-high potency includes: Betamethasone dipropionate glycol (augmented) 0.05% Cream, Ointment, Lotion; Clobetasol 17-propionate 0.05% Cream, Ointment, Lotion; Halobetasol propionate 0.05% Ointment.

High potency includes: Amcinonide 0.1% Ointment, Cream, Lotion; Betamethasone dipropionate 0.05% Ointment, Cream, Lotion; Betamethasone valerate 0.1% Ointment; Fluocinonide 0.05% Cream, Ointment, Gel; Halobetasol propionate 0.05% Cream; Mometasone furoate 0.1% Ointment.

Moderate Potency TCS

Recommended for Trunk, Extremities, Scalp & Hairy skin areas for: Alopecia areata; Atopic dermatitis; Contact dermatitis (severe); Lichen sclerosus (vulva); Nummular eczema; Perianal inflammation (severe); Scabies (after scabicide); Seborrheic dermatitis; Severe dermatitis; Severe intertrigo (short-term); Stasis dermatitis.

Moderate to low potency agents should be used when treatment involves large body surface area.

Duration of treatment: May be used for up to 3 months when treating non-facial or non-intertriginous areas.

Occlusive dressings should be avoided.

Low Potency TCS

Recommended for thin skin areas like Face, Neck, Intertriginous or Genital areas for: Dermatitis (face, eyelids, diaper region); Intertrigo; Perianal inflammation.

These are agents of choice for children, pregnant women, elderly or for treating large areas.

Available TCS Combinations with Antibiotics

• Betamethasone + Neomycin (Topical)
• Hydrocortisone + Gentamicin (Topical)
• Hydrocortisone + Neomycin (Topical)

Available TCS Combinations with Antifungals

• Beclometasone + Clotrimazole
• Betamethasone + Clotrimazole
• Clobetasol + Clotrimazole
• Dexamethasone + Clotrimazole
• Diflucortolone + Isoconazole
• Hydrocortisone + Miconazole (Topical)

Available TCS Combinations with Antibiotics and Antifungals

• Beclometasone + Clotrimazole + Gentamicin
• Beclometasone + Clotrimazole + Gentamicin + Clioquinol
• Betamethasone + Clotrimazole + Gentamicin
• Betamethasone + Clotrimazole + Neomycin
• Betamethasone + Tolnaftate + Gentamicin
• Betamethasone + Tolnaftate + Gentamicin + Clioquinol
• Betamethasone + Tolnaftate + Neomycin + Clioquinol
• Clobetasol + Ketoconazole + Neomycin
• Clobetasol + Miconazole + Gentamicin
• Clobetasone + Miconazole + Gentamicin
• Dexamethasone + Clotrimazole + Gentamicin
• Dexamethasone + Clotrimazole + Neomycin
• Dexamethasone + Miconazole + Neomycin
• Fluocinolone + Miconazole + Neomycin
• Miconazole + Beclometasone + Neomycin
• Miconazole + Clobetasol + Neomycin
• Triamcinolone + Econazole + Gentamicin

Contributed by: Anuolu Bank-Oni, PharmD, CDE, BCGP

Acetylsalicylic acid (ASA) works by inhibiting platelet aggregation and has been the mainstay in reducing the risk of primary cardiovascular events, such as myocardial infarction and stroke. However, its role as primary preventative therapy has been scrutinized.  To determine if ASA can be used in a patient, it is important to consider the patient’s cardiovascular risk, age, bleeding risk, and willingness to adhere to an ASA regimen. Adverse effects associated with acetylsalicylic acid include bleeding (gastrointestinal, cerebral), renal impairment, and gastrointestinal ulceration. Higher doses are associated with a higher risk of experiencing an adverse effect. Some research has shown that weight and gender may affect the efficacy of ASA therapy.

A meta-analysis¹ of individual patient data conducted by Rothwell and his research team demonstrated that bodyweight may play a role in the efficacy of ASA. The analysis showed that ASA dosed between 75 mg and 100 mg may only reduce the risk of cardiovascular events in patients that weigh less than 70 kg. Patients who weigh more than 70 kg may require at least 300 mg of ASA to achieve a similar effect.

Some evidence also exists that indicates ASA efficacy may be affected by gender—in primary prevention, ASA reduces the risk of stroke in women but not in men; it reduces the risk of myocardial infarction in men but not in women.

Medication adherence is an important factor to consider in patients on ASA therapy. Discontinuing use of ASA (in the absence of major surgery or bleeding) may increase the risk of cardiovascular events². Healthcare professionals should consider discontinuing ASA in patients with certain risk factors, who are scheduled for major surgery.

Listed below is a summary of some of the recommendations provided by various Clinical Practice Guidelines and research teams.

Current Recommendations

American College of Chest Physicians (ACCP)

The ACCP suggests ASA (75 mg to 100 mg daily) in patients aged 50 years and older without symptomatic cardiovascular disease. The guidelines state that ASA reduces total mortality in patients when taken for at least 10 years, regardless of their cardiovascular disease risk.

American Diabetes Association (ADA)

The ADA guidelines published in 2018 provide guidance on the use of ASA in patients with diabetes. Low-dose ASA (75 mg – 162 mg daily) may be used in primary prevention of cardiovascular events in patients with type 1 or type 2 diabetes with increased cardiovascular risk. This includes patients who are at least 50 years old, are not at increased risk of bleeding, and have at least one of the following risk factors: family history of premature atherosclerotic cardiovascular disease, hypertension, dyslipidaemia, smoking, or chronic kidney disease.

American Geriatrics Society (AGS)

The AGS Beers Criteria recommends avoiding the chronic use of daily doses of ASA greater than 325 mg in patients aged 65 years and older. If there are no suitable alternatives, consider using a gastroprotective medication to reduce the risk of gastrointestinal bleeds and peptic ulcer disease. The Beers Criteria recommends cautiously prescribing ASA for primary prevention of cardiovascular events in patients 80 years and older.

American Diabetes Association, American Heart Association & American College of Cardiology Foundation Joint Statement

In addition to the ADA guidelines already discussed, the joint statement suggests that low-dose ASA (75 mg – 162 mg daily) may be appropriate for patients with diabetes at intermediate cardiovascular risk (younger patients with at least one risk factor, or older patients with no risk factors, or patients with 10-year cardiovascular risk of 5–10%).

Cardiovascular risk should be evaluated using an assessment tool, such as the UKPDS Risk Engine, ARIC CHD Risk Calculator, or the ADA Risk Assessment Tool Diabetes PHD. Risk should be reassessed periodically, as risk factors may develop over time.

European Society of Cardiology (ESC)

The ESC recommends the use of ASA in primary prevention of cardiovascular events in men and women who have no increased risk of bleeding, and with a risk of major cardiovascular events (death, myocardial infarction, and stroke) of greater than 2 per 100 subject-years.

United States Preventive Services Task Force (USPSTF)³

The USPSTF guidelines recommend starting low-dose ASA in patients between the ages of 50 and 59 years who have at least a 10% 10-year risk of cardiovascular disease, are not at increased risk of bleeding, and have a life expectancy of at least 10 years. It is recommended for the prevention of cardiovascular events and colorectal cancer. To achieve benefit in colorectal cancer prevention, patients will need to take ASA for at least 5 to 10 years.

Although the optimal dose of ASA is not known, doses of 75 mg and 100 mg daily, and 100 mg and 325 mg every other day have been found to be effective. The risk of GI bleeds increases with dose and patients should be regularly assessed for adverse events.

Patients with hypertension^4,5,8

The Cochrane review shows that ASA reduces myocardial infarction, increases major haemorrhage and minor bleeding, and has no significant effect on strokes. Due to the significant bleeding risk, ASA is not recommended in primary prevention of cardiovascular events in patients with hypertension. Time of ASA dosing may affect blood pressure in patients with hypertension. Some research has shown that administering ASA at bedtime may result in lower blood pressure in patients with mild essential hypertension.

Patients with low ankle brachial index⁹

A low ankle brachial index increases the risk of cardiovascular and cerebrovascular events. Aspirin therapy may not reduce the risk of cardiovascular events in patients with a low ankle brachial index. More research is needed in this patient population to determine the role ASA may play in the management of cardiovascular disease.

Conclusion

The current guidelines indicate that although acetylsalicylic acid may reduce the risk of cardiovascular events, there is an increased bleeding risk. ASA may not be beneficial in patients below the age of 50 and over the age of 70. Each case should be assessed individually to determine appropriateness.

An optimal dose and frequency of administration have not been established. However, it is prudent to use the lowest effective dose to minimize the risk of adverse events. ASA has been shown to be beneficial in secondary prevention of cardiovascular events. Its role in the primary prevention of cardiovascular events has been controversial and requires additional research.

About the author

Anuolu Bank-Oni is the principal medical writer and consultant of Pharmέcrit. A graduate from the University at Buffalo, SUNY, NY with a Doctor of Pharmacy degree, she is also a Certified Diabetes Educator and a Board-Certified Geriatric Pharmacist.  Anuolu has a combined experience of over ten years in pharmacy practice in US and Canada and her clinical experience includes mentoring, facilitating, and training of healthcare professionals.   She effectively combines her therapeutic expertise with her ability to clearly and accurately convey complex scientific information to a target audience, such as patients, general public, healthcare professionals, and regulators

References

1. Rothwell PM, et al. Effects of aspirin on risks of vascular events and cancer according to body weight  and dose: analysis of individual patient data from randomised trials. Lancet. 2018 Aug 4;392(10145):387-399. doi: 10.1016/S0140-6736(18)31133-4. Epub 2018 Jul 17
2. Sundstrom, J et al. Low-Dose Aspirin Discontinuation and Risk of Cardiovascular Events: A Swedish Nationwide, Population-Based Cohort Study. 2017 Sep 26;136(13):1183-1192. doi: 10.1161/CIRCULATIONAHA.117.02832
3. Bibbins-Domingo, K. Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2016;164:836-845. doi:10.7326/M16-0577
4. Lip GY, et al.  Antiplatelet agents and anticoagulants for hypertension. Cochrane Database Syst Rev. 2011 Dec 7;(12):CD003186. doi:10.1002/14651858.CD003186.pub3.
5. Griffin, G. Antiplatelet therapy and anticoagulation in patients with hypertension. Am Fam Physician. 2005 Mar 1;71(5):897-9.
6. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes-2018. Diabetes Care.2018 Jan;41(Suppl 1):S86-S104. doi: 10.2337/dc18-S009.
7. DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 – . Record No. 114918, Aspirin for primary prevention of cardiovascular disease; [Cited 2019 March 28]. Available from http://www.dynamed.com/login.aspx?direct=true&site=DynaMed&id=114918. Registration and login required
8. Hermida RC, et al. Aspirin administered at bedtime, but not on awakening, has an effect on ambulatory blood pressure in hypertensive patients. J Am Coll Cardiol. 2005 Sep 20;46(6):975-83.
9. Fowkes FG, et al. Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial. 2010 Mar 3;303(9):841-8. doi: 10.1001/jama.2010.221.
10. Halvorsen S, et al. Aspirin therapy in primary cardiovascular disease prevention: a position paper of the European Society of Cardiology working group on thrombosis. J Am Coll Cardiol. 2014 Jul 22;64(3):319-27. doi: 10.1016/j.jacc.2014.03.049.
11. Vandvik PO, et al. Primary and secondary prevention of cardiovascular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. 2012 Feb;141(2 Suppl):e637S-e668S. doi: 10.1378/chest.11-2306.
12. Fick DM, et al. American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc.2015 Nov;63(11):2227-46. doi: 10.1111/jgs.13702. Epub 2015 Oct 8.
13. Pignone M, et al. Aspirin for primary prevention of cardiovascular events in people with diabetes: a position statement of the American Diabetes Association, a scientific statement of the American Heart Association, and an expert consensus document of the American College of Cardiology Foundation. Diabetes Care. 2010 Jun;33(6):1395-402. doi: 10.2337/dc10-0555.
14. Aspirin_PI [Internet]. [Cited 2019 March 28]. Available From: https://www.bayer.ca/omr/online/aspirin-pm-en.pdf

Following a safety review of cough and cold products containing opioids, Health Canada is advising that children and adolescents (under 18 years of age) should not use cough and cold products containing codeine, hydrocodone and normethadone, as a precautionary measure.

Health Canada’s safety review found that there is limited evidence to support the effectiveness of these products in children and adolescents (under 18 years of age). In addition, while the review did not find any strong evidence linking cough and cold products that contain opioids with opioid use disorders in children and adolescents, it did find that the early use of opioids may be a factor in problematic substance use later in life.

In Nigeria, codeine is widely available without a prescription in low-dose formulations to treat cough and cold.

Source: Health Canada, Important Safety Information, February 18, 2019

US Food & Drug Administration (FDA) has concluded there is an increased risk of death with Febuxostat compared to another gout medicine, Allopurinol. This conclusion is based on our in-depth review of results from a safety clinical trial that found an increased risk of heart-related death and death from all causes with Febuxostat.

FDA recommends that Febuxostat should be reserved for use only in patients who have failed or do not tolerate allopurinol. Counsel patients about the cardiovascular risk with Febuxostat and advise them to seek medical attention immediately if they experience any of the following symptoms:

• Chest pain
• Shortness of breath
• Rapid or irregular heartbeat
• Numbness or weakness on one side of your body
• Dizziness
• Trouble talking
• Sudden severe headache

Febuxostat monograph in EMDEX has been updated to reflect this important safety information. See Febuxostat (under Pharmacovigilance).

Source: FDA Drug Safety Communication, February 21, 2019

Health Canada (January 31, 2019) – Health Canada has completed a safety review of hydrochlorothiazide and has found that prolonged use of the drug could increase a person’s risk for non-melanoma skin cancer.

Hydrochlorothiazide is a prescription drug used to treat high blood pressure and swelling. It is known to make skin more sensitive to ultraviolet radiation and sunlight, meaning patients can get sunburned more easily.

Health Canada reviewed the best available evidence on the issue. Findings suggest an increased risk of non-melanoma skin cancer for patients who have used hydrochlorothiazide for more than three years. However, it is important to note that the studies reviewed had significant limitations. For example, there was a lack of patient data on sun exposure and severity, and duration of high blood pressure. Such data could help clarify the cause of the increased risk.

In light of these findings, Health Canada has concluded that prolonged use of hydrochlorothiazide may be associated with a risk of non-melanoma skin cancer that is at least four times the risk of not using hydrochlorothiazide.

Because of the seriousness of this risk and the wide use of this drug, Health Canada is taking a precautionary approach and is working with manufacturers to update the Canadian product safety information to reflect this new risk.

Important safety information for patients:

• Talk to your healthcare provider or pharmacist if you are using hydrochlorothiazide and have any concerns regarding your risk for non-melanoma skin cancer.
• Inform your healthcare provider if you identify any new skin lesions, such as moles or changes to existing skin lesions.
• Limit your exposure to sunlight and avoid using tanning equipment as it can increase the risk of non-melanoma skin cancer. Use adequate protection when exposed to sunlight (e.g., sunscreen with SPF 30 or higher, clothing, and a hat).
• Talk to your healthcare provider if you think that you may be at a particularly higher risk for non-melanoma skin cancer (e.g., if you have light-coloured skin, if you have a personal or family history of skin cancer, or if you are receiving ongoing immunosuppressive therapy).

Important information for healthcare providers:

• Research findings suggest an increased risk of non-melanoma skin cancer with prolonged use of hydrochlorothiazide. However, because of important limitations in the studies, substantial uncertainty remains regarding these findings.
• Patients taking hydrochlorothiazide should be informed of the risk of non-melanoma skin cancer. They should be advised to regularly check their skin for new lesions or changes to existing ones, and to report any suspicious skin lesions to their healthcare provider.
• Patients taking hydrochlorothiazide should be advised to limit exposure to sunlight, avoid using tanning equipment, and use adequate protection (e.g., sunscreen with SPF 30 or higher, clothing, and hat) when exposed to sunlight to minimize the risk of non-melanoma skin cancer.
• Alternatives to hydrochlorothiazide may be considered for patients who are at particularly higher risk for non-melanoma skin cancer (e.g., patients who have light-coloured skin, who have a personal or family history of skin cancer, or who are receiving ongoing immunosuppressive therapy).

Source: https://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2019/68976a-eng.php

In 2013, the WHO-PEN (Package of Essential NCD Interventions) guidelines for managing type 2 diabetes in low-resource settings included diet, physical activity and metformin as first-line treatment; sulfonylurea as second-line treatment (or first-line treatment if metformin is contraindicated); and insulin as third-line treatment.

The newly released 2018 guidelines for diabetes treatment intensification in non-pregnant adults with diabetes mellitus has two main takeaways:

• The newer oral hypoglycaemic agents were not found to be superior to metformin and sulfonylurea. These agents include dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), sodium-glucose co-transporter 2 inhibitors (SGLT-2 inhibitors) and thiazolidinediones (TZDs). The guidelines consider their use as second- and third-line treatment for hyperglycaemia in type 2 diabetes.
• Lack of evidence of the better effectiveness of insulin analogues vs human insulin. Human insulin has a better resource-use profile and is the preferred insulin for adults with type 1 diabetes and in adults with type 2 diabetes for whom insulin is indicated

Key recommendations in the updated 2018 guidelines

Recommendation #1: Give a sulfonylurea* to patients with type 2 diabetes who do not achieve glycaemic control** with metformin alone or who have contraindications to metformin (strong recommendation, moderate-quality evidence).

Remarks

*Glibenclamide should be avoided in patients aged 60 years and older. Sulfonylureas with a better safety record for hypoglycaemia (e.g. gliclazide) are preferred in patients for whom hypoglycaemia is a concern (people who are at risk of falls, people who have impaired awareness of hypoglycaemia, people who live alone, people who drive or operate machinery as part of their job).

**The WHO PEN protocol recommends a target fasting blood glucose of <7 mmol/L (126 mg/dl). However, an individualized approach is encouraged in setting the patient’s target level for glycaemic control, taking into account their comorbidities, risks from medication side-effects and their likely benefit from tight glycaemic control in view of life expectancy.

Recommendation #2: Introduce human insulin treatment to patients with type 2 diabetes who do not achieve glycaemic control with metformin and/or sulfonylurea (strong recommendation, very low-quality evidence).

Recommendation #3: If insulin is unsuitable*, a DPP-4 inhibitor, SGLT-2 inhibitor or a TZD may be added (weak recommendation, very low-quality evidence).

Remark

*Insulin treatment could be unsuitable when circumstances make its use difficult (e.g. persons who live alone and are dependent on others to inject them with insulin).

Recommendation #4: Use human insulin to manage blood glucose in adults with type 1 diabetes, and in adults with type 2 diabetes for whom insulin is indicated (strong recommendation, low-quality evidence**).

Remarks

* Recommendation 4 covers both short-acting (regular human insulin (RHI) and intermediate-acting human insulin (NPH insulin).

**The recommendation is strong because evidence of the better effectiveness of insulin analogues is lacking and human insulin has a better resource-use profile.

Recommendation #5: Consider long-acting insulin analogues to manage blood glucose in adults with type 1 or type 2 diabetes who have frequent severe hypoglycaemia with human insulin (weak recommendation,* moderate-quality evidence for severe hypoglycaemia).

Remark

*Recommendation 5 is a weak recommendation reflecting the lack of, or very low-quality evidence for, any of the long-term outcomes such as chronic diabetes complications and mortality, and the considerably higher costs for long-acting insulin analogues compared to intermediate-acting human insulin.

The National Guideline for the prevention and control of diabetes in Nigeria is in the works. According to the Health Minister, the guideline will ensure standardized protocol for medical care and patient self-management education to prevent acute complication and reduce the risk of long-term complications among Nigerians living with the disease. It is expected to be completed in 2021.

The recommendations contained in the WHO-PEN guidelines are relevant to low-resource countries like Nigeria and can be adopted pending the completion of our national guidelines. Click here for the 2013 edition

The 2018 update is available here

Is there a link between push-up exercise capacity and future cardiovascular events in active adult men?

Cardiovascular disease (CVD) remains the leading cause of death worldwide. In addition to long-recognized risk factors for CVD, such as smoking, hypertension, and diabetes, the unfavourable health consequences of physical inactivity on cardiovascular health have been well established. Studies have suggested that physical activity provides cardiovascular benefits independent of other modifiable CVD risk factors associated with a lower incidence of multiple diseases, including CVD, diabetes, cancer, and Alzheimer disease. A recent US study further suggested that moderate to vigorous physical activity could significantly reduce premature mortality and prolong life expectancy. Given this robust scientific evidence, the American Heart Association added physical activity to its My Life Check—Life’s Simple 7 campaign to reduce the burden of CVD and improve overall health.

American Heart Association has promoted assessment of physical activity in clinical settings and workplaces. There’s growing evidence for objectively assessing cardiorespiratory fitness (CRF) as a vital sign in health care settings. However, unlike anthropometric measurements and serum biomarkers, physical activity and CRF assessments have largely been neglected by clinicians. The most commonly used physical activity assessments are the patient’s self-reported history and health and lifestyle questionnaires. However, objectively measured CRF levels are often significantly lower than expected based on self-reported physical activity. Although good performance on accurate and objective CRF assessment tools such as exercise tolerance tests has been inversely associated with future CVD, these examinations are expensive, time-consuming, and often require professional facilities and trained personnel to administer.

A new study examined baseline performance on commonly performed physical fitness assessments (push-up capacity and submaximal treadmill tests) and its association with subsequent incident CVD events in a cohort of occupationally active men.

This study found that push-up capacity was inversely associated with 10-year risk of CVD events among men aged 21 to 66 years. Thus, push-up capacity, a simple, no-cost measure, may provide a surrogate estimate of functional status among middle-aged men.

Conclusions:

In this 10-year longitudinal study, participants able to complete more than 40 push-ups were associated with a significant reduction in incident CVD event risk compared with those completing fewer than 10 push-ups, which may be explained by significant differences in recognized CVD risk factors at baseline among the groups. The findings suggest that being able to perform a greater number of push-ups at baseline is associated with a lower incidence of CVD events among active adult men. Thus, results from this study suggest that it is reasonable for clinicians to assess functional status during clinical evaluations by using basic questions regarding activity. Further research is warranted to determine the association of push-up capacity with CVD risk in the general population and the potential use of push-ups as a clinical assessment tool.

Source:

Yang J, Christophi CA, Farioli A, et al. Association Between Push-up Exercise Capacity and Future Cardiovascular Events Among Active Adult Men. JAMA Netw Open. 2019;2(2):e188341. doi:10.1001/jamanetworkopen.2018.8341

British Columbia CA – Jeffrey Baglot developed a large ulcer that eventually perforated and required surgery to be repaired, following the use of the powerful anti-inflammatory drug. He was prescribed Ketorolac by Dr. Clasina Fourie (Abbotsford Regional Hospital, BC) during a flareup of his Crohn’s disease in 2011.

Within days, he developed an ulcer at the beginning of his small intestine. The two-centimetre ulcer ultimately ruptured and needed to be surgically repaired. Baglot ended up in another hospital for more than two months.

Baglot, now 33, thought he was going to die.

“My body was shutting down,” he testified in B.C. Supreme Court last year.

Baglot initiated the lawsuit against Dr. Fourie and won. She was ordered to pay nearly $900,000 in damages on Jan. 31.

Justice Diane Cheryl MacDonald said Fourie’s “negligence has had a devastating impact on Mr. Baglot’s life.”

“Today Mr. Baglot is totally disabled, homebound and isolated. Without the prescribing error, I find that it is more likely than not that Mr. Baglot would have continued to have Crohn’s disease but that he would have worked and been a contributing member of society,” MacDonald said.

Review of SAFETY considerations when prescribing Ketorolac

Concern over the high incidence of reported adverse effects with ketorolac trometamol has led to its withdrawal in some countries while in others its permitted dosage and maximum duration of treatment have been reduced. The recommended maximum duration for parenteral therapy is 2 days in the UK; if required, patients should be transferred to oral therapy with another analgesic. In the USA it is recommended that the maximum combined duration of use of parenteral and oral ketorolac should not exceed 5 days. Complications associated with Ketorolac misuse include potential kidney failure, liver damage and gastrointestinal bleeding. There’s also increased risk of heart attack and stroke.

WARNING

Ketorolac tromethamine, a nonsteroidal anti-inflammatory drug (NSAID), is indicated for the short-term (up to 5 days in adults) management of moderately severe acute pain that requires analgesia at the opioid level. Oral ketorolac tromethamine is indicated only as continuation treatment following IV or IM dosing of ketorolac tromethamine, if necessary. The total combined duration of use of oral ketorolac tromethamine and ketorolac tromethamine injection should not exceed 5 days.

Ketorolac tromethamine is not indicated for use in pediatric patients and it is NOT indicated for minor or chronic painful conditions. Increasing the dose of ketorolac tromethamine beyond the label recommendations will not provide better efficacy but will increase the risk of developing serious adverse events.

GASTROINTESTINAL RISK

Ketorolac tromethamine can cause peptic ulcers, gastrointestinal bleeding and/or perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Therefore, ketorolac tromethamine is CONTRAINDICATED in patients with active peptic ulcer disease, in patients with recent gastrointestinal bleeding or perforation, and in patients with a history of peptic ulcer disease or gastrointestinal bleeding. Elderly patients are at greater risk for serious gastrointestinal events.

CARDIOVASCULAR THROMBOTIC EVENTS

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use.

Ketorolac tromethamine is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.

RENAL RISK

Ketorolac tromethamine is CONTRAINDICATED in patients with advanced renal impairment and in patients at risk for renal failure due to volume depletion.

RISK OF BLEEDING

Ketorolac tromethamine inhibits platelet function and is, therefore, CONTRAINDICATED in patients with suspected or confirmed cerebrovascular bleeding, patients with hemorrhagic diathesis, incomplete hemostasis and those at high risk of bleeding.

Ketorolac tromethamine is CONTRAINDICATED as prophylactic analgesic before any major surgery.

HYPERSENSITIVITY

Hypersensitivity reactions, ranging from bronchospasm to anaphylactic shock, have occurred and appropriate counteractive measures must be available when administering the first dose of ketorolac tromethamine injection.

Ketorolac tromethamine is CONTRAINDICATED in patients with previously demonstrated hypersensitivity to ketorolac tromethamine or allergic manifestations to aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs).

INTRATHECAL OR EPIDURAL ADMINISTRATION

Ketorolac tromethamine is CONTRAINDICATED for intrathecal or epidural administration due to its alcohol content.

RISK DURING LABOR AND DELIVERY

The use of ketorolac tromethamine in labour and delivery is CONTRAINDICATED because it may adversely affect fetal circulation and inhibit uterine contractions.

CONCOMITANT USE WITH NSAIDs

Ketorolac tromethamine is CONTRAINDICATED in patients currently receiving aspirin or NSAIDs because of the cumulative risk of inducing serious NSAID-related side effects.

SPECIAL POPULATIONS

Dosage should be adjusted for patients 65 years or older, for patients under 50 kg (110 lbs.) of body weight and for patients with moderately elevated serum creatinine. Doses of ketorolac tromethamine injection are not to exceed 60 mg (total dose per day) in these patients.

DOSAGE AND ADMINISTRATION

Ketorolac Tromethamine Tablets:

Ketorolac tromethamine tablets are indicated only as continuation therapy to ketorolac tromethamine injection, and the combined duration of use of ketorolac tromethamine injection and ketorolac tromethamine tablets is not to exceed 5 (five) days, because of the increased risk of serious adverse events.

The recommended total daily dose of ketorolac tromethamine tablets (maximum 40 mg) is significantly lower than for ketorolac tromethamine injection (maximum 120 mg).

Excerpts:

1. CBC News
2. MARTINDALE – The Complete Drug Reference
3. DailyMed – FDA-approved label information

January 21, 2019: The Ghanaian Food and Drugs Authority (FDA) has issued a public safety alert for cosmetic products with undeclared steroids, hydroquinone and mercury. The agency is warning the public about the potential health hazards associated with the use of these cosmetic products. Investigations by the agency revealed that these cosmetic products on the market contain harmful substances which are not declared on the product labels.

The agency has directed the companies whose products contain these substances (mercury, hydroquinone and steroids) to initiate an immediate recall of the affected products from the market. It stated that these substances are not permitted in cosmetic products due to their potential for severe adverse reactions, especially with prolonged use. Some of the adverse effects associated with these noxious substances include:

• Permanent neurological damage in children (prenatal and neonatal) exposed to mercury during pregnancy and/or lactation
• Kidney toxicity
• Fertility problems
• Birth defects
• Gastrointestinal toxicity
• Liver toxicity
• Skin infections
• Skin cancer
• Hyperpigmentation/Ochronosis

The FDA is advising the general public:

1. Not to purchase any of these cosmetic products as indicated
2. Immediately discontinue the use and return all such products to the retail shops from where they were purchased or to the FDA
3. Report to the FDA any adverse effects arising from the use of any cosmetic product through the FDA’s Safety Monitoring System

The list of companies and products that contain the substances that are not permitted in cosmetic products are:

DIMD Limited

1. Perfect White Beauty Lotion (Clobetasol, Hydroquinone)
2. Day By Day Men Perfect Body Lotion (Betamethasone)

Banare Limited

1. Ahoofe Foundation Body Cream (Mercury, Hydroquinone)

France Mod Limited

1. Fair & White So White Skin Perfecter Brightening and Moisturizing Body Milk (Hydroquinone)

IVO Ghana Limited

1. Zoe Peau Sublime Beauty Lotion (BN:AF50.04000002.09:15) (Mercury, Betamethasone, Hydroquinone)
2. Zoe Peau Sublime Beauty Lotion (BN: not stated) (Mercury, Betamethasone, Hydroquinone)
3. Body Clear Lightening Lotion (BN: not stated) (Mercury, Hydroquinone)
4. Zoe Peau Sublime Face Corrective Cream (BN: not stated) (Mercury, Clobetasol, Betamethasone)
5. Body Fashion Body Milk (BN: not stated) (Mercury, Hydroquinone)
6. HT7 Hyprogel Body Lotion (BN: not stated) (Betamethasone)
7. Beauty Clinic Whitening Lotion (BN: AF51.0500 0001) (Mercury, Hydroquinone)

Magic Dodo Ltd

1. Dodo Beauty Lightening Lotion (BN: 006114) (Mercury, Hydroquinone)
2. Marie France Skin Care (BN: 006045) (Mercury, Betamethasone, Hydroquinone)

Nouvelle Parfumrie Gandour Ghana Limited

1. Tiatio Concentrated Serum (Betamethasone, Clobetasol, Hydroquinone)
2. Bravia Unifying Body Cream (BN: 1006618) (Hydroquinone)
3. Bronze Tone Cocoa Butter and Honey Extracts (Hydroquinone)
4. Passionella Complexion Unifying Serum (Hydroquinone)
5. Passionella Brightening Cream (BN:241540) (Hydroquinone)
6. Fluo Pommade a Huile de Ricin (Betamethasone)
7. Bravia Lotion (Mercury, Clobetasol, Hydroquinone)
8. Doctoress Creme (Clobetasol)
9. Pure Skin Vanishing Care Body Cream (Clobetasol, Hydroquinone)
10. Senophine Creme (Clobetasol)
11. Abana Facial Creme (Mercury, Clobetasol, Hydroquinone)
12. Bronze Tone Maxi Tone Cocoa Butter & Honey Extract Lotion (Hydroquinone)
13. Maxilight Lightening & Purifying Body Lotion (Clobetasol, Hydroquinone)
14. G&G Body Cream (Mercury, Clobetasol, Hydroquinone)

Paradise Cosmetics Limited

1. Bioskin Lightening Body Lotion (BN: 750) (Hydroquinone, Clobetasol)
2. Bioskin Lightening Body Lotion (BN: 847) (Clobetasol, Hydroquinone)
3. Clair-Liss Genial Lightening Body Cream (BN: B9834) (Clobetasol, Hydroquinone)
4. Clair-Liss Genial Lightening Body Cream (9816) (Clobetasol, Hydroquinone)
5. Sivoclair Lightening Body Lotion (BN-3560) (Clobetasol, Hydroquinone)
6. Goldskin Clarifying Body Lotion with Argan Oil (BN: 740) (Clobetasol, Hydroquinone)
7. Goldskin Fast Action Cream with Argan Oil (BN: G07025) (Clobetasol)
8. Peau Claire Lightening Body Cream (BN: 3926) (Clobetasol, Hydroquinone)
9. Biocarrot Lightening Body Lotion (BN: 167) (Clobetasol, Hydroquinone)

Stopover JRA Enterprise

1. RA Foundation Body Cream (Mercury, Hydroquinone)

Universal Basic Company Limited

1. Tendrina Special Hand and Body Complexion Lotion (BN: 139) (Betamethasone)
2. Tendrina Complexion Cream (BN: CT 4003) (Betamethasone)
3. Tendrina Hand and Body Complexion Lotion (BN: not legible) (Betamethasone)
4. TC 35 Clear Complexion Milk (BN: 14352) (Betamethasone)

 

Source: Ghana Food and Drugs Authority (FDA). Press Release; 2019 Jan 21. Available here: https://fdaghana.gov.gh/images/stories/pdfs/Press%20release/PRESS%20RELEASE%202.pdf