American Diabetes Association - 2012 Recommendations

In the Diabetes Care, January supplement, ADA has published 2012 recommendations.  The following posts are some of highlights of the recommendations and comparison against the CDA 2008 recommendations:

Criteria for testing diabetes in asymptomatic adult individuals (ADA recommendations)

1.       Testing should be considered in all adults who are overweight (BMI ≥ 25kg/m²) and who have one or more additional risk factors:

·         Physical inactivity

·         First-degree relative with diabetes

·         High-risk race/ethnicity (e.g., African American, Latino, Native American, Asian American, Pacific Islander)

·         Women who delivered a baby weighing > 9 lb or who were diagnosed with GDM

·         Hypertension (BP≥140/90 mmHg or on therapy for hypertension

·         HDL < 0.90 mmol/L and/or TG > 2.82 mmol/L

·         Women with PCOS

·         A1C ≥ 7.5%, IGT, or IFG on previous testing

·         Other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis nigricans)

·         History of CVD

2.       In the absence of the above criteria, testing for diabetes should begin at age 45 years

3.     If results are normal, testing should be repeated at least at 3-year intervals, with consideration of more frequent testing depending on initial results (e.g., those with prediabetes should be tested yearly) and risk status.

NOTE: CDA guidelines recommend screening for diabetes every 3 years in individuals ≥ 40 years of age.  More frequent and/or earlier testing should be considered in people with additional risk factors for diabetes (same risk factors as ADA, but also includes schizophrenia and other risk factors in appendix 1, S194 of 2008 recommendations.)

Bottomline:  ADA recommendations are more strict with screening for diabetes

Diagnosis of Diabetes

Did you know that A1C > or = 6.5% using a standardized, validated assay, in the absence of conditions that affect the accuracy of the A1C can be used to diagnose diabetes?

There is a position states by the Canadian Diabetes Association that was posted in July 2011 - http://www.diabetes.ca/documents/for-professionals/CJD--July_2011--Position_Statement.pdf

For factors that can affect A1C include erythropoiesis, altered hemoglobin, alcoholism, chronic renal failure, erythrocyte destruction, assays, etc.  See website above for more detailed information.

Ontario Narcotic Strategy - List of Drugs

By Mary Nelson

Folic acid 5mg & obesity (BMI>30kg/m2)

At the CDA 2011 conference, folic acid 5mg/d is recommended for patients with Type 2 DM and obesity > 30kg/m2.  This is based on a theoretical "evidence" - where a larger volume of distribution requires a larger dose of folic acid.  Why 5mg?  Because it comes in a 5mg tablet (prescription only).  No direct evidence to support or refute this recommendation.

Hyperuricemia and Gout

By: Annette Vedelago


1) Natural history of gout

Unusual for gout to occur under age 30 in males or under age 50 in females

Four stages:        -   asymptomatic hyperuricemia
                             -   acute gouty arthritis

                             -   intercritical gout

                             -   chronic tophaceous gout

2) Pathophysiology

• Increase in UA from a decrease in urine  acid excretion or
• increase purine breakdown most commonly secondary to drugs (chemotherapy, diuretics, low dose aspirin), disease (malignancies, renal dysfunction, psoriasis), and dietary (beer, fish, red meat)

3) Asymptomatic hyperuricemia

• > 360 μmoL/L for females
• > 420 μmoL/L for males

The incidence of acute gout after 20 years of sustained hyperuricemia is:

• 0.1% – 0.5% for UA concentrations between 420 - 540 μmoL/L
• 5% for UA > 504 μmoL/L

4) Clinical pearl

Asymptomatic hyperuricemia usually does not require treatment with some exceptions. 

5) Drugs and conditions associated with hyperuricemia ¹

Drugs

•   alcohol
•  cyclosporine
•  cytotoxic chemotherapy
• diuretics
•  ethambutol
•  interferon + ribavirin
•  levodopa
•  nicotinic acid
•  pyrazinamide
•  salicylates, low-dose
•  tacrolimus
•  teriparatide

Conditions

•  alcohol consumption
•  atherosclerosis
•  diabetes
•  hyperlipidemia
•  hypertension
•  intrinsic renal disease
•  ischemic heart disease
•  metabolic syndrome
•  myeloproliferative disorders and some cancers  
•  obesity

What is the concern of diuretics with gout? ²

Loop (e.g. furosemide) and thiazide diuretics decrease the excretion and increase the concentration of uric acid.

hydrochlorothiazide-induced gout:    ~ 1%  increased when dose >25 mg/d

6) Diagnostic rule

• consider male gender
• previous patient reported arthritis attack
• onset within one day
• joint redness
• 1st MTP joint
• hypertension or > CVD risk and UA > 360 μmoL/L

Reference 1

7) What non-pharmacological therapies are recommended? ²

Acute attack: rest, elevate limb, ice, avoid contact

Maintenance: useful and may decrease the need for preventative medications

             Diet: compliance with low purine diets is poor, recommend one less portion of meat or fish per day; drink wine instead of beer; drink a glass of skimmed milk each day. Low fat dairy, fiber, vitamin C, and whole grains are associated with decreased gout.
Low calorie diet more beneficial/acceptable then low purine diet!

               Avoid: liver, kidney, shellfish, gravy, sardine, sweetbread, sugar drinks and yeast extract.

               Lifestyle: Weight loss, Smoking cessation, decrease alcohol binging (especially beer)

                                drink 2 L water/day (unless contraindicated), mild-moderate intensity exercise.

8) Indications for antihyperuricemic therapy ¹

• 2 attacks/year
•  severe or polyarticular attacks
•  presence of tophaceous gout
•  radiographic evidence of joint damage due to gout
•  severe/persistent hyperuricemia (> 720 μmoL/L)
•  hypoxanthine-guanine phosphoribosyl ransferase (HGPRT) deficiency or prhosphoribosyl perophosphate (PRPP) synthetase overactivity ( both ­ uric acid production)
•  uric acid nephropathy, nephrolithiasis (uric acid or calcium stones)
•  24-hour urinary uric acid excretion > 1000 mg, particularly in males < 25 years and premenopausal women
•  prophylaxis of hyperuricemia prior to administration of cytotoxic agents

Reference 1

Reference 1

Reference 1

Reference 1

Clinical pearls  – NSAIDs

• Contraindicated with decreased renal function (Clcr < 30 mL/min), GI) ulcer, heart failure, previous allergy to NSAID.
• Indomethacin is used historically, however others are also effective and cause less CNS adverse effects
• GI prophylaxis should be considered in the presence of a history of PUD/GI bleed or age > 70 (PPI or misoprostol 200 μg TID – QID)
• High doses for 1^st 24-72 hours, then stop or use lowest effective dose x 1-2 weeks

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Clinical pearls  – Colchicine

Dose:  1.2 mg stat then 0.6 mg 1 hour later (FDA); no further doses for 3 days (CPS) other dosing schedules have been used: 0.6 mg bid x 1-3 days, then daily x1-2 weeks

Limiting dose to less than 3 tablets on day 1 then 1-2 tablets/day will greatly decrease diarrhea/GI side effects

Use ½ dose if taking concomitant strong CYP3A4 inhibitor and normal renal/hepatic function (CPS) see CPS for other doses

Monitor:  CBC (neutropenia), CK (rhabdomyolysis may increase with statins/fibrates), renal function q6 months

Prophylaxis when starting allopurinol:  0.6 daily – bid (or 1 mg daily) x 3 – 6 months.

NOT COVERED ON ODB
Vitamin C   

1000 – 1500 mg/day may reduce relative risk of gout by 34 – 45%

However, doses over 1000 mg increases risk of kidney stones (oxalate or uric acid) in those who have had a previous kidney stone

•       May increase excretion of uric acid.

Clinical pearls  – Allopurinol

Wait 1-2 weeks after inflammation subsides before initiating NEVER START OR STOP ALLOPURINOL DURING AN ACUTE ATTACK

Prophylax with colchicine (0.6 daily – bid) or NSAID low dose x 3 – 6 months while titrating allopurinol

D/C if rash since rash may precede serious hypersensitivity reactions (20-30% mortality)

Start low:  100 – 200 mg daily and increase by 100 mg weekly based on UA levels (CPS)  or start at 100 mg daily and increase q2 – 4 weeks (RxFiles)

Maximum 800 mg daily if normal renal function, otherwise reduced.

If eGFR < 50 mL/min, start at 50 mg/day and titrate by 50 mg doses, maximum 300 mg/day.  (http://www.rxfiles.com/)

CrCl 10 – 20 mL/min max. maintenance dose 100 mg daily

CrCl < 10 mL/min max maintenance dose 100 mg q2-3 days

Divided doses if > 300 mg daily (improved GI tolerability)

After food

↑INR possible with warfarin – monitor

↑toxicity of azathioprine

Before starting:  LFT; Cr (CrCl); CBC

Febuxostat (Uloric ©)

80 mg daily more effective than allopurinol 300 mg daily in bringing UA to goal (<360 μmoL/L)

May be used if CrCl > 30 mL/min

Alternative to allopurinol if hypersensitive to allopurinol

BUT – more expensive, NOT COVERED ON ODB, if normal renal function, allopurinol dose may be increased above 300 mg (800 mg max)

Contraindicated with azathioprine, mercaptopurine or theophylline!

Conclusions

Treat acute gout before deciding upon need for UA lowering Tx

Consider iatrogenic causes (ie. Drugs)

Never start or stop allopurinol (or febuxostat) during acute attack

Use prophylaxis with colchicine or NSAID x 3-6 months while titrating dose of allopurinol (or            
               febuxostat

References

1.  Therapeutic choices. Canadian pharmacists Association, 2011

2.  www.RxFiles.ca (Accessed Oct 17, 2011)

Annette's Phun Pharmacy Phacts - Narcotic Safety and Awareness Act

Citalopram (Celexa) & Abnormal Heart Rhythms

On August 24, 2011, the US FDA has recommended the following:


RECOMMENDATION: Citalopram causes dose-dependent QT interval prolongation. Citalopram should no longer be prescribed at doses greater than 40 mg per day. Citalopram should not be used in patients with congenital long QT syndrome. Patients with congestive heart failure, bradyarrhythmias, or predisposition to hypokalemia or hypomagnesemia because of concomitant illness or drugs, are at higher risk of developing Torsade de Pointes.

Data Summary 

FDA has received post-marketing reports of QT interval prolongation and Torsade de Pointes associated with Celexa and its generic equivalents. In addition, FDA has evaluated the results of a thorough QT study assessing the effects of 20-mg and 60-mg doses of citalopram on the QT interval in adults. In this randomized, multi-center, double-blind, placebo-controlled, crossover study, 119 subjects received citalopram 20 mg per day (Day 9), citalopram 60 mg per day (Day 22), and placebo. The overall summary of findings is presented in Table 1 

Table 1: Increase in the Corrected QT Interval for Citalopram (FDA Analysis) 

Citalopram Dose	Increase in QT Interval (ms)	90% Confidence Interval (ms)
20 mg/day	8.5	(6.2, 10.8)
60 mg/day	18.5	(16.0, 21.0)
40 mg/day	12.6*	(10.9, 14.3)*

*Estimate based on the relationship between citalopram blood concentration and QT interval.

Compared to placebo, maximum mean prolongations in the individually corrected QT intervals were 8.5 and 18.5 milliseconds (ms) for 20 mg and 60 mg citalopram, respectively. For 40 mg citalopram, prolongation of the corrected QT interval was estimated to be 12.6 ms. 

As a result of this thorough QT study, FDA has determined that citalopram causes dose-dependent QT interval prolongation and should no longer be used at doses above 40 mg per day. Important safety information about the potential for QT interval prolongation and Torsade de Pointes with drug dosage and usage recommendations are being added to the package inserts of Celexa and its generic equivalents.

What does this mean for our patients with depression and anxiety that have felt a benefit from the increased dose of citalopram 60mg?

Consider the following:

1.  Discuss with the patient the US FDA recommendations and possible increase risk of QT prolongation.

2.  Suggest monitor ECG, serum K+ and Mg+ (regularly if maintaining dose of 60mg)

3.  If tapering to citalopram 40mg, follow up with the patient accordingly to ensure no relapse (e.g., within the month)

4.  If relapse occurs, consider switching to sertraline (max dose = 200mg/d) or augmenting with bupropion (depending on the diagnosis of treatment)  {e.g., if depression+anxiety, consider sertraline.  If major depressive disorder only, consider adding bupropion (bupropion may increase anxiety)}

If you have any other suggestions or comments, please feel free to share on this blog!

References:
1.  http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm269481.htm
2. http://www.fda.gov/Drugs/DrugSafety/ucm269086.htm