The Family Practice Newsletter
Canagliflozin
(Invokana®)
August 2013
Inside this Issue

New PO DM2 Agent:
Canagliflozin
(Invokana®)

Fun in the Sun
**Updated**
Comprehensive
$4 List Available
www.doctorsfp.com
Newsletter Contact Information:
Megan Keller, PharmD
MKELLER4@OhioHealth.com
Doctors Hospital Family Practice
2030 Stringtown Road, Suite 300
Grove City, Ohio 43123
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Amy Gillman, PharmD Candidate
The FDA approved a new
antihyperglycemic medication with a
novel insulin-independent mechanism
on March 29, 2013. Canagliflozin
(Invokana) was approved as an adjunct
to diet and exercise as a monotherapy or
in combination with other agents to
improve glycemic control. FDA
approval was granted via nine clinical
trials assessing over 10,285 patients
with type II diabetes.
Canagliflozin inhibits the sodiumglucose cotransporter 2 (SGLT2) which
is responsible for reabsorption of almost
all glucose in the renal tubules. As a
SGLT2 inhibitor, canagliflozin
decreases reabsorption of glucose in the
proximal renal tubule. Urinary glucose
excretion (UGE) does not occur until
the glucose concentration exceeds the
renal threshold for glucose thus
surpassing the renal tubular resorptive
capacity; canagliflozin decreases the
renal threshold for glucose resulting in
increased UGE. This mechanism
ultimately lowers blood glucose and
decreases A1c 0.77-1.03% as a
monotherapy. Other clinically
significant benefits of canagliflozin are
weight loss, decreased systolic and
diastolic blood pressure, and an increase
in HDL-C.
The increased excretion of sugar
through the urinary tract creates a
breeding ground for infection;
consequently, the most common adverse
effect associated with canagliflozin is
genital mycotic infections in both males
and females. Patients with a history of
infection or uncircumcised males are at
increased risk. Other notable adverse
effects are dose-related LDL elevation,
frequent daytime urination,
hypotension, hyperkalemia, UTIs, and
an increased risk of hypoglycemia when
used with secretagogues or insulin. In
addition, for any patients taking a UGT
enzyme inducer (ex. rifampin,
phenytoin, phenobarbital, ritonavir)
with an eGFR<60 mL/min, consider
using a different antihyperglycemic
agent.
Canagliflozin is available in a 100 mg
(yellow) or 300 mg (white) oral tablet.
Initial dosing is 100 mg once daily prior
to the first meal of the day. Dosage may
be increased to a maximum of 300 mg
once daily in patients with an eGFR ≥
60 mL/min. Dose dependent changes in
renal function are possible upon
initiation, therefore renal function
should be monitored frequently and
canagliflozin should be discontinued if
eGFR is consistently <45 mL/min. Any
volume depletion should be corrected
prior to initiation. The price of 30
tablets is $315.72.
One condition for approval was that five
post-marketing studies are to be
completed which will assess
cardiovascular effects, risk of
malignancies, pancreatitis, severe
hypersensitivity reactions,
photosensitivity, liver abnormalities,
adverse pregnancy outcomes, and
pediatric efficacy/safety.
Ultimately, canagliflozin is anticipated
to be a valuable new option for patients
with type II diabetes. It may be a good
alternative for patients who are resistant
to injectable therapies, have experienced
intolerable side effects with other
antihyperglycemics, or have yet to
achieve control of their diabetes with
other combinations.
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The Family Practice Newsletter – August 2013
Fun in the Sun
Ryan Hamm, PharmD Candidate

Recently, the FDA set forth new
regulations for OTC sunscreen products
(effective in June 2012).
So why now?

According to the CDC, skin cancer rates
are on the rise. From 2000 to 2009, skin
cancer rates have increased by 1.9% a
year. In that same time frame, mortality
increased by 1% a year. Skin cancer is
also the most common form of cancer in
the U.S. Shockingly, only about 32% of
adults and between 7-14% of teens
reported using protective sunscreens
when outside in 2008. These alarming
statistics indicate that we are failing to
prevent the most common form of
cancer in the country, and it is one that
is almost completely preventable.


will be labeled as “broad
spectrum”, and also must be SPF
15 or higher to make these claims.
Products not meeting broad
spectrum or SPF 15 regulations will
be labeled with warnings that they
protect against sunburns, but not
against skin cancer or premature
skin aging.
Products can no longer use terms
such as “waterproof”,
“sweatproof”, or “sunblock” to
describe their products.
Sunscreens cannot claim immediate
protection (eg. Now says “apply 15
minutes before sun exposure”), and
cannot claim protection lasting
more than 2 hours before
reapplying, unless approved by the
FDA.
“Water resistance” time claims will
now be tested when referring to
water and sweat exposure, and will
be listed as either “40 minutes” or
“80 minutes”.
Possible future changes?
http://www.cdc.gov/cancer/skin/statistics/race.htm
Changes made?

Sun Safety Reminders
1.
2.
3.
4.
Reapply sunscreen at least every 2
hours. Reapply more often if you
are in water or sweating profusely.
Cover skin with long sleeve shirts,
pants, sunglasses, and widebrimmed hats when possible.
Limit exposure to the sun, and try
to avoid sun exposure during the
timeframe of 10 a.m. to 2 p.m.
Always use sunscreens with SPF
values of 15+.
Resources for your Patients


The U.S. Environmental Protection
Agency’s Sunwise Program is a
great resource for teaching children
how to stay safe in the sun.
http://www2.epa.gov/sunwise.
The National Cancer Institute’s
(NCI) website has wonderful
information about detecting,
diagnosing, and the symptoms and
treatment of melanoma.
http://www.cancer.gov/cancertopics
/types/melanoma
The FDA is also considering other
changes besides these, which may be
applied in the near future. The FDA is
considering banning any sunscreen
claims of SPFs greater than 50 (they
would be labeled as SPF 50+).
The FDA now issues a standard test
to determine if sunscreen products
offer protection against both UVA
(mostly responsible for skin cancer
and premature skin aging) and
UVB (mostly responsible for
sunburn) rays. Ones that pass this
http://www.fda.gov/forconsumers/consumerupdates/ucm258416.htm
References:
New PO DM2 Agent: Canagliflozin (Invokana ®)
1. Busko, M. Invokana Tops Januvia as Third-Line Therapy, With Drawbacks. Diabetes Care. Published online: 16 April 2013.
http://www.medscape.com/viewarticle/782571.
2. Canagliflozin. Drug Monograph. Lexi-Comp. Copyright 2013. Cited: 12 June 2013.
3. FDA Approves Invokana to Treat Type 2 Diabetes. FDA News Release. U.S. Food and Drug Administration. 29 March 2013.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm345848.htm.
4. Invokana: canagliflozin tablets. Janssen Pharmaceutical Companies. Last updated: 03 June 2013. http://www.invokanahcp.com/.
5. Schernthaner G, Gross JL, Rosenstock J, et al. Canagliflozin Compared with Sitagliptin for Patients with Type 2 Diabetes Who Do Not Have Adequate
Glycemic Control with Metformin plus Sulfonylurea. Diabetes Care. 5 April 2013. www.care.diabetesjournals.org.
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The Family Practice Newsletter – August 2013
Fun in the Sun
1. Center for Disease Control and Prevention (CDC). Skin Cancer: Statistics and Sun-Protective Behavior rates. Available at:
http://www.cdc.gov/cancer/skin/statistics/behavior.htm Accessed on: 6/6/2013.
2. National Cancer Institute (NCI). Melanoma Information. Available at: http://www.cancer.gov/cancertopics/types/melanoma. Accessed on: 6/12/2013.
3. U.S. Environmental Protection Agency (EPA). Sunwise Program. Available at: http://www2.epa.gov/sunwise. Accessed 6/12/2013.
4. U.S. Food and Drug Administration (FDA). Consumer updates: FDA Sheds Light on Suncreens. Available at:
http://www.fda.gov/forconsumers/consumerupdates/ucm258416.htm Accessed on: 6/6/2013
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