Hospital Pharmacy - February 2018 - 23

Current FDA-Related Drug Information

INVOKAMET XR (CANAGLIFLOZIN; METFORMIN HYDROCHLORIDE) (NDA-205879)
Edited Boxed Warning
(additions underlined)
** WARNING: LACTIC ACIDOSIS and LOWER LIMB AMPUTATION
** Lactic Acidosis
** Post-marketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and
resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by
nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metforminassociated lactic acidosis was characterized by elevated blood lactate levels (> 5 mmol/Liter), anion gap acidosis
(without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels
generally >5 mcg/mL .
** Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs
(e.g., cationic drugs such as topiramate), age 65 years old or greater, having a radiological study with contrast,
surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, and
hepatic impairment.
** Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided
in the full prescribing information.
** If metformin-associated lactic acidosis is suspected, immediately discontinue INVOKAMET and institute general
supportive measures in a hospital setting. Prompt hemodialysis is recommended
** Risk of Lower Limb Amputation
** An approximately 2-fold increased risk of lower limb amputations associated with canagliflozin, a component of
INVOKAMET, was observed in CANVAS and CANVAS-R, two large, randomized, placebo-controlled trials in
patients with type 2 diabetes who had established cardiovascular disease (CVD) or were at risk for CVD.
** Amputations of the toe and midfoot were most frequent; however, amputations involving the leg were also
observed. Some patients had multiple amputations, some involving both limbs.
** Before initiating, consider factors that may increase the risk of amputation, such as a history of prior amputation,
peripheral vascular disease, neuropathy, and diabetic foot ulcers.
** Monitor patients receiving INVOKAMET for infection, new pain or tenderness, sores or ulcers involving the lower
limbs, and discontinue if these complications occur.

JEVTANA KIT (CABAZITAXEL) (NDA-201023)
Edited Boxed Warning
Additions and/or revisions underlined:
WARNING: NEUTROPENIA AND HYPERSENSITIVITY
Neutropenia: Neutropenic deaths have been reported. Monitor for neutropenia with frequent blood cell counts.
JEVTANA is contraindicated in patients with neutrophil counts of less than or equal to 1,500 cells/mm3. Primary
prophylaxis with G-CSF is recommended in patients with high-risk clinical features.

THYRO-TABS (LEVOTHYROXINE SODIUM) (NDA 021116)
Edited Boxed Warning
PLR conversion; newly added section:
WARNING: NOT FOR TREATMENT OF OBESITY OR FOR WEIGHT LOSS
Thyroid hormones, including THYRO-TABS, either alone or with other therapeutic agents, should not be used for the
treatment of obesity or for weight loss.
In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction.
Larger doses may produce serious or even life threatening manifestations of toxicity, particularly when given in
association with sympathomimetic amines such as those used for their anorectic effects.

Table of Contents for the Digital Edition of Hospital Pharmacy - February 2018