[AF] Consulta Dapagliflozina

Mar Abr 22 10:23:06 CEST 2014

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Dapagliflozin: Drug information

(For additional information see "Dapagliflozin: Patient drug information")

For abbreviations and symbols that may be used in Lexicomp (show table)

Brand Names: U.S. Farxiga

Pharmacologic Category Antidiabetic Agent, Sodium-Glucose Cotransporter 2 (SGLT2) 

Inhibitor; Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor

Dosing: Adult Note: If present, correct volume depletion prior to initiation.

Type 2 diabetes mellitus: Oral: Initial: 5 mg once daily in the morning, with or without food; may 

increase to 10 mg once daily

Dosing: Geriatric Refer to adult dosing.

Dosing: Renal Impairment

eGFR ≥60 mL/minute/1.73 m : No dosage adjustment necessary.

eGFR <60 mL/minute/1.73 m : Initial: Use not recommended. In patients already taking dapagliflozin 

(when baseline eGFR was ≥60 mL/minute/1.73 m ) that experience a persistent decrease in 

eGFR to <60 mL/minute/1.73 m , dapagliflozin should be discontinued.

eGFR <30 mL/minute/1.73 m : Use is contraindicated.

ESRD: Use is contraindicated.

Hemodialysis: Use is contraindicated.

Dosing: Hepatic Impairment

Mild to moderate hepatic impairment (Child-Pugh class A, B): No dosage adjustment necessary.

Severe hepatic impairment (Child-Pugh class C): No dosage adjustment provided in manufacturer’s 

labeling (has not been studied).

Dosage Forms: U.S. Excipient information presented when available (limited, particularly for 

generics); consult specific product labeling.

Tablet, Oral: 

Farxiga: 5 mg, 10 mg

Generic Equivalent Available: U.S. No

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Medication Guide An FDA-approved patient medication guide, which is available with the 

product information and at http://packageinserts.bms.com/medguide/medguide_farxiga.pdf, must be 

dispensed with this medication.

Administration Administer in the morning, with or without food

Use Type 2 diabetes mellitus: As an adjunct to diet and exercise to improve glycemic control in 

adults with type 2 diabetes mellitus

Medication Safety Issues

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs 

which have a heightened risk of causing significant patient harm when used in error.

Adverse Reactions Significant

1% to 10%:

Endocrine & metabolic: Mild hypoglycemia (plus insulin or other oral antidiabetic therapy: 40% to 

43%), dyslipidemia (2% to 3%), hypovolemia (1%; includes dehydration, hypovolemia, 

orthostatic hypotension, hypotension)

Gastrointestinal: Nausea (3%), constipation (2%)

Genitourinary: Fungal vaginosis (7% to 8%; includes [in order of frequency] vulvovaginal mycotic 

infection, vaginal infection, vulvovaginal candidiasis, vulvovaginitis, genital infection, genital 

candidiasis, fungal genital infection, vulvitis, genitourinary tract infection, vulval abscess, 

vaginitis bacterial), urinary tract infection (4% to 6%: includes [in order of frequency] urinary 

tract infection, cystitis, Escherichia urinary tract infection, genitourinary tract infection, 

pyelonephritis, trigonitis, urethritis, kidney infection, prostatitis), increased urine output (3% to 

4%: includes [in order of frequency] pollakiuria, polyuria, and urine output increased), 

genitourinary fungal infections (mycotic; in males: 3%; includes [in order of frequency] 

balanitis, fungal genital infection, balanitis candida, genital candidiasis, genital infection, 

penile infection, balanoposthitis, balanoposthitis infective, genital infection, posthitis), dysuria 

(2%)

Hematologic & oncologic: Increased hematocrit (1%, hematocrit >55%)

Infection: Influenza (2% to 3%)

Neuromuscular & skeletal: Back pain (3% to 4%), limb pain (2%)

Respiratory: Nasopharyngitis (6% to 7%)

Frequency not defined:

Dermatologic: Urticaria

Endocrine & metabolic: Increased LDL cholesterol, increased serum phosphate

Hypersensitivity: Hypersensitivity reaction (angioedema, urticaria, hypersensitivity)

Neuromuscular & skeletal: Bone fracture (in patients with moderate renal impairment)

Renal: Decreased estimated GFR, increased serum creatinine

<1% (Limited to important or life-threatening): Bladder neoplasm

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Contraindications History of serious hypersensitivity to dapagliflozin or any component of the 

formulation; severe renal impairment, end-stage renal disease (ESRD), or patients on dialysis

Warnings/Precautions

Concerns related to adverse effects:

• Genital mycotic infections: May increase the risk of genital mycotic infections (eg, vulvovaginal 

• Hypersensitivity reactions: Patients may experience hypersensitivity reactions (eg, angioedema, 

• Hypotension: May cause symptomatic hypotension due to intravascular volume depletion, 

• Lipid abnormality: May cause LDL-cholesterol (C) elevation; monitor LDL-C and treat as 

• Renal effects: Abnormalities in renal function (decreased eGFR, increased serum creatinine) 

mycotic infection, vulvovaginal candidiasis, vulvovaginitis, candida balanitis, balanoposthitis). 

Patients with a history of these infections or uncircumcised males are at greater risk.

urticaria), with some being severe. Discontinue dapagliflozin if hypersensitivity occurs and 

treat as appropriate.

especially in patients with renal impairment (ie, eGFR <60 mL/minute/1.73 m ), elderly, 

patients on other antihypertensives (eg, diuretics, ACE inhibitors, or angiotensin receptor 

blockers [ARBs]), or those with low systolic blood pressure. Assess volume status prior to 

initiation in patients at risk of hypotension and correct if depleted; monitor signs and 

symptoms of hypotension after initiation.

needed.

may occur; elderly patients and patients with preexisting renal impairment may be at greater 

risk. Assess renal function prior to initiation and periodically during treatment; dapagliflozin 

should not be initiated if initial eGFR is <60 mL/minute/1.73 m and should be discontinued 

when eGFR is persistently <60 mL/minute/1.73 m . Use is contraindicated in severe renal 

impairment (<30 mL/minute/1.73 m ) and ESRD.

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Disease-related concerns:

• Bladder cancer: Newly diagnosed bladder cancer occurred more frequently in dapagliflozin 

patients; causal relationship could not be established. Do not use in patients with active 

bladder cancer; weigh the benefits of glycemic control versus the unknown risks for cancer 

recurrence in patients with a history of bladder cancer.

• Diabetic ketoacidosis: Should not be used in patients with diabetic ketoacidosis (DKA).

• Hepatic impairment: Weigh benefits versus risk in patients with severe hepatic impairment (has 

• Renal impairment: Glycemic efficacy may be less and adverse reactions (eg, renal-related 

not been studied).

adverse reactions, bone fractures) may be higher with moderate renal impairment (eGFR 30 

to <60 mL/minute/1.73 m ); dapagliflozin should not be initiated in this population and should 

be discontinued when eGFR is persistently <60 mL/minute/1.73 m . Use is contraindicated in 

severe renal impairment (<30 mL/minute/1.73 m ) and ESRD.

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• Type 1 diabetes mellitus: Should not be used in patients with type 1 diabetes mellitus (insulin-
dependent, IDDM); has not been studied.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency 

adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug 

interactions database for more detailed information.

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Special populations:

• Elderly: Elderly patients may be predisposed to symptoms related to intravascular volume 

depletion (eg, hypotension, orthostatic hypotension, dizziness, syncope, and dehydration) 

and renal impairment or failure.

Metabolism/Transport Effects Substrate of P-glycoprotein, UGT1A9

Drug Interactions

(For additional information: Launch Lexi-Interact™ Drug Interactions Program)

Corticosteroids (Orally Inhaled): May diminish the hypoglycemic effect of Antidiabetic Agents. In some 

instances, corticosteroid-mediated HPA axis suppression has led to episodes of acute adrenal 

crisis, which may manifest as enhanced hypoglycemia, particularly in the setting of insulin or 

other antidiabetic agent use. Risk C: Monitor therapy

Corticosteroids (Systemic): May diminish the hypoglycemic effect of Antidiabetic Agents. In some 

instances, corticosteroid-mediated HPA axis suppression has led to episodes of acute adrenal 

crisis, which may manifest as enhanced hypoglycemia, particularly in the setting of insulin or 

other antidiabetic agent use. Risk C: Monitor therapy

DULoxetine: Hypotensive Agents may enhance the orthostatic hypotensive effect of DULoxetine. Risk 

C: Monitor therapy

Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemic Agents.

Risk C: Monitor therapy

Hypoglycemic Agents: May enhance the adverse/toxic effect of other Hypoglycemic Agents. Risk C: 

Monitor therapy

Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: 

Monitor therapy

Loop Diuretics: May diminish the hypoglycemic effect of Hypoglycemic Agents. Risk C: Monitor 

therapy

Luteinizing Hormone-Releasing Hormone Analogs: May diminish the therapeutic effect of Antidiabetic 

Agents. Risk C: Monitor therapy

MAO Inhibitors: May enhance the hypoglycemic effect of Hypoglycemic Agents. Risk C: Monitor 

therapy

Pegvisomant: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy

Salicylates: May enhance the hypoglycemic effect of Hypoglycemic Agents. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Hypoglycemic 

Agents. Selective Serotonin Reuptake Inhibitors may increase the serum concentration of 

Hypoglycemic Agents. Management: Consider increased monitoring of glycemic control with 

concomitant use of a hypoglycemic agent and an SSRI. Dosage adjustments of the hypoglycemic 

agent may be necessary upon SSRI initiation or discontinuation. Risk C: Monitor therapy

Somatropin: May diminish the hypoglycemic effect of Antidiabetic Agents. Risk D: Consider therapy 

modification

Thiazide Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Pregnancy Risk Factor C (show table)

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Pregnancy Implications Adverse events were observed in animal reproduction studies. 

Alternate therapies are recommended especially during the second and third trimesters.

Lactation Excretion in breast milk unknown/not recommended

Breast-Feeding Considerations It is not known if dapagliflozin is excreted into breast milk. 

Due to the potential for serious adverse reactions in the nursing infant, the manufacturer recommends 

a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the 

importance of treatment to the mother.

Dietary Considerations Individualized medical nutrition therapy (MNT) based on ADA 

recommendations is an integral part of therapy.

Pricing: U.S.

Tablets (Farxiga Oral)

5 mg (30): $347.04

10 mg (30): $347.04

Disclaimer: The pricing data provide a representative AWP and/or AAWP price from a single 

manufacturer of the brand and/or generic product, respectively. The pricing data should be used for 

benchmarking purposes only, and as such should not be used to set or adjudicate any prices for 

reimbursement or purchasing functions. Pricing data is updated monthly.

Monitoring Parameters Blood glucose, HbA ; renal function (baseline and periodically during 

treatment); LDL-C; monitor for genital mycotic infections and hypersensitivity reactions; monitor blood 

pressure

Reference Range Recommendations for glycemic control in nonpregnant adults with diabetes 

(ADA, 2013):

HbA : <7% (a more aggressive [<6.5%] or less aggressive [<8%] HbA goal may be targeted based 

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on patient-specific characteristics)

Preprandial capillary plasma glucose: 70-130 mg/dL

Peak postprandial capillary blood glucose: <180 mg/dL

International Brand Names Forxiga (AU, CZ, DE, DK, EE, ES, GB, KP, NL, NO, NZ, SE)

Mechanism of Action By inhibiting sodium-glucose cotransporter 2 (SGLT2) in the proximal 

renal tubules, dapagliflozin reduces reabsorption of filtered glucose from the tubular lumen and lowers 

the renal threshold for glucose (RT ). SGLT2 is the main site of filtered glucose reabsorption; 

reduction of filtered glucose reabsorption and lowering of RT result in increased urinary excretion of 

glucose, thereby reducing plasma glucose concentrations.

Pharmacodynamics/Kinetics

Protein binding: 91%

Metabolism: Primarily mediated by UGT1A9 to an inactive metabolite (dapagliflozin 3-O-glucuronide); 

CYP-mediated metabolism (minor).

Bioavailability: 78%

Half-life elimination: ~12.9 hours

Time to peak, plasma: 2 hours

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Excretion: Urine (75%; < 2% as parent drug); feces (21%; ~15% as parent drug)

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REFERENCES

1. American Diabetes Association. Standards of Medical Care in Diabetes--2013. Diabetes Care. 2013;36(Suppl 

1):S11-S66. [PubMed 23264422]

2. Farxiga [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; January 2014.

Un abrazo.

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Ramón Díaz-Alersi