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  • Forxiga
    / Astra Zeneca


    Active Ingredient
    Dapagliflozin (propanediol monohydrate) 5 mg, 10 mg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Film Coated Tablets

    7/14/28/30/90/98 X 5 mg

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    Film Coated Tablets

    30 X 10 mg

    partial basket chart 58567 6545

    Related information


    Dosage

    Monotherapy and add-on combination therapy: The recommended dose is 10 mg dapagliflozin once daily for monotherapy and add-on combination therapy with other glucose-lowering medicinal products including insulin. When dapagliflozin is used in combination with insulin or an insulin secretagogue, such as a sulphonylurea, a lower dose of insulin or insulin secretagogue may be considered to reduce the risk of hypoglycaemia.
    Renal impairment: The efficacy of dapagliflozin is dependent on renal function, and efficacy is reduced in patients who have moderate renal impairment and likely absent in patients with severe renal impairment. Forxiga is not recommended for use in patients with moderate to severe renal impairment (patients with creatinine clearance [CrCl] < 60 ml/min or estimated glomerular filtration rate [eGFR] < 60 ml/min/1.73 m². No dosage adjustment is indicated in patients with mild renal impairment.
    Hepatic impairment: No dosage adjustment is necessary for patients with mild or moderate hepatic impairment. In patients with severe hepatic impairment, a starting dose of 5 mg is recommended. If well tolerated, the dose may be increased to 10 mg.
    Elderly (≥ 65 years): In general, no dosage adjustment is recommended based on age. Renal function and risk of volume depletion should be taken into account. Due to the limited therapeutic experience in patients 75 years and older, initiation of dapagliflozin therapy is not recommended.
    Paediatric population: The safety and efficacy of dapagliflozin in children aged 0 to < 18 years have not yet been established. No data are available.
    Method of administration: This drug can be taken orally once daily at any time of day with or without food. Tablets are to be swallowed whole.


    Indications

    Indicated in adults aged 18 years and older with type 2 diabetes mellitus to improve glycaemic control as:
    Monotherapy: When diet and exercise alone do not provide adequate glycaemic control in patients for whom use of metformin is considered inappropriate due to intolerance.
    Add-on combination therapy: In combination with other glucose-lowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control.


    Contra-Indications

    Hypersensitivity to the active substance or to any of the excipients.


    Special Precautions

    This drug should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
    Renal impairment: The efficacy of dapagliflozin is dependent on renal function, and efficacy is reduced in patients who have moderate renal impairment and likely absent in patients with severe renal impairment . In subjects with moderate renal impairment (patients with CrCl < 60 ml/min or eGFR < 60 ml/min/1.73 m²), a higher proportion of subjects treated with dapagliflozin had adverse reactions of increase in creatinine, phosphorus, parathyroid hormone (PTH) and hypotension, compared with placebo. Forxiga is not recommended for use in patients with moderate to severe renal impairment (patients with CrCl < 60 ml/min or eGFR < 60 ml/min/1.73 m²). Forxiga has not been studied in severe renal impairment (CrCl < 30 ml/min or eGFR < 30 ml/min/1.73 m²) or end-stage renal disease (ESRD).
    Monitoring of renal function is recommended as follows: Prior to initiation of dapagliflozin and at least yearly, thereafter.  Prior to initiation of concomitant medicinal products that may reduce renal function and periodically thereafter . For renal function approaching moderate renal impairment, at least 2 to 4 times per year. If renal function falls below CrCl < 60 ml/min or eGFR < 60 ml/min/1.73 m², dapagliflozin treatment should be discontinued.
    Hepatic impairment: There is limited experience in clinical trials in patients with hepatic impairment. Dapagliflozin exposure is increased in patients with severe hepatic impairment.
    Use in patients at risk for volume depletion, hypotension and/or electrolyte imbalances: Dapagliflozin is not recommended for use in patients receiving loop diuretics or who are volume depleted, e.g. due to acute illness (such as gastrointestinal illness).
    Caution should be exercised in patients for whom a dapagliflozin-induced drop in blood pressure could pose a risk, such as patients with known cardiovascular disease, patients on anti-hypertensive therapy with a history of hypotension or elderly patients. For patients receiving dapagliflozin, in case of intercurrent conditions that may lead to volume depletion, careful monitoring of volume status (e.g. physical examination, blood pressure measurements, laboratory tests including haematocrit) and electrolytes is recommended. Temporary interruption of treatment with dapagliflozin is recommended for patients who develop volume depletion until the depletion is corrected.
    Ketoacidosis: Reports of ketoacidosis, including life-threatening and fatal cases, have been identified in post marketing surveillance in patients with type 1 and type 2 diabetes mellitus receiving sodium glucose co-transporter-2 (SGLT2) inhibitors, including FORXIGA.
    The reports were seen in patients treated with type 2 diabetes and type 1 diabetes. FORXIGA is not indicated for the treatment of patients with type 1 diabetes mellitus.
    See prescribing information for full details.


    Side Effects

    Very common: Hypoglycemia.
    Common: Vulvovaginitis, Balanitis and related genital infections, Urinary tract
    infection, Dizziness, Rash, Back pain, Dysuria, Polyuria, Haematocrit increased, Creatinine renal clearance decreased, Dyslipidaemia.
    See prescribing information for full details.


    Drug interactions

    Pharmacodynamic interactions
    Diuretics: Dapagliflozin may add to the diuretic effect of thiazide and loop diuretics and may increase the risk of dehydration and hypotension.
    Insulin and insulin secretagogues: Insulin and insulin secretagogues, such as sulphonylureas, cause hypoglycaemia. Therefore, a lower dose of insulin or an insulin secretagogue may be required to reduce the risk of hypoglycaemia when used in combination with dapagliflozin.
    Pharmacokinetic interactions
    The metabolism of dapagliflozin is primarily via glucuronide conjugation mediated by UDP glucuronosyltransferase 1A9 (UGT1A9).
    In in vitro studies, dapagliflozin neither inhibited cytochrome P450 (CYP) 1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, nor induced CYP1A2, CYP2B6 or CYP3A4. Therefore, dapagliflozin is not expected to alter the metabolic clearance of coadministered medicinal products that are metabolised by these enzymes.
    Effect of other medicinal products on dapagliflozin
    Interaction studies conducted in healthy subjects, using mainly a single dose design, suggest that the pharmacokinetics of dapagliflozin are not altered by metformin, pioglitazone, sitagliptin, glimepiride, voglibose, hydrochlorothiazide, bumetanide, valsartan, or simvastatin.
    Following coadministration of dapagliflozin with rifampicin (an inducer of various active transporters and drugmetabolising enzymes) a 22% decrease in dapagliflozin systemic exposure (AUC) was observed, but with no clinically meaningful effect on 24-hour urinary glucose excretion. No dose adjustment is
    recommended. A clinically relevant effect with other inducers (e.g. carbamazepine, phenytoin, phenobarbital) is not expected.
    Following coadministration of dapagliflozin with mefenamic acid (an inhibitor of UGT1A9), a 55% increase in dapagliflozin systemic exposure was seen, but with no clinically meaningful effect on 24-hour urinary glucose excretion. No dose adjustment is recommended.
    Effect of dapagliflozin on other medicinal products
    In interaction studies conducted in healthy subjects, using mainly a single-dose design, dapagliflozin did not alter the pharmacokinetics of metformin, pioglitazone, sitagliptin, glimepiride, hydrochlorothiazide, bumetanide, valsartan, digoxin (a P-gp substrate) or warfarin (S-warfarin, a CYP2C9 substrate), or the anticoagulatory effects of warfarin as measured by INR. Combination of a single dose of dapagliflozin 20 mg and simvastatin (a CYP3A4 substrate) resulted in a 19% increase in AUC of simvastatin and 31% increase in AUC of simvastatin acid. The increase in simvastatin and simvastatin acid exposures are not considered clinically relevant.
    Interference with 1,5-anhydroglucitol (1,5-AG) Assay: Monitoring glycemic control with 1,5-AG assay is not recommended as measurements of 1,5AG are
    unreliable in assessing glycemic control in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control.


    Pregnancy and Lactation

    Pregnancy: There are no data from the use of dapagliflozin in pregnant women. Studies in rats have shown toxicity to the developing kidney in the time period corresponding to the second and third trimesters of human pregnancy. Therefore, the use of dapagliflozin is not recommended during the second and third trimesters of pregnancy. When pregnancy is detected, treatment with dapagliflozin should be discontinued.
    Lactation: It is unknown whether dapagliflozin and/or its metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. Dapagliflozin should not be used while breast-feeding.
    See prescribing information for full details.


    Overdose

    Dapagliflozin did not show any toxicity in healthy subjects at single oral doses up to 500 mg (50 times the maximum recommended human dose). These subjects had detectable glucose in the urine for a dose-related period of time (at least 5 days for the 500 mg dose), with no reports of dehydration, hypotension or electrolyte imbalance, and with no clinically meaningful effect on QTc interval. The incidence of hypoglycaemia was similar to placebo. In clinical studies where once-daily doses of up to 100 mg (10 times the maximum recommended human dose) were administered for 2 weeks in healthy subjects and type 2 diabetes subjects, the incidence of hypoglycaemia was slightly higher than placebo and was not dose-related. Rates of adverse events including dehydration or hypotension were similar to placebo, and there were no clinically meaningful dose-related changes in laboratory parameters, including serum electrolytes and biomarkers of renal function. In the event of an overdose, appropriate supportive treatment should be initiated as dictated by the patient’s clinical status. The removal of dapagliflozin by haemodialysis has not been studied.


    Important notes

    Storage: Store below 30°C.


    Manufacturer
    AstraZeneca AB Gärtunavägen Sweden
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