Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use

General
Onglyza should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. Onglyza is not a substitute for insulin in insulin-requiring patients.

Acute Pancreatitis
Use of DPP4 inhibitors has been associated with a risk of developing acute pancreatitis. Patients should be informed of the characteristic symptoms of acute pancreatitis; persistent, severe abdominal pain. If pancreatitis is suspected, Onglyza should be discontinued; if acute pancreatitis is confirmed, Onglyza should not be restarted. Caution should be exercised in patients with a history of pancreatitis.
In post-marketing experience of saxagliptin, there have been spontaneously reported adverse reactions of acute pancreatitis.



Renal impairment.

A single dosage adjustment is recommended in patients with moderate or severe renal Impairment. Saxagliptin is contraindicated for use in patients with end-stage renal disease (ESRD) requiring haemodialysis.

Assessment of renal function is recommended prior to initiation of Onglyza and in keeping with routine care, renal assessment should be done periodically thereafter (see sections 4.2 and 5.2).


Hepatic impairment Saxagliptin should be used with caution in patients with moderate hepatic impairment, and is not recommended for use in patients with severe hepatic impairment (see section 4.2).

Use with medicinal products known to cause hypoglycaemia

Sulphonylureas and insulin are known to cause hypoglycaemia. Therefore, a lower dose of sulphonylurea or insulin may be required to reduce the risk of hypoglycaemia when used in combination with Onglyza.

Hypersensitivity reactions Onglyza must not be used in patients who have had any serious hypersensitivity reaction to a dipeptidyl peptidase 4 (DPP4) inhibitor- (see section 4.3) During postmarketing experience, including spontaneous reports and clinical trials, the following adverse reactions have been reported with the use of saxagliptin: serious hypersensitivity reactions, including anaphylactic reaction, anaphylactic shock and, angioedema


If a serious hypersensitivity reaction to saxagliptin is suspected, Onglyza should be discontinued, assess for other potential causes for the event, and institute alternative treatment for diabetes (see section4.8).



Skin disorders
Ulcerative and necrotic skin lesions have been reported in extremities of monkeys in non-clinical toxicology studies (see section 5.3). skin lesions were not observed at an increased incidence in clinical trials,.
Postmarketing reports of rash have been described in the DPP4 inhibitor class. Rash is also noted as an adverse reactionfor Onglyza (see section 4.8). Therefore, in keeping with routine care of the diabetic patient, monitoring for skin disorders, such as blistering, ulceration or rash, is recommended.

Bullous pemphigoid
Postmarketing cases of bullous pemphigoid requiring hospitalisation have been reported with DPP4 inhibitor use, including saxagliptin. In reported cases, patients typically responded to topical or systemic immunosuppressive treatment and discontinuation of the DPP4 inhibitor. If a patient develops blisters or erosions while receiving saxagliptin and bullous pemphigoid is suspected, this medicinal product should be discontinued and referral to a dermatologist should be considered for diagnosis and appropriate treatment (see section 4.8).


Cardiac failure

Experience in NYHA class III-IV is still limited. In the SAVOR trial a small increase in the rate for hospitalization for heart failure was observed in the saxagliptin treated patients compared to placebo, although a causal relationship has not been established (see section 5.1). Additional analysis did not indicate a differential effect among NYHA classes. Caution is warranted if Onglyza is used in patients who have known risk factors for hospitalization for heart failure, such as a history of heart failure or moderate to severe renal impairment. Patients should be advised of the characteristic symptoms of heart failure, and to immediately report such symptoms.

Arthralgia
Joint pain, which may be severe, has been reported in postmarketing reports for DPP4 inhibitors (see section 4.8). Patients experienced relief of symptoms after discontinuation of the medication and some experienced recurrence of symptoms with reintroduction of the same or another DPP4 inhibitor. Onset of symptoms following initiation of drug therapy may be rapid or may occur after longer periods of treatment. If a patient presents with severe joint pain, continuation of drug therapy should be individually assessed.

Immunocompromised patients Immunocompromised patients, such as patients who have undergone organ transplantation or patients diagnosed with human immunodeficiency syndrome, have not been studied in the Onglyza clinical program. Therefore, the efficacy and safety profile of saxagliptin in these patients has not been established.

Use with potent CYP 3A4 inducers Using CYP3A4 inducers like carbamazepine, dexamethasone, phenobarbital, phenytoin, and rifampicin may reduce the glycaemic lowering effect of Onglyza (see section 4.5).

Lactose

The tablets contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, e total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Effects on Driving

4.7 Effects on ability to drive and use machines

Onglyza may have a negligible influence on the ability to drive and use machines.
when driving or using machines, it should be taken into account that dizziness has been reported in studies with saxagliptin. In addition, patients should be alerted to the risk of hypoglycaemia when Onglyza is used in combination with other antidiabetic medicinal products known to cause hypoglycaemia (e.g. insulin, sulphonylureas).