Adverse reactions : תופעות לוואי

4.8 Undesirable effects
The following adverse reactions can occur during treatment with Pharepa 25,000 IU/5 ml.
The frequency data on adverse reactions are based on the following categories:

Very common          ≥1/10
Common               1/100 to <1/10
Uncommon
≥1/1000 to <1/100
Rare
≥1/10,000 to <1/1000
Very rare          <1/10,000
Not known          Cannot be estimated from the
available data

Blood and lymphatic system disorders
Very common:    Depending on the heparin dosage, increased incidence of bleeding, especially from skin, mucous membranes,
wounds, gastrointestinal and urogenital tract.

Common:         At the start of treatment, type 1 heparin induced thrombocytopenia not mediated by antibodies (platelet count: 100,000-150,000/μl), without thrombosis.
Rare:           Type 2 heparin-induced, antibody mediated thrombocytopenia (platelet count: <100,000/μl or a rapid fall in the platelet count to <50% of the initial count), with arterial and venous thrombosis or emboli, consumption coagulopathy, skin necrosis at the injection site, petechiae, melaena.
The anticoagulant effect of heparin may be reduced.
In patients without heparin hypersensitivity, the fall in platelet count usually occurs 6-14 days after the start of heparin treatment. In patients with pre-existing heparin hypersensitivity, the fall in platelet count can occur after just a few hours.
Very rare:      Type 2 thrombocytopenia can occur after a delay of several weeks after the end of heparin treatment (Spinler S A: New concepts in heparin-induced thrombocytopenia: Diagnosis and management, J Thromb Thrombolysis
21(1), 17-21, 2006: FDA MedWatch Safety Alert. Heparin
Sodium
Injection. December 8, 2006).
If type 2 thrombocytopenia occurs, heparin should be stopped immediately.
Other treatment measures depend on the nature and
severity of symptoms.
Further parenteral heparin administration is absolutely contraindicated.

Immune system disorders
Uncommon:      Allergic reactions with symptoms such as nausea, headache, rise in temperature, limb pain, urticaria, vomiting, pruritus, dyspnoea, bronchospasm and a fall in blood pressure. Local and generalized hypersensitivity, including angioedema.

Very rare:      Occurrence of anaphylactic shock, especially in sensitised patients who have previously received heparin.
Endocrine disorders
Rare:           Hypoaldosteronism, associated with hyperkalaemia and metabolic acidosis, especially in patients with renal impairment and diabetes.


Vascular disorders

Very rare:        Vasospasm.

Hepatobiliary disorders
Very common: Elevation of serum transaminases (AST, ALT), gamma- glutamyl transpeptidase (gamma-GT), LDH and lipase.


Reproductive system disorders
Very rare:      Priapism.

Skin and subcutaneous tissue disorders
Uncommon:       Transient alopecia, skin necrosis.

Musculoskeletal and connective tissue disorders
Not known:       Osteoporosis may develop after prolonged use (months), mostly when higher doses are used and
especially in patients with a predisposition to it.


General disorders and administration site conditions Common:           Local tissue reactions at the injection site (induration, redness, discoloration and small haematomas).

Very rare:          Calcinosis at the injection site, mainly in patients with severe kidney failure.


Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il