Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Patients with AHP subtypes other than acute intermittent porphyria (AIP) 
The efficacy and safety data in patients with AHP subtypes other than AIP (hereditary coproporphyria (HCP), variegate porphyria (VP) and ALA dehydratase-deficient porphyria (ADP)) are limited (see section 5.1). This should be taken into consideration when assessing the individual benefit-risk in these rare AHP subtypes.

Anaphylactic reaction

In clinical studies, anaphylaxis occurred in one patient who had a history of allergic asthma and atopy (see section 4.8). Signs and symptoms of anaphylaxis should be monitored. If anaphylaxis occurs, administration of this medicinal product should be immediately discontinued and appropriate medical treatment should be instituted.

Effects on renal function

Increases in serum creatinine levels and decreases in eGFR have been reported during treatment with givosiran. In the placebo-controlled study, the median increase in creatinine at month 3 was 6.5 µmol/L (0.07 mg/dL) and resolved or stabilised by month 6 with continued monthly treatment with 2.5 mg/kg givosiran.

Progression of renal impairment has been observed in some patients with pre-existing renal disease.
Careful monitoring of renal function during treatment is required in such cases .

Transaminase elevations

Transaminase elevations have been observed in patients treated with givosiran. Transaminase elevations primarily occurred between 3 to 5 months following initiation of treatment (see section 4.8).

Liver function tests should be performed prior to initiating treatment. These tests should be repeated monthly during the first 6 months of treatment, and as clinically indicated thereafter. Interrupting or discontinuing treatment should be considered for clinically relevant transaminase elevations. In case of subsequent improvement in transaminase levels, resumption of treatment at a 1.25 mg/kg dose after interruption could be considered (see section 4.2). There are limited data on efficacy and safety of the lower dose, particularly in patients who previously experienced transaminase elevations. There are no data on sequentially increasing the 1.25 mg/kg dose to the 2.5 mg/kg dose after dose interruption for transaminase elevations (see section 4.8).

Blood homocysteine increased

Blood homocysteine levels may be increased in patients with AHP, vitamin deficiencies, or chronic kidney disease. During treatment with givosiran, increases in blood homocysteine levels have been observed compared to levels before treatment (see section 4.8). The clinical relevance of the elevations in blood homocysteine during treatment with givosiran is unknown. However, homocysteine elevations have been previously associated with an increased risk of thromboembolic events.

Measurement of blood homocysteine levels prior to initiating treatment and monitoring for changes during treatment with givosiran is recommended. In patients with elevated homocysteine levels, homocysteine-lowering therapy can be considered.


Excipients

This medicinal product contains less than 1 mmol sodium (23 mg) per mL, that is to say essentially ‘sodium-free’.

Effects on Driving

4.7    Effects on ability to drive and use machines

Givlaari has no or negligible influence on the ability to drive and use machines.