Adverse reactions : תופעות לוואי

6    ADVERSE REACTIONS
The following potential adverse reactions are described in Warnings and Precautions (5): -     Decrease in systemic blood pressure [see Warnings and Precautions (5.2)].
-     Bleeding [see Warnings and Precautions (5.4)].

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Pulmonary Arterial Hypertension

In a 12-week placebo-controlled study (TRIUMPH I) of 235 patients with PAH (WHO Group 1 and nearly all NYHA Functional Class III), the most commonly reported adverse reactions on Tyvaso included: cough and throat irritation; headache, gastrointestinal effects, muscle, jaw or bone pain, dizziness, flushing and syncope. Table 1 lists the adverse reactions that occurred at a rate of at least 4% and were more frequent in patients treated with Tyvaso than with placebo.


Table 1: Adverse Events in ≥ 4% of PAH Patients Receiving
Tyvaso and More Frequent∗ than Placebo in TRIUMPH 1
Treatment n (%)
Adverse Event
Tyvaso                Placebo n = 115               n = 120
Cough                       62 (54)               35 (29)
Headache                      47 (41)               27 (23)
Throat Irritation /                 29 (25)               17 (14)
Pharyngolaryngeal Pain
Nausea                      22 (19)               13 (11)
Flushing                     17 (15)                1 (<1)
Syncope                       7 (6)                 1 (<1)
*More than 3% greater than placebo



The safety of Tyvaso was also studied in a long-term, open-label extension study in which 206 patients were dosed for a mean duration of 2.3 years, with a maximum exposure of 5.4 years. Eighty-nine percent (89%) of patients achieved the target dose of 9 breaths, 4 times daily. Forty-two percent (42%) achieved a dose of 12 breaths 4 times daily. The adverse events during this chronic dosing study were qualitatively similar to those observed in the 12-week placebo controlled trial.

In a prospective, observational study comparing patients taking Tyvaso (958 patient-years of exposure) and a control group (treatment with other approved therapies for PAH; 1094 patient-years), Tyvaso was associated with a higher rate of cough (16.2 vs. 10.9 per 100 patient-years), throat irritation (4.5 vs. 1.2 per 100 pt-years), nasal discomfort (2.6 vs. 1.3 per 100 pt-years), and hemoptysis (2.5 vs. 1.3 per 100 pt- years) compared to the control group.

Pulmonary Hypertension Associated with ILD
In a 16-week, placebo-controlled study (INCREASE) of 326 patients with PH-ILD (WHO Group 3), adverse reactions were similar to the experience in studies of PAH.



6.2 Post-Marketing Experience

The adverse reaction of angioedema has been identified during the post-approval use of Tyvaso.
Because this reaction is reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure: 
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
 http://sideeffects.health.gov.il