Trepulmix

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ANNEX I 
SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Trepulmix 1 mg/ml solution for infusion 
Trepulmix 2.5 mg/ml solution for infusion 
Trepulmix 5 mg/ml solution for infusion 
Trepulmix 10 mg/ml solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Trepulmix 1 mg/ml solution for infusion: 
 
One ml of solution contains 1 mg treprostinil (as sodium salt). 
Each 10 ml vial of solution contains 10 mg treprostinil (as sodium salt). 
 
Excipients with known effect  
Each 10 ml vial contains 36.8 mg (1.60 mmol) sodium. 
 
Trepulmix 2.5 mg/ml solution for infusion: 
 
One ml of solution contains 2.5 mg treprostinil (as sodium salt). 
Each 10 ml vial of solution contains 25 mg treprostinil (as sodium salt). 
 
Excipients with known effect 
Each 10 ml vial contains 37.3 mg (1.62 mmol) sodium. 
 
Trepulmix 5 mg/ml solution for infusion: 
One ml of solution contains 5 mg treprostinil (as sodium salt). 
Each 10 ml vial of solution contains 50 mg treprostinil (as sodium salt). 
 
Excipients with known effect  
Each 10 ml vial contains 39.1 mg (1.70 mmol) sodium. 
 
Trepulmix 10 mg/ml solution for infusion: 
One ml of solution contains 10 mg treprostinil (as sodium salt). 
Each 10 ml vial of solution contains 100 mg treprostinil (as sodium salt). 
 
Excipients with known effect  
Each 10 ml vial contains 37.4 mg (1.63 mmol) sodium. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for infusion. 
 
Clear colourless to slightly yellow solution, free from visible particles with a pH of 6.0 – 7.2 and an 
osmolality between 253 and 284 mOsm/kg. 
 
 



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4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Trepulmix is indicated for the treatment of adult patients with WHO Functional Class (FC) III or IV 
and: 

- inoperable chronic thromboembolic pulmonary hypertension (CTEPH), or  
- persistent or recurrent CTEPH after surgical treatment  

to improve exercise capacity. 
 
4.2 Posology and method of administration 
Treatment with Trepulmix should be initiated and monitored only by clinicians experienced in the 
treatment of pulmonary hypertension. Treatment should be initiated under close medical supervision 
in a medical setting able to provide intensive care. 
 
Posology 
 
The recommended initial infusion rate is 1.25 ng/kg/min. If this initial dose is poorly tolerated, the 
infusion rate should be reduced to 0.625 ng/kg/min. 
 
Dose adjustments 
The infusion rate should be increased under medical supervision in increments of up to 1.25 ng/kg/min 
per week for the first four weeks of treatment and then up to 2.5 ng/kg/min per week.   
 
The dose should be adjusted on an individual basis and under medical supervision in order to achieve 
a maintenance dose at which symptoms improve and which is tolerated by the patient.  
 
During the follow-up phase of a clinical trial in CTEPH patients, the mean doses reached after 12 
months were 31 ng/kg/min, after 24 months 33 ng/kg/min, and after 48 months 39 ng/kg/min. The 
respective maximum doses observed in the clinical trial were 52 ng/kg/min, 54 ng/kg/min and 
50 ng/kg/min respectively. 
 
Abrupt withdrawal or sudden marked reductions in the dose of treprostinil may cause a rebound of 
symptoms of chronic thromboembolic pulmonary hypertension. It is therefore recommended that 
interruption of treprostinil therapy is avoided and that the infusion is re-started as soon as possible 
after an abrupt accidental dose reduction or interruption. The optimal strategy for reintroducing 
treprostinil infusion needs to be determined on a case by case basis by medically qualified personnel. 
In most cases, after an interruption of up to 4 hours, restarting of treprostinil infusion can be done 
using the same dose rate; interruptions for up to 24 hours may require a dose reduction of up to 50% of 
the most recent dose with a subsequent uptitration to the clinically effective dose. Longer periods of 
interruption may require the dose of treprostinil to be re-titrated from even lower flow rates. In any 
case, the reintroduction of treprostinil should be under medical supervision. 
 
Special populations 
Hepatic impairment 
The initial dose of Trepulmix should be decreased to 0.625 ng/kg/min and incremental dose increases 
should be made cautiously (see section 5.2). Increments could be reduced to 0.625 ng/kg/min per dose 
increase, the final decision on the dose increments is at the discretion of the supervising physician. 
Please note that “Severe hepatic impairment (Child-Pugh Class C) is listed as contraindication for use 
of treprostinil, see section 4.3. 
 
Renal impairment 
As no clinical studies have been carried out in patients with renal impairment, the treatment 
recommendations are not established for patients with renal impairment. As treprostinil and its 
metabolites are excreted mainly through the urinary route, caution is recommended when treating 
patients with renal impairment in order to prevent deleterious consequences related to the possible 
increase of systemic exposure. 



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Elderly  
No pharmacokinetic data of treprostinil in elderly is available. Caution is recommended when treating 
elderly patients due to higher incidence of hepatic and / or renal impairment. 
 
  
Obese patients 
Therapy of obese patients (weight ≥ 30% above ideal weight) should be initiated and increased with 
doses calculated based on their ideal weight. See section 5.2 for more information. 
 
Paediatric population 
There is no relevant use of treprostinil in children and adolescents for the indication of CTEPH. 
 
Method of administration 
 
Trepulmix is for subcutaneous use. It is administered undiluted by continuous infusion via a 
subcutaneous catheter using an ambulatory infusion pump. 
  
The healthcare professional responsible for the therapy must ensure that the patient is fully trained and 
competent to use the chosen infusion device.  All patients must be trained in preparation of the 
treprostinil infusion reservoir and priming of the infusion delivery tubing and connection. Written 
guidance, either from the pump manufacturer or specially tailored advice by the prescribing physician 
must be made available to the patient. This includes the required normal drug delivery actions, advice 
how to manage occlusions and other pump alarms, and details whom to contact in an emergency. 
 
In order to avoid interruptions in drug delivery, the patient must have access to a backup infusion 
pump and subcutaneous infusion sets in the event that the administration equipment should suffer an 
accidental malfunction. 
 
The ambulatory infusion pump used to administer undiluted Trepulmix subcutaneously, should be: 

• small and lightweight, 
• capable of adjusting infusion rates in increments of 0.002 ml/h or less, 
• fitted with occlusion, low battery, programming error and motor malfunction alarms, 
• accurate to within +/- 6% of the programmed delivery rate  
• positive pressure driven (continuous or pulsated). 

 
The reservoir must be made of polypropylene or glass. 
 
Patients must be thoroughly trained in the use and programming of the pump, and the connection and 
care of the infusion set. 
 
Flushing the infusion line whilst connected to the patient may lead to accidental overdose. For more 
information on the symptoms and treatment of overdose please refer to Section 4.9 of this document. 
 
Trepulmix is available at concentrations of 1, 2.5, 5 and 10 mg/ml. 
 
For subcutaneous infusion, Trepulmix is delivered without further dilution at a calculated 
subcutaneous infusion rate (ml/h) based on a patient’s dose (ng/kg/min), weight (kg), and the vial 
strength (mg/ml) of Trepulmix being used. During use a single reservoir (syringe) of undiluted 
Trepulmix can be administered up to 72 hours at 37°C. The subcutaneous infusion rate is calculated 
using the following formula: 
 
 
 
 
 
*Conversion factor of 0.00006 = 60 min/hour x 0.000001 mg/ng 

Subcutaneous 
Infusion Rate 

(ml/h) 
= 

Dose (ng/kg/min) x Weight (kg) x 0.00006* 

Trepulmix Vial Strength (mg/ml) 



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To avoid calculation errors due to the complex formula please check the dose calculation tables 
below. For each medicinal product strength one dose calculation table is available. 
 
Example calculations for subcutaneous infusion are as follows: 
 
Example 1: 
 
For a 60 kg person at the recommended initial dose of 1.25 ng/kg/min using the 1 mg/ml Trepulmix 
Vial Strength, the infusion rate would be calculated as follows: 
 

Subcutaneous 
Infusion Rate 

(ml/h) 
= 1.25 ng/kg/min x 60 kg x 0.00006 =  0.005 ml/h 1 mg/ml 

 
 
Example 2: 
 
For a 65 kg person at a dose of 40 ng/kg/min using the 5 mg/ml Trepulmix Vial Strength, the infusion 
rate would be calculated as follows: 
 

Subcutaneous 
Infusion Rate 

(ml/h) 
= 

40 ng/kg/min x 65 kg x 0.00006 
=  0.031 ml/h 5 mg/ml 

 
 

 
Table 1-1 provides guidance for subcutaneous infusion delivery rates of Trepulmix 1 mg/ml for 
patients of different body weights corresponding to doses of up to 42.5 ng/kg/min. 
 
Table 1-1: 

Infusion rate setting of subcutaneous pump (ml/h) for Trepulmix 1 mg/ml 
 

Patient Weight (kg) 
Dose 
(ng/kg/min) 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 
1.25 0.002 0.002 0.003 0.003 0.003 0.004 0.004 0.005 0.005 0.005 0.006 0.006 0.006 0.007 0.007 0.008 
2.5 0.004 0.005 0.005 0.006 0.007 0.008 0.008 0.009 0.010 0.011 0.011 0.012 0.013 0.014 0.014 0.015 
3.75 0.006 0.007 0.008 0.009 0.010 0.011 0.012 0.014 0.015 0.016 0.017 0.018 0.019 0.020 0.021 0.023 
5 0.008 0.009 0.011 0.012 0.014 0.015 0.017 0.018 0.020 0.021 0.023 0.024 0.026 0.027 0.029 0.030 
6.25 0.009 0.011 0.013 0.015 0.017 0.019 0.021 0.023 0.024 0.026 0.028 0.030 0.032 0.034 0.036 0.038 
7.5 0.011 0.014 0.016 0.018 0.020 0.023 0.025 0.027 0.029 0.032 0.034 0.036 0.038 0.041 0.043 0.045 
8.75 0.013 0.016 0.018 0.021 0.024 0.026 0.029 0.032 0.034 0.037 0.039 0.042 0.045 0.047 0.050 0.053 
10 0.015 0.018 0.021 0.024 0.027 0.030 0.033 0.036 0.039 0.042 0.045 0.048 0.051 0.054 0.057 0.060 
11.25 0.017 0.020 0.024 0.027 0.030 0.034 0.037 0.041 0.044 0.047 0.051 0.054 0.057 0.061 0.064 0.068 
12.5 0.019 0.023 0.026 0.030 0.034 0.038 0.041 0.045 0.049 0.053 0.056 0.060 0.064 0.068 0.071 0.075 
13.75 0.021 0.025 0.029 0.033 0.037 0.041 0.045 0.050 0.054 0.058 0.062 0.066 0.070 0.074 0.078 0.083 
15 0.023 0.027 0.032 0.036 0.041 0.045 0.050 0.054 0.059 0.063 0.068 0.072 0.077 0.081 0.086 0.090 
16.25 0.024 0.029 0.034 0.039 0.044 0.049 0.054 0.059 0.063 0.068 0.073 0.078 0.083 0.088 0.093 0.098 
17.5 0.026 0.032 0.037 0.042 0.047 0.053 0.058 0.063 0.068 0.074 0.079 0.084 0.089 0.095 0.100 0.105 
18.75 0.028 0.034 0.039 0.045 0.051 0.056 0.062 0.068 0.073 0.079 0.084 0.090 0.096 0.101 0.107 0.113 
20 0.030 0.036 0.042 0.048 0.054 0.060 0.066 0.072 0.078 0.084 0.090 0.096 0.102 0.108 0.114 0.120 
21.25 0.032 0.038 0.045 0.051 0.057 0.064 0.070 0.077 0.083 0.089 0.096 0.102 0.108 0.115 0.121 0.128 
22.5 0.034 0.041 0.047 0.054 0.061 0.068 0.074 0.081 0.088 0.095 0.101 0.108 0.115 0.122 0.128 0.135 
23.75 0.036 0.043 0.050 0.057 0.064 0.071 0.078 0.086 0.093 0.100 0.107 0.114 0.121 0.128 0.135 0.143 
25 0.038 0.045 0.053 0.060 0.068 0.075 0.083 0.090 0.098 0.105 0.113 0.120 0.128 0.135 0.143 0.150 
27.5 0.041 0.050 0.058 0.066 0.074 0.083 0.091 0.099 0.107 0.116 0.124 0.132 0.140 0.149 0.157 0.165 
30 0.045 0.054 0.063 0.072 0.081 0.090 0.099 0.108 0.117 0.126 0.135 0.144 0.153 0.162 0.171 0.180 
32.5 0.049 0.059 0.068 0.078 0.088 0.098 0.107 0.117 0.127 0.137 0.146 0.156 0.166 0.176 0.185 0.195 
35 0.053 0.063 0.074 0.084 0.095 0.105 0.116 0.126 0.137 0.147 0.158 0.168 0.179 0.189 0.200 0.210 
37.5 0.056 0.068 0.079 0.090 0.101 0.113 0.124 0.135 0.147 0.158 0.169 0.180 0.191 0.203 0.214 0.225 
40 0.060 0.072 0.084 0.096 0.108 0.120 0.132 0.144 0.156 0.168 0.180 0.192 0.204 0.216 0.228 0.240 
42.5 0.064 0.077 0.089 0.102 0.115 0.128 0.140 0.153 0.166 0.179 0.191 0.204 0.217 0.230 0.242 0.255 
The shaded areas indicate the highest infusion rate which is possible with a 3 ml syringe change every three 
days. 



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Table 1-2 provides guidance for subcutaneous infusion delivery rates of Trepulmix 2.5 mg/ml for 
patients of different body weights corresponding to doses of up to 42.5 ng/kg/min. 
 
Table 1-2: 

Infusion rate setting of subcutaneous pump (ml/h) for Trepulmix 2.5 mg/ml 
 

Patient Weight (kg) 
Dose 
(ng/kg/min) 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 

5 0.003 0.004 0.004 0.005 0.005 0.006 0.007 0.007 0.008 0.008 0.009 0.010 0.010 0.011 0.011 0.012 
6.25 0.004 0.005 0.005 0.006 0.007 0.008 0.008 0.009 0.010 0.011 0.011 0.012 0.013 0.014 0.014 0.015 
7.5 0.005 0.005 0.006 0.007 0.008 0.009 0.010 0.011 0.012 0.013 0.014 0.014 0.015 0.016 0.017 0.018 

8.75 0.005 0.006 0.007 0.008 0.009 0.011 0.012 0.013 0.014 0.015 0.016 0.017 0.018 0.019 0.020 0.021 
10 0.006 0.007 0.008 0.010 0.011 0.012 0.013 0.014 0.016 0.017 0.018 0.019 0.020 0.022 0.023 0.024 

11.25 0.007 0.008 0.009 0.011 0.012 0.014 0.015 0.016 0.018 0.019 0.020 0.022 0.023 0.024 0.026 0.027 
12.5 0.008 0.009 0.011 0.012 0.014 0.015 0.017 0.018 0.020 0.021 0.023 0.024 0.026 0.027 0.029 0.030 
13.75 0.008 0.010 0.012 0.013 0.015 0.017 0.018 0.020 0.021 0.023 0.025 0.026 0.028 0.030 0.031 0.033 

15 0.009 0.011 0.013 0.014 0.016 0.018 0.020 0.022 0.023 0.025 0.027 0.029 0.031 0.032 0.034 0.036 
16.25 0.010 0.012 0.014 0.016 0.018 0.020 0.021 0.023 0.025 0.027 0.029 0.031 0.033 0.035 0.037 0.039 
17.5 0.011 0.013 0.015 0.017 0.019 0.021 0.023 0.025 0.027 0.029 0.032 0.034 0.036 0.038 0.040 0.042 
18.75 0.011 0.014 0.016 0.018 0.020 0.023 0.025 0.027 0.029 0.032 0.034 0.036 0.038 0.041 0.043 0.045 

20 0.012 0.014 0.017 0.019 0.022 0.024 0.026 0.029 0.031 0.034 0.036 0.038 0.041 0.043 0.046 0.048 
21.25 0.013 0.015 0.018 0.020 0.023 0.026 0.028 0.031 0.033 0.036 0.038 0.041 0.043 0.046 0.048 0.051 
22.5 0.014 0.016 0.019 0.022 0.024 0.027 0.030 0.032 0.035 0.038 0.041 0.043 0.046 0.049 0.051 0.054 
23.75 0.014 0.017 0.020 0.023 0.026 0.029 0.031 0.034 0.037 0.040 0.043 0.046 0.048 0.051 0.054 0.057 

25 0.015 0.018 0.021 0.024 0.027 0.030 0.033 0.036 0.039 0.042 0.045 0.048 0.051 0.054 0.057 0.060 
27.5 0.017 0.020 0.023 0.026 0.030 0.033 0.036 0.040 0.043 0.046 0.050 0.053 0.056 0.059 0.063 0.066 
30 0.018 0.022 0.025 0.029 0.032 0.036 0.040 0.043 0.047 0.050 0.054 0.058 0.061 0.065 0.068 0.072 

32.5 0.020 0.023 0.027 0.031 0.035 0.039 0.043 0.047 0.051 0.055 0.059 0.062 0.066 0.070 0.074 0.078 
35 0.021 0.025 0.029 0.034 0.038 0.042 0.046 0.050 0.055 0.059 0.063 0.067 0.071 0.076 0.080 0.084 

37.5 0.023 0.027 0.032 0.036 0.041 0.045 0.050 0.054 0.059 0.063 0.068 0.072 0.077 0.081 0.086 0.090 
40 0.024 0.029 0.034 0.038 0.043 0.048 0.053 0.058 0.062 0.067 0.072 0.077 0.082 0.086 0.091 0.096 

42.5 0.026 0.031 0.036 0.041 0.046 0.051 0.056 0.061 0.066 0.071 0.077 0.082 0.087 0.092 0.097 0.102 
The shaded areas indicate the highest infusion rate which is possible with a 3 ml syringe change every three 
days. 
 
Table 1-3 provides guidance for subcutaneous infusion delivery rates of Trepulmix 5 mg/ml for 
patients of different body weights corresponding to doses of up to 80 ng/kg/min. 
 
Table 1-3: 

 
Infusion rate setting of subcutaneous pump (ml/h) for Trepulmix 5 mg/ml 

 
Patient Weight (kg) 

Dosis 
(ng/kg/min) 35 40 45 50 55 60 65 70 75 80 85 90 95 100 

10 0.004 0.005 0.005 0.006 0.007 0.007 0.008 0.008 0.009 0.010 0.010 0.011 0.011 0.012 
12.5 0.005 0.006 0.007 0.008 0.008 0.009 0.010 0.011 0.011 0.012 0.013 0.014 0.014 0.015 
15 0.006 0.007 0.008 0.009 0.010 0.011 0.012 0.013 0.014 0.014 0.015 0.016 0.017 0.018 

17.5 0.007 0.008 0.009 0.011 0.012 0.013 0.014 0.015 0.016 0.017 0.018 0.019 0.020 0.021 
20 0.008 0.010 0.011 0.012 0.013 0.014 0.016 0.017 0.018 0.019 0.020 0.022 0.023 0.024 

22.5 0.009 0.011 0.012 0.014 0.015 0.016 0.018 0.019 0.020 0.022 0.023 0.024 0.026 0.027 
25 0.011 0.012 0.014 0.015 0.017 0.018 0.020 0.021 0.023 0.024 0.026 0.027 0.029 0.030 

27.5 0.012 0.013 0.015 0.017 0.018 0.020 0.021 0.023 0.025 0.026 0.028 0.030 0.031 0.033 
30 0.013 0.014 0.016 0.018 0.020 0.022 0.023 0.025 0.027 0.029 0.031 0.032 0.034 0.036 

32.5 0.014 0.016 0.018 0.020 0.021 0.023 0.025 0.027 0.029 0.031 0.033 0.035 0.037 0.039 
35 0.015 0.017 0.019 0.021 0.023 0.025 0.027 0.029 0.032 0.034 0.036 0.038 0.040 0.042 

37.5 0.016 0.018 0.020 0.023 0.025 0.027 0.029 0.032 0.034 0.036 0.038 0.041 0.043 0.045 
40 0.017 0.019 0.022 0.024 0.026 0.029 0.031 0.034 0.036 0.038 0.041 0.043 0.046 0.048 

42.5 0.018 0.020 0.023 0.026 0.028 0.031 0.033 0.036 0.038 0.041 0.043 0.046 0.048 0.051 
45 0.019 0.022 0.024 0.027 0.030 0.032 0.035 0.038 0.041 0.043 0.046 0.049 0.051 0.054 

47.5 0.020 0.023 0.026 0.029 0.031 0.034 0.037 0.040 0.043 0.046 0.048 0.051 0.054 0.057 
50 0.021 0.024 0.027 0.030 0.033 0.036 0.039 0.042 0.045 0.048 0.051 0.054 0.057 0.060 
55 0.023 0.026 0.030 0.033 0.036 0.040 0.043 0.046 0.050 0.053 0.056 0.059 0.063 0.066 
60 0.025 0.029 0.032 0.036 0.040 0.043 0.047 0.050 0.054 0.058 0.061 0.065 0.068 0.072 
65 0.027 0.031 0.035 0.039 0.043 0.047 0.051 0.055 0.059 0.062 0.066 0.070 0.074 0.078 
70 0.029 0.034 0.038 0.042 0.046 0.050 0.055 0.059 0.063 0.067 0.071 0.076 0.080 0.084 
75 0.032 0.036 0.041 0.045 0.050 0.054 0.059 0.063 0.068 0.072 0.077 0.081 0.086 0.090 
80 0.034 0.038 0.043 0.048 0.053 0.058 0.062 0.067 0.072 0.077 0.082 0.086 0.091 0.096 

The shaded areas indicate the highest infusion rate which is possible with a 3 ml syringe change every three 
days. 
 



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Table 1-4 provides guidance for subcutaneous infusion delivery rates of Trepulmix 10 mg/ml for 
patients of different body weights corresponding to doses of up to 155 ng/kg/min. 
 
Table 1-4: 

Infusion rate setting of subcutaneous pump (ml/h) for Trepulmix 10 mg/ml 
 

Patient Weight (kg) 
Dosis 

(ng/kg/min) 35 40 45 50 55 60 65 70 75 80 85 90 95 100 
50 0.011 0.012 0.014 0.015 0.017 0.018 0.020 0.021 0.023 0.024 0.026 0.027 0.029 0.030 
55 0.012 0.013 0.015 0.017 0.018 0.020 0.021 0.023 0.025 0.026 0.028 0.030 0.031 0.033 
60 0.013 0.014 0.016 0.018 0.020 0.022 0.023 0.025 0.027 0.029 0.031 0.032 0.034 0.036 
65 0.014 0.016 0.018 0.020 0.021 0.023 0.025 0.027 0.029 0.031 0.033 0.035 0.037 0.039 
70 0.015 0.017 0.019 0.021 0.023 0.025 0.027 0.029 0.032 0.034 0.036 0.038 0.040 0.042 
75 0.016 0.018 0.020 0.023 0.025 0.027 0.029 0.032 0.034 0.036 0.038 0.041 0.043 0.045 
80 0.017 0.019 0.022 0.024 0.026 0.029 0.031 0.034 0.036 0.038 0.041 0.043 0.046 0.048 
85 0.018 0.020 0.023 0.026 0.028 0.031 0.033 0.036 0.038 0.041 0.043 0.046 0.048 0.051 
90 0.019 0.022 0.024 0.027 0.030 0.032 0.035 0.038 0.041 0.043 0.046 0.049 0.051 0.054 
95 0.020 0.023 0.026 0.029 0.031 0.034 0.037 0.040 0.043 0.046 0.048 0.051 0.054 0.057 

100 0.021 0.024 0.027 0.030 0.033 0.036 0.039 0.042 0.045 0.048 0.051 0.054 0.057 0.060 
105 0.022 0.025 0.028 0.032 0.035 0.038 0.041 0.044 0.047 0.050 0.054 0.057 0.060 0.063 
110 0.023 0.026 0.030 0.033 0.036 0.040 0.043 0.046 0.050 0.053 0.056 0.059 0.063 0.066 
115 0.024 0.028 0.031 0.035 0.038 0.041 0.045 0.048 0.052 0.055 0.059 0.062 0.066 0.069 
120 0.025 0.029 0.032 0.036 0.040 0.043 0.047 0.050 0.054 0.058 0.061 0.065 0.068 0.072 
125 0.026 0.030 0.034 0.038 0.041 0.045 0.049 0.053 0.056 0.060 0.064 0.068 0.071 0.075 
130 0.027 0.031 0.035 0.039 0.043 0.047 0.051 0.055 0.059 0.062 0.066 0.070 0.074 0.078 
135 0.028 0.032 0.036 0.041 0.045 0.049 0.053 0.057 0.061 0.065 0.069 0.073 0.077 0.081 
140 0.029 0.034 0.038 0.042 0.046 0.050 0.055 0.059 0.063 0.067 0.071 0.076 0.080 0.084 
145 0.030 0.035 0.039 0.044 0.048 0.052 0.057 0.061 0.065 0.070 0.074 0.078 0.083 0.087 
150 0.032 0.036 0.041 0.045 0.050 0.054 0.059 0.063 0.068 0.072 0.077 0.081 0.086 0.090 
155 0.033 0.037 0.042 0.047 0.051 0.056 0.060 0.065 0.070 0.074 0.079 0.084 0.088 0.093 

 
Shaded areas indicate the highest infusion rate supported by a 3 ml syringe change every three days. 
 
4.3 Contraindications 
 
• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
• Pulmonary veno-occlusive disease. 
• Severe decompensated left heart failure. 
• Severe hepatic impairment (Child-Pugh Class C). 
• Active gastrointestinal ulcer, intracranial haemorrhage, gastrointestinal injury or other 

gastrointestinal bleeding.  
• Congenital or acquired valvular defects with clinically relevant myocardial dysfunction not related 

to pulmonary hypertension. 
• Severe coronary heart disease or unstable angina 
• Myocardial infarction within the last six months 
• Severe arrhythmias 
• Cerebrovascular events (e.g. transient ischaemic attack, stroke) within the last three months. 
• Co-administration with other prostanoids 
 
4.4 Special warnings and precautions for use 
 
General therapy 
The decision to initiate therapy with treprostinil should take into consideration the high probability 
that continuous infusion will have to be continued for a prolonged period. Thus the patient's ability to 
accept and to be responsible for an indwelling catheter and infusion device should be carefully 
considered. The clinical team responsible for the therapy must ensure that the patient is fully trained 
and competent to use the chosen infusion device (see section 4.2). 
 
Treprostinil is a potent pulmonary and systemic vasodilator. In subjects presenting with low systemic 
arterial pressure, treprostinil treatment may increase the risk of systemic hypotension. Treatment is not 
recommended for patients with systolic arterial pressure of less than 85 mmHg. 



8 

It is recommended to monitor systemic blood pressure and heart rate during any change in dose with 
instructions to stop the infusion if symptoms of hypotension develop, or a systolic blood pressure of 
85 mmHg or lower is detected. 
 
If a patient develops pulmonary oedema while on treprostinil, the possibility of an concomitant 
pulmonary veno-occlusive disease should be considered. The treatment should be stopped as 
pulmonary veno-occlusive disease is a contraindication for therapy with treprostinil (see section 4.3). 
 
Caution is advised in situations where treprostinil may increase the risk of bleeding by inhibiting 
platelet aggregation (see section 4.5 and 4.8).   
 
Withdrawal 
Abrupt withdrawal or sudden marked reductions in the dose of treprostinil may cause a rebound in 
pulmonary hypertension (see section 4.2).  
 
Special populations 
Patients with hepatic and renal impairment should be dosed cautiously (see section 4.2). 
As treprostinil and its metabolites are excreted mainly through the urinary route, caution is 
recommended when treating patients with renal impairment in order to prevent deleterious 
consequences related to the possible increase of systemic exposure (see section 4.2). 
 
Sodium content 
Trepulmix 1 mg/ml solution for infusion 
This medicinal product contains 36.8 mg sodium per 10 ml vial of 1mg/ml, equivalent to 1.8% of the 
WHO recommended maximum daily intake of 2 g sodium for an adult. 
 
Trepulmix 2.5 mg/ml solution for infusion 
This medicinal product contains 37.3 mg mg sodium per 10 ml vial of 2.5 mg/ml, equivalent to 1.9% 
of the WHO recommended maximum daily intake of 2 g sodium for an adult. 
 
Trepulmix 5 mg/ml solution for infusion 
This medicinal product contains 39.1 mg sodium per 10 ml vial of 5 mg/ml, equivalent to 2.0% of the 
WHO recommended maximum daily intake of 2 g sodium for an adult. 
 
Trepulmix 10 mg/ml solution for infusion 
This medicinal product contains 37.4 mg sodium per 10 ml vial of 10 mg/ml, equivalent to 1.9% of the 
WHO recommended maximum daily intake of 2 g sodium for an adult. 
 
To be taken into consideration by patients on a controlled sodium diet. 
 
Concomitant medicinal products 
Concomitant administration of cytochrome P450 (CYP2C8) enzyme inhibitors (as gemfibrozil) may 
lead to increased exposure (both Cmax and AUC) to treprostinil. With an increased exposure there is a 
likelihood of a higher incidence of adverse events associated with the administration of treprostinil. 
Therefore, a dose reduction should be considered (see section 4.5).  
 
Concomitant administration of CYP2C8 enzyme inducers (for example rifampicin) may result in a 
decreased exposure to treprostinil. At a reduced exposure, it is likely to have decreased clinical 
efficacy. Therefore, a higher dose of treprostinil is to be considered (see section 4.5). 
 



9 

4.5 Interaction with other medicinal products and other forms of interaction 
 
Concomitant administration with diuretics, antihypertensive agents, or other vasodilators 
 
Concomitant administration of treprostinil with diuretics, antihypertensive agents or other vasodilators 
increases the risk of systemic hypotension.  
 
Concomitant administration with platelet aggregation inhibitors, including NSAIDs and anticoagulants 
 
Treprostinil may inhibit platelet function. Concomitant administration of treprostinil with platelet 
aggregation inhibitors, including NSAIDs, nitric oxide donors or anticoagulants may increase the risk 
of bleeding. Surveillance of patients taking anticoagulants should be closely maintained. The 
concomitant use of other platelet inhibitors should be avoided in patients taking anticoagulants.  
 
Concomitant administration with cytochrome P450 (CYP2C8) enzyme inducers/inhibitors  
 
Gemfibrozil and other CYP2C8 inhibitors 
Pharmacokinetic studies in humans with oral treprostinil diolamine indicated that the concomitant 
administration of cytochrome P450 (CYP2C8) enzyme inhibitor gemfibrozil doubles the exposure 
(both Cmax and AUC) to treprostinil. In case a CYP2C8 inhibitor (e.g. gemfibrozil, trimethoprim and 
deferasirox) is added to or omitted from the patient’s treatment after the titration phase, a dose 
adjustment of treprostinil has to be considered. 
 
Rifampicin and other CYP2C8 inducers 
Pharmacokinetic studies in humans with oral treprostinil diolamine indicated that the concomitant 
administration of CYP2C8 enzyme inducer rifampicin resulted in a reduced (by about 20%) exposure 
to treprostinil. In case rifampicin is added to or omitted from the patient’s treatment after the titration 
phase, a dose adjustment of treprostinil has to be considered. 
 
Also other CYP2C8 inducers (e.g. phenytoin, carbamazepine, phenobarbital and St. John's Wort) may 
lead to reduced exposure to treprostinil. In case a CYP2C8 inhibitor is added to or omitted from the 
patient’s treatment after the titration phase, a dose adjustment of treprostinil has to be considered. 
 
Concomitant administration with bosentan 
In a pharmacokinetic study in humans, in which bosentan (250 mg/day) and treprostinil diolamine 
(oral dose of 2 mg/day) were administered concomitantly, no pharmacokinetic interaction between 
treprostinil and bosentan was observed.  
 
Concomitant administration with sildenafil  
In a pharmacokinetic study in humans, in which sildenafil (60mg/day) and treprostinil diolamine (oral 
dose of 2 mg/day) were administered concomitantly, no pharmacokinetic interaction between 
treprostinil and sildenafil was observed. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
There are no or limited amount of data from the use of treprostinil in pregnant women. Animal studies 
are insufficient with respect to effects on pregnancy (see section 5.3). Treprostinil should only be used 
during pregnancy if the potential benefit to the mother justifies the potential risk to the foetus. 
 
Women of child-bearing potential 
Contraception is recommended during treprostinil treatment. 
 
Breast-feeding 
It is not known whether treprostinil is excreted in human milk. Breastfeeding women taking 
treprostinil should be advised to discontinue breastfeeding. 



10 

 
4.7 Effects on ability to drive and use machines 
 
Treprostinil has minor influence on the ability to drive and use machines at the initiation of treatment 
or dose adjustments. They may be accompanied by undesirable effects such as symptomatic systemic 
hypotension or dizziness which may impair ability to drive and operate machinery. 
 
4.8 Undesirable effects 
 
Summary of safety profile 
In addition to local effects resulting from the administration of treprostinil by subcutaneous infusion 
such as infusion site pain and infusion site reaction, adverse reactions with treprostinil are related to 
the pharmacological properties of prostacyclins. 
 
Tabulated summary of adverse reactions 
The adverse reactions are presented as MedDRA preferred terms under the MedDRA system organ 
class. The incidence of the adverse reactions below are expressed according to the following 
categories: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare 
(≥1/10,000 to <1/1,000); very rare (<1/10,000).  
 
System organ class Adverse reaction Incidence 
Nervous system disorders Headache Very common 
 Dizziness Common 
Eye disorders Eyelid oedema Uncommon 
Cardiac disorders Vasodilatation Very common 
 Hypotension Common 
Gastrointestinal disorders Diarrhoea Very common 
 Nausea Very common 
 Dyspepsia Uncommon 
 Vomiting Uncommon 
Skin and subcutaneous tissue 
disorders 

Rash Common 

 Pruritus Uncommon 
 Exanthema Uncommon 
Musculoskeletal, connective 
tissue disorders 

Jaw pain Very common 

 Myalgia, arthalgia Common 
 Pain in extremities Common 
 Back pain Uncommon 
General disorders and 
administration site conditions 

Infusion site pain, infusion site 
reaction, bleeding or 
haematoma 

Very common 

 Oedema Common 
 Flushing Common 
 Decreased appetite Uncommon 
 Fatigue Uncommon 
 
Description of selected adverse reactions 
Bleeding events  
Due to its effects on platelet aggregation, treprostinil may increase the risk of bleeding, as observed by 
an increased incidence of epistaxis and gastrointestinal (GI) bleeding (including GI haemorrhage, 
rectal haemorrhage, gum haemorrhage and melaena) in controlled clinical trials in PAH. 
 



11 

Events Observed During Clinical Practice: 
In addition to adverse reactions reported from clinical trials in PAH patients, the following events have 
been identified during post-approval use of treprostinil in other indications. Because they are reported 
voluntarily from a population of unknown size, estimates of frequency cannot be made. The following 
events were reported: infusion site infection, subcutaneous infusion site abscess formation, 
thrombocytopenia, and bone pain. 
In addition, generalised rashes, sometimes macular or papular in nature, and cellulitis have been 
infrequently reported. 
 
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. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.* 
 
4.9 Overdose 
 
Symptoms of overdose with treprostinil include flushing, headache, hypotension, nausea, vomiting, 
and diarrhoea. Patients experiencing symptoms of overdose should, after consultation with their 
physician, immediately reduce their dose of treprostinil depending on the severity of the symptoms 
until the symptoms of overdose have resolved. Dosing should be recommenced with caution under 
medical control and patients monitored closely for recurrence of unwanted symptoms. 
 
No antidote is known. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antithrombotic agents, platelet aggregation inhibitors excl. heparin 
ATC code: B01AC21 
 
Mechanism of action  
Treprostinil is a prostacyclin analogue. 
It exerts a direct vasodilation effect on the pulmonary and systemic arterial circulation and, inhibits 
platelet aggregation.   
 
Clinical efficacy and safety  
In a randomised, multi-centre, controlled clinical trial, a total of 105 male (53.3%) and female (46.7%) 
adult patients with inoperable CTEPH or persistent or recurrent CTEPH after pulmonary 
endarterectomy (18-88 years of age, mean 64 years) were treated. Patients were required to have 
CTEPH classified as severe, as defined by an un-encouraged six-minute walk test (6MWT) of between 
150 and 400 meters and a classification in the WHO/NYHA functional class III or IV. Patients were 
divided into two treprostinil treatment groups (53 high dose and 52 low dose patients, treated with 
subcutaneous infusion for a total of 24 weeks) as follows. In the high dose group, patients were 
administered a subcutaneous dose via infusion pump that increased from approximately 1 to a target 
dose of approximately 30 ng/kg/min for the first 12 weeks, followed by 12 weeks of stable perfusion; 
in the low dose group, the target dose was approximately 3 ng/kg/min following the same schedule.  
  
The primary efficacy analysis was based on the individual difference between the 6MWT data at 
baseline and after 24 weeks. Treprostinil improved the six-minute walk distance (6MWT, six-minute 
walk test: baseline vs. 24 weeks of treatment) by a mean of 45.43 m in the high dose group versus 3.83 
m in the low dose group (p<0.05, ANCOVA). Exploratory secondary efficacy (low vs. high) 
measures, after 24 weeks of treatment, showed -significant improvements in New York Heart 
Association functional (NYHA ) class, haemodynamic parameters (mean pulmonary vascular 



12 

resistance, mean pulmonary arterial pressure, mean cardiac output, and mean cardiac index) and 
median pro-BNP (brain natriuretic peptide values) in favor of the high dose group. No significant 
differences between the two test groups in the number of patients showing a "clinical worsening", 
defined as a reduction of 6MWD of 20% compared to baseline, worsening of NYHA functional class 
and/or hospitalisation due to CTEPH with the need of additional pulmonary hypertension specific 
treatment, were observed. High dose treprostinil showed no significant changes in the Borg Dyspnoea 
Score (measured during the 6MWT), or the summed Quality of Life score as assessed by the 
Minnesota Living with Heart Failure Questionnaire. 
 
5.2 Pharmacokinetic properties 
 
Distribution 
In humans, steady-state plasma concentrations are usually achieved within 15 to 18 hours of the 
initiation of either subcutaneous or intravenous infusion of treprostinil. Steady-state plasma 
concentrations of treprostinil are dose-proportional at infusion rates of 2.5 up to 125 ng/kg/min.  
 
The mean apparent elimination half-life following subcutaneous administration ranged from 1.32 to 
1.42 hours after infusions over 6 hours, 4.61 hours after infusions over 72 hours, and 2.93 hours after 
infusions lasting at least three weeks. The mean volume of distribution for treprostinil ranged from 
1.11 to 1.22 l/kg, and plasma clearance ranged from 586.2 to 646.9 ml/kg/h. Clearance is lower in 
obese subjects (BMI > 30 kg/m2). 
 
In a seven-day chronic pharmacokinetic study in 14 healthy volunteers with treprostinil doses ranging 
from 2.5 to 15 ng/kg/min administered by subcutaneous infusion, steady state plasma treprostinil 
concentrations reached peak levels twice (at 1 a.m. and 10 a.m. respectively) and trough levels twice 
(at 7 a.m. and 4 p.m. respectively). The peak concentrations were approximately 20% to 30% higher 
than the trough concentrations. 
 
Elimination 
In a study conducted on healthy volunteers using [14C] radioactive treprostinil, 78.6% and 13.4% of 
the subcutaneous radioactive dose were recovered in the urine and faeces respectively over a period of 
224 hours. No single major metabolite was observed. Five metabolites were detected in the urine, 
ranging from 10.2% to 15.5% of the dose administered. These five metabolites accounted for a 
combined total of 64.4%. Three are products of oxidation of the 3-hydroxyloctyl side chain, one is a 
glucuroconjugated derivative (treprostinil glucuronide) and one is unidentified. Only 3.7% of the dose 
was recovered in the urine as unchanged parent drug. 
 
An in vitro study demonstrated no inhibitory potential of treprostinil to human hepatic microsomal 
cytochrome P450 isoenzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A). 
 
Moreover, administration of treprostinil had no inducing effect on hepatic microsomal protein, total 
cytochrome (CYP) P 450 content or on the activities of the isoenzymes CYP1A, CYP2B and CYP3A. 
 
Hepatic Insufficiency  
In patients with portopulmonary hypertension and mild (n=4) or moderate (n=5) hepatic insufficiency, 
treprostinil at a subcutaneous dose of 10 ng/kg/min for 150 minutes had an AUC 0-24 h that was 
increased 260 % and 510 %, respectively, compared to healthy subjects. Clearance in patients with 
hepatic insufficiency was reduced by up to 80% compared to healthy adults (see section 4.2). 
 
Elderly patients 
In a multivariate analysis of pooled studies, patients in the age group ≥65 years had a small reduction 
in plasma clearance of treprostinil. However, most publications regarded either healthy volunteers or 
patient with PAH. CTEPH patients were rarely described. Age stratification was not performed in any 
publication. As only few studies reported on PK parameters but none reported both on CTEPH 
indication and PK data, no information is available on the pharmacokinetics of treprostinil in elderly 
patients. 



13 

5.3. Preclinical safety data 
 
Preclinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity, genotoxicity, and toxicity to reproduction. 
 
In 13 and 26 week studies continuous subcutaneous infusions of treprostinil sodium caused infusion 
site reactions in rats and dogs (oedema/erythema, masses/swellings, pain/sensitivity to touch). In dogs 
severe clinical effects (hypoactivity, emesis, loose stool and infusion site oedema) and death 
(associated with intestinal intussusceptions and rectal prolapse) were observed in animals administered 
≥300ng/kg/min. Mean steady state plasma treprostinil levels of 7.85ng/ml were measured in these 
animals. Plasma levels of this order may be achieved in humans treated with treprostinil infusions at 
>50ng/kg/min. 
 
As a continuously sufficient exposure to treprostinil has not been proven for any dosage tested in the 
reproductive studies in rats, these studies might be insufficient regarding possible effects on fertility, 
prenatal and postnatal development. 
 
No long-term animal studies have been performed to evaluate treprostinil’s carcinogenic potential.   
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Sodium citrate  
Hydrochloric acid  
Metacresol  
Sodium hydroxide 
Sodium chloride  
Water for injections  
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products. 
 
6.3 Shelf life 
 
Unopened vial  
3 years 
 
After first opening  
30 days 
 
During use with continuous subcutaneous infusion 
Chemical, physical and microbial in-use stability of a single container (syringe) of undiluted 
Trepulmix administered subcutaneously has been demonstrated for 72 h at 37°C.  
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
For in-use storage times and conditions see section 6.3. 
 
6.5 Nature and contents of container  
 
Trepulmix 1 mg/ml solution for infusion: 10 ml type I clear glass vial sealed with a rubber teflon-
coated stopper and fitted with a yellow cap. 



14 

Trepulmix 2.5 mg/ml solution for infusion: 10 ml type I clear glass vial sealed with a rubber teflon-
coated stopper and fitted with a blue cap. 
Trepulmix, 5 mg/ml solution for infusion: 10 ml type I clear glass vial sealed with a rubber teflon-
coated stopper and fitted with a green cap. 
Trepulmix, 10 mg/ml solution for infusion: 10 ml type I clear glass vial sealed with a rubber teflon-
coated stopper and fitted with a red cap. 
 
Each carton contains one vial. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
SciPharm Sàrl 
7, Fausermillen 
L-6689 Mertert 
Luxembourg 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/19/1419/001 
EU/1/19/1419/002 
EU/1/19/1419/003 
EU/1/19/1419/004 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
 
 
10. DATE OF REVISION OF THE TEXT 
 



15 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A.  MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 



16 

  
A.  MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
Amomed Pharma GmbH 
Storchengasse 1 
1150 Vienna 
Austria 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  
 
Medicinal product subject to restricted medical prescription. 
 
C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic safety update reports (PSURs)  
 
The requirements for submission of PSURs for this medicinal product are set out in the list of 
Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC 
and any subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT   
 
• Risk management plan (RMP) 

 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance 
activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the 
marketing authorisation and any agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 



17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



19 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON BOX – 1 mg/ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Trepulmix 1 mg/ml solution for infusion  
 
treprostinil 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml of solution for infusion contains 1 mg treprostinil (as treprostinil sodium). 
 
1 vial with 10 ml contains 10 mg of treprostinil. 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium citrate, sodium chloride, sodium hydroxide, hydrochloric acid , metacresol and water for 
injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for infusion. 
 
Contains 1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Subcutaneous use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



20 

9. SPECIAL STORAGE CONDITIONS 
 
No special storage conditions.  
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
SciPharm Sàrl 
7, Fausermillen 
L-6689 Mertert 
Luxembourg 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/19/1419/001  
 
 
13. BATCH NUMBER<, DONATION AND PRODUCT CODES> 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
<Justification for not including Braille accepted.> 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifies included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 



21 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL – 1mg/ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Trepulmix 1 mg/ml solution for infusion  
treprostinil 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER<, DONATION AND PRODUCT CODES> 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
10 mg/10 ml 
 
 
6. OTHER 
 
SciPharm (Logo) 



22 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON BOX – 2.5 mg/ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Trepulmix 2.5 mg/ml solution for infusion 
 
treprostinil 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml of solution for infusion contains 2.5 mg treprostinil (as treprostinil sodium). 
 
Each 10 ml vial contains 25 mg of treprostinil, as treprostinil sodium. 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium citrate, sodium chloride, sodium hydroxide, hydrochloric acid , metacresol and water for 
injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for infusion. 
 
Contains 1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Subcutaneous use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



23 

9. SPECIAL STORAGE CONDITIONS 
 
No special storage conditions. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
SciPharm Sàrl 
7, Fausermillen 
L-6689 Mertert 
Luxembourg 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/19/1419/002  
 
 
13. BATCH NUMBER<, DONATION AND PRODUCT CODES> 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
<Justification for not including Braille accepted.> 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifies included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 



24 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL – 2.5 mg/ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Trepulmix 2.5 mg/ml solution for infusion 
treprostinil 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER<, DONATION AND PRODUCT CODES> 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
25 mg/10 ml 
 
 
6. OTHER 
 
SciPharm (Logo) 



25 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON BOX – 5 mg/ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Trepulmix 5 mg/ml solution for infusion 
 
treprostinil 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml of solution for infusion contains 5 mg treprostinil (as treprostinil sodium). 
 
Each 10 ml vial contains 50 mg of treprostinil, as treprostinil sodium. 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium citrate, sodium chloride, sodium hydroxide, hydrochloric acid , metacresol and water for 
injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for infusion. 
 
Contains 1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Subcutaneous use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



26 

9. SPECIAL STORAGE CONDITIONS 
 
No special storage conditions. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
SciPharm Sàrl 
7, Fausermillen 
L-6689 Mertert 
Luxembourg 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/19/1419/003  
 
 
13. BATCH NUMBER<, DONATION AND PRODUCT CODES> 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
<Justification for not including Braille accepted.> 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifies included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 



27 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL – 5 mg/ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Trepulmix 5 mg/ml solution for infusion 
treprostinil 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER<, DONATION AND PRODUCT CODES> 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
50 mg/10 ml 
 
 
6. OTHER 
 
SciPharm (Logo) 



28 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
CARTON BOX – 10 mg/ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Trepulmix 10 mg/ml solution for infusion 
 
treprostinil 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml of solution for infusion contains 10 mg treprostinil (as treprostinil sodium). 
 
Each 10 ml vial contains 100 mg of treprostinil, as treprostinil sodium. 
 
 
3. LIST OF EXCIPIENTS 
 
Sodium citrate, sodium chloride, sodium hydroxide, hydrochloric acid , metacresol and water for 
injections. 
 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for infusion. 
 
Contains 1 vial 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
Subcutaneous use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



29 

9. SPECIAL STORAGE CONDITIONS 
 
No special storage conditions. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
SciPharm Sàrl 
7, Fausermillen 
L-6689 Mertert 
Luxembourg 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/19/1419/004  
 
 
13. BATCH NUMBER<, DONATION AND PRODUCT CODES> 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
<Justification for not including Braille accepted.> 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifies included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 



30 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL – 10 mg/ml 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Trepulmix 10 mg/ml solution for infusion 
treprostinil 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER<, DONATION AND PRODUCT CODES> 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
100 mg/10 ml 
 
 
6. OTHER 
 
SciPharm (Logo) 



31 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



32 

 
Package leaflet: Information for the user 

 
Trepulmix 1 mg/ml solution for infusion 

Trepulmix 2.5 mg/ml solution for infusion 
Trepulmix 5 mg/ml solution for infusion 
Trepulmix 10 mg/ml solution for infusion 

 
treprostinil 

 
Read all of this leaflet carefully before you start using this medicine because it contains important 
information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet: 
1. What Trepulmix is and what it is used for 
2.  What you need to know before you use Trepulmix 
3.  How to use Trepulmix 
4.  Possible side effects 
5.  How to store Trepulmix 
6.  Contents of the pack and other information 
 
 
1. What Trepulmix is and what it is used for  
 
What Trepulmix is 
The active ingredient of Trepulmix is treprostinil. 
Treprostinil belongs to a group of medicines which work in a similar way to the naturally occurring 
prostacyclins. Prostacyclins are hormone-like substances which reduce blood pressure by relaxing 
blood vessels, causing them to widen, which allows the blood to flow more easily. Prostacyclins can 
also have an influence in preventing blood from clotting. 
 
What Trepulmix is used to treat 
Trepulmix is used for the treatment of adult patients with inoperable chronic thromboembolic 
pulmonary hypertension (CTEPH), or persistent or recurrent CTEPH after surgical treatment 
(severity classified WHO Functional Class (FC) III or IV), to improve exercise capacity and 
symptoms of the disease. Chronic thromboembolic pulmonary hypertension is a condition where 
your blood pressure is too high in the blood vessels between the heart and the lungs causing 
shortness of breath, dizziness, tiredness, fainting, palpitations or abnormal heartbeat, dry cough, 
chest pain and swollen ankles or legs. 
 
How Trepulmix works 
Trepulmix lowers blood pressure within the pulmonary artery by improving blood flow and reducing 
the amount of work for the heart. Improved blood flow leads to an increased supply of oxygen to the 
body and reduced strain on the heart, causing it to function more effectively. Trepulmix improves 
the symptoms associated with CTEPH and the ability to exercise in patients who are limited in terms 
of activity.  
 
 



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2. What you need to know before you use Trepulmix 
 
Do not use Trepulmix: 
- if you are allergic to treprostinil or any of the other ingredients of this medicine (listed in section 

6). 
- if you have been diagnosed with a disease called “pulmonary veno-occlusive disease”. This is a 

disease in which the blood vessels that carry blood through your lungs become swollen and 
clogged resulting in a higher pressure in the blood vessels between the heart and the lungs. 

- if you have severe liver disease 
- if you have a heart problem, for example: 

• a heart attack (myocardial infarction) within the last six months 
• severe changes in heart rate 
• severe coronary heart disease or unstable angina 
• a heart defect has been diagnosed, such as a faulty heart valve that causes the 

heart to work poorly 
• any disease of the heart which is not being treated or not under close 

medical observation 
- if you are at a specific high risk of bleeding – for example active stomach ulcers, injuries or 

other bleeding conditions 
- if you have had a stroke within the last 3 months, or any other interruption of blood supply to 

the brain 
 
Warnings and precautions 
Talk to your doctor before using Trepulmix if you: 
- suffer from any liver disease 
- suffer from kidney disease 
- have been advised that you are medically obese (BMI greater than 30 kg/m2) 
- are on a low sodium diet 
 
During your treatment with Trepulmix, tell your doctor: 
- if your blood pressure decreases (hypotension) 
- if you experience a rapid increase in breathing difficulties or persistent cough (this can be 

related to congestion in the lungs or asthma or other condition), consult your doctor 
immediately. 

- if you have excessive bleeding as treprostinil may increase the risk, by preventing your blood 
from clotting 

 
Children and adolescents 
Trepulmix must not be used in children and adolescents. 
   
Other medicines and Trepulmix 
Tell your doctor if you are taking/using, have recently taken/used or might take/use any other 
medicines. Please tell your doctor if you are taking: 
- medicines used to treat high blood pressure (antihypertensive medicines or other vasodilators) 
- medicines used to increase the rate of urination (diuretics) including furosemide 
- medicines that stop blood clotting (anticoagulants) such as warfarin, heparin or nitric oxide 

based products 
- any non-steroidal anti-inflammatory (NSAID) medicines (e.g. acetylsalicylic acid, ibuprofen) 
- medicines which may enhance or weaken the effects of Trepulmix (e.g. gemfibrozil, rifampicin, 

trimethoprim, deferasirox, phenytoin, carbamazepine, phenobarbital, St. John's wort.), as your 
doctor may need to adjust the dosage of Trepulmix. 

 
Pregnancy and breast-feeding 
Trepulmix is not recommended if you are pregnant, planning to become pregnant, or think that you 
might be pregnant, unless considered essential by your doctor. The safety of this medicine for use 
during pregnancy has not been established. 
 
Contraception is strongly recommended during Trepulmix treatment. 



34 

 
Trepulmix is not recommended for use in breast-feeding, unless considered essential by your doctor. 
You are advised to stop breast-feeding if Trepulmix is prescribed for you, because it is not known 
whether this medicine passes into breast milk.  
 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before taking this medicine. 
Driving and using machines 
Trepulmix may induce low blood pressure with dizziness or fainting. In such a case do not drive or 
operate machinery and ask your doctor for advice. 
 
Trepulmix contains sodium 
Please tell your doctor if you are on a controlled sodium diet. They will take into account:  
Trepulmix 1 mg/ml solution for infusion 
This medicine contains 36.8 mg sodium (main component of cooking/table salt) in each vial. This is 
equivalent to 1.8% of the recommended maximum daily dietary intake of 
sodium for an adult.  
 
Trepulmix 2.5 mg/ml solution for infusion 
This medicine contains 37.3 mg sodium (main component of cooking/table salt) in each vial. This is 
equivalent to 1.9% of the recommended maximum daily dietary intake of 
sodium for an adult.  
 
Trepulmix 5 mg/ml solution for infusion 
This medicine contains 39.1 mg sodium (main component of cooking/table salt) in each vial. This is 
equivalent to 2.0% of the recommended maximum daily dietary intake of 
sodium for an adult.  
 
Trepulmix 10 mg/ml solution for infusion 
This medicine contains 37.4 mg sodium (main component of cooking/table salt) in each vial. This is 
equivalent to 1.9% of the recommended maximum daily dietary intake of 
sodium for an adult.  
 
 
3.  How to use Trepulmix 
 
Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not 
sure. 
 
Trepulmix is administered undiluted as a continuous subcutaneous infusion (under the skin) via a 
small tube (cannula) which is located in your abdomen or thigh; 
 
Trepulmix is pushed through the tubing by a portable pump.  
 
Before you leave the hospital or clinic, your doctor will tell you how to prepare Trepulmix and at 
what rate the pump should deliver your treprostinil. Information on how to use the pump correctly 
and what to do if it stops working should also be given to you. The information should also tell you 
who to contact in an emergency. 
 
Flushing of the infusion line whilst connected may cause accidental overdose. 
 
Adult patients 
Trepulmix is available as 1 mg/ml, 2.5 mg/ml, 5 mg/ml or 10 mg/ml solution for infusion. Your doctor 
will determine the infusion rate and dose appropriate for your condition. 
 
Elderly patients 
No special dose adjustments are necessary for these patients. 



35 

 
Patients with liver or kidney disease 
Your doctor will determine the infusion rate and dose appropriate for your condition. 
 
Infusion rate 
The infusion rate can be reduced or increased on an individual basis under medical supervision only. 
 
The aim of adjusting the infusion rate is to establish an effective maintenance rate which improves 
symptoms of CTEPH while minimising any undesirable effects. 
 
If your symptoms increase or if you need complete rest, or are confined to your bed or chair, or if any 
physical activity brings on discomfort and your symptoms occur at rest, do not increase your dose 
without medical advice. Trepulmix may no longer be sufficient to treat your disease and another 
treatment may be required. 
 
If you use more Trepulmix than you should 
If you accidentally overdose  Trepulmix, you may experience nausea, vomiting, diarrhoea, low blood 
pressure (dizziness, light-headedness or fainting), skin flushes and/or headaches. 
 
If any of these effects become severe you should contact your doctor or hospital immediately. Your 
doctor may reduce or discontinue the infusion until your symptoms have disappeared. Trepulmix 
solution for infusion will then be reintroduced at a dose level recommended by your doctor. 
 
If you stop using Trepulmix 
Always use Trepulmix as directed by your doctor or hospital specialist. Do not stop using Trepulmix 
unless your doctor has advised you to. 
 
Abrupt withdrawal or sudden reductions in the dose of Trepulmix may cause the pulmonary arterial 
hypertension to return with the potential for rapid and severe deterioration in your condition. 
 
If you have any further questions on the use of this medicine, ask your doctor. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Very common (may affect more than 1 in 10 people) 
• widening of blood vessels  
• pain around the infusion site 
• reaction around the infusion site 
• bleeding or bruising around the infusion site 
• headaches 
• nausea 
• diarrhoea 
• jaw pain 

 
Common (may affect up to 1 in 10 people) 
• dizziness 
• light-headedness or fainting due to low blood pressure 
• skin rashes 
• muscle pain (myalgia) 
• joint pain (arthralgia) 
• swelling of feet, ankles, legs or fluid retention 
• hot flush 
• pain in arms and / or legs 
 



36 

Uncommon (may affect up to 1 in 100 people) 
• swollen eyelids (eyelid oedema) 
• indigestions 
• vomiting 
• skin itches 
• exanthema 
• back pain 
• decreased appetite 
• tiredness 
 
Other possible side effects observed in pulmonary arterial hypertension (PAH) patients: 
• bleeding episodes such as: as nose bleeds, coughing up blood, blood in the urine, bleeding from 

the gums, blood in the faeces 
 
Other possible side effects observed during clinical practice: 
• infection at the infusion site 
• abscess at the infusion site 
• a decrease of blood clotting cells (platelets) in the blood (thrombocytopenia) 
• bone pain 
• skin rashes with discolouration or raised bumps 
• tissue infection under the skin (cellulitis) 
 
Reporting of side effects 
If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this 
leaflet. You can also report side effects directly via the national reporting system listed in Appendix 
V.* By reporting side effects you can help provide more information on the safety of this medicine. 
 
 
5. How to store Trepulmix  
 
Keep this medicine out of the sight and reach of children. 
 
 
Do not use this medicine after the expiry date that is stated on the carton and vial after “EXP”. The 
expiry date refers to the last day of that month. 
 
This medicinal product does not require any special storage conditions. 
 
A Trepulmix vial must be used or discarded within 30 days after first opening.  
 
During continuous subcutaneous infusion, a single reservoir (syringe) of undiluted Trepulmix must be 
used within 72 hours.  
 
Do not use this medicine if you notice any damage to the vial, discolouration or other signs of 
deterioration.  
 
Do not throw away any medicines via waste water or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 
6. Contents of the pack and other information 
 
What Trepulmix contains 
The active substance is treprostinil.  
 
Trepulmix 1 mg/ml solution for infusion 
Each ml of solution contains 1 mg treprostinil (as sodium salt). 



37 

Each 10 ml vial of solution contains 10 mg treprostinil (as sodium salt).  
 
Trepulmix 2.5 mg/ml solution for infusion 
Each ml of solution contains 2.5 mg treprostinil (as sodium salt) 
Each 10 ml vial of solution contains 25 mg treprostinil (as sodium salt). 
 
Trepulmix 5 mg/ml solution for infusion 
Each ml of solution contains 5 mg treprostinil (as sodium salt). 
Each 10 ml vial of solution contains 50 mg treprostinil (as sodium salt). 
 
Trepulmix 10 mg/ml solution for infusion 
Each ml of solution contains 10 mg treprostinil (as sodium salt). 
Each 10 ml vial of solution contains 100 mg treprostinil (as sodium salt). 
 
The other ingredients are: 
Sodium citrate, sodium chloride, sodium hydroxide, hydrochloric acid, metacresol and water for 
injections. See section 2, “Trepulmix contains sodium”. 
 
What Trepulmix looks like and the contents of the pack 
Trepulmix is a clear colourless to slightly yellow solution, available in a 10 ml clear glass vial sealed 
with a rubber stopper and a colour coded cap: 
 
Trepulmix 1 mg/ml solution for infusion  
Trepulmix 1 mg/ml solution for infusion has a yellow rubber cap. 
 
Trepulmix 2.5 mg/ml solution for infusion 
Trepulmix 2.5 mg/ml solution for infusion has a blue rubber cap. 
 
Trepulmix 5 mg/ml solution for infusion 
Trepulmix 5 mg/ml solution for infusion has a green rubber cap. 
 
Trepulmix 10 mg/ml solution for infusion 
Trepulmix 10 mg/ml solution for infusion has a red rubber cap. 
 
Each carton contains one vial. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation holder  
SciPharm Sàrl 
7, Fausermillen 
L-6689 Mertert 
Luxembourg 
 
Manufacturer 
Amomed Pharma GmbH 
Storchengasse 1 
1150 Vienna 
Austria 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A.  MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
	C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT  
	A. LABELLING
	B. PACKAGE LEAFLET