Posaconazole SP

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Posaconazole SP 40 mg/ml oral suspension 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml of oral suspension contains 40 mg of posaconazole. 
 
For a full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Oral suspension 
White suspension 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications  
 
Posaconazole SP is indicated for use in the treatment of the following fungal infections in adults (see 
section 5.1): 
 
-  Invasive aspergillosis in patients with disease that is refractory to amphotericin B or 

itraconazole or in patients who are intolerant of these medicinal products; 
-  Fusariosis in patients with disease that is refractory to amphotericin B or in patients who are 

intolerant of amphotericin B; 
-  Chromoblastomycosis and mycetoma in patients with disease that is refractory to itraconazole 

or in patients who are intolerant of itraconazole; 
-  Coccidioidomycosis in patients with disease that is refractory to amphotericin B, itraconazole or 

fluconazole or in patients who are intolerant of these medicinal products; 
- Oropharyngeal candidiasis: as first-line therapy in patients who have severe disease or are 

immunocompromised, in whom response to topical therapy is expected to be poor. 
 
Refractoriness is defined as progression of infection or failure to improve after a minimum of 7 days 
of prior therapeutic doses of effective antifungal therapy. 
 
Posaconazole SP is also indicated for prophylaxis of invasive fungal infections in the following 
patients: 
 
- Patients receiving remission-induction chemotherapy for acute myelogenous leukemia (AML) 

or myelodysplastic syndromes (MDS) expected to result in prolonged neutropenia and who are 
at high risk of developing invasive fungal infections;  

- Hematopoietic stem cell transplant (HSCT) recipients who are undergoing high-dose 
immunosuppressive therapy for graft versus host disease and who are at high risk of developing 
invasive fungal infections. 

 
4.2 Posology and method of administration 
 
Treatment should be initiated by a physician experienced in the management of fungal infections or in 
the supportive care in the high risk patients for which posaconazole is indicated as prophylaxis. 
 
Recommended dosage is shown in Table 1. 
 



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Table 1. Recommended dose according to indication 
Indication Dose and duration of therapy 

Refractory Invasive Fungal 
Infections (IFI)/Intolerant 
patients with IFI 

400 mg (10 ml) twice a day. In patients who cannot tolerate a 
meal or a nutritional supplement, Posaconazole SP should be 
administered at a dose of 200 mg (5 ml) four times a day. 
Duration of therapy should be based on the severity of the 
underlying disease, recovery from immunosuppression, and 
clinical response. 

Oropharyngeal Candidiasis Loading dose of 200 mg (5 ml) once a day on the first day, 
then 100 mg (2.5 ml) once a day for 13 days. 
Each dose of Posaconazole SP should be administered with a 
meal, or with a nutritional supplement in patients who cannot 
tolerate food to enhance the oral absorption and to ensure 
adequate exposure. 

Prophylaxis of Invasive 
Fungal Infections 

200 mg (5 ml) three times a day. Each dose of Posaconazole 
SP should be administered with a meal, or with a nutritional 
supplement in patients who cannot tolerate food to enhance 
the oral absorption and to ensure adequate exposure. The 
duration of therapy is based on recovery from neutropenia or 
immunosuppression. For patients with acute myelogenous 
leukemia or myelodysplastic syndromes, prophylaxis with 
Posaconazole SP should start several days before the 
anticipated onset of neutropenia and continue for 7 days after 
the neutrophil count rises above 500 cells per mm3. 

 
There are limited pharmacokinetic data in patients with severe gastrointestinal dysfunction (such as 
severe diarrhoea). Patients who have severe diarrhoea or vomiting should be monitored closely for 
breakthrough fungal infections. 
 
The oral suspension must be shaken well before use. 
 
Use in renal impairment: An effect of renal impairment on the pharmacokinetics of posaconazole is 
not expected and no dose adjustment is recommended (see section 5.2). 
 
Use in hepatic impairment: There are limited pharmacokinetic data in patients with hepatic 
impairment; therefore, no recommendation for dose adjustment can be made. In the small number of 
subjects studied who had hepatic impairment, there was an increase in exposure and half-life with a 
decrease in hepatic function (see sections 4.4 and 5.2). 
 
Use in children: Safety and efficacy in children and adolescents below the age of 18 years have not 
been established. Therefore posaconazole is not recommended for use in patients below 18 years of 
age (see sections 5.1 and 5.2). 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients. 
 
Co-administration with ergot alkaloids (see section 4.5). 
 
Co-administration with the CYP3A4 substrates terfenadine, astemizole, cisapride, pimozide, 
halofantrine or quinidine since this may result in increased plasma concentrations of these medicinal 
products, leading to QTc prolongation and rare occurrences of torsades de pointes (see sections 4.4 
and 4.5). 
 
Co-administration with the HMG-CoA reductase inhibitors simvastatin, lovastatin and atorvastatin 
(see section 4.5). 



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4.4 Special warnings and precautions for use 
 
Hypersensitivity: There is no information regarding cross-sensitivity between posaconazole and other 
azole antifungal agents. Caution should be used when prescribing Posaconazole SP to patients with 
hypersensitivity to other azoles. 
 
Hepatic toxicity: Hepatic reactions (e.g. mild to moderate elevations in ALT, AST, alkaline 
phosphatase, total bilirubin and/or clinical hepatitis) have been reported during treatment with 
posaconazole. Elevated liver function tests were generally reversible on discontinuation of therapy and 
in some instances these tests normalised without interruption of therapy. Rarely, more severe hepatic 
reactions with fatal outcomes have been reported.  
Posaconazole should be used with caution in patients with severe hepatic impairment. In these 
patients, the prolonged elimination half-life may lead to increased exposure. 
 
Monitoring of hepatic function: Patients who develop abnormal liver function tests during 
Posaconazole SP therapy must be routinely monitored for the development of more severe hepatic 
injury. Patient management should include laboratory evaluation of hepatic function (particularly liver 
function tests and bilirubin). Discontinuation of Posaconazole SP should be considered if clinical signs 
and symptoms are consistent with development of liver disease. 
 
QTc prolongation: Some azoles have been associated with prolongation of the QTc interval. 
Posaconazole SP must not be administered with medicinal products that are substrates for CYP3A4 
and are known to prolong the QTc interval (see sections 4.3 and 4.5). Posaconazole SP should be 
administered with caution to patients with pro-arrhythmic conditions such as: 
• Congenital or acquired QTc prolongation 
• Cardiomyopathy, especially in the presence of cardiac failure 
• Sinus bradycardia 
• Existing symptomatic arrhythmias 
• Concomitant use with medicinal products known to prolong the QTc interval (other than those 

mentioned in section 4.3). 
Electrolyte disturbances, especially those involving potassium, magnesium or calcium levels, should 
be monitored and corrected as necessary before and during posaconazole therapy. 
 
Posaconazole is an inhibitor of CYP3A4 and should only be used under specific circumstances during 
treatment with other medicinal products that are metabolised by CYP3A4 (see section 4.5). 
 
Rifabutin: Concomitant use with posaconazole should be avoided unless the benefit to the patient 
outweighs the risk (see section 4.5). 
 
Rifamycin antibacterials (rifampicin, rifabutin), certain anticonvulsants (phenytoin, carbamazepine, 
phenobarbital, primidone), efavirenz and cimetidine: Posaconazole concentrations may be 
significantly lowered in combination; therefore, concomitant use with posaconazole should be avoided 
unless the benefit to the patient outweighs the risk (see section 4.5). 
 
This medicinal product contains approximately 1.75 g of glucose per 5 ml of suspension. Patients with 
glucose-galactose malabsorption should not take this medicine. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Effects of other medicinal products on posaconazole: 
Posaconazole is metabolised via UDP glucuronidation (phase 2 enzymes) and is a substrate for p-
glycoprotein (P-gp) efflux in vitro. Therefore, inhibitors (e.g. verapamil, ciclosporin, quinidine, 
clarithromycin, erythromycin, etc.) or inducers (e.g. rifampicin, rifabutin, certain anticonvulsants, etc.) 
of these clearance pathways may increase or decrease posaconazole plasma concentrations, 
respectively. 



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Rifabutin (300 mg once a day) decreased the Cmax (maximum plasma concentration) and AUC (area 
under the plasma concentration time curve) of posaconazole to 57 % and 51 %, respectively. 
Concomitant use of posaconazole and rifabutin and similar inducers (e.g. rifampicin) should be 
avoided unless the benefit to the patient outweighs the risk. See also below regarding the effect of 
posaconazole on rifabutin plasma levels.  
 
Efavirenz (400 mg once a day) decreased the Cmax and AUC of posaconazole by 45 % and 50 %, 
respectively. Concomitant use of posaconazole and efavirenz should be avoided unless the benefit to 
the patient outweighs the risk.  
 
Phenytoin (200 mg once a day) decreased the Cmax and AUC of posaconazole by 41 % and 50 %, 
respectively. Concomitant use of posaconazole and phenytoin and similar inducers (e.g. 
carbamazepine, phenobarbital, primidone) should be avoided unless the benefit to the patient 
outweighs the risk. 
 
H2 receptor antagonists and proton pump inhibitors: Posaconazole plasma concentrations (Cmax and 
AUC) were reduced by 39 % when posaconazole was administered with cimetidine (400 mg twice a 
day) due to reduced absorption possibly secondary to a decrease in gastric acid production. 
Concomitant use of posaconazole and cimetidine should be avoided unless the benefit to the patient 
outweighs the risk. The effect of other H2 receptor antagonists (e.g. famotidine, ranitidine) and proton 
pump inhibitors (e.g. omeprazole) that may suppress gastric acidity for several hours on plasma levels 
of posaconazole has not been studied but a reduction in bioavailability may occur so that co-
administration should be avoided if possible.  
 
Effects of posaconazole on other medicinal products: 
Posaconazole is a potent inhibitor of CYP3A4. Co-administration of posaconazole with CYP3A4 
substrates may result in large increases in exposure to CYP3A4 substrates as exemplified by the 
effects on tacrolimus, sirolimus, atazanavir and midazolam below. Caution is advised during co-
administration of posaconazole with CYP3A4 substrates administered intravenously and the dose of 
the CYP3A4 substrate may need to be reduced. If posaconazole is used concomitantly with CYP3A4 
substrates that are administered orally, and for which an increase in plasma concentrations may be 
associated with unacceptable adverse events, plasma concentrations of the CYP3A4 substrate and/or 
adverse events should be closely monitored and the dose adjusted as needed. Several of the interaction 
studies were conducted in healthy volunteers in whom a higher exposure to posaconazole occurs 
compared to patients administered the same dose. The effect of posaconazole on CYP3A4 substrates 
in patients might be somewhat lower than that observed in healthy volunteers, and is expected to be 
variable between patients due to the variable posaconazole exposure in patients. The effect of co-
administration with posaconazole on plasma levels of CYP3A4 substrates may also be variable within 
a patient, unless posaconazole is administered in a strictly standardised way with food, given the large 
food effect on posaconazole exposure (see section 5.2). 
 
Terfenadine, astemizole, cisapride, pimozide, halofantrine and quinidine (CYP3A4 substrates):  
Co-administration of posaconazole and terfenadine, astemizole, cisapride, pimozide, halofantrine or 
quinidine is contraindicated. Co-administration may result in increased plasma concentrations of these 
medicinal products, leading to QTc prolongation and rare occurrences of torsades de pointes (see 
section 4.3). 
 
Ergot alkaloids: Posaconazole may increase the plasma concentration of ergot alkaloids (ergotamine 
and dihydroergotamine), which may lead to ergotism. Co-administration of posaconazole and ergot 
alkaloids is contraindicated (see section 4.3). 
 
HMG-CoA reductase inhibitors metabolised through CYP3A4 (e.g. simvastatin, lovastatin, and 
atorvastatin): Posaconazole may substantially increase plasma levels of HMG-CoA reductase 
inhibitors that are metabolised by CYP3A4. Treatment with these HMG-CoA reductase inhibitors 



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should be discontinued during treatment with posaconazole as increased levels have been associated 
with rhabdomyolysis (see section 4.3). 
 
Vinca alkaloids: Posaconazole may increase the plasma concentration of vinca alkaloids (e.g. 
vincristine and vinblastine), which may lead to neurotoxicity. Therefore, concomitant use of 
posaconazole and vinca alkaloids should be avoided unless the benefit to the patient outweighs the 
risk. If co-administered, then it is recommended that dose adjustment of vinca alkaloids be considered. 
 
Rifabutin: Posaconazole increased the Cmax and AUC of rifabutin by 31 % and 72 %, respectively. 
Concomitant use of posaconazole and rifabutin should be avoided unless the benefit to the patient 
outweighs the risk (see also above regarding the effect of rifabutin on plasma levels of posaconazole). 
If these medicinal products are co-administered, careful monitoring of full blood counts and adverse 
events related to increased rifabutin levels (e.g. uveitis) is recommended. 
 
Ciclosporin: In heart transplant patients on stable doses of ciclosporin, posaconazole 200 mg once 
daily increased ciclosporin concentrations requiring dose reductions. Cases of elevated ciclosporin 
levels resulting in serious adverse events, including nephrotoxicity and one fatal case of 
leukoencephalopathy, were reported in clinical efficacy studies. When initiating treatment with 
posaconazole in patients already receiving ciclosporin, the dose of ciclosporin should be reduced (e.g. 
to about three quarters of the current dose). Thereafter blood levels of ciclosporin should be monitored 
carefully during co-administration, and upon discontinuation of posaconazole treatment, and the dose 
of ciclosporin should be adjusted as necessary. 
 
Tacrolimus: Posaconazole increased Cmax and AUC of tacrolimus (0.05 mg/kg body weight single 
dose) by 121 % and 358 %, respectively. Clinically significant interactions resulting in hospitalisation 
and/or posaconazole discontinuation were reported in clinical efficacy studies. When initiating 
posaconazole treatment in patients already receiving tacrolimus, the dose of tacrolimus should be 
reduced (e.g. to about one third of the current dose). Thereafter blood levels of tacrolimus should be 
monitored carefully during co-administration, and upon discontinuation of posaconazole, and the dose 
of tacrolimus should be adjusted as necessary. 
 
Sirolimus: Repeat dose administration of oral posaconazole (400 mg twice daily for 16 days) increased 
the Cmax and AUC of sirolimus (2 mg single dose) an average of 6.7-fold and 8.9-fold (range 3.1 to 
17.5-fold), respectively, in healthy subjects. The effect of posaconazole on sirolimus in patients is 
unknown, but is expected to be variable due to the variable posaconazole exposure in patients. Co-
administration of posaconazole with sirolimus is not recommended and should be avoided whenever 
possible. If it is considered that co-administration is unavoidable, then it is recommended that the dose 
of sirolimus should be greatly reduced at the time of initiation of posaconazole therapy and that there 
should be very frequent monitoring of trough concentrations of sirolimus in whole blood. Sirolimus 
concentrations should be measured upon initiation, during co-administration, and at discontinuation of 
posaconazole treatment, with sirolimus doses adjusted accordingly. It should be noted that the 
relationship between sirolimus trough concentration and AUC is changed during co-administration 
with posaconazole. As a result, sirolimus trough concentrations that fall within the usual therapeutic 
range may result in sub-therapeutic levels. Therefore trough concentrations that fall in the upper part 
of the usual therapeutic range should be targetted and careful attention should be paid to clinical signs 
and symptoms, laboratory parameters and tissue biopsies.  
 
HIV Protease Inhibitors: As HIV protease inhibitors are CYP3A4 substrates, it is expected that 
posaconazole will increase plasma levels of these antiretroviral agents. Following co-administration of 
oral posaconazole (400 mg twice daily) with atazanavir (300 mg once daily) for 7 days in healthy 
subjects Cmax and AUC of atazanavir increased by an average of 2.6-fold and 3.7-fold (range 1.2 to 26-
fold), respectively. Following co-administration of oral posaconazole (400 mg twice daily) with 
atazanavir and ritonavir (300/100 mg once daily) for 7 days in healthy subjects Cmax and AUC of 
atazanavir increased by an average of 1.5-fold and 2.5-fold (range 0.9 to 4.1-fold), respectively. The 
addition of posaconazole to therapy with atazanavir or with atazanavir plus ritonavir was associated 
with increases in plasma bilirubin levels. Frequent monitoring for adverse events and toxicity related 



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to antiretroviral agents that are substrates of CYP3A4 is recommended during co-administration with 
posaconazole.  
 
Midazolam and other benzodiazepines metabolised by CYP3A4: In a study in healthy volunteers 
posaconazole (200 mg once daily for 10 days) increased the exposure (AUC) of IV midazolam 
(0.05 mg/kg) by 83 %. In another study in healthy volunteers, repeat dose administration of oral 
posaconazole (200 mg twice daily for 7 days) increased the Cmax and AUC of IV midazolam (0.4 mg 
single dose) by an average of 1.3- and 4.6-fold (range 1.7 to 6.4-fold), respectively; Posaconazole 
400 mg twice daily for 7 days increased the IV midazolam Cmax and AUC by 1.6 and 6.2-fold (range 
1.6 to 7.6-fold), respectively. Both doses of posaconazole increased Cmax and AUC of oral midazolam 
(2 mg single oral dose) by 2.2 and 4.5-fold, respectively. In addition, oral posaconazole (200 mg or 
400 mg) prolonged the mean terminal half-life of midazolam from approximately 3-4 hours to 8-
10 hours during co-administration.  
Due to the risk of prolonged sedation it is recommended that dose adjustments should be considered 
when posaconazole is administered concomitantly with any benzodiazepine that is metabolised by 
CYP3A4 (e.g. midazolam, triazolam, alprazolam). 
 
Calcium channel blockers metabolised through CYP3A4 (e.g. diltiazem, verapamil, nifedipine, 
nisoldipine): Frequent monitoring for adverse events and toxicity related to calcium channel blockers 
is recommended during co-administration with posaconazole. Dose adjustment of calcium channel 
blockers may be required. 
 
Digoxin: Administration of other azoles has been associated with increases in digoxin levels. 
Therefore, posaconazole may increase plasma concentration of digoxin and digoxin levels need to be 
monitored when initiating or discontinuing posaconazole treatment. 
 
Sulfonylureas: Glucose concentrations decreased in some healthy volunteers when glipizide was co-
administered with posaconazole. Monitoring of glucose concentrations is recommended in diabetic 
patients. 
 
4.6 Pregnancy and lactation 
 
There is insufficient information on the use of posaconazole in pregnant women. Studies in animals 
have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. 
 
Women of childbearing potential have to use effective contraception during treatment. Posaconazole 
must not be used during pregnancy unless the benefit to the mother clearly outweighs the potential risk 
to the foetus. 
 
Posaconazole is excreted into the milk of lactating rats (see section 5.3). The excretion of 
posaconazole in human breast milk has not been investigated. Breast-feeding must be stopped on 
initiation of treatment with posaconazole. 
 
4.7 Effects on ability to drive and use machines 
 
No studies on the effects of posaconazole on the ability to drive and use machines have been 
performed. 
 
4.8 Undesirable effects 
 
The safety of posaconazole has been assessed in > 2,400 patients and healthy volunteers enrolled in 
clinical trials and from post-marketing experience. The most frequently reported serious related 
adverse events included nausea, vomiting, diarrhoea, pyrexia, and increased bilirubin.  

Table 2. Treatment-related adverse events (TRAE) by body system and frequency  
Common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000) 



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Blood and lymphatic system 
disorders 
Common: 
Uncommon: 
 
Rare: 

 
 
neutropenia 
thrombocytopenia, leukopenia, anaemia, eosinophilia, 
lymphadenopathy 
haemolytic uraemic syndrome, thrombotic 
thrombocytopenic purpura, pancytopenia, coagulopathy, 
haemorrhage 

Immune system disorders 
Uncommon: 
Rare: 

 
allergic reaction 
hypersensitivity reaction  

Endocrine disorders 
Rare: 

 
adrenal insufficiency, blood gonadotropin decreased 

Metabolism and nutrition 
disorders 
Common: 
Uncommon: 

 
 
electrolyte imbalance, anorexia 
hyperglycaemia 

Psychiatric disorders 
Rare: 

 
psychotic disorder, depression 

Nervous system disorders 
Common: 
Uncommon: 
Rare: 

 
paresthesia, dizziness, somnolence, headache 
convulsion, neuropathy, hypoaesthesia, tremor 
cerebrovascular accident, encephalopathy, peripheral 
neuropathy, syncope 

Eye disorders 
Uncommon: 
Rare: 

 
blurred vision 
diplopia, scotoma 

Ear and labyrinth disorder 
Rare: 

 
hearing impaired 

Cardiac disorders 
Uncommon:  
 
Rare: 

 
long QT syndrome§, electrocardiogram abnormal§, 
palpitations 
torsade de pointes, sudden death, ventricular tachycardia, 
cardio-respiratory arrest, cardiac failure, myocardial 
infarction  

Vascular disorders 
Uncommon: 
Rare: 

 
hypertension, hypotension 
pulmonary embolism, deep vein thrombosis 

Respiratory, thoracic and 
mediastinal disorders 
Rare: 

 
 
pulmonary hypertension, interstitial pneumonia, pneumonitis

Gastrointestinal disorders 
Common: 
 
Uncommon: 
Rare: 

 
vomiting, nausea, abdominal pain, diarrhoea, dyspepsia, dry 
mouth, flatulence 
pancreatitis 
gastrointestinal haemorrhage, ileus  

Hepatobiliary disorders 
Common: 
 
 
Uncommon: 
Rare: 

 
liver function tests raised (ALT increased, AST increased, 
bilirubin increased, alkaline phosphatase increased, GGT 
increased) 
hepatocellular damage*, hepatitis, jaundice, hepatomegaly 
hepatic failure, hepatitis cholestatic, cholestasis, 



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hepatosplenomegaly, liver tenderness, asterixis  

Skin and subcutaneous tissue 
disorders 
Common: 
Uncommon: 
Rare: 

 
 
rash  
mouth ulceration, alopecia 
Stevens Johnson syndrome, vesicular rash 

Musculoskeletal and connective 
tissue disorders 
Uncommon:  

 
 
back pain 

Renal and urinary disorders  
Uncommon: 
Rare:  

 
acute renal failure, renal failure, blood creatinine increased  
renal tubular acidosis, interstitial nephritis  

Reproductive system and breast 
disorders 
Uncommon: 
Rare:  

  
 
menstrual disorder 
breast pain 

General disorders and 
administration site conditions  
Common: 
Uncommon: 
Rare: 

 
 
pyrexia (fever), asthenia, fatigue 
oedema, pain, chills, malaise 
tongue oedema, face oedema 

Investigations 
 
 
Uncommon: 

 
medicine level changed  

§ See section 4.4. 
* During post-marketing surveillance severe hepatic injury with fatal outcome has been reported (see section 4.4). 
 
4.9 Overdose 
 
During clinical trials, patients who received posaconazole doses up to 1,600 mg/day experienced no 
different adverse reactions from those reported with patients at the lower doses. Accidental overdose 
was noted in one patient who took 1,200 mg twice a day for 3 days. No adverse reactions were noted 
by the investigator. 
 
Posaconazole is not removed by haemodialysis. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antimycotics for systemic use-triazole derivatives,  
ATC code: J02A C04. 
 
Mechanism of action 
Posaconazole inhibits the enzyme lanosterol 14α-demethylase (CYP51), which catalyses an essential 
step in ergosterol biosynthesis.  
 



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Microbiology 
Posaconazole has been shown in vitro to be active against the following microorganisms: Aspergillus 
species (Aspergillus fumigatus, A. flavus, A. terreus, A. nidulans, A. niger, A. ustus), Candida species 
(Candida albicans, C. glabrata, C. krusei, C. parapsilosis, C. tropicalis, C. dubliniensis, C. famata, C. 
inconspicua, C. lipolytica, C. norvegensis, C. pseudotropicalis), Coccidioides immitis, Fonsecaea 
pedrosoi, and species of Fusarium, Rhizomucor, Mucor, and Rhizopus. The microbiological data 
suggest that posaconazole is active against Rhizomucor, Mucor, and Rhizopus, however the clinical 
data are currently too limited to assess the efficacy of posaconazole against these causative agents. 
 
Resistance 
Clinical isolates with decreased susceptibility to posaconazole have been identified. The principle 
mechanism of resistance is the acquisition of substitutions in the target protein, CYP51.  
 
Combination with other antifungal agents 
The use of combination antifungal therapies should not decrease the efficacy of either posaconazole or 
the other therapies; however, there is currently no clinical evidence that combination therapy will 
provide an added benefit. 
 
Pharmacokinetic / Pharmacodynamic relationships: 
A correlation between total medicinal product exposure divided by MIC (AUC/MIC) and clinical 
outcome was observed. The critical ratio for subjects with Aspergillus infections was ~200. It is 
particularly important to try to ensure that maximal plasma levels are achieved in patients infected 
with Aspergillus (see sections 4.2 and 5.2 on recommended dose regimens and the effects of food on 
absorption). 
 
Clinical experience 
Invasive aspergillosis 
Oral posaconazole 800 mg/day in divided doses was evaluated for the treatment of invasive 
aspergillosis in patients with disease refractory to amphotericin B (including liposomal formulations) 
or itraconazole or in patients who were intolerant of these medicinal products in a non-comparative 
salvage therapy trial. Clinical outcomes were compared with those in an external control group 
derived from a retrospective review of medical records. The external control group included 
86 patients treated with available therapy (as above) mostly at the same time and at the same sites as 
the patients treated with posaconazole. Most of the cases of aspergillosis were considered to be 
refractory to prior therapy in both the posaconazole group (88 %) and in the external control group 
(79 %). 
 
As shown in Table 3, a successful response (complete or partial resolution) at the end of treatment was 
seen in 42 % of posaconazole-treated patients compared to 26 % of the external group. However, this 
was not a prospective, randomised controlled study and so all comparisons with the external control 
group should be viewed with caution.  
 
Table 3. Overall efficacy of posaconazole at the end of treatment for invasive aspergillosis in 
comparison to an external control group  
 Posaconazole External control group 
Overall Response 45/107 (42 %) 22/86 (26 %) 
Success by Species   
 All mycologically confirmed 
 Aspergillus spp.1 

 
34/76 

 
(45 %) 

 
19/74 

 
(26 %) 

 A. fumigatus 12/29 (41 %) 12/34 (35 %) 
 A. flavus 10/19 (53 %) 3/16 (19 %) 
 A. terreus 4/14 (29 %) 2/13 (15 %) 
 A. niger 3/5 (60 %) 2/7 (29 %) 
 
                                                      
1 Includes other less common species or species unknown 



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Fusarium spp.: 11 of 24 patients who had proven or probable fusariosis were successfully treated with 
posaconazole 800 mg/day in divided doses for a median of 124 days and up to 212 days. Among 
eighteen patients who were intolerant or had infections refractory to amphotericin B or itraconazole, 
seven patients were classed as responders.  
 
Chromoblastomycosis/Mycetoma: 9 of 11 patients were successfully treated with posaconazole 
800 mg/day in divided doses for a median of 268 days and up to 377 days. Five of these patients had 
chromoblastomycosis due to Fonsecaea pedrosoi and 4 had mycetoma, mostly due to Madurella 
species. 
 
Coccidioidomycosis: 11 of 16 patients were successfully treated (at the end of treatment complete or 
partial resolution of signs and symptoms present at baseline) with posaconazole 800 mg/day in divided 
doses for a median of 296 days and up to 460 days. 
 
Treatment of azole-susceptible Oropharyngeal Candidiasis (OPC) 
A randomised, evaluator-blind, controlled study was completed in HIV-infected patients with azole-
susceptible oropharyngeal candidiasis (most patients studied had C. albicans isolated at baseline). The 
primary efficacy variable was the clinical success rate (defined as cure or improvement) after 14 days 
of treatment. Patients were treated with posaconazole or fluconazole oral suspension (both 
posaconazole and fluconazole were given as follows: 100 mg twice a day for 1 day followed by 
100 mg once a day for 13 days). 
 
The clinical response rates from the above study are shown in the Table 4 below. 
Posaconazole was shown to be non-inferior to fluconazole for clinical success rates at Day 14 as well 
as 4 weeks after the end of treatment. 
 
Table 4. Clinical success rates in Oropharyngeal Candidiasis 
Endpoint Posaconazole Fluconazole 

Clinical success rate at Day 14 91.7 % (155/169) 92.5 % (148/160) 
Clinical success rate 4 weeks after end of treatment 68.5 % (98/143) 61.8 % (84/136) 
Clinical success rate was defined as the number of cases assessed as having a clinical response (cure or improvement) divided 
by the total number of cases eligible for analysis. 
 
Prophylaxis of Invasive Fungal Infections (IFIs) (Studies 316 and 1899) 
Two randomised, controlled prophylaxis studies were conducted among patients at high risk for 
developing invasive fungal infections. 
 
Study 316 was a randomised, double-blind trial of posaconazole oral suspension (200 mg three times a 
day) versus fluconazole capsules (400 mg once daily) in allogeneic hematopoietic stem cell transplant 
recipients with graft-versus-host disease (GVHD). The primary efficacy endpoint was the incidence of 
proven/probable IFIs at 16 weeks post-randomization as determined by an independent, blinded 
external expert panel. A key secondary endpoint was the incidence of proven/probable IFIs during the 
on-treatment period (first dose to last dose of study medicinal product + 7 days). The majority 
(377/600, [63 %]) of patients included had Acute Grade 2 or 3 or chronic extensive (195/600, 
[32.5 %]) GVHD at study start. The mean duration of therapy was 80 days for posaconazole and 
77 days for fluconazole. 
 
Study 1899 was a randomised, evaluator-blinded study of posaconazole oral suspension (200 mg three 
times a day) versus fluconazole suspension (400 mg once daily) or itraconazole oral solution (200 mg 
twice a day)  in neutropenic patients who were receiving cytotoxic chemotherapy for acute 
myelogenous leukemia or myelodysplastic syndromes. The primary efficacy endpoint was the 
incidence of proven/probable IFIs as determined by an independent, blinded external expert panel 
during the on-treatment period. A key secondary endpoint was the incidence of proven/probable IFIs 
at 100 days post-randomization. New diagnosis of acute myelogenous leukemia was the most common 
underlying condition (435/602, [72 %]). The mean duration of therapy was 29 days for posaconazole 
and 25 days for fluconazole/itraconazole. 



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In both prophylaxis studies, aspergillosis was the most common breakthrough infection. See Table 5 
and 6 for results from both studies. There were fewer breakthrough Aspergillus infections in patients 
receiving posaconazole prophylaxis when compared to control patients. 
 
Table 5. Results from clinical studies in prophylaxis of Invasive Fungal Infections. 

Study Posaconazole Controla P-Value 
Proportion (%) of patients with proven/probable IFIs 

On-treatment periodb 
1899d 7/304 (2) 25/298 (8) 0.0009 
316e 7/291 (2) 22/288 (8) 0.0038 

Fixed-time periodc 
1899d 14/304 (5) 33/298 (11) 0.0031 
316 d 16/301 (5) 27/299 (9) 0.0740 

FLU = fluconazole; ITZ = itraconazole; POS = posaconazole. 
a: FLU/ITZ (1899); FLU (316). 
b: In 1899 this was the period from randomization to last dose of study medicinal product plus 7 days; in 316 it was the 

period from first dose to last dose of study medicinal product plus 7 days. 
c: In 1899, this was the period from randomization to 100 days post-randomization; in 316 it was the period from the 

baseline day to 111 days post-baseline. 
d: All randomized  
e: All treated  

 



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Table 6. Results from clinical studies in prophylaxis of Invasive Fungal Infections. 
Study Posaconazole Controla  

Proportion (%) of patients with proven/probable Aspergillosis 
On-treatment periodb 

1899d 2/304 (1) 20/298 (7)  
316e 3/291 (1) 17/288 (6)  

Fixed-time periodc 
1899d 4/304 (1) 26/298 (9)  
316 d 7/301 (2) 21/299 (7)  

FLU = fluconazole; ITZ = itraconazole; POS = posaconazole. 
a: FLU/ITZ (1899); FLU (316). 
b: In 1899 this was the period from randomization to last dose of study medicinal product plus 7 days; in 316 it was the 

period from first dose to last dose of study medicinal product plus 7 days. 
c: In 1899, this was the period from randomization to 100 days post-randomization; in 316 it was the period from the 

baseline day to 111 days post-baseline. 
d: All randomized  
e: All treated  
 
In Study 1899, a significant decrease in all cause mortality in favour of posaconazole was observed 
[POS 49/304 (16 %) vs. FLU/ITZ 67/298 (22 %) p= 0.048]. Based on Kaplan-Meier estimates, the 
probability of survival up to day 100 after randomization, was significantly higher for posaconazole 
recipients; this survival benefit was demonstrated when the analysis considered all causes of death 
(P= 0.0354) as well as IFI-related deaths (P = 0.0209). 
 
In Study 316, overall mortality was similar (POS, 25 %; FLU, 28 %); however, the proportion of IFI-
related deaths was significantly lower in the POS group (4/301) compared with the FLU 
group (12/299; P= 0.0413). 
 
Use in paediatric patients 
Sixteen patients 8-17 years of age were treated with 800 mg/day in a study for invasive fungal 
infections. Based on the available data in 16 of these paediatric patients, the safety profile appears to 
be similar to patients ≥ 18 years of age. 
 
Additionally, twelve patients 13-17 years of age received 600 mg/day for prophylaxis of invasive 
fungal infections (Studies 316 and 1899). The safety profile in these patients < 18 years of age appears 
similar to the safety profile observed in adults. Based on pharmacokinetic data in 10 of these 
paediatric patients, the pharmacokinetic profile appears to be similar to patients ≥ 18 years of age. 
 
Safety and efficacy in paediatric patients below the age of 18 years have not been established.  
 
Electrocardiogram evaluation 
Multiple, time-matched ECGs collected over a 12 hour period were obtained before and during 
administration of posaconazole (400 mg twice daily with high fat meals) from 173 healthy male and 
female volunteers aged 18 to 85 years. No clinically relevant changes in the mean QTc (Fridericia) 
interval from baseline were observed. 
 
5.2 Pharmacokinetic properties 
 
Absorption  
Posaconazole is absorbed with a median tmax of 3 hours (fed patients). The pharmacokinetics of 
posaconazole are linear following single and multiple dose administration of up to 800 mg when taken 
with a high fat meal. No further increases in exposure were observed when doses above 800 mg daily 
were administered to patients and healthy volunteers. In the fasting state, AUC increased less than in 
proportion to dose above 200 mg. In healthy volunteers under fasting conditions, dividing the total 



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daily dose (800 mg) into 200 mg four times daily compared to 400 mg twice daily, was shown to 
increase posaconazole exposure by 58 % over 48 hours. 
 
Effect of food on oral absorption in healthy volunteers 
The AUC of posaconazole is about 2.6 times greater when administered with a non-fat meal or 
nutritional supplement (14 grams fat) and 4 times greater when administered with a high-fat meal 
(~ 50 grams fat) relative to the fasted state. Posaconazole should be administered with food or a 
nutritional supplement (see section 4.2). 
 
Distribution 
Posaconazole is slowly absorbed and slowly eliminated with a large apparent volume of distribution 
(1,774 litres) and is highly protein bound (> 98 %), predominantly to serum albumin. 
 
Metabolism 
Posaconazole does not have any major circulating metabolites and its concentrations are unlikely to be 
altered by inhibitors of CYP450 enzymes. Of the circulating metabolites, the majority are glucuronide 
conjugates of posaconazole with only minor amounts of oxidative (CYP450 mediated) metabolites 
observed. The excreted metabolites in urine and faeces account for approximately 17 % of the 
administered radiolabelled dose. 
 
Excretion 
Posaconazole is slowly eliminated with a mean half-life (t½) of 35 hours (range 20 to 66 hours). After 
administration of 14C-posaconazole, radioactivity was predominantly recovered in the faeces (77 % of 
the radiolabelled dose) with the major component being parent compound (66 % of the radiolabelled 
dose). Renal clearance is a minor elimination pathway, with 14 % of the radiolabelled dose excreted in 
urine (< 0.2 % of the radiolabelled dose is parent compound). Steady-state is attained following 7 to 
10 days of multiple-dose administration. 
 
Pharmacokinetics in special populations 
Children (< 18 years) 
Following administration of 800 mg per day of posaconazole as a divided dose for treatment of 
invasive fungal infections, mean trough plasma concentrations from 12 patients 8 - 17 years of age 
(776 ng/ml) were similar to concentrations from 194 patients 18 - 64 years of age (817 ng/ml). No 
pharmacokinetic data are available from paediatric patients less than 8 years of age. Similarly, in the 
prophylaxis studies, the mean steady-state posaconazole average concentration (Cav) was comparable 
among ten adolescents (13-17 years of age) to Cav achieved in adults (≥ 18 years of age). 
 
Gender 
The pharmacokinetics of posaconazole are comparable in men and women. 
 
Elderly (≥ 65 years) 
An increase in Cmax (26 %) and AUC (29 %) was observed in elderly subjects (24 subjects ≥ 65 years 
of age) relative to younger subjects (24 subjects 18 - 45 years of age). However, in clinical efficacy 
trials, the safety profile of posaconazole between the young and elderly patients was similar. 
 
Race 
There was a slight decrease (16 %) in the AUC and Cmax of posaconazole in Black subjects relative to 
Caucasian subjects. However, the safety profile of posaconazole between the Black and Caucasian 
subjects was similar. 
 
Renal impairment 
Following single-dose administration, there was no effect of mild and moderate renal impairment 
(n=18, Cl cr ≥ 20 ml/min/1.73 m2) on posaconazole pharmacokinetics; therefore, no dose adjustment is 
required. In subjects with severe renal impairment (n=6, Cl cr < 20 ml/min/1.73 m2), the AUC of 
posaconazole was highly variable [> 96 % CV (coefficient of variance)] compared to other renal 
groups [< 40 % CV]. However, as posaconazole is not significantly renally eliminated, an effect of 



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severe renal impairment on the pharmacokinetics of posaconazole is not expected and no dose 
adjustment is recommended. Posaconazole is not removed by haemodialysis. 
 
Hepatic impairment 
In a study with small number of subjects (n=12) who had hepatic impairment, there was an increase in 
exposure associated with prolongation of half-life in hepatic impaired patients (26.6, 35.3, and 
46.1 hours for the mild, moderate and severe groups, respectively compared to 22.1 hours in subjects with 
normal hepatic function). An approximately 2-fold increase in steady-state AUC is estimated in patients 
with severe hepatic impairment. Due to the limited pharmacokinetic data in patients with hepatic 
impairment, posaconazole should be used with caution in patients with severe hepatic impairment 
since the prolonged half-life that may occur will lead to increased exposure. 
 
5.3 Preclinical safety data 
 
As observed with other azole antifungal agents, effects related to inhibition of steroid hormone 
synthesis were seen in repeated-dose toxicity studies with posaconazole. Adrenal suppressive effects 
were observed in toxicity studies in rats and dogs at exposures equal to or greater than those obtained 
at therapeutic doses in humans.  
 
Neuronal phospholipidosis occurred in dogs dosed for ≥ 3 months at lower systemic exposures than 
those obtained at therapeutic doses in humans. This finding was not seen in monkeys dosed for one 
year. In twelve-month neurotoxicity studies in dogs and monkeys, no functional effects were observed 
on the central or peripheral nervous systems at systemic exposures greater than those achieved 
therapeutically. 
 
Pulmonary phospholipidosis resulting in dilatation and obstruction of the alveoli was observed in the 
2-year study in rats. These findings are not necessarily indicative of a potential for functional changes 
in humans. 
 
No effects on electrocardiograms, including QT and QTc intervals, were seen in a repeat dose safety 
pharmacology study in monkeys at systemic exposures 4.6-fold greater than the exposures obtained at 
therapeutic doses in humans. Echocardiography revealed no indication of cardiac decompensation in a 
repeat dose safety pharmacology study in rats at a systemic exposure 1.4-fold greater than that 
achieved therapeutically. Increased systolic and arterial blood pressures (up to 29 mm-Hg) were seen 
in rats and monkeys at systemic exposures 1.4-fold and 4.6-fold greater, respectively, than those 
achieved with therapeutic doses. 
 
Reproduction, peri- and postnatal development studies were conducted in rats. At exposures lower 
than those obtained at therapeutic doses in humans, posaconazole caused skeletal variations and 
malformations, dystocia, increased length of gestation, reduced mean litter size and postnatal viability. 
In rabbits, posaconazole was embryotoxic at exposures greater than those obtained at therapeutic 
doses. As observed with other azole antifungal agents, these effects on reproduction were considered 
to be due to a treatment-related effect on steroidogenesis. 
 
Posaconazole was not genotoxic in in vitro and in vivo studies. Carcinogenicity studies did not reveal 
special hazards for humans. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Polysorbate 80 
Simeticone 
Sodium benzoate (E211) 
Sodium citrate dihydrate 



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Citric acid monohydrate 
Glycerol 
Xanthan gum 
Liquid glucose 
Titanium dioxide (E171) 
Artificial cherry flavour containing benzyl alcohol and propylene glycol 
Purified water 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
Unopened container: 2 years 
 
After first opening the container: 4 weeks. 
 
6.4 Special precautions for storage 
 
Do not freeze. 
 
6.5 Nature and contents of container 
 
105 ml of oral suspension in a 123 ml bottle (glass amber type IV) closed with a plastic child-resistant 
cap (polypropylene) and a measuring spoon (polystyrene) with 2 graduations: 2.5 ml and 5 ml. 
 
6.6 Special precautions for disposal  
 
No special requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
SP Europe 
Rue de Stalle, 73 
B-1180 Bruxelles 
Belgium 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/05/321/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
25 October 2005 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web 
site: http://www.emea.europa.eu/ 



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17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 
A. MANUFACTURING AUTHORISATION HOLDER 

RESPONSIBLE FOR BATCH RELEASE 
 
B. CONDITIONS OF THE MARKETING AUTHORISATION 
 



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A MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH 
RELEASE 

 
Name and address of the manufacturer responsible for batch release 
 
Schering-Plough S.A., 2, rue Louis Pasteur; 14200 Hérouville St Clair, France 
 
 
B CONDITIONS OF THE MARKETING AUTHORISATION 
 
• CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON 

THE MARKETING AUTHORISATION HOLDER 
 
Medicinal product subject to restricted medical prescription. (See Annex I: Summary of Product 
Characteristics, 4.2) 
 
• CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
Not applicable. 
 
 
 
 
 



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ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



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20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
BOTTLE (Outer Carton) 

 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Posaconazole SP 40 mg/ml oral suspension 
posaconazole 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each ml of oral suspension contains 40 mg of posaconazole. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains also liquid glucose. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
One bottle of 105 ml of oral suspension 
Measuring spoon 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use 
Shake well before use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP  
Any product remaining four weeks after opening the bottle should be discarded. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not freeze. 



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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 
 
SP Europe 
Rue de Stalle, 73 
B-1180 Bruxelles, Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/05/321/001  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Posaconazole SP 



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PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
BOTTLE (Bottle label) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Posaconazole SP 40 mg/ml oral suspension 
posaconazole 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each ml of oral suspension contains 40 mg of posaconazole. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains also liquid glucose. 
See leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
One bottle of 105 ml of oral suspension 
Measuring spoon 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use 
Shake well before use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
 
8. EXPIRY DATE 
 
EXP  
Any product remaining four weeks after opening the bottle should be discarded. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not freeze. 



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24 

 
 
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 
 
SP Europe 
Rue de Stalle, 73 
B-1180 Bruxelles, Belgium 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/05/321/001  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 



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B. PACKAGE LEAFLET 



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PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Posaconazole SP 40 mg/ml oral suspension 
posaconazole 

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

if their symptoms are the same as yours. 
- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, 

please tell your doctor or pharmacist. 
 
In this leaflet:  
1. What Posaconazole SP is and what it is used for 
2. Before you take Posaconazole SP 
3. How to take Posaconazole SP 
4. Possible side effects 
5. How to store Posaconazole SP 
6. Further information 
 
 
1. WHAT POSACONAZOLE SP IS AND WHAT IT IS USED FOR 
 
Posaconazole SP belongs to a group of medicines called triazole antifungal agents. These medicines 
are used to prevent and treat a wide variety of fungal infections. Posaconazole SP works by killing or 
stopping the growth of some types of fungi that can cause infections in humans. 
 
Posaconazole SP can be used to treat the following types of fungal infections in adults: 
- Infections caused by fungi of the Aspergillus family that have not improved during treatment 

with the anti-fungal medicines amphotericin B or itraconazole or when these medicines have 
had to be stopped; 

- Infections caused by fungi of the Fusarium family that have not improved during treatment with 
amphotericin B or when amphotericin B has had to be stopped; 

- Infections caused by fungi that cause the conditions known as chromoblastomycosis and 
mycetoma that have not improved during treatment with itraconazole or when itraconazole has 
had to be stopped; 

- Infections due to fungi called Coccidioides that have not improved during treatment with one or 
more of amphotericin B, itraconazole or fluconazole or when these medicines have had to be 
stopped; 

- Infections in the mouth or throat area (known as “thrush”) caused by fungi called Candida, 
which are initial infections. 

 
Posaconazole SP can be used to prevent fungal infections in patients whose immune systems may be 
weakened due to other medicines or diseases. 
 
 
2. BEFORE YOU TAKE POSACONAZOLE SP 
 
Do not take Posaconazole SP 
- If you are allergic (hypersensitive) to posaconazole or to any of the other ingredients of 

Posaconazole SP. 
- If you are taking medicines that contain ergot alkaloids (used to treat migraines). Posaconazole 

can increase the blood levels of these medicines, which can lead to severe reductions in blood 
flow to some parts of the body and damage tissues. 



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- If you are taking any of the following medicines. Posaconazole can increase the blood levels of 
these medicines, which can lead to very serious disturbances in heart rhythm: 
• terfenadine (used to treat allergies) 
• astemizole (used to treat allergies) 
• cisapride (used to treat stomach problems) 
• pimozide (used to treat symptoms of Tourette's disorder) 
• halofantrine (used to treat malaria) 
• quinidine (used to treat abnormal heart rhythms). 

- If you are taking simvastatin, lovastatin, atorvastatin and some similar medicines (called HMG-
 CoA reductase inhibitors or statins) that are used to treat high cholesterol levels in the blood. 
 
Please see the section “Taking other medicines” for information on other medicines which may 
interact with Posaconazole SP. 
 
Take special care with Posaconazole SP 
Ask your doctor or pharmacist for advice before taking any medicine. In addition to the medicines 
named above that must not be taken with posaconazole because of the risk of heart rhythm 
disturbances, there are other medicines that carry a risk of rhythm problems that may be greater when 
they are taken with posaconazole. Please make sure you tell your doctor about all the medicines you 
are taking (prescribed or non prescribed). 
 
Tell your doctor: 
- If you have ever had an allergic reaction to other medicines of the azole or triazole family. 

These include ketoconazole, fluconazole, itraconazole and voriconazole. 
- If you have or have had liver problems. You may need special blood tests to be done while you 

are taking Posaconazole SP. 
- If you have kidney problems and are taking medicines that affect the kidney. 
- If you develop severe diarrhoea or vomiting, as these conditions may limit the effectiveness of 

Posaconazole SP. 
- If you have ever been told that you have any of the following conditions: 

• An abnormal heart rhythm tracing (ECG) that shows a problem called long QTc interval 
• A weakness of the heart muscle or heart failure 
• A very slow heartbeat 
• Any heart rhythm disturbance 
• Any problem with amounts of potassium, magnesium or calcium in your blood. 

 
Please note that Posaconazole SP is only for use in adults (older than 18 years of age). 
 
Taking other medicines 
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, 
including medicines obtained without a prescription. 
Please look at the list of medicines that must not be taken while you are taking Posaconazole SP that is 
given above.  
There are other medicines that can sometimes be given while you are taking Posaconazole SP but 
special care may be needed. 
 
Certain medicines may increase (possibly increasing the risk of side effects) or decrease (possibly 
causing lack of effectiveness) the blood levels of posaconazole.  
Medicines that can decrease blood levels of posaconazole include:  
• Rifabutin and rifampicin (used to treat certain infections). If you are already being treated with 

rifabutin, your blood counts and some possible side effects to rifabutin will need to be 
monitored. 

• Some medicines used to treat or prevent fits, such as phenytoin, carbamazepine, phenobarbital, 
primidone.  

• Efavirenz, which is used to treat HIV infection.  



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• Medicines used to decrease stomach acid such as cimetidine and ranitidine or omeprazole and 
similar medicines that are called proton pump inhibitors. 

 
Posaconazole SP may increase (possibly increasing the risk of side effects) the blood levels of some 
other medicines. These include: 
• Vincristine, vinblastine and other vinca alkaloids (used to treat cancer) 
• Ciclosporin (used in transplant surgery) 
• Tacrolimus and sirolimus (used in transplant surgery) 
• Rifabutin (used to treat certain infections) 
• Medicines used to treat HIV called protease inhibitors (including lopinavir and atazanavir, 

which are given with ritonavir) and non nucleoside reverse transcriptase inhibitors (NNRTIs) 
• Midazolam, triazolam, alprazolam and some similar medicines called benzodiazepines (used as 

sedatives or muscle relaxants) 
• Diltiazem, verapamil, nifedipine, nisoldipine and some of the other medicines called calcium 

channel blockers (used to treat high blood pressure) 
• Digoxin (used to treat heart failure) 
• Sulfonylureas such as glipizide (used to treat high blood sugar). 
 
Taking Posaconazole SP with food and drink 
Each dose of Posaconazole SP should be taken with food or a nutritional supplement if you are unable 
to tolerate food to enhance the oral absorption. See section 3 of this leaflet for more information on 
how to take the suspension. 
 
Pregnancy and breast-feeding 
Tell your doctor if you are or think you are pregnant before you start to take Posaconazole SP. Do not 
use Posaconazole SP during pregnancy unless you are told by your doctor. You should use effective 
contraception while you are taking Posaconazole SP if you are a woman who could become pregnant. 
Contact your doctor immediately if you become pregnant while being treated with Posaconazole SP. 
 
Do not breast-feed while being treated with Posaconazole SP.  
 
Driving and using machines 
There is no information on the effect of Posaconazole SP on the ability to drive and use machines. 
Please inform your doctor if you experience any effects that may cause you to have problems with 
driving or using other machinery such as sleepiness or blurred vision. 
 
Important information about some of the ingredients of Posaconazole SP 
Posaconazole SP contains approximately 1.75 g of glucose per 5 ml of suspension. You should not 
take this medicine if you have a condition called glucose-galactose malabsorption and should take note 
of this amount of glucose if you need to watch your sugar intake for any reason. 
 
 
3. HOW TO TAKE POSACONAZOLE SP 
 
Posaconazole SP must only be used as directed by your doctor. Your doctor will monitor your 
response and condition to determine how long Posaconazole SP needs to be given and whether any 
change is needed to your daily dose.  



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Indication Dose  
Treatment of refractory 
Fungal Infections  
 

Take 400 mg (two 5 ml spoonfuls) of the suspension twice a 
day with food or with a nutritional supplement if you are 
unable to tolerate food. If you are not able to take food or 
nutritional supplement, your doctor will tell you to take 
200 mg (one 5 ml spoonful) four times a day.  

Initial treatment of Thrush On the first day of treatment take 200 mg (one 5 ml spoonful) 
once. After the first day, take 100 mg (2.5 ml) once a day with 
food or nutritional supplement if you are unable to tolerate 
food. 

Prevention of serious Fungal 
Infections 

Take 200 mg (one 5 ml spoonful) three times a day with food 
or nutritional supplement if you are unable to tolerate food. 

 
If you take more Posaconazole SP than you should 
If you are concerned that you may have taken too much, contact your doctor or healthcare professional 
immediately. 
 
If you forget to take Posaconazole SP 
If you have missed a dose, take it as soon as you remember and then carry on as before. However, if it 
is almost time for your next dose, take your dose when it is due. Do not take a double dose to make up 
for a forgotten dose.  
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Posaconazole SP can cause side effects, although not everybody gets them.  
 
Common side effects (occurring in at least 1 in 100 patients) are: 
Headache, dizziness, numbness or tingling 
Sleepiness 
Nausea (feeling or being sick), loss of appetite, stomach pain, diarrhoea, upset stomach, vomiting, 
wind, dry mouth 
Abnormal liver function tests 
Rash  
Weakness, tiredness 
A decrease in white blood cells (that can increase the risk of infections)  
Fever 
Abnormal levels of salts in the blood. 
 
Uncommon side effects (occurring in at least 1 in 1,000 patients) are: 
Anaemia, low numbers of cells called platelets that help the blood to clot, low numbers of some types 
of white blood cells, enlargement of lymph glands 
Allergic reaction  
High blood levels of glucose 
Disturbances in feeling or moving, tremor, fits 
Heart rhythm problems including very fast heartbeat (palpitations), abnormal findings on heart tests 
(like ECGs that show heart rhythm)  
High or low blood pressure 
Inflammation of the pancreas  
Inflammation of liver, liver damage, jaundice (yellow colour of the skin or the eyes) 
Problems with kidney function, failure of the kidneys  
Menstrual disorder 
Blurred vision 
Hair loss, itching 
Mouth ulcers 



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Shivering, generally feeling unwell or weak 
Scattered body pain, including in muscles and joints, back pain 
Fluid retention, altered medicine levels. 
 
Rare side effects (occurring in at least 1 in 10,000 patients) are: 
Pneumonia and other lung damage 
Low numbers of all blood cells, blood clotting disorder, bleeding 
Severe allergic reactions, including widespread blistering rash and skin peeling 
Poor functioning of the adrenal gland 
Altered brain function, fainting  
Sudden behaviour changes, problems with thinking or speech 
Pain, weakness, numbness, or tingling in the arm or leg 
Depression 
Double vision, a blind or dark spot in the visual field 
Hearing problems  
Heart failure or heart attack, heart rhythm disorders 
Stroke, blood clots in brain, limbs or lungs 
Bleeding into the gut 
Inflammation or failure of the liver, rarely leading to death 
Enlargement of both the liver and spleen, liver tenderness 
Blistering rash, large purple discolourations on the skin caused by bleeding underneath the skin  
Inflammation of the kidneys  
Breast pain 
Swelling of the face or tongue. 
 
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please 
tell your doctor or pharmacist. 
 
 
5. HOW TO STORE POSACONAZOLE SP 
 
Keep out of the reach and sight of children. 
 
Do not freeze. 
 
Do not use Posaconazole SP after the expiry date which is stated on the label. The expiry date refers to 
the last day of that month. 
 
If you have any suspension left in a bottle more than four weeks after it was first opened, you should 
not use this medicine. Please return the bottle containing any left over suspension to your pharmacist. 
 
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to 
dispose of medicines no longer required. These measures will help to protect the environment. 
 
 
6. FURTHER INFORMATION 
 
What Posaconazole SP contains 
 
- The active substance in Posaconazole SP oral suspension is posaconazole. Each millilitre of oral 

suspension contains 40 milligrams of posaconazole. 
- The other ingredients in the suspension are polysorbate 80, simeticone, sodium benzoate 

(E211), sodium citrate dihydrate, citric acid monohydrate, glycerol, xanthan gum, liquid 
glucose, titanium dioxide (E171), artificial cherry flavour containing benzyl alcohol and 
propylene glycol, and purified water. 

 



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What Posaconazole SP looks like and contents of the pack 
 
Posaconazole SP is a white, cherry flavoured, 105 ml oral suspension packaged in amber glass bottles. 
A measuring spoon is provided with each bottle for measuring 2.5 and 5 ml doses of the oral 
suspension. 
 
Marketing Authorisation Holder and Manufacturer 
 
Marketing Authorisation Holder:  
SP Europe 
Rue de Stalle, 73 
B-1180 Bruxelles 
Belgium 
 
Manufacturer:  
SP S.A. 
2, rue Louis Pasteur 
F-14200 Hérouville St Clair 
France 
 
For any information about this medicinal product, please contact the local representative of the 
Marketing Authorisation Holder: 
 
België/Belgique/Belgien 
Rue de Stalle/Stallestraat 73 
B-1180 Bruxelles/Brussel/Brüssel 
Tél/Tel: + 32-(0)2 370 92 11 
 

Luxembourg/Luxemburg 
Rue de Stalle 73 
B-1180 Bruxelles/Brüssel 
Belgique/Belgien 
Tél/Tel: + 32-(0)2 370 92 11 
 

България 
Ийст Парк Трейд Център 
Бул. „Н.Й.Вапцаров” 53А, ет. 2 
BG-София 1407  
Тел.: +359 2 806 3030 
 

Magyarország 
Alkotás u. 53. 
H-1123 Budapest 
Tel.: +36 1 457-8500 

Česká republika 
Na Příkopě 25 
CZ-110 00 Praha 1 
Tel: +420 221771250 
 

Malta 
168 Christopher Street 
MT-VLT02 Valletta 
Tel: + 356-21 23 21 75 
 

Danmark 
Lautrupbjerg 2 
DK-2750 Ballerup 
Tlf: + 45-44 39 50 00 
 

Nederland 
Maarssenbroeksedijk 4 
NL-3542 DN Utrecht 
Tel: + 31-(0)800 778 78 78 
 

Deutschland 
Thomas-Dehler-Straße 27 
D-81737 München  
Tel: + 49-(0)89 627 31-0 
 

Norge 
Pb. 398 
N-1326 Lysaker  
Tlf: + 47 67 16 64 50 

Eesti 
Järvevana tee 9 
EE-11314 Tallinn 
Tel: + 372 654 96 86 
 

Österreich 
Am Euro Platz 2 
A-1120 Wien 
Tel: + 43-(0) 1 813 12 31 
 

Ελλάδα Polska 



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Αγίου Δημητρίου 63 
GR-174 55 Άλιμος  
Tηλ.: + 30-210 98 97 300 
 

Ul. Taśmowa 7 
PL-02-677 Warszawa 
Tel.: + 48-(0)22 478 41 50 
 

España 
Km. 36, Ctra. Nacional I 
E-28750 San Agustín de Guadalix – Madrid 
Tel: + 34-91 848 85 00 
 

Portugal 
Rua Agualva dos Açores 16 
P-2735-557 Agualva-Cacém 
Tel: +351-21 433 93 00 
 

France 
92 rue Baudin  
F-92300 Levallois-Perret 
Tél: + 33-(0)1 41 06 35 00 
 

România 
Şos. Bucureşti-Ploieşti, nr. 17-21,  
Băneasa Center, et. 8, sector 1 
RO-013682 Bucureşti 
Tel. + 40 21 233 35 30 
 

Ireland 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW 
Tel: +44-(0)1 707 363 636 
 

Slovenija 
Dunajska 22 
SI-1000 Ljubljana 
Tel: + 386 01 3001070 
 

Ísland 
Hörgatún 2 
IS-210 Garðabær 
Sími: + 354 535 70 00 
 

Slovenská republika 
Strakova 5 
SK-811 01 Bratislava 
Tel: + 421 (2) 5920 2712 
 

Italia 
Via fratelli Cervi snc, 
Centro Direzionale Milano Due 
Palazzo Borromini 
I-20090 Segrate (Milano) 
Tel: + 39-02 21018.1 
 

Suomi/Finland 
PL 86/PB 86 
FIN-02151 Espoo/Esbo 
Puh/Tel: + 358-(0)20-7570 300 
 

Κύπρος 
Οδός Αγίου Νικολάου, 8 
CY-1055 Λευκωσία 
Τηλ: +357-22 757188 
 

Sverige 
Box 6185 
S-102 33 Stockholm 
Tel: + 46-(0)8 522 21 500 
 

Latvija 
Bauskas 58a -401 
Rīga, LV-1004  
Tel: + 371-7 21 38 25 
 

United Kingdom 
Shire Park 
Welwyn Garden City 
Hertfordshire AL7 1TW - UK 
Tel: + 44-(0)1 707 363 636 
 

Lietuva 
Kęstučio g. 65/40 
LT-08124 Vilnius 
Tel. + 370 52 101868 
 

 

 
This leaflet was last approved on  
 
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web site: 
http://www.emea.europa.eu/ 


	ANNEX ISUMMARY OF PRODUCT CHARACTERISTICS
	A MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCHRELEASE
	B CONDITIONS OF THE MARKETING AUTHORISATION
	A. LABELLING
	B. PACKAGE LEAFLET