Pentasa Sachet 4g prolonged release granules

To update section 2.0 & 4.0 of the leaflet

Drug reaction with eosinophilia and systemic symptoms (DRESS) is moved from ‘Very rare’ to ‘Not known’ in section 4.8 SmPC in line with the PRAC recommendation. In the ADR table in section 4.8 SmPC a footnote is added to urine discolouration with reference to the new warning re urine discolouration in section 4.4 SmPC. 

Update to Section 4.4, to add sentence 'Cases of nephrolithiases have been reported with the use of mesalazine including stones with a 100% mesalazine content. It is recommended to ensure adequate fluid intake during treatment.'

Update to Section 4.8, to add column for 'Not known (cannot be estimated from the available data' and include 'Nephrolithiasis' in the Renal and Urinary disorders row

Update to Section 4.2, to add sentence 'Alternatively the entire content of the sachet can be taken with yogurt and consumed immediately.'

SmPC Section 9 update - Added date of last renewal

Section 4.8

“Photosensitivity” added as a rare side effect with the footnote “More severe reactions are reported in patients with pre-existing skin conditions such as atopic dermatitis and atopic eczema.”

Other minor updates in the table in Section 4.8:

-          “blood disorders” updated to “altered blood counts”

-          “allergic exanthema” reworded to “dermatitis allergic” and relocated to section for skin and subcutaneous tissue disorders

-          “drug fever” moved to section for general disorders and administration site conditions.

Section 4.6:

Sentence update: “Mesalazine is known to cross the placental barrier and its concentration in umbilical cord plasma is lower than the concentration in maternal plasma.  The metabolite acetyl-mesalazine is found at similar concentrations in umbilical cord and maternal plasma. “

New sentence: “The underlying condition itself (Inflammatory bowel disease (IBD) may increase risks for adverse pregnancy outcome.”

New text:  “There are no adequate and well controlled studies of Pentasa use in pregnant women. Limited published human data on mesalazine show no increase in the overall rate of congenital malformations.  Some data show an increased rate of preterm birth, stillbirth, and low birth weight; however, these adverse pregnancy outcomes are also associated with active inflammatory bowel disease. “

Section 4.8

Adverse events updated, see SPC for full updated list.

Section 4.9

New sentences:

“Since Pentasa is an amino salicylate, symptoms of salicylate toxicity may occur.  Symptoms of salicylate over dosage are well described in the literature.  “

“There is no specific antidote and the management of overdose is supportive and symptomatic. The treatment at hospital includes close monitoring of renal function.”

Deleted text:

“There is no specific antidote and treatment is symptomatic and supportive.”

“Management of overdose in man:

Symptomatic treatment at hospital. Close monitoring of renal function. Intravenous infusion of electrolytes may be used to promote diuresis.”

Section 5.1

New sections:

“It has been established that mesalazine is the active component of sulphasalazine which is used for the treatment of ulcerative colitis and Crohn’s disease.  Based on clinical results, the therapeutic value of mesalazine after oral as well as rectal administration appears to be due to local effect on the inflamed intestinal tissue, rather than to systemic effect.  There is information suggesting that severity of colonic inflammation in ulcerative colitis patients treated with mesalazine is inversely correlated with mucosal concentrations of mesalazine. “

“The mechanism of action of mesalazine is not fully understood although mechanisms such as activation of the γ-form of peroxisome proliferator-activated receptors (PPAR-γ) and inhibition of nuclear factor-kappa B (NF-κB) in the intestinal mucosa has been implicated. “

“It is currently unknown which, if any, of these mechanisms play a predominant role in the clinical efficacy of mesalazine.”

Sections 5.2 and 5.3

Full updates, see SPC for text.

Section 4.6:

Sentence update: “Mesalazine is known to cross the placental barrier and its concentration in umbilical cord plasma is lower than the concentration in maternal plasma.  The metabolite acetyl-mesalazine is found at similar concentrations in umbilical cord and maternal plasma. “

New sentence: “The underlying condition itself (Inflammatory bowel disease (IBD) may increase risks for adverse pregnancy outcome.”

New text:  “There are no adequate and well controlled studies of Pentasa use in pregnant women. Limited published human data on mesalazine show no increase in the overall rate of congenital malformations.  Some data show an increased rate of preterm birth, stillbirth, and low birth weight; however, these adverse pregnancy outcomes are also associated with active inflammatory bowel disease. “

Section 4.8

Adverse events updated, see SPC for full updated list.

Section 4.9

New sentences:

“Since Pentasa is an amino salicylate, symptoms of salicylate toxicity may occur.  Symptoms of salicylate over dosage are well described in the literature.  “

“There is no specific antidote and the management of overdose is supportive and symptomatic. The treatment at hospital includes close monitoring of renal function.”

Deleted text:

“There is no specific antidote and treatment is symptomatic and supportive.”

“Management of overdose in man:

Symptomatic treatment at hospital. Close monitoring of renal function. Intravenous infusion of electrolytes may be used to promote diuresis.”

Section 5.1

New sections:

“It has been established that mesalazine is the active component of sulphasalazine which is used for the treatment of ulcerative colitis and Crohn’s disease.  Based on clinical results, the therapeutic value of mesalazine after oral as well as rectal administration appears to be due to local effect on the inflamed intestinal tissue, rather than to systemic effect.  There is information suggesting that severity of colonic inflammation in ulcerative colitis patients treated with mesalazine is inversely correlated with mucosal concentrations of mesalazine. “

“The mechanism of action of mesalazine is not fully understood although mechanisms such as activation of the γ-form of peroxisome proliferator-activated receptors (PPAR-γ) and inhibition of nuclear factor-kappa B (NF-κB) in the intestinal mucosa has been implicated. “

“It is currently unknown which, if any, of these mechanisms play a predominant role in the clinical efficacy of mesalazine.”

Sections 5.2 and 5.3

Full updates, see SPC for text.