Raceca

COMPOSITION

Each Capsule contains;

Racecadotril……………. 100mg  

Each Dispersible Tablet contains;                        

Racecadotril……………10mg

                  

DESCRIPTION
Racecadotril, also known as acetorphan, is an antidiarrheal drug which acts as a peripherally acting enkephalinase  inhibitor.Unlike other medications used to treat diarrhea, which reduce intestinal motility, racecadotril has an antisecretory effect—it reduces the secretion of water and electrolytes into the intestine.It is available in France since 20 years (where it was first introduced in 1993 and is widely used) and other European countries, as well as most of South America and some South East Asian countries,  and it  lunched in United States since October 2012. It is sold under the tradenames Hidrasec or, in France, Tiorfan. In Italy it is sold under the trade name Tiorfix and in Nepal it was introduced by Alive pharmaceuticals under the trade name Raceca.
A small randomized controlled trial found racecadotril to significantly reduce the duration and volume of watery diarrhea in children when given as an adjunct to oral rehydration therapy.
Thiorphan is the active metabolite of racecadotril.

Chemical structures of racecadotril and its two metabolites thiorphan and acetyl-thiorphan. The arrows indicate the sites of metabolization; the asterisk indicates the chiral center of the molecule.

PHARMACODYNAMIC

MECHANISM OF ACTION;

[3-acetylmercapto-2-benzylpropanoyl] - glycine, benzyl ester, is a lipophilic derivative of thiorphan.

 Racecadotril is rapidly converted in the body to thiorphan, a potent enkephalinase inhibitor. Enkephalins are endogenous opioid peptides secreted by myenteric and sub  mucosal neurons in the digestive tract. The enkephalins by activating the δ opioid receptor, inhibit the secretion of Cl–  and fluids thus reducing the loss of fluids and electrolytes during diarrhea.

The anti- secretory  mechanisms are independent of effects on intestinal motility, differentiating this compound from µ- opiate   receptor  agonists  like  loperamide  and diphenoxylate. Experimental studies in rodents and human volunteers demonstrated no delay on gastrointestinal transit or increase in experimental bacterial proliferation in small bowel of germ free piglets with racecadotril as compared to loperamide.

PHARMACOKINETICS ]

 Onset

A.    INITIAL RESPONSE;

                         1.PLASMA ENKEPHALINASE INHIBITION, ORAL ;  30 minutes ( 100mg orally)

B.     PEAK RESPONSE;
      

                             1. ACUTE DIARRHEA,ORAL; with in 24 hours

                             

                             2. .PLASMA ENKEPHALINASE INHIBITION, ORAL ; 60 minutes( 100mg orally)

DURATION

A.    SINGLE DOSE;

1.PLASMA ENKEPHALINASE  INHIBITION ORAL;  upto 8 hours( 100mg orally)

           

  a.  The biological half life of enkephalinase activity was approximately 3 hours following oral doses of 30 to 300mg in healthy subjects.

 Absorption:

 Racecadotril is quickly absorbed orally in intestinal tract and get converted into its active metabolite Thiorphan.The inhibiting activity of the plasmatic encephalinase appears in 30 minute. The duration of inhibiting activity on the plasma encephalinase is of approximately 3 hours. The half life is 3-4 hours. The bioavailability data of Racecadotril is not available.

Distribution:    

    The racecadotril is fixed at 90% on plasma proteins (mainly albumin).. The available data suggests that it does not cross the hemato-encephalic barrier at the oral dose upto 20mg/kg.

Metabolism:

Racecadotril is a prodrug, which hydrolyzed to thiorphan as active metabolites and thiorphan methylester as inactive metabolite.

Elimination:

Racecadotril is eliminated in the urine. The repeated administration of racecadotril does not modify its pharmacokinetic properties and does not involve accumulation in the body.

Renal way: Elimination in form of metabolites

Fecal way: Elimination in the form of metabolite

INDICATIONS AND DOSAGE;

A.    DIARRHEA – ACUTE

1.      OVERVIEW ;

                              

                 EFFICACY;   Adult;   effective,

                                       Pediatric;  effective

                DOCUMENTATION;  Adult;  good,

                                                Pediatric; good

2.      SUMMERY;

Oral therapy has been effective in treating acute diarrhea in adults and children, and comparable in efficacy to loperamide.

A reduced requirements for rehydration has been seen during racecadotril therapy.

3.      ADULT;

ORAL racecadotril has been superior to placebo and effective as oral loperamide in the treatment of ACUTE DIARRHEA of presumed infections origin in randomized, double-blind studies( Baumer et al,1992;Matheson & Noble,2000; Vetel Et al,1999; Lecomte,2000). The Usual  dose in these studies was 100 milligram (mg) three times daily.

b. In one study ( n=70), using stool weight as the criterion for anti secretory activity, the mean stool weight  during the first day of treatment was 355g with racecadotril 100mg three times daily compared to 499 g in placebo group( 29% decreases with Racecadotril). The frequency of diarrheic stools after the first day was reduced significantly by Racecadotril ( Hamza et al, 1999; ). A further study ( n=193) reported that incident of diarrhea was reduced by 30% with racecadotril compared to placebo;racecadotril significantly reduced the diarrhea associated symptoms, such as abdominal pain,anal burning, abdominal distension and nausea ( Baumer et al, 1992)

4.      PEDIATRIC ;

a.      Oral racecadotril 1.5 milligrams/ kilogram (mg/kg) three times daily has been effective as an adjuvant to oral rehydration in the treatment of acute diarrhea in infants and children ( 3 months to 4 years of age) in placebo controlled studies  ( cezard et al,2001; Salazar-Lindo et al,2000; Matheson & Noble,2000) Efficacy of the drug was comparable to loperamide in one trailinvolving the children 2 to 10 years of age(Turck et al,1999).

b.      In  one study involving hospitalized children 3 months to 4 years of age,therapy with racecadotril   and oral rehydration significantly reduced the stool output during the first 2 days of treatment; stool output was approximately 60% of that in children receiving Placebo/rehydration. The need for oral rehydration was reduced in    racecadotril group The drug was efficacious regardless of rotavirus status ( Cezard et al, 2001).

B.     DIARRHEA – HIV-RELATED

1.      OVERVIEW ;

   EFFICACY;   Adult , good

   DOCUMENTATION;   Adult, good

2.      SUMMARY  ;

-Effective in the chronic diarrhea observed in these patients.

3.      ADULT  ;

a.      Racecadotril has been effective for the treatment of chronic diarrhea in the patients with HIV infection  or AIDS ,including those refractory to conventional anti- diarrheal therapy( BEAUGERIE et al,1996;Matheson & Noble,2000),In one large study( n=174) involving the patients with HIV infection and chronic Diarrhea,significantly more patients receiving Racecadotril ( 100 or 200 milligrams (mg) three times daily) experienced a one-third reduction in stool number then those treated with placebo(36 versus 23%) Efficacy was greater with Racecadotril in the patients without cryptosporidium infection (Matheson & Noble,2000)

                         

Adult: 100 mg tid, up to 7 days.

Infant(above 3 months) and children( upto 12 years) ; 1.5mg/kg body

Food(before/after)

May be taken with or without food

NOTE;   Racecadotril is highly efficious in non–inflammatory acute watery diarrhea(AWD) or secretory diarrhea lasting for hours to days with copious fluid loss &rapid Life threating dehydration which are caused by the pathogen like Rotavirus,vibrio cholera &Enterotoxigenic E scherichia Coli (ETEC) bacteria which are associated with the poor sanitation & contaminated water in  the developing country like Nepal,Bangladesh,India etc INVESTIGATIONAL USES;  The drug was shown to Amerorate nalaxone precipted opoid withdrawn symptoms by peripheral administration of Enkephalinase inhibitors in the rats. PLACES IN THE THERAPY; Ø  A. Racecadotril appears to be equally effective and less toxic alternative to anti-motility agent ( e.g loperamide,diphenoxylate) in the management of acute diarrhea.The lack of abdominal distension ,and toxic megacolon , which are concerned with anti-motility agents,constipation may be less with Racecadotril.CNS effects appears minimal, reducing chances of respiratory depression or physical dependence. Ø  Racecadotril should be considered 1st line or 2nd line therapy in the treatment of acute diarrhea in children &elderly.

CONTRA-INDICATIONS

Hypersensitivity to Racecadotril or any of the other product components.

PRECAUTIONS/ warning

Breast feeding, Renal insufficiency & pregnancy;

 Care must be taken while prescribing Racecadotril in the above outline condition due to insufficient safety data. However it can be prescribe if benefit factors over weights the risk in these subject.

Diabetes:

 In the event of diabetes, to take account of the quantity of sugar contained in the drug formulation.

Dysenteries:

    Racecadotril should not be used as treatment of first intention in the acute dysenteries with presence of blood and significant fever.

Broad Spectrum Antibiotic

Racecadotril should not be used in the event of diarrhoea occurring during broad spectrum antibiotic treatment.

Adverse Reactions

The efficacy of racecadotril in acute diarrhoea is not associated with adverse gastrointestinal effects and fewer patients on racecadotril therapy suffered from abdominal distension .However in children below two years of age where blood brain barrier is immature it can cause depression.  Caution  is also advocated in using racecadotril in disorders of carbohydrate intolerance due to the presence of saccharose as an excipient.The  commonest A.R that can occur with Racecdotril are Vomiting, nausea, constipation, abdominal pain, thirst, vertigo and headache.

STORAGE AND HANDLING INSTRUCTIONS

Store in a cool dry place, protect from light.

PRESENTATION:

RACECA is available in a blister of 10 Tablets.

Each box of RACECA contains 5 X 10’s