ITC on Anti-ulcerant

Md. Tanbir Ashraf Bhuiyan

Portfolio Manager

a Novartis company
Gastric Acid (HCl) & Hyperacidity

Hydrochloric acid (HCl) secreted by parietal

cells of the stomach helps in the preparation
of food for digestion.

Hyperacidity: An excessive degree of acidity is

called hyperacidity.
 Mechanism of Acid
HCL Production in Stomach
Cl- H+

Parietal Cell in
Stomach Lining Proton Pump
ATPase
Influence

Cl- K+ Acetylcholine
receptor

H2 receptor binds Gastrin receptor

binds
binds

H = Histamine
A = Acetylcholine
G = Gastrin
Complications of Hyperacidity

 Peptic ulcer
Gastric ulcer
Duodenal ulcer

 Gastro Esophageal Reflux Disease (GERD)

Esophagitis
Heartburn

 Zollinger-Ellison Syndrome

 Cancer
Complications of Hyperacidity

Peptic ulcer: A lesion of the skin or a mucous membrane

such as the one lining the stomach or duodenum that is
accompanied by formation of pus and necrosis of surrounding
tissue, usually resulting from hyperacidity.

Gastric /stomach ulcer: Ulcer in stomach

Duodenal ulcer: Ulcer in duodenum
Symptomatic difference between Gastric Ulcer and Duodenal Ulcer

Feature Gastric Ulcer Duodenal Ulcer

Onset of Pain Felt soon after eating, Hunger pain felt two
but not when lying down hours after food
Vomiting Considerable No vomiting
Appetite Afraid to eat Good
Diet Lives on milk & fish Eats almost anything
Weight Losses weight No loss in weight
Gastro-esophageal reflux disease (GERD)

• Gastroesophageal refers to the stomach and esophagus, and reflux

means to flow back or return of acidic stomach juices/food/fluids, back
up into the esophagus

• Main concerning: Heartburn

• Other manifest: Esophagitis
Erosive esophagitis

• Symptoms: Heartburn, regurgitation, Dysphagia,

Chest pain, Pulmonary Complications, Barrett's Esophagitis
and Carcinoma of the Esophagus

• The symptom pattern is very similar in GERD patients with/without

esophagitis – heartburn is the most common occurring in almost 100%
of patients.
Zollinger-Ellison Syndrome

Gastric hypersecretion and hyperacidity, fulminating

intractable atypical peptic ulceration, and hyperplasia of the
islet cells of the pancreas.

In Zollinger-Ellison syndrome, a tumor (a gastrinoma) secretes

the hormone gastrin, which stimulates the secretion of gastric
acid. This leads to the development of ulcers in the stomach
and duodenum (the first part of the small intestine).
Medication

 Antacid
 Proton Pump Inhibitors (PPI)
Omeprazole
Lansoprazole
Pantoprazole
 H2-receptor antagonist Esomeprazole

Ranitidine Rabeprazole

Famotidine
Roxatidine
Cimetidine
H2-receptor Antagonist: Servipep

Brand : Servipep
Generic : Famotidine
Dosage Form : Tablet
Strength : 20 mg & 40 mg
Therapeutic Class : Anti-ulcerant (H2-receptor antagonist)
Pack Size : Servipep 20mg tablet: 5x10’s
Servipep 40mg tablet: 5x10’s
Price : Servipep 20: 2.67 /tab & 133.50 /pack
Servipep 40: 5.06 /tab & 253.00 /pack
H2-receptor Antagonist: Servipep

Dosage

Gastric & Duodenal Ulcer: 40mg at bed time

Maintenance: 20mg twice daily

GERD: Symptomatic – 20mg BID

Erosive – 40mg BID
Maintenance – 20mg BID
 Mechanism of Action
HCL of Servipep
Cl- H+

Parietal Cell in Proton Pump

Stomach Lining ATPase
Influence

Cl- K+ Acetylcholine
receptor

H2 receptor Gastrin receptor

-
Servipep
binds

binds
binds

H = Histamine
A = Acetylcholine
G = Gastrin
Proton Pump Inhibitor (PPI)

Proton pump inhibitors (PPI) are a group of drugs whose main action
is a pronounced and long-lasting reduction of gastric acid production.

PPIs act by irreversibly blocking the hydrogen/potassium adenosine

triphosphatase enzyme system (the H+/K+ ATPase, or, more common,
gastric proton pump) of the gastric parietal cell. The proton pump is
the terminal stage in gastric acid secretion, being directly responsible
for secreting H+ ions into the gastric lumen.

Targeting the terminal-step in acid production, as well as the

irreversible nature of the inhibition, results significantly more effective
than H2 antagonists and reduce gastric acid secretion by up to 99%.

PPIs are given in an inactive form. In an acid environment, the inactive

drug is protonated and rearranges into its active form. As described
above, the active form will covalently and irreversibly bind to the
gastric proton pump, deactivating it.
 Mechanism of Action
HCL of PPI
Cl- H+

PPI - Proton Pump

ATPase
Influence

Cl- K+ Acetylcholine
receptor

H2 receptor binds Gastrin receptor

binds
binds

H = Histamine
A = Acetylcholine
G = Gastrin
Proton Pump Inhibitor (PPI)

Indication:

• Gastro-Esophageal Reflux Disease (GERD)

• Peptic Ulcer Disease (Gastric ulcer, Duodenal ulcer)
• Eradication of Helicobacter pylori (triple therapy with
antibiotics)
• Acid related dyspepsia
• NSAID-associated duodenal or gastric ulcer &
gastroduodenal erosions
• Zollinger – Ellison Syndrome
Sandoz’s PPI

Omeprazole : Probitor®

Esomeprazole : Neptor®
Probitor
Brand : Probitor

Generic : Omeprazole

Dosage Form : Capsule (enteric coated pellets)

Strength : 20 mg & 40 mg

Therapeutic Class : Anti-ulcerant (Proton Pump Inhibitor)

Pack Size : Probitor 20mg capsule: 10x4’s

Probitor 40mg capsule: 7x4’s

Price : Probitor 20: 5.87 /cap & 234.80 /pack

Probitor 40: 9.00 /cap & 252.00 /pack
Probitor
 Poorly soluble in water - dissolved well in alkaline solutions - rapidly activated at
low pH
 Max.plasma conc. - 2 hrs
 Bioavailability - dependent on formulation - increases with enteric coating and
dosage increment
 Systemic bioavailability - unaffected by food
 Oral absorption: 50 - 65 %
 Fecal excretion: 20 %
 Plasma half life: 0.5 - 1.5 hrs (mean – 1 hr)
 Plasma protein binding: 95 %
 Undergoes rapid and complete metabolism
 Unchanged Omeprazole - not found in the urine
Probitor
Dosage & Administration:

Peptic ulcer: 20 or 40mg once daily. 8 weeks for gastric ulcer & 4 weeks
of duodenal ulcer. 20mg once daily for long term maintenance dose.

GERD: 20-40mg once daily for 4-12 weeks. 20mg once daily as
maintenance dose.

Eradication of Helicobacter pylori: 40mg daily in divided doses

combined with antibacterial in triple therapy

With NSAID: 20mg daily

Zollinger-Ellison Syndrome: 60mg (3 cap. of 20mg) once daily. Doses up

to 120mg 3 times daily.

Acid-related Dyspepsia: 20mg daily for 2-4 weeks

Probitor
Dosage & Administration:

Elderly: Dose adjustment required

Children: Not recommended below 2 years

Impaired renal function: Dose adjustment not required

Impaired hepatic function: Dose adjustment required

Pregnancy & lactation: US FDA pregnancy category C. May be used if

potential benefit justifies the risk to the patients.

Drug Interactions: Delay elimination of Diazepam, Phenytoin, Warfarin.

No interaction with food. In case of use with digoxin, 10% increase in
absorption.
Probitor: Key Selling Points
 Healing rates higher than Ranitidine

 No clinically significant side effects (well documented safety profile)

 Superior to Lansoprazole, Pantoprazole & Rabeprazole in GERD

 Superior tolerability profile than Lansoprazole & Pantoprazole

 Can be taken regardless of meal, that is, better absorption profile

 Wide range of indications in acid/ GI related disorders

 Recommended in children over 2 years of age (Lansoprazole,

Pantoprazole & Rabeprazole are not recommended)
Probitor: Key Selling Points

 Brand of Sandoz which ensures High Quality and Global Reliability

 Manufactured at Sandoz Tongi Plant, EU certified plant

 Manufactured at Sandoz Tongi Plant, one of the global supply

points for Sandoz to export products to different countries on the
Globe including European market

 Consistent Quality without price game (no cut or increase)

Probitor: Competition
Omeprazole is the highest selling generic in Bangladesh Pharma
market with the value sale of 293 cr. tk. and +15% growth.

Vales Sales (cr.)

Sl. Brand Company
1 SECLO Square 74.27
LOSECTIL
2 Eskayef 38.67
XELDRIN
3 ACI 28.42
4 COSEC Drug Int. 16.60
5 OMEP Aristo 16.38
6 PPI Acme
IMS 2Q/2009, July ’08 – Jun ‘09
10.55
Probitor: Promotional Strategy

Pay-off Line / Brand Slogan: …caring the best way

Promotional activities:
 Brand promotion – printed materials
 Physician’s sample
 Regular & innovative gimmick
 Special gift
 Special & innovative campaign (frequent)
Neptor
Brand : Neptor

Generic : Esomeprazole

Dosage Form : Capsule (enteric coated pellets)

Strength : 20 mg & 40 mg

Therapeutic Class : Anti-ulcerant (Proton Pump Inhibitor)

Pack Size : Neptor 20mg capsule: 4x10’s

Neptor 40mg capsule: 3x10’s

Price : Neptor 20: 8 /cap & 280 /pack

Neptor 40: 12 /cap & 360 /pack
Neptor

 Max.plasma conc. – 1.5 hrs

 Should be taken at least 01 hour before meals. Foods decrease
the absorption of Esomeprazole about 33-53%
 Bioavailability: 90%
 Plasma half life: 1.0 - 1.5 hrs
 Plasma protein binding: 97%
 Extensively metabolized in the liver by cytocrome P450 enzyme
system
 Approximately 80% of an oral dose is excreted as inactive
metabolites in the urine. Rest through fecal excretion.
Neptor
Dosage & Administration:

GERD: 20 or 40mg once daily for 4-8 weeks. 20mg once daily as
maintenance dose.

Eradication of Helicobacter pylori: 40mg once daily for 10 days

combined with antibacterial in triple therapy

With NSAID: 20-40mg once daily for up to 6 months

Zollinger-Ellison Syndrome: 40mg twice daily

Pediatric (>1year): 10 or 20mg for 1-11 yrs & 20 or 40mg for >11 yrs
once daily up to 8 weeks
Neptor
Dosage & Administration:

Elderly: Dose adjustment NOT required

Children: Recommended for 1 year & above

Impaired renal function: Dose adjustment NOT required

Impaired hepatic function: Dose adjustment NOT required

Pregnancy & lactation: US FDA pregnancy category B. Should be used

only if clearly needed.
Neptor

Side Effects:
Well tolerated. Nausea, vomiting, diarrhoea, constipation, abdominal pain,
flatulence and headache are common.

Drug Interactions:
Absorption of ketoconazole and itraconazole can decrease during
Esomeprazole treatment. When combined with diazepam, citalopram,
imipramine, clomipramine, and phenytoin the plasma concentration of these
drugs may be increased and a dose reduction could be needed. Concomitant
administration resulted in a 45% decrease in clearance of diazepam and 13%
increase in plasma level of phenytoin in epileptic patients.
Neptor: Key Selling Points

 First PPI developed as an active isomer

 Superior to Pantoprazole in the management of GERD

 Only PPI that got the approval for children of 1 year & above
(Pantorpazole & Raberpazole are not recommended under 18 years)

 US FDA pregnancy category B

 Alternative dosing flexibility - the enteric coated granules of capsule

can also be mixed with a small amount of water or preferably with
acidic juice as orange or apple juice and swallowed immediately.
Neptor: Competition
Esomeprazole is the highest growing generic in Bangladesh Anti-
ulcerant market with the value sale of 71 cr. tk. and +45% growth.

Vales Sales (cr.)

Sl. Brand Company
1 Maxpro Renata 19.10
2 Sergel Healthcare 17.51
3 Esonix Incepta 8.05
4 Nexum Square 6.85
5 Maxima Acme 3.86
6 NEPTOR Sandoz 2.56

IMS 2Q/2009, July ’08 – Jun ‘09

Neptor: Promotional Strategy

Pay-off Line / Brand Slogan:

Novel, Effective & Placid Therapy Of Reflux diseases

Promotional activities:
 Scientific promotion – printed materials, RTD
 Physician’s sample
 Regular & innovative gimmick
 Special gift
 Special & innovative campaign
 TM

Tiemonium Methylsulphate

…antispasmodic with a difference

Product – At a Glance

Brand : Zeum™

Generic : Tiemonium Methylsulphate INN

Dosage Form : Tablet
Strength : 50 mg
Therapeutic Class : Antispasmodic & Anticholinergic
Pack Size : 5x10
Physician’s Sample : 1x4
Price : 325 /pack & 6.50 /tab
Indication Zeum

ZEUM reduces smooth muscle spasms of the

intestine, biliary system, uterus & urinary bladder.

It is indicated for the pain in gastrointestinal, biliary,

urinary and gynaecological diseases, such as
gastroenteritis, diarrhea, dysentry, biliary colic,
enterocolitis, cholecystitis, colonopathies, mild
cystitis & spasmodic dysmenorrhoea.
Smooth muscle
Smooth muscle is an involuntary muscle, found within the
layer of large and small arteries and veins, the bladder,
uterus, male and female reproductive tracts,
gastrointestinal tract, respiratory tract, the ciliary muscle,
and iris of the eye.

Smooth muscle is fundamentally different from skeletal

muscle and cardiac muscle.

Smooth muscle regulated by Nervous system

Smooth Muscle Spasm
A spasm is a sudden, involuntary contraction of a muscle, a group
of muscles, or a hollow organ, or a similarly sudden contraction of
an orifice. It is sometimes accompanied by a sudden burst of pain.

A subtype of spasms is colic, an episodic pain due to spasms of

smooth muscle in a particular organ.

Series of spasms or permanent spasms are called a spasmism.

Mechanism: Smooth Muscle Spasm

CNS
Release of different chemical mediators
(Acetylcholine, Histamine, etc.)

Binds to specific receptors on

smooth muscle surface
Ca++ Influx
Contraction of
Smooth muscle

Smooth Muscle
Spasm / Pain
Mechanism: Zeum
Zeum…antispasmodic with a difference

Antispasmodic with triple mode of action

- competitive blockade of Acetylcholine
- inhibition of release of intracellular Ca++
- competitive blockade of Histamine

Antispasmodic with triple site of action

- Digestive
- Urinary
- Gynecological
Comparison: Other antispasmodics

Hyoscine / Scopolamine
- Passes the blood-brain-barrier & placental barrier
- Dependency develops, abuse potential

Dicycloverine and Mebeverine

- Relieves smooth muscle spasm of GIT ONLY
- Slows Ca++ influx, TIemonium inhibits release
- No effect on Histamine
Dosage Guideline Zeum

2-6 ZEUM tablets daily

in divided doses
Use in Special Population Zeum
Safety & Tolerability:
 Side effects are very rare.
 It does not readily cross Blood-Brain-Barrier & therefore CNS
side effects are rare.
 Unlike hyoscine, Tiemonium has no reported abuse potential.

Pregnancy & Lactation: In absence of sufficient data, yet not recommended. May be
used considering risk-benefit ratio.

Pediatric use: Safety & effectiveness yet not established.

Zeum: Competition

Tiemonium is the highest selling generic in antispasmodic market

with the value sale of 28 cr. tk. and +20% growth.

Brand Company Value (cr.) Growth(%)

Algin Renata 7.04 41
Visceralgine Nuvista 5.68 13
Viset Healthcare 3.21 19
Onium Orion 3.00 -9
Veralgin Aristo 2.11 23

IMS 2Q/2009, July ’08 – Jun ‘09