APPROVED PROFESSIONAL INFORMATION FOR LAANERO

SCHEDULING STATUS

S4

1 NAME OF THE MEDICINE

LAANERO

(

15

mg

Delayed Release Capsule

s

)

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each

LAANERO

delayed released

capsule contains lansoprazole

15 mg.

Contains sugar: 88,4 mg

(70 mg sugar spheres (sucrose) and 18,4 mg sucrose).

For full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

P

ink/Green

coloured

size '3' Hard

gelatine

capsules imprinted with 'H' on cap and '166' on body filled

with white to off

-

white pellets.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Posology:

Duodenal ulcer:

The recommended dosage is 30 mg (two 15 mg capsules) once a day for 2 to 4 weeks. Patients may

respond

adequately

to

15

mg

(one

capsule)

daily

for

2

to

4

weeks,

and

therefore

individual

dose

adjustments should be considered.

LAANERO

is indicated for

Helicobacter pylori-

positive duodenal ulcers as part of an eradication program,

with appropriate antibiotics.

Oesophagitis due to gastro-oesophageal reflux:

The recommended dosage is 30 mg (two 15 mg capsules) once a day for 4 weeks. Depending on the

endoscopic results, a repeat course of 4 weeks may be necessary. Patients may respond adequately to

15 mg daily for 4 weeks with a second 4-week treatment period, at the same dosage, depending on

endoscopic results.

Maintenance treatment for the prevention of gastro-oesophageal reflux:

One 15 mg capsule once a day for a maximum period of one year. No clinical information is available for

treatment longer than one year.

Functional dyspepsia:

Adults: 15 to 30 mg (two 15 mg capsules) once a day for 2 to 4 weeks.

Special populations:

Elderly:

No dose adjustment is necessary. However, 30 mg (two 15 mg capsules) per day is the maximum daily

dose.

Renal impairment:

No dose adjustment is necessary in renal failure. This also applies to patients on dialysis.

Paediatric population:

Safety and efficacy in children have not been established.

Method of administration:

For oral use.

LAANERO

should preferably be taken before a meal.

LAANERO

is contraindicated in:

Acute interstitial nephritis

Acute interstitial

nephritis

(AIN)

has

been

observed

in

patients

taking

proton

pump

inhibitors

(PPIs)

including

LAANERO

.

Acute

interstitial

nephritis

may

occur

at

any

point

during

PPI

therapy

and

is

generally

attributed

to

an

idiopathic

hypersensitivity

reaction.

Healthcare

professional

(HCP)

should

frequently monitor renal function and check the urine for haematuria and/or proteinuria in patients on

treatment with PPIs such as

LAANERO

. Discontinue

LAANERO

if acute interstitial nephritis develops.

Malignant disease:

Treatment with

LAANERO

may alleviate the symptoms of malignant ulcers and can delay diagnosis.

Therefore, the possibility of malignancy of a gastric ulcer or a malignant disease of the oesophagus

should be excluded prior to treatment with

LAANERO

.

Malabsorption:

Proton pump inhibitors such as

LAANERO

have been reported to result in a substantial reduction in

cyanocobalamin (Vitamin B

12

) absorption, probably related to the increase in gastric pH, and indicating

a

potential

risk

of

vitamin

deficiency

with

long

-

term

therapy.

UK

li

censed

product

information

recommends that severely ill children, who may have borderline body stores of cyanocobalamin, should

have

serum

vitamin

B

12

concentrations

monitored

if

they

require

long

-

term

therapy.

Proton

pump

inhibitors such as

LAANERO

have a

lso been reported to impair the bioavailability of dietary vitamin C.

Fat malabsorption, secondary to increased deconjugation of bile acids caused by bacterial overgrowth

in the jejunum, has also been reported with proton pump inhibitors such as

LAANERO

tr

eatment. For

the suggestion that proton pump inhibitors such as

LAANERO

can cause calcium malabsorption, see

(

Effects on the Musculoskeletal System

).

Subacute cutaneous lupus erythematosus (SCLE):

Proton pump inhibitors such as

LAANERO

are associated with

very infrequent cases of SCLE. If lesions

occur, especially in sun

-

exposed areas of the skin, and if

accompanied by arthralgia, the patient should

seek medical help promptly and the health care professional should consider stopping

LAANERO

. SCLE

after pre

vious treatment with a proton pump inhibitor such as

LAANERO

may increase the risk of SCLE

with other proton pump inhibitors.

Alcohol and CNS depressants:

LAANERO

may

lead

to

drowsiness

and

impaired

concentration

that

may

be

aggravated

by

the

simultaneous intake of alcohol or other central nervous system depressants.

Hypomagnesaemia:

Severe hypomagnesaemia has been reported with the use of PPIs like lansoprazole, as contained in

LAANERO

for

at

least

three

months

and

in

most

cases

for

a

year.

Serious

manifestations

of

hypomagnesaemia such as fatigue, tetany, delirium, convulsions, dizziness and ventricular dysrhythmia

can occur, but they may begin insidiously and be

overlooked. Other serious events include tremors,

carpo

-

pedal

spasm,

atrial

fibrillation,

supraventricular

tachycardia,

and

abnormal

QT

interval.

Hypomagnesaemia

also

produces

impaired

parathyroid

hormone

secretion

which

may

lead

to

hypocalcaemia. In most

affected patients, hypomagnesaemia improved after magnesium replacement

and discontinuation of the PPI.

For patients expected to be on prolonged treatment or who take

LAANERO

with digoxin or medicines

that may cause hypomagnesaemia (e.g. diuretics), heal

th care

professionals should consider measuring

magnesium levels before starting

LAANERO

treatment and periodically during treatment.

Bone fracture:

PPIs like lansoprazole, as contained in

LAANERO

, especially if used in high doses and over long periods

(o

ver 1 year), may increase the risk of hip, wrist and spine fracture, predominantly in the elderly or in

presence of other recognised risk factors. Reports suggest that PPIs may increase the overall risk of

fracture

by

10

–

40

%.

Some

of

this

increase

may b

e

due

to

other

risk factors.

Patients

at

risk

of

osteoporosis

should

receive

care

according

to

current

clinical

guidelines

and

they

should

have

an

adequate intake of vitamin D and calcium.

Clostridium difficile associated diarrhoea (CDAD):

PPIs

like

lansoprazole,

as

contained

in

LAANERO

has

been

linked

to

an

increased

risk

of

enteric

infections such as CDAD. A diagnosis of CDAD should be considered

for patients taking

LAANERO

who

develop diarrhoea that does not improve.

Symptoms include watery stool, abdominal pain, and fever, and patients may go on to develop more

serious intestinal conditions. Factors that may predispose an individual to developing CDAD include

advanced age, certain chronic medical conditions, and taking broad spectrum antibiotics. Treatment for

CDAD includes the replacement of fluids and electrolytes and the use of special antibiotics.

Reflux Oesophagitis gastric glandular cysts:

Diagnosis of reflux oesophagitis should be confirmed by endoscopy.

Effects related to acid inhibition:

During long-term treatment, gastric glandular cysts have been reported in increased frequency. These

physiological changes result from pronounced inhibition of gastric acid secretion.

Gastrointestinal infections caused by bacteria:

Decreased gastric acidity increases gastric counts of bacteria normally present in the gastrointestinal

tract. Treatment with

LAANERO

may lead to an increased risk of

gastrointestinal infections such as

Salmonella, Campylobacter, Shigella or Clostridium di

fficile.

Presence of alarm symptoms:

In

the

presence

of

symptoms

such

as,

significant

unintentional

weight

loss,

recurrent

vomiting,

dysphagia,

haematemesis

or melaena,

and

when

gastric

ulcer is

suspected

or

present, malignancy

should be excluded, as treatment with

LAANERO

may alleviate

symptoms and delay diagnosis.

H. pylori:

In patients suffering from gastro-duodenal ulcers, the possibility of

H. pylori

infection as an etiological

factor should be considered.

Long term use:

Because of limited safety data for patients on maintenance treatment for longer than 1-year, regular

review of the treatment should be regularly performed in these patients.

Colitis:

Colitis has occurred in patients taking lansoprazole as contained in

LAANERO

.

Therefore, in the case

of severe and/or persistent diarrhoea, discontinuation of therapy should be considered.

Interference with laboratory tests

Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumours. To

avoid

this

interference,

lansoprazole

treatment

should

be

stopped

for

at

least

5

days

before

CgA

measurements. If CgA and gastrin levels have not returned to reference range after initial measurement,

measurements should be repeated 14 days after cessation of proton pump inhibitor treatment.

LAANERO

contains sucrose:

Patients

with

rare

hereditary

problems

of

fructose

intolerance,

glucose-galactose

malabsorption

or

sucrase-isomaltase insufficiency should not take this medicine.

Effects

of

lansoprazole

on

other

medicinal

products

Medicinal

products

with

pH

dependent

absorption:

Lansoprazole

may interfere

with

the

absorption

of

other

medicinal

products

where

gastric

pH

is

an

important determinant of oral bioavailability.

HIV protease inhibitors:

Co-administration of

LAANERO

is contraindicated with HIV protease inhibitors for which absorption is

dependent on acidic intragastric pH, such as atazanavir and nelfinavir, due to significant reduction in

their bioavailability (see section 4.3).

Ketoconazole and itraconazole:

The

absorption

of

ketoconazole

and

itraconazole from the

gastrointestinal tract

is

enhanced

by

the

presence of gastric acid. Administration of

LAANERO

may result in sub-therapeutic concentrations of

ketoconazole and itraconazole and the combination should be avoided.

Digoxin:

Co-administration of

LAANERO

and digoxin may lead to increased digoxin plasma levels. The plasma

levels of digoxin should therefore be monitored, and the dose of digoxin adjusted if necessary, when

initiating and ending

LAANERO

treatment.

Methotrexate:

Concomitant use with high-dose methotrexate may elevate and prolong serum levels of methotrexate

and/or its metabolite, possibly leading to methotrexate toxicities.

Warfarin:

Monitoring of patients receiving concomitant warfarin is recommended. Increased INR and prothrombin

time in patients receiving

LAANERO

and warfarin concomitantly have been reported. Increases in INR

and prothrombin time may lead to abnormal bleeding and even death.

Medicinal products metabolised by P450 enzymes:

LAANERO

may increase plasma concentrations of medicinal products that are metabolised by CYP3A4.

Caution is advised when combining

LAANERO

with medicinal products which are metabolised by this

enzyme and have a narrow therapeutic window.

Theophylline:

LAANERO

reduces the plasma concentration of theophylline, which may decrease the expected clinical

effect

at

the

dose.

Patient

monitoring

should

be

taken

in

co-administration

of

LAANERO

with

theophylline.

Tacrolimus:

Co-administration of lansoprazole increases the plasma concentrations of tacrolimus (a CYP3A and P-

gp substrate).

LAANERO

exposure increased the mean exposure of tacrolimus by up to 81 %.

Monitoring of tacrolimus plasma concentrations is advised when concomitant treatment with

LAANERO

is initiated or ended.

Medicinal products transported by P-glycoprotein:

LAANERO

has been observed to inhibit the transport protein, P-glycoprotein (P-gp) in vitro. The clinical

relevance of this is unknown.

Effects of other medicinal products on lansoprazole Medicinal products which inhibit CYP2C19:

Fluvoxamine:

A

dose

reduction

may

be

considered

when

combining

LAANERO

with

the

CYP2C19

inhibitor

fluvoxamine. The plasma concentrations of

LAANERO

increase up to 4-fold.

Medicinal products which induces CYP2C19 and CYP3A4:

Enzyme inducers affecting CYP2C19 and CYP3A4 such as rifampicin, and St John´s wort (

Hypericum

perforatum

) can markedly reduce the plasma concentrations of

LAANERO

.

Others:

Sucralfate/Antacids:

Sucralfate/Antacids may decrease the bioavailability of

LAANERO

. Therefore,

LAANERO

should be

taken at least 1 hour after taking these medicinal products.

Non-steroidal anti-inflammatory medicinal products:

No

clinically

significant

interactions

of

LAANERO

with

non-steroidal

anti-inflammatory

medicinal

products have been demonstrated, although no formal interactions studies have been performed.

LAANERO

in contraindicated in pregnancy and lactation (see section 4.3).

Pregnancy:

Adequate and well-controlled studies in humans have not been done.

Breastfeeding:

It

is

not

known

whether

lansoprazole

is

distributed

into

breast

milk.

However,

lansoprazole

or

its

metabolites

are

distributed

into

the

milk

of

rats.

Because

lansoprazole

has

been

shown

to

cause

tumorigenic

effects

in

animals,

a

decision

should

be

made

as

to

whether

breastfeeding

should

be

discontinued

or

the

medication

withdrawn,

taking

into

account

the

importance

of

LAANERO

to

the

mother.

Fertility:

No human data on the effect of lansoprazole on fertility are available. Reproductive studies in pregnant

rats and rabbits revealed no lansoprazole-related impairment of fertility.

LAANERO

may lead to drowsiness and impaired concentration including vertigo, visual disturbance and

somnolence

. Patients should be advis

ed, particularly at the initiation of therapy, against taking charge of

vehicles or machinery or performing potentially hazardous tasks where loss of concentration could lead

to accidents.

Summary of the safety profile:

Side effects are grouped in order of frequent, less frequent and frequency unknown.

Tabulated summary of adverse reactions:

Reporting of suspected adverse reactions

Reporting

suspected

adverse

reactions

after

authorisation

of

the

medicine

is

important.

It

allows

continued monitoring of the benefit/risk balance of the medicine. Health care

providers are asked to

report any suspected adverse reactions to SAHPRA via the “6.04 Adverse Drug Reactions Reporting

Form”, found online under SAHPRA’s publications:

https://www.sahpra.org.za/Publications/Index/8

or to the Holder of certificate of registration through the

mail:

pvg.cdma@heterogroups.com

.

Treatment is symptomatic and supportive. In the case of suspected overdose, the patient should be

monitored. Lansoprazole, as contained in

LAANERO

, is not significantly eliminated by haemodialysis. If

necessary, charcoal and symptomatic therapy is recommended.

A.11.4.3 Medicines acting on the gastrointestinal tract.

5.1 Pharmacodynamic properties

Lansoprazole

is

a

specific

proton

pump

(H+,

K+-ATPase)

inhibitor

(PPI)

of the

gastric

parietal

cell.

Lansoprazole

inhibits

gastric

acid

secretion

in

a

dose

related

manner

irrespective

of

the

source

of

stimulation.

Gastric

secretory

functions

recover

gradually

following

discontinuation

of

the

medicine.

Lansoprazole has no effect on histamine, gastrin or cholinergic receptors.

Absorption & Distribution:

Following

oral

administration,

lansoprazole

is

well

absorbed

with

a

resultant

bioavailability

of

approximately 78 %. The bioavailability is decreased if lansoprazole is taken with food. Peak serum

concentrations

are

achieved

approximately

1

to

2

hours

following

ingestion.

Lansoprazole

is

highly

protein bound (97 %).

Biotransformation:

Lansoprazole is extensively metabolised by the liver. The metabolism of lansoprazole is mainly catalysed

by the enzyme CYP2C19. The enzyme CYP3A4 also contributes to the metabolism. Sulphone, sulphide

and 5-hydroxyl derivatives of lansoprazole have been identified in plasma. These metabolites have very

little or no antisecretory activity.

Elimination:

Lansoprazole metabolites are excreted by both the renal and biliary route.

The plasma elimination half-

life ranges from 1 to 2 hours following single or multiple doses in healthy subjects. There is no evidence

of accumulation following multiple doses in healthy subjects.

Characteristics in specific groups of subjects or patients:

Elderly:

The

clearance

of

lansoprazole

is

decreased

in

the

elderly,

with

elimination

half-life

increased

approximately 50 % to 100 %. Peak plasma levels were not increased in the elderly.

Renal impairment:

In patients with severe renal insufficiency, plasma protein binding is decreased by 1,0 to 1,5 %. Patients

with renal insufficiency have a shortened elimination half-life and decreased total AUC (free and bound).

AUC for free lansoprazole in plasma, is not related to the degree of renal impairment, and C

max

and T

max

are not different from patients with healthy kidneys. No dosage adjustment is necessary in patients with

renal insufficiency.

Hepatic impairment:

In patients with various degrees of chronic hepatic disease, the mean plasma half-life of lansoprazole is

prolonged from 1,5 hours to 3,2 to 7,2 hours. An increase in mean AUC up to 500 % is observed at

steady state in hepatically-impaired patients compared to healthy subjects. Dose reduction in patients

with severe hepatic disease should be considered.

Paediatric population:

Safety and efficacy in children have not been established.

Medicine loading:

Magnesium carbonate

Corn starch

Low substituted Hydroxy propyl cellulose

Hydroxy propyl cellulose

Purified water

Sub coating:

Corn starch

Low substituted Hydroxy propyl cellulose

Purified water

Enteric coating:

Methacrylic acid copolymer

Talc

Titanium dioxide

Triethyl citrate

Ploysorbate 80

Purified water.

Contains sugar: 88,4 mg

(70 mg sugar spheres (sucrose) and 18,4 mg sucrose).

Not applicable.

24 months.

Store at or below 25 °C.

KEEP OUT OF REACH OF CHILDREN.

HDPE containers:

Blister packs:

7 capsules packed in OPA/PVC aluminum foil blister.

Pack sizes for

Blisters: 7, 14, 28’s and 105 capsules per carton.

Not all pack sizes might be marketed.

Keep in original packaging until required for use.

Hetero Drugs South Africa (Pty) Ltd

Waterfall Corporate Campus,

Building No.2, First Floor,

74 Waterfall Drive,

Midrand, 2066

Telephone number: 012 644 1220

e-mail address:

nokuthula.n@heterodrugs.com

56/11.4.3/0763.762

18 June 2024