Imipenem cilastatin training

Technical Discussion on Imipenem and Cilastatin

1. IMIPEN
®
500
imipenem/ cilastatin
500 mg /500 mg injection
Prepared By:
Masum Chowdhury
Product Executive
PMD
APPROPRIATE, ALTERNATIVE,
EMPIRIC ANTIBIOTIC THERAPY

2. Reviews,
Overviews, &
Updates of
Carbapenem

3. History of Carbapenem
In the 1970sBeecham research Laboratories
identified a Carbapenem group, called olivanic
acid, which were beta-lactamase inhibitors and
broad spectrum antibiotics.
Imipenem has one of the widest spectrum
of the beta-lactam antibiotics. It is active
against nearly all common bacterial species,
including those resistant to
aminoglycosides and newer Cephalosporin.

4. History of Carbapenem
The Carbapenem are a group of bicyclic
beta-lactam compounds with a common
Carbapenem nucleus.
Imipenem is one of them.
Imipenem has high activity against
both aerobic and anaerobic, atypical
bacteria

5. We Introduces a New Unique
Family in antibiotic segment
Carbapenem
1.Meropenem
2.Imipenem + cilastatin
3.Ertapenem

6. We Introduces a New concept in
this Family……..
Carbapenem
Feropenem
®
Tablet
Which is approved by FDA
Very recently

7. Distribution of nosocomial infections among adult patients in medical intensive care units
UTI 31%
PNEU 27%
BSI 19%
GI 5%
CVS 4%
ENT 4%
LRTI 4% Other 5%
Blood stream Infections

8. In 1970s Merck, Sharp and Dohme
Research Laboratoriesindependently
identified thienamycin, derived from
streptococcus catteleya.
History of IMIPEN

9. What is IMIPEN®500 ?
IMIPENfor intravenous use is supplied
as a white sterile powder in 100 mL
vials. Each 100 ml vial contains 500 mg
of imipenem equivalent and 500 mg
cilastatin equivalent.

10. Therapeutic Class
Cilastatinis a competitive,
reversible and specific inhibitor
of dehydropeptidase-Ienzyme.

11. Therapeutic Uses ofIMIPEN
®
500
Intra-abdominal infections
Lower respiratory tract infections
Febrile Neutropenia
Gynaecological infections
Septicaemia
Genitourinary tract infections
Bone and joint infections
Skin and soft tissue infections
Endocarditis

12. The importance of using the most
appropriate empiric antibiotic early
to treat nosocomial infections
Nosocomial infections in
ICU

13. Antibiotic Prescribing in
The
ICU

14. Choosing an appropriate
antibioticfor ICU
Patients in the ICU displaying signs of sepsis
belong to one of the following categories:
infected with a known organism from an
identified site
infected with a known organism from an
unidentified site
infected, but no causal agent has been
identified
uninfected.

15. Choosing an appropriate
antibioticfor ICU
Occasionally the clinical signs of an
infection suggest the causal organism
and the appropriate antibiotic.
However, the choice of antibiotic is often
guided by the results of microbiological
investigation.

16. Correlation between organism and
site of infection

17. Spectrum of activity of some antibiotics

18. Spectrum of activity of some antibiotics
FROM THIS DISCUSSIONS I LIKE TO
SAY
THAT
IMIPEN®500IS THE MOST
ADVANCE , APPROPRIATE,
ALTERNATIVE,
EMPIRICAL
ANIBIOTIC THERAPY

19. 81.9%
58.9%
0.0%
20.0%
40.0%
60.0%
80.0%
100.0%
Empiric Antibiotic
Therapy Appropriate
(n=238)
Empiric Antibiotic
Therapy Inappropriate
(n=56)
Patients with
Clinical Success, % p<0.05
*Successful outcome was defined as resolution with no change in treatment.
Davey P et al. Presented at the International Society of Pharmacoeconomics and
Outcomes Research Sixth Annual International Meeting, 2001.
In an observational study (n=348) in patients with acute peritonitis, IAI
patients with adequate empiric therapy were significantly more likely to
have successful clinical outcomes.*
Appropriate Empiric Therapy for IAI:
Successful Clinical Outcome

20. Abdominal sepsis
Sepsis originating from the large bowel such as
peritonitis, abdominal abscesses, gangrenous
appendicitis and diverticulitis.
Infection Types:Mixed Aerobic & anaerobic
Infections
Doses & administrations:500mg
imipenem/cilastatin given 6 or 8 hourly is
recommended.
Maximum dose should be increased to
1000mgthree or four times daily.

21. Intra-abdominal Infections
Appendicitis
Peritonitis
Intra-abdominal Abscess
Diverticulitis
Antibiotic-Associated Diarrhea
(Clostridium difficile)
Food Poisoning/Traveler’s Diarrhea
Helicobacter pylori
Pelvic Inflammatory Disease

22. Intra-abdominal Infections
Infections contained within the peritoneum or
retroperitoneal space.
Peritoneal cavity contains:
Stomach
Jejunum, Ileum
Appendix
Large intestine (colon)
Liver, gallbladder and spleen
Retroperitoneal space:
Duodenum
Pancreas
Kidneys

23. Appendicitis
One of the most common causes of intra-
abdominal infections.
Treatment:Both Surgical and Antibiotics
Depends on presentation of appendix:
Normal, inflamed, gangrenous or perforated
Begin antibiotics before appendectomy is
performed
Appropriate Therapy:Imipenem
Continue antibiotics for 7 to 10 days if appendix
is perforated or gangrenous (Switch to oral
equivalents)

24. Deep Gynaecological &
Obstetric Infections
Septic abortions, postoperative
infections after vaginal hysterectomy and
infections. Similar to the intra-abdominal
infections. These infections are caused
by a aerobic & anaerobic flora
Doses & administrations:500mg
imipenem/cilastatin given 6 or 8 hourly is
recommended.
Maximum dose should be increased to 1000mg
three or four times daily.

25. Empirical Treatment of
Septicaemia
IMIPEN
®
500 is effective in patients
with Bacterial septicemia
Doses & Administrations
The dose should be 500 to
1000mg every 6 to 8 hr depending
on the severity of infections.

26. Lower Respiratory Tract Infection
In patients with pneumoniae caused by
Gram –Negative pathogens IMIPEN
®
500
at a dose of 1000mg three times daily
may be used.

27. Cystic fibrosis
In patients with cystic fibrosis IMIPEN
®
500at a dose of 1000mg three times
daily may be used.

28. Urinary Tract infections
IMIPEN
®
500at a dose of 500mg three
times daily can be used in cases of
hospital acquired lower or upper urinary
tract infections.

29. Infections in Neutropenic
Patients
First Line Therapy:IMIPEN
®
500
Conventional Antibiotic:
Aminoglycosides + Cephalosporin's
Dose: The dose documented in 1gm every
6 hours.

30. Bone & Joint Infections
IMIPEN
®
500 has been used to treat
osteomyelitis resulting from accidents or
prosthesis implantation, involving gram
–positive and gram negative organisms.
Dose: The dose documented in 1gm every
6 hours.

31. Skin & soft tissue
infections
Moderately severe to severe soft
tissue infections.
Success rate: 95%

32. Where u will promote IMIPEN 500
INTENSIVE CARE UNIT
IMIPEN(imipenem/cilastatin) as
empirical monotherapy for serious
bacterial infections in the………
ICU

33. Why IMIPEN
®
500 is used in ICU ?
IMIPEN 500 (imipenem/cilastatin)is
used as empirical monotherapy in
intensive care unit (ICU) patients with
serious bacterial infections.

34. Serious bacterial infectionsare
common in patients in the intensive care
unit (ICU) and they result in considerable
morbidity and mortality.
What is Serious Bacterial
Infections ?

35. Approximately 45% of the 10,038 ICU
patients included in the European
Prevalence of Infection in Intensive Care
(EPIC) Survey of 1992 had at least one
bacterial infection [1].
Serious Bacterial Infections
enhances Morbidity rate in ICU?

36. Pneumonia and other lower respiratory
tract infections (LRTIs) are the most
prevalent infections (64.7%), followed by
urinary tract (17.6%) and bloodstream
infections (12.0%).
What are the Serious Bacterial
Infections occur in ICU ?
Fifty-five percent of ICU-acquired infections
are polymicrobial.

37. What is CAPD PERITONITIS ?
CAPDmeans continues
ambulatory peritoneal dialysis
(CAPDPERITONITIS)

38. CAPD
Primary response, relapse and overall
cure rate were 93%, 4%, 89%
respectively in imipenem/cilastatin
treatment.

39. Success rate in IMIPEN
®
500
It can be concluded that
Imipenem/cilastatinfirst-line
treatment is highly efficient in CAPD
peritonitis.

40. Why IMIPEN
®
500called
Broad Spectrum Antibiotic ?
The activity of IMIPEN
®
500against an
unusually broad spectrum of pathogens
makes it particularly useful in the
treatment of polymicrobic mixed
aerobic/anaerobic infections as well as
initial therapy prior to the identification of
the causative organisms.

41. Dosage and Administration
of IMIPEN
®
500
The dosage recommendations for
IMIPEN
®
500(for intravenous use only)
represent the quantity of imipenem to be
administered. An equivalent amount of
cilastatin is also present.

42. Dosage and Administration
of IMIPEN
®
500
The total daily dosage of IMIPEN
®
500
should be based on the type or severity
of infection and given in equally divided
doses based on consideration of degree
of susceptibility of the pathogens, renal
function and body-weight.

43. Adult Dosage Schedule for
Patients
Most infections respond to a daily
dose of 1-2 gadministered in 3-4
divided doses.

44. Adult Dosage Schedule for
Patients
For the treatment of moderate infection,
a 1 g b.i.d.dosage regimen may also be
used.

45. Adult Dosage Schedule for
Patients
In infections due to less susceptible
organisms, the daily dosage of IMIPEN
®
500may be increased to a maximum of
4 g/day or 50 mg/kg/day, whichever is
lower.

46. Adult Dosage Schedule for
Patients
Each dose of 250 -500mg of IMIPEN
®
500should be given by intravenous
infusion over 20 to 30 minutes.

47. Adult Dosage Schedule for
Patients
Each dose 1000 mgshould be infused
over 40 to 60 minutes. In patients who
develop nausea during the infusion,
the rate of infusion may be slowed.
In patients who develop nausea
during the infusion, the rate of
infusion may be slowed.

48. IV dosage schedule for adults with normal
renal function and body weight
Severity of
Infection
Dose of IMIPEN Dosage Interval Total Daily
Moderate 500mg
1000mg
8 hrs 1.5gm
Severe –
Full susceptible
500mg 6 hrs 2gm
Severe and/or
Life threatening
–due to less
susceptible
organisms
1000mg
1000mg
8 hrs
6 hrs
3gm
4gm

49. Due to high antimicrobial activity of
IMIPEN
®
500, it is recommended that
the maximum total daily dosage not
exceed 50 mg/kg/day or 4 g/day.
However cystic fibrosis patients with
normal renal function have been treated
with IMIPEN
®
500at doses up to 90
mg/kg/day in divided doses not
exceeding 4 g/day.
Maximum Dose for Patients
with Normal Renal Function

50. IMIPEN
®
500has been used
successfully as monotherapy in
immunocompromised cancer patients for
confirmed or suspected infections such
as sepsis.
Maximum Dose for Patients
with Normal Renal Function

51. Paediatric Dosing Schedule
(3 months or older)
For children and infants the following
dosage schedule is recommended:
CHILDREN >40kg body weight
should receive adult doses.

52. Paediatric Dosing Schedule
(3 months or older)
CHILDREN AND INFANTS <40 kg
body weight should receive 15 mg/kg
at six-hour intervals.The total daily
dose should not exceed 2 g.

53. TREATMENT OF SERIOUS INFECTIOUS
COMPLICATIONS IN BURNED PATIENTS WITH -
IMIPENEM/CILASTATIN
The use of Imipenem/Cilastatin in the
treatment of severe infections in patients
with extensive deep Burns.
The results of the treatment were evaluated as
very good (80.0%) . The symptoms of infection
initially resolved before the 36th hour.

54. TREATMENT OF SERIOUS INFECTIOUS
COMPLICATIONS IN BURNED PATIENTS WITH -
IMIPENEM/CILASTATIN
Imipenem/Cilastatin is a correct choice in
empirical treatment and improved serious
cases, including mixed infections, with
multiresistant bacterial pathogens.

55. Treatment of uncomplicated gonorrhea
with single-dose imipenem-cilastatin.
Single 500-mg intramuscular doses of
imipenem-cilastatin cured 116 (95%) of
122 men and 9 of 9 women with
uncomplicated gonorrhea due to beta-
lactamase-negative Neisseria
gonorrhoeae. Most co-existing
Chlamydia trachomatis infections
persisted. Imipenem-cilastatin is
effective for uncomplicated gonorrhea .

56. Mode of Action of IMIPEN
Imipenem prevents the bacteria from making
the cell wall, so the cells die. Cilastatin sodium
is added to prevent an enzyme made by the
kidneys from breaking down the antibiotic
imipenem. The drug is used to treat gram
positive and negative bacteria. It is used to treat
infections of the lower respiratory tract, urinary
tract, abdomen, pelvis, skin, bones and joints.

57. Pharmacokinetics
IV admin only
half life of both drugs approx 1 hour
when given together 2/3 of dose of Imipenem is
excreted unchanged in urine; remaining 1/3 in
hyrolysed form
< 1%excreted in bile -too little to disturb
colonic flora
plasma protein binding of Imipenem only
20%
Cilastatin excreted almost entirely by kidney

58. Reconstitution, Intravenous
Solution
IMIPEN
®
500for intravenous infusion is
supplied as a white sterile powder in
vials containing 500 mg imipenem
equivalent and 500 mg cilastatin
equivalent.

59. Reconstitution, Intravenous
Solution
IMIPEN
®
500is buffered with sodium
bicarbonate to provide solutions in the
pH range of 6.5 to 8.5.There is no
significant change in pH when solutions
are prepared and used as directed.

60. Reconstitution of IMIPEN
®
IV
Dose of IMIPEN
®
IV
(mg of Imipenem)
Volume of Diluent
to be Added (ml)
Approximate
average
concentration of
Imipen IV
(mg/ml of
Imipenem)
500 100 5
A suggested procedure is to add approximately 10 mL from
the appropriate infusion solution to the vial. Shake well and
transfer the resulting suspension to the infusion solution
container.

61. Where can you keep my
medicine?
Imipenem-cilastatin is usually given in a
hospital. You may be given imipenem-
cilastatin to take home to complete your
treatment. If you are given this medicine
to take at home, store at room
temperature or as directed until it is time
to mix the medicine.

62. Compatibility
IMIPEN
®
500is compatible with the following infusion fluids:
0.9% sodium chloride intravenous infusion
5% or 10% glucose intravenous infusion
5% glucose intravenous infusion with 0.02% sodium bicarbonate
5% glucose and 0.9% sodium chloride intravenous infusion
5% glucose with 0.225% sodium chloride intravenous infusion
5% glucose with 0.15% potassium chloride intravenous infusion
2.5% and 10% mannitol intravenous infusion
normosol-M in 5% glucose intravenous infusion.

63. IMIPEN
®
IV
Price Informations
Brand Name MRP/Tk. MRP/Unit Price
IMIPEN
®
500
Tk.1150.00 Tk.1150.00

64. Competitors
Price Informations
NO

65. Target Doctors
Pediatricians
Gynecologists
Obstetricians
Gasenterologists
Urologists
Medicine Specialists

66. Target Promotional Area
ICU
Hospital
Clinics

67. Questions

68. THANK YOU ALL
THIS IS THE END OF OUR
PRESENTATION.
Prepared By