INJECTIONS FORMULA AND PROCEDURE




MASTER FORMULA



COMPOSITION

Each 2ml Vial Contains:


· ACTIVE INGREDIENT

Amikacin USP ………………………..………………..…. 100mg
(As Amikacin Sulphate)



· INACTIVE INGREDIENT

Sodium Meta Bisulfite BP/USP……………………….……1.3mg
Sodium Citrate BP/USP……………………………………. 5.0mg
Sulfuric Acid BP/USP …………….Q.S to Adjust pH 3.5 and 5.5
Water for Injection BP/USP…………..…………... Q.S to 2.0ml

DESCRIPTION OF METHOD OF MANUFACTURE.

PROCEDURE:

All the ingredients are checked and released prior to issue for manufacture.
The ingredients are weighed in the presence of Production Pharmacist and rechecked at the time of formulation, and the weights are recorded in the formula card
The ingredients are transferred to the formulation area.
The equipment utensils and the area‘s are checked for proper cleanliness and insured that no trace of foreign matter is visible and that there is no trace of any chemical left behind of any previous product.
Check that the quality of water meets the USP standard before formulation and ensure that it is freshly prepared and the Q.C stickers is available.
Rinse the container with freshly prepared Pyrogen free distilled water.
Measure the water quantity, record the temperature and Bubble Nitrogen through water to remove the traces of Oxygen in a mixing tank and add while mixing the preservatives.
Transfer the active medicament to the tank while stirring and record the temperature and pH. of the solution.
Adjust the pH of the solution slowly by intermittent additions of Hydrochloric Acid keeping the temperature of liquid at a desirable level. Adjust the volume with remaining quantity of water for injection and record pH.
Request the Q.C to draw the sample and after released by the QC, filter the liquid aseptically through 0.2 micron filter in sterile container under Nitrogen blanket and fill the liquid in sterilized Ampoule under sterile conditions.
Inspect Ampoule visually to ensure the contents are free of any particulate.
Pack in accordance with laid down GMP standards Equipments/machinery used for the manufacturing of
Injections / Infusions

Yes No
Yes No
Yes No
Yes No
Yes No
Yes No
Yes No
Yes No
Yes No
Yes No
Yes No
Yes No
Yes No
Yes No
Yes No


1. R O Plant
2. Water Deionizer
3. Distillation Plant
4. WFI Storage Tank
5. Mixing Tank
6. Pressure Regulator with Microbial Filter
7. Vial Washing Machine
8. Vial Sterilizer
9. Vial filling Machine
10. Vial sealing Machine
11. Ampoule Washing Machine
12. Ampoule Sterilizer
13. Ampoule Filling/Sealing Machine
14. Pressure Tank
15. Filtration Unit

The physical parameter carried out for the releases of the product
(In process)


1. PHYSICAL VERIFICATION OF INGREDIENTS FOR QUALITY AND QUANTITY.
2. FOLLOWING CHECK ARE CARRIED OUT FOR INPROCESS CONTROL OF PARENTRALS.

a. Av. Volume of ampoules/bottles/vials.
b. pH of the solution.
c. Identifications of Active drug.
d. Code. No. for infusions.
e. Deformation of ampoules/bottles / vials.
f. Particles in ampoules / vials / bottles.
g. LAL test.

3. IN HOUSE PACKAGING CHECKS FOR PARENTRALS.

a. Product name
b. Batch No.
c. Manufacture Date
d. Expiry Date
e. Manufacturing License No.
f. Registration No.
g. Price
h. Labeling
i. Printing
j. Over all view.
k. Grammage of carton
Source of Water

Ground Water


1. Fit for drinking approved by PCSIR.
2. Copy of Certificate Attached.

ENCLOSURE – 09(a)

Water for Injection (BP/USP)

Equipment/Machinery used for the preparation of
“Water For Injection (BP/USP)”
1. Filters
2. De – Ionizer
3. RO – Plant
4. Distillation Plant
5. WFI Storage Tank

Specifications:

Sr. #
TEST PARAMETERS
SPECIFICATIONS

01
Description
A clear, odourless and tasteless liquid.
02
Acidity or Alkalinity
Must be complies to BP.
03
Ammonium
Not more than 0.2 PPM.
04
Calcium/Magnesium
Not more than 0.5 ml of 0.01 EDTA Should be used to produce blue color.
05
Heavy metals
Not more than 0.1 PPM.
06
Chloride
Solution remains clear within 15 minutes or not more than 5 PPM.
07
Nitrate
Not more than 2PPM.
08
Sulphate
No change in appearance within 1 hour.
09
Oxidisable Substance
The solution should remain faintly pink.
10
Residue on evaporation
Should not more than 0.001%.
11
Bacterial Endotoxins
NMT 0.25 units/ml.
12
Conductivity at 25C
NMT 1.3 mS/cm







(Master Formula)

COMPOSITION

Each 1ml contains:


· ACTIVE INGREDIENT

ARTEMETHER BAN..………………….………… 80 mg
(As Sodium)



· INACTIVE INGREDIENT

Edetate Sodium BP/USP…….……….……………….... 1.0mg
NaOH BP/USP….. Q.S to adjust pH between 11.0 and 12.5
Water for Injection BP/USP………… Q.S to


DESCRIPTION OF METHOD OF MANUFACTURE

PROCEDURE:

All the ingredients are checked and released prior to issue for manufacture.
The ingredients are weighed in the presence of Production Pharmacist and rechecked at the time of formulation, and the weights are recorded in the formula card
The ingredients are transferred to the formulation area.
The equipment utensils and the area‘s are checked for proper cleanliness and insured that no trace of foreign matter is visible and that there is no trace of any chemical left behind of any previous product.
Check that the quality of water meets the USP standard before formulation and ensure that it is freshly prepared the Q.C stickers is available.
Rinse the container with freshly prepared pyrogen free distilled water.
Measure the water quantity, record the temperature and bubble Nitrogen through water to remove the traces of Oxygen in a mixing tank and add while mixing the preservatives.
Transfer the active medicament to the tank while stirring and record the temperature and pH. of the solution.
Adjust the pH of the solution slowly by intermittent additions of NaOH solution keeping the temperature of liquid at a desirable level. Adjust the volume with remaining quantity of water for injection and record pH.
Filter the liquid aseptically through 0.2 micron filter in sterile container under Nitrogen blanket and fill the liquid.
Transfer the prepared solution to the sterilized apyrogenized vials equivalent to 40mg of Omeprazole and shift to the Lyophilization chamber (freezed dryer).
After the completion of Lyophilization process transfer the vial to the quarantine area.
Request the Q.C to draw the sample.
Inspect vial visually to ensure the contents are free of any particulate matter.
Pack in accordance with laid down GMP standards.
METHOD OF ANALYSIS
Injection NN 80mg/1ml


Ø Description:
A clear to light yellow colour solution in glass ampoule.

Ø Identification: (Artemether)
The chromatogram of the assay preparation exhibits a major peak for Artemether and , the retention time of which corresponds to the exhibited in the chromatogram of standard preparation as obtained in the assay.

Ø Assay:- (HPLC)

Mobile Phase: Prepare a mixture of acetonitrile and distilled water in the ratio of 70 volumes of acetonitrile and 30 volume of water and 0.05 ml of glacial acetic acid/100ml. filter and degassed mixture of the prepared solution.

Sample preparation:
Mix the contents of 10 ampoules, take sample equivalent to 160mg and make up volume 100ml with mobile phase. Filter through 0.45 micron filter.

Standard preparation:
Weigh accurately Artemether and ref. standard and prepare equal concentrations as mentioned above.

Procedure:
Inject the standard preparations and sample preparation, the tailing factor should not be more than 2% and calculate the contents of active ingredients.

Flow rate 2.0 ml
Pressure 350 Kg
Wave length 215 nm
Column Length 150 mm
Column I.D. 4.6 mm
Injection volume 20 ul

OBSERVATIONS & CALCULATIONS:

Peak area / height of Artemether sample preparation = A
Peak area / height of Artemether standard preparation = B

Limit:
Artemether 90 ----- 110 % of the labeled amount.

The physical parameter carried out for the releases of the product
(In process)


4. PHYSICAL VERIFICATION OF INGREDIENTS FOR QUALITY AND QUANTITY.
5. FOLLOWING CHECK ARE CARRIED OUT FOR INPROCESS CONTROL OF PARENTRALS.

a. Av. Volume of ampoules/bottles/vials.
b. pH of the solution.
c. Identifications of Active drug.
d. Code. No. for infusions.
e. Deformation of ampoules/bottles / vials.
f. Particles in ampoules / vials / bottles.
g. LAL test.

6. IN HOUSE PACKAGING CHECKS FOR PARENTRALS.

a. Product name
b. Batch No.
c. Manufacture Date
d. Expiry Date
e. Manufacturing License No.
f. Registration No.
g. Price
h. Labeling
i. Printing
j. Over all view.
k. Grammage of carton

COMPOSITION

Each vial contains:


q ACTIVE INGREDIENT:

Azithromycin USP…….…………………...…..….. 500mg
(As Dihydrate)


q IN-ACTIVE INGREDIENT:

Citric Acid Anhydrous BP/USP …..………………413.6 mg
NaOH BP/USP………………………………………114 mg
pH …………………………………………………4.0 --- 6.0
Water for Injection BP/USP (re – constitution) ……... 10ml


Method of analysis
AZIT 500mg/vial

COMPOSITION: Each vial contains:
AZITHROMYCIN USP ………………………….500mg
DESCRIPTION: White to pale yellow powder in glass vials.

IDENTIFICATION: - To 1 g powder in test tube, add 5 ml of 1 M hydrochloric acid, shake well, add 0.5 ml of 0.05 M iodine solution, and shake vigorously. Brown precipitates appear which convert to brown black tinny particles.

pH (When constituted as directed): Between 4.0 and 6.0
STERILITY TEST: Conforms to USP
Bacterial Endotoxin: Confirms to USP

ASSAY:-
METHOD OF ANALYSIS:

Sample Preparation:

Reconstitute the average dry powder for injection, take sample equivalent to 200 mg Azithromycin USP. Transfer to a separatory funnel, add 10 ml of water and extract with 3 x 30 ml of chloroform. Collect the chloroform layer and evaporate it on water bath at 50 – 60 C to dryness. Dissolve the residue in 50 ml of glacial acetic acid, Titrate with 0.1M perchloric acid using 0.05 ml crystal violet solution as indicator till the bluish green colour is produced.
Each ml of 0.1M perchloric acid is equivalent to 37.45.mg of Azithromycin.

Blank:
To 50 ml of glacial acetic acid, Titrate with 0.1M perchloric acid using 0.05 ml crystal violet solution as indicator till the bluish green colour is produced.

Observations & Calculations:

Sample taken = 200 mg

Volume of 0.1M perchloric acid used for sample. = A

Volume of 0.1M perchloric acid used for blank. = B

Net volume of 0.1M perchloric acid used for sample. = A - B

Azithromycin % = D X 37.45 X 100
200

Limit: The contents of Azithromycin should be 90.0 --- 110.0% of the label claim.










MASTER FORMULA



COMPOSITION

Each 1ml Ampoule Contains:


· ACTIVE INGREDIENT

Buprenorphine HCl BP ………………..….….0.324mg
Equivalent to Buprenorphine BP …………..…….0.3mg



· INACTIVE INGREDIENT

Dextrose (Anhydrous) BP/USP…….……….……50mg
HCl BP/USP….. Q.S to adjust pH between 3.5 and 5.5
Water for Injection BP/USP…………..….. Q.S to 1.0ml





DESCRIPTION OF METHOD OF MANUFACTURE.

PROCEDURE:

All the ingredients are checked and released prior to issue for manufacture.
The ingredients are weighed in the presence of Production Pharmacist and rechecked at the time of formulation, and the weights are recorded in the formula card
The ingredients are transferred to the formulation area.
The equipment utensils and the area‘s are checked for proper cleanliness and insured that no trace of foreign matter is visible and that there is no trace of any chemical left behind of any previous product.
Check that the quality of water meets the USP standard before formulation and ensure that it is freshly prepared and the Q.C stickers is available.
Rinse the container with freshly prepared Pyrogen free distilled water.
Measure the water quantity, record the temperature and Bubble Nitrogen through water to remove the traces of Oxygen in a mixing tank and add while mixing the preservatives.
Transfer the active medicament to the tank while stirring and record the temperature and pH. of the solution.
Adjust the pH of the solution slowly by intermittent additions of Hydrochloric Acid keeping the temperature of liquid at a desirable level. Adjust the volume with remaining quantity of water for injection and record pH.
Request the Q.C to draw the sample and after released by the QC, filter the liquid aseptically through 0.2 micron filter in sterile container under Nitrogen blanket and fill the liquid in sterilized Ampoule under sterile conditions.
Inspect Ampoule visually to ensure the contents are free of any particulate.
Pack in accordance with laid down GMP standards.
PHARMACOLOGICAL & CLINICAL DATA

A. DESCRIPTION
XX is a synthetic opioid agonist-antagonistic analgesic. The active ingredient of XX is Buprenorphine hydrochloride, [N-cyclopropylmethyl-7alpha-(1-(S)-hydroxy-1,2,2-trimethylpropyl- 6-,14-endoethano-6,7,8,14-tetrahydronororipavine hydrochloride].
Buprenorphine hydrochloride is a highly lipophilic ring C bridges oripavine derivative of thebaine.

B. CHEMICAL STRUCTURE

C. INDICATIONS
Strong analgesic for short-term (not more than 1 week) relief of moderate to severe pain, including post-operative and terminal pain. XX Injection should be employed when sublingual administration is not practical e.g. pre- or peri-operatively. It is not recommended for use in children.
Buprenorphine does not have an approved role in opioid dependence rehabilitation programs.

D. CLINICAL PHARMACOLOGY
XX is a parenteral opioid analgesic with 0.3 mg XX being approximately equivalent to 10 mg morphine sulfate in analgesic and respiratory depressant effects in adults. Pharmacological effects occur as soon as 15 minutes after intramuscular injection and persist for 6 hours or longer. Peak pharmacologic effects usually are observed at 1 hour. When used intravenously, the times to onset and peak effect are shortened.
The limits of sensitivity of available analytical methodology precluded demonstration of bioequivalence between intramuscular and intravenous routes of administration. In postoperative adults, pharmacokinetic studies have shown elimination half-lives ranging from 1.2-7.2 hours (mean 2.2 hours) after intravenous administration of 0.3 mg of Buprenorphine. A single, ten-patient, pharmacokinetic study of doses of 3 µg/kg in children (age 5-7 years)

showed a high inter-patient variability, But suggests that the clearance of the drug may be higher in children than in adults. This is supported by at least one repeat-dose study in postoperative pain that showed an optimal inter-dose interval of 4-5 hours in pediatric patients as opposed to the recommended 6-8 hours in adults.
Buprenorphine, in common with morphine and other phenolic opioid analgesics, is metabolized by the liver and its clearance is related to hepatic blood flow. Studies in patients anesthetized with 0.5% halothane have shown that this anesthetic decreases hepatic blood flow by about 30%.
Mechanism of Analgesic Action: XX exerts its analgesic effect via high affinity binding to µ subclass opiate receptors in the central nervous system. Although XX may be classified as a partial agonist, under the conditions of recommended use it behaves very much like classical µ agonists such as morphine. One unusual property of XX observed in in vitro studies is its very slow rate of dissociation from its receptor. This could account for its longer duration of action than morphine, the unpredictability of its reversal by opioid antagonists, and its low level of manifest physical dependence.
Narcotic Antagonist Activity: Buprenorphine demonstrates narcotic antagonist activity and has been shown to be equipotent with naloxone as an antagonist of morphine in the mouse tail flick test.
Cardiovascular Effects: XX may cause a decrease or, rarely, an increase in pulse rate and blood pressure in some patients.
Effects on Respiration: Under usual conditions of use in adults, both XX and morphine show similar dose-related respiratory depressant effects. At adult therapeutic doses, XX (0.3 mg Buprenorphine) can decrease respiratory rate in an equivalent manner to an equianalgesic dose of morphine (10 mg).

E. CONTRA-INDICATIONS
Pregnancy and Lactation (see Use in Pregnancy and Use in Lactation).
XX should not be administered to patients who have been shown to be hypersensitive to Buprenorphine.

F. WARNINGS
Because of the narcotic antagonist activity of Buprenorphine, use in individuals dependent on other opioids may result in withdrawal effects.
Use in Pregnancy
Category C. Narcotic analgesics may cause respiratory depression in the newborn infant. Therefore, during the last 2-3 hours before expected delivery, these products should only be used after weighing the needs of the mother against the risk to the foetus.



Buprenorphine readily crosses the placental barrier. The safety of Buprenorphine in pregnancy has not been established and therefore it should not be used in women who are pregnant or who are likely to become pregnant unless the potential benefits outweigh the possible risks.
Australian categorisation definition of:
Category C
Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human foetus or neonate without causing malformations. These effects may be reversible. Accompanying text above should be consulted for further details.
Use in Lactation
It is not known whether Buprenorphine is secreted in breast milk and safety in the new born has not been established. Therefore, it should not be given to nursing mothers.

G. PRECAUTIONS
Cardiovascular Effects: Buprenorphine may cause a slight reduction in pulse rate and blood pressure in some patients.
Head Injury and Increased Intracranial Pressure: Although there is no clinical experience in patients with elevated cerebrospinal fluid (CSF) pressure caused by head injury or intracranial lesions, Buprenorphine should be used with caution. Experience with other opioid analgesics indicates that respiratory depressant effects may elevate CSF pressure due to vasodilation from the CO2 retention. This may be markedly exaggerated with pre-existing elevation of CSF pressure or head injury or intracranial lesions. Furthermore, Buprenorphine produces miosis and may change the level of consciousness, thus interfering with patient evaluation. The miosis is more marked than with morphine and persists for more than 24 hours.
Respiratory Depression: As with most analgesic drugs acting at the opiate receptor, Buprenorphine may cause respiratory depression and whilst this is rarely of clinical significance, it should be used with caution in patients with either compromised respiratory function or those given respiratory depressant drugs, especially as there is no fully effective antagonist.
Respiratory depression following sublingual Buprenorphine is more likely to occur with doses exceeding 0.4 mg.
Should respiratory depression occur to clinically undesirable degree, supportive measures should be used to maintain adequate ventilation and oxygenation. The effects of Buprenorphine are only partially reversed by standard narcotic reversal agents, such as naloxone.
Hepatic Dysfunction: Because Buprenorphine is metabolised by the liver, the intensity and duration of its action may be altered in those individuals with impaired hepatic function.

H. OVERDOSAGE
Symptoms: There is limited experience of accidental or intentional overdosage at the present time, But doses in the range 3 to 7 mg have been administered intravenously without producing clinically significant respiratory effects. Extrapolating from the animal pharmacology of the agent, respiratory depression is likely to occur in the event of overdosage, together with cardiovascular depression and some CNS effects, such as sedation. Therefore, the respiratory and cardiac status of the patient should be carefully monitored.
Treatment: Primary attention should be given to the re-establishment of adequate respiratory exchange. Oxygen, intravenous fluids, vasopressors and other supportive measures should be employed as indicated. Intravenous naloxone given repeatedly may be partially effective.

I. DRUG INTERACTIONS
(a) Monoamine Oxidase Inhibitors: Until further information is available, Buprenorphine should be used with caution in patients receiving monoamine oxidase inhibitors as these may intensify its adverse effects.
(b) CNS Depressants: Buprenorphine may cause some drowsiness, and this could be potentiated by other centrally-acting agents such as long acting benzodiazepines, volatile anaesthetics and certain induction agents. Hence, amBulant patients should be warned not to drive or operate machinery if affected.
(c) Narcotic Antagonist Activity: Buprenorphine demonstrates narcotic antagonist activity and has been shown to reverse the effects of peri-operatively administered narcotics. It may, therefore, precipitate mild withdrawal symptoms in narcotic addicts and it should be given with care, initially, to patients previously treated with narcotic analgesics.

J. ADVERSE REACTIONS
Drowsiness, or sleep from which the patient can easily be aroused, occurs in most patients, particularly in the post-operative period.
Gastrointestinal System: Nausea and vomiting have been reported in 9% and 7% of patients respectively, and may be worse in amBulatory patients. Administering a lower dose, or having the patient lie down may alleviate these effects.
Dry mouth and constipation have rarely been reported.
Central Nervous System: Often associated with nausea and vomiting, But less frequently, are headache and symptoms of dizziness (1%) and sweating (1%). Improved mood or mild euphoria has been reported in 0.28% of cases.
Hallucinations and other psychotomimetic effects have rarely been reported.

Respiratory System: Significant respiratory depression has been observed infrequently and is rarely of clinical significance.
Genito-urinary: Difficulty in urination has occurred in less than 1% of patients.
Cardiovascular: Slight bradycardia and hypotension occur. Tachycardia and hypertension have been rarely reported.
Other: For XX Injection, localised skin reactions at the injection site and hypersensitivity symptoms have been rarely reported, with one reported case of anaphylactic reaction.



Gastrointestinal System: Nausea and vomiting have been reported in 9% and 7% of patients respectively, and may be worse in amBulatory patients. Administering a lower dose, or having the patient lie down may alleviate these effects.
Dry mouth and constipation have rarely been reported.
Central Nervous System: Often associated with nausea and vomiting, But less frequently, are headache and symptoms of dizziness (1%) and sweating (1%). Improved mood or mild euphoria has been reported in 0.28% of cases.
Hallucinations and other psychotomimetic effects have rarely been reported.

Respiratory System: Significant respiratory depression has been observed infrequently and is rarely of clinical significance.
Genito-urinary: Difficulty in urination has occurred in less than 1% of patients.
Cardiovascular: Slight bradycardia and hypotension occur. Tachycardia and hypertension have been rarely reported.
Other: For XX Injection, localised skin reactions at the injection site and hypersensitivity symptoms have been rarely reported, with one reported case of anaphylactic reaction.



MASTER FORMULA



COMPOSITION

Each 2ml ampoule Contains:


· ACTIVE INGREDIENT

CIMETIDINE BP ………………………..………………..…. 200mg
(As HCl)



· INACTIVE INGREDIENT

Sodium Meta Bisulfite BP/USP……………………….……1.3mg
Sodium Citrate BP/USP……………………………………. 5.0mg
Sulfuric Acid BP/USP …………….Q.S to Adjust pH 3.8 and 6.0
Water for Injection BP/USP…………..…………... Q.S to 2.0ml







MASTER FORMULA



COMPOSITION

Each 50ml vial contains:


· ACTIVE INGREDIENT

Ciprofloxacin USP …….…….………..………… …100mg
(As Lactate)



· INACTIVE INGREDIENT

Sodium Chloride BP/USP……………….………….…….… 0.9g
Lactic Acid BP/USP….……Q.S to adjust pH between 3.5 and 4.5
Water for Injection BP/USP…….….………..…..….. Q.S to 50ml

PHARMACOLOGICAL & CLINICAL DATA


A. Chemical Structure
B. Description
A fluoroquinolone is the salt of 1-cyclopropyl-6-fluora-1, 4-dihydro-4-oxa-7-(1-piperazinyl)-3-quinolinecarboxylic acid. It is a faintly yellowish to light yellow crystalline substance with a molecular weight of 385.8. Its empirical formula is C17H18FN3O3.
Ciprofloxacin is 1-cyclopropyl-6-fluoro-1, 4-drhydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid. Its empirical formula is C17H18FN3O3 and its molecular weight is 331.4 It is a faintly yellowish to light yellow crystalline substance.
Ciprofloxacin differs from other quinolones in that it has a fluorine atom at the 6-position, a piperazine moiety at the 7-position, and a cyclopropyl ring at the 1-position.

C. Indications and Usage
UTI, respiratory, ENT, eye, skin and soft tissue, bone, joint, pelvic, biliary tract, intra-abdominal and Gl infection. Gonorrhoea. Severe systemic infection. Gram-negative pneumonia (not for first line treatment in pneumococcal pneumonia). Prophylaxis in upper Gl surgery or endoscopy.

D. Warnings
NOT FOR OPHTHALMIC USE. NOT FOR INJECTION.
XX should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some following the first dose, have been reported



in patients receiving systemic quinolones. Serious acute hypersensitivity reactions may require immediate emergency treatment.

E. Precautions
Do not use this medicine if you have had a severe allergic reaction to this medicine or another fluoroquinolone antibiotic. A severe reaction includes a severe rash, hives, breathing difficulties, or dizziness. If you experience difficulty breathing; tightness of chest; swelling of eyelids, face, or lips; or if you develop a rash or hives, tell your doctor immediately. For women: if you plan on becoming pregnant, discuss with your doctor the benefits and risks of using this medicine during pregnancy. It is unknown if this medicine is excreted in breast milk. Do not breast-feed while taking this medicine.

F. Adverse Reactions
In Phase 3 clinical trials, a total of 564 patients were treated with XX. Adverse events with at least remote relationship to treatment included headache (1.2%) and pruritus (0.4%). The following treatment-related adverse events were each reported in a single patient: migraine, hypesthesia, paresthesia, fungal dermatitis, cough, rash, urticaria, and alopecia.

G. Storage Conditions:
Store below 30°C. Keep out of reach of children.







DOSAGE AND ADMINISTRATION

DOSAGE AND DIRECTIONS FOR USE:
Dosage and Duration of Treatment:
The dosage of XX IV is determined by the severity and type of infection, the sensitivity of the causative organism(s) and the age, mass and renal function of the patient. The usual dose is 100 mg - 200 mg IV every 12 hours. For severe and/or complicated infections 400 mg may be administered every 12 hours (i.e. bd). Intravenous therapy should be discontinued as soon as oral ciprofloxacin therapy can be substituted. The normal duration of intravenous therapy is up to 7 days.

Cystic fibrosis:
In cystic fibrosis patients the normal dose is 200 mg IV twice daily. The low body mass of these patients should, however, be taken into consideration when determining dosage (5-10 mg/kg/day).

Directions for Intravenous Administration:
XX IV should be administered by intravenous infusion over a period of 60 minutes. Slow infusion into a large vein will minimize patient discomfort and reduce the risk of venous irritation. The infusion solution can be infused either directly or after mixing with the other compatible infusion solutions.
The XX IV infusion solution is compatible with physiological saline, Ringer solution and Ringer lactate solution, 5% and 10% glucose solutions, 10% fructose solution, and 5% glucose solution with 0.225% NaCl or 0.45% NaCl. When ciprofloxacin infusion solutions are mixed with compatible infusion solutions, for microbiological reasons and light sensitivity these solutions should be administered shortly after admixture.

Important incompatibilities:
Unless compatibility with other infusion solutions/drugs has been confirmed, the infusion solution must always be administered separately. The visual signs of incompatibility are e.g. precipitation, clouding and discolouration.
Incompatibility appears with all infusion solutions/drugs that are physically or chemically unstable at the pH of the solution (e.g. penicillins, heparin solutions), especially on combination with solutions adjusted to an alkaline pH (pH of the ciprofloxacin infusion solutions: 3.9-4.5).
Any remaining solution should be discarded.

Impaired Renal or Liver Function:
In patients with reduced renal function, the half-life of ciprofloxacin is prolonged and the dosage needs to be adjusted.
For patients with changing renal function or patients with renal impairment and hepatic insufficiency, monitoring of drug serum levels provides the most reliable basis for dose adjustment.





MASTER FORMULA


COMPOSITION

Each 2ml contains:


· ACTIVE INGREDIENT

TOBRAMYCIN USP ….………...……………...……….… .20mg
(as TOBRAMYCIN Sulphate)


· INACTIVE INGREDIENT

1. Benzyl alcohol USP .…………………………………. 18mg
2. Sodium Metabisulphite BP ..………………………….. 6.4mg
3. Disod. Edetate BP/USP ……………………………… 0.1mg
4. Sulfuric acid BP/USP……QS to adjust pH between 3.0 to 6.5
5. Water for Injection BP/USP .……………………………QS to 2ml






DESCRIPTION OF METHOD OF MANUFACTURE.

PROCEDURE:

All the ingredients are checked and released prior to issue for manufacture.
The ingredients are weighed in the presence of Production Pharmacist and rechecked at the time of formulation, and the weights are recorded in the formula card
The ingredients are transferred to the formulation area.
The equipment utensils and the area‘s are checked for proper cleanliness and insured that no trace of foreign matter is visible and that there is no trace of any chemical left behind of any previous product.
Check that the quality of water meets the USP standard before formulation and ensure that it is freshly prepared and the Q.C stickers is available.
Rinse the container with freshly prepared Pyrogen free distilled water.
Measure the water quantity, record the temperature and Bubble Nitrogen through water to remove the traces of Oxygen in a mixing tank and add while mixing the preservatives.
Transfer the active medicament to the tank while stirring and record the temperature and pH. of the solution.
Adjust the pH of the solution slowly by intermittent additions of Hydrochloric Acid keeping the temperature of liquid at a desirable level. Adjust the volume with remaining quantity of water for injection and record pH.
Request the Q.C to draw the sample and after released by the QC, filter the liquid aseptically through 0.2 micron filter in sterile container under Nitrogen blanket and fill the liquid in sterilized Ampoule under sterile conditions.
Inspect Ampoule visually to ensure the contents are free of any particulate.
Pack in accordance with laid down GMP standards.
MASTER FORMULA


COMPOSITION

Each 2ml Ampoule Contains:


· ACTIVE INGREDIENT

TRAMADOL HCl BP …………………………..100mg


· INACTIVE INGREDIENT

Dextrose (Anhydrous) BP/USP…….……….……50mg
HCl BP/USP….. Q.S to adjust pH between 3.0 and 5.5
Water for Injection BP/USP…………..….. Q.S to 2.0ml





DESCRIPTION OF METHOD OF MANUFACTURE.

PROCEDURE:

All the ingredients are checked and released prior to issue for manufacture.
The ingredients are weighed in the presence of Production Pharmacist and rechecked at the time of formulation, and the weights are recorded in the formula card
The ingredients are transferred to the formulation area.
The equipment utensils and the area‘s are checked for proper cleanliness and insured that no trace of foreign matter is visible and that there is no trace of any chemical left behind of any previous product.
Check that the quality of water meets the USP standard before formulation and ensure that it is freshly prepared and the Q.C stickers is available.
Rinse the container with freshly prepared Pyrogen free distilled water.
Measure the water quantity, record the temperature and Bubble Nitrogen through water to remove the traces of Oxygen in a mixing tank and add while mixing the preservatives.
Transfer the active medicament to the tank while stirring and record the temperature and pH. of the solution.
Adjust the pH of the solution slowly by intermittent additions of Hydrochloric Acid keeping the temperature of liquid at a desirable level. Adjust the volume with remaining quantity of water for injection and record pH.
Request the Q.C to draw the sample and after released by the QC, filter the liquid aseptically through 0.2 micron filter in sterile container under Nitrogen blanket and fill the liquid in sterilized Ampoule under sterile conditions.
Inspect Ampoule visually to ensure the contents are free of any particulate.
Pack in accordance with laid down GMP standards


MASTER FORMULA



COMPOSITION

Each 5ml Ampoule Contains:


· ACTIVE INGREDIENT

Tranexamic Acid USP ………………………..………………..….250mg



· INACTIVE INGREDIENT

Sodium Meta Bisulfite BP/USP……………………….……1.3mg
Sodium Citrate BP/USP……………………………………. 5.0mg
Sulfuric Acid BP/USP …………….Q.S to Adjust pH 6.5 and 8.0
Water for Injection BP/USP…………..…………... Q.S to 5.0ml






DESCRIPTION OF METHOD OF MANUFACTURE.

PROCEDURE:

All the ingredients are checked and released prior to issue for manufacture.
The ingredients are weighed in the presence of Production Pharmacist and rechecked at the time of formulation, and the weights are recorded in the formula card
The ingredients are transferred to the formulation area.
The equipment utensils and the area‘s are checked for proper cleanliness and insured that no trace of foreign matter is visible and that there is no trace of any chemical left behind of any previous product.
Check that the quality of water meets the USP standard before formulation and ensure that it is freshly prepared and the Q.C stickers is available.
Rinse the container with freshly prepared Pyrogen free distilled water.
Measure the water quantity, record the temperature and Bubble Nitrogen through water to remove the traces of Oxygen in a mixing tank and add while mixing the preservatives.
Transfer the active medicament to the tank while stirring and record the temperature and pH. of the solution.
Adjust the pH of the solution slowly by intermittent additions of Hydrochloric Acid keeping the temperature of liquid at a desirable level. Adjust the volume with remaining quantity of water for injection and record pH.
Request the Q.C to draw the sample and after released by the QC, filter the liquid aseptically through 0.2 micron filter in sterile container under Nitrogen blanket and fill the liquid in sterilized Ampoule under sterile conditions.
Inspect Ampoule visually to ensure the contents are free of any particulate.
Pack in accordance with laid down GMP standar METHOD OF ANALYSIS
Injection T 250mg/5ml


Ø Description:
A clear colourless solution.

Ø Identification: (Tranexamic Acid)
The chromatogram of the assay preparation exhibits a major peak for Tranexamic Acid and, the retention time of which corresponds to the exhibited in the chromatogram of standard preparation as obtained in the assay.

Ø pH 6.5 -------------8.0
Ø Sterility Testing (Confirms to USP)
Ø Assay:- (HPLC)
Mobile Phase: Prepare a mixture of acetonitrile and distilled water in the ratio of 70 volumes of acetonitrile and 30 volume of water and 0.05 ml of glacial acetic acid/100ml. filter and degassed mixture of the prepared solution.

Sample preparation:
Mix the contents of 10 ampoules, take sample equivalent to 20mg of Tranexamic Acid and make up volume 50ml with mobile phase. Filter through 0.40 micron filter.

Standard preparation:
Weigh accurately Tranexamic Acid and ref. standard and prepare equal concentrations as mentioned above.

Procedure:
Inject the standard preparations and sample preparation, the tailing factor should not be more than 2% and calculate the contents of active ingredients.

Flow rate 2.0 ml
Pressure 350 Kg
Wave length 420 nm
Column Length 150 mm
Column I.D. 4.6 mm
Injection volume 20 ul

OBSERVATIONS & CALCULATIONS:
Peak area / height of Tranexamic Acid sample preparation = A
Peak area / height of Tranexamic Acid standard preparation = B






MASTER FORMULA



COMPOSITION

Each 1ml Ampoule Contains:


· ACTIVE INGREDIENT

SODIUM HYALURANATE BP…………………..10mg


· INACTIVE INGREDIENT

Sodium Chlorid BP/USP…….……….…………8.5mg
Monobasic Sod. Phosphate BP/USP…….……….0.1mg
Dibasic Sod. Phosphate BP/USP…….……….… 1.2mg
NaOH BP/USP….. Q.S to adjust pH between 6.8 and 8.0
Water for Injection BP/USP…………..….. Q.S to 1.0ml





DESCRIPTION OF METHOD OF MANUFACTURE.

PROCEDURE:

All the ingredients are checked and released prior to issue for manufacture.
The ingredients are weighed in the presence of Production Pharmacist and rechecked at the time of formulation, and the weights are recorded in the formula card
The ingredients are transferred to the formulation area.
The equipment utensils and the area‘s are checked for proper cleanliness and insured that no trace of foreign matter is visible and that there is no trace of any chemical left behind of any previous product.
Check that the quality of water meets the USP standard before formulation and ensure that it is freshly prepared and the Q.C stickers is available.
Rinse the container with freshly prepared Pyrogen free distilled water.
Measure the water quantity, record the temperature and Bubble Nitrogen through water to remove the traces of Oxygen in a mixing tank and add while mixing the preservatives.
Transfer the active medicament to the tank while stirring and record the temperature and pH. of the solution.
Adjust the pH of the solution slowly by intermittent additions of Hydrochloric Acid keeping the temperature of liquid at a desirable level. Adjust the volume with remaining quantity of water for injection and record pH.
Request the Q.C to draw the sample and after released by the QC, filter the liquid aseptically through 0.2 micron filter in sterile container under Nitrogen blanket and fill the liquid in sterilized Ampoule under sterile conditions.
Inspect Ampoule visually to ensure the contents are free of any particulate.
Pack in accordance with laid down GMP standards.





MASTER FORMULA



COMPOSITION

Each 2ml Ampoule Contains:


· ACTIVE INGREDIENT

Ranitidine USP ………………………..………………..…. 50mg
(As HCl)



· INACTIVE INGREDIENT

Sodium Meta Bisulfite BP/USP……………………….……1.3mg
Sodium Citrate BP/USP……………………………………. 5.0mg
Sulfuric Acid BP/USP …………….Q.S to Adjust pH 6.7 and 7.3
Water for Injection BP/USP…………..…………... Q.S to 2.0ml














DESCRIPTION OF METHOD OF MANUFACTURE

PROCEDURE:

All the ingredients are checked and released prior to issue for manufacture for method
The ingredients are weighed in the presence of Production Pharmacist and Q.C inspector and rechecked at the time of formulation, and the weights are recorded in the formula card
The ingredients are transferred to the formulation area.
The equipment utensils and the area‘s are checked for proper cleanliness and insured that no trace of foreign matter is visible and that there is no trace of any chemical left behind of any previous product.
Check that the quality of water meets the BP standard before formulation and ensure that it is freshly prepared the Q.C stickers is available.
Rinse the container with freshly prepared pyrogen free distilled water.
Measure the water quantity, record the temperature and bubble Nitrogen through water to remove the traces of Oxygen in a mixing tank and add while mixing the preservatives.
Transfer the active medicament to the tank while stirring and record the temperature and pH. of the solution.
Adjust the pH of the solution slowly by intermittent additions of Hydrochloric Acid keeping the temperature of liquid at a desirable level. Adjust the volume with remaining quantity of water for injection and record pH.
Request the Q.C to draw the sample and after released by the QC, filter the liquid aseptically through 0.2 micron filter in sterile container under Nitrogen blanket and fill the liquid in sterilized vials under sterile conditions.
Inspect vials visually to ensure the contents are free of any particulate matte.
Pack in accordance with laid down GMP standards.
The packed batch is sent under controlled conditions.
METHOD OF ANALYSIS
Infusion XX 100mg/50ml


Description: Clear greenish yellow, solution in glass vials.

pH: between 3.5 and 4.6

Identification: The retention time of sample solution corresponds to the retention time of standard
solution in assay.
STERILITY TEST: - Conforms to USP.
ENDOTOXIN/PYROGEN TEST: Confirms to USP
Assay (Ciprofloxacin): 90 — 110 % of the label’s claim
(as Lactate)
Carry out the method for liquid chromatography, Appendix III D, using the following solutions. For solution (1) dilute a quantity of the intravenous infusion with sufficient of the mobile phase to produce a solution containing the equivalent of 0.5% w/v of Ciprofloxacin. Solution (2) contains 0.058% w/v ciprofloxacin hydrochloride EPCRS in the mobile phase. Solution (3) contains 0.025% w/v of ciprofloxacin impurity C EPCRS (ethylene-diamine compound) in solution (2). For solution (4) dilute 1 volume of solution (3) to 100 volumes with the mobile phase.
The chromatographic procedure may be carried out using (a) a stainless steel column (150mm x 4.6mm) packed with stationary phase C (5um) (Nucleosil C18 is suitable), (b) as the mobile phase with a flow rate of 1.5ml per minute a mixture of 13 volumes of acetonitrile and 87 volumes of a 0.245% w/v solution of orthophosphoric acid the pH of which has been adjusted to 3.0 with triethylamin and (c) a detection wavelength of 278nm. Maintain the temperature of the column at 40o.
The assay is not valid unless, in the chromatogram obtained with solution (3), the resolution factor between the peaks due to ciprofloxacin and ciprofloxacin impurity C is at least 1.5.Calculate the content of C17H18FN3O3 in the intravenous infusion using the declared content of C17H19CIFN3O3 is equivalent to 0.9010mg of C17H18FN3O3.
(MASTER FORMULA)

COMPOSITION

Each vial contains:


· ACTIVE INGREDIENT

RABEPRAZOLE INN..…………………...………… 20 mg
(As Sodium)

· INACTIVE INGREDIENT

Edetate Sodium BP/USP…….……….……………….... 1.0mg
NaOH BP/USP….. Q.S to adjust pH between 11.0 and 12.5
Water for Injection BP/USP………… Q.S to form the solution
for Lyophilization














DESCRIPTION OF METHOD OF MANUFACTURE

PROCEDURE:

All the ingredients are checked and released prior to issue for manufacture.
The ingredients are weighed in the presence of Production Pharmacist and rechecked at the time of formulation, and the weights are recorded in the formula card
The ingredients are transferred to the formulation area.
The equipment utensils and the area‘s are checked for proper cleanliness and insured that no trace of foreign matter is visible and that there is no trace of any chemical left behind of any previous product.
Check that the quality of water meets the USP standard before formulation and ensure that it is freshly prepared the Q.C stickers is available.
Rinse the container with freshly prepared pyrogen free distilled water.
Measure the water quantity, record the temperature and bubble Nitrogen through water to remove the traces of Oxygen in a mixing tank and add while mixing the preservatives.
Transfer the active medicament to the tank while stirring and record the temperature and pH. of the solution.
Adjust the pH of the solution slowly by intermittent additions of NaOH solution keeping the temperature of liquid at a desirable level. Adjust the volume with remaining quantity of water for injection and record pH.
Filter the liquid aseptically through 0.2 micron filter in sterile container under Nitrogen blanket and fill the liquid.
Transfer the prepared solution to the sterilized apyrogenized vials equivalent to 40mg of Omeprazole and shift to the Lyophilization chamber (freezed dryer).
After the completion of Lyophilization process transfer the vial to the quarantine area.
Request the Q.C to draw the sample.
Inspect vial visually to ensure the contents are free of any particulate matter.
Pack in accordance with laid down GMP standards.
PHARMACOLOGICAL & CLINICAL DATA

A. Description:
Rabeprazole belongs to a class of antisecretory compounds (substituted benzimidazole proton-pump inhibitors) that do not exhibit anticholinergic or histamine H 2 -receptor antagonist properties, but suppress gastric acid secretion by inhibiting the gastric H + K + ATPase at the secretory surface of the gastric parietal cell. Because this enzyme is regarded as the acid (proton) pump within the parietal cell, rabeprazole has been characterized as a gastric proton pump inhibitor. Rabeprazole blocks the final step of gastric acid secretion. In gastric parietal cells, rabeprazole is protonated, accumulates, and is transformed to an active sulfenamide.

B. Indications:
It is an alternative in patients for whom oral administration of Rabeprazole is not indicated.
GHI i.v . is indicated in the treatment of :
1. .Sequential-therapy(step-up) from oral GHI, e.g. A patient previously on oral GHI who is temporarily unable to
take oral medication for any reason.
2. .Active duodenal ulcer with bleeding or severe erosions.
3. .Active gastric ulcer with bleeding or severe erosions.
4. .Short-term treatment of erosive or ulcerative gastroesophageal reflux disease (GERD)
5. .Prevention of acid-aspiration .
6. .Stress-induced mucosal injury in critical care.
7. .Pathological hypersecretory conditions, including Zollinger-Ellison syndrome.

C. Contra-Indications:
Rabeprazole is contraindicated in patients with known hypersensitivity to rabeprazole, substituted benzimidazoles or to any component of the formulation.

D. Warnings And Precautions:
It is an alternative in patients in whom oral administration of rabeprazole is not indicated.Symptomatic response to therapy with rabeprazole does not preclude the presence of gastric malignancy.

E. Side-Effects:
Adverse events with rabeprazole are mild to moderate in intensity and included malaise, diarrhoea, nausea, skin eruptions, headache and dizziness. Abnormal laboratory findings (increased hepatic enzymes, LDH, blood urea nitrogen) with rabeprazole were similar in incidence and severity with comparator agents and reversible with cessation of therapy.

F. Drug Interactions:
Rabeprazole sodium undergoes an almost complete, mainly non-enzymatic metabolism with renal elimination of the metabolites, CYP 450 enzymes contributed to the fraction of metabolism mediated enzymatically. Rabeprazole does not have clinically significant interactions with other drugs metabolized by the CYP450 system, such as warfarin, theophylline, diazepam and phenytoin.

G. Overdosage:
Rabeprazole is extensively protein bound and is not readily dialyzable. In the event of overdosage, treatment should be symptomatic and supportive.

H. Storage:
Store below 30°C. Protect from light.


MASTER FORMULA



COMPOSITION

Each 5ml Ampoule Contains:


· ACTIVE INGREDIENT

PIRACETAM BP ………………………..………………... 1.0gm



· INACTIVE INGREDIENT

Sodium Metaby Suphite BP/USP……………………….… 10mg
NaOH BP/USP……………..…… Q.S to Adjust pH 5.5 and 7.0
Sulfuric Acid BP/USP …………….Q.S to Adjust pH 5.5 and 7.0
Water for Injection BP/USP…………..…………... Q.S to 5.0ml





DESCRIPTION OF METHOD OF MANUFACTURE.

PROCEDURE:

All the ingredients are checked and released prior to issue for manufacture.
The ingredients are weighed in the presence of Production Pharmacist and rechecked at the time of formulation, and the weights are recorded in the formula card
The ingredients are transferred to the formulation area.
The equipment utensils and the area‘s are checked for proper cleanliness and insured that no trace of foreign matter is visible and that there is no trace of any chemical left behind of any previous product.
Check that the quality of water meets the USP standard before formulation and ensure that it is freshly prepared and the Q.C stickers is available.
Rinse the container with freshly prepared Pyrogen free distilled water.
Measure the water quantity, record the temperature and Bubble Nitrogen through water to remove the traces of Oxygen in a mixing tank and add while mixing the preservatives.
Transfer the active medicament to the tank while stirring and record the temperature and pH. of the solution.
Adjust the pH of the solution slowly by intermittent additions of Hydrochloric Acid keeping the temperature of liquid at a desirable level. Adjust the volume with remaining quantity of water for injection and record pH.
Request the Q.C to draw the sample and after released by the QC, filter the liquid aseptically through 0.2 micron filter in sterile container under Nitrogen blanket and fill the liquid in sterilized Ampoule under sterile conditions.
Inspect Ampoule visually to ensure the contents are free of any particulate.
Pack in accordance with laid down GMP standards.

METHOD OF ANALYSIS
Injection HIL 1.0gm/5ml

Ø Description:
A clear to light yellow colour solution in glass ampoule.

Ø Identification: (Piracetam)
The chromatogram of the assay preparation exhibits a major peak for Piracetam and , the retention time of which corresponds to the exhibited in the chromatogram of standard preparation as obtained in the assay.

Ø Assay:- (HPLC)

Mobile Phase: Prepare a mixture of acetonitrile and distilled water in the ratio of 70 volumes of acetonitrile and 30 volume of water and 0.05 ml of glacial acetic acid/100ml. filter and degassed mixture of the prepared solution.

Sample preparation:
Mix the contents of 10 ampoules, take sample equivalent to 100mg of Piracetam and make up volume 100ml with mobile phase. Filter through 0.45 micron filter.

Standard preparation:
Weigh accurately Piracetam and ref. standard and prepare equal concentrations as mentioned above.

Procedure:
Inject the standard preparations and sample preparation, the tailing factor should not be more than 2% and calculate the contents of active ingredients.

Flow rate 2.0 ml
Pressure 350 Kg
Wave length 205 nm
Column 150 mm x BDS x C18 x 5 micron
Column I.D. 4.6 mm
Injection volume 20 ul

OBSERVATIONS & CALCULATIONS:

Peak area / height of Piracetam sample preparation = A
Peak area / height of Piracetam standard preparation = B

Limit:
Piracetam 90 ----- 110 % of the labeled amount.






PHARMACOLOGICAL & CLINICAL DATA

I. Description:
Rabeprazole belongs to a class of antisecretory compounds (substituted benzimidazole proton-pump inhibitors) that do not exhibit anticholinergic or histamine H 2 -receptor antagonist properties, but suppress gastric acid secretion by inhibiting the gastric H + K + ATPase at the secretory surface of the gastric parietal cell. Because this enzyme is regarded as the acid (proton) pump within the parietal cell, rabeprazole has been characterized as a gastric proton pump inhibitor. Rabeprazole blocks the final step of gastric acid secretion. In gastric parietal cells, rabeprazole is protonated, accumulates, and is transformed to an active sulfenamide.

J. Indications:
It is an alternative in patients for whom oral administration of Rabeprazole is not indicated.
GHI i.v . is indicated in the treatment of :
8. .Sequential-therapy(step-up) from oral GHI, e.g. A patient previously on oral GHI who is temporarily unable to
take oral medication for any reason.
9. .Active duodenal ulcer with bleeding or severe erosions.
10. .Active gastric ulcer with bleeding or severe erosions.
11. .Short-term treatment of erosive or ulcerative gastroesophageal reflux disease (GERD)
12. .Prevention of acid-aspiration .
13. .Stress-induced mucosal injury in critical care.
14. .Pathological hypersecretory conditions, including Zollinger-Ellison syndrome.

K. Contra-Indications:
Rabeprazole is contraindicated in patients with known hypersensitivity to rabeprazole, substituted benzimidazoles or to any component of the formulation.

L. Warnings And Precautions:
It is an alternative in patients in whom oral administration of rabeprazole is not indicated.Symptomatic response to therapy with rabeprazole does not preclude the presence of gastric malignancy.

M. Side-Effects:
Adverse events with rabeprazole are mild to moderate in intensity and included malaise, diarrhoea, nausea, skin eruptions, headache and dizziness. Abnormal laboratory findings (increased hepatic enzymes, LDH, blood urea nitrogen) with rabeprazole were similar in incidence and severity with comparator agents and reversible with cessation of therapy.

N. Drug Interactions:
Rabeprazole sodium undergoes an almost complete, mainly non-enzymatic metabolism with renal elimination of the metabolites, CYP 450 enzymes contributed to the fraction of metabolism mediated enzymatically. Rabeprazole does not have clinically significant interactions with other drugs metabolized by the CYP450 system, such as warfarin, theophylline, diazepam and phenytoin.

O. Overdosage:
Rabeprazole is extensively protein bound and is not readily dialyzable. In the event of overdosage, treatment should be symptomatic and supportive.

P. Storage:
Store below 30°C. Protect from light.
DOSAGE AND ADMINISTRATION

DOSAGE AND DIRECTIONS FOR USE:
The intravenous administration is recommended only in cases where the oral administration is not indicated. As soon as an oral therapy is possible the intravenous therapy should be discontinued.
Recommended dose is intravenous administration of the content of one vial ( 20 mg rabeprazole ) Once daily. Parenteral routes of administration other than intravenous are not recommended.
Injection: The content of the vial needs to be reconstituted with 5 ml sterile water for injection, which should be given slowly over 5-15 min.
Infusion: For intravenous infusion the reconstituted solution should be further diluted and administered as short-term infusion over 15-30 min.
Compatibility with various I.V. fluids
GHI I.V. is compatible with Dextrose injection, Dextrose saline injection.
Dosage In Special Populations: No dosage adjustment is necessary in elderly patients, in patients with renal disease or in patients with mild to moderate hepatic impairment. Administration of rabeprazole to patients with mild to moderate liver impairment results in increased exposure and decreased elimination. Due to the lack of clinical data on rabeprazole in patients with severe hepatic impairment, caution should be exercised in these patients.
Reconstitution
To reconstitute add 5 ml of sterile water for injection to make a solution.
After preparation, the reconstituted solution must be used within 4 hours and the unused portion discarded. As with all parenteral admixtures, the reconstituted or further diluted solution should be examined for change in colour, precipitation, haziness or leakage .The unused portion should be discarded.
pH of the reconstituted solution : Between 11.2-12.5



(Master Formula)

COMPOSITION

Each 1ml ampoule contains:


· ACTIVE INGREDIENT

PIROXICAM USP..………………….………………… 20 mg



· INACTIVE INGREDIENT

Propylene Glycol BP/USP …………………………….. 0.4ml
Sodium metabysulphite BP/USP ………………………. 4.0mg
Edetate Sodium BP/USP…….……….……………….... 1.0mg
NaOH BP/USP……... Q.S to adjust pH between 5.0 and 7.0
Water for Injection BP/USP……… Q.S to form 1ml ampoule

.