INJECTION

A-EXARIN

20mg/40mg/60mg/80mg/100mg

(Enoxaparin Sodium Injection USP)

THIS LEAFLET CONTAINSIMPORTANT PRODUCT USE AND SAFETY INFORMATION, PLEASE READ CAREFULLY AND RETAIN FOR FURTHER REFERENCE.

A-EXARIN 20mg

Enoxaparin Sodium Injection USP

Each pre-filled syringe contains:
Enoxaparin Sodium USP 20mg
(Derived from porcine intestinal mucosa)
Water for Injection USP q.s.

A-EXARIN 40mg

Enoxaparin Sodium Injection USP

Each pre-filled syringe contains:
Enoxaparin Sodium USP 40mg
(Derived from porcine intestinal mucosa)
Water for Injection USP q.s.

A-EXARIN 60mg

Enoxaparin Sodium Injection USP

Each pre-filled syringe contains:
Enoxaparin Sodium USP 60mg
(Derived from porcine intestinal mucosa)
Water for Injection USP q.s.

A-EXARIN 80mg

Enoxaparin Sodium Injection USP

Each pre-filled syringe contains:
Enoxaparin Sodium USP 80mg
(Derived from porcine intestinal mucosa)
Water for Injection USP q.s.

A-EXARIN 100mg

Enoxaparin Sodium Injection USP

Each pre-filled syringe contains:
Enoxaparin Sodium USP 100mg
(Derived from porcine intestinal mucosa)
Water for Injection USP q.s.

Pharmaceutical form : Solution for injection in pre-filled syringe (Injection)

THERAPEUTIC INDICATIONS

Enoxaparin is indicated in adults for:·
- Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients, in particular those undergoing ortho paedic or general surgery including cancer surgery.·
-  Prophylaxis of venous thromboembolic disease in medical patients with an acute illness (such as acute heart failure, respiratory insufficiency, severe infections or rheumatic diseases) and reduced mobility at increased risk of venous thromboembolism.·
- Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE)o excluding PE likely to require thrombolytic therapy or surgery.·
-  Prevention of thrombus formation in extra corporeal circulation during haemodialysis.·
- Acute coronary syndrome:

        -Treatment of unstable angina and Non ST-segment elevation myocardial infarction NSTEMI), in combination with oral acetylsalicylic acid.
        -Treatment of acute ST-segment elevation myocardial infarction (STEM I) including patients to be managed medically or with subsequent percutaneous coronary intervention (PCI).

Posology and method of administration Posology

Posology
            -  Prophylaxis of venous thromboembolic disease in moderate and high risk surgical patients Individual thromboembolic risk for patients can be estimated using validated risk stratification model
            - In patients at moderate risk of thromboembolism, the recommended dose of enoxaparin sodium is 2,000 IU (20 mg) once daily by subcutaneous (SC)injection. Preoperative initiation (2 hours before surgery) of enoxaparin sodium 2,000 IU (20 mg) was proven effective and safe in moderate risk surgery.
            - In moderate risk patients, enoxaparin sodium treatment should be maintained for a minimal period of 7-10 days whatever the recovery status (e.g.mobility). Prophylaxis should be continued until the patient no longer has significantly reduced mobility.
            -  In patients at high risk of thromboembolism, the recommended dose of enoxaparin sodium is 4.000 IU (40 mg) once daily given by SC injection preferably started 12 hours before surgery. If there is a need for earlier than12 hours enoxaparin sodium preoperative prophylactic initiation (e.g. high risk patient waiting for a differed orthopaedic surgery), the last injection should be administered no later than 12 hours prior to surgery and resumed 12 hours after surgery.
           - For patients who undergo major orthopaedic surgery an extended thrombo prophylaxis up to 5 weeks is recommended.
            -  For patients with a high venous thromboembolism (VTE) risk who undergo abdominal or pelvic surgery for cancer an extended thrombo prophylaxis up to 4 weeks is recommended.
           - Prophylaxis of venous thromboembolism in medical patients

The recommended dose of enoxaparin sodium is 4,000 IU (40 mg) once daily by SC injection. Treatment with enoxaparin sodium is prescribed for at least 6 to 14 days whatever the recovery status(e.g. mobility). The benefit is not established for a treatment longer than 14days.

Treatment of DVT and PE

‍Enoxaparin sodium can be administered SC either as a once daily injection of 150 I Mg (1.5 mg/kg) or as twice daily injections of 100 IU/kg (1 mg/kg).

The regimen should be selected by the physician based on an individual assessment including evaluation of the thromboembolic risk and of the risk of bleeding. The dose regimen of 150 IU/kg(1.5 mg/kg) administered once daily should be used in uncomplicated patients with low risk of VTE recurrence. The dose regimen of 100 I Ufkg (1 mglkg)administered twice daily should be used in all other patients such as those with obesity, with symptomatic PE, cancer, recurrent VTE or proximal (vena i Iiaca) thrombosis.

Enoxaparin sodium treatment is prescribed for an average period of 10 days. Oral anticoagulant therapy should be initiated when appropriate (see -Switch between enoxaparin sodium andoralanficoagulants").·

     -Prevention of thrombus formation during haemodialysis

The recommended dose is 100 IU/kg (1mglicg) of enoxaparin sodium.

For patients with a high risk of haemorrhage, the dose should be reduced to 50111/kg (0.5 mg/kg) for double vascular access or 75 IU/kg (0.75 mgrkg) for single vascular access.

During haemodialysis. enoxaparin sodium should be introduced into the arterial line of the circuit at the beginning of the dialysis session. The effect of this dose is usually sufficient for a4-hour session; however, if fibrin rings are found, for example after a larger than normal session, a further dose of 50IU to 100 IU/kg (0.5 to 1 mghcg) maybe given.

No data are available in patients using enoxaparin sodium for prophylaxis or treatment and during haemodialysis sessions.·

- Acute coronary syndrome: treatment of unstable angina and NSTEMI and treatment of acute STEM!·
- For treatment of unstable angina and NSTEMI, the recommended dose of enoxaparin sodium is 100 111/kg (1 mgikg) every 12 hours by SC injection administered in combination with antiplatelet therapy. Treatment should be maintained for a minimum of 2 days and continued until clinical stabilization. The usual duration of treatment is 2 to 8days.

Acetylsalicylic acid is recommended for all patients without contraindications at an initial oral loading dose of 150-300mg (in acetylsalicylic acid-naive patients) and a maintenance dose of 75-325mg/daylong-term regardless of treatment strategy.·

          -For treatment of acute STEMI, the recommended dose of enoxaparin sodium is a single intravenous (IV) bolus of 3.000 IU (30 mg) plus a 100 lUlkg (1 mgfkg) SC dose followed by 100 It.likg (1 mg/kg) administered SC every 12hours (maximum 10.000 IU (100 mg) for each of the first two SC doses).Appropriate antiplatelet therapy such as oral acetylsalicylic acid (75 mg to325 mg once daily) should be administered concomitantly unless contraindicated. The recommended duration of treatment is 8 days or until hospital discharge, whichever comes first. When administered in conjunction with a thrombolytic(fibrin specific or non-fibrin specific). enoxaparin sodium should be given between 15 minutes before and 30 minutes after the start of fibrinolytic therapy.

o  For dosage in patients 75 years of age, see paragraph'ElderlY.
o  For patients managed with PCI. if the last dose of enoxaparin sodium SC was given less than 8 hours before balloon inflation. no additional dosing is needed. If the last SC administration was given more than 8 hours before balloon inflation, an IV bolus of 30 lUlkg (0.3 mgikg) enoxaparin sodium should be administered.·
- Paediatric population

The safety and efficacy of enoxaparin sodium in paediatric population have not been established. ·
-  Elderly

For all indications except STEMI, no dose reduction is necessary in the elderly patients. unless kidney function is impaired.

For treatment of acute STEMI , in elderly patients z75 years of age. an initial IV bolus ust not be used. Initiate dosing with 75 Ill/kg (0.75 mg/kg) SC every 12 hours maximum 7,500 IU (75 mg) for each of the first two SC doses only, followed by 75/kg (0.75 mglkg) SC dosing for the remaining doses). For dosage in elderly patients lh impaired kidney function, see below -renal impairment

.• Severe renal impairment

Enoxaparin sodium is not recommended for patients with end stage renal disease creatinine clearance <15 mUmin) due to lack of data in this population outside the prevention of thrombus formation in extra corporeal circulation during haemodialysis. Dosage table for patients with severe renal impairment (creatinine clearance [15-30] ml/min):

The recommended dosage adjustment do not apply to the haemodialysis indication.·

         -Moderate and mild renal impairment

Although no dose adjustment is recommended in patients with moderate (creatinine clearance 30-50 mLimin) and mild (creatinine clearance 50-80 mUmin) renal impairment. careful clinical monitoring is advised.

Method of administration

Enoxaparin should not be administered by the intramuscular route.·

        -For the prophylaxis of venous thrombo-embolic disease following surgery, treatment of DVT and PE, treatment of unstable angina and NSTEMI, enoxaparin sodium should be administered by SC injection.·
       - For acute STEMI. treatment is to be initiated with a single IV bolus injection immediately followed by a SC injection.·
       - For the prevention of thrombus formation in the extra corporeal circulation during haemodialysis. it is administered through the arterial line of a dialysis circuit. The pre-filled disposable syringe is ready for immediate use.·
        - SC injection technique: Injection should be made preferably when the patient is lying down. Enoxaparin sodium is administered by deep SC injection.

Do not expel the air bubble from the syringe before the injection to avoid the loss of drug when using pre-filled syringes. When the quantity of drug to be injected requires to be adjusted based on the patient's body weight. use the graduated pre-filled syringes to reach the required volume by discarding the excess before injection. Please be aware that in some cases it is not possible to achieve an exact dose due to the graduations on the syringe, and in such case the volume shall be rounded up to the nearest graduation.

The administration should be alternated between the left and right anterolateral or posterolateral abdominal wall.

The whole length of the needle should be introduced vertically into a skin fold gently held between the thumb and index finger. The skin fold should not be released until the injection is complete. Do not rub the injection site after administration.

Note for the pre-filled syringes fitted with an automatic safety system: The safety system is triggered at the end of the injection.

In case of self-administration, patient should be advised to follow instructions provided in the patient information leaflet included in the pack of this medicine.·

            - IV (bolus) Injection (for acute STEM! indication only):

For acute STEMI, treatment is to be  initiated with a single IV bolus injection immediately followed by a SC injection.

Enoxaparin sodium should be administered through an IV line. It should not be mixed or co- administered with other medications. To avoid the possible mixture of enoxaparin sodium with other drugs. the IV access chosen should be flushed with a sufficient amount of saline or dextrose solution prior to and following the IV bolus administration of enoxaparin sodium to clear the port of drug. Enoxaparin sodium may be safely administered with normal saline solution (0.9%) or 5% dextrose in water.

Initial 3,000IU(30 mg) bolus

For the initial 3,000 IU (30 mg) bolus, using an enoxaparin sodium graduated pre-filled syringe, expel the excessive volume to retain only 3,000 IU (30 mg) in the syringe. The 3,000 IU (30 mg)dose can then be directly injected into the IV line.• Additional bolus for PCI when last SC administration was given more than 8 hours before balloon inflation For patients being managed with PCI, an additional IV bolus of 30 IU/kg (0.3 mg/kg) is to be administered if last SC administration was given more than 8 hours before balloon inflation. In order to assure the accuracy of the small volume to be injected, it is recommended to dilute the drug to 300 IU/mL(3 mg/mL).To obtain a 300 IU/mL (3 mg/mL) solution, using a 6,000 IU (60 mg) enoxaparin sodium prefilled syringe, it is recommended to use a 50 mL infusion bag (i.e. using either normal saline solution (0.9%) or5% dextrose in water) as follows: Withdraw 30 mL from the infusion bag with a syringe and discard the liquid. Inject the complete contents of the 6,000 IU(60 mg) enoxaparin sodium pre-filled syringe into the 20 mL remaining in the bag. Gently mix the contents of the bag. Withdraw the required volume of diluted solution with a syringe for administration into the IV line. After dilution is completed, the volume to be injected can be calculated using the following formula [Volume of diluted solution (mL) = Patient weight (kg) x 0.1]or using the table below. It is recommended to prepare the dilution immediately before use. Volume to be injected through IV line after dilution is completed at a concentration of 300 IU (3 mg)/ml ·      Arterial line injection: It is administered through the arterial line of a dialysis circuit for the prevention of thrombus formation in the extra corporeal circulation during haemodialysis.·      Switch between enoxaparin sodium and oral anticoagulants Switch between enoxaparin sodium and vitamin K antagonists (VKA) Clinical monitoring and laboratory tests[prothrombin time expressed as the International Normalized Ratio (INR)] must be intensified to monitor the effect of VKA. As there is an interval before the VKA reaches its maximum effect, enoxaparin sodium therapy should be continued at a constant dose for as long as necessary in order to maintain the INR with in the desired therapeutic range for the indication in two successive tests. For patients currently receiving a VKA, the VKA should be discontinued and the first dose of enoxaparin sodium should be given when the INR has dropped below the therapeutic range.• Switch between enoxaparin sodium and direct oral anticoagulants (DOAC) For patients currently receiving enoxaparin sodium, discontinue enoxaparin sodium and start the DOAC 0 to 2 hours before the time that the next scheduled administration of enoxaparin sodium would be due as per DOAC label. For patients currently receiving a DOAC, the first dose of enoxaparin sodium should be given at the time the next DOAC dose would be taken. Administration in spinal/epidural anaesthesia or lumbar puncture Should the physician decide to administer anticoagulation in the context of epidural or spinal anaesthesia/analgesia or lumbar puncture, careful neurological monitoring is recommended due to the risk of neuraxial haematomas. -At doses used for prophylaxis A puncture-free interval of at least 12hours shall be kept between the last injection of enoxaparin sodium atprophy lactic doses and the needle or catheter placement. For continuous techniques, a similar delay of at least 12 hours should be observed before removing the catheter. For patients with creatinine clearance[15-30] mL/min, consider doubling the timing of puncture/catheter placement or removal to at least 24 hours.The 2 hours preoperative initiation of enoxaparin sodium 2,000 IU (20 mg) is not compatible with neuraxial anaesthesia.-At doses used for treatment A puncture-free interval of at least 24hours shall be kept between the last injection of enoxaparin sodium at curative doses and the needle or catheter placement. For continuous techniques, a similar delay of 24 hours should be observed before removing the catheter. For patients with creatinine clearance[15-30] mL/min, consider doubling the timing of puncture/catheter placement or removal to at least 48 hours. Patients receiving the twice daily doses(i.e. 75 IU/kg (0.75 mg/kg) twice daily or 100 IU/kg (1 mg/kg) twice-daily)should omit the second enoxaparin sodium dose to allow a sufficient delay before catheter placement or removal. Anti-Xa levels are still detectable at these time points, and these delays are not a guarantee that neuraxial hematoma will be avoided. Likewise, consider not using enoxaparinsodium until at least 4 hours after the spinal/epidural puncture or after the catheter has been removed. The delay must be based on a benefit-risk assessment considering both the risk for thrombosis and the risk for bleeding in the context of the procedure and patient risk factors.
‍
Contraindications

Enoxaparin sodium is contraindicated inpatients with:

• Hypersensitivity to enoxaparin sodium, heparin or its derivatives, including other low molecular weight heparins(LMWH)

• History of immune mediated heparin-induced thrombocytopenia (HIT) within the past 100 days or in the presence of circulating antibodies.

• Active clinically significant bleeding and conditions with a high risk of haemorrhage, including recent haemorrhagic stroke, gastrointestinal ulcer, presence of malignant neoplasm at high risk of bleeding, recent brain, spinal or ophthalmic surgery, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities;

• Spinal or epidural anaesthesia or loco-regional anaesthesia when enoxaparin sodium is used for treatment in the previous 24 hours.

Special warnings and precautions for use
‍Enoxaparin should not be used interchangeably with other medicines belonging to the group of low molecular weight heparins. This is because they are not exactly the same and do not have the same activity and instructions for use. Talk to your doctor or pharmacist before using Enoxaparin if:

• you have ever had a reaction to heparin that caused a severe drop in the number of your platelets

you are going to receive spinal or epidural anesthesia or lumbar puncture (see Operations and Anaesthetics): a delay should be respected between Enoxaparin use and this procedure·

- you have had a heart valve fitted·
- you have endocarditis (an infection of the inner lining of the heart)
-you have history of gastric ulcer you have had a recent stroke·
- you have high blood pressure·
-you have diabetes or problems with blood vessels in the eye caused by diabetes (called diabetic retinopathy)·
- you have had an operation recently on your eyes or brain·
- you are elderly (over 65 years old) and especially if you are over 75 years old you have kidney problems·
-you have liver problems·
- you are underweight or overweight·
-you have high level of potassium in your blood (this may be checked with a blood test) are currently using medicines which affect bleeding (see section below - Other medicines)
You may have a blood test before you start using this medicine and at intervals while you are using it; this is to check the level of the clotting cells(platelets) and potassium in your blood.
‍

Interaction with other medicinal products and other forms of interaction

Concomitant use not recommended:

• Medicinal products affecting haemostasis

It is recommended that some agents which affect haemostasis should be discontinued prior to enoxaparin sodium therapy unless strictly indicated. If the combination is indicated, enoxaparin sodium should be used with careful clinical and laboratory monitoring when appropriate. These agents include medicinal products such as:

-Systemic salicylates, acetylsalicylic acid at anti-inflammatory doses, and NSAIDs including ketorolac

,- Other thrombolytics (e.g. alteplase,reteplase, streptokinase, tenecteplase, urokinase) and anticoagulants.

Concomitant use with caution:

The following medicinal products may be administered with caution concomitantly with enoxaparin sodium:

• Other medicinal products affecting haemostasis such as
:- Platelet aggregation inhibitors including acetylsalicylic acid used at antiaggregant dose (cardioprotection),clopidogrel, ticlopidine, and glycoprotein IIb/Illa antagonists indicated in acute coronary syndrome due to the risk of bleeding. -Dextran 40,

-Systemic glucocorticoids.
• Medicinal products increasing potassium levels:

Medicinal products that increase serum potassium levels may be administered concurrently with enoxaparin sodium under careful clinical and laboratory monitoring.

Fertility, pregnancy and lactation

Pregnancy
In humans, there is no evidence that enoxaparin crosses the placental barrier during the second and third trimester of pregnancy. There is no information available concerning the first trimester.

Pregnant women receiving enoxaparin sodium should be carefully monitored for evidence of bleeding or excessive anticoagulation and should be warned of the haemorrhagic risk. Overall, the data suggest that there is no evidence for an increased risk of haemorrhage, thrombocytopenia or osteoporosis with respect to the risk observed in non-pregnant women, other than that observed in pregnant women with prosthetic heart valves.

If an epidural anaesthesia is planned, it is recommended to withdraw enoxaparin sodium treatment before.

Breastfeeding
It is not known whether unchanged enoxaparin is excreted in human breast milk. In lactating rats, the passage of enoxaparin or its metabolites in milk is very low. The oral absorption of enoxaparin sodium is unlikely. Enoxaparin can be used during breastfeeding.

Fertility
There are no clinical data for enoxaparin sodium in fertility. Animal studies did not show any effect on fertility.

Effects on ability to drive and use machines

Enoxaparin sodium has no or negligible influence on the ability to drive and use machines.

Undesirable effects

Very common (may affect more than 1 in 10people)·

- Bleeding.·
- Increases in liver enzymes.

‍Common (may affect up to 1 in 10 people)·

- You bruise more easily than usual. This could be because of a blood problem with low platelet counts.·
- Pink patches on your skin. These are more likely to appear in the area you have been injected with Enoxaparin.·
- Skin rash (hives, urticaria).·
- Itchy red skin.·
- Bruising or pain at the injection site.·
- Decreased red blood cell count.·
- High platelet counts in the blood.·
- Headache.

Uncommon (may affect up to 1 in 100 people)·
- Sudden severe headache. This could be a sign of bleeding in the brain.·
- feeling of tenderness and swelling in your stomach. You may have bleeding in your stomach.·
- Large red irregularly shaped skin lesions with or without blisters.·
-Skin irritation (local irritation).·
-You notice yellowing of your skin or eyes and your urine becomes darker in colour. This could be a liver problem.

‍Rare (may affect up to 1 in 1,000people)·
- Severe allergic reaction. The signs may include: a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue.·
- Uncommon (may affect up to 1 in100 people)·      Sudden severe headache. This could be a sign of bleeding in the brain.·
-  A feeling of tenderness and swelling in your stomach. You may have bleeding in your stomach.·
- Large red irregularly shaped skin lesions with or without blisters.·
- Skin irritation (local irritation).·
-You notice yellowing of your skin or eyes and your urine becomes darker in colour. This could be a liver problem.·
-Rare (may affect up to 1 in1,000 people)·
-Severe allergic reaction. The signs may include: a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue. ·

- Increased potassium in your blood. This is more likely to happen in people with kidney problems or diabetes. Your doctor will be able to check this by carrying out a blood test.·
- An increase in the number of eosinophils in your blood. Your doctor will be able to check this by carrying out a blood test.·
- Hair loss.·
- Osteoporosis (a condition where your bones are more likely to break) after long term use.·
-  Tingling, numbness and muscular weakness (particularly in the lower part of your body) when you have had a spinal puncture or a spinal anaesthetic.·
-  Lost of control over your bladder or bowel (so you cannot control when you go to the toilet).·
- Hard mass or lump at the injection site.

Overdose

Signs and symptoms
Accidental overdose with enoxaparin sodium after IV, extracorporeal or SC administration may lead to haemorrhagic complications. Following oral administration of even large doses, it is unlikely that enoxaparin sodium will be absorbed.

Management
The anticoagulant effects can be largely neutralized by the slow IV injection of protamine. The dose of protamine depends on the dose of enoxaparin sodium injected; 1 mg protamine neutralizes the anticoagulant effect of 100 IU (1 mg) of enoxaparin sodium, if enoxaparin sodium was administered in the previous 8 hours. An infusion of 0.5 mg protamine per 100 IU (1 mg) of enoxaparin sodium may be administered if enoxaparin sodium was administered greater than 8 hours previous to the protamine administration, or if it has been determined that a second dose of protamine is required. After 12 hours of the enoxaparin sodium injection, protamine administration may not be required. However, even with high doses of protamine, the anti-Xa activity of enoxaparin sodium is never completely neutralized (maximum about 60%) (see the prescribing information for protamine salts).

Pharmacodynamic properties

‍Pharmacotherapeutic group: Antithromboticagent, heparin group, ATC code: B01AB05

Enoxaparin is a biosimilar medicinal product. Detailed information is available on the website of the Medicines and Healthcare products Regulatory Agency.

Pharmacodynamic effects

Enoxaparin is a LMWH with a mean molecular weight of approximately 4,500 daltons, in which the antithrombotic and anticoagulant activities of standard heparin have been dissociated. The drug substance is the sodium salt.

In the in vitro purified system, enoxaparin sodium has a high anti-Xa activity (approximately 100 IU/mg) and low anti-lla or anti thrombin activity (approximately 28 IU/mg), with a ratio of 3.6. These anticoagulant activities are mediated through anti- thrombin III (ATIII)resulting in anti-thrombotic activities in humans.

Pharmacokinetic properties
‍General characteristics

The pharmacokinetic parameters of enoxaparin sodium have been studied primarily in terms of the time course of plasma anti-Xa activity and also by anti-lla activity, at the recommended dosage ranges after single and repeated SC administration and after single IV administration. The quantitative determination of anti-Xa and anti-lla pharmacokinetic activities was conducted by validated amidolytic methods.

Absorption
The absolute bioavailability of enoxaparin sodium after SC injection, based on anti-Xa activity, is close to 100%.

Different doses and formulations and dosing regimens can be used.

The mean maximum plasma anti-Xa activity level is observed 3 to 5 hours after SC injection and achieves approximately0.2, 0.4, 1.0 and 1.3 anti-Xa IU/mL following single SC administration of 2,000IU, 4,000 IU, 100 IU/kg and 150 IU/kg (20 mg, 40 mg, 1 mg/kg and 1.5 mg/kg)doses, respectively.

A3,000 IU (30 mg) IV bolus immediately followed by a 100 IU/kg (1 mg/kg) SC every 12 hours provided initial maximum anti-Xa activity level of 1.16 IU/mL (n=16) and average exposure corresponding to 88% of steady-state levels. Steady-state is achieved on the second day of treatment.

After repeated SC administration of 4,000IU (40 mg) once daily and 150 IU/kg (1.5 mg/kg) once daily regimens in healthy volunteers, the steady-state is reached on day 2 with an average exposure ratio about 15% higher than after a single dose. After repeated SC administration of the 100 IU/kg (1 mg/kg) twice daily regimen, the steady-state is reached from day 3 to 4 with mean exposure about 65% higher than after a single dose and mean maximum and trough anti-Xa activity levels of about 1.2 and 0.52 IU/mL, respectively.

Injection volume and dose concentration over the range 100-200 mg/mL does not affect pharmacokinetic parameters in healthy volunteers.

Enoxaparin sodium pharmacokinetics appears to be linear over the recommended dosage ranges.

ntra-patient and inter-patient variability is low. Following repeated SC administration no accumulation takes place.

Plasma anti-lla activity after SC administration is approximately ten-fold lower than anti-Xa activity. The mean maximum anti-Ila activity level is observed approximately 3 to 4 hours following SC injection and reaches 0.13 IU/mL and 0.19 IU/mL following repeated administration of 100 IU/kg (1 mg/kg) twice daily and 150 IU/kg (1.5 mg/kg)once daily, respectively.

Distribution
The volume of distribution of enoxaparin sodium anti-Xa activity is about 4.3 litres and is close to the blood volume.

Biotransformation
Enoxaparin sodium is primarily metabolized in the liver by desulfation and/or depolymerization to lower molecular weight species with much reduced biological potency.

‍Elimination
‍Enoxaparin sodium is a low clearance drug with a mean anti-Xa plasma clearance of 0.74 L/h after a 150 IU/kg (1.5 mg/kg)6-hour IV infusion.

Elimination appears monophasic with a half-life of about 5 hours after a single SC dose to about 7 hours after repeated dosing.

Renal clearance of active fragments represents about 10% of the administered dose and total renal excretion of active and non-active fragments 40% of the dose.

STORAGE:

Store between 20°C and 25°C, excursions permitted between 15°C and 30°C.

SHELF LIFE

24 Months

HOW SUPPLIED:

A-EXARIN (Enoxaparin Sodium Injection USP) 20mg/40mg/60mg/80mg & 100mg are supplied in 1mL pre filled glass syringe.
‍

A-Exarin

A-Ligcaine 1.0/2.0

(Lidocaine Hydrochloride Injection USP)

THIS LEAFLET CONTAINSIMPORTANT PRODUCT USE AND SAFETY INFORMATION, PLEASE READ CAREFULLY AND RETAIN FOR FURTHER REFERENCE.

DESCRIPTION

A-Ligcaine (Lidocaine Hydrochloride Injection USP) is a local anesthetic which is a sterile, nonpyrogenic solution intended for parenteral injection. Lidocaine hydrochloride is chemically designated as 2-(Diethylamino)-2, 6-acetoxylidide monohydrochloride and has the following structural formula:

**NHCOCH2N(C2H5)2 * HCI**

COMPOSITION

Each mL Contains:
Lidocaine
Hydrochloride USP      10 mg
Sodium Chloride USP     7 mg
Methylparaben USP     1 mg
(As Preservative)
Water for Injection        q.s.

A-Ligcaine 2.0

Each mL Contains
Lidocaine
Hydrochloride USP 20 mg
Sodium Chloride USP 6 mg
Methylparaben USP 1 mg
(As Preservative)
Water for Injection q.s.

INDICATION AND USAGE

A-Ligcaine (Lidocaine Hydrochloride Injection USP) is indicated for the production of local anesthesia, by infiltration techniques, such as percutaneous injection, and by peripheral nerve block techniques, such as brachial plexus and inter-costal, when the accepted procedures for these techniques as described in standard textbooks are observed.

CLINICAL PHARMACOLOGY

Mechanism of Action
Lidocaine HCI stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action.

Hemodynamics: Excessive blood levels may cause changes in cardiac output, total peripheral resistance, and mean arterial pressure. With central neural blocade these changes may be attributable to block of autonomic fibres, a direct depressant effect of the local anaesthetic agent on various components of the cardiovascular system. The net effect is normally a modest hypotension when the recommended dosages are not exceeded.

Pharmacokinetics and Metabolism: Information derived from diverse formulations, concentrations and usages reveals that lidocaine HCI is completely absorbed following parenteral administration, its rate of absorption depending, for example, upon various factors such as the site of administration and the presence or absence of a vasoconstrictor agent. Except for intravascular administration, the highest blood levels are obtained following intercostal nerve block and the lowest after subcutaneous administration.

The plasma binding of Lidocaine HCI is dependent on drug concentration, and the fraction bound decreases with increasing concentration. At concentrations of 1 to 4 mcg of free base/mL, 60to 80% of Lidocaine HCl is protein bound. Binding is also dependent on the plasma concentration of the alpha-1-acid glycoprotein.

Lidocaine HCI crosses the blood-brain and placental barriers, presumably by passive diffusion.

Lidocaine HCI is metabolized rapidly by the liver, and metabolites and unchanged drug are excreted by the kidneys. Biotransformation includes oxidative N-dealkylation, ring hydroxylation, cleavage of the amide linkage, and conjugation. N-dealkylation, a major pathway of biotransformation, yields the metabolites monoethylglycinexylidide and glycinexylidide. The pharmacological/toxicological actions of these metabolites are similar to, but less potent than, those of Lidocaine HCI. Approximately 90%of Lidocaine HCl administered is excreted in the form of various metabolites, and less than 10% is excreted unchanged. The primary metabolite in urine is aconjugate of 4-hydroxy-2,6-dimethylaniline.

Studies of lidocaine metabolism following intravenous bolus injections have shown that the elimination halh-life of this agent is typically 1.5 to 2 hours. Because of the rapid rate at which Lidocaine HCI is metabolized, any condition that affects liver function may alter lidocaine kinetics. The half-life may be prolonged two-fold or more in patients with liver dysfunction. Renal dysfunction does not affect Lidocaine HCI kinetics but may increase the accumulation of metabolites.

Factors such as acidosis and the use of CNS stimulants and depressants affect the CNS levels of Lidocaine HCI required to produce overt systemic effects. Objective adverse manifestations become increasingly apparent with increasing venous plasma levels above 6 mcg freebase/mL. In the rhesus monkey arterial blood levels of 18 to 21 mcg/mL havebeen shown to be threshold for convulsive activity.

CONTRADICTIONS
‍Lidocaine HCL is contraindicated inpatients with a known history of hypersentivity to local anaesthetics of the amide type.

WARNINGS AND PRECAUTIONS

Lidocaine hydrochloride injection for infiltration and nerve block should be employed only by clinicians who are well versed in diagnosis and management of dose-related toxicity and other acute emergencies that might arise from the block to be employed and then only after ensuring the immediate availability of oxygen, other resuscitative drugs, cardio pulmonary equipment and the personnel needed for proper management of toxic reactions and related emergencies (see also adverse reactions and precautions). Delay in proper management of dose-related toxicity, underventilation from any cause and/or altered sensitivity may lead to the development of acidosis, cardiac arrest and, possibly, death.

‍PRECAUTIONS
General
‍The safety and effectiveness of Lidocaine HCI depend on proper dosage, correct technique, adequate precautions, and readiness for emergencies. Standard textbooks should be consulted for specific techniques and precautions for various regional anesthetic procedures.

‍Pregnancy
Teratogenic Effects: Pregnancy Category B
‍Reproduction studies have been performed in rats at doses up to 6.6 times the human dose and have revealed no evidence of harm to the fetus caused by Lidocaine HCI. There are, however, no adequate and well-controlled studies in pregnant women. Animal reproduction studies are not always predictive of human response. General consideration should be given to this fact before administering Lidocaine HCI to women of child bearing potential, especially during early pregnancy when maximum organogenesis takes place.

‍Nursing Mothers
‍It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when lidocaine HCI is administered to a nursing woman.

‍Pediatric Use
‍Dosages in children should be reduced, commensurate with age, body weight and physical condition

‍ADVERSE REACTIONS
‍In common with other local anaesthetics, adverse reactions to Lidocaine are rare and are usually the result of raised plasma concentrations due to accidental intravascular injection, excessive dosage or rapid absorption from highly vascular areas, or may result from a hypersensitivity, idiosyncrasy or diminished tolerance on the part of the patient. Systemic toxicity mainly involves the central nervous system and/or the cardiovascular system.

DOSAGE AND ADMINISTRATION

The usual adult IV bolus dose is 50-100 mg administered at a rate of approximately 25-50 mg per minute. If the desired response is not achieved, a second dose may be administered 5 minutes after completion of the first injection. Not more than 200-300 mg should be administered during a one hour period. Elderly patients and those with congestive heart failure or cardiogenic shock may require smaller bolus doses.

Maintenance infusion of a 0.2 or 0.4%solution in 5% glucose.

Adults: 20-50 micrograms/kg/minute (1-4mg/minute in an average 70 kg adult).

Slower infusion rates should be used inpatients with congestive heart failure or liver disease; no dosing modification appears necessary in patients with renal failure. When arrhythmias reappear during a constant infusion of Lidocaine, a small bolus may be given to rapidly increase plasma concentration of the drug; the infusion rate is increased simultaneously. The infusion should be terminated as soon as the patient's basic cardiac rhythm appears to be stable or at the earliest sign of toxicity.

Infants and children may be given an initial IV bolus of 0.5-1 mg/kg. This dose may be repeated according to the response of the patient, but the total dose should not exceed 3-5 mg/kg. A maintenance IV infusion of 10-50 micrograms/kg per minute may be given via an infusion pump.

STORAGE:

Store at a temperature not exceeding 30’C.

SHELF LIFE

24 Months

HOW SUPPLIED:

A-Ligcaine 1.0/2.0 (Lidocaine Hydrochloride Injection USP) is supplied in 30 mL Glass Vial.
‍

A-Ligcaine

A-Ligcaine Plus

(Lidocaine Hydrochloride Injection USP)

THIS LEAFLET CONTAINSIMPORTANT PRODUCT USE AND SAFETY INFORMATION, PLEASE READ CAREFULLY AND RETAIN FOR FURTHER REFERENCE.

DESCRIPTION

A-Ligcaine Plus(Lidocaine Hydrochloride & Epinephrine Injection USP) containing a local anesthetic agent, Lidocaine Hydrochloride, and a vasoconstrictor, Epinephrine (as bitartrate) and are administered parenterally by injection. The solutions contain lidocaine hydrochloride which is chemically designated asacetamide, 2-(diethylamino)-N-(2,6-dimethylphenyl)-monohydrochloride, and Epinephrine is ( - )-3,4-Dihydroxy-α- [(Methylamino) methyl] benzyl alcoho has th following structural formula;

COMPOSITION

Each mL Contains:
Lidocaine Hydrochloride USP 20 mg
Epinephrine Bitartrate USP 0.01 mg
(As Base)
Sodium Chloride USP 6.5 mg
Potassium Metabisulfite USP 1.2 mg
Disodium Edetate USP 0.25mg
Water for Injection q.s.

INDICATION AND USAGE

A-Ligcaine Plus(Lidocaine Hydrochloride & Epinephrine Injection USP) solutions are indicated for the production of local anesthesia for dental procedures by nerve block or infiltration techniques.
Only accepted procedures for these techniques as described in standard textbooks are recommended.

CLINICAL PHARMACOLOGY

Mechanism of Action
Lidocaine stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of nerve impulses, thereby effecting local anesthetic action.

Pharmacokinetics and Metabolism:
Information derived from diverse formulations, concentrations and usages reveals that lidocaine HCI is completely absorbed following parenteral administration, its rate of absorption depending, for example, upon various factors such as the site of administration and the presence or absence of a vasoconstrictor agent. Except for intravascular administration, the highest blood levels are obtained following intercostal nerve block and the lowest after subcutaneous administration.

The plasma binding of Lidocaine is dependent on drug concentration, and the fraction bound decreases with increasing concentration. At concentrations of 1 to 4 μg of free base/mL, 60 to 80% of Lidocaine is protein bound. Binding is also dependent on the plasma concentration of the alpha-1-acid glycoprotein.

Lidocaine crosses the blood-brain and placental barriers, presumably by passive diffusion.

Lidocaine is metabolized rapidly by the liver, and metabolites and unchanged drug are excreted by the kidneys. Biotransformation includes oxidative N-dealkylation, ring hydroxylation, cleavage of the amide linkage, and conjugation. N-dealkylation, a major pathway of biotransformation, yields the metabolites monoethylglycinexylidide and glycinexylidide. The pharmacological/toxicological actions of these metabolites are similar to, but less potent than, those of Lidocaine . Approximately 90% of Lidocaine administered is excreted in the form of various metabolites, and less than 10% is excreted unchanged. The primary metabolite in urine is a conjugate of 4-hydroxy-2,6-dimethylaniline.

Studies of lidocaine metabolism following intravenous bolus injections have shown that the elimination half-life of this agent is typically 1.5 to 2 hours. Because of the rapid rate at which Lidocaine HCI is metabolized, any condition that affects liver function may alter lidocaine kinetics. The half-life may be prolonged two-fold or more in patients with liver dysfunction. Renal dysfunction does not affect Lidocaine HCI kinetics but may increase the accumulation of metabolites.

Factors such as acidosis and the use of CNS stimulants and depressants affect the CNS levels of Lidocaine HCI required to produce overt systemic effects. Objective adverse manifestations become increasingly apparent with increasing venous plasma levels above 6 mcg freebase/mL. In the rhesus monkey arterial blood levels of 18 to 21 mcg/mL havebeen shown to be threshold for convulsive activity.

CONTRADICTIONS
A-Ligcaine Plus(Lidocaine Hydrochloride & Epinephrine Injection USP)is contraindicated in patients with a known history of hypersensitivity to local anesthetics of the amide type or to any components of the injectable formulations.

WARNINGS AND PRECAUTIONS

A-Ligcaine Plus(Lidocaine Hydrochloride & Epinephrine Injection USP) solutions contain potassium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in non asthmatic people.

Lidocaine hydrochloride and epinephrine injection, USP, along with other local anesthetics, is capable of producing methemoglobinemia. The clinical signs of methemoglobinemia are cyanosis of the nail beds and lips, fatigue and weakness. If methemoglobinemia does not respond to administration of oxygen, administration of methylene blue intravenously 1-2 mg/kg body weight over a 5 minute period is recommended.

‍Pregnancy
Teratogenic Effects: Pregnancy Category B
Reproduction studies have been performed in rats at doses up to 6.6 times the human dose and have revealed no evidence of harm to the fetus caused by Lidocaine . There are, however, no adequate and well-controlled studies in pregnant women. Animal reproduction studies are not always predictive of human response. General consideration should be given to this fact before administering Lidocaine HCI to women of child bearing potential, especially during early pregnancy when maximum organogenesis takes place.

‍Nursing Mothers
‍It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when lidocaine is administered to a nursing woman.

‍Pediatric Use
‍Dosages in children should be reduced, commensurate with age, body weight and physical condition

‍ADVERSE REACTIONS
Adverse experiences following the administration of lidocaine are similar in nature to those observed with other amide-type local anesthetic agents. These adverse experiences are, in general, dose-related and may result from high plasma levels (which may be caused by excessive dosage, rapid absorption, unintended intravascular injection or slow metabolic degradation), injection technique, volume of injection, hypersensitivity, idiosyncrasy or diminished tolerance on the part of the patient. Serious adverse experiences are generally systemic in nature.

DOSAGE AND ADMINISTRATION

Dosage requirements should be determined on an individual basis. In oral inﬁltration and / or mandibular block, initial dosages of 1.0 - 5.0mL (1/2 to 2.5 cartridges) of Lidocaine HCl 2%and epinephrine 1:100,000or lidocaine HCl 2% and epinephrine1:50,000 are usually effective.

Adult
For normal healthy adults, the amount of lidocaine HCI administered should be kept below500 mg, and in any case, should not exceed 7 mg/kg (3.2 mg/lb) of body weight

.Pediatric
‍Pediatric patients : It is difficult to recommend a maximum dose of any drug for pediatric patients since this varies as a function of age and weight. For pediatric patients of less than ten years who have a normal lean body mass and normal body development, the maximum dose maybe determined by the application of one of the standard pediatric drug formulas (e.g., Clark's rule). For example, in pediatric patients of five years weighing 50 Ibs, the dose of lidocaine hydrochloride should not exceed 75-100mg when calculated according to Clark's rule. In any case, the maximum dose of lidocaine hydrochloride should not exceed 7 mg/kg (3.2 mg/lb) of body weight.

STORAGE:

Store at 20°C to 25°C (Control room temperature). Preserve in light-resistant containers. Do not Auto-Clave (contain Epinephrine) Keep out of the reach of children.

SHELF LIFE

24 Months

HOW SUPPLIED:

A-Ligcaine Plus(Lidocaine Hydrochloride & Epinephrine Injection USP) is supplied in 30 mL Glass Vial.
‍

A-Ligcaine Plus

AFLUOR

(Fluorescein Sodium Injection IP)

THIS LEAFLET CONTAINSIMPORTANT PRODUCT USE AND SAFETY INFORMATION, PLEASE READ CAREFULLY AND RETAIN FOR FURTHER REFERENCE.

DESCRIPTION

AFLUOR (Fluorescein Sodium Injection IP) is a sterile solution for use intravenously as a diagnostic aid. Its chemical name is spiro[isobenzofuran-1 (3H),9'-[9H]xanthene]-3-one,3'6'-dihydroxy, disodium salt.The active ingredient is represented by the chemical structure:

AFLUOR (Fluorescein Sodium Injection IP) is supplied as a sterile, unpreserved, unit dose aqueous solution, that has a pH of 8.0 – 9.8 and an osmolality of 572-858 mOsm/kg.

COMPOSITION

Each mL Contains:
Fluorescein Sodium IP 200 mg
Water for InjectionIP q.s.

INDICATIONS

AFLUOR (Fluorescein Sodium Injection IP) is indicated in diagnostic ﬂuorescein angiography or angioscopy of the retina and iris vasculature.

CLINICAL PHARMACOLOGY

Mechanism of Action
AFLUOR (Fluorescein Sodium Injection IP) responds to electromagnetic radiation and light between the wavelengths of 465 to 490 nm and ﬂuorescein , i.e., emits light at wavelengths of 520 to 530 nm. Thus, the hydrocarbon is excited by blue light and emits light that appears yellowish green. Following intravenous injection of ﬂuorescein sodium in an aqueous solution, the unbound fraction of the ﬂuorescein can be excited with a blue light ﬂash from a fundus camera as it circulates through the ocular vasculature, and the yellowish green ﬂuorescein of the dye is captured by the camera. In the fundus, the ﬂuorescein of the dye demarcates the retinal and/or choroidal vasculature under observation, distinguishing it from adjacent areas/structures.

Pharmacokinetics
Distribution :
Within 7 to 14 seconds after IV administration into the antecubital vein, ﬂuorescein usually appears in the central retinal artery of the eye. Within a few minutes of IV administration of ﬂuorescein sodium, a yellowish discoloration of the skin occurs, which begins to fade 6 to 12 hours after dosing. Various estimates of volume of distribution indicate that ﬂuorescein distributes into interstitial space(0.5 L/kg).

Metabolism:
Fluorescein is metabolized to ﬂuorescein monoglucuronide. After IV administration of ﬂuorescein sodium (14 mg/kg) to 7 healthy subjects, approximately 80% of ﬂuorescein in plasma was converted to glucuronide conjugate after a period of 1 hour post dose.

Excretion: Fluorescein and its metabolite are mainly eliminated via renal excretion. After IV administration, the urine remains slightly ﬂuorescent for 24 to 36 hours. A renal clearance of 1.75 mL/min/kg and a hepatic clearance (due to conjugation) of1.50 mL/min/kg have been estimated. The systemic clearance of ﬂuorescein was essentially complete by 48 to 72 hours after administration of 500 mg ﬂuorescein.
‍

DOSAGE AND ADMINISTRATIONS

Adult Dose:
‍The recommended dosage of AFLUOR(Fluorescein Sodium Injection IP) via intravenous administration.

Pediatric Dose
For children, the dose is 7.7 mg/kg(actual body weight)up to a maximum of 500 mg, via intravenous infusion calculated on the basis of35 mg for each 10 lbs. (4.54 kg) of body weight.

Preparation for Administration:
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Do not mix or dilute with other solutions or drugs.

Administration:
Inject the dose (over 5-10 seconds is normally recommended) into the antecubital vein, after taking precautions to avoid extravasation. A syringe, ﬁlled with AFLUOR (Fluorescein Sodium Injection IP), may be attached to transparent tubing and a 23 gauge butterﬂy needle for injection. Insert the needle and draw the patient's blood to the hub of the syringe so that a small air bubble separates the patient's blood in the tubing from the ﬂuorescein. With the room lights on, slowly inject the blood back into the vein while watching the skin over the needle tip. If the needle has extravasated, the patient's blood will be seen to bulge the skin and the injection should be stopped before any ﬂuorescein is injected. When assured that extravasation has not occurred, the room light may be turned off and the ﬂuorescein injection completed. Luminescence usually appears in the retina and choroidal vessels in 7 to 14 seconds and can be observed by standard viewing equipment.
‍

CONTRAINDICATIONS

AFLUOR (Fluorescein Sodium Injection IP) is contraindicated in patients with known hypersensitivity to ﬂuorescein sodium or any other ingredients in this product. Rare cases of death due to anaphylaxis have been reported. Fluorescein sodium can induce serious intolerance reactions. These reactions of intolerance are always unpredictable but they are more frequent in patients who have previously experienced an adverse reaction after ﬂuorescein injection (symptoms other than nausea and vomiting) or in patients with history of allergy such as food or drug induced urticaria, asthma, eczema, allergic rhinitis. Detailed questioning of each patient is recommended before the angiography to evaluate any prior history of allergy.

WARNINGS & PRECAUTIONS
Respiratory Reactions
Caution should be exercised inpatients with a history of allergy or bronchial asthma. An emergency tray should always be available. If a potential allergy is suspected, an intradermal skin test may be performed prior to intravenous administration, i.e., 0.05 mL injected intradermally to be evaluated 30 to 60 minutes following injection. Given the sensitivity and speciﬁcity of skin testing, a negative skin test is not proof that a patient is not allergic to ﬂuorescein.

Severe local tissue damage
Extravasation during injection can result in severe local tissue damage due to high pH of ﬂuorescein solution. The following complications resulting from extravasation of ﬂuorescein have been noted to occur: Sloughing of the skin, superﬁcial phlebitis, subcutaneous granuloma, and toxic neuritis along the median nerve in the antecubital area. Complications resulting from extravasation can cause severe pain in the arm for up to several hours. When extravasation occurs, the injection should be discontinued and conservative measures to treat damaged tissue and to relieve ain should be implemented

ADVERSE EFFECTS
Skin and urine discoloration:
The most common reaction is discoloration of the skin and urine. Skin will attain a temporary yellowish discoloration. Urine attains a bright yellow color. Discoloration of the skin usually fades in 6 to 12 hours and usually fades in urine in 24 to 36 hours.

Gastrointestinal Reaction:
The next most common adverse reaction is nausea. Vomiting, and gastrointestinal distress have also occurred. A strong taste may develop after injection.

Hypersensitivity Reactions:
Symptoms and signs of hypersensitivity have occurred. Generalized hives and itching, bronchospasm and anaphylaxis have been reported.

Cardiopulmonary Reactions:
Syncope and hypotension may occur. Cardiac arrest, basilar artery ischemia, severe shock and death may occur rarely.
Neurologic Reactions:
Headache may occur. Convulsions may rarely occur following injection.

Thrombophlebitis:
Thrombophlebitis at the injection site has been reported. Extravasation of the solution at the injection site causes intense pain at the site and a dull aching pain in the injected arm.

USE IN SPECIFIC POPULATIONS

Pregnancy: Pregnancy Category C. Adequate animal reproduction studies have not been conducted with ﬂuorescein sodium. It is also not known whether ﬂuorescein sodium can cause fetal harm when administered to a pregnant woman. Fluorescein sodium should be given to a pregnant woman only if clearly needed.

Nursing Mothers:
Fluorescein sodium has been demonstrated to be excreted in human milk. Caution should be exercised when ﬂuorescein sodium is administered to a nursing woman.

Pediatric Use:
Pediatric patients have been included in clinical studies. No overall differences in safety or effectiveness have been observed between pediatric and adult patients.

Geriatric Use:
No overall differences in safety or effectiveness have been observed between elderly and other adult patients.

STORAGE:

Protected from light. Store at a temperature not exceeding 30°C.

SHELF LIFE

24 Months

HOW SUPPLIED:

AFLUOR (Fluorescein Sodium Injection IP) is supplied in 3 mL glass vial.
‍

AFLUOR 3mL

AFLUOR-10 /3mL

(Fluorescein Injection USP)

THIS LEAFLET CONTAINSIMPORTANT PRODUCT USE AND SAFETY INFORMATION, PLEASE READ CAREFULLY AND RETAIN FOR FURTHER REFERENCE.

DESCRIPTION

AFLUOR-10 (Fluorescein Injection USP) is a sterile solution for use intravenously as a diagnostic aid. Its chemical name is spiro[isobenzofuran-1 (3H),9'-[9H]xanthene]-3-one,3'6'-dihydroxy, disodium salt. The active ingredient is represented by the chemical structure:

AFLUOR-10 (Fluorescein Injection USP) is supplied as a sterile, unpreserved, unit dose aqueous solution, that has a pH of 8.0 – 9.8 and an osmolality of 400- 650 mOsm/kg.

COMPOSITION

Each mL Contains:
Fluorescein Sodium USP 100 mg
Water for Injection USP q.s.

INDICATIONS

AFLUOR-10 (Fluorescein Injection USP) is indicated in diagnostic ﬂuorescein angiography or angioscopy of the retina and iris vasculature.

CLINICAL PHARMACOLOGY

Mechanism of Action
AFLUOR-10 (Fluorescein Injection USP) responds to electromagnetic radiation and light between the wavelengths of 465 to 490 nm and ﬂuorescein , i.e., emits light at wavelengths of 520 to 530 nm. Thus, the hydrocarbon is excited by blue light and emits light that appears yellowish green. Following intravenous injection of ﬂuorescein sodium in an aqueous solution, the unbound fraction of the ﬂuorescein can be excited with a blue light ﬂash from a fundus camera as it circulates through the ocular vasculature, and the yellowish green ﬂuorescein of the dye is captured by the camera. In the fundus, the ﬂuorescein of the dye demarcates the retinal and/or choroidal vasculature under observation, distinguishing it from adjacent areas/structures.

Pharmacokinetics
Distribution :
Within 7 to 14 seconds after IV administration into the antecubital vein, ﬂuorescein usually appears in the central retinal artery of the eye. Within a few minutes of IV administration of ﬂuorescein sodium, a yellowish discoloration of the skin occurs, which begins to fade 6 to 12 hours after dosing. Various estimates of volume of distribution indicate that ﬂuorescein distributes into interstitial space(0.5 L/kg).

Metabolism:
Fluorescein is metabolized to ﬂuorescein monoglucuronide. After IV administration of ﬂuorescein sodium (14 mg/kg) to 7 healthy subjects, approximately 80% of ﬂuorescein in plasma was converted to glucuronide conjugate after a period of 1 hour post dose.

Excretion:
Fluorescein and its metabolite are mainly eliminated via renal excretion. After IV administration, the urine remains slightly ﬂuorescent for 24 to 36 hours. A renal clearance of 1.75 mL/min/kg and a hepatic clearance (due to conjugation) of1.50 mL/min/kg have been estimated. The systemic clearance of ﬂuorescein was essentially complete by 48 to 72 hours after administration of 500 mg ﬂuorescein.
‍

DOSAGE AND ADMINISTRATIONS

Adult Dose:
‍The recommended dosage of AFLUOR-10 (Fluorescein Injection USP) via intravenous administration.

Pediatric Dose
For children, the dose is 7.7 mg/kg(actual body weight)up to a maximum of 500 mg, via intravenous infusion calculated on the basis of35 mg for each 10 lbs. (4.54 kg) of body weight.

Preparation for Administration:
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Do not mix or dilute with other solutions or drugs.

Administration:
Inject the dose (over 5-10 seconds is normally recommended) into the antecubital vein, after taking precautions to avoid extravasation. A syringe, ﬁlled with AFLUOR -10 (Fluorescein Injection USP), may be attached to transparent tubing and a 23 gauge butterﬂy needle for injection. Insert the needle and draw the patient's blood to the hub of the syringe so that a small air bubble separates the patient's blood in the tubing from the ﬂuorescein. With the room lights on, slowly inject the blood back into the vein while watching the skin over the needle tip. If the needle has extravasated, the patient's blood will be seen to bulge the skin and the injection should be stopped before any ﬂuorescein is injected. When assured that extravasation has not occurred, the room light may be turned off and the ﬂuorescein injection completed. Luminescence usually appears in the retina and choroidal vessels in 7 to 14 seconds and can be observed by standard viewing equipment.
‍

CONTRAINDICATIONS

AFLUOR-10 (Fluorescein Injection USP) is contraindicated in patients with known hypersensitivity to ﬂuorescein sodium or any other ingredients in this product. Rare cases of death due to anaphylaxis have been reported. Fluorescein sodium can induce serious intolerance reactions. These reactions of intolerance are always unpredictable but they are more frequent in patients who have previously experienced an adverse reaction after ﬂuorescein injection (symptoms other than nausea and vomiting) or in patients with history of allergy such as food or drug induced urticaria, asthma, eczema, allergic rhinitis. Detailed questioning of each patient is recommended before the angiography to evaluate any prior history of allergy.

WARNINGS & PRECAUTIONS
Respiratory Reactions
Caution should be exercised inpatients with a history of allergy or bronchial asthma. An emergency tray should always be available. If a potential allergy is suspected, an intradermal skin test may be performed prior to intravenous administration, i.e., 0.05 mL injected intradermally to be evaluated 30 to 60 minutes following injection. Given the sensitivity and speciﬁcity of skin testing, a negative skin test is not proof that a patient is not allergic to ﬂuorescein.

Severe local tissue damage
Extravasation during injection can result in severe local tissue damage due to high pH of ﬂuorescein solution. The following complications resulting from extravasation of ﬂuorescein have been noted to occur: Sloughing of the skin, superﬁcial phlebitis, subcutaneous granuloma, and toxic neuritis along the median nerve in the antecubital area. Complications resulting from extravasation can cause severe pain in the arm for up to several hours. When extravasation occurs, the injection should be discontinued and conservative measures to treat damaged tissue and to relieve pain should be implemented

ADVERSE EFFECTS
Skin and urine discoloration:
The most common reaction is discoloration of the skin and urine. Skin will attain a temporary yellowish discoloration. Urine attains a bright yellow color. Discoloration of the skin usually fades in 6 to 12 hours and usually fades in urine in 24 to 36 hours.

Gastrointestinal Reaction:
The next most common adverse reaction is nausea. Vomiting, and gastrointestinal distress have also occurred. A strong taste may develop after injection.

Hypersensitivity Reactions:
Symptoms and signs of hypersensitivity have occurred. Generalized hives and itching, bronchospasm and anaphylaxis have been reported.

Cardiopulmonary Reactions:
Syncope and hypotension may occur. Cardiac arrest, basilar artery ischemia, severe shock and death may occur rarely.
Neurologic Reactions:
Headache may occur. Convulsions may rarely occur following injection.

Thrombophlebitis:
Thrombophlebitis at the injection site has been reported. Extravasation of the solution at the injection site causes intense pain at the site and a dull aching pain in the injected arm.

USE IN SPECIFIC POPULATIONS

Pregnancy:
Pregnancy Category C. Adequate animal reproduction studies have not been conducted with ﬂuorescein sodium. It is also not known whether ﬂuorescein sodium can cause fetal harm when administered to a pregnant woman. Fluorescein sodium should be given to a pregnant woman only if clearly needed.

Nursing Mothers:
Fluorescein sodium has been demonstrated to be excreted in human milk. Caution should be exercised when ﬂuorescein sodium is administered to a nursing woman.

Pediatric Use:
Pediatric patients have been included in clinical studies. No overall differences in safety or effectiveness have been observed between pediatric and adult patients.

Geriatric Use:
No overall differences in safety or effectiveness have been observed between elderly and other adult patients.

STORAGE:

Protected from light. Store at a temperature not exceeding 30°C.

SHELF LIFE

24 Months

HOW SUPPLIED:

AFLUOR-10 (Fluorescein Injection USP) is supplied in 3 mL glass vial.
‍

AFLUOR-10

APPASONE /2mL

(Dexamethasone Sodium Phosphate Injection USP)

THIS LEAFLET CONTAINSIMPORTANT PRODUCT USE AND SAFETY INFORMATION, PLEASE READ CAREFULLY AND RETAIN FOR FURTHER REFERENCE.

DESCRIPTION

APPASONE (Dexamethasone Sodium Phosphate Injection USP) is a water-soluble inorganic ester of Dexamethasone which produces a rapid response even when injected intramuscularly.
Dexamethasone Sodium Phosphate, C22H28FNa2O8P,has a molecular weight of 516.41 and chemically is Pregn-4-ene-3, 20- dione,9-fluoro-11, 17-dihydroxy-16-methyl-21 (phosphonooxy)-, disodium salt, (11β, 16α). It occurs as a white to creamy white powder, is exceedingly hygroscopic, is soluble in water and its solutions have a pH between 7.0 and 8.5.It has the following structural formula:
‍

COMPOSITION

Each mL Contains:
Dexamethasone Sodium Phosphate USP
Eq. to Dexamethasone Phosphate 4 mg
Methylparaben USP 0.15% w/v
PropylparabenUSP 0.02% w/v
(As preservatives)
Water for Injection USP q.s.

INDICATIONS

A. Intravenous or intramuscular administration. When oral therapy is not feasible and the strength, dosage form, and route of administration of the drug reasonably lend the preparation to the treatment of the condition, those products labeled for intravenous or intramuscular use are indicated as follows:
‍1. Endocrine Disorders: Primary or secondary adrenocortical insuﬃciency (hydrocortisone or cortisone is the drug of choice; synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy, mineralocorticoid supplementation is of particular importance).
Acute adrenocortical insuﬃciency (hydrocortisone or cortisone is the drug of choice; mineralocorticoid supplementation may be necessary, particularly when synthetic analogs are used).
Preoperatively, and in the event of serious trauma or illness, in patients with known adrenal insuﬃciency or when adrenocortical reserve is doubtful. Shock unresponsive to conventional therapy if adrenocortical insuﬃciency exists or is suspected.
Congenital adrenal hyperplasia.
Nonsuppurative thyroiditis.
Hypercalcemia associated with cancer.

‍2. Rheumatic disorders: As adjunctive therapy for short-term administration(to tide the patient over an acute episode or exacerbation) in:
Post-traumatic osteoarthritis.
Synovitis of osteoarthritis.
Rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases
may require low-dose maintenance therapy).
Acute and subacute bursitis.
Epicondylitis.
Acute nonspecific tenosynovitis.
Acute gouty arthritis.
Psoriatic arthritis.
Ankylosing spondylitis.

3. Collagen diseases. During an exacerbation or as maintenance therapy in selected cases of:
Systemic lupus erythematosus
Acute rheumatic carditis.

‍4. Dermatologic Diseases:
‍Pemphigus.
Severe erythema multiforme (Stevens-Johnson Syndrome).
Exfoliative dermatitis.
Bullous dermatitis herpetiformis.
Severe seborrheic dermatitis.
Severe psoriasis.
Mycosis fungoides.

‍5. Allergic States. Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment in:
Bronchial asthma.
Contact dermatitis.
Atopic dermatitis.
Serum sickness.
Seasonal or perennial allergic rhinitis.
Drug hypersensitivity reactions.
Urticarial transfusion reactions.
Acute noninfectious laryngeal edema (epinephrine is the drug of first choice).

6. Ophthalmic Diseases. Severe acute and chronic allergic and inflammatory processes involving the eye, such as:
Herpes zoster ophthalmicus.
Iritis, iridocyclitis.
Chorioretinitis.
Diffuse posterior uveitis and choroiditis.
Optic neuritis.
Sympathetic ophthalmia.
Anterior segment inflammation.
Allergic conjunctivitis.
Allergic corneal marginal ulcers.
Keratitis.

‍7. Gastrointestinal diseases. To tide the patient over a critical period of the diseasein:
Ulcerative colitis (systemic therapy).
Regional enteritis(systemic therapy).

‍8. Respiratory diseases:
Symptomatic Sarcoidosis.
Berylliosis.
Fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate anti-tuberculosis chemotherapy.
Loeﬄer's syndrome not manageable by other means.
Aspiration pneumonitis.

‍9. Hematologic disorders:
‍Acquired (autoimmune) hemolytic anemia.
Idiopathic thrombocytopenic purpura in adults (I.V. only; I.M. administration is contraindicated).
Secondary thrombocytopenia in adults.
Erythroblastopenia (RBC anemia).
Congenital (erythroid) hypoplastic anemia.

‍10. Neoplastic diseases. For palliative management of:
Leukemias and lymphomas in adults.
Acute leukemia of childhood.

‍11. Edematous states. To induce diuresis or remission of proteinuria in the nephrotic syndrome, without uremia, of the idiopathic type or that due to lupus erythematosus.

‍12. Nervous system.
Acute exacerbations of multiple sclerosis.

‍13. Miscellaneous.
Tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate anti-tuberculosis chemotherapy.
Trichinosis with neurologic or myocardial involvement.
Diagnostic testing of adrenocortical hyperfunction.
Cerebral edema of diverse etiologies in conjunction with adequate neurological evaluation and management.

B. Intra-articular or soft tissue administration.
‍When the strength and dosage form of the drug lend the preparation to the treatment of the condition, those products labeled for intra- articular or soft tissue administration are indicated as adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in:
‍Synovitis of osteoarthritis.
Rheumatoid arthritis.
Acute and subacute bursitis.
Acute gouty arthritis.
Epicondylitis.
Acute nonspecific tenosynovitis.
Post-traumatic osteoarthritis.

C .Intralesional administration. When the strength and dosage form of the drug lend the preparation to the treatment of the condition, those products labeled for intralesional administration are indicated for: Keloids.
‍Localized hypertrophic, infiltrated, inflammatory lesions of: lichen planus, psoriatic plaques, granuloma annulare, and lichen simplex chronicus(neurodermatitis).
Discoid lupus erythematosus.
Necrobiosis lipoidica diabeticorum.
Alopecia areata.
They also may be useful in cystic tumors of anaponeurosis tendon (ganglia).

CONTRAINDICATIONS

Systemic fungal infections.
‍
WARNINGS
Serious Neurologic Adverse Reactions with Epidural Administration
Serious neurologic events, some resulting in death, have been reported with epidural injection of corticosteroids. Specific events reported include, but are not limited to, spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke. These serious neurologic events have been reported with and without use of fluoroscopy. The safety and effectiveness of epidural administration of corticosteroids have not been established, and corticosteroids are not approved for this use.
In patients on corticosteroid therapy subject to any unusual stress, increased dosage of rapidly acting corticosteroids before, during and after the stressful situation is indicated. Corticosteroids may mask some signs of infection, and new infections may appear during their use. There may be decreased resistance and inability to localize infection when corticosteroids are used.
Prolonged use of corticosteroids may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections due to fungi or viruses.
Children who are on immunosuppressant drugs are more susceptible to infections than healthy children. Chickenpox and measles, for example, can have a more serious or even fatal course in children on immunosuppressant corticosteroids. In such children, or in adults who have not had these diseases, particular care should be taken to avoid exposure .If exposed, therapy with varicella zoster immune globulin (VZIG)or pooled intravenous immunoglobulin (IVIG), as appropriate, may be indicated. If chickenpox develops, treatment with antiviral agents may be considered.
Similarly, corticosteroids should be used with great care in patients with known or suspected Strongyloides (threadworm) infestation. In such patients, corticosteroidinduced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia.

Usage in Pregnancy. Since adequate human reproduction studies have not been done with corticosteroids, use of these drugs in pregnancy, nursing mothers or women of childbearing potential requires that the possible benefits of the drug be weighed against the potential hazards to the mother and embryo or fetus. Infants born of mothers who have received substantial doses of corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism. Average and large doses of cortisone or hydrocortisone can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium. These effects are less likely to occur with the synthetic derivatives except when used in large doses. Patients with a stressed myocardium should be observed carefully and the drug administered slowly since premature ventricular contractions may occur with rapid administration. Dietary salt restriction and potassium supplementation may be necessary. All corticosteroids increase calcium excretion. While on corticosteroid therapy patients should not be vaccinated against smallpox. Other immunization procedures should not be undertaken in patients who are on corticosteroids, especially in high doses, because of possible hazards of neurological complications and lack of antibody response.The use of APPASONE (Dexamethasone Sodium Phosphate Injection USP) inactive tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for the management of the disease in conjunction with an appropriate anti-tuberculosis regimen. If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary as reactivation of the disease may occur. During prolonged corticosteroid therapy, these patients should receive chemoprophylaxis. Because rare instances of anaphylactoid reactions have occurred in patients receiving parenteral corticosteroid therapy, appropriate precautionary measures should be taken prior to administration, especially when the patient has a history of allergy to any drug.

PRECAUTIONS

Drug-induced secondary adrenocortical insuﬃciency may be minimized by gradual reduction of dosage. This type of relative insuﬃciency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted. Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently. There is an enhanced effect of corticosteroids in patients with hypothyroidism and in those with cirrhosis. Corticosteroids should be used cautiously in patients with ocular herpes simplex for fear of corneal perforation. The lowest possible dose of corticosteroid should be used to control the condition under treatment, and when reduction in dosage is possible, the reduction must be gradual. Psychotic derangements may appear when corticosteroids are used ranging from euphoria, insomnia, mood swings, personality changes, and severe depression to frank psychotic manifestations. Also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids. Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia.
Steroids should be used with caution in nonspecific ulcerative colitis, if there is a probability of impending perforation, abscess or other pyogenic infection, also in diverticulitis, fresh intestinal anastomoses, active or latent peptic ulcer, renal insuﬃciency, hypertension, osteoporosis, and myasthenia gravis.
Growth and development of infants and children on prolonged corticosteroid therapy should be carefully followed. Patients who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chickenpox or measles and, if exposed, to obtain medical advice. Intra-articular injection of a corticosteroid may produce systemic as well as local effects. Appropriate examination of any joint fluid present is necessary to exclude aseptic process. A marked increase in pain accompanied by local swelling, further restriction of joint motion, fever, and malaise are suggestive of septic arthritis. If this complication occurs and the diagnosis of sepsis is confirmed, appropriate antimicrobial therapy should be instituted. Local injection of a steroid into a previously infected joint is to be avoided. Corticosteroids should not be injected into unstable joints. Although controlled clinical trial shave shown corticosteroids to be effective in speeding the resolution of acute exacerbations of multiple sclerosis they do not show that they affect the ultimate outcome or natural history of the disease. The studies do show that relatively high doses of corticosteroids are necessary to demonstrate a significant effect. Since complications of treatment with glucocorticoids are dependent on the size of the dose and the duration of treatment a risk/benefit decision must be made in each individual case as to dose and duration of treatment and as to whether daily or intermittent therapy should be used.

ADVERSE REACTIONS

Fluid and electrolyte disturbances:
Sodium retention
Fluid retention
Congestive heart failure in susceptible patients
Potassium loss
Hypokalemic alkalosis
Hypertension
‍
Musculoskeletal:
Muscle weakness
Steroid myopathy
Loss of muscle mass
Osteoporosis
Vertebral compression fractures
Aseptic necrosis of femoral and humeral heads
Pathologic fracture of long bones

Gastrointestinal:
Peptic ulcer with possible subsequent perforation and hemorrhage
Pancreatitis
Abdominal distention
Ulcerative esophagitis
‍
Dermatological:
Impaired wound healing
Thin fragile skin
Facial erythema
Increased sweating
May suppress reactions to skin tests
Petechiae and ecchymoses

Neurological:
Convulsions Increased intracranial pressure with papilledema (pseudotum or cerebri) usually after treatment
Vertigo
Headache
‍
Ophthalmic:
‍Posterior subcapsular cataracts
Increased intraocular pressure
Glaucoma

Endocrine:
Menstrual irregularities
Development of cushingoid state
Suppression of growth in children
Secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress, as in trauma, surgery, or illness
Decreased carbohydrate tolerance
Manifestations of latent diabetes mellitus
Increased requirements for insulin or oral hypoglycemic agents in diabetics

Metabolic:
Negative nitrogen balance due to protein catabolism

Miscellaneous:
‍Hyperpigmentation or hypopigmentation
Subcutaneous and cutaneous atrophy
Sterile abscess
Postinjection flare, following intra-articular use
Charcot-like arthropathy
Itching, burning, tingling in the ano-genital region

DOSAGE AND ADMINISTRATION

A. Intravenous or intra muscular administration.
The initial dosage of APPASONE (Dexamethasone Sodium Phosphate Injection USP) may vary from 0.50 mg/day to 9.0 mg/day depending on the specific disease entity being treated. Insituations of less severity, lower doses will generally suﬃce while in selected patients higher initial doses may be required. Usually the parenteral dosage ranges are one-third to one-half the oral dose given every 12 hours. However, in certain overwhelming, acute, life-threatening situations, administration of dosages exceeding the usual dosages may be justified and may be in multiples of the oral dosages. For the treatment of unresponsive shock high pharmacologic doses of this product are currently recommended. Reported regimens range from 1 to 6 mg/kg of body weight as a single intravenous injection to 40 mg initially followed by repeat intravenous injection every 2 to 6 hours while shock persists. For the treatment of cerebral edema in adults an initial intravenous dose of 10 mg is recommended followed by 4 mg intramuscularly every six hours until maximum response has been noted. This regimen may be continued for several days postoperatively in patients requiring brain surgery. Oral dexamethasone, 1 to 3 mg t.i.d., should be given as soon as possible and dosage tapered off over a period of five to seven days. Nonoperative cases may require continuous therapy to remain free of symptoms of increased intracranial pressure. The smallest effective dose should be used in children, preferably orally. This may approximate 0.2mg/kg/24 hours in divided doses. In treatment of acute exacerbations of multiple sclerosis daily doses of 200 mg of prednisolone for a week followed by 80 mg every other day or 4–8 mg Dexamethasone every other day for 1 month have been shown to be effective. The initial dosage should be maintained or adjusted until a satisfactory response is noted. If after a reasonable period of time there is a lack of satisfactory clinical response, APPASONE(Dexamethasone Sodium Phosphate Injection USP)should be discontinued and the patient transferred to other appropriate therapy. It should be emphasized that dosage requirements are variable and must be individualized on the basis of the disease under treatment and the response of the patient .After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage which will maintain an adequate clinical response is reached. It should be kept in mind that constant monitoring is needed in regard to drug dosage. Included in the situations which may make dosage adjustments necessary are changes in clinical status secondary to remissions or exacerbations in the disease process, the patient’s individual drug responsiveness and the effect of patient exposure to stressful situations not directly related to the disease entity undertreatment. In this later situation it may be necessary to increase the dosage of APPASONE (Dexamethasone Sodium Phosphate Injection USP) for a period of time consistent with the patient’s condition. If after a long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly. B. Intra-articular, soft tissue or intralesional administration. The dose for instrasynovial administration is usually 2 to 4 mg for large joints and 0.8 to 1 mg for small joints. For soft tissue and bursal injections a dose of 2 to 4 mg is recommended. Ganglia require a dose of 1 to 2 mg. A dose of 0.4 to 1 mg is used for injection into tendon sheaths. Injection into intervertebral joints should not be attempted at any time and hip joint injection cannot be recommended as an oﬃce procedure. Intra synovial and soft tissue injections should be employed only when affected areas are limited to 1 or 2 sites. It should be remembered that corticoids provide palliation only and that other conventional or curative methods of therapy should be employed when indicated. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Frequency of injection usually ranges from once every 3 to 5 days to once every2 to 3 weeks. Frequent intra-articular injection may cause damage to joint tissue.

STORAGE:

Store protected from light. Store at controlled room temperature.

SHELF LIFE

24 Months

HOW SUPPLIED:

APPASONE / 2mL (Dexamethasone Sodium Phosphate Injection USP) is supplied in a 2 mL glass vial.
‍

INJECTION

A-EXARIN

20mg/40mg/60mg/80mg/100mg

(Enoxaparin Sodium Injection USP)

THIS LEAFLET CONTAINSIMPORTANT PRODUCT USE AND SAFETY INFORMATION, PLEASE READ CAREFULLY AND RETAIN FOR FURTHER REFERENCE.

A-EXARIN 20mg

Enoxaparin Sodium Injection USP

A-EXARIN 40mg

Enoxaparin Sodium Injection USP

A-EXARIN 60mg

Enoxaparin Sodium Injection USP

A-EXARIN 80mg

Enoxaparin Sodium Injection USP

A-EXARIN 100mg

Enoxaparin Sodium Injection USP

THERAPEUTIC INDICATIONS

Posology and method of administration Posology

Interaction with other medicinal products and other forms of interaction

﻿Fertility, pregnancy and lactation

Effects on ability to drive and use machines

Undesirable effects

Overdose

STORAGE:

SHELF LIFE

HOW SUPPLIED:

A-Exarin

A-Ligcaine 1.0/2.0

(Lidocaine Hydrochloride Injection USP)

THIS LEAFLET CONTAINSIMPORTANT PRODUCT USE AND SAFETY INFORMATION, PLEASE READ CAREFULLY AND RETAIN FOR FURTHER REFERENCE.

DESCRIPTION

NHCOCH2N(C2H5)2 * HCI

COMPOSITION

A-Ligcaine 2.0

INDICATION AND USAGE

CLINICAL PHARMACOLOGY

﻿WARNINGS AND PRECAUTIONS

﻿DOSAGE AND ADMINISTRATION

STORAGE:

SHELF LIFE

HOW SUPPLIED:

A-Ligcaine

A-Ligcaine Plus

(Lidocaine Hydrochloride Injection USP)

THIS LEAFLET CONTAINSIMPORTANT PRODUCT USE AND SAFETY INFORMATION, PLEASE READ CAREFULLY AND RETAIN FOR FURTHER REFERENCE.

DESCRIPTION

COMPOSITION

INDICATION AND USAGE

CLINICAL PHARMACOLOGY

﻿WARNINGS AND PRECAUTIONS

﻿DOSAGE AND ADMINISTRATION

STORAGE:

SHELF LIFE

HOW SUPPLIED:

A-Ligcaine Plus

AFLUOR

(Fluorescein Sodium Injection IP)

THIS LEAFLET CONTAINSIMPORTANT PRODUCT USE AND SAFETY INFORMATION, PLEASE READ CAREFULLY AND RETAIN FOR FURTHER REFERENCE.

DESCRIPTION

COMPOSITION

INDICATIONS

CLINICAL PHARMACOLOGY

DOSAGE AND ADMINISTRATIONS

CONTRAINDICATIONS

USE IN SPECIFIC POPULATIONS

STORAGE:

SHELF LIFE

HOW SUPPLIED:

AFLUOR 3mL

AFLUOR-10 /3mL

(Fluorescein Injection USP)

THIS LEAFLET CONTAINSIMPORTANT PRODUCT USE AND SAFETY INFORMATION, PLEASE READ CAREFULLY AND RETAIN FOR FURTHER REFERENCE.

DESCRIPTION

COMPOSITION

INDICATIONS

CLINICAL PHARMACOLOGY

DOSAGE AND ADMINISTRATIONS

CONTRAINDICATIONS

USE IN SPECIFIC POPULATIONS

STORAGE:

SHELF LIFE

Fertility, pregnancy and lactation

**NHCOCH2N(C2H5)2 * HCI**

WARNINGS AND PRECAUTIONS

DOSAGE AND ADMINISTRATION

WARNINGS AND PRECAUTIONS

DOSAGE AND ADMINISTRATION