OCULAR INJECTION

APPACARPINE

(Pilocarpine Nitrate Ophthalmic Solution USP 0.5%w/v)

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

DESCRIPTION

APPACARPINE (Pilocarpine Nitrate Ophthalmic Solution USP 0.5%w/v) is a clear, colour less sterile ophthalmic solution. Not for injection. For Intracameral administration. Its contains no preservative. It is used as direct acting miotic.The active ingredient is represented by the chemical:

APPACARPINE (Pilocarpine Nitrate Ophthalmic Solution USP 0.5%w/v) is a clear, colour less sterile ophthalmic solution. Not for injection. For Intracameral administration. Its contains no preservative. It is used as direct acting miotic.

Structural formula: C11H17N3O5
Molecular Weight: 271.27 g/mol
Chemical Name: 2(3H)-Furanone, 3-ethyldihydro-4-[(1-methyl-1H-imidazol-5- yl)methyl]-, (3S-cis)-, mononitrate.

COMPOSITION

Each ml contains:
Pilocarpine Nitrate USP      0.5%w/v
Aqueous Vehicle                     q.s.

DOSAGE FORM

Ophthalmic Solution

ADVANTAGES

Ÿ  Ready to use on convenient 1ml glass vial
Ÿ  Sterile solution without preservative
Ÿ  Non Toxic
Ÿ  Miotic reaction by contraction of Iris.

INDICATIONS

APPACARPINE (Pilocarpine Nitrate Ophthalmic Solution USP 0.5%w/v) for intracameral administration to induce prompt miosis during cataract surgery with I.O.L implant 

CONTRAINDICATIONS

APPACARPINE (Pilocarpine Nitrate Ophthalmic Solution USP0.5%w/v) is contra indicated where papillary constriction is undesirable e.g in cases of acute iritic and with known hypersensitivity to any of the ingredients of the formulation.

ADVERSE EFFECTS

No untowards reactions have been reported from the use of APPACARPINE (Pilocarpine Nitrate Ophthalmic Solution USP 0.5%w/v).

CAUTION

To be used with caution on patients with hypersensitivity.

STORAGE

Preserve in tight, light resistant containers, Store below 30°C.
Do not allow to Freeze.

SHELF LIFE

24 Months

HOW SUPPLIED:

APPACARPINE (Pilocarpine Nitrate Ophthalmic Solution USP 0.5%w/v) is supplied in 1 mL glass vial.

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APPACARPINE

MYDRIA PFS

(Tropicamide, Phenylephrine Hydrochloride and Lidocaine Hydrochloride Injection) (Preservative Free Sterile Solution)

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

DESCRIPTION

Mydria PFS Injection is a solution which is injected into the eye.it contains three active substances:-Tropicamide which belongs to a group of medicines blocking the passage of impulses through particular nerves (known as anticholinergics),-Phenylephrine Hydrochloride Which belongs to a group of medicines mimicking the effects of impulses conveyed through particular nerves(known as alpha sympathomimetics).Lidocaine Hydrochloride which belongs to a class of drugs called amide type local anesthetics

COMPOSITION

Each ml contains:
Tropicamide                                    IP                  0.2mg
Phenylephrine Hydrochloride IP                       3.1mg
Lidocaine Hydrochloride              IP                   10mg
Water for Injections                                                   q.s.

INDICATION

Mydria PFS Injection is used in adults only. It will be administered by ophthalmic surgeon by injection into the eye at the beginning of cataract surgery(cloudiness of the lens), in order to enlarge the pupil of your eye (mydriasis) and to obtain anaesthesia in your eye during the surgical procedure.

CLINICAL PHARMACOLOGY

A) Pharmacodynamic  Properties                                      Mydria PFS Injection is a solution for intracameral injection which combines two synthetic mydriatic agents (Tropicamide - anticholinergic, and Phenylephrine Hydrochloride - alpha sympathomimetic) and one local anesthetic (Lidocaine Hydrochloride).

B) Mechanism of Action
Phenylephrine is a direct acting sympathomimetic agent. It causes mydriasis via the stimulation of alpha-adrenergic receptors of the pupillary dilator(the resulting contraction of the pupillary dilator causes pupil dilation).There is almost no cycloplegic effect. Tropicamide is a para sympatholytic agent, which acts by binding to and blocking the M4 muscarinic receptors of the eye muscles. It prevents the iris sphincter muscle and ciliary body muscle from responding to cholinergic stimulation, producing dilation of the pupil and paralysis of the ciliary muscle (cyclopegia). Lidocaine Hydrochloride is a local anesthetic of the amide type. It acts by inhibiting the ionic refluxes required for the initiation and conduction of impulses, there by stabilising the neuronal membrane.

C) Pharmacodynamic Effects
Although Tropicamide as a mono therapy produces both mydriasis and cycloplegia, additional mydriasis occurs if sympathomimetic agents such as phenylephrine are used simultaneously. Such synergistic combinations are commonly prescribed to achieve maximal dilation of the pupil for cataract extraction. As an average, 95% of the dilation measured before the viscoelastic injection was obtained within 30 seconds after a single 200-uL.

Posology and method of  Administration
Intracameral use. One pre-filled syringe for single eye use.
Mydria PFS must be administered by an ophthalmic surgeon.

Posology
Mydria PFS should only be used in patients who have already demonstrated, at pre-operative assessment, a satisfactory pupil dilation with topical mydriatic therapy

.Adults: Slowly inject, by intracameral route,0.2 ml of Mydria PFS in one injection, at the start of the surgical procedure. 

Special Population
Elderly:                    No   dose   adjustment  is    necessary.
Paediatric population: The safety and efficacy of Mydria PFS in children aged 0 to 18 years have not been established.

Method of Administration
Intracameral use The following procedure should be followed:
1.Five minutes before performing the pre-operative antiseptic procedure and the first incision, one to two drops of anaesthetic eye drops should be instilled in the eye.
2.At the beginning of surgery, 0.2 ml of Mydria PFS is slowly injected in only one injection by anophthalmic surgeon, via intracameral route, through the side port or principal port.

CONTRAINDICATIONS

-Hypersensitivity to the active substances (Phenylephrine Hydrochloride, Tropicamide and Lidocaine Hydrochloride) or to any of the excipients which is used in formulation of Mydria PFS Injection.
- Known hypersensitivity to anaesthetics of the amide type.
- Known hypersensitivity to atropine derivatives.

WARNINGS AND PRECAUTIONS

Special  warnings                                                                                                                                         The recommended dose is 0.2 ml of Mydria PFS Injection; no additional dose should be injected as no significant add-on effect has been demonstrated, and as increased endothelial cell loss was observed. Corneal endothelial toxicity has not been reported at the recommended dose of, Mydria PFS Injection; nevertheless, due to limited data, this risk cannot be excluded.
There is no clinical experience with Mydria PFS Injection in:
- Insulin-dependent or uncontrolled diabetic patients,
- Patients with corneal disease, especially those with any coexisting endothelial cell impairment,
- Patients with history of uveitis,
- Patients with pupillary abnormalities or presenting an ocular traumatism,
- Patients with very dark irides,
- Cataract surgery when combined with corneal transplantation.

There is no experience in patients at risk of floppy iris syndrome with Mydria PFS Injection. Such patients should benefit of a step-by-step pupil dilation strategy starting with the administration of mydriatic eye drops. There is no clinical experience during cataract surgery with Mydria PFS Injection in patients treated with topical mydriatics and for whom pupil constriction (or even miosis) occurs during surgery. Mydria PFS Injection is not recommended to be used in cataract surgery when combined with vitrectomy, due to the vasoconstricting effects of Phenylephrine. Mydria PFS Injection is not recommended in subjects with a shallow anterior chamber or a history of acute narrow angle glaucoma.

Special   precautions   for us
Mydria PFS Injection was shown to produce undetectable or very low systemic concentrations of active substances, Since systemic effects of Phenylephrine and Lidocaine are dose dependent, it is unlikely that these effects occur with Mydria PFS Injection. However, as the risk cannot be excluded, it is reminded that:-Phenylephrine has sympathomimetic activity that might affect patients in the event of hypertension, cardiac disorders, hyperthyroidism, atherosclerosis or prostate disorders and all subjects presenting with a contraindication to the systemic use of pressor amines;-Lidocaine should be used with caution in patients with epilepsy, myasthenia gravis, cardiac conduction disturbances, congestive heart failure, bradycardia, severe shock, impaired respiratory function or impaired renal function with a creatinine clearance of less than 10mL/minute. 

Interaction with other medicinal products and other forms of interaction
No   interaction  studies  have  been  performed   with  Mydria  PFS  Injection. Since the systemic exposure is expected to be very low, systemic interactions are unlikely. 

Fertility, pregnancy and lactation
Pregnancy
 There are no adequate data from the use of Phenylephrine Hydrochloride and Tropicamide in pregnant women. Animal studies are insufficient with respect to effects on pregnancy, embryonic/foetal development, parturition and postnatal development. Although animal studies have revealed no evidence of harm to the foetus, Lidocaine Hydrochloride crosses the placenta and should not be administered during pregnancy. Even though a negligible systemic uptake is expected, a low systemic exposure cannot be excluded. Therefore, Mydria PFS Injection should not be used during pregnancy. 

Breastfeeding 
No data are available concerning the secretion of Phenylephrine Hydrochloride or Tropicamide into breast milk. However, Phenylephrine Hydrochloride is poorly absorbed orally, implying that absorption by the infant would be negligible. On the other hand, infants may be very sensitive to anticholinergics, and despite the expected negligible systemic exposure, tropicamide is therefore not recommended during breastfeeding. Small amounts of Lidocaine are secreted into breast milk and there is a possibility of an allergic reaction in the infant. Therefore, Mydria PFS Injection should not be used during breastfeeding. 

Fertility
There is no information on whether Mydria PFS Injection may affect fertility in human males or females. 

Effects on  ability to   drive  and use   machines
Mydria PFS Injection has a moderate influence on the ability to drive and use machines, due to its mydriatic effect. Consequently, after cataract surgery with one Mydria PFS Injection, the patient should be advised not to drive and/or use machines while the visual disturbances persist.

Overdose
Systemic effects
Due to single administration and low expected systemic passage of Mydria PFS Injection, the risk of systemic effects due to overdose is considered minimal. The symptoms of Phenylephrine Ophthalmic overdose are likely to be effects resulting from systemic absorption, including extreme tiredness, sweating, dizziness, a slow heartbeat, and coma. Because severe toxic reaction to Phenylephrine is of rapid onset and short duration, treatment is primarily supportive. Prompt injection of a rapidly acting alphaadrenergic blocking agent such as Phentolamine (dose 2 to 5 mg in intravenous use) has been recommended. The symptoms of Tropicamide Ophthalmic overdose include headache, fast heartbeat, dry mouth and skin, unusual drowsiness, and flushing. Systemic effects from Tropicamide are not expected. Should an overdose occur causing local effects, e.g. sustained mydriasis, pilocarpine or 0.25% w/v physostigmine should be applied. In the event of excessive absorption of lidocaine intothe bloodstream, symptoms may include CNS effects (such as convulsions, unconsciousness and possibly respiratory arrest) and cardiovascular reactions (such as hypotension, myocardial depression, bradycardia and possibly cardiac arrest).Treatment of a patient suffering from systemic toxicity of Lidocaine consists of arresting the convulsions and ensuring adequate ventilation with oxygen, if necessary by assisted or controlled ventilation (respiration).

Special Precautions for Disposal
For single eye  use  only.        
Use immediately after first opening of the PFS.
Warning: Do not use if pouches are damaged or broken. Open under aseptic conditions only. The content of the pouch packs are guaranteed as sterile. 
The solution should be visually inspected and should only be used if it is a clear, slightly brownish-yellow and practically free from visible particles solution.
Mydria PFS must be administered by intracameral injection, by an ophthalmic surgeon in the recommended aseptic conditions of cataract surgery.

Handling   Instruction
To prepare the product for intracameral injection, please adhere to the following instructions:
)Remove the syringe from Its pouch packaging in a sterile environment.
2)Remove the cap from the tip of  the  syringe barrel.
3)Open the cannula and firmly screw it onto the lock fitting.
4)Depress the plunger and discard the first 0.1 to 0.3 ml of fluid.
5)Slowly inject the 0.2 ml syringe volume into the anterior chamber of the eye, as only one injection, through the side port or principal port.
6)After    use,    discard    the   remaining    solution    appropriately.    Do not keep it for subsequent    use. Any unused medicinal product or waste material should be disposed of in accordance with local requirements. Discard used needles in a sharps container.

Incompatibilities                                                                     No incompatibility with most commonly used products in cataract surgery was reported in literature with the active ingredients, and during clinical trials. For usual viscoelastic, this was also confirmed by a pharmaceutical interaction test.

STORAGE

Store below 30°C, Do not allow to freeze.

SHELF LIFE

24 Months

HOW SUPPLIED:

Mydria PFS 1 mL Injection is supplied in 2.25 mL Glass Syringe along with one Angular cannula.

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MYDRIA PFS

TRI-ACE

(Triamcinolone Acetonide Injectable Suspension USP)

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

DESCRIPTION

Tri-Ace (Triamcinolone Acetonide Injectable Suspension USP) is a synthetic glucocorticoid corticosteroid with anti-inflammatory action. This formulation is suitable for Intravitreal, intra- muscular and intra-articular use. This formulation is not for intravenous injection.

COMPOSITION

Each ml contains:
Triamcinolone           Acetonide
USP                             40mg
In Sterile Aqueous Base   q.s.

INDICATIONS

Intramuscular: Intramuscular administration of Tri-Ace(Triamcinolone Acetonide Injectable Suspension USP) is indicated for the replacement therapy in adrenal insufficiency; suppression of allergic and inflammation responses.

Intra-articular: : Tri-Ace (Triamcinolone Acetonide Injectable Suspension USP) is indicated for intra-articular or intrabursal administration, and for injections into tendon sheaths, 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 non-specific tenosynovitis, post-traumatic osteoarthritis.
Ophthalmic: Tri-Ace (Triamcinolone Acetonide Injectable Suspension USP) is indicated for sympathetic ophthalmia, temporal arteritis, uveitis, and ocular inflammatory conditions unresponsive to topical corticosteroids.

CLINICAL PHARMACOLOGY

Glucocorticoids, naturally occurring and synthetic, are adrenocortical steroids that are readily absorbed from the gastrointestinal tract. Naturally occurring glucocorticoids (Hydrocortisone and Cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. Synthetic analogues such as triamcinolone are primarily used for their anti-inflammatory effects in disorders of many organs systems. Tri-Ace (Triamcinolone Acetonide Injectable Suspension USP) has an extended duration of effect which may be sustained over a period of several weeks. Studies indicate that following a single intra muscular dose of 60 mg to 100 mg of Triamcinolone Acetonide, adrenal suppression occurs within 24 to 48 hours and then gradually returns to normal, usually in 30 to 40 days. This finding correlates closely with the extended duration of therapeutic action achieved with the drug

DOSAGE AND ADMINISTRATION

General: For children from 6 to 12 years, initial dose is 40 mg. Initial systemic dose for adults and children over 12 years is 40 to 80 mg. For adults, maximum daily dose is 80 to 100 mg. For local areas, dose for adults is up to 10 mg for smaller and 40 mg for larger areas.
Systemic: Intramuscular dosing: The suggested initial dose is 60 mg, injected deeply into the gluteal muscle. Dosage is usually adjusted within the range of 40 mg to 80 mg, depending upon patient response and duration of relief.
Local: Intra-articular dosing: 2.5 mg to 5 mg for smaller joints and from 5 mg to 15 mg for larger joints, depending on the specific disease entity being treated. For adults, doses up to 10 mg for smaller areas and up to 40 mg for larger areas have usually been sufficient.
Dosage For Treatment Of Ophthalmic Diseases: The initial recommended dose of Tri-Ace (Triamcinolone Acetonide Injectable Suspension USP) is 4 mg (100 microliters of 40 mg/ml suspension) with subsequent dosage as needed over the course of treatment.

SIDE-EFFECTS

General: Anaphylactic reactions, aggravation or masking of infections, hypertension, syncope, congestive heart failure, arrhythmias, necrotising  angitis, thromboembolism, thrombophlebitis. sodium retention, muscular weakness, fatigue, steroid myopathy, loss of muscle mass, osteoporosis, vertebral compression fractures, delayed healing of fractures, aseptic necrosis of femoral and humeral heads, pathologic fractures of long bones and spontaneous fractures. peptic ulcer with possible subsequent perforation and haemorrhage, pancreatitis, abdominal distension and ulcerative oesophagitis.

Following Intra-articular Administration:
Undesirable reactions have included post-injection flare, transient pain, occasional irritation at the injection site, sterile abscess formation, hyper-and hypopigmentation, charcot-like arthropathy and occasional brief increase in joint discomfort.

CONTRAINDICATIONS

Corticosteroids are generally contraindicated in patients with systemic infections. Tri-Ace (Triamcinolone Acetonide Injectable Suspension USP) is also contraindicated in patients with sensitivity to the active ingredients or excipients. Intramuscular corticosteroid preparations are contraindicated for idiopathic thrombocytopenic purpura and should not be used in cerebral malaria.

WARNINGS & PRECAUTIONS

⚫           Tri-Ace (Triamcinolone Acetonide Injectable Suspension USP) is a suspension; so it should not be administered intravenously.
⚫           Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing's syndrome and hyperglycemia. Monitor patients for these conditions and taper doses gradually.
⚫           Infections: Increased susceptibility to new infection and increased risk of exacerbation, dissemination or reactivation of latent infection.
⚫           Elevated blood  pressure,  salt and  water  retention and  hypokalaemia: Monitor blood pressure and sodium, potassium serum levels.
⚫           Behavioral and mood disturbances: May include euphoria, insomnia, mood swings, personality changes, severe depression and psychosis.
⚫           GI perforation: Increased risk in patients with certain GI disorders.
⚫           Decreases in bone density: Monitor bone density in patients receiving long-term corticosteroid therapy.
⚫           Live or live-attenuated vaccines: Should not be administered to patients receiving immunosuppressive doses of corticosteroids.
⚫           Negative effects on growth and development: Monitor pediatric patients on long-term corticosteroid therapy.
⚫           Use in pregnancy: Fetal harm can occur when used in first trimester of pregnancy.
⚫           Neuromuscular effects: An acute generalized myopathy has been observed with high doses of corticosteroids.
⚫           Use In the elderly: The common adverse effects of systemic Corticosteroids such as osteoporosis or hypertension may be associated with more serious consequences in old age.

DRUG INTERACTIONS

Amphotericin B injection and potassium-depleting agents: Patients should be observed for hypokalemia.
Anticholinesterases: Effects of the anticholinesterase agents may be antagonised. Anticoagulants (oral): Corticosteroids may potentiate or decrease anticoagulant action. Patients receiving oral anticoagulants and corticosteroids should be closely monitored.
Antidiabetics: Corticosteroids may increase blood glucose; diabetic control should be monitored, especially when corticosteroids are initiated, discontinued, or changed in dosage. Antitubercular drugs Isoniazid-serum concentrations may be decreased. Cyclosporine: Monitor for evidence of increased toxicity of cyclosporine when the two are used concurrently.
Digitalis Glycosides: Co-administration may enhance the possibility of digitalis toxicity. Estrogens, including oral contraceptives: Half-life of corticosteroid and concentration may be increased with decreased clearance. Hepatic Enzyme Inducers (e.g. Barbiturates, phenytoin, carbamazepine, rifampicin): There may be increased metabolic clearance of Triamcinolone Acetonide. Patients should be carefully observed for possible diminished effect of steroid and the dosage of Tri-Ace(Triamcinolone Acetonide Injectable Suspension USP) should be adjusted accordingly.
Ketoconazole: Corticosteroid clearance maybe decreased, resulting in increased effects. Non- depolarising muscle relaxants: Corticosteroids may decrease or enhance the neuromuscular blocking action.
Non-Steroidal Anti-Inflammatory Drugs(NSAIDs): Corticosteroids may increase the incidence and/or severity of GI bleeding and ulceration associated with NSAIDs. Also, corticosteroids can reduce serum salicylate levels and therefore decrease their effectiveness. Aspirin should be used cautiously in conjunction with corticosteroids in patients with hypoprothrombinemia.
VACCINES: Neurological complications and lack of antibody response may occur when patients taking corticosteroids are vaccinated.

STORAGE

Store below 30°C. Protected from light. Do not allow to freeze. Keep out of reach of children.

SHELF LIFE

24 Months

HOW SUPPLIED:

Tri-Ace (Triamcinolone Acetonide Injectable Suspension USP) is supplied in 1 mL glass vial.

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TRI-ACE