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.
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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).
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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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