sirolimus intravitreal (pending FDA approval)

Action and Spectrum

Actions and spectrum: 

sirolimus intravitreal is a medication used in ophthalmology. Its action is primarily immunosuppressive and anti-inflammatory. It works by inhibiting the activity of mTOR (mammalian target of rapamycin), which is involved in cell growth and proliferation. By inhibiting mTOR, sirolimus helps suppress the immune response and reduces inflammation in the eye. 

The spectrum of sirolimus intravitreal is focused on the treatment of certain eye conditions, like macular edema and diabetic macular edema due to retinal vein occlusion. It can be used in cases of non-infectious uveitis and proliferative vitreoretinopathy. sirolimus intravitreal is administered directly into the eye to target the specific eye-related conditions and achieve localized therapeutic effects. 

Drug Interaction

Adverse Reaction

None

Black Box Warning

Black Box Warning: 

sirolimus intravitreal does not have a specific black box warning. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: sirolimus intravitreal should not be used in individuals with a known hypersensitivity or allergic reaction to sirolimus or any of its components. 
• Active Eye Infection: sirolimus intravitreal is contraindicated in individuals with active eye infections, including bacterial, viral, or fungal infections of the eye. The presence of an infection can increase the risk of complications. 
• Severe Ocular Inflammation: Individuals with severe ocular inflammation may increase the risk of complications with sirolimus intravitreal treatment and may be contraindicated from receiving this therapy. 

Caution: 

• Intraocular Pressure (IOP) Monitoring: sirolimus intravitreal may increase intraocular pressure, leading to a condition known as ocular hypertension. Regular monitoring of IOP is recommended during treatment. 
• Use in Immunocompromised Patients: sirolimus intravitreal should be used with caution in patients with compromised immune systems, as it may increase the risk of infections or impair the immune response. 
• Bleeding Risk: sirolimus intravitreal may increase the risk of bleeding in the eye. Caution should be used in patients with bleeding disorders or those receiving anticoagulant therapy. 
• Preexisting Eye Conditions: sirolimus intravitreal should be used cautiously in patients with preexisting eye conditions such as retinal detachment, macular hole, or other retinal disorders, as it may exacerbate these conditions.

Comorbidities: 

• Diabetes: Many patients receiving sirolimus intravitreal may have underlying diabetes, as conditions like diabetic macular edema are commonly treated with this medication. 
• Hypertension: Hypertension is a common comorbidity seen in patients with ocular diseases such as retinal vein occlusion or neovascular age-related macular degeneration. 
• Cardiovascular Disease: Patients with ocular diseases requiring sirolimus intravitreal may also have comorbid cardiovascular conditions, including heart disease or peripheral vascular disease. 
• Renal Impairment: sirolimus is primarily metabolized by the kidneys, so patients with pre-existing renal impairment may require careful monitoring and dosage adjustments. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category C 

Lactation: N/A  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

sirolimus, also known as rapamycin, is a macrocyclic lactone immunosuppressive agent with potent antiproliferative properties. When administered intravitreally, sirolimus exerts its pharmacological effects locally within the eye. 

sirolimus intravitreal inhibits the activity of mammalian target of rapamycin (mTOR), proliferation, and angiogenesis. By blocking mTOR, sirolimus interferes with the signalling pathways involved in the development of neovascularization and the proliferation of cells implicated in ocular diseases, such as diabetic macular edema and neovascular age-related macular degeneration.  

Pharmacodynamics: 

The pharmacodynamics of sirolimus intravitreal involve the inhibition of mammalian target of rapamycin (mTOR), which plays a crucial role in cellular signalling, proliferation, and angiogenesis. By inhibiting mTOR, sirolimus interferes with the signalling pathways involved in neovascularization and cellular proliferation in the eye. 

sirolimus intravitreal has anti-inflammatory effects. It suppresses the release of pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α), and inhibits the activation and migration of immune cells, thereby reducing inflammation and preventing tissue damage in the eye. 

Overall, sirolimus intravitreal acts by modulating cellular signalling pathways, reducing angiogenesis, inhibiting cellular proliferation, and suppressing inflammation, leading to therapeutic benefits in ocular conditions associated with abnormal blood vessel growth and inflammation.  

Pharmacokinetics: 

Absorption 

sirolimus is directly injected into the vitreous cavity of the eye, bypassing the need for systemic absorption. The drug remains localized within the eye and does not undergo significant systemic absorption. 

Distribution 

After administration, sirolimus distributes within the vitreous humor, retina, and other ocular tissues. Its distribution is primarily limited to the site of injection, with minimal systemic distribution. 

Metabolism 

sirolimus undergoes metabolism primarily within the ocular tissues. Enzymatic processes within the eye may contribute to the biotransformation of sirolimus, although the specific metabolic pathways are not well characterized. 

Elimination and excretion 

sirolimus and its metabolites are eliminated from the eye primarily through local elimination processes, such as diffusion and clearance within the ocular tissues. 

Adminstartion

Administration: 

• Preparation: The healthcare professional prepares the sirolimus intravitreal injection according to the manufacturer’s instructions. This may involve reconstitution or dilution of the medication. 
• Prepping the eye: The patient’s eye is cleansed and sterilized using an antiseptic solution to reduce the risk of infection. 
• Local anesthesia: It is given to numb the eye and surrounding area, ensuring that the procedure is as comfortable as its possible for patient. 
• Injection: Using a fine needle or cannula, the healthcare professional carefully inserts the sirolimus solution into the vitreous cavity of the eye.  
• Monitoring: After the injection, the healthcare professional closely monitors the patient for any immediate adverse reactions or complications. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: sirolimus intravitreal 

Pronounced: (sigh-ROH-lih-mus in-truh-VY-treel)  

Why do we use sirolimus intravitreal? 

• Diabetic Macular Edema (DME): sirolimus can help reduce macular edema, which is a common complication of diabetic retinopathy.  
• Retinal Vein Occlusion (RVO): sirolimus can be used to treat macular edema which is caused by retinal vein occlusion, a condition where a retinal vein is blocked. It helps improve vision by reducing swelling and improving retinal function. 
• Non-Infectious Uveitis: sirolimus may be used to manage non-infectious uveitis, which is inflammation of the uvea (middle layer of the eye). It helps suppress the immune response and reduce inflammation in the eye. 
• Proliferative Vitreoretinopathy (PVR): sirolimus can be used in the treatment of proliferative vitreoretinopathy, a condition where scar tissue forms in the retina and vitreous cavity.