Why is Restasis a hazardous drug? Clarifying Risks for Patients and Handlers

October 7, 2025 •

3 min read

The National Institute for Occupational Safety and Health (NIOSH) officially classifies cyclosporine as a hazardous drug, leading to confusion for those prescribed Restasis, the ophthalmic emulsion containing cyclosporine. While the systemic form of the medication carries significant health risks, the ophthalmic version, Restasis, poses minimal systemic risk to the patient when used correctly. The 'hazardous' label primarily applies to the raw drug substance and its handling in a healthcare setting, not to the patient's routine eye drop application.

Quick Summary

Restasis is classified as a hazardous drug due to its active ingredient, cyclosporine, which poses systemic risks when taken orally. However, the topical ophthalmic formulation results in negligible systemic absorption, making it safe for patient use with proper handling. The hazardous classification mostly impacts healthcare workers who handle the raw drug substance, requiring specific precautions under guidelines like USP <800>.

Key Points

Cyclosporine, not Restasis, is the hazardous substance: The active ingredient, cyclosporine, is classified as a hazardous drug, but this is based on the systemic risks associated with oral or intravenous administration.
Topical use minimizes systemic risk: When used as prescribed, the ophthalmic formulation of Restasis leads to minimal, if any, systemic absorption of cyclosporine, eliminating the systemic hazards like carcinogenicity for the patient.
Handling regulations for raw substance: The hazardous classification under USP <800> dictates strict safety protocols for healthcare workers and pharmacists who handle the raw cyclosporine material or prepare the medication.
Patient risk is mainly contamination: For patients, the primary risk involves improper handling of the eye drop vial, which can lead to bacterial contamination and cause eye infection.
Discard single-use vials immediately: Single-use vials must be discarded after each use to prevent contamination, as they lack preservatives.
Proper administration is key to safety: Following careful steps like hand washing and not touching the dropper tip are crucial for patient safety during administration.

Restasis is a commonly prescribed ophthalmic emulsion used to increase tear production in patients with chronic dry eye disease. Its active ingredient is cyclosporine, a potent immunosuppressant. For patients using the medication as intended, the drug is considered safe. The 'hazardous' designation, however, is a formal classification based on the inherent properties of the drug substance, primarily relevant to healthcare professionals and those handling the raw chemical.

The Hazardous Nature of Cyclosporine

The hazardous classification of cyclosporine stems from the potential systemic effects observed with oral or intravenous administration. Studies have shown that when cyclosporine is absorbed systemically, it can lead to severe health consequences. The International Agency for Research on Cancer (IARC) classifies cyclosporine as a Group 1 carcinogen, meaning it is carcinogenic to humans. This classification is based on observations of lymphomas and other malignancies in patients receiving systemic cyclosporine. Animal studies with high oral doses have also shown teratogenicity and embryofetal toxicity, indicating a risk of birth defects and harm to a fetus. It is important to note that these risks are associated with systemic exposure, not the minimal exposure from ophthalmic use.

USP <800> and Healthcare Worker Safety

The United States Pharmacopeia (USP) General Chapter <800> provides standards for the safe handling of hazardous drugs in healthcare settings. Because cyclosporine is on the NIOSH list of hazardous drugs, all healthcare personnel who prepare or administer the medication must follow specific containment and safety protocols to minimize occupational exposure. This applies to activities like manufacturing, compounding, and managing spills. The rules exist to protect workers who may be exposed to the drug's raw form or concentrated solutions, which is a very different scenario from a patient self-administering a few drops.

Healthcare Worker Handling Precautions

Personal Protective Equipment (PPE): Healthcare professionals should wear appropriate PPE, including gloves, when handling the raw cyclosporine substance or cleaning up spills.
Safe Handling Procedures: Compounding or preparation should occur in a controlled environment to prevent aerosolization or surface contamination.
Disposal: Hazardous waste protocols should be followed for disposing of expired medication, contaminated materials, and equipment.
Spill Management: Staff should be trained in proper procedures for containing and cleaning up any spills to prevent widespread exposure.

Patient Safety and Proper Use of Restasis

For the patient, the primary risks associated with Restasis are not systemic, but rather linked to improper handling of the eye drops. The most common side effects are local, such as temporary burning or stinging. Serious risks for patients revolve around contamination or injury from the vial itself.

Patient Handling Instructions

Wash Hands: Always wash your hands with soap and water before handling the eye drop vial.
Avoid Contamination: Do not allow the dropper tip to touch your eye, eyelid, hands, or any other surface. A contaminated dropper can transfer bacteria and cause a serious eye infection.
Discard Single-Use Vials: If you are using single-use vials, discard the vial immediately after administering the drops, even if there is liquid left inside.
Remove Contact Lenses: Remove contact lenses before applying the drops and wait at least 15 minutes before reinserting them.

Systemic Cyclosporine vs. Ophthalmic Restasis: A Comparison


Feature	Systemic Cyclosporine (Oral)	Ophthalmic Restasis (Topical)
Purpose	Prevents organ transplant rejection, treats autoimmune diseases	Increases tear production in chronic dry eye disease
Active Ingredient	Cyclosporine	Cyclosporine (0.05%)
Absorption	Absorbed throughout the body; high systemic concentration	Minimal to undetectable systemic absorption
Carcinogenicity	Classified as a human carcinogen (IARC Group 1)	No carcinogenic risk for ophthalmic use
Teratogenicity	Potential risk shown in animal studies at high doses	Not an expected risk due to minimal absorption
Hazardous Classification	Listed as a hazardous drug by NIOSH	Hazardous classification primarily for raw substance and handler safety
Patient Handling	Swallowed or injected; handled by professionals	Self-administered eye drops; careful sterile handling required
Primary Risks	Cancer, nephrotoxicity, immune suppression	Ocular burning, stinging, eye infection from contamination

Conclusion

While Restasis contains cyclosporine, a substance classified as hazardous due to its systemic effects, this label does not imply the eye drops are inherently dangerous for the patient. The hazardous classification is mainly a regulatory designation that mandates special handling precautions for healthcare workers and in industrial settings to prevent occupational exposure to the more potent systemic forms or raw material. Patients can safely use Restasis by following standard sterile handling instructions. By understanding this critical distinction, patients can feel confident in their medication, and healthcare workers can ensure a safe working environment. For further information on handling protocols, consult the official guidelines from USP and NIOSH.

Frequently Asked Questions

Yes, Restasis is safe for patient use when administered properly. The hazardous classification is based on the systemic effects of high doses of its active ingredient, cyclosporine, but the topical eye drop formulation results in negligible systemic absorption, making it safe for patients.

Systemic cyclosporine is considered hazardous because it is a potent immunosuppressant associated with significant risks, including potential carcinogenicity (classified as a Group 1 carcinogen by IARC) and reproductive toxicity at high oral doses.

Systemic use involves oral or intravenous administration, where the drug is absorbed throughout the body and can have widespread effects. Ophthalmic use involves applying the medication directly to the eye, resulting in very little to no systemic absorption.

No. The risk of cancer associated with cyclosporine is linked to high, systemic doses. Restasis is a topical ophthalmic emulsion, and its use is not associated with an increased risk of cancer.

Patients should wash their hands before use, avoid touching the dropper tip to any surface (including the eye), and discard single-use vials immediately after use to prevent contamination and eye infection.

Under guidelines like USP <800>, healthcare workers must follow special procedures for all hazardous drugs, including those with cyclosporine. This protects them from potential occupational exposure, particularly during manufacturing or compounding of the raw substance.

No, you should remove contact lenses before applying Restasis. Wait at least 15 minutes after administration before reinserting your lenses. This prevents irritation and potential medication absorption by the contacts.