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Cenegermin-bkbj

Class: EENT Drugs, Miscellaneous
Chemical Name: Human beta-nerve growth factor (β-NGF)-(1-118)-peptide (noncovalent dimer) produced in Escherichia coli
Molecular Formula: C583H908N166O173S8
CAS Number: 1772578-74-1
Brands: Oxervate

Medically reviewed by Drugs.com. Last updated on Nov 4, 2019.

Introduction

Recombinant form of human nerve growth factor.1 2 3 4 5

Uses for Cenegermin-bkbj

Neurotrophic Keratitis

Topical treatment of neurotrophic keratitis (designated an orphan drug by FDA for this use8 ).1 3 5 7

Neurotrophic keratitis is a rare degenerative corneal disease caused by trigeminal nerve damage resulting in partial or total loss of corneal sensation.3 7 9 10 Loss of corneal sensory innervation reduces protective (e.g., lacrimation) reflexes and alters levels of trophic neuromodulators that support corneal epithelial cell homeostasis, leading to impaired corneal wound healing and progressive ocular surface changes (ranging up to stromal melting and corneal perforation).7 9 10

Cenegermin-bkbj Dosage and Administration

Administration

Ophthalmic Administration

Apply 0.002% ophthalmic solution topically to the affected eye(s).1 2

For topical ophthalmic use only.1

Remove contact lenses prior to administration; wait ≥15 minutes after administration before reinserting contact lenses.1

Instill ophthalmic solution 15 minutes before any other ophthalmic ointment, gel, or other viscous drops.1 If more than one topical ophthalmic drug used, administer the drugs at least 15 minutes apart to avoid diluting the preparations.1

Blink several times after administering each dose to ensure that the drug covers the surface of the eye.1

If a dose is missed, resume usual administration schedule with the next scheduled dose.1 Do not administer an extra dose to make up for a missed dose.1

Assembly and Use of Kit Components

Available in a kit containing a carton of seven 1-mL multiple-dose vials of the drug in an insulated package, 8 vial adapters, 45 pipettes and sterile disinfectant wipes, and a card for recording administration.1 (See Storage under Stability.)

Do not shake the vials.1

Prepare only the number of vials required for use during a single day (1 vial for treatment of one eye, 2 vials for treatment of both eyes).1

When initiating treatment immediately after receiving the drug from a pharmacy, allow first vial to thaw at room temperature up to 25°C (may take up to 30 minutes) prior to preparation for use.1

Pierce vial stopper with an adapter from the kit.1 Do not remove vial adapter following connection to the vial.1

Prior to removing a dose from the vial, clean the adapter with a disinfectant wipe and then screw a pipette into the adapter.1

Once pipette is properly filled, disconnect it from the adapter and administer the dose directly from the pipette into the conjunctival fornix.1

Withdraw each dose just prior to administration with a new pipette for each application in each eye.1 If the drop misses the eye during administration and no ophthalmic solution remains in the pipette, use a new pipette to withdraw and administer dose.1

Consult manufacturer's instructions for detailed information regarding preparation and ocular administration.1

Dosage

Pediatric Patients

Neurotrophic Keratitis
Ophthalmic

Children ≥2 years of age: Instill 1 drop in the affected eye(s) 6 times daily at 2-hour intervals for 8 weeks.1

Adults

Neurotrophic Keratitis
Ophthalmic

Instill 1 drop in the affected eye(s) 6 times daily at 2-hour intervals for 8 weeks.1

Special Populations

No special population dosage recommendations at this time.1

Cautions for Cenegermin-bkbj

Contraindications

  • Manufacturer states none known.1

Warnings/Precautions

Warnings and Precautions

Use with Contact Lenses

Remove contact lenses prior to administration; may be reinserted 15 minutes following administration.1

Presence of contact lens could limit distribution of the drug onto the area of the corneal lesion.1

Eye Discomfort

May cause mild to moderate eye discomfort (e.g., eye pain).1

Specific Populations

Pregnancy

Data not available regarding use in pregnant women.1

In animal studies, no adverse effects on the fetus or offspring were observed.1

Lactation

Not known whether cenegermin distributes into milk following topical application to the eye,1 affects breast-fed infants, or affects milk production.1

Consider benefits of breast-feeding along with importance of the drug to the woman and any potential adverse effects of the drug on the breast-fed infant.1

Pediatric Use

Safety and efficacy in pediatric patients supported by adequate and well-controlled studies in adults and additional safety data in pediatric patients ≥2 years of age.1 2

Geriatric Use

In clinical trials of cenegermin-bkbj, 43.5% of patients were ≥65 years of age.1 No overall differences in safety and efficacy relative to younger adults.1

Common Adverse Effects

Eye pain,1 5 corneal deposits,1 3 foreign body sensation,1 ocular hyperemia,1 ocular inflammation,1 5 increased lacrimation.1

Interactions for Cenegermin-bkbj

No formal drug interaction studies to date.1

Cenegermin-bkbj Pharmacokinetics

Absorption

Bioavailability

Extent of systemic exposure following ocular administration is unknown.1

Distribution

Extent

Not known if the drug is distributed into milk following topical administration to the eye.1

Stability

Storage

Ophthalmic

Solution

Unopened vials in pharmacy: Temperature not exceeding −20°C.1 Dispense carton containing 7 cenegermin-bkbj vials in the manufacturer-provided insulated package.1

Unopened vials following dispensing from pharmacy: 2–8°C for ≤14 days; remove carton containing vials of drug from insulated package and refrigerate within 5 hours after leaving pharmacy.1 Do not refreeze.1

Vials with inserted vial adapter: 2–25°C for 12 hours.1 Discard 12 hours after connecting adapter to vial.1

Actions

  • Recombinant form of human nerve growth factor (a neurotrophin involved in the differentiation, growth, and survival of neurons) that is produced in Escherichia coli.1 2 3 4 11 12

  • Acts at specific, high-affinity tropomyosin kinase receptor A (TrkA) (a neurotrophin receptor in the tyrosine kinase receptor family) and the nonselective, low-affinity p75NTR receptor (a pan-neurotrophin receptor in the tumor necrosis factor receptor superfamily) in the anterior segment of the eye to support corneal innervation and integrity.1 2 4 11 12

Advice to Patients

  • Importance of reading the manufacturer's patient information and instructions for use of cenegermin-bkbj before initiating therapy with the drug and each time the prescription is refilled.1

  • Importance of learning and adhering to proper methods of preparation, including handling and assembly of the kit components (vials, vial adapters, pipettes), and administration of cenegermin-bkbj.1 Importance of using a new pipette for each application and of not touching the eye with the tip of the pipette.1 (See Assembly and Use of Kit Components under Dosage and Administration.)

  • Importance of separating the administration times of cenegermin ophthalmic solution and any other ophthalmic preparation by ≥15 minutes to avoid diluting the preparations and of administering cenegermin 15 minutes before any ophthalmic ointment, gel, or other viscous drops.1

  • Importance of removing contact lenses prior to administration of each ophthalmic dose; may reinsert contact lenses 15 minutes following administration.1

  • Importance of following the manufacturer's instructions regarding proper storage of cenegermin-bkbj ophthalmic solution.1 (See Storage under Stability.) Importance of removing from the refrigerator and preparing for use only the number of vials that will be used during a single day.1

  • Vision may be blurred for a short time following administration; importance of waiting until vision clears before driving or using machinery.1

  • Mild to moderate eye discomfort may occur following administration; importance of informing clinician if more serious adverse reactions occur.1

  • If a dose is missed, importance of resuming the usual administration schedule with the next scheduled dose.1 Do not administer an extra dose to make up for a missed dose.1 Advise patients to consider setting an alarm as a reminder to improve adherence to the every-2-hour, 6-times-daily dosing schedule.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Cenegermin-bkbj (recombinant)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Ophthalmic

Solution

0.002%

Oxervate (available in a kit containing seven 1-mL multiple-dose vials of the drug in an insulated package, 8 vial adapters, 45 pipettes and sterile disinfectant wipes, and a dose card)

Dompé

AHFS DI Essentials™. © Copyright 2021, Selected Revisions November 4, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Dompé U.S. Inc. Oxervate (cenegermin-bkbj) ophthalmic solution prescribing information. Boston, MA; 2018 Aug.

2. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 761094Orig1s000. Summary review. From FDA website. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/761094Orig1s000SumR.pdf

3. Bonini S, Lambiase A, Rama P, et al. Phase II randomized, double-masked, vehicle-controlled trial of recombinant human nerve growth factor for neurotrophic keratitis. Ophthalmology. 2018; 125:1332-43.

4. Ferrari MP, Mantelli F, Sacchetti M, et al. Safety and pharmacokinetics of escalating doses of human recombinant nerve growth factor eye drops in a double-masked, randomized clinical trial. BioDrugs. 2014; 28:275–83.

5. Bonini S, Lambiase A, Rama P, et al for the REPARO Study Group. Phase I trial of recombinant human nerve growth factor for neurotrophic keratitis. Ophthalmology. 2018; 125:1468-71.

6. Dompé Farmaceutici, L'Aquila, Italy: Personal communication.

7. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 761094Orig1s000. Clinical review(s). From FDA website. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/761094Orig1s000MedR.pdf

8. US Food and Drug Administration. Search orphan drug designations and approvals. From FDA website. Accessed 2019 Jun 12. http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm

9. Versura P, Giannaccare G, Pellegrini M et al. Neurotrophic keratitis: current challenges and future prospects. Eye Brain. 2018; 10:37-45. http://www.ncbi.nlm.nih.gov/pubmed/29988739?dopt=AbstractPlus

10. Sacchetti M, Lambiase A. Diagnosis and management of neurotrophic keratitis. Clin Ophthalmol. 2014; 8:571-9. http://www.ncbi.nlm.nih.gov/pubmed/24672223?dopt=AbstractPlus

11. Aloe L, Rocco ML, Bianchi P et al. Nerve growth factor: from the early discoveries to the potential clinical use. J Transl Med. 2012; 10:239. http://www.ncbi.nlm.nih.gov/pubmed/23190582?dopt=AbstractPlus

12. Rocco ML, Soligo M, Manni L et al. Nerve Growth Factor: Early Studies and Recent Clinical Trials. Curr Neuropharmacol. 2018; 16:1455-1465. http://www.ncbi.nlm.nih.gov/pubmed/29651949?dopt=AbstractPlus

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