Prostaglandin analogues

Latisse

Approved 24 Dec 2008TopicalSolution/drops

Indications

LATISSE ® (bimatoprost ophthalmic solution) 0.03% is indicated to treat hypotrichosis of the eyelashes by increasing their growth including length, thickness and darkness. LATISSE ® is a prostaglandin analog, indicated to treat hypotrichosis of the eyelashes by increasing their growth including length, thickness and darkness. ( 1 )

Contraindications

LATISSE ® is contraindicated in patients with hypersensitivity to bimatoprost or to any of the ingredients [ see Adverse Reactions (6.2) ]. Hypersensitivity. ( 4 )

Warnings and precautions

Concurrent administration of LATISSE ® and intraocular pressure (IOP)-lowering prostaglandin analogs in ocular hypertensive patients may decrease the IOP-lowering effect. Patients using these products concomitantly should be closely monitored for changes to their IOP. ( 5.1 ) Pigmentation of the eyelids and iris may occur. Iris pigmentation is likely to be permanent. ( 5.2 , 5.3 )

5.1Effects on Intraocular Pressure

Bimatoprost ophthalmic solution ( LUMIGAN ® ) lowers intraocular pressure (IOP) when instilled directly to the eye in patients with elevated IOP. In clinical trials, in patients with or without elevated IOP, LATISSE ® lowered IOP, however, the magnitude of the reduction was not cause for clinical concern. In ocular hypertension studies with LUMIGAN ® , it has been shown that exposure of the eye to more than one dose of bimatoprost daily may decrease the intraocular pressure lowering effect.

In patients using LUMIGAN ® or other prostaglandin analogs for the treatment of elevated intraocular pressure, the concomitant use of LATISSE ® may interfere with the desired reduction in IOP. Patients using prostaglandin analogs including LUMIGAN ® for IOP reduction should only use LATISSE ® after consulting with their physician and should be monitored for changes to their intraocular pressure.

5.2Iris Pigmentation

Increased iris pigmentation has occurred when bimatoprost solution was administered. Patients should be advised about the potential for increased brown iris pigmentation which is likely to be permanent [see Adverse Reactions (6.2) ] . The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. The long term effects of increased pigmentation are not known.

At a glance

Brand name: Latisse
Active substance: bimatoprost
Drug class: Prostaglandin analogues
Route: Topical
Dosage form: Solution/drops
Applicant: Abbvie
Status: Prescription
FDA approval: 24 Dec 2008
Application: NDA022369-001
RxCUI: 831948

Indications

Warnings and precautions

5.1Effects on Intraocular Pressure

5.2Iris Pigmentation

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

There are no adequate and well-controlled studies of LATISSE ® (bimatoprost ophthalmic solution) 0.03% administration in pregnant women. There is no increase in the risk of major birth defects or miscarriages based on bimatoprost postmarketing experience. In embryofetal development studies, administration of bimatoprost to pregnant mice and rats during organogenesis resulted in abortion and early delivery at oral doses at least 33 times (mice) or 94 times (rats) the human exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on the area under the curve (AUC).

These adverse effects were not observed at 2.6 times (mice) and 47 times (rats) the human exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC. In pre/postnatal development studies, administration of bimatoprost to pregnant rats from organogenesis to the end of lactation resulted in reduced gestation length and fetal body weight, and increased fetal and pup mortality at oral doses at least 41 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC.

No adverse effects were observed in rat offspring at exposures estimated at 14 times the human exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC. Because animal reproductive studies are not always predictive of human response LATISSE ® 0.03% should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Data Animal Data In an embryofetal development rat study, abortion was observed in pregnant rats administered bimatoprost orally during organogenesis at 0.6 mg/kg/day (94 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC). The No Observed Adverse Effect Level (NOAEL) for abortion was 0.3 mg/kg/day (estimated at 47 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily based on AUC).

No abnormalities were observed in rat fetuses at doses up to 0.6 mg/kg/day. In an embryofetal development mouse study, abortion and early delivery were observed in pregnant mice administered bimatoprost orally during organogenesis at doses greater than or equal to 0.3 mg/kg/day (33 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC).

The NOAEL for abortion and early delivery was 0.1 mg/kg/day (2.6 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC). No abnormalities were observed in mouse fetuses at doses up to 0.6 mg/kg/day (72 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC).

In a pre/postnatal development study, treatment of pregnant rats with bimatoprost orally from gestation day 7 to lactation day 20 resulted in reduced gestation length, increased late resorptions, fetal deaths, and postnatal pup mortality, and reduced pup body weight at doses greater than or equal to 0.3 mg/kg/day. These effects were observed at exposures at least 41 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC.

The NOAEL for postnatal development and mating performance of the offspring was 0.1 mg/kg/day (estimated at 14 times the human systemic exposure following topical ophthalmic administration of bimatoprost 0.03% to the cornea or conjunctival sac bilaterally once daily, based on AUC).

Adverse reactions

The following adverse reactions are described elsewhere in the labeling: Effects on Intraocular Pressure [ see Warnings and Precautions (5.1) ] Iris Pigmentation [ see Warnings and Precautions (5.2) ] Lid Pigmentation [ see Warnings and Precautions (5.3) ] Hair Growth Outside the Treatment Area [ see Warnings and Precautions (5.4) ] Intraocular Inflammation [ see Warnings and Precautions (5.5) ] Macular Edema [ see Warnings and Precautions (5.6) ] Hypersensitivity [ see Contraindications (4) ] Most common adverse reactions (incidence approximately 3% to 4%) are eye pruritus, conjunctival hyperemia, and skin hyperpigmentation.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AbbVie at 1-800-678-1605 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The following information is based on clinical trial results from a multicenter, double-masked, randomized, vehicle-controlled, parallel study including 278 adult patients for four months of treatment.

The most frequently reported adverse reactions were eye pruritus, conjunctival hyperemia, skin hyperpigmentation, ocular irritation, dry eye symptoms, and periorbital erythema. These reactions occurred in less than 4% of patients. Additional adverse reactions seen in clinical trials experience include foreign body sensation, hair growth abnormal, and iris hyperpigmentation. Additional adverse reactions reported with bimatoprost ophthalmic solution ( LUMIGAN ® ) for the reduction of intraocular pressure include, ocular dryness, visual disturbance, ocular burning, eye pain, blepharitis, cataract, superficial punctate keratitis, eye discharge, tearing, photophobia, allergic conjunctivitis, asthenopia, conjunctival edema, iritis, infections (primarily colds and upper respiratory tract infections), headaches, and asthenia.

6.2Postmarketing Experience

The following adverse reactions have been identified during postapproval use of LATISSE ® . Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The reactions include dry skin of the eyelid and/or periocular area, eye swelling, eyelid edema, hordeolum, hypersensitivity (local allergic reactions), lacrimation increased, madarosis and trichorrhexis (temporary loss of a few lashes to loss of sections of eyelashes, and temporary eyelash breakage, respectively), periorbital and lid changes associated with periorbital fat atrophy and skin tightness resulting in deepening of eyelid sulcus and eyelid ptosis, rash (including macular and erythematous), skin discoloration (periorbital), skin exfoliation of the eyelid and/or periorbital area, trichiasis, and vision blurred.

Latisse

Indications

Contraindications

Warnings and precautions

5.1Effects on Intraocular Pressure

5.2Iris Pigmentation

At a glance

Two medicines in one question?

Latisse

Indications

Contraindications

Warnings and precautions

5.1Effects on Intraocular Pressure

5.2Iris Pigmentation

At a glance

Two medicines in one question?

5.3Lid Pigmentation

5.4Hair Growth Outside the Treatment Area

5.5Intraocular Inflammation

5.6Macular Edema

5.7Contamination of

5.8Use with Contact Lenses

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trial Experience

6.2Postmarketing Experience

Composition

Official product information