Latanoprost

Products

Latanoprost is commercially available as eye drops in dropper bottles and as monodoses (Xalatan, generic, auto-generic, 50 µg/ml). It is also available as a fixed combination with timolol (Xalacom, generic, auto-generic). Latanoprost was developed in the 1980s as part of a collaboration between Columbia University in New York and Pharmacia in Uppsala, Sweden (Stjernschantz, 2001). It was approved in the United States, the EU, and many countries in 1996. Eye drops are stored either cool or at room temperature, depending on the product.

Structure and properties

Latanoprost (C26H40O5, Mr = 432.6 g/mol) is a derivative of prostaglandin F2α. It exists as a colorless to slightly yellowish oil that is practically insoluble in water. Latanoprost is a lipophilic prodrug and is converted in the cornea by esterases by cleavage of the isopropyl ester to the active latanoprost acid and to isopropanol. Esterification serves to increase permeability and bioavailability.

Effects

Latanoprost (ATC S01EE01) lowers intraocular pressure primarily by increasing uveoscleral outflow of aqueous humor. The effects are due to agonism at the prostaglandin F receptor (FP receptor). Prostaglandin F2α is the natural ligand at this receptor. Binding leads to increased expression of metalloproteases in the ciliary muscle, promoting degradative processes in the extracellular matrix (remodeling). As a result, aqueous humor passes more easily through the tissue. The effects last for more than 24 hours because the cornea acts as a depot for the drug, from which latanoprost is continuously released.

Indications

For lowering intraocular pressure in open-angle glaucoma and elevated intraocular pressure (ocular hypertension).

Dosage

According to the SmPC. The drops are placed in the eyes once daily in the evening (1 drop). Do not apply more frequently, otherwise the effect will be reduced. Contact lenses should be removed before administration and reinserted 15 minutes later. See also under Administering eye drops.

Contraindications

  • Hypersensitivity

For complete precautions, see the drug label.

Interactions

Concomitant use of a second prostaglandin analogue may increase intraocular pressure . In contrast, other antiglaucomatous agents, such as timolol, may result in an increased reduction in pressure. Eye drops should be administered at least 5 minutes apart. Latanoprost is incompatible with thiomersal.

Adverse effects

The most common possible adverse effects include:

  • Eye irritation such as a burning, scratching, itching, stinging, and a foreign body sensation.
  • Increased blood flow to the eye
  • Hyperpigmentation of the iris: increase in the amount of brown pigment in the iris, permanent change in eye color.
  • Conjunctivitis
  • Eyelid rim inflammation
  • Changes in eyelashes and vellus hairs on the eyelid: increase in length, thickness, pigmentation and number of eyelashes.
  • Eye pain

Due to the positive effect on eyelashes, a drug containing the prostaglandin analogue bimatoprost has been developed and approved to promote eyelash growth (USA: Latisse).