Dorzolamide
JFDA label: TRUSOPT Ophthalmic Solution
Mechanism of Action
Reversible inhibition of the enzyme carbonic anhydrase resulting in reduction of hydrogen ion secretion at renal tubule and an increased renal excretion of sodium, potassium, bicarbonate, and water to decrease production of aqueous humor; also inhibits carbonic anhydrase in central nervous system to retard abnormal and excessive discharge from CNS neurons
Indications
Approved
- Elevated intraocular pressure
Contraindications
Source: Lexicomp
- Hypersensitivity to dorzolamide or any component of the formulation Absolute
Adverse Reactions
Renal and urinary disorders (1)
Not Known Urolithiasis
Immune system disorders (1)
Not Known Local ocular hypersensitivity reaction
Gastrointestinal disorders (4)
Not Known Bitter taste · fatigue · headache · nausea
Skin and subcutaneous tissue disorders (1)
Not Known Skin rash
Musculoskeletal and connective tissue disorders (1)
Not Known Weakness
Other (12)
Not Known blurred vision · Burning sensation of eyes · conjunctivitis · eye discomfort · eye redness · eyelid irritation · iridocyclitis · lacrimation · photophobia · stinging of eyes · superficial punctate keratitis · xerophthalmia
Dosing
Source: Lexicomp
Warnings & Precautions
Source: Lexicomp
Bacterial keratitis
Inadvertent contamination of multiple-dose ophthalmic solutions has caused bacterial keratitis.
Ocular effects
Local ocular adverse effects (primarily conjunctivitis and lid reactions) were reported with chronic administration; many resolved upon discontinuation of drug therapy. Choroidal detachment has been reported after filtration procedures.
Sulfonamide (“sulfa”) allergy
Dorzolamide is a sulfonamide; although administered ocularly, systemic absorption may occur and could result in hypersensitivity. Discontinue use if signs of hypersensitivity or a serious reaction occur.
Systemic effects
Systemic absorption and adverse effects (similar to sulfonamides) including, blood dyscrasias, Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias may occur with ophthalmic use. Disease-related concerns:
Corneal endothelium
Use with caution in patients with low endothelial cell counts; may be at increased risk of corneal edema.
Hepatic impairment
Use with caution in patients with hepatic impairment (has not been studied).
Renal impairment
Use is not recommended in patients with severe renal impairment (CrCl Concurrent drug therapy issues:
Drug-drug interactions
Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed. Special populations:
Contact lens wearers
Some products contain benzalkonium chloride which may be absorbed by soft contact lenses; remove lens prior to administration and wait 15 minutes before reinserting. Other warnings/precautions:
Appropriate use
Should be used in combination with therapeutic interventions for the treatment of acute angle-closure glaucoma.
Pregnancy & Lactation
Pregnancy
Adverse events have been observed in animal reproduction studies following systemic administration. IOP is usually lower during pregnancy. If topical medications for the treatment of glaucoma in pregnant women cannot be discontinued because small increases in IOP cannot be tolerated, the minimum effective dose should be used in combination with punctual occlusion to decrease exposure to the fetus (Johnson, 2001).
Lactation
It is not known if dorzolamide is excreted in breast milk. Due to the potential for serious adverse reactions in the nursing infant, the manufacturer recommends a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother.
Monitoring
| Clinical pearl | Ophthalmic exams and IOP periodically |
|---|
Chemistry & Properties
| Formula | C10H16N2O4S3 |
|---|---|
| Molecular weight | 324.45 g/mol |
| IUPAC name | (4S,6S)-4-(ethylamino)-6-methyl-7,7-dioxo-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonamide |
| CAS | 120279-96-1 |
| PubChem CID | 5284549 |
| InChIKey | IAVUPMFITXYVAF-XPUUQOCRSA-N |
| logP | 0.61 (XLogP 0.4) |
| Polar surface area | 106.33 Ų |
| H-bond acceptors / donors | 6 / 2 |
| Drug-likeness (QED) | 0.85 |
| Lipinski violations | 0 |
SMILES
CCN[C@H]1C[C@H](C)S(=O)(=O)c2sc(S(N)(=O)=O)cc21Biology & Pharmacokinetics
Pharmacokinetics
| BBB penetrant | No |
|---|
Enzyme interactions
| Enzyme | Role | Detail |
|---|---|---|
| CYP2C19 | Substrate | — |
| CYP2C9 | Substrate | — |
| CYP3A4 | Substrate | — |
Receptor binding (top 5)
| Target | Action | Affinity |
|---|---|---|
| carbonic anhydrase 12 (CA12) | Inhibitor | pKi 8.5 |
| carbonic anhydrase 7 (CA7) | Inhibitor | pKi 8.5 |
| Carbonic Anhydrase Isozymes, CA II | Binding | pKi 8.0 |
| carbonic anhydrase 14 (CA14) | Inhibitor | pKi 7.8 |
| Carbonic Anhydrase Isozymes, CA IX | Binding | pKi 7.3 |
Transporters
BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)
Registered Products (13)
| Brand | Form / strength | Pack | Agent | Citizen (JOD) |
|---|---|---|---|---|
| Optodrop 2% Eye Drop Solution | Ophthalmic Solution as(Hcl)2 % | 5 ml | Sun Set Drug Store | 3.050 |
| Dorzox | Solution 2 % | 5 ml | ORIENT DRUG STORE CO | 3.240 |
| TRUSOPT Ophthalmic Solution | Ophthalmic Solution 2 % | 5 ml | Adatco Drug Store | 3.780 |
| Ozolamide Eye Drops | Ophthalmic Solution 2 % | 5 ml | Nabulsi Drug Store | 4.180 |
| Optodrop Co | Vial 0.5 %, 2 % | 1 vial | Sun Set Drug Store | 4.590 |
| Twinzol | Injection 5 mg/ml, 20 mg/ml | 5 ml | Nabulsi Drug Store | 4.590 |
| Twinzol Single Dose Ophthalmic Solution | Ophthalmic Solution 22.26 mg/ml/0.2 ml, 6.83 mg/ml/0.2 ml | (6 strip each of 5 UNT) | Nabulsi Drug Store | 4.830 |
| Apisopt Eye Drops | Ophthalmic Solution as Hcl 20 mg/1 ml | 5 ml | Amman Pharmaceutical Indusries | 5.970 |
| Daromed 2% E/D | Ophthalmic Solution 2 % | 5 ml | Dar Al Dawa Development and Investment Co Ltd/Jordan | 5.970 |
| COSOPT Ophthalmic Solution | Ophthalmic Solution 0.5 %, 2 % | 5 ml | Adatco Drug Store | 6.340 |
| Daromed-T | Solution 0.5 %, 2 % | 5 ml | Dar Al Dawa Development and Investment Co Ltd/Jordan | 7.430 |
| Xolamol | Solution 0.5 %w/v, (as Hcl ) 2 % w/v | 5 ml | شركة مستودع ادوية الايمان | 7.960 |
| Apisopt plus Eye Drops | Ophthalmic Solution as maleate 5 mg/ml, as HCL 2 % | 5 ml | Amman Pharmaceutical Industries Co | 8.960 |