1040-5488/14/9112-e298/0 VOL. 91, NO. 12, PP. e298Ye300 OPTOMETRY AND VISION SCIENCE Copyright * 2014 American Academy of Optometry
CLINICAL CASE
Accidental Overdose of Travoprost Denise Goodwin* and Dina H. Erickson*
ABSTRACT Purpose. To report systemic symptoms after an overdose of travoprost. Case Report. We report a patient who, instead of artificial tears, inadvertently used travoprost every 15 minutes for 7 hours after LASIK (laser-assisted in situ keratomileusis) surgery. She experienced abrupt, severe abdominal cramps and sudden, severe menstrual bleeding, which subsided quickly upon discontinuation of the drug. Conclusions. Because of the few systemic adverse effects, prostaglandin analogs are widely used for the treatment of glaucoma. Travoprost should be taken once daily; therefore, overdose is extremely uncommon. Systemic prostaglandins have been found to be mediators of uterine activity and are used to induce labor and terminate pregnancies. The high dose of this topical medication, as well as the compromised cornea, makes this case unique. The unusual circumstances observed in this case greatly expand our knowledge regarding the potential adverse effects of travoprost. (Optom Vis Sci 2014;91:e298Ye300) Key Words: travoprost, bimatoprost, prostaglandin analogs, drug-related side effects, adverse reactions
S
ince the introduction of prostaglandin analogs in the mid-1990s, they have become frontline therapy for the treatment of glaucoma and ocular hypertension. The few systemic and ocular adverse effects, as well as the significant ability to reduce intraocular pressure (IOP), brought them to the forefront of glaucoma therapy. However, there still exist a number of ocular and systemic adverse effects that are potentially serious to the patient. Travoprost ophthalmic solution, 0.004% (Travatan Z, Alcon Laboratories, Inc, Fort Worth, TX), is a topical prostaglandin eye drop that should be taken once per day in the evening to help reduce IOP. Although not indicated for eyelash growth, travoprost has been shown to cause thickening and lengthening of the eyelashes.1Y3 Bimatoprost ophthalmic solution, 0.03% (Latisse, Allergan, Inc, Irvine, CA), another topical prostaglandin, is applied to the base of the upper lashes at night to make the eyelashes longer and darker. Although the commercially available concentration has recently been decreased from 0.03 to 0.01%, bimatoprost 0.03% ophthalmic solution (Lumigan) has also been used once daily to reduce IOP. Because of the nature of these medications, overdose is extremely uncommon. We report systemic symptoms in a patient who, instead of artificial tears, used travoprost every 15 minutes for 7 hours after LASIK (laser-assisted in situ keratomileusis)
*OD, FAAO Pacific University College of Optometry, Forest Grove, Oregon (both authors).
surgery. This case greatly expands our knowledge regarding the adverse effects and potential uses of topical prostaglandins.
CASE REPORT A 25-year-old woman presented for her comprehensive eye examination with an interest in LASIK surgery. Her ocular and medical health were unremarkable. With the intent of promoting eyelash growth, she had been using bimatoprost for 3 months with minimal eyelash changes. She was given a sample bottle of travoprost to use at night on the base of her lashes to determine if it had better efficacy. However, she was told to discontinue bimatoprost for 4 weeks before the LASIK surgery and to not start travoprost until after her 1-week postoperative examination. Bilateral LASIK surgery was uneventful. At the 1-day postoperative examination, the corneal flap was well placed with minimal fluorescein staining around the edge of the wound. It was verified that she was taking the prescribed prednisolone acetate 1% four times per day, ciprofloxacin 0.3% four times per day, and nonpreserved artificial tears every 30 to 60 minutes. Around 2:30 PM, 6 hours after her 1-day postoperative examination, she ran out of the artificial tears and opened what she thought was a new bottle of artificial tears. This was later verified to be travoprost. The eyes continued to feel dry so she started using the drops more and more frequently. She estimated that she was instilling them in both eyes about every 10 to 15 minutes. At 5:00 PM, she experienced abrupt, severe abdominal cramps and sudden, severe menstrual bleeding. She reported that she was
Optometry and Vision Science, Vol. 91, No. 12, December 2014
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
Accidental Overdose of TravoprostVGoodwin and Erickson
bleeding so hard that it was ‘‘dripping into the toilet.’’ She had never had menstrual cramps previously, and the first day of her menstruation was generally light. She also reported having a negative home pregnancy test the day before the LASIK procedure and that it was not her usual menstruating time. At 9:30 PM, it was discovered that she was using the wrong drops. At that point, more than half the 2.5-mL bottle of travoprost was used. About an hour after discontinuation of travoprost, the symptoms began to resolve. The next morning, the abdominal pain was gone and the quantity of bleeding had normalized. The eyes had moderate hyperemia, consistent with the appearance of those who use prostaglandin drops for glaucoma treatment.
e299
as the compromised cornea, makes this case unusual. However, patients who are pregnant or trying to become pregnant should be aware of the potential risks of this medication. Because systemic prostaglandins can induce abortion, travoprost should be avoided in pregnant women or by women attempting to become pregnant. If their use is necessary during pregnancy, efforts to minimize systemic absorption can decrease the risk of miscarriage or premature labor. This includes correct dosing, eyelid closure, and punctal occlusion.
ACKNOWLEDGMENTS The authors have received no outside financial support for this research and declare that no conflicting relationship exists for either author. Received May 12, 2014; accepted September 1, 2014.
DISCUSSION Topical travoprost is a prostaglandin used in the treatment and management of glaucoma patients to lower IOP. The most common ocular side effects include conjunctival hyperemia, eye irritation, eyelash lengthening, iris pigmentation changes, eyelid pigmentation, and deepening of the upper eyelid sulcus.1Y6 Less common but potentially more visually serious adverse effects include anterior uveitis, cystoid macular edema, and the reactivation of herpes simplex keratitis.4,7 Very few systemic adverse effects of ophthalmic prostaglandins have been reported in the literature. Chest tightness with the use of ocular prostaglandins has been reported.8 Other systemic adverse events include nasopharyngitis, upper respiratory tract infection, and headache.6 Prostaglandins are reported to have no effect on heart rate or blood pressure.1,3,9 Oral, sublingual, intramuscular, and intravaginal prostaglandins have been found to be mediators of uterine activity.10,11 Prostaglandins have been used to prompt contraction of the uterine smooth muscle and cervical ripening during the induction of labor. The prostaglandin misoprostol has been used to terminate pregnancies by inducing labor.12 It has also been used to complete spontaneous, incomplete miscarriage13 and dilate and soften the cervix a few hours before surgical abortion procedures.10,14 Because animal studies have shown a high incidence of abortion when exposure is 80 times the human dose, the topical prostaglandins are classified as category C according to the US Food and Drug Administration.15 However, De Santis et al.15 reported that 9 of 10 pregnant women taking latanoprost once daily delivered normal fetuses. One woman had an early spontaneous abortion 2 weeks after discontinuing treatment, and it was determined that the association between latanoprost and miscarriage was unlikely. Lee16 reports a single case of abdominal cramping caused by travoprost but not with latanoprost or unoprostone. The cramping started 30 minutes after topical instillation and lasted for about 2 hours on three consecutive occasions. Peak systemic plasma concentration of travoprost occurs within 30 minutes of dosing, and elimination from human plasma is generally around 1 hour after dosing.1 This may account for the rapid onset of symptoms in our patient, as well as the quick resolution after discontinuation of the drops. This case greatly expands our knowledge about the potential adverse effects of travoprost. The high dose of medication, as well
REFERENCES 1. Al-Jazzaf AM, DeSantis L, Netland PA. Travoprost: a potent ocular hypotensive agent. Drugs Today (Barc) 2003;39:61Y74. 2. Li N, Chen XM, Zhou Y, Wei ML, Yao X. Travoprost compared with other prostaglandin analogues or timolol in patients with openangle glaucoma or ocular hypertension: meta-analysis of randomized controlled trials. Clin Experiment Ophthalmol 2006;34:755Y64. 3. Mizoue S, Nakano T, Fuse N, Iwase A, Matsumoto S, Yoshikawa K. Travoprost with sofZia(R) preservative system lowered intraocular pressure of Japanese normal tension glaucoma with minimal side effects. Clin Ophthalmol 2014;8:347Y54. 4. Hollo G. The side effects of the prostaglandin analogues. Expert Opin Drug Saf 2007;6:45Y52. 5. Netland PA, Landry T, Sullivan EK, Andrew R, Silver L, Weiner A, Mallick S, Dickerson J, Bergamini MV, Robertson SM, Davis AA, Travoprost Study Group. Travoprost compared with latanoprost and timolol in patients with open-angle glaucoma or ocular hypertension. Am J Ophthalmol 2001;132:472Y84. 6. Parrish RK, Palmberg P, Sheu WP, XLT Study Group. A comparison of latanoprost, bimatoprost, and travoprost in patients with elevated intraocular pressure: a 12-week, randomized, maskedevaluator multicenter study. Am J Ophthalmol 2003;135:688Y703. 7. Alm A, Grierson I, Shields MB. Side effects associated with prostaglandin analog therapy. Surv Ophthalmol 2008;53(Suppl. 1): S93Y105. 8. Rajan MS, Syam P, Liu C. Systemic side effects of topical latanoprost. Eye (Lond) 2003;17:442Y4. 9. Alm A, Stjernschantz J. Effects on intraocular pressure and side effects of 0.005% latanoprost applied once daily, evening or morning. A comparison with timolol. Scandinavian Latanoprost Study Group. Ophthalmology 1995;102:1743Y52. 10. Bygdeman M. Prostaglandin analogues and their uses. Baillieres Clin Obstet Gynaecol 1992;6:893Y903. 11. O’Brien WF. The role of prostaglandins in labor and delivery. Clin Perinatol 1995;22:973Y84. 12. Pluchon M, Winer N. [Misoprostol in case of termination of pregnancy in the second and third trimesters. Trials]. J Gynecol Obstet Biol Reprod (Paris) 2014;43:162Y8. 13. Tsalacopoulos G, Bloch B, Rush JM. Missed abortion treated with intramuscular 15-(S)-15-methyl-prostaglandin F2 alpha. S Afr Med J 1982;61:828Y30.
Optometry and Vision Science, Vol. 91, No. 12, December 2014
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
e300 Accidental Overdose of TravoprostVGoodwin and Erickson 14. Natrajan PK, Tzingounis VA. Cervical dilation with prostaglandin F2 alpha for first trimester abortion. South Med J 1986;79:830Y1. 15. De Santis M, Lucchese A, Carducci B, Cavaliere AF, De Santis L, Merola A, Straface G, Caruso A. Latanoprost exposure in pregnancy. Am J Ophthalmol 2004;138:305Y6. 16. Lee YC. Abdominal cramp as an adverse effect of travoprost. Am J Ophthalmol 2005;139:202Y3.
Denise Goodwin Pacific University College of Optometry 2043 College Way Forest Grove, OR 97116 e-mail: [email protected]
Optometry and Vision Science, Vol. 91, No. 12, December 2014
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
CLINICAL CASE
Accidental Overdose of Travoprost Denise Goodwin* and Dina H. Erickson*
ABSTRACT Purpose. To report systemic symptoms after an overdose of travoprost. Case Report. We report a patient who, instead of artificial tears, inadvertently used travoprost every 15 minutes for 7 hours after LASIK (laser-assisted in situ keratomileusis) surgery. She experienced abrupt, severe abdominal cramps and sudden, severe menstrual bleeding, which subsided quickly upon discontinuation of the drug. Conclusions. Because of the few systemic adverse effects, prostaglandin analogs are widely used for the treatment of glaucoma. Travoprost should be taken once daily; therefore, overdose is extremely uncommon. Systemic prostaglandins have been found to be mediators of uterine activity and are used to induce labor and terminate pregnancies. The high dose of this topical medication, as well as the compromised cornea, makes this case unique. The unusual circumstances observed in this case greatly expand our knowledge regarding the potential adverse effects of travoprost. (Optom Vis Sci 2014;91:e298Ye300) Key Words: travoprost, bimatoprost, prostaglandin analogs, drug-related side effects, adverse reactions
S
ince the introduction of prostaglandin analogs in the mid-1990s, they have become frontline therapy for the treatment of glaucoma and ocular hypertension. The few systemic and ocular adverse effects, as well as the significant ability to reduce intraocular pressure (IOP), brought them to the forefront of glaucoma therapy. However, there still exist a number of ocular and systemic adverse effects that are potentially serious to the patient. Travoprost ophthalmic solution, 0.004% (Travatan Z, Alcon Laboratories, Inc, Fort Worth, TX), is a topical prostaglandin eye drop that should be taken once per day in the evening to help reduce IOP. Although not indicated for eyelash growth, travoprost has been shown to cause thickening and lengthening of the eyelashes.1Y3 Bimatoprost ophthalmic solution, 0.03% (Latisse, Allergan, Inc, Irvine, CA), another topical prostaglandin, is applied to the base of the upper lashes at night to make the eyelashes longer and darker. Although the commercially available concentration has recently been decreased from 0.03 to 0.01%, bimatoprost 0.03% ophthalmic solution (Lumigan) has also been used once daily to reduce IOP. Because of the nature of these medications, overdose is extremely uncommon. We report systemic symptoms in a patient who, instead of artificial tears, used travoprost every 15 minutes for 7 hours after LASIK (laser-assisted in situ keratomileusis)
*OD, FAAO Pacific University College of Optometry, Forest Grove, Oregon (both authors).
surgery. This case greatly expands our knowledge regarding the adverse effects and potential uses of topical prostaglandins.
CASE REPORT A 25-year-old woman presented for her comprehensive eye examination with an interest in LASIK surgery. Her ocular and medical health were unremarkable. With the intent of promoting eyelash growth, she had been using bimatoprost for 3 months with minimal eyelash changes. She was given a sample bottle of travoprost to use at night on the base of her lashes to determine if it had better efficacy. However, she was told to discontinue bimatoprost for 4 weeks before the LASIK surgery and to not start travoprost until after her 1-week postoperative examination. Bilateral LASIK surgery was uneventful. At the 1-day postoperative examination, the corneal flap was well placed with minimal fluorescein staining around the edge of the wound. It was verified that she was taking the prescribed prednisolone acetate 1% four times per day, ciprofloxacin 0.3% four times per day, and nonpreserved artificial tears every 30 to 60 minutes. Around 2:30 PM, 6 hours after her 1-day postoperative examination, she ran out of the artificial tears and opened what she thought was a new bottle of artificial tears. This was later verified to be travoprost. The eyes continued to feel dry so she started using the drops more and more frequently. She estimated that she was instilling them in both eyes about every 10 to 15 minutes. At 5:00 PM, she experienced abrupt, severe abdominal cramps and sudden, severe menstrual bleeding. She reported that she was
Optometry and Vision Science, Vol. 91, No. 12, December 2014
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
Accidental Overdose of TravoprostVGoodwin and Erickson
bleeding so hard that it was ‘‘dripping into the toilet.’’ She had never had menstrual cramps previously, and the first day of her menstruation was generally light. She also reported having a negative home pregnancy test the day before the LASIK procedure and that it was not her usual menstruating time. At 9:30 PM, it was discovered that she was using the wrong drops. At that point, more than half the 2.5-mL bottle of travoprost was used. About an hour after discontinuation of travoprost, the symptoms began to resolve. The next morning, the abdominal pain was gone and the quantity of bleeding had normalized. The eyes had moderate hyperemia, consistent with the appearance of those who use prostaglandin drops for glaucoma treatment.
e299
as the compromised cornea, makes this case unusual. However, patients who are pregnant or trying to become pregnant should be aware of the potential risks of this medication. Because systemic prostaglandins can induce abortion, travoprost should be avoided in pregnant women or by women attempting to become pregnant. If their use is necessary during pregnancy, efforts to minimize systemic absorption can decrease the risk of miscarriage or premature labor. This includes correct dosing, eyelid closure, and punctal occlusion.
ACKNOWLEDGMENTS The authors have received no outside financial support for this research and declare that no conflicting relationship exists for either author. Received May 12, 2014; accepted September 1, 2014.
DISCUSSION Topical travoprost is a prostaglandin used in the treatment and management of glaucoma patients to lower IOP. The most common ocular side effects include conjunctival hyperemia, eye irritation, eyelash lengthening, iris pigmentation changes, eyelid pigmentation, and deepening of the upper eyelid sulcus.1Y6 Less common but potentially more visually serious adverse effects include anterior uveitis, cystoid macular edema, and the reactivation of herpes simplex keratitis.4,7 Very few systemic adverse effects of ophthalmic prostaglandins have been reported in the literature. Chest tightness with the use of ocular prostaglandins has been reported.8 Other systemic adverse events include nasopharyngitis, upper respiratory tract infection, and headache.6 Prostaglandins are reported to have no effect on heart rate or blood pressure.1,3,9 Oral, sublingual, intramuscular, and intravaginal prostaglandins have been found to be mediators of uterine activity.10,11 Prostaglandins have been used to prompt contraction of the uterine smooth muscle and cervical ripening during the induction of labor. The prostaglandin misoprostol has been used to terminate pregnancies by inducing labor.12 It has also been used to complete spontaneous, incomplete miscarriage13 and dilate and soften the cervix a few hours before surgical abortion procedures.10,14 Because animal studies have shown a high incidence of abortion when exposure is 80 times the human dose, the topical prostaglandins are classified as category C according to the US Food and Drug Administration.15 However, De Santis et al.15 reported that 9 of 10 pregnant women taking latanoprost once daily delivered normal fetuses. One woman had an early spontaneous abortion 2 weeks after discontinuing treatment, and it was determined that the association between latanoprost and miscarriage was unlikely. Lee16 reports a single case of abdominal cramping caused by travoprost but not with latanoprost or unoprostone. The cramping started 30 minutes after topical instillation and lasted for about 2 hours on three consecutive occasions. Peak systemic plasma concentration of travoprost occurs within 30 minutes of dosing, and elimination from human plasma is generally around 1 hour after dosing.1 This may account for the rapid onset of symptoms in our patient, as well as the quick resolution after discontinuation of the drops. This case greatly expands our knowledge about the potential adverse effects of travoprost. The high dose of medication, as well
REFERENCES 1. Al-Jazzaf AM, DeSantis L, Netland PA. Travoprost: a potent ocular hypotensive agent. Drugs Today (Barc) 2003;39:61Y74. 2. Li N, Chen XM, Zhou Y, Wei ML, Yao X. Travoprost compared with other prostaglandin analogues or timolol in patients with openangle glaucoma or ocular hypertension: meta-analysis of randomized controlled trials. Clin Experiment Ophthalmol 2006;34:755Y64. 3. Mizoue S, Nakano T, Fuse N, Iwase A, Matsumoto S, Yoshikawa K. Travoprost with sofZia(R) preservative system lowered intraocular pressure of Japanese normal tension glaucoma with minimal side effects. Clin Ophthalmol 2014;8:347Y54. 4. Hollo G. The side effects of the prostaglandin analogues. Expert Opin Drug Saf 2007;6:45Y52. 5. Netland PA, Landry T, Sullivan EK, Andrew R, Silver L, Weiner A, Mallick S, Dickerson J, Bergamini MV, Robertson SM, Davis AA, Travoprost Study Group. Travoprost compared with latanoprost and timolol in patients with open-angle glaucoma or ocular hypertension. Am J Ophthalmol 2001;132:472Y84. 6. Parrish RK, Palmberg P, Sheu WP, XLT Study Group. A comparison of latanoprost, bimatoprost, and travoprost in patients with elevated intraocular pressure: a 12-week, randomized, maskedevaluator multicenter study. Am J Ophthalmol 2003;135:688Y703. 7. Alm A, Grierson I, Shields MB. Side effects associated with prostaglandin analog therapy. Surv Ophthalmol 2008;53(Suppl. 1): S93Y105. 8. Rajan MS, Syam P, Liu C. Systemic side effects of topical latanoprost. Eye (Lond) 2003;17:442Y4. 9. Alm A, Stjernschantz J. Effects on intraocular pressure and side effects of 0.005% latanoprost applied once daily, evening or morning. A comparison with timolol. Scandinavian Latanoprost Study Group. Ophthalmology 1995;102:1743Y52. 10. Bygdeman M. Prostaglandin analogues and their uses. Baillieres Clin Obstet Gynaecol 1992;6:893Y903. 11. O’Brien WF. The role of prostaglandins in labor and delivery. Clin Perinatol 1995;22:973Y84. 12. Pluchon M, Winer N. [Misoprostol in case of termination of pregnancy in the second and third trimesters. Trials]. J Gynecol Obstet Biol Reprod (Paris) 2014;43:162Y8. 13. Tsalacopoulos G, Bloch B, Rush JM. Missed abortion treated with intramuscular 15-(S)-15-methyl-prostaglandin F2 alpha. S Afr Med J 1982;61:828Y30.
Optometry and Vision Science, Vol. 91, No. 12, December 2014
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
e300 Accidental Overdose of TravoprostVGoodwin and Erickson 14. Natrajan PK, Tzingounis VA. Cervical dilation with prostaglandin F2 alpha for first trimester abortion. South Med J 1986;79:830Y1. 15. De Santis M, Lucchese A, Carducci B, Cavaliere AF, De Santis L, Merola A, Straface G, Caruso A. Latanoprost exposure in pregnancy. Am J Ophthalmol 2004;138:305Y6. 16. Lee YC. Abdominal cramp as an adverse effect of travoprost. Am J Ophthalmol 2005;139:202Y3.
Denise Goodwin Pacific University College of Optometry 2043 College Way Forest Grove, OR 97116 e-mail: [email protected]
Optometry and Vision Science, Vol. 91, No. 12, December 2014
Copyright © American Academy of Optometry. Unauthorized reproduction of this article is prohibited.
