Ординатура / Офтальмология / Английские материалы / Clinical Ocular Pharmacology 5th edition_Bartlett, Jaanus_2008
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746 CHAPTER 35 Ocular Adverse Drug Reactions to Systemic Medications
The practitioner should record both prescribed and self-administered medications for each patient, including drug dosage, duration of therapy, and any adverse reactions noted by the patient. If ocular side effects are discovered in the examination, it is wise to advise the prescribing practitioner so that appropriate remedial action may be considered. If no side effects are uncovered but the patient is using one or more of the high-risk medications discussed in this chapter, the patient should be monitored appropriately so that any significant adverse reaction can be detected before serious consequences develop. If adverse events not previously reported are discovered in association with medication use, practitioners are encouraged to report such findings to the Food and Drug Administration. Forms are available for reporting ADRs (Figure 35-16), and electronic reporting via the Internet is also encouraged (www.fda.gov/ medwatch). Reporting may also occur to one of the other drug registries in the United States and Canada (Figure 35-17).
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CHAPTER 35 Ocular Adverse Drug Reactions to Systemic Medications |
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Appendix 35-1
Common and Critical Ocular Adverse Drug Reactions From Systemic Drugs
|
|
OADR (including WHO classification |
Prevention/Risks/ |
|
Drug |
of causality, where available) |
Considerations |
Management |
|
|
|
|
|
|
amiodarone (Cordarone) |
“Certain” corneal microdeposits, ocular |
No prevention known; baseline |
Follow-up examination periodically, |
|
(anti-arrhythmic) |
surface dryness, blepharoconjunctivitis, |
assessment and reevaluation every |
perhaps every 6 months.Those with any |
|
|
|
photosensitivity/bright lights/glare, colored |
6 months. |
visual disturbance should be advised |
|
|
halos around lights, visual sensations, |
As corneal opacities are dependent |
to seek care promptly. |
|
|
hazy vision, periocular pigmentation |
on dosage and duration of treatment, |
Take a careful history. If patient is not |
|
|
“Probable/likely” loss of eyelashes/brows, |
monitor accordingly. Keratopathy is |
taking or has not taken amiodarone (or |
|
|
corneal ulceration, anterior subcapsular |
generally present by 3 months of use. |
chloroquine), patient should be referred |
|
|
opacities, nonarteritic ischemic optic |
No keratopathy may be seen with |
for consideration of Fabry disease. |
|
|
neuropathy (NAION), intracranial |
100–200 mg/day, but will be seen |
Amiodarone-induced optic neuropathy |
|
|
hypertension. |
when dosage is 400–1,400 mg/day. |
occurs over months (vs. days to weeks |
|
|
“Possible” autoimmune reaction |
Warn patients about seeking care if |
with NAION), vision ranges from |
|
|
(dry mouth and eye) |
visual disturbances occur (rare). |
20/20–20/200 (never NLP), edema of |
|
|
|
The symptoms are almost exclusively |
the disc may last for months (longer |
|
|
|
related to the keratopathy. Lens |
than NAION), and usually occurs |
|
|
|
opacities have not been shown |
within weeks of initiation of amiodarone. |
|
|
|
to decrease vision. |
Note that diagnosis of NAION vs. |
|
|
|
UV-filtering lenses may decrease |
amiodarone-induced optic neuropathy |
|
|
|
the keratopathy. |
may be difficult given that most patients |
|
|
|
|
on this therapy are also at greatest risk for |
|
|
|
|
NAION. |
|
|
|
|
Consultation with prescribing practitioner. |
|
|
|
|
Discontinue if medically acceptable risk. |
digoxin (Lanoxin and |
“Certain” decreased vision (hazy, |
Color changes are expected with |
Symptoms may be absent or may occur as |
|
|
others), digitoxin |
blurred, dim); decreased CV (yellow or |
toxicity related to digoxin, though |
soon as 1 day after administration but |
(digitalis glycosides |
blue tinge, colored halos around lights); |
are only half as common if toxicity |
usually at 2 weeks and rarely after years. |
|
|
for certain cardiac |
flickering or flashing lights (reversible). |
is related to digitoxin use. |
Monitor CV (blue-yellow) with D-15 |
|
arrhythmias, congestive |
Specifically, digoxin can give visual |
Take a good drug history as concomitant |
or Farnsworth-Munsell 100-hue test. |
|
heart failure) |
hallucinations and mydriasis; digitoxin |
quinidine use can double serum |
Changes should be reported to the |
|
|
can give extraocular muscle paresis, |
concentration of digitalis drugs. |
prescribing physician for consideration |
|
|
photophobia. |
|
of concomitant cardiac digitalis toxicity. |
tamsulosin (Flomax) and |
“Certain” intraoperative floppy iris syndrome |
Inquire as to whether a patient is using |
Surgeon may have the patient discontinue |
|
|
other α1-adrenoceptor |
(IFIS—flaccid iris stroma billows on |
or has ever used tamsulosin prior to |
the medication for a period of time before |
|
antagonists |
irrigation, iris prolapse toward incisions, |
referral for ocular surgery. Advise |
the surgery to minimize the risk and the |
• |
alfuzosin (Uroxatral) |
intraoperative miosis; primarily with |
surgeon. |
degree of IFIS manifestations.This might |
• |
doxazosin (Cardura) |
tamsulosin); amblyopia, blurred vision |
|
be measured by the patient’s blood |
• |
terazosin (Hytrin) |
|
|
pressure and urinary retention. |
(hypertension, urinary |
|
|
Intraoperative methods may reduce the |
|
|
retention usually in benign |
|
|
risk of complications due to IFIS. |
|
prostatic hypertrophy) |
|
|
|
Medications Systemic to Reactions Drug Adverse Ocular 35 CHAPTER 748
lovastatin (Mevacor), |
“Possible” or “unlikely” cataracts |
|
simvastatin (Zocor), |
|
|
and other statins |
|
|
(cholesterol lowering) |
|
|
sildenafil (Viagra), and |
“Certain” changes in color perception |
|
other phosphodiesterase-5 |
(blue, blue/green, pink, yellow tinges, |
|
(PDE-5) inhibitors: |
dark colors appear darker); blurred |
|
• |
tadalafil (Cialis) |
vision (central haze, transient |
• |
vardenafil (Levitra) |
decreased vision); changes in light |
(erectile dysfunction) |
perception (flashes, increased |
|
|
|
perception of brightness); ERG |
|
|
changes, conjunctival hyperemia, |
|
|
ocular pain, photophobia (all reversible) |
|
|
“Possible” effects (all possibly due to |
|
|
the associated activity and not the drug) |
|
|
mydriasis, retinal vascular accidents, |
|
|
subconjunctival hemorrhages, anterior |
|
|
ischemic optic neuropathy (NAION), |
|
|
central serous chorioretinopathy (CSCR) |
hydroxychloroquine |
“Certain” whorl-like opacity in corneal |
|
(Plaquenil) |
epithelium, rarely associated with vision |
|
(treatment of various |
loss or other symptoms (reversible). |
|
inflammatory disorders, |
“Certain” maculopathy (characteristically |
|
including rheumatoid |
bilateral, reproducible Amsler grid and |
|
arthritis, systemic |
VF defects); early relative scotomata |
|
lupus erythematosus, |
(paracentral) (may not advance); later |
|
dermatologic conditions) |
retinal changes, CV loss, absolute scotomata, |
|
|
|
decreased vision (irreversible and |
|
|
may advance). |
Regular comprehensive ophthalmic examinations.
Side effects are based on the dose and are noted 15–30 minutes after ingestion (peak 60 minutes) corresponding to blood drug concentration (sildenafil). Keep doses <100mg
Dose-related incidence of ocular side effects (sildenafil):
•40–50% at 200 mg
•10% at 100 mg
•3% at 50 mg
Those who have a history of a previous NAION or retinitis pigmentosa (PDE-6 mutations) in self or family members should be advised against using these drugs.
Corneal deposits are generally reversible and do not affect vision.
There is no mechanism of prevention of retinopathy but early detection
is essential. Baseline exam within
1 year of starting medication including acuity, Amsler, CV, VF (central 10°), fundus photographs (multifocal ERG optional). Comprehensive ophthalmic examinations as follows:
•age 20–29 once
•age 30–39, seen twice
•age 40–64, every 2–4 years
•age >65, every 1–2 years
Any transient or unilateral defects are not considered drug-related. No evidence that the drug worsens preexisting macular degeneration.
Regular interval comprehensive examinations depending on individual patient risk factors. Cataracts have not been shown to form in normal therapeutic doses.
CV and light perception changes are transient and related to blood concentration.
Those who have experienced any transient losses of vision on any of these drugs should be advised against their use.Though NAION is a serious condition with permanent loss of vision, men using these drugs tend to have the risk factors associated with NAION.Twenty-five cases of NAION have been published with one rechallenge, with an additional 86 cases of visual disturbances.With over
27 million men having used sildenafil, this number is relatively small. Consider stopping the drug if CSCR persists.
Patients should be counseled about corneal deposits; however, no change in medication is normally required. Detection is the key to limiting any damage due to irreversible retinopathy.
Increased risk:
•dose >6.5 mg/kg/day (usually >400 mg/day)
•kidney or liver disease
•>5 years of use
•Elderly (thin) patients
•Obese patients
Follow-up examinations (if none of the risk factors listed above):
•age <40, in 2–4 years
•age 40–64, in 2 years
•age >65, in 1–2 years ANNUAL examinations if:
•>5 years of use
•Obese, or thin
•Progressive macular disease
•Renal/liver disease
•Dose >6.5 mg/kg/day
Medications Systemic to Reactions Drug Adverse Ocular 35 CHAPTER
Continued
749
Appendix 35-1
Common and Critical Ocular Adverse Drug Reactions From Systemic Drugs—cont’d
|
|
OADR (including WHO classification |
Prevention/Risks/ |
|
|
Drug |
of causality, where available) |
Considerations |
Management |
||
|
|
|
|
||
chloroquine (Aralen) |
(as for hydroxychloroquine) |
OADRs for chronic chloroquine use |
Note: for chloroquine, see annually for |
||
(now as an anti-malarial |
|
|
are more significant and occur sooner |
doses <3.0 mg/kg body weight; every |
|
|
treatment only) |
|
|
than do hydroxychloroquine OADRs. |
3–6 months if >3.0 mg/kg body weight, or |
|
|
|
|
However, this medication is not being |
if short, obese, have renal/liver impairment, |
|
|
|
|
used chronically. |
or have been on the drug for years. |
quinine |
Mild toxicity: slight reduction of visual acuity, |
Regular comprehensive eye |
Central vision may recover;VFs may |
||
(treatment of leg cramps, |
“flickering” of vision, concentric loss of |
|
examinations as toxicity is |
recover over months or remain permanent. |
|
|
formerly for malarial |
VFs, impaired night vision. |
|
uncommon at normal doses |
CV and dark adaptation changes are |
|
treatment) |
Severe/overdose: sudden complete |
• |
normal dose is <2 g/day (maximum) |
usually permanent. |
|
|
loss of vision with fixed, dilated pupils. |
• |
toxicity at >4 g/day |
|
|
|
|
• |
lethal dose is ~8 g |
|
Gold salts (parenteral, oral) |
“Certain” corneal stromal deposition |
Baseline comprehensive examination. |
Care based on regular comprehensive |
||
(rheumatoid arthritis) |
(yellow-brown gold particles, sparing the |
Advise if symptoms develop to seek |
care guidelines based on all individual |
||
|
|
periphery and superior cornea), anterior |
|
care. |
patient risk factors. |
|
|
subcapsular cataract. |
|
|
|
|
|
“Possible” deposit in conjunctiva. |
|
|
|
Corticosteroids |
Delayed corneal epithelial wound healing, |
Patients should be advised of the OADRs |
Timing of follow-up examinations depends |
||
• |
prednisone |
PSC, decreased resistance to infection, |
|
of these medications and the need for |
on doses and duration of treatment, |
• |
others |
decreased tear lysozyme, eyelid and |
|
careful monitoring as many OADRs are |
required every 6 months for cataract |
(inflammatory conditions, |
conjunctiva hyperemia/edema/angioneurotic |
|
asymptomatic. |
formation, but sooner for IOP and |
|
|
including rheumatoid |
edema, subconjunctival hemorrhage, |
The main OADRs of systemically |
retinal/nerve concerns.Those with any |
|
|
arthritis, autoimmune, |
translucent blue sclera, increased IOP, |
|
administered steroids occur with oral |
visual disturbance must be advised to |
|
respiratory) |
myopia, exophthalmos, intracranial |
|
use, with little concern with nasal |
seek care. Surgical removal of |
[See Carnahan, MC et al |
hypertension causing papilledema, |
|
administration, even long-term. |
steroid-induced PSC is similar to |
|
|
for review on steroid |
diplopia, EOM paresis and eyelid ptosis, |
(Topical ophthalmic use, which causes |
conventional PSC. |
|
|
OADRs from other routes |
retinal hemorrhages (secondary to |
|
the most significant anterior and |
IOP elevation is asymptomatic, so must be |
|
of administration, including |
injection), central serous choroidopathy, |
|
IOP-related effects, must be carefully |
detected with diligent and timely follow-up |
|
inhalation] |
abnormal ERG/VEP, retinal embolic |
|
monitored.) |
examinations including applanation |
|
|
phenomenon (injection). |
|
|
tonometry. The timing depends on the type |
|
|
|
|
|
of steroid, route, duration and individual |
patient factors. If IOP is elevated, taper off of steroids if possible in conjunction with prescribing practitioner. If not advisable, determine if patient is on lowest possible dose to maintain effect for condition being treated. Use antiglaucoma agents to lower IOP and monitor according to glaucoma risk protocols (threshold VF, stereoscopic examination and photographs, optic disc and NFL imaging).
Medications Systemic to Reactions Drug Adverse Ocular 35 CHAPTER 750
Nonsteroidal |
May increase bleeding tendencies |
Baseline comprehensive examination |
|
anti-inflammatory drugs |
(subconjunctival hemorrhage, retinal |
including dilated fundus examination. |
|
(NSAIDs, general): |
hemorrhage). |
|
|
• |
ibuprofen (Motrin) |
Blurred vision, CV changes, photophobia, |
|
• |
naproxen (Naprosyn, |
Stevens-Johnson syndrome, vertigo. |
|
|
Anaprox) |
|
|
• |
oxaprozin (Daypro) |
|
|
• |
piroxicam (Feldene) |
“Possible” or “Unlikely” corneal opacities |
Baseline comprehensive examination |
indomethacin (Indocin) |
(reversible), with or without photophobia |
including dilated fundus examination |
|
|
|
(rare); diplopia. Other ADRs as other NSAIDs. |
with photographs. |
|
|
Unknown classification of optic neuritis, |
|
|
|
intracranial hypertension. |
|
Pigmentary changes (discrete RPE pigment scattering perifoveally with depigmented surround; can be in retinal periphery); accompanying CV loss, visual acuity,VF defects, decreased
dark adaptation.
acetylsalicylic acid |
Subconjunctival hemorrhage, retinal |
|
(Aspirin) |
hemorrhage |
|
clomiphene (Clomid) |
Visual symptoms (reversible) include |
|
(nonsteroidal agent for the |
blurred vision, flashes, scintillations, |
|
treatment of infertility) |
prolonged afterimages,“heat waves” in vision. |
|
COX-2 inhibitorsa: |
“Certain” conjunctivitis, blurred vision |
|
• |
rofecoxib (Vioxx) |
(range from spots in vision to temporary |
• |
celecoxib (Celebrex) |
blindness to blurred vision) (mostly with |
• |
valdecoxib (Bextra) |
rofecoxib and celecoxib) |
•lumiracoxib (Prexige)
•nimesulide (Ainex)
•etolodac (Lodine)
(anti-inflammatory selective |
|
|
for COX-2) |
|
|
Retinoids: |
“Certain” abnormal meibomian gland |
|
• |
isotretinoin (Accutane) |
secretion/gland atrophy, increased tear |
• |
vitamin A (all-trans-retinoic |
film osmolarity, decreased tolerance |
|
acid) |
to CL, ocular discomfort, blepharo- |
• |
tretinoid (vesanoid) |
conjunctivitis, keratitis, corneal opacities, |
• |
acitretin (Soriatane) |
decreased vision, photophobia; decreased |
• |
etretinate (Tegison) |
dark adaptation, myopia; intracranial |
(cystic acne, psoriasis, |
hypertension (IH). |
|
other skin disorders) |
“Probable/likely” decreased CV (temporary), |
|
|
|
loss of dark adaptation (permanent) |
Comprehensive eye examinations.
Onset may occur in days after initiation but usually disappear after discontinuation.
Comprehensive eye examinations
Question or test for dark adaptation, CV, and ocular surface dryness (phenol thread,TBUT, corneal staining);
delay CL fitting and/or counsel that lens wear may be limited or uncomfortable during the course of therapy and until approximately 1 month afterward.
Explain risk/benefit in patients with retinitis pigmentosa, preexisting
Symptoms are generally rare. Consider monitoring patients on high doses.
Stevens-Johnson syndrome requires immediate discontinuation of the drug and referral to primary care provider. Topical supportive therapies (e.g., steroids) will be required.
Regular comprehensive eye examinations recommended according to protocols; include VFs, CV as needed. Consider more frequent examinations if high doses being used.
Optic neuritis or intracranial hypertension may warrant discontinuation. Consider neuroimaging for persistent diplopia.
Functional improvement on discontinuation (up to 6–12 months), although the pigmentary changes of the retina are generally irreversible.
Avoid these agents before/after surgery, following trauma, hyphema.
Persistence of symptoms post discontinuation of therapy is rare. Patient reassurance is the only management.
Visual symptoms resolve on discontinuation with no long-term effects to vision.
Advise to return for examination if any symptoms of ocular discomfort, redness, or decreased CL wear become apparent (usually by 4 weeks). Urgent examination if decreased vision, headaches, or transient visual obscurations.
Test/retest for ocular surface dryness, decreased CV, optic discs for edema.
It is very important to recognize
Medications Systemic to Reactions Drug Adverse Ocular 35 CHAPTER
Continued
751
Appendix 35-1
Common and Critical Ocular Adverse Drug Reactions From Systemic Drugs—cont’d
|
OADR (including WHO classification |
Prevention/Risks/ |
|
Drug |
of causality, where available) |
Considerations |
Management |
|
|
|
|
|
“Possible” corneal ulceration, eyelid |
night blindness, significant ocular |
isotretinoin-induced intracranial |
|
edema, diplopia, optic neuritis, |
surface dryness. Review all possible |
hypertension. Onset of blurred vision |
|
permanent dry eye, subconjunctival |
adverse effects and accompanying |
and headaches is usually 2–3 months after |
|
hemorrhage. |
symptoms. |
starting therapy (range of 5 days to |
|
“Unlikely” limbal infiltrates, corneal |
Consider UV blocking lenses due to |
2 years); however, patients may be |
|
neovascularization, keratoconus, |
photosensitization. |
asymptomatic. |
|
activation of herpes simplex, |
Note the implications of pregnancy |
Discontinuation usually results in |
|
exophthalmos, pupil abnormalities, |
and the use of this drug (pregnancy |
resolution of the IH, though other |
|
vitreous disturbance, glaucoma. |
category X). |
measures may be taken to reduce the |
|
“Conditional/unclassifiable” |
|
intracranial pressure. Discontinuation |
|
cataracts, decreased accommodation, |
|
should also occur if nyctalopia develops. |
|
iritis, cortical blindness, peripheral |
|
|
|
VF loss, retinal findings, scleritis. |
|
|
topiramate (Topamax) |
“Certain” acute glaucoma (bilateral) |
Education of patient as to possible |
The medication should be stopped and the |
(epilepsy, migraine |
(includes anterior chamber shallowing |
symptoms as well as to importance |
patient treated with hyperosmotics, |
headaches, weight loss) |
secondary to suprachoroidal effusions |
of follow-up.Time to onset is 3–14 days |
cycloplegics, and topical IOP-lowering |
|
with acute myopia (6–8D), increased |
after initiation so examination should |
agents. Treatment with peripheral |
|
IOP,VF defects, hyperemia, mydriasis, |
occur within and just after 2 weeks |
iridectomy is not beneficial. |
|
ocular pain, decreased vision). |
of starting the medication. |
|
|
“Probable/likely” blepharospasm, |
|
|
|
oculogyric crisis, retinal bleeds, uveitis. |
|
|
|
“Possible” scleritis, teratogenic effects |
|
|
|
(including ocular malformations). |
|
|
vigabatrin (Sabril) |
“Certain” irreversible VF constriction |
Regular comprehensive ophthalmic |
Patients taking this drug should have |
(anticonvulsant) |
(bilateral, concentric with temporal and |
assessments. Baseline screening of |
regular peripheral VF examinations (every |
|
macular sparing); cone dysfunction can |
VF, CV (preferably Farnsworth-Munsell). |
6 months), and consideration should be |
|
cause CV loss; visual acuity can be |
If symptoms develop, do ERG and |
given to electrodiagnostic testing (normal |
|
affected. |
VF every 6 months. |
or abnormal responses on ERG and VEP |
|
|
VF loss occurs in 10–50% and appears |
tracings), and especially EOG (most |
|
|
to be dose-related (1.4–4.5 g/day).Visual |
sensitive). |
|
|
symptoms can develop from several |
It has been suggested that, if seizures can |
|
|
months to several years. |
be controlled with a lower dosage, it may |
|
|
|
not require discontinuation. |
pamidronate disodium |
“Certain” blurred vision, pain, photophobia, |
Patients should be advised of the serious |
If persistent decreased vision or ocular |
(Aredia), and other |
ocular irritation, nonspecific conjunctivitis. |
OADRs of these medications. |
pain/redness occurs, ophthalmic care |
bisphosphonates |
“Certain” episcleritis, anterior (rarely |
Symptoms of vision-threatening |
must be sought. |
• alendronic acid |
posterior) uveitis, anterior (rarely |
conditions such as uveitis and |
No treatment for nonspecific conjunctivitis |
(Fosamax) |
posterior) scleritis |
scleritis must be clear to the patient |
as will usually decrease on subsequent |
Medications Systemic to Reactions Drug Adverse Ocular 35 CHAPTER 752
• |
ibandronate |
“Probable/Likely” periocular edema, lid |
• |
zolendronate (Zometa) |
edema, orbital edema. |
• |
risendronate sodium |
“Possible” retrobulbar neuritis, yellow vision, |
|
(Actonel) |
diplopia, cranial nerve palsy, ptosis, visual |
• |
clodronate (Bonefos) |
hallucinations. |
• |
etidronate disodium |
|
|
(Didrocal) |
|
• |
olpadronate |
|
(inhibits calcium resorption |
|
|
|
in malignancy, Paget disease, |
|
|
osteolytic bone metastasis |
|
|
[breast cancer, multiple |
|
|
myeloma]) |
|
cetirizine (Zyrtec)b |
“Certain” oculogyric crisis. |
|
(H1 selective antagonist for |
|
|
|
seasonal/chronic allergic |
|
|
rhinitis, urticaria) |
|
tamoxifen (Nolvadex) |
“Certain” crystalline retinopathy |
|
(chemotherapy for primary |
(intraretinal crystals), posterior |
|
|
metastatic breast cancer) |
subcapsular cataracts; whorl |
|
|
keratopathy.VA is rarely affected. |
carmustine (BiCNU, |
“Certain” vision loss (up to NLP) with |
BCNU) |
retinal complications (infarction, |
(chemotherapy agent, i.v. |
periarteritis/phlebitis, branch artery |
administration) |
occlusions, nerve fiber layer |
|
hemorrhage, macular edema). |
ethambutol (Myambutol) |
Optic neuropathy is usually retrobulbar |
(anti-tuberculosis) |
and bilateral manifesting as reduced |
|
visual acuity, CV, or central scotomata. |
|
Bitemporal VF defects may occur if the |
|
chiasm is affected. |
with a view to seeking care if any |
injections; however, nonsteroidal |
symptoms develop. |
anti-inflammatory agents (NSAIDs) may be |
Onset of serious OADRs (i.e., scleritis) |
useful. Similarly, episcleritis may require |
is usually within 6–48 hours |
NSAIDs but not require discontinuation. |
if i.v. drug administration. |
For anterior uveitis (or more uncommonly |
|
posterior or bilateral anterior uveitis), |
|
intensive topical therapies and/or systemic |
|
medications may be needed. In some |
|
cases, the drug will require discontinuation |
|
for the inflammation to resolve. |
|
Discontinuation is required for resolution |
|
of scleritis, even on full medical therapy. |
Regular comprehensive ophthalmic assessments. Patients should be informed of this possible unusual OADR.
Baseline exam within the first year
of using tamoxifen, including slit-lamp, fundus biomicroscopy, CV,Amsler, VFs. Presence of macular degeneration,
PSC cataracts are not a contraindication to treatment.
Keep doses <6.5 mg/kg/day for 5 years or less.
Retinal vascular changes and VL may be prevented by passing the internal carotid artery catheter beyond the ophthalmic artery before releasing the drug.
Informed consent is critical, as despite regular ophthalmic exams, optic neuropathy can occur at any stage and any dosage and the loss of vision
can be irreversible and severe. Baseline examination with visual acuity,VFs, CV, dilated fundus examination including optic nerve assessment.
Dose-related incidence of ocular side effects occurs, with:
•50% for 60–100 mg/kg/day
•5-6% for 25 mg/kg/day
•1% <15 mg/kg/day
Cessation of the drug causes rapid resolution of the episode.
Complete eye examinations every 6 months to 2 years depending on
dosage and duration of treatment; sooner if symptoms are noted.
Small crystals without decrease in VA or edema, consult but usually do not discontinue drug. Significant CV loss may warrant discontinuation.
If retinal changes develop, the risk/benefit ratio must be considered with the oncologist and patient.
Discontinue drug at any sign of decreased acuity, CV or VF defect. Consider contrast sensitivity testing. Optic atrophy not usually noted for months (2–5) after onset.
Consider monthly examinations even at lower doses for patients at risk of toxicity (diabetes, renal failure, alcoholism, ethambutol-induced peripheral neuropathy, and older patients and children).
Consider optical coherence tomography to pick up early toxicity (swelling of the nerve fiber layer) and chronic toxicity (nerve fiber layer thinning).
Medications Systemic to Reactions Drug Adverse Ocular 35 CHAPTER
Continued
753
Appendix 35-1
Common and Critical Ocular Adverse Drug Reactions From Systemic Drugs—cont’d
|
OADR (including WHO classification |
Prevention/Risks/ |
|
Drug |
of causality, where available) |
Considerations |
Management |
|
|
|
|
rifabutin |
“Certain” uveitis. |
|
(treatment or prophylaxis |
Others: optic neuropathy, corneal |
|
|
for tuberculosis) |
endothelial deposits, discoloration |
|
|
of tears (pink). |
methotrexate |
“Unlikely” optic neuritis. |
|
(immune modulation in |
|
|
|
rheumatoid, other |
|
|
inflammatory conditions) |
|
isoniazid |
“Unlikely” optic neuritis. |
|
(anti-tuberculosis) |
|
|
Tetracyclines |
Conjunctival deposits (black/brown) |
|
• |
tetracycline |
(with tetracycline); bluish discoloration |
• |
doxycycline |
of sclera (with minocycline). |
• |
minocycline |
Intracranial hypertension (IH); although |
|
|
most patients are symptomatic and are |
|
|
diagnosed promptly, others have no |
|
|
symptoms and may have optic disc |
|
|
edema long before a diagnosis is made. |
|
|
(The association between IH and |
|
|
doxycycline is the least established.) |
chloramphenicol |
Optic neuritis (retrobulbar or papillitis) |
|
(antibacterial) |
bilateral VA reduction from 20/100 to 5/400, |
|
|
|
dense central scotomata; optic disc edema/ |
|
|
hyperemia, dilated retinal veins, peripapillary |
|
|
hemorrhages; late optic atrophy. |
|
|
Note: Most cases of optic neuritis have |
|
|
occurred in children with cystic fibrosis |
|
|
who were treated with large daily dosages |
|
|
of the drug, from 1 to 6 g daily. |
|
|
(Note: aplastic anemia is also a risk, but |
|
|
risk with topical ophthalmic agents has |
|
|
been grossly overplayed.) |
atovaquone (Mepron) |
“Whorl-like” (verticillate) keratopathy. |
|
(antiparasitic) |
|
|
Ophthalmic examinations recommended monthly for doses >15 mg/kg/day.
Monitoring of fundus for signs of tuberculosis periodically. Fluconazole may increase the bioavailability of rifabutin and therefore increase the risk of ADRs.
Regular comprehensive ophthalmic assessments. Patients should be informed of this possible unusual OADR.
Optic neuritis is not dose-dependent. Ensure other drugs being taken are not implicated.
Patients should be carefully counseled to seek evaluation in the event of the development of blurred vision (static or transient) and/or headaches, as well as double vision. Periodic examinations may be required as some cases are asymptomatic.
Avoid vitamin A and concomitant retinoid use.
Patients who are to receive long-term chloramphenicol therapy should be given a comprehensive baseline examination consisting of VA,VF, CV, and dilated fundus examination.
The risk is minimized with <25 mg/kg/day for <3 months. Patients (or parents) should be encouraged to be alert to the development of peripheral neuritis,
a possible precursor sign to VL.
Drug may be used in cases of resistance to usual treatments for toxoplasmosis, such as in immune deficiency.
Discontinuation of rifabutin and initiation of topical steroid therapy results in clinical improvement.
If appears to be related to drug, discontinue in conjunction with prescribing practitioner. Monitor for resolution of VA and VF, though expect variable results.
(as above with ethambutol, methotrexate)
The onset of symptoms is usually ≤ 8 weeks from initiation, though may be hours or up to one year. Because patients can be asymptomatic, periodic examination is warranted for patients on long-term therapy.
Discontinuation of treatment usually shows resolution to IH and disc edema, but other interventions may be required. Some may have residual disc swelling, pallor, VF loss.
Visual symptoms can occur 10 days but usually after several months/years of treatment. Peripheral neuritis may precede the visual complaints by 1–2 weeks. Once signs
or symptoms of optic neuropathy are detected, promptly discontinue drug in consultation with the prescribing physician.
Pretreatment VA or VF are not usually achieved despite some visual recovery.
Keratopathy subsides once drug therapy is discontinued.
Medications Systemic to Reactions Drug Adverse Ocular 35 CHAPTER 754
sulfonamides |
Allergic reactions (lid swelling, |
Take a careful drug history as part of |
|
(antibacterial) |
conjunctivitis, localized angioneurotic |
the comprehensive ophthalmic |
|
|
|
edema, exfoliative dermatitis); myopia. |
examination. Inquire about previous |
|
|
Erythema multiforme (Stevens-Johnson |
reactions to medications.After |
|
|
syndrome, or SJ) is life-threatening and |
eliminating progression of nuclear |
|
|
shows ocular involvement in 69% of |
sclerosis and other causes of |
|
|
cases (mild in 40%, moderate in 25%, |
increased myopia, drug might be |
|
|
and severe in 4%). Late complications can |
implicated. |
|
|
occur; usually in the form of severe ocular |
Patients of Japanese or Korean |
|
|
surface disease and trichiasis. |
descent are at greater risk of |
|
|
“Possible” uveitis. |
Stevens-Johnson syndrome. |
Carbonic anhydrase |
Stevens-Johnson syndrome (see sulfonamides |
Risk of SJ syndrome is greater in patients |
|
inhibitorsc: |
above); myopia, as with sulfonamides. |
of Japanese or Korean descent and |
|
• |
acetazolamide (Diamox) |
Aplastic anemia (10–25 rate in |
has been reported more with |
• |
dichlorphenamide |
CAI-treated patients), other blood |
methazolamide. |
|
(Daranide) |
dyscrasias (42%–66% of all are aplastic |
Short-term therapy (<2 weeks) does |
• |
methazolamide |
anemia) (no reports in topical |
not require screening. |
|
(Neptazane) |
administrations). |
Aplastic anemia peaks at 2–3 months of |
(glaucoma; acetazolamide |
Also, respiratory distress with lung |
use, usually occurring by 6 months |
|
also as anticonvulsant, |
disorders; osteomalacia on |
of use. Onset of other dyscrasias is |
|
to treat intracranial |
anti-convulsants; metabolic acidosis/ |
more variable, sometimes taking years |
|
hypertension, to lessen air |
coma in renal deficiency/diabetic |
to manifest. |
|
hunger in high altitudes) |
nephropathy; ammonia poisoning |
|
|
|
|
with cirrhosis; hypo-potassium; |
|
|
|
enhanced trough levels of cyclosporine. |
|
cidofovir (Vistide) |
“Highly probable” uveitis (related to |
Keep vigilant in any patient on cidofovir, |
|
(treatment of |
immune-recovery uveitis, or IRU), hypotony, |
especially if it has previously been |
|
cytomegalovirus (CMV) |
macular edema, preretinal macular gliosis. |
used to treat cytomegalovirus. |
|
retinitis, i.v.) |
Uveitis seen especially if i.v. cidofovir |
Consider measuring serum creatinine |
|
|
|
has been administered previously. |
(may be elevated indicating poor |
|
|
Recurrences are common and VL is |
clearance of drug). CD4+ count may rise. |
|
|
more significant than that due to CMV |
|
|
|
retinitis alone. |
|
Oral contraceptives |
Ocular surface dryness, decreased tear |
Include oral contraceptive and |
|
(OCP); hormone |
secretion and goblet cell density, CL |
hormone replacement therapy |
|
replacement |
intolerance. |
in drug case history. |
|
therapy (HRT) |
Symptoms and signs of dry eye increase |
Women who are taking or considering |
|
(OCP multiple uses; |
with duration of menopause and use |
OCPs or HRT should be informed |
|
including pregnancy |
of HRT; Schirmer scores continue |
of the potential increased risk |
|
prevention, menstrual |
to decrease over time. Estrogen-only HRT |
of dry eye syndrome with this therapy. |
|
Allergy is managed by withdrawal of the drug and supportive therapies (consider steroids). Reduce or discontinue the drug in consultation with the prescribing
physician. Positive dechallenge will occur if the refractive error change subsides within several days or weeks.
SJ syndrome is life-threatening—drug
must be discontinued and patients referred urgently. Immediate (steroids) and possible long-term severe dryness and ocular surface disease will require aggressive management.
Drug withdrawal and treatment for uveitis. See SJ syndrome under sulfonamides. Blood abnormalities are noted before
symptoms. Early treatment is associated with improved long-term outcomes.
Long-term CAIs:
First 6 months of therapy:
•CBC,WBC with differential, hemoglobin, hematocrit, platelet
count every 1–2 months Thereafter, same tests every 6 months
Symptoms include: sore throat, fever, easy bruising, petechiae, nosebleeds, fatigue, jaundice.
Topical corticosteroids and cycloplegia as per usual treatment of uveitis; severe uveitis may warrant discontinuation/ substitution of another therapy. Some advocate not using cidofovir due to the risk of IRU.
As with many other symptomatic but not lifeor vision-threatening ADR, the risks/benefits of the drug must be weighed with the patient’s symptoms and ocular surface signs, and considerations to both ocular surface therapies as well as drug dosage reduction or discontinuation.
Medications Systemic to Reactions Drug Adverse Ocular 35 CHAPTER
Continued
755