Download DRUGS AND PREGNANCY

DRUGS AND PREGNANCY
Adrea R. Benkoff, M.D.
Diagnostic Ophthalmic Drugs
Therapeutic Ophthalmic Drugs
 Relative Benefit to Mother
 Side Effects in Pregnant Patients
 Potential Risk to Fetus
 Structural or Visceral Abnormalities
 Altered Physiologic Function of Nursing Baby
TERATOGEN
 An Agent That By Acting During the
Embryonic or Fetal Period Produces
Morphologic or Functional Malformations
That Become Apparent Postnatal
SOURCES
 Case Reports
 Individual Experience
 Animal Studies
SYSTEMIC EFFECTS
 Oral Medications
 Topical Medications
 Absorbed Systemically by Drainage
Through Nasopharyngeal Mucosa
 Secreted in Breast Milk
FDA CATEGORIES FOR
DRUG USE IN PREGNANCY

Category A--- Adequate and well controlled studies have failed to demonstrate a risk to
the fetus in the first trimester of pregnancy (and there is no evidence of risk in later
trimesters).

Category B--- Animal reproduction studies have failed to demonstrate a risk to the fetus
and there are no adequate and well-controlled studies in pregnant women.

Category C--- Animal reproduction studies have shown an adverse effect on the fetus
and there are no adequate and well-controlled studies in humans, but potential benefits
may warrant use of the drug in pregnant women despite potential risks.

Category D--- There is positive evidence of human fetal risk based on adverse reaction
data from investigational or marketing experience or studies in humans, but potential
benefits may warrant use of the drug in pregnant women despite potential risks.

Category X--- Studies in animals or humans have demonstrated fetal abnormalities and
/or there is positive evidence of human fetal risk based on adverse reaction data from
investigational or marketing experience, and the risks involved in use of the drug in
pregnant women clearly outweigh potential benefits.
DIAGNOSTIC AGENTS
 TOPICAL ANESTHETICS
 No Teratogenic Effects
 MYDRIATIC/CYCLOPLEGIC AGENTS
 No Animal Studies on Drops
 Systemic Use of Atropine, Epinephrine, Homatropine or
Phenylephrine
 Minor, Non-Life-Threatening Malformations
 Systemic Scopalamine
 Fetal Tachycardia and Heart Rate Variability
DIAGNOSTIC AGENTS
 Systemic Phenylephrine
 Fetal Hypoxia and Bradycardia
 Unknown if Excreted in Breast Milk
 Low Weight Infants are Susceptible to Systemic
Hypertension with 2.5% or 10% Phenylephrine Drops
 Avoid Use in Nursing Mothers
 All Mydriatic/Cycloglegic Drops – Category C
 Relatively Contraindicated Due to Fetal Hypoxia in Late
Pregnancy and Delivery
DIAGNOSTIC AGENTS
 FLUORESCEIN DYE
 Crosses Placenta
 Enters Fetus in Humans and Animals
 No Adverse Effects Reported in Humans
 Category C Rating
 Avoid Angiography on Pregnant Patients Especially Those in
the First Trimester
 Detected in Breast Milk
 Stop Breastfeeding for Hours or Days if Used Topically or by
IV
DIAGNOSTIC AGENTS
 INDOCYANINE GREEN DYE
 Used Non-Ophthalmically in Pregnant Women for
Measuring Hepatic Blood Flow
 No Adverse Effects on Mother or Fetus
 Does Not Cross Placenta
 Not Known if Present in Breast Milk
 Pregnancy Category C Rating
 Use Only if Clearly Indicated
GLAUCOMA MEDICATIONS
 INCIDENCE OF GLAUCOMA
 Low in Women of Child-Bearing Age
 DISEASE SEVERITY
 Young Mothers May Tolerate Small Increases in IOP
During Pregnancy
 Decrease or Hold Treatment to Limit Risk to Fetus
Beta-Adrenergic Antagonists
 Topical Medications Include: Betagan, Betimol, Istalol,
Ocupress, and Timoptic
 Systemic Side Effects in General
 Respiratory Distress, Bradycardia, Heart Failure, Fatigue,
Depression
 Topical Medications Bypass Hepatic Metabolism and Are
Not Inactivated (unlike oral beta-blockers)
 Despite Low Dosage
 In Children: Bradycardia & Apnea
Beta-Adrenergic Antagonists
 Systemic Therapy Effects in Pregnancy





Apnea
Intrauterine Growth Retardation
Neonatal Depression at Birth (Low APGAR)
Postnatal Hypoglycemia
Bradycardia
 Effects of Topical Use in Pregnancy
 Case Reports of Timolol Show Both No Effects and
Adverse Effects
 Case Report: Decrease Concentration From 0.5% to
0.25% Decreased Fetal Arrythmia
Beta-Adrenergic Antagonists
 Beta-Blockers and Breast Feeding
 Secreted and Concentrated in Breast Milk
 Case Report: Apnea in 18 mo/old Child Being Breast Fed
 Rating- Pregnancy Category C
 Potential for Serious Adverse Side Effects
 Discontinue Nursing or Discontinue Drug, Taking Into
Account the Importance of the Drug to the Mother
Carbonic Anhydrase Inhibitors
 Oral Agents (Acetazolamide/Diamox)
 Animal Studies: Malformations, Electrolyte Imbalance
 National Collaborative Perinatal Project
 No Incidence in Major or Minor Fetal Abnormalities in Infants
Where Mothers Took Medication at Different Stages of
Pregnancy
 Study Size Considered Too Small
 Hepatic and Renal Effects on Infants Being Breast Fed
Carbonic Anhydrase Inhibitors
 Topical Agents (Dorzolamide/Trusopt and
Brinzolamide/Azopt)
 Published Reports Limited
 No Adverse Effects Reported
 Not Known if Excreted in Breast Milk
 Rating – Pregnancy Category C
 Discontinue Nursing or Discontinue Drug, Taking into
Account the Importance of the Drug to the Mother
Sympathomimetics
 Epinephrine (Epifrin)
 Stimulates Both Alpha and Beta Adrenergic Receptors
 Human Studies: Systemic Use in First Trimester
Associated with Minor and Major Anomalies-- Inguinal
Hernias
 Rating-- Pregnancy Category C
Sympathomimetics
 Dipivefrin Hydrochloride (Propine)




Prodrug of Epinephrine Converted by Corneal Enzymes
Animal Studies: Negative for Side Effects
Not Known if Excreted in Breast Milk
Rating-- Pregnancy Category B
 Brimonidine (Alphagan P)—Apraclonidine Hydrochloride (Iopidine)
 Selective Alpha-2 Adrenergic Agonists
 Case Reports: No Adverse Side Effects During Pregnancy
 Not Known if Excreted in Breast Milk
 Alphagan P Caused CNS Depression, Somnolence, Apnea in Neonates and
Infants
 Rating–
 Alphagan P– Pregnancy Category B
 Iopidine– Pregnancy Category C
Prostaglandin Analogues
 Latanaprost (Xalatan), Bimatoprost (Lumigan),
Travoprost (Travatan)
 Prostaglandins Action in Labor
 Causes Uterine Contractions of Uterine Smooth Muscles
 Animal Studies of Systemic Prostaglandins
 Increase Risk of Abortion or Preterm Delivery
Prostaglandin Analogues
 Human Studies of Topical Prostaglandins
 Case Studies: No Adverse Effect on Pregnancy or Neonatal
Outcome
 Excretion in Breast Milk
 Positive in Animal Studies
 Unknown in Humans
 Rating—Pregnancy Category C
 Because of Potential Effects on Uterine Muscle Contractibility
 Prostaglandin Should Be Avoided in Women Who Are Pregnant
or Desire to Become Pregnant
Miotics
 Parasympathomimetic Agents
 Includes Direct Acting Cholinergic Agents: Pilocarpine &
Carbachol
 Animal Studies:
 Pilocarpine--Limb Abnormalities
 Carbachol– Cervical Vertebrae Abnormalities
 Human Study: Systemic Pilocarpine
 No Side Effects in First 4 Months of Gestation
 Near Term: Neonatal Hyperthermia, Seizures, Restlessness
 Rating—Pregnancy Category C
CORTICOSTEROIDS
 Systemic Corticosteroids
 Increase Risk of Stillbirth
 Intrauterine Growth Retardation and Adrenal Insufficiency
 Topical Corticosteroids
 Animal Studies:
 Developmental and Teratogenic Effects Including Cleft Lip,
Cleft Palate & Sex Organ Abnormalities in Mice
CORTICOSTEROIDS
 Excreted in Breast Milk
 Present if Administered Systemically
 Suppressed Growth or Interferes with Endogenous
Production
 Unknown if Present as a Topical Medication
 Rating—Pregnancy Category C
 Avoid Use During Nursing Given Potential Serious
Adverse Reactions.
ANTIBIOTICS
 Erythromycin & Polymyxin B
 No Known Congenital Defects
 Aminoglycosides
 Gentamycin, Streptomycin, Tobramycin, Neomycin
 Case Studies in Humans: Used IV with No Teratogenic
Abnormalities
 Animal Studies: Hearing Loss, Nephrotoxicity
ANTIBIOTICS
 Sulfonamides
 Animal Studies: Increase Cleft Palate and Other Bony
Abnormalities
 Human Case Reports: Hyperbilirubinemia in Infant if
Used During Third Trimester of Pregnancy
 Fluoroquinolones
 Animal Studies of Topical Ciloxan, Ocuflox, Quixin,
Vigamox & Zymar:
 No Teratogenic Effects
 Animal Studies with High Doses
 Decrease Body Weights, Delayed Skeletal Development
 Tetracycline
ANTIBIOTICS
 Human Case Reports– Systemic Use:
 Permanent Discoloration of Teeth in Offspring
 Excreted in Breast Milk
 Positive with Systemic Erythromycin, Tetracycline &
Ciprofloxacin
 Maternal Medications Usually Compatible with Breast
Feeding By American Academy of Pediatrics
 Rating:
 Pregnancy Category B--Erythromycin
 Pregnancy Category C--Gentamycin, Neomycin,
Polymyxin B, Sulfonamides, Fluoroquinolones
 Pregnancy Category D-- Tetracycline
ANTIVIRALS
 Topical: Trifluridine (Viroptic) & Vidarabine ( Vira-A)
 For Treatment of HSV Keratitis
 Rating– Pregnancy Category C
 Avoid in Pregnancy Due to Teratogenic and Tumorgenicity
Effect
 Oral: Acyclovir (Zovirax) & Valacyclovir (Valtrex)
 For Treatment of Epithelial Corneal Disease
 Rating--Pregnancy Category B
THERAPY FOR CHOROIDAL
NEOVASCULARIZATION
 Verteporfin (Visudyne)
 Human Studies: None
 Animal Studies: Increase Anophthalmia and
Microphthalmia in Rat Fetuses
 Rating– Pregnancy Category C
 Pegaptanib (Macugen)
 Human Studies: None
 Animal Studies: No Maternal or Fetal Abnormalities
 Rating– Pregnancy Category B
THERAPY FOR CHOROIDAL
NEOVASCULARIZATION
 Bevacizumab (Avastin)
 Human Studies: None
 Animal Studies: Teratogenic in Rabbits, Disrupts
Angiogenesis
 Rating – Pregnancy Category C
 Ranibizumab (Lucentis)
 Human Studies: None
 Animal Studies : None
 Rating-- Pregnancy Category C
ANTI-INFLAMMATORY
DRUGS
 Cyclosporine (Restasis)




Immunomodulator
Animal Studies: No Abnormalities
Breast Milk: Excreted When Used Systemically
Rating—Pregnancy Category C
 NSAIDS
 Flurbiprofen (Ocufen)
 Animal Studies: Embryocidal, Prolonged Gestation,
Retarded Growth
ANTI-INFLAMMATORY
DRUGS
 Diclofenac (Voltaren)
 Animal Studies: Crosses Placenta
 Nepafenac (Nevanac)
 Animal Studies: Crosses Placenta
 Found in Breast Milk
 Bromfenac (Xibrom)
 Ketorolac (Acular)
 All NSAIDS Rating- Pregnancy Category C
 Affects Fetal Cardiovascular System
MEDICAL MARIJUANA
 Crosses Placenta
 Contains Toxins-- Decrease Oxygen to Fetus
 Increases Miscarriage, Low Birth Weight, Premature
Birth, Developmental Delays, Behavioral and Learning
Problems, Increase Childhood Leukemia
 Excreted in Breast Milk
 Active Ingredient THC-- Impairs Infant Motor
Development
COMMUNICATION
 Clear Indication for Use
 Relative Benefits vs. Potential Risks
 Birth Defects Occur in 2% or More of All Neonates.
Drugs Used Coincidently Might Be Wrongly Implicated as
Contributing to a Birth Defect
 Discussion with Patient and Obstetrician
DOSAGE
 Minimal Effective Dose
 Shortest Duration
 Limit Systemic Absorption of Drops
 Nasolacrimal Duct Occlusion
 Eyelid Closure
 Removal of Excess Medication with Absorbent Material
OPHTHALMIC OINTMENTS
 Safety Profile Different from Drops
 Ointment Creates Reservoir of Active Drug
 Prolonged Absorption Time
 Reduced Serum Level of Medication
 May Create Lower Therapeutic Level Within Eye
DIAGNOSTIC AGENTS
 Routine Use of Anesthetic Drops or Dilating Drops
Should be Avoided
 UNLESS:
 New Symptoms Occur
 Monitoring of Specific Disease (i.e. Diabetic Retinopathy)
 Lowest Concentration and Duration
 Tropicamide 0.5%
 Fluorescein Dye and ICG Dye
 Vitreoretinal Specialists Avoid Use During Pregnancy
 Use OCT instead
THERAPEUTIC AGENTS
 Corticosteroids
 Use Topically with Caution
 Antibiotics
 Erythromycin—Relatively Safe
 Tetracycline—Avoid
 Fluoroqinolones—Effects Unknown
THERAPEUTIC AGENTS
 Antivirals
 Topical Viroptic & Vira-A – Avoid Because of Tumor
Formation and Teratogenic Effect
 Oral Zovirax & Valtrex – Relatively Safe For Treatment of
Epithelial Keratitis
 Anti-Inflammatory Drugs
 Restasis – Use Only if Clearly Needed
 NSAIDS – Avoid Use in Late Pregnancy Because of Fetal
Cardiovascular System Complications
THERAPEUTIC AGENTS
 Glaucoma Treatment
 Prostaglandins
 Avoid Due to Effects on Uterine Contractility
 Topical Beta Blockers
 Reported Positive and Negative for Fetal Side Effects
 Topical Carbonic Anhydrase Inhibitors
 Relatively Safe After First Trimester
 Propine & Alphagan
 Both are Pregnancy Category B
 Avoid Use of Alphagan at Term of Pregnancy Due to Reports
of Apnea and Somnolence in Neonates
NURSING MOTHER
 Dilating Drops – Avoid Due to Infant Systemic
Hypertension
 Fluorescein Dye – If Use Necessary, Must Stop
Breastfeeding for Hours or Days
 Corticosteroids – Potentially Serious Side Effects
 Antibiotics – American Academy of Pediatrics
Classified Erythromycin, Gentamycin, Tetracycline &
Ciprofloxacin as “Maternal Medications Usually
Compatible with Breast Feeding”
NURSING MOTHER
 Antivirals
 Topicals – Avoid Unless Benefit Outweighs Risk
 Orals – Found in Breast Milk, Use with Caution
 Anti-Inflammatory Drugs
 Restasis & NSAIDS – Use with Caution
 Glaucoma Treatment
 Propine & Alphagan P – Not Known if Excreted in Breast
Milk
 Beta Blockers, CA Inhibitors, Pilocarpine, Carbachol,
Epifrin, Iopidine, Prostaglandins – Discontinue Nursing or
Discontinue Drug
GUIDELINES
FOR
MANAGEMENT
HSV KERATITIS DURING
PREGNANCY
 Epithelial Lesions
 Frequently Dendritic and Often Contain Live Virus
 Dendrites May Heal Spontaneously After Debridement
and Lubrication
 Topical Viroptic Used in Appropriate Dosage Unlikely to
Cause Fetal Damage
 Stromal Keratitis
 Herpetic Eye Disease Study– Topical Antiviral Therapy
with Topical Steroids Reduces Progression and Duration
of Disease
HSV KERATITIS DURING
PREGNANCY
 Iridocyclitis
 Addition of Oral Zovirax to Topical Antiviral Therapy and
Corticosteroid was Beneficial
 No Fetal Abnormalities from Oral Zovirax or Valtrex
Reported
OPTIC NEURITIS IN FIRST TRIMESTER
DUE TO DEMYLENATING DISEASE
 Optic Neuritis Treatment Trial
 IV Methylprednisolone
 Faster Resolution of the Visual Loss but Did NOT Affect
Long-Term Outcome After 6 Months
 Decrease Risk of Recurrence of Optic Neuritis and
Development of MS in the Future
 No IV Steroids
 Only Observation in the First Trimester as the Risk of
Fetal Abnormalities Outweighs the Benefit of Faster
Visual Recovery
CHRONIC UVEITIS
 Mainstay of Treatment
 Topical Cycloplegia
 No Teratogenic Effects
 Topical Corticosteroids
 No Teratogenic Effects
 If Oral Steroids and/or Nonsteroidals (Methotrexate)
Are Needed
 NO Methotrexate-- Known Teratogen
 NO Systemic Steroids– Risk of Cleft Lip and Palate
 Consider Periocular or Intravitreal Steroids
 Secondary to Reduced Systemic Levels
 Weigh Risk/Benefits to Patient
GLAUCOMA DURING PREGNANCY
AND LACTATION
 Several Glaucoma Medications Have Potential Adverse Effects in
the Fetus or Breastfeeding Infant
 Beta-Blockers—Class C
 Alpha 2 Agonists (Alphagan P)– Class B
 Prostaglandin Analogues– Class C
 Topical and Oral Carbonic Anhydrase Inhibitors– Class C
 Alternatives Include:
 Laser Trabeculoplasty
 Observation OFF Treatment
 Avoid Glaucoma Surgery
 Because of Anesthetic Concerns, Surgical Positioning and Intra
and Peri-Operative Medications
WORSENING OF GLAUCOMA IN DRUGS
USED TO TREAT ECLAMPSIA AND
PREMATURE LABOR
 Management of Premature Labor and Eclampsia
 Beta-Mimetics
 Rarely Causes Acute Angle-Closure Glaucoma
 Magnesium Sulfate
 Ptosis, Accommodative and Convergence Insufficiency with
Diplopia and/or Pupillary Abnormalities
 Antiprostaglandins (Indocin)
 Decreases IOP Lowering Effect of Epinephrine in Glaucoma
Patients
 After Treatment for Premature Labor, Pregnant Woman
is Given Glucocorticoids for 2 Days Before Delivery
 Glaucoma May Worsen After Steroid Therapy