bimatoprost (Rx)

Brand and Other Names:Latisse, Lumigan
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

ophthalmic solution

  • 0.01% (Lumigan)
  • 0.03% (Latisse, generic)

Elevated Intraocular Pressure

Indicated for reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension

Lumigan (0.01%): Instill 1 gtt in affected eye qDay in evening

Hypotrichosis of the Eyelashes

Indicated to treat hypotrichosis of the eyelashes by increasing their growth including length, thickness, and darkness

Latisse (0.03%): 1 gtt on disposable sterile applicator and apply evenly along skin of upper eyelid margin at base of eyelasheson each eye once nightly

Safety & efficacy not established

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Interactions

Interaction Checker

and bimatoprost

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    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

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            Contraindicated (0)

              Serious - Use Alternative (4)

              • latanoprost

                latanoprost, bimatoprost. unspecified interaction mechanism. Avoid or Use Alternate Drug. Combined use of 2 or more ophthalmic prostaglandins may decrease the IOP lowering effect or cause paradoxical elevations in IOP.

              • latanoprostene bunod ophthalmic

                bimatoprost, latanoprostene bunod ophthalmic. unspecified interaction mechanism. Avoid or Use Alternate Drug. Combined use of 2 or more ophthalmic prostaglandins may decrease the IOP lowering effect or cause paradoxical elevations in IOP.

              • tafluprost

                tafluprost, bimatoprost. unspecified interaction mechanism. Avoid or Use Alternate Drug. Combined use of 2 or more ophthalmic prostaglandins may decrease the IOP lowering effect or cause paradoxical elevations in IOP.

              • travoprost ophthalmic

                travoprost ophthalmic, bimatoprost. unspecified interaction mechanism. Avoid or Use Alternate Drug. Combined use of 2 or more ophthalmic prostaglandins may decrease the IOP lowering effect or cause paradoxical elevations in IOP.

              Monitor Closely (31)

              • aspirin

                bimatoprost, aspirin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • aspirin rectal

                bimatoprost, aspirin rectal. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • bromfenac ophthalmic

                bimatoprost, bromfenac ophthalmic. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • celecoxib

                bimatoprost, celecoxib. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • choline magnesium trisalicylate

                bimatoprost, choline magnesium trisalicylate. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • diclofenac

                bimatoprost, diclofenac. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • diclofenac ophthalmic

                bimatoprost, diclofenac ophthalmic. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • diflunisal

                bimatoprost, diflunisal. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • etodolac

                bimatoprost, etodolac. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • fenoprofen

                bimatoprost, fenoprofen. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • flurbiprofen

                bimatoprost, flurbiprofen. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • flurbiprofen ophthalmic

                bimatoprost, flurbiprofen ophthalmic. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • ibuprofen

                bimatoprost, ibuprofen. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • ibuprofen IV

                bimatoprost, ibuprofen IV. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • ibuprofen/famotidine

                bimatoprost, ibuprofen/famotidine. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • indomethacin

                bimatoprost, indomethacin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • ketoprofen

                bimatoprost, ketoprofen. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • ketorolac

                bimatoprost, ketorolac. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • ketorolac intranasal

                bimatoprost, ketorolac intranasal. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • ketorolac ophthalmic

                bimatoprost, ketorolac ophthalmic. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • meclofenamate

                bimatoprost, meclofenamate. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • mefenamic acid

                bimatoprost, mefenamic acid. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • meloxicam

                bimatoprost, meloxicam. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • nabumetone

                bimatoprost, nabumetone. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • naproxen

                bimatoprost, naproxen. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • nepafenac ophthalmic

                bimatoprost, nepafenac ophthalmic. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • oxaprozin

                bimatoprost, oxaprozin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • piroxicam

                bimatoprost, piroxicam. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • salsalate

                bimatoprost, salsalate. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • sulindac

                bimatoprost, sulindac. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              • tolmetin

                bimatoprost, tolmetin. unspecified interaction mechanism. Use Caution/Monitor. There are conflicting reports from studies of either increased or decreased IOP when ophthalmic prostaglandins are coadministered with NSAIDs (either systemic or ophthalmic).

              Minor (0)

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                Adverse Effects

                >10%

                Conjunctival hyperemia (25-45%)

                Growth of eyelashes (15-45%)

                Ocular pruritus (15-45%)

                1-10%

                Ocular dryness (3-10%)

                Visual disturbance (3-10%)

                Ocular burning (3-10%)

                Foreign body sensation (3-10%)

                Ocular pain (3-10%)

                Pigmentation of the periocular skin (3-10%)

                Blepharitis (3-10%)

                Cataract (3-10%)

                Superficial punctate keratitis (3-10%)

                Eyelid erythema (3-10%)

                Ocular irritation (3-10%)

                Eyelash darkening (3-10%)

                Ocular discharge (1-3%)

                Tearing (1-3%)

                Photophobia (1-3%)

                Allergic conjunctivitis (1-3%)

                Asthenopia (1-3%)

                Increases in iris pigmentation (1-3%)

                Conjunctival edema (1-3%)

                Frequency Not Defined

                Periorbital erythema

                Eye swelling

                Eyelids: burning sensation, edema, irritation, pruritus

                Iris hyperpigmentation

                Lacrimation increased

                Madarosis and trichorrhexis

                Periorbital and lid changes associated with a deepening of the eyelid sulcus

                Rash (including macular, erythematous, and pruritic limited to the eyelids and periorbital region)

                Skin discoloration (periorbital)

                Blurred vision

                Postmarketing Reports

                Effects on intraocular pressure

                Iris pigmentation

                Lid pigmentation

                Hair growth outside treatment area

                Intraocular inflammation

                Macular edema

                Hypersensitivity

                Hordeolum

                Trichiasis

                Asthma-like symptoms

                Dizziness

                Dyspnea

                Eyelid edema

                Hypersensitivity reaction including signs and symptoms of eye allergy and allergic dermatitis

                Hypertension

                Nausea

                Dry skin of the eyelid and/or periocular area

                Periorbital fat atrophy and skin tightness resulting in deepening of eyelid sulcus and eyelid ptosis

                Skin exfoliation of the eyelid and/or periorbital area

                Lid changes associated with periorbital fat atrophy, leading to skin tightness

                Enophthalmos and eyelid retraction

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                Warnings

                Contraindications

                Hypersensitivity

                Cautions

                Macular edema, including cystoid macular edema, reported; the 0.01% strength should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema

                Prostaglandin analogs, including bimatoprost, reported to cause intraocular inflammation; because these products may exacerbate inflammation, use caution in patients with active intraocular inflammation

                The 0.01% strength contains benzalkonium chloride, which may be absorbed by and cause discoloration of soft contact lenses; contact lenses should be removed prior to instillation and may be reinserted 15 minutes following administration

                Bacterial keratitis reported; associated with use of multiple-dose containers of topical ophthalmic products; containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of ocular epithelial surface

                May gradually change eyelashes and vellus hair in treated eye; these changes include increased length, thickness, and number of lashes; eyelash changes are usually reversible upon discontinuation of treatment

                Potential for hair growth to occur in areas where solution comes in repeated contact with skin surface; carefully blot any excess from the eyelid margin to avoid it running onto cheek or other skin areas

                Not recommended for patients <16 years

                Pigmentation

                • May cause darkening of the iris and lid darkening to periorbital pigmented tissues and eyelashes
                • Pigmentation change is due to increased melanin content in melanocytes rather than to increase in number of melanocytes
                • After discontinuation of bimatoprost, pigmentation of iris is likely to be permanent, while pigmentation of periorbital tissue and eyelash changes have been reported to be reversible in some patients
                • Patients who receive treatment should be informed of possibility of increased pigmentation
                • While treatment with 0.01% can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly
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                Pregnancy & Lactation

                Pregnancy

                There are no adequate and well-controlled studies in pregnant women; there is no increase in risk of major birth defects or miscarriages based on bimatoprost postmarketing experience; administered during pregnancy only if potential benefit justifies potential risk to fetus

                Lactation

                Not known whether topical ocular treatment with this product could result in sufficient systemic absorption to produce detectable quantities in human milk; the developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from therapy

                Pregnancy Categories

                A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

                B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

                C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

                D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

                X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

                NA: Information not available.

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                Pharmacology

                Mechanism of Action

                Prostaglandin analog

                Lowers intraocular pressure by increasing outflow of aqueous humor through both trabecular meshwork and uveoscleral routes

                Eyelash growth is believed to occur by increasing the percent of hairs in, and the duration of the anagen or growth phase

                Administration

                Absorption: No significant systemic accumulation

                Peak plasma time: ≤10 min

                Onset of action: 4hr (IOP reduction)

                Peak effect: 8-12hr

                Peak plasma concentration: 0.08 ng/mL

                AUC: 0.09 nghr/mL

                Distribution

                Protein binding: 88%

                Vd: 0.67 L/kg

                Metabolism

                Oxydation; N-deethylation and glucuronidation

                Elimination

                Half Life: 45 min

                Total blood clearance: 1.5 L/hg/kg

                Excretion: Urine (67%); feces (25%)

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                Administration

                Intraocular Administration (Lumigan)

                Avoid allowing tip of dispensing container to contact the eye, surrounding structures, fingers, or any other surface to avoid contamination of the solution

                Remove contact lenses before instilling eye drops; may reinserted 15 minutes following administration

                Administer eye drops at least 5 minutes apart if used concomitantly with other topical ophthalmic drug products to lower intraocular pressure

                Topical Administration (Latisse)

                Avoid allowing tip of dispensing container to contact the eye, surrounding structures, fingers, or any other surface to avoid contamination of the solution

                Ensure the face is clean, makeup and contact lenses are removed

                Using disposable applicator, apply evenly along skin of upper eyelid margin at base of eyelashes

                Upper lid margin in the area of lash growth should feel lightly moist without runoff; blot any excess solution runoff outside upper eyelid margin with tissue or other absorbent cloth

                Dispose of applicator after single use; repeat process for opposite eyelid margin using a new sterile applicator

                Do not reuse applicators and do not use any other brush/applicator to apply

                Do not apply to lower eyelash line

                Additional applications will not increase growth of eyelashes

                Upon discontinuation, eyelash growth is expected to return to its pretreatment level

                Storage

                Store at 2-25ºC (36-77ºF)

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                Images

                BRAND FORM. UNIT PRICE PILL IMAGE
                Lumigan ophthalmic (eye)
                -
                0.01 % drops
                Lumigan ophthalmic (eye)
                -
                0.01 % drops
                Lumigan ophthalmic (eye)
                -
                0.01 % drops
                bimatoprost ophthalmic (eye)
                -
                0.03 % drops
                bimatoprost ophthalmic (eye)
                -
                0.03 % drops
                bimatoprost ophthalmic (eye)
                -
                0.03 % drops
                bimatoprost ophthalmic (eye)
                -
                0.03 % drops
                bimatoprost ophthalmic (eye)
                -
                0.03 % drops
                bimatoprost ophthalmic (eye)
                -
                0.03 % drops
                bimatoprost ophthalmic (eye)
                -
                0.03 % drops
                bimatoprost ophthalmic (eye)
                -
                0.03 % drops
                bimatoprost ophthalmic (eye)
                -
                0.03 % drops
                bimatoprost ophthalmic (eye)
                -
                0.03 % drops
                bimatoprost base of the eyelashes
                -
                0.03 % drops
                bimatoprost base of the eyelashes
                -
                0.03 % drops
                Latisse base of the eyelashes
                -
                0.03 % drops
                Latisse base of the eyelashes
                -
                0.03 % drops

                Copyright © 2010 First DataBank, Inc.

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                Patient Handout

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                Patient Education
                bimatoprost ophthalmic (eye)

                BIMATOPROST SOLUTION - OPHTHALMIC

                (bye-MAT-oh-prost)

                COMMON BRAND NAME(S): Lumigan

                USES: Bimatoprost is used to treat high pressure inside the eye due to glaucoma (open-angle type) or other eye diseases (such as ocular hypertension). Lowering high pressure inside the eye can help prevent blindness. This medication works by regulating the flow of fluid within the eye to maintain a normal pressure.

                HOW TO USE: Apply this medication in the affected eye(s), usually once a day in the evening, or as directed by your doctor. Do not use bimatoprost more often because it will not work as well.To apply eye drops, wash your hands first. To avoid contamination, do not touch the dropper tip or let it touch your eye or any other surface.Bimatoprost contains a preservative that may stain contact lenses. If you are wearing contact lenses, remove them before using your eye drops. Wait at least 15 minutes after each dose before putting your lenses back in.Tilt your head back, look upward, and pull down the lower eyelid to make a pouch. Hold the dropper directly over your eye and place one drop into the pouch. Look downward and gently close your eyes for 1 to 2 minutes. Place one finger at the corner of your eye (near the nose) and apply gentle pressure. This will prevent the medication from draining out. Try not to blink and do not rub your eye. Repeat these steps for your other eye if so directed.Do not rinse the dropper. Replace the dropper cap after each use, and keep the cap tightly closed.If you are using another kind of eye medication (such as drops or ointments), wait at least 5 minutes before applying other medications. Use eye drops before eye ointments to allow the eye drops to enter the eye.Use this medication regularly in order to get the most benefit from it. Remember to use it at the same time each day. Keep using bimatoprost even if you feel well. Most people with glaucoma or high pressure in the eye do not have symptoms.

                SIDE EFFECTS: Burning/stinging/irritation/redness of the eye, feeling as if something is in your eye, dry eyes, watering eyes, and increased sensitivity to light may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.This medication may slowly (over months to years) cause brown discoloration of the colored portion of the eye (iris). If you are using bimatoprost in only one eye, only that iris may change color. An increase in eyelash number/length/thickness, darkening of the eyelashes/eyelids, or eyelid changes may also occur in the treated eye. These changes may be permanent, but the long-term effects are uncertain. Notify your doctor if this occurs, and schedule regular eye exams to monitor it.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: vision changes, eye pain/swelling, swelling/redness of the eyelids.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

                PRECAUTIONS: Before using bimatoprost, tell your doctor or pharmacist if you are allergic to it; or to similar drugs (such as latanoprost, travoprost); or if you have any other allergies. This product may contain inactive ingredients (such as preservatives like benzalkonium chloride), which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: eye problems (such as macular edema, iritis, uveitis, lens extraction/aphakia).If you develop an eye infection or injury, or have eye surgery, check with your doctor about the continued use of your current bottle of bimatoprost. You may be advised to start using a new bottle.This drug may cause temporary unstable vision. Do not drive, use machinery, or do any activity that requires clear vision until you are sure you can perform such activities safelyDuring pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

                DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug are: eyelash treatment (such as topically applied bimatoprost).

                OVERDOSE: This medicine may be harmful if swallowed. If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

                NOTES: Do not share this medication with others.Laboratory and/or medical tests (such as eye exams) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

                MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Use your next dose at the regular time. Do not double the dose to catch up.

                STORAGE: Store between 36-77 degrees F (2-25 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

                Information last revised March 2022. Copyright(c) 2022 First Databank, Inc.

                IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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                Formulary

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                The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

                Tier Description
                1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
                2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
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                NC NOT COVERED – Drugs that are not covered by the plan.
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                Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.