washington pharmacy advisory committee meeting · 11/15/2017 · acute myeloid leukemia (aml)...

Washington Pharmacy Advisory Committee Meeting

November 15, 2017

Stephanie Christofferson, Pharm.D., MBA

Agenda Topics

2

Indications Dosage & Formulations Guideline Updates

Colony Stimulating Factors

Colony Stimulating Factors- Overview

• Myelosuppressive chemotherapy can induce neutropenia and febrile

• Colony Stimulating Factors (CSF) decrease the likelihood of neutropenic complications

• Prophylactic CSF use can reduce the severity, risk, and duration of febrile neutropenia and decrease rates of infection

• Two classifications of CSF:

− Granulocyte colony-stimulating factors (G-CSF): Filgrastim (Neupogen), filgrastim-sndz (Zarxio), pegfilgrastim (Neulasta), and tbo-filgrastim (Granix)

− Granulocyte-macrophage colony stimulating factor (GM-CSF): Sargramostim (Leukine)

4

Colony Stimulating Factors- IndicationsDrug Cancer patients receiving

myelosuppressive chemo– to reduce incidence of infection (febrile neutropenia)

Acute Myeloid Leukemia (AML) patients receiving chemo

Bone Marrow Transplant (BMT)

Peripheral Blood Progenitor Cell Collection & Therapy

Hematopoietic Syndrome of Acute Radiation Syndrome

Severe Chronic Neutropenia

filgrastim (Neupogen)

X X (Following induction or

consolidation chemotherapy – reduces

time to neutrophil recovery and the duration

of fever in adults)

X (Cancer patients receiving BMT –

to reduce duration of

neutropenia and febrile

neutropenia)

X X (Increases survival in

patients acutely exposed to

myelosuppressive doses of radiation)

X (Reduce the

incidence and duration of

neutropenia in symptomatic patients with

congenital neutropenia,

cyclic neutropenia, or

idiopathic neutropenia)

filgrastim-sndz (Zarxio)

X X (Following induction or

consolidation chemotherapy – reduces

time to neutrophil recovery and the duration

of fever in adults)

X (Cancer patients receiving BMT –

to reduce duration of

neutropenia and febrile

neutropenia)

X --- X (Reduce the

incidence and duration of

neutropenia in symptomatic patients with

congenital neutropenia,

cyclic neutropenia, or

idiopathic 5

Colony Stimulating Factors- Indications

Drug Cancer patients receiving myelosuppressive chemo–

to reduce incidence of infection (febrile

neutropenia)

Acute Myeloid Leukemia (AML) patients receiving

chemo


Peripheral Blood

Progenitor Cell Collection &

Therapy

Hematopoietic Syndrome of Acute

Radiation Syndrome


pegfilgrastim (Neulasta)

X --- --- --- X (Increases survival in

patients acutely exposed to

myelosuppressive doses of radiation)

---

sargramostim (Leukine)

--- X (Following induction for

patients 55 years old and older; shorten time to

neutrophil recovery, and to reduce incidence of severe and

life-threatening infections)

X (For myeloid

reconstitution after BMT;

treatment of BMT failure or

engraftment delay)

X --- ---

tbo-filgrastim (Granix)

X --- --- --- --- ---

6

Colony Stimulating Factors- Dosing and FormulationsDrug Cancer patients

receiving myelosuppressive chemo – to reduce incidence of infection (febrile neutropenia)

Acute Myeloid Leukemia (AML) patients receiving chemotherapy


Peripheral Blood Progenitor Cell Collection and Therapy

Hematopoietic Syndrome of Acute Radiation Syndrome


Availability

filgrastim (Neupogen)

5 mcg/kg/day‚ administered as a single daily injection by SC bolus‚ by short IV infusion (15 to 30 min), or conti. IV infusion; dose may be inc. by increments of 5 mcg/ kg for each chemo cycle according to duration & severity of ANC nadir

5 mcg/kg/day as single daily injection by SC inj. short IV infusion (15 to 30 min), or conti. IV infusion; dose may be increased by increments of 5 mcg/ kg for each chemo cycle according to the duration & severity of ANC nadir

10 mcg/kg/day given as IV infusion no longer than 24 hrs; during periods of neutrophil recovery, the daily dose should be titrated against neutrophil response dosing schedule

10 mcg/kg/day SC; give for at least 4 days before the first leukapheresis procedure and continued until the last leukapheresis

10 mcg/kg as single daily SC inj.; administer as soon as possible after suspected/ confirmed exposure to radiation doses > 2 gray (Gy)

Starting Dose: Congenital Neutropenia: 6 mcg/kg SC twice daily; Idiopathic or Cyclic Neutropenia: 5 mcg/kg SC daily

SDV: 300 mcg/1 mL, 480 mcg/1.6 mL prefilled single-use syringes; (SingleJect®): 300 mcg/0.5 mL, 480 mcg/0.8 mL

filgrastim-sndz (Zarxio)

5 mcg/kg/day as single daily injection by SC inj., short IV infusion (15 to 30 min), or conti. IV infusion; doses may be inc. by increments of 5 mcg/kg for each chemo cycle according to the duration & severity of ANC nadir

5 mcg/kg/day as single daily injection by SC in., short IV infusion (15 to 30 min), or continuous IV infusion; doses may be inc. by increments of 5 mcg/kg for each chemo cycle according to the duration & severity of ANC nadir

10 mcg/kg/day given as IV infusion no longer than 24 hrs; during periods of neutrophil recovery, dose/day should be titrated to the neutrophil response dose schedule

10 mcg/kg/day by SC injection; give for at least 4 days before the first leukapheresis procedure and continued until the last leukapheresis

--- Starting Dose: Congenital Neutropenia: 6 mcg/kg SC twice daily; Idiopathic or Cyclic Neutropenia: 5 mcg/kg SC daily

Prefilled single-use syringe: 300 mcg/0.5 mL 480 mcg/0.8 mL

7

Colony Stimulating Factors- Dosing and FormulationsDrug Cancer patients

receiving myelosuppressive chemo – to reduce

incidence of infection (febrile

neutropenia)

Acute Myeloid Leukemia (AML)

patients receiving chemotherapy

Bone Marrow Transplant (BMT) Peripheral Blood

Progenitor Cell Collection and Therapy

Hematopoietic Syndrome of Acute Radiation

Syndrome

Severe Chronic

Neutropenia

Availability

pegfilgrastim (Neulasta)

6 mg SC once/ chemo cycle;

pediatric (weight < 45 kg) dosing is

weight based per dosing schedule in

PI

--- --- --- 2 doses, 6 mg each, given SC 1 week apart; pediatric (weight < 45 kg) dosing is weight based per dosing schedule in PI; first dose given as soon as possible

after suspected / confirmed radiation

exposure of > 2 gray; 2nd

dose given 1 week after

--- 6 mg/0.6 mL Neulasta: single use prefilled syringe for

manual use; Neulasta Onpro

Delivery Kit: single use delivery kit: 1 prefilled syringe

copackaged with 1 on-body injector for

HCP admin.

sargramostim (Leukine)

--- 250 mcg/m2/day given IV over 4 hours

starting approximately day 11 or 4 days

following completion of induction chemo, if

the day 10 bone marrow is hypoplastic

with < 5% blasts

250mcg/m2/day given IV over 2 hours beginning 2 to 4 hours

after bone marrow infusion, and not < 24 hours after the last

dose of chemo or radiotherapy; therapy should begin when

post-marrow infusion ANC is < 500 cells/mm3 and continued until ANC is > 1,500 cells/mm3

for 3 consecutive days; treatment of BMT failure or

engraftment delay: 250 mcg/m2/day given IV over 2

hours for 14 days

250 mcg/ m2/day adm.

IV over 24 hours or SC once daily; Conti. until

ANC is > 1,500 cells/mm³ for 3 consecutive

days

--- --- 250 mcg vial

8

Colony Stimulating Factors- Dosing and Formulations

Drug Cancer patients receiving myelosuppressive

chemotherapy – to reduce incidence of infection (febrile neutropenia)

Acute Myeloid Leukemia (AML)

patients receiving chemotherapy


Peripheral Blood Progenitor Cell Collection and

Therapy

Hematopoietic Syndrome of

Acute Radiation Syndrome


Availability

tbo-filgrastim (Granix)

5 mcg/kg/day as a SC injection until expected

neutrophil nadir is passed and neutrophil

count is in normal range

--- --- --- --- --- 300 mcg/0.5 mL, 480 mcg/0.8 mL single use, preservative-

free prefilled syringe with needle guard

(healthcare professional

administered); without needle guard

(self- or HCP-administered)

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Colony Stimulating Factors- Clinical Considerations

• Warnings− Granulocyte colony-stimulating factors (G-CSF):

− E. coli-derived proteins

− Splenic rupture

− Acute respiratory distress syndrome (ARDS)

− Alveolar hemorrhage

− Severe sickle cell crisis

− Growth factors for any tumor type

− Cutaneous vasculitis

− Thrombocytopenia

− Capillary leak syndrome (CLS)

− Glomerulonephritis

− Granulocyte-macrophage colony stimulating factor (GM-CSF):− Excessive leukemic myeloid blasts

− Benzyl alcohol

− Fluid retention

− Respiratory symptoms/dyspnea

− Growth factors for any tumor type

• Pregnancy− All products Category C; published data on filgrastim are insufficient to inform prescribers of the drug-associated risk

• Pediatrics− The safety and efficacy of filgrastim (Neupogen), filgrastim-sndz (Zarxio), and pegfilgrastim (Neulasta) have been established

10

Colony Stimulating Factors- Clinical Considerations

• Guideline Updates

− National Comprehensive Cancer Network (NCCN), v2.2017

− Safety data appear similar between filgrastim (Neupogen) and pegfilgrastim (Neulasta)

− There are insufficient head-to-head comparative studies on the clinical benefits of G-CSFs and GM-CSFs.

− Subcutaneous filgrastim, filgrastim-sndz, tbo-filgrastim, and pegfilgrastim prophylactically reduce the risk of febrile neutropenia

− Administration recommendation:

• Day after chemo, up to 3 – 4 days after chemo

• Same-day administration of pegfilgrastim no longer recommended

− Sargramostim is no longer recommended for prophylactic

− Biosimilars: filgrastim-sndz is recommended in the same instances as filgrastim; NCCN does not recommend switching between biosimilars and their corresponding reference products during treatment.

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Erythropoiesis Stimulating Proteins

Erythropoiesis Stimulating Proteins- Overview

• Disease states such as chronic kidney disease (CKD), cancer, diabetes, heart disease, rheumatoid arthritis, or inflammatory bowel disease can cause anemia

• Erythropoietin is a glycoprotein produced in the kidneys that stimulates RBC production from bone marrow

• Recombinant human epoetin alfa (rHuEPO) is a glycoprotein manufactured by recombinant DNA technology that has the same biological effects as endogenous erythropoietin

• Epogen and Procrit are identical rHuEPO products that contain the identical amino acid sequence of isolated natural erythropoietin

• Darbepoetin (Aranesp) is an erythropoiesis-stimulating agent similar to rHuEPO; has 2 additional N-glycosylation sites which slow its clearance

• PEG-EPO (Mircera) is a synthetic, continuous erythropoietin receptor activator; slowed clearance due to the addition of the conjugated PEG polymer

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Erythropoiesis Stimulating Proteins- IndicationDrug Anemia

Associated w/ (CKD)

Anemia Assoc. w/ Non-Myeloid Malignancies*

Anemia Assoc. w/ Chronic Renal Failure (CRF)

Anemia Assoc. w/ Zidovudine Therapy in HIV

Allogenic RBC Transfusion Reduction

Not Indicated For:

darbepoetin (Aranesp)

X X • Patients receiving myelosuppressive therapy when anticipated outcome is cure or in whom anemia can be managed by transfusion

• Patients receiving hormonal agents, therapeutic biologic products, or radiotherapy unless receiving concomitant myelosuppressive chemotherapy

• Substitute for red blood cell (RBC) transfusion in patients who require immediate correction of anemia

PEG-EPO (Mircera)

X • Treatment of anemia in patients receiving cancer chemotherapy


rHuEPO (Epogen)

X X X X • Patients receiving hormonal agents, therapeutic biologic products, or radiotherapy unless receiving concomitant myelosuppressive chemotherapy

• Patients receiving myelosuppressive therapy when the anticipated outcome is cure or in in whom anemia can be managed by transfusion


• Patients undergoing cardiac or vascular surgery • Patients who are willing to donate autologous blood pre-

operatively

rHuEPO (Procrit)

X X X X

* When minimum of 2 additional months chemotherapy is planned 14

Erythropoiesis Stimulating Proteins- Dosage

Drug CRF Zidovudine-Treated HIV-Infected

Patients

Chemotherapy-Associated Anemia in Cancer Patients

Surgery

Starting Dose Starting Dose Starting Dose Target Hb (g/dL) Starting Dose

darbepoetin (Aranesp)

Dialysis: Adults: 0.45 mcg/kg IV or SC once weekly or 0.75 mcg/ kg every 2 weeks

Pediatrics: 0.45 mcg/kg IV or SC once weekly

Not on Dialysis: Adults: 0.45 mcg/kg IV or SC every 4 weeks Pediatrics: 0.45 mcg/ kg IV or SC once weekly or 0.75 mcg/ kg every 2 weeks

--- 2.25 mcg/kg SC once weekly or 500 mcg SC every 3 weeks*

Sufficient to avoid RBC transfusion

---

PEG-EPO (Mircera) All Adults: 0.6 mcg/kg IV or SC once every 2 weeks --- --- --- ---

rHuEPO (Epogen, Procrit)

Dialysis: Adults: 50-100 units/kg IV or SC 3 times weekly

Pediatrics: 50 units/ kg IV or SC 3 times weekly

Not on Dialysis Adults: 50-100 units/ kg IV or SC 3 times weekly

Adults: 100 units/kg IV or SC 3 times weekly

Adults: 150 units/ kg SC 3 times weekly or 40,000 units SC once weekly* Pediatrics: 600 units/kg IV weekly (max 40,000 units weekly)*

Sufficient to avoid RBC transfusion

Adults: 300 units/kg SC daily for 10 days prior to surgery, day of surgery, and 4 days after surgery OR 600 units/kg once weekly starting 3 weeks prior to, and on day of surgery

15

Erythropoiesis Stimulating Proteins- Formulation

Drug Single-Dose Vials Multiple Dose Vials Prefilled Syringe and SureClickAutoinjectors

darbepoetin (Aranesp) 25, 40, 60, 100, 200, 300 mcg/mL in 1 mL vials

--- 10 mcg/0.4 mL, 25 mcg/0.42 mL, 40 mcg/0.4 mL, 60 mcg/0.3 mL, 100 mcg/0.5 mL, 150 mcg/0.3 mL, 200 mcg/0.4 mL, 300 mcg/0.6 mL, 500 mcg/1 mL

PEG-EPO (Mircera) --- --- 30 mcg/0.3 mL, 50 mcg/0.3 mL, 75 mcg/0.3 mL, 100 mcg/0.3 mL, 150 mcg/0.3 mL, 200 mcg/0.3 mL

rHuEPO* (Epogen, Procrit) 2,000, 3,000, 4,000, 10,000 units/mL in 1 mL vials (Epogen) 2,000, 3,000, 4,000, 10,000, 40,000 units/mL in 1 mL vials (Procrit)

10,000 units/mL in 2 mL vial** 20,000 units/mL in 1 mL vial**

---

* All formulations of rHuEPO contain albumin ** Contains preservative 16

Erythropoiesis Stimulating Proteins- Clinical Considerations

• Warnings

− Contraindicated in uncontrolled HTN and hypersensitivity to albumin (human), mammalian cell-derived products, and Pure Red Cell Aplasia (PRCA)

− Multidose vials contains benzyl alcohol

− Boxed Warnings:

− Increased risk of death, MI, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression or recurrence

− Chronic kidney disease- experienced greater risks for death, serious adverse CV reactions, and stroke

− Cancer patients- ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence

− Perisurgical patients- increased the rate of DVT when not receiving prophylactic anticoagulation

− Increased mortality, MI, stroke, and thromboembolism

− DVT

− HTN in chronic renal disease

− Seizures

− Pure Red Cell Aplasia

17


• Pregnancy: Category C

− Previously, rHuEPO was assigned Pregnancy Category C - labeling was updated in compliance with the Pregnancy and Lactation Labeling Rule (PLLR); data are too limited with rHuEPO in pregnant women to inform of a drug-associated risk; use of rHuEPO from multidose vials is contraindicated in pregnant women

• Pediatrics:

− rHuEPO

− Pharmacokinetic profiles of rHuEPO are similar in both adults and children

− FDA Approved:

• Treatment of anemia in CRF who require dialysis- ages 1 month to 16 years

• Treatment of anemia due to concurrent myelosuppressive chemotherapy- ages 5 to 18 years

− Data exist to support the use rHuEPO in patients 8 months to 17 years old with zidovudine-treated HIV infection

− Darbepoetin/PEG-EPO

− Safety and efficacy have not been established in initial treatment of CKD or in the transition from another erythropoietin in CKD patients < 1 yo

− Safety and efficacy have not been established for chemotherapy-induced anemia

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• National Comprehensive Cancer Network (NCCN) guidelines, v2.2017 − ESAs are associated with an increased risk of thrombosis, decreased survival, and shortened time to tumor

− ESAs should be discontinued once the course of chemotherapy has been completed and anemia resolves

− There is not enough evidence to support the use of ESAs for the treatment of anemia related to myelosuppressive chemotherapy with curative intent, patients receiving non-myelosuppressive therapy, or patients with cancer not receiving therapy.

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Neuropathic Pain

Neuropathic Pain- Indications

Drug GenericPost-Herpetic

Neuralgia (PHN) Diabetic Peripheral Neuropathy (DPN)

Neuropathic Pain

Fibromyalgia Other Indications

duloxetine(Cymbalta)

X X X XMajor depressive disorder; generalized anxiety disorder; chronic musculoskeletal pain

duloxetine (Irenka)

X XMajor depressive disorder; generalized anxiety disorder; chronic musculoskeletal pain

gabapentin (Neurontin)

X X

Adjunctive therapy in the treatment of partial seizures with and without secondary generalization in patients > 12 yo with epilepsy; adjunctive therapy in the treatment of partial seizures in pediatric patients age 3 to 12 years

gabapentin (Gralise)

X

gabapentin enacarbil (Horizant)

XTreatment of moderate-to-severe primary restless legs syndrome in adults

lidocaine (Lidoderm, DermacinRx PHN Pak)

X X

milnacipran (Savella)X

pregabalin(Lyrica)

X X X XPartial onset seizures as adjunctive therapy

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Neuropathic Pain- Dosage and FormulationDrug Initial Dose Maximum Dose Availability

duloxetine(Cymbalta)

DPN: 60 mg dailyFibromyalgia: 30 mg dailyChronic musculoskeletal pain: 30 mg daily

60 mg daily 20 mg, 30 mg, 60 mg capsules

duloxetine (Irenka)

DPN: 60 mg dailyChronic musculoskeletal pain: 30 mg daily

60 mg daily 40 mg delayed-release capsules

gabapentin (Neurontin)

300 mg 3 times a day 3,600 mg/day (3 times daily);50 mg/kg/day (pediatrics)

100 mg, 300 mg, 400 mg capsules 600 mg, 800 mg tablets 250 mg/5 mL solution

gabapentin (Gralise)

300 mg/day 1,800 mg/day (once daily) 300 mg, 600 mg ER tablets 30-day starter pack

gabapentin enacarbil (Horizant)

600 mg/day for 3 days 600 mg twice daily 300 mg, 600 mg extended-release tablets

lidocaine (Lidoderm, DermacinRx PHN Pak)

Apply up to 3 patches to affected area once daily for up to 12 hours within a 24-hour period

--- 5% patch

milnacipran(Savella)

12.5 mg daily, titrated up to 50 mg twice daily over the course of 1 week

100 mg twice daily 12.5 mg, 25 mg, 50 mg, 100 mg tablets 4-week titration pack

pregabalin(Lyrica)

DPN: 150 mg/day in 3 divided doses PHN: 150 mg/day in 2 to 3 divided doses Fibromyalgia: 150 mg/day in 2 divided doses Neuropathic pain: 150 mg/day in 2 divided doses

DPN: 300 mg/day PHN: 300 to 600 mg/day Fibromyalgia: 300 to 450 mg/day Neuropathic Pain: 300 to 600 mg/day

25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, 300 mg capsules 20 mg/mL solution

22

Neuropathic Pain – Clinical Considerations

Drug Pediatric Pregnancy Renal Impairment Hepatic Impairment

duloxetine Not studied Category CCrCl < 30 mL/min: not

recommended

Contraindicated in severe hepatic impairment; avoid in heavy alcohol users or chronic liver disease

gabapentin

Indicated for seizures, but not

studied for neuropathic pain

indications

Category C(not evaluated for use

during pregnancy)

Dosage adjustments required; renal insufficiency not studied in pediatric

patients N/A

lidocaine Not studied Category B N/AContraindicated in severe hepatic impairment

milnacipran Not studied Category C Dosage adjustments requiredContraindicated in severe hepatic impairment; avoid in heavy alcohol users or chronic liver disease

pregabalin Not studied Category C Dosage adjustments required N/A

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Neuropathic Pain – Clinical Considerations

• Warnings

− Reports of suicidal behavior or ideation with antiepileptic drugs, including gabapentin and pregabalin

− Boxed warning for duloxetine and milnacipran (Savella) regarding the risk of suicide

• Major Drug Interactions

− SNRIs (duloxetine and milnacipran) are contraindicated in patients using with monoamine oxidase inhibitors (MAOIs)

− Risk of serotonin syndrome or neuroleptic malignant syndrome-like reactions with SNRIs is heightened with use of other serotonergic drugs

− Increased risk of bleeding when SNRIs used in combination with anticoagulants, including NSAIDs and aspirin

− Avoid use of lidocaine patches with Class I antiarrhythmics (e.g., tocainide and mexiletine) due to additive toxicity

• SNRIs, gabapentin, and pregabalin should be tapered over 1 week whenever possible

• Note that pregabalin (Lyrica) is a C-V controlled substance; some states now classify gabapentin as C-V as well due to postmarketingreports of abuse or misuse

• Professional guidelines suggest different first- and second-line treatments based on indication

• Factors for product selection may include:

• FDA-approved indication(s)

• Adverse effect profiles

• Ability to treat comorbidities (e.g., seizures, depression)

• Drug interactions and contraindications

24

Ophthalmics, Anti-Inflammatory/Immunomodulator

Ophthalmics, Anti-Inflammatory/Immunomodulator- Indications, Dosage, Formulation, and Clinical Considerations

cyclosporine (Restasis, Restasis Multidose) lifitegrast (Xiidra)

Indication

Increase tear production in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca (dry eye disease)

Treatment of signs and symptoms of dry eye disease in adults

Dosage 1 drop in each eye twice daily (12 hours apart) 1 drop in each eye twice daily (12 hours apart)

Availability

0.05% ophthalmic emulsion in 0.4 mL single-use, preservative-free containers (trays of 30 or 60)

Restasis Multidose: 5.5 mL of 0.05% ophthalmic emulsion in a 10 mL bottle (preservative-free)

5% ophthalmic emulsion in 0.2 mL single-use, preservative-free containers (carton of 60 single-use containers stored in foil pouches of 5 containers/pouch)

Mechanism of Action Immunomodulator; reduces ocular inflammation Lymphocyte function-associate antigen-1 (LFA-1) antagonist

Onset of Action 4-6 weeks Up to 12 weeks

Contraindications Known hypersensitivity to cyclosporine or excipients None

Common AdverseEffects

Ocular burning; conjunctival hyperemia, discharge, epiphora, eye pain, foreign body sensation, pruritus, stinging, and visual disturbances (blurring).

Instillation site irritation, dysgeusia, and decreased visual acuity

Age Range ≥ 16 years ≥ 17 years

Pregnancy Category C No data

Geriatrics No differences in safety and efficacy observed

26

Ophthalmics, Anti-Inflammatory/Immunomodulator- Guideline Updates

27

• No new guidelines since 2016

−Did not include lifitegrast (Xiidra)

Ophthalmic Antibiotics

Ophthalmic Antibiotics- IndicationsAntibiotic Class Drug Generic Indication(s) Age Range

Aminoglycosides

gentamicinointment/solution

XSuperficial ocular infections involving the conjunctiva or cornea All, except neonates

tobramycin solution(Tobrex)

XSuperficial ocular infections involving the conjunctiva or cornea ≥ 2 months

tobramycin ointment(Tobrex)

Treatment of external infections of the eye and its adnexa ≥ 2 months

Fluoroquinolones

besifloxacin(Besivance)

Bacterial conjunctivitis ≥ 1 year

ciprofloxacin solution(Ciloxan)

XBacterial conjunctivitis Corneal ulcers

≥ 1 year

ciprofloxacin oint(Ciloxan)

Bacterial conjunctivitis ≥ 2 years

gatifloxacin 0.5% (Zymaxid)

XBacterial conjunctivitis ≥ 1 year

levofloxacin 0.5% X Bacterial conjunctivitis ≥ 1 year

moxifloxacin 0.5% (Moxeza)

Bacterial conjunctivitis ≥ 4 months

moxifloxacin 0.5% (Vigamox)

XBacterial conjunctivitis Neonates to adults

ofloxacin(Ocuflox)

XBacterial conjunctivitis Corneal ulcers

≥ 1 year

29

Ophthalmic Antibiotics- IndicationsAntibiotic Class Drug Generic Indication(s) Age Range

Macrolides

azithromycin (AzaSite)

Bacterial conjunctivitis ≥ 1 year

erythromycin (Ilotycin)

X

Superficial ocular infections involving the conjunctiva or cornea For ophthalmia neonatorum due to Chlamydia trachomatis Prophylaxis of ophthalmia neonatorum due to Neisseria gonorrhoeae

Newborn infants to adults

Other

bacitracin X Superficial ocular infections involving the conjunctiva or cornea

bacitracin/polymyxin B XSuperficial ocular infections involving the conjunctiva or cornea

natamycin(Natacyn)

Fungal blepharitis, conjunctivitis, and keratitis Adults

neomycin/polymyxin B/ bacitracin

XBacterial conjunctivitis Superficial ocular infections

Adults

neomycin/polymyxin B/ gramicidin

XBacterial conjunctivitis Superficial ocular infections

Adults

polymyxin B/ trimethoprim(Polytrim)

X

Bacterial conjunctivitis BlepharoconjunctivitisSuperficial ocular infections

≥ 2 months

sulfacetamide(Bleph-10)

X

Bacterial conjunctivitis Superficial ocular infections Adjunctive therapy with systemic sulfonamide therapy for trachoma

≥ 2 months

30

Ophthalmic Antibiotics- Dosage and Formulation

Drug Dosage for Blepharitis or Conjunctivitis Dropper Dosage for Corneal Ulcers Availability

gentamicin ointment½ inch 2 to 3 times a day 3 mg/g ointment

3.5 g tube

gentamicin solution1 to 2 drops every 4 hours, up to 2 drops every hour for severe infections

0.3% solution 5 mL, 15 mL

tobramycin ointment (Tobrex)

½ inch 2 to 3 times a day up to every 3 to 4 hours; dosing based on severity of infection

3 mg/g ointment 3.5 g tube

tobramycin solution (Tobrex)

1 to 2 drops every 4 hours; in severe infections, 2 drops hourly until improvement, then taper

0.3% solution 5 mL

besifloxacin(Besivance)

1 drop 3 times daily 4 to 12 hours apart for 7 days 0.6% suspension 5 mL

ciprofloxacin solution (Ciloxan)

1 to 2 drops every 2 hours while awake for 2 days, then 1 to 2 drops every 4 hours while awake for 5 days

Day 1: 2 drops every 15 minutes for 6 hours, then every 30 minutes Day 2: 2 drops every hour Days 3–14: 2 drops every 4 hours

0.3% solution 5 mL

ciprofloxacin ointment (Ciloxan)

½ inch 3 times a day for 2 days, then ½ inch twice daily for 5 days

3 mg/g ointment 3.5 g tube

gatifloxacin 0.5% (Zymaxid)

Day 1: 1 drop every 2 hours (up to 8 times) while awake; Days 2–7: 1 drop given 2 to 4 times a day while awake

0.5% solution 2.5 mL

31



levofloxacin 0.5%

Days 1–2: 1 to 2 drops every 2 hours (up to 8 times) while awake; Days 3–7: 1 to 2 drops every 4 hours while awake (up to 4 times)

0.5% solution 5 mL

moxifloxacin 0.5% (Moxeza)

1 drop 2 times daily for 7 days 0.5% solution 3 mL

moxifloxacin 0.5% (Vigamox)

1 drop 3 times a day for 7 days 0.5% solution 3 mL

ofloxacin 0.3% (Ocuflox)

1 to 2 drops every 2 to 4 hours for 2 days; then 1 to 2 drops 4 times daily for 5 days

Days 1–2: 1 to 2 drops every 30 minutes, while awake; awaken at approximately 4 and 6 hours after retiring and instill 1 to 2 dropsDays 3-7: 1 to 2 drops hourly while awakeDays 7-9: through treatment completion: 1 to 2 drops 4 times daily

0.3% solution 5 mL, 10 mL

azithromycin (AzaSite)

1 drop in the affected eye(s) twice daily (8 to 12 hours apart) for the first 2 days then 1 drop daily for the next 5 days

1% solution 2.5 mL

erythromycin (Ilotycin)

½ inch to affected eye(s) up to 6 times daily 0.5% ointment 3.5 g tube

bacitracin½ inch every 3 to 4 hours for 7 to 10 days 500 units/g ointment

3.5 g tube

32



bacitracin/polymyxin BThin film every 3 to 4 hours for 7 to 10 days 500 units-10,000

units/g ointment 3.5 g tube

natamycin (Natacyn)1 drop every 1 to 2 hours, reduced to 6 to 8 times daily after the first 3 to 4 days

5% suspension 15 mL

neomycin/polymyxin B/ bacitracin

½ inch every 3 to 4 hours for 7 to 10 days depending on severity of infection

3.5 mg/g-10,000 units/g- 400 units/g ointment 3.5 g tube

neomycin/polymyxin B/ gramicidin

1 to 2 drops every 4 hours for 7 to 10 days; up to 2 drops every hour for severe infections

1.75 mg/mL- 10,000 units/mL-0.025 mg/mL solution 10 mL

polymyxin B/ trimethoprim (Polytrim)

1 drop every 3 hours up to 6 doses daily for 7 to 10 days

10,000 units/mL-1 mg/mL solution 10 mL

sulfacetamide½ inch 4 times daily and bedtime for 7 to 10 days The ointment may be used adjunctively with sulfacetamide solution

10% ointment 3.5 g tube

sulfacetamide(Bleph-10)

1 to 2 drops every 2 to 3 hours initially, while awake; less frequently at night for 7 to 10 days Dosing dependant on severity of infection

10% solution 5 mL, 15 mL

33

Ophthalmic Antibiotics- Guideline Updates

• No new guidelines

34

Ophthalmic Antibiotic-Steroid Combinations

Ophthalmic Antibiotic-Steroid Combinations- Indication, Dosage, Formulation, and AvailabilityNote: All products indicated for corticosteroid-responsive inflammatory ocular conditions for which a corticosteroid is indicated and where bacterial infection or a risk of bacterial infection exists.

Drug Ointment Dosage Dropper Dosage Availability Generic

0.1% dexamethasone/ 0.35% neomycin base/ 10,000 units polymyxin B sulfate (Maxitrol)

Apply every 3-4 hours 1-2 drops every 3-4 hours 5 mL suspension, 3.5 g ointment

X

0.1% dexamethasone/ 0.3% tobramycin (TobraDex)

½ inch up to 3 or 4 times daily 1-2 drops every 4-6 hours During the first 24-48 hours, the dosage may be increased to 1-2 drops every 2 hours

2.5, 5, and 10 mL suspension, 3.5 g ointment

X

0.05% dexamethasone/ 0.3% tobramycin (TobraDex ST)

1 drop every 4-6 hours; During the initial 24-48 hours, dosage may be increased to 1 drop every 2 hours

5 mL suspension

1% hydrocortisone/ 0.35% neomycin sulfate/ 10,000 units polymyxin B suspension

1-2 drops every 3-4 hours 7.5 mL suspension

X

1% hydrocortisone/ 0.35% neomycin base/ 400 units bacitracin zinc/ 10,000 units polymyxin B ointment

Apply every 3-4 hours 3.5 g ointment

X

0.5% loteprednol/ 0.3% tobramycin suspension (Zylet)

1-2 drops every 4-6 hoursDuring the first 24-48 hours, the dosage may be increased to 1-2 drops every 2 hours

5 and 10 mL suspension

36

Ophthalmic Antibiotic-Steroid Combinations- Indication, Dosage, Formulation, and AvailabilityNote: All products indicated for corticosteroid-responsive inflammatory ocular conditions for which a corticosteroid is indicated and where bacterial infection or a risk of bacterial infection exists.

Drug Ointment Dosage Dropper Dosage Availability Generic

1% prednisolone/ 0.3% gentamicin base suspension (Pred-G)

0.6% prednisolone/ 0.3% gentamicin base ointment (Pred-G S.O.P.)

½ inch 1-3 times daily 1 drop 2-4 times daily;During the first 24-48 hours, the dosage may be increased to 1 drop every hour

5 mL suspension

3.5 g ointment

0.23% prednisolone/ 10% sulfacetamide solution

0.2% prednisolone/ 10% sulfacetamide suspension (Blephamide)

0.2% prednisolone/ 10% sulfacetamide ointment (Blephamide S.O.P.)

½ inch up to 3 or 4 times daily 1-3 drops every 1-4 hours

5 and 10 mL solution

5 and 10 mL suspension

3.5 g ointment

X

37

Ophthalmic Antibiotic-Steroid Combinations- Guideline Updates


38

Ophthalmics for Allergic Conjunctivitis

Ophthalmics for Allergic Conjunctivitis- IndicationsDrug Class Drug Generic Indication(s) Age Range

Antihistamines

alcaftadine (Lastacaft) Prevention of itching of the eye due to allergic conjunctivitis ≥ 2 years

azelastine X Treatment of itching of the eye associated with allergic conjunctivitis ≥ 3 years

bepotastine (Bepreve) Treatment of ocular itching associated with allergic conjunctivitis ≥ 2 years

emedastine (Emadine) Temporary relief of the signs and symptoms of allergic conjunctivitis ≥ 3 years

epinastine (Elestat®) X Prevention of itching of the eye due to allergic conjunctivitis ≥ 3 years

ketotifen (Alaway OTC, Zaditor OTC)

XTemporary relief of itchy eyes due to pollen, ragweed, grass, animal hair, and dander ≥ 3 years

olopatadine (Patanol) X Treatment of the signs and symptoms of allergic conjunctivitis ≥ 3 years

olopatadine (Pataday) Treatment of ocular itching associated with allergic conjunctivitis ≥ 3 years

olopatadine (Pazeo) Treatment of ocular itching associated with allergic conjunctivitis ≥ 2 months

Mast Cell Stabilizers

cromolyn XTreatment of vernal keratoconjunctivitis, vernal conjunctivitis, and vernal keratitis ≥ 4 years

lodoxamide (Alomide)Treatment of vernal keratoconjunctivitis, vernal conjunctivitis, and vernal keratitis ≥ 2 years

nedocromil (Alocril) Treatment of itching associated with allergic conjunctivitis ≥ 3 years

40

Ophthalmics for Allergic Conjunctivitis- Dosage and Formulations

Drug Class Drug Dosage (in affected eye[s]) Availability

Antihistamines

alcaftadine (Lastacaft) 1 drop once daily 0.25% solution (3mL)

azelastine 1 drop twice daily 0.05% solution (6 mL)

bepotastine (Bepreve) 1 drop twice daily 1.5% solution (5, 10 mL)

emedastine (Emadine) 1 drop up to 4 times daily 0.05% solution (5 mL)

epinastine (Elestat) 1 drop twice daily 0.05% solution (5 mL)

ketotifen(Alaway OTC, Zaditor OTC)

1 drop twice daily at an interval of 8 to 12 hours 0.025% solution (Zaditor OTC: 5 mL; Alaway OTC: 10 mL)

olopatadine (Patanol) 1 drop twice daily at an interval of 6 to 8 hours 0.1% solution (5 mL)

olopatadine (Pataday) 1 drop once daily 0.2% solution (2.5 mL)

olopatadine (Pazeo) 1 drop once daily 0.7% solution (2.5 mL)

Mast Cell Stabilizers

cromolyn 1-2 drops 4-6 times daily 4% solution (10 mL)

lodoxamide (Alomide) 1-2 drops 4 times daily for up to 3 months 0.1% solution (10 mL)

nedocromil (Alocril) 1-2 drops twice a day 2% solution (5 mL)

41

Ophthalmics for Allergic Conjunctivitis- Guideline Updates


42

Ophthalmics, Anti-Inflammatories

Ophthalmics, Anti-Inflammatories- IndicationsDrug Class Drug Generic Indication(s)

Corticosteroids

dexamethasone (Maxidex)

• Treatment of corticosteroid-responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe

• Corneal injury

dexamethasone sodium phosphate

X


• Corneal injury

difluprednate (Durezol)• Treatment of inflammation and pain associated with ocular surgery• Treatment of endogenous anterior uveitis

fluorometholone (FML) XTreatment of corticosteroid-responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe

fluorometholone(FML Forte)

Treatment of corticosteroid-responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe

fluorometholone(FML S.O.P.)


fluorometholone acetate (Flarex)


loteprednol 0.5% gel, ointment (Lotemax)

Treatment of post-operative inflammation and pain following ocular surgery

loteprednol 0.5% suspension (Lotemax)


• Treatment of post-operative inflammation following ocular surgery

44

Ophthalmics, Anti-Inflammatories- IndicationsDrug Class Drug Generic Indication(s)

Corticosteroids

prednisolone acetate 1% (Omnipred, Pred Forte)

X• Treatment of corticosteroid-responsive inflammatory conditions of the palpebral

and bulbar conjunctiva, cornea, and anterior segment of the globe• Treatment of corneal injury (Omnipred)

prednisolone acetate 0.12% (Pred Mild)

Treatment of mild to moderate noninfectious allergic and inflammatory disorders of the lid, conjunctiva, cornea, and sclera (including chemical and thermal burns)

prednisolone sodium phosphate

X• Treatment of inflammatory conditions of the palpebral and bulbar conjunctiva,

cornea, and anterior segment of the globe• Corneal injury

rimexolone (Vexol)• Treatment of anterior uveitis• Treatment of post-operative inflammation after ocular surgery

Corticosteroids – Intravitreal

dexamethasone (Ozurdex)

• Treatment of macular edema following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO)

• Treatment of non-infectious uveitis affecting the posterior segment of the eye• Treatment of diabetic macular edema

fluocinolone 0.19 mg (Iluvien)

Treatment of diabetic macular edema in patients who have been previously treated with a course of corticosteroids and did not have a clinically significant rise in intraocular pressure

fluocinolone 0.59 mg (Retisert)

Treatment of chronic non-infectious uveitis affecting the posterior segment of the eye

triamcinolone acetonide (Triesence)

• Treatment of sympathetic ophthalmia, temporal arteritis, uveitis, and ocular inflammatory conditions unresponsive to topical corticosteroids

• Visualization during vitrectomy

45

Ophthalmics, Anti-Inflammatories- Indications

Drug Class Drug Generic Indication(s)

NSAIDs

bromfenac (Prolensa, BromSite)

X• Treatment of post-operative inflammation and reduction of ocular pain secondary to

cataract extraction/surgery

diclofenac X• Treatment of post-operative inflammation secondary to cataract extraction• Temporary relief of pain and photophobia in patients undergoing corneal refractive surgery

flurbiprofen (Ocufen) X Inhibition of intraoperative miosis

ketorolac 0.4% (Acular LS)

XReduction of ocular pain, burning, and stinging after corneal refractive surgery

ketorolac 0.45% (Acuvail)Treatment of pain and inflammation following cataract surgery

ketorolac 0.5%(Acular)

• Treatment of inflammation following cataract surgery• Temporary relief from ocular itching related to seasonal allergic conjunctivitis

nepafenac(Ilevro, Nevanac)

Treatment of pain and inflammation associated with cataract surgery

46

Ophthalmics, Anti-Inflammatories- Dosage and FormulationDrug Dosage Availability

dexamethasone 0.1% suspension (Maxidex)

Apply 1 to 2 drops to the conjunctival sac of the affected eye(s) every 4 to 6 hours; in severe disease, may administer drops hourly, tapering to discontinuation as the inflammation subsides

5 mL

dexamethasone sodium phosphate 0.1% solution

Apply 1 to 2 drops to the conjunctival sac of the affected eye(s) every hour during the day and every 2 hours at night; reduce frequency to every 4 hours once a favorable response occurs

5 mL

difluprednate 0.05% emulsion (Durezol)

Inflammation and pain with ocular surgery: Apply 1 drop to the conjunctival sac of the affected eye(s) 4 times daily beginning 24 hours after surgery and continuing for 2 weeks post-op, then twice daily for another week, then taper based on responseEndogenous anterior uveitis: Apply 1 drop to the conjunctival sac of the affected eye 4 times daily for 14 days followed by tapering, as clinically indicated

5 mL

fluorometholone 0.1% suspension (FML)

Apply 1 drop to the conjunctival sac of the affected eye(s) 2 to 4 times daily (may be used every 4 hours during initial 24 to 48 hours)

5, 10, 15 mL

fluorometholone 0.25% suspension (FML Forte)

Apply 1 drop to the conjunctival sac of the affected eye(s) 2 to 4 times daily (may be used every 4 hours during initial 24 to 48 hours)

5, 10 mL

fluorometholone 0.1% ointment (FML S.O.P.)

Apply half-inch ribbon to the conjunctival sac of the affected eye(s) 1 to 3 times daily (may be used every 4 hours during initial 24 to 48 hours)

3.5 g

fluorometholone acetate 0.1% suspension (Flarex)

Apply 1 to 2 drops to the conjunctival sac of the affected eye(s) 4 times daily (may be used as 2 drops every 2 hours during initial 24 to 48 hours)

5 mL

loteprednol 0.5% gel (Lotemax) Apply 1 to 2 drops into the conjunctival sac of the affected eye(s) 4 times daily starting 24 hours after surgery for 2 weeks

5 g

loteprednol 0.5% ointment (Lotemax)

Apply half-inch ribbon into the conjunctival sac of the affected eye(s) 4 times daily starting 24 hours after surgery for 2 weeks

2.5 g

47


loteprednol 0.5% suspension (Lotemax)

Anti-inflammatory: Apply 1 to 2 drops 4 times daily (up to every hour during the first week, if necessary) Cataract surgery: Apply 1 to 2 drops 4 times a day starting 24 hours after surgery for 2 weeks

5, 10, 15 mL

prednisolone acetate 1% suspension (Omnipred, Pred Forte)

Omnipred: Apply 2 drops to the affected eye(s) 4 times daily Pred Forte: Apply 1 to 2 drops into the conjunctival sac of the affected eye(s) 2 to 4 times daily (may increase dosing frequency during the initial 24 to 48 hours if needed)

1, 5, 10, 15 mL

prednisolone acetate 0.12% suspension (Pred Mild)

Apply 1 to 2 drops to the conjunctival sac of the affected eye(s) 2 to 4 times daily (may increase dosing frequency during the initial 24 to 48 hours if needed)

5, 10 mL

prednisolone sodium phosphate 1% solution

Apply 1 to 2 drops to the conjunctival sac of the affected eye(s) every hour during the day and every 2 hours at night; reduce frequency once a favorable response occurs

10 mL

rimexolone 1% solution (Vexol) Anterior uveitis: Apply 1 to 2 drops every hour (while awake) for 1 week, then every 2 hours for the second week, then taper off until resolved Ocular surgery: Apply 2 drops 4 times a day starting 24 hours after surgery for a duration of 2 weeks

5, 10 mL

dexamethasone (Ozurdex) Implanted intravitreally by healthcare provider 0.7 mg implant

fluocinolone (Iluvien) Surgically implanted inferior to the optic disc and posterior to the equator of the eye; designed to release drug over 36 months

0.19 mgimplant

fluocinolone (Retisert) Surgically implanted into posterior segment of the affected eye(s); designed to release drug over 30 months

5 g

triamcinolone acetonide(Triesence)

Inflammation: 4 mg intravitreallyVisualization: 1 to 4 mg intravitreally

40 mg/mL vial

48


bromfenac 0.07% solution (Prolensa)

Apply 1 drop once daily to affected eye(s) starting 1 day prior to surgery, continued on the day of surgery and through the first 14 days post-op

3 mL

bromfenac 0.075% solution (BromSite)

Apply 1 drop to affected eye (s) twice daily starting 1 day prior to surgery, continued on the day of surgery and through the first 14 days post-op

5 mL

bromfenac 0.09% solution Apply 1 drop to affected eye(s) twice daily starting 24 hours post-op for 2 weeks 1.7, 2.5 mL

diclofenac 0.1% solution Cataract surgery: Apply 1 drop to affected eye(s) 4 times daily starting 24 hours post-op for 2 weeks Refractive surgery: Apply 1 to 2 drops within 1 hour prior to surgery, then 1 to 2 drops 15 minutes post-op, then 1 to 2 drops 4 times a day for up to 3 days

2.5, 5 mL

flurbiprofen sodium 0.03% solution (Ocufen)

Beginning 2 hours before surgery, instill 1 drop to affected eye(s) every 30 minutes for a total of 4 drops 2.5 mL

ketorolac tromethamine 0.4% solution (Acular LS)

Apply 1 drop to affected eye(s) 4 times a day for up to 4 days as needed for burning or stinging following refractive surgery

5 mL

ketorolac tromethamine 0.45% solution (Acuvail)

Apply 1 drop to affected eye(s) twice daily beginning 1 day prior to surgery and continuing through the first 2 weeks post-op

0.4 mL single-use vials

ketorolac tromethamine 0.5% solution (Acular)

For cataracts: 1 drop 4 times per day beginning 24 hours after surgery and continuing through the first 2 weeks of the postoperative period For allergic conjunctivitis: 1 drop to affected eye(s) 4 times a day

5 mL

nepafenac 0.3% suspension (Ilevro)

Apply 1 drop to affected eye(s) once daily beginning 1 day prior to surgery; continue on the day of surgery, and through the first 2 weeks post-op; Administer an additional drop 30 to 120 minutes prior to surgery

1.7, 3 mL

nepafenac 0.1% suspension (Nevanac)

Apply 1 drop to affected eye(s) 3 times daily beginning 1 day prior to surgery; continue on the day of surgery, and through the first 2 weeks post-op

3 mL

49

Ophthalmics, Anti-Inflammatories- Guideline Updates


50

Ophthalmics, Glaucoma Agents

Ophthalmics, Glaucoma Agents- Indications

Drug Class Drug Generic Reduction of Elevated IOP in Ocular Hypertension

Reduction of Elevated IOP in Open-Angle Glaucoma

Miotics, Topical pilocarpine X X X

Sympathomimetics

apraclonidine (Iopidine) 0.5%only

X* X*

brimonidine (Alphagan P) 0.2% only

X X

Beta-blockers

betaxolol (Betoptic S) 0.5%only

X X

carteolol X X X

levobunolol (Betagan) X X X

metipranolol X X X

timolol (Betimol, Timoptic, Timoptic XE, Timoptic in Ocudose)

X X X

timolol long-acting (LA) (Istalol)

X X

Carbonic Anhydrase Inhibitors

brinzolamide (Azopt) X X

dorzolamide (Trusopt) X X X

52

IOP = intraocular pressure* indicated as short-term adjunctive therapy in patients on maximally tolerated therapies

Ophthalmics, Glaucoma Agents- Indications

Drug Class Drug Generic Reduction of Elevated IOP in Ocular Hypertension

Reduction of Elevated IOP in Open-Angle Glaucoma

Combination Products

brimonidine/brinzolamide (Simbrinza)

X X

brimonidine/timolol (Combigan)

X** X**

dorzolamide/timolol(Cosopt, Cosopt PF)

X X** X**

Prostaglandin Analogs

bimatoprost (Lumigan)0.03% only X X

latanoprost (Xalatan) X X X

tafluprost (Zioptan) X X

travoprost (Travatan Z) X X X

unoprostone (Rescula) X X

53

IOP = intraocular pressure** indicated as adjunctive or replacement therapy

Ophthalmic Glaucoma Agents- Dosage and AvailabilityDrug Strength Dosage Availability

pilocarpine1%, 2%, and 4%

Adults, adolescents, and children ≥ 2 years: 1 drop up to 4 times daily Infants and Children < 2 years: 1 drop of the 1% solution 3 times daily

15 mL

apraclonidine (Iopidine) 0.5% 1 to 2 drops 3 times daily 5, 10 mL

apraclonidine (Iopidine)1%

1 drop 1 hour prior to laser surgery; 1 drop immediately following a laser surgical procedure

5, 10 mL

brimonidine (Alphagan P) 0.1% and 0.15% 1 drop 3 times daily 5, 10, 15 mL

brimonidine 0.2% 1 drop 3 times daily 5, 10, 15 mL

betaxolol 0.5% 1 to 2 drops twice daily 5, 10, 15 mL

betaxolol (Betoptic S) 0.25% 1 drop twice daily 10, 15 mL

carteolol 1% 1 drop twice daily 5, 10, 15 mL

levobunolol (Betagan) 0.5% 1 to 2 drops once or twice daily 5, 10, 15 mL

metipranolol 0.3% 1 drop twice daily 5 mL

timolol(Betimol, Timoptic, Timoptic XE, Timoptic in Ocudose)

0.25% and 0.5% 1 drop twice daily

0.25% – 5, 10 mL 0.5% – 5, 10, 15 mL Ocudose (0.25%, 0.5%): 0.2 mL x 60 blister packs

timolol gel forming solution (Timoptic XE)

0.25% and 0.5% 1 drop daily 0.25% – 5 mL 0.5% – 5 mL

timolol long-acting (LA) (Istalol)

0.5% 1 drop daily 2.5, 5 mL

54

Ophthalmic Glaucoma Agents- Dosage and Availability

Drug Strength Dosage Availability

brinzolamide (Azopt) 1% 1 drop 3 times daily 10, 15 mL

dorzolamide (Trusopt) 2% 1 drop 3 times daily 10 mL

brimonidine/brinzolamide (Simbrinza)

0.2%/1% 1 drop 3 times daily8 mL

brimonidine/timolol (Combigan)

0.2%/0.5% 1 drop twice daily 5, 10, 15 mL

dorzolamide/timolol(Cosopt, Cosopt PF)

2%/0.5% 1 drop twice dailyCosopt: 10 mL Cosopt PF: 0.2 single-dose vials (60/carton)

bimatoprost (Lumigan) 0.01% and 0.03% 1 drop daily in evening 2.5, 5, 7.5 mL

latanoprost (Xalatan) 0.005% 1 drop daily in evening 2.5 mL

tafluprost (Zioptan) 0.0015% 1 drop daily in evening Pouches with 10 x 0.3 mL single-usecontainers

travoprost (Travatan Z) 0.004% 1 drop daily in evening 2.5, 5 mL

unoprostone (Rescula) 0.15% 1 drop twice daily 5 mL

55

Ophthalmic Glaucoma Agents- Guideline Update


56

Otic Antibiotics

Otic Antibiotics- IndicationsDrug Generic Indication(s)

ciprofloxacin 0.2% solution (Cetraxal) XAcute otitis externa due to susceptible isolates of Pseudomonas aeruginosa or Staphylococcus aureus in pediatrics (age ≥ 1 year) and adults

ciprofloxacin/dexamethasone (Ciprodex Otic)

• Acute otitis media in pediatric patients (age ≥ 6 months) with tympanostomy tubes • Acute otitis externa in pediatric (age ≥ 6 months), adult, and elderly patients

ciprofloxacin 0.3%/fluocinolone acetonide 0.025% solution (Otovel)

Acute otitis media in pediatric patients (age ≥ 6 months) with tympanostomy tubes due to S. aureus, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and P. aeruginosa

ciprofloxacin 0.2%/hydrocortisone 1% suspension (Cipro HC Otic)

Acute otitis externa in adult and pediatric patients (≥ 1 year) due to Pseudomonas aeruginosa, Staphylococcus aureus, and Proteus mirabilis.

neomycin 3.3 mg/colistin 3 mg/thonzonium 0.05%/ hydrocortisone 1% per mL (Coly-mycin S)

• Treatment of superficial bacterial infections of the external auditory canal in adult and pediatric patients

• Treatment of infections of mastoidectomy and fenestration cavities in adults and pediatrics

neomycin sulfate/polymyxin B/hydrocortisone (Cortisporin)

X

• Treatment of superficial bacterial infections of the external auditory canal in adults and pediatric patients (≥ 2 years)

• Treatment of infections of mastoidectomy and fenestration cavities (suspension only) in adults and pediatric patients (≥ 2 years)

ofloxacin X

• Otitis externa in adults and pediatric patients (≥ 6 months) • Chronic suppurative otitis media in patients ≥ 12 years with perforated tympanic membranes • Acute otitis media in pediatric patients (≥ 1 year) with tympanostomy tubes

58

Otic Antibiotics- Dosage and Formulations

Drug Dosage (in affected ear[s])Duration

(days)Age

PackageSize

ciprofloxacin 0.2% solution (Cetraxal) 1 single-use vial twice daily7 ≥ 1 year old

14 vials (0.25 mL)

ciprofloxacin/ dexamethasone (Ciprodex Otic)

4 drops twice daily 7 ≥ 6 months old

7.5 mL bottle

ciprofloxacin 0.3% / fluocinolone acetonide 0.025% solution (Otovel)

1 single-use vial twice daily7 ≥ 6 months old

14 vials (0.25 mL)

ciprofloxacin 0.2% / hydrocortisone 1% suspension (Cipro HC Otic)

3 drops to affected ear twice daily 7 ≥ 1 year old

10 mL bottle

neomycin 3.3 mg/ colistin 3 mg/ thonzonium 0.05%/ hydrocortisone 1% per mL (Coly-mycin S)

Peds: 3-4 drops 3-4 times dailyAdults: 4-5 drops 3-4 times daily

10 None specified5 mL bottle

neomycin sulfate / polymyxin B / hydrocortisone (Cortisporin)

Peds: 3 drops 3-4 times dailyAdults: 4 drops 3-4 times daily

10 ≥ 2 years old10 mL bottle

ofloxacin for otitis externa 6 months – < 13 years: 5 drops daily≥ 13 years: 10 drops daily

7≥ 6 months old 5, 10 mL

bottles; 0.25 mL

single-use vials

ofloxacin for otitis media in pediatric patients 5 drops twice daily 10 1-12 years old

ofloxacin for chronic suppurative otitis media 10 drops twice daily 14 ≥ 12 years old

59

Otic Antibiotics- Guideline Update


60

Otic Anti-Infectives and Anesthetics

Otic Anti-Infectives and Anesthetics- Indication, Dosage, and Availability

Drug Strength Indication Dosage (in affected ear[s]) Availability

acetic acid 2% For the treatment of otitis externa 4-6 drops every 2-3 hours 15 mL

acetic acid / hydrocortisone (Acetasol HC)

2%/1% For the treatment of otitis externa

Day 1: Use cotton wick, moisten with 3-5 drops every 4-6 hoursSubsequent days: Remove wick and use 3-5 drops 3-4 times per day

10 mL

acetic acid in aluminum acetate

2% For the treatment of otitis externa 4-6 drops every 2-3 hours 60 mL

62

Otic Anti-Infectives and Anesthetics- Guideline Update


63

Antihistamines, Minimally Sedating-

Antihistamines, Minimally Sedating- Indications

Drugs Rx OTC Generic Indications

acrivastine/pseudoephedrine (PSE) (Semprex D)

X Relief of symptoms associated with seasonal allergic rhinitis (AR) in adults and children 12 years of age and older

cetirizine tablets, oral liquid X X X • Temporary relief of symptoms due to hay fever or other respiratory allergies (sneezing; runny nose; itchy, watery eyes; itchy throat or nose) in adults and children 2 years of age and older

• Relief of symptoms associated with seasonal AR due to allergens such as ragweed, grass, and tree pollens in adults and children 2 years of age and older

• Relief of symptoms associated with perennial AR due to allergens such as dust mites, animal dander, and molds in adults and children 6 months of age and older

• Treatment of uncomplicated skin manifestations of chronic idiopathic urticaria (CIU) in adults and children 6 months of age and older

cetirizine ODT(Zyrtec Allergy ODT)

X • Temporary relief of symptoms of upper respiratory allergies (sneezing; runny nose; itchy, watery eyes; itchy throat or nose) in adults and children 6 months of age and older

• Relief of itching due to urticaria in patients in adults and children 6 months and older

cetirizine/PSE (Zyrtec-D OTC 12 Hour)

X X Temporary relief of symptoms associated with sinusitis, allergic rhinitis, and other upper respiratory allergies (nasal congestion, sneezing; runny nose; itchy, watery eyes; itchy throat or nose) in adults and children 12 years and older

desloratadine (Clarinex, Clarinex Redi-Tabs)

X X • Relief of nasal and non-nasal symptoms of seasonal AR in patients 2 years of age and older • Relief of nasal and non-nasal symptoms of perennial AR in patients 6 months of age and older • Symptomatic relief of pruritus, reduction in the number of hives, and size of hives in patients with CIU 6

months of age and older

desloratadine/PSE(Clarinex-D 12-Hour)

X Relief of nasal and non-nasal symptoms of seasonal AR, including nasal congestion in adults and children 12 years of age and older

fexofenadine (Allegra)

X X Relief of symptoms associated with hay fever or other upper respiratory allergies (sneezing; runny nose; itchy, watery eyes; itchy throat or nose) in adults and children 12 years and older

65

Antihistamines, Minimally Sedating- Indications

Drugs Rx OTC Generic Indications

fexofenadine (Allegra Oral Suspension)


fexofenadine ODT (Allegra ODT)


fexofenadine/PSE(Allegra-D 12 and 24 Hour)

X X Relief of symptoms associated with seasonal AR in adults and children 12 years of age and older

levocetirizine (Xyzal) X X • Relief of symptoms associated with seasonal AR in adults and children 2 years of age and older • Relief of symptoms associated with perennial AR in adults and children 6 months of age and older • Treatment of uncomplicated skin manifestations of CIU in adults and children 6 months of age and older

levocetirizine (Xyzal Allergy 24HR)

X Temporary relief of runny nose, sneezing, itchy/watery eyes, and itching of the nose or throat due to hay fever or other respiratory allergies in patients 6 to 64 years of age

loratadine (Alavert, Claritin) X X Temporary relief of symptoms due to hay fever or other respiratory allergies in adults and children 6 years of age and older (syrup for ages 2 years and older)

loratadine ODT (Alavert Quick Dissolving, Claritin Redi-Tabs, Claritin Liqui-Gels)

X X Temporary relief of symptoms due to hay fever or other respiratory allergies in adults and children 6 years of age and older

loratadine chewable tablet, syrup (Children’s Claritin)

X Temporary relief of symptoms due to hay fever or other respiratory allergies in patients 2 years of age and older

loratadine/PSE (Alavert Allergy & Sinus, Claritin-D 12 Hour, Claritin-D 24 Hour)

X X Temporary relief of symptoms (sinus nasal congestion, runny nose, sneezing, itchy nose, watery eyes) due to common cold, hay fever, or other respiratory allergies or sinusitis in adults and children 12 years of age and older

66

Antihistamines, Minimally Sedating- Dosage and Formulations

Drug Adult Dose Pediatric Dose Availability OTC/Rx

acrivastine/PSE (Semprex-D) 1 capsule 4 times daily --- 8 mg/60 mg capsules Rx

cetirizine (Zyrtec, Zyrtec ODT) 5 or 10 mg daily; 65 years and older: 5 mg daily

6 – 11 years: 5 or 10 mg daily 2 – 5 years: 2.5 – 5 mg (½ – 1 tsp or 5

mg chewable tab) daily 12 – 23 months: may increase to 2.5

mg (½ tsp) every 12 hrs6 – 11 months: 2.5 mg (½ tsp) daily

10 mg tablets 1 mg/mL syrup

Rx

5 mg and 10 mg tablets; 5 mg and 10 mg chewable tablets; 1 mg/mL syrup; 10 mg ODT; 10 mg liquid filled

capsules

OTC

cetirizine/PSE (Zyrtec-D 12 Hr) 1 tablet twice daily --- 5 mg/120 mg ER (12 hour) tablets OTC

desloratadine (Clarinex, Clarinex Redi-Tabs)

5 mg daily 6 – 11 years: 2.5 mg (1 tsp) daily 12 months – 5 years: 1.25 mg (½ tsp)

daily 6 – 11 months: 1 mg (2 mL) daily

5 mg tablets; 0.5 mg/mL syrup; 2.5 mg and 5 mg ODT Rx

desloratadine/PSE (Clarinex-D 12-Hour)

1 tablet every 12 hours --- 2.5 mg/120 mg ER (12 hour) tablets Rx

fexofenadine (Allegra) 60 mg twice daily or 180 mg daily

--- 60 mg and 180 mg tablets OTC

fexofenadine oral suspension (Allegra Oral Suspension)

60 mg (2 tsp) twice daily 2 – 11 years: 30 mg (1 tsp) twice daily 6 mg/mL oral suspension OTC

fexofenadine ODT (Allegra ODT) 60 mg twice daily 6 – 11 years: 30 mg twice daily on an empty stomach

30 mg orally disintegrating tablet OTC

67

Antihistamines, Minimally Sedating- Dosages and FormulationsDrug Adult Dose Pediatric Dose Availability OTC/Rx

fexofenadine/PSE 12-hour (Allegra-D 12 hour)

1 tablet twice daily --- 60 mg /120 mg ER (12 hour) tablets OTC

fexofenadine/pseudoephedrine 24-hour (Allegra-D 24 hour)

1 tablet once daily on an empty stomach (ages ≥ 12 years)

--- 180 mg /240 mg ER (24 hour) tablets OTC

levocetirizine (Xyzal, Xyzal Allergy 24HR)

5 mg once daily in the evening; OTC – 2.5 mg (1/2 tablet) may be appropriate for less severe

symptoms

6 – 11 years: 2.5 mg (1/2 tablets or 1 tsp) once daily in the evening

6 months – 5 years (Rx only): 1.25 mg (½ tsp) once daily in the evening

Xyzal: 5 mg tablets 0.5 mg/mL oral solution

Rx

Xyzal Allergy 24HR: 5 mg tablets 0.5 mg/mL oral solution

OTC

loratadine (Claritin) 10 mg daily 6 – 11 years: 5 mg every 12 hours or 10 mg (2 tsp) syrup once daily

2 – 5 years: 5 mg (1 tsp) syrup once daily

10 mg tablets; 5mg and 10 mg ODT; 1 mg/mL syrup (for children); 10 mg

liquid filled capsules

OTC

loratadine chewable tablet (Children’s Claritin)

10 mg (2 chew tablets) daily 6 – 11 years: 10 mg (2 chew tablets) daily 2 – 5 years: 5 mg (1 chew tablet) daily

5 mg chewable tablets OTC

loratadine/PSE 12-hour 1 tablet twice daily --- 5 mg/120 mg ER (12 hour) tablets OTC

loratadine/pseudoephedrine 24-hour

1 tablet daily --- 10 mg/240 mg ER (24 hour) tablets OTC

68

Antihistamines, Minimally Sedating-Guideline Update


69

Histamine2-Receptor Antagonists

Histamine2-Receptor Antagonists- IndicationsDrug Generic Indication

cimetidine (Tagamet, Tagamet HB 200) X • Short-term treatment of active DU and benign GU up to 8 weeks • Long-term prophylaxis of DU at a reduced dose after ulcer healing for up to 5 years • Treatment of pathological hypersecretory states (e.g., Zollinger-Ellison syndrome, systemic mastocytosis,

multiple endocrine adenomas) • Treatment of EE and GERD for up to 12 weeks • Prevention of upper GIB in critically ill patients • Treatment and prevention of heartburn, acid indigestion, or sour stomach (OTC only)

famotidine (Pepcid, Pepcid AC, Pepcid Suspension)

X • Short-term treatment of active DU and benign GU for up to 8 weeks • Maintenance therapy of DU after ulcer healing • Short-term relief of symptomatic esophagitis, GERD, and pathological hypersecretory conditions • Treatment and prevention of heartburn, acid indigestion, or sour stomach (OTC only)

famotidine, calcium carbonate, magnesium hydroxide (Pepcid Complete, Tums Dual Action)

X Relief of heartburn associated with acid indigestion or sour stomach (OTC only)

nizatidine (Axid) X • Treatment (up to 8 weeks) and maintenance of DU at a reduced dose after ulcer healing for up to 1 year • Treatment of active, benign GU up to 8 weeks • Treatment of EE and GERD up to 12 weeks • Treatment and prevention of heartburn, acid indigestion, or sour stomach (OTC only)

ranitidine (Zantac, Zantac EFFERdose) X • Short-term treatment of active DU for up to 8 weeks • Short-term treatment of active, benign GU for up to 6 weeks • Maintenance therapy of DU and GU at a reduced dose after ulcer healing for up to 1 year • Treatment of pathological hypersecretory conditions • Treatment and maintenance of EE • Treatment of GERD • Treatment and prevention of heartburn, acid indigestion, or sour stomach (OTC only)

71DU = duodenal ulcer; EE = erosive esophagitis; GU = gastric ulcer; GERD = gastroesophageal reflux disease; GIB = gastrointestinal bleed

Histamine2-Receptor Antagonists- Dosage and FormulationDrug Dosing Availability

cimetidine (Tagamet, Tagamet HB 200)

Active DU: 800 mg at bedtime OR 300 mg 4 times daily with meals and at bedtime OR 400 mg twice daily Maintenance DU: 400 mg at bedtime Erosive esophagitis/GERD in adults and adolescents: 800 mg twice daily OR 400 mg 4 times daily Benign GU: 800 mg at bedtime OR 300 mg 4 times daily with meals and at bedtime Hypersecretory conditions: Start at 300 mg 4 times daily with meals and at bedtime up to 2,400 mg daily Pyrosis (heartburn), acid dyspepsia (acid indigestion), or sour stomach prophylaxis for patients ≥ 12 years: 200 mg (OTC only) up to 30 minutes prior to meals that are known to cause symptoms once daily or twice daily. Pyrosis (heartburn), acid dyspepsia (acid indigestion), or sour stomach treatment for patients ≥ 12 years: 200 mg (OTC only) once daily or twice daily

Prescription: 300 mg/5 mL solution 200, 300, 400, 800 mg tablet

OTC: 200 mg tablet

famotidine (Pepcid, Pepcid AC)

Active DU: 40 mg at bedtime OR 20 mg twice daily Maintenance DU: 20 mg at bedtime GERD: 20 mg twice daily Erosive esophagitis: 20 or 40 mg twice daily GU: 40 mg at bedtimeHypersecretory conditions: Start at 20 mg every 6 hours up to 160 mg every 6 hours Pyrosis (heartburn), acid dyspepsia (acid indigestion), or sour stomach prophylaxis for patients ≥ 12 years: 10 mg to 20 mg (OTC only) given 15 minutes to 1 hour prior to eating a meal which is expected to cause symptoms. No more than 2 tablets daily. Pyrosis (heartburn), acid dyspepsia (acid indigestion), or sour stomach treatment for patients ≥ 12 years: 10 mg to 20 mg (OTC only) given 1 to 2 times per day. Pediatric GERD: 0.5 mg/kg/dose once daily (patients < 3 months of age); 0.5 mg/kg/dose twice daily (patients ages 3 months to 1 yr); 1 mg/kg/day in 2 divided doses ≤ 40 mg twice daily (patients ages 1 to 16 years of age) Peptic ulcer: 0.5 mg/kg/day at bedtime or in 2 divided doses ≤ 40 mg daily (patients ages 1 to 16 years)

Prescription: 40 mg/5 mL suspension 20, 40mg tablet

OTC: 20 mg chewable tablet 10 mg gelcap 10, 20 mg tablet

72

Histamine2-Receptor Antagonists- Dosage and FormulationDrug Dosing Availability

famotidine, calcium carbonate, magnesium hydroxide (Pepcid Complete, Tums Dual Action)

Relief of heartburn associated with acid indigestion or sour stomach for patients ≥ 12 years: chew 1 tablet and swallow (Do not use > 2 tablets in 24 hours)

OTC: 10 mg famotidine, 800 mg calcium carbonate, 165 mg magnesium hydroxide chewable tablet

nizatidine (Axid) Active DU or GU: 300 mg at bedtime OR 150 mg twice daily Maintenance DU: 150 mg at bedtime GERD: 150 mg twice daily Erosive esophagitis: 150 mg twice daily

Prescription: 15 mg/mLsolution 150, 300 mg capsule

ranitidine (Zantac) Active DU: 300 mg after the evening meal or at bedtime OR 150 mg twice daily Maintenance DU: 150 mg at bedtime GERD: 150 mg twice daily Erosive esophagitis: 150 mg 4 times daily Maintenance erosive esophagitis: 150 mg twice daily GU: 150 mg twice daily Maintenance GU: 150 mg at bedtime Hypersecretory conditions: Start at 150 mg twice daily up to 6 g daily in patients with severe disease Pyrosis (heartburn), acid dyspepsia (acid indigestion), or sour stomach prophylaxis for patients ≥ 12 years: 75—150 mg (OTC only) immediately before eating or up to 60 minutes before consuming food and beverages that may cause heartburn. Do not take > 2 tablets daily. Pyrosis (heartburn), acid dyspepsia (acid indigestion), or sour stomach treatment for patients ≥ 12 years: 75—150 mg (OTC only) once or twice daily

Pediatric (1 month to 16 years) Treatment DU and GU: 2 to 4 mg/kg twice daily up to 300 mg daily Maintenance DU and GU: 2 to 4 mg/kg once daily up to 150 mg daily GERD and Erosive esophagitis: 5 to 10 mg/kg daily, given in 2 divided doses

Prescription: 15 mg/mL syrup 150, 300 mg tablet 150, 300 mg capsule

OTC: 75, 150 mg tablet

73

Histamine2-Receptor Antagonists- Guideline Update


74

Glucocorticoids, Oral

Glucocorticoids, Oral- Indication, Dosage, and Availability

Drug Generic Dosage Availability

betamethasone (Celestone Soluspan) Adults and adolescents: 0.6 to 7.2 mg per day depending on specific condition treated Children: 0.02 to 0.3 mg/kg/day in 3 or 4 divided doses, depending on the specific condition

Oral solution: 0.6 mg/5 mL

budesonide (Entocort EC) X Treatment of mild to moderate active Crohn’s disease: Adults: 9 mg once daily in the morning for up to 8 weeks. Repeated 8 week courses can be given for recurring episodes of active disease; Children 8 to 17 years who weigh >25 kg: 9 mg orally once daily for up to 8 weeks, followed by 6 mg once daily for 2 weeks Maintenance of clinical remission of mild to moderate Crohn’s disease: Adults: 6 mg once daily for up to 3 months; treatment for > 3 months has not been shown to be beneficial

Enteric-coated capsule: 3 mg

budesonide extended-release (Uceris) Induction of remission in adults with active, mild to moderate ulcerative colitis: 9 mg orally once daily in the morning with or without food for up to 8 weeks

Extended-release capsule: 9 mg

cortisone X 25-300 mg per day or on alternate days, depending on specific condition treated Tablet: 25 mg

deflazacort (Emflaza) Treatment of Duchenne muscular dystrophy (DMD): patients 5 years of age and older: 0.9 mg/kg/day; discontinue gradually when administered for more than a few days; tablets may be crushed and mixed with applesauce; the dose should be consumed immediately; the oral suspension should be mixed with 3 to 4 ounces of juice (except grapefruit juice) or milk and administered immediately; unused drug should be discarded 1 month after opening the container

Tablet: 6 mg, 18 mg, 30 mg, 36 mg; Oral suspension: 22.75 mg/mL

76

Glucocorticoids, Oral- Indication, Dosage, and AvailabilityDrug Generic Dosage Availability

dexamethasone (Dexpak, Dexamethasone Intensol, Locort 7-Day, Locort 11-Day, ZonaCort 7-Day, ZonaCort11-Day)

X Adults: 0.75 to 9 mg per day, in 2 to 4 divided doses, depending on specific condition treated; children: 0.03-0.3 mg/kg per day, in 2 to 4 divided doses, depending on the specific condition treated; for Locort 7-Day, Locort 11-Day, ZonaCort 7 and ZonaCort 11 only – 0.02 to 0.3 mcg/kg/day in 3 to 4 divided doses

Tablet: 0.5 mg, 0.75 mg, 1 mg, 1.5 mg, 2 mg, 4 mg, and 6 mg; Dexpak: 1.5 mg tablets in 6, 10, and 13 day supply (taperpak); Elixir: 0.5 mg/ml; Oral solution: 0.5 mg/5 mL; Intensol oral solution: 1 mg/mL; Locortand ZonaCort: 1.5 mg tablets; 27 tablets in 7 day supply and 41 tablets in 11 day supply blister packs

hydrocortisone (Cortef) X Adults: 20-240 mg per day, in 2 to 4 divided doses, depending on specific condition treated; Children: 2-8 mg/kg per day, in 3 to 4 divided doses, depending on specific condition treated

Tablet: 5 mg, 10 mg, 20 mg

methylprednisolone (Medrol)

X Adults: General dosage: 4-48 mg per day in 4 divided doses; Hypercalcemia associated with certain types of cancer: 32-80 mg per day; Tuberculous meningitis: 48-64 mg per day; gradually taper after 1 to 2 weeks and stop by 4 to 6 weeks Children: 0.5-1.7 mg/kg per day in 2 to 4 divided doses, depending on specific condition treated

Tablet: 2, 4, 8, 16, 32; 4 mg in 21-tablet dosepak

prednisolone (Flo-Pred, Millipred, Orapred, Orapred ODT, Pediapred, Prelone)

X Adults: 5-60 mg per day in 3 to 4 divided doses, depending on specific condition treated; Children: 0.14-2 mg/kg per day in 3 to 4 divided doses

Tablet: 5 mg; 5 mg in 6 day 21-tablet and 12 day 48-tablet dose packs; Oral liquid: 5 mg/5 mL, 10 mg/5mL, 15 mg/5 mL, 20 mg/5 mL, and 25 mg/5 mL; Orally disintegrating tablet: 10, 15, and 30 mg

77

Glucocorticoids, Oral- Indication, Dosage, and Availability

Drug Generic Dosage Availability

prednisone X Primary or secondary adrenocortical insufficiency: Adults: 5 mg each morning, 2.5 mg each evening; Children: 4-5 mg/m2 given 1 to 4 times per day; Congenital adrenal hyperplasia: Adults: 2.5-5 mg once daily at bedtime; Children: 12-13 mg/m2 given in 2 to 3 divided doses; Other indications to modify the body’s immune response: Adults: 5-100 mg daily, depending on specific diagnosis and patient response; Children: 0.05-2 mg/kg per day, depending on specific diagnosis and patient response

Tablet: 1, 2.5, 5, 10, 20, and 50 mg; Oral solution: 5 mg/5 mL

prednisone DR (Rayos)

Adults and Children: Initial dose: 5 mg administered once daily; Maintenance dose: Use lowest dosage that will maintain an adequate clinical response, depending on specific condition treated; Swallow tablet whole

Tablet: 1, 2, and 5 mg

prednisone (Prednisone Intensol)

Adults and Children: 5-60 mg per day, depending on specific condition treated Oral solution: 5 mg/mL (contains30% alcohol)

78

Glucocorticoids, Oral- Guidelines

• American Academy of Neurology (AAN), 2016

− Treatment of Duchenne muscular dystrophy

− Prednisone

• Prednisone should be made available for improving strength and pulmonary function

• Prednisone may be provided for reducing scoliosis surgery needs, improving timed motor function, and delaying cardiomyopathy onset by 18 years of age

− Deflazacort (Emflaza)

• Deflazacort may be provided for delaying age at loss of ambulation and improving timed motor function and strength

• Deflazacort may be offered for reducing scoliosis surgery needs, delaying cardiomyopathy onset, pulmonary function improvement, and increasing survival at 5–15 years of follow-up

− Prednisone versus deflazacort (Emflaza)

• Deflazacort and prednisone may be equivalent in motor function improvement

• Prednisone may be linked to greater weight gain in the first years of therapy versus deflazacort

• Deflazacort may be connected with a greater risk of cataracts compared to prednisone

http://www.neurology.org/content/86/5/465.full.pdf+html79

Smoking Cessation

Smoking Cessation- Indication

Drug Generic Indication

Nicotine Replacement Therapies (NRT)

nicotine chewing gum; buccal OTC (Nicorette) X For use as an aid to smoking cessation treatment

nicotine lozenge OTC (Commit, Nicorette) X For use as an aid to smoking cessation treatment

nicotine inhaler (Nicotrol Inhaler) For use as an aid to smoking cessation treatment

nicotine nasal spray (Nicotrol NS) For use (≤ 6 continuous months) as an aid to smoking cessation for the relief of nicotine withdrawal symptoms as a part of a comprehensive behavioral smoking cessation program

nicotine transdermal OTC (Nicoderm CQ) X For use as an aid to smoking cessation as part of comprehensive behavioral smoking cessation program

nicotine transdermal OTC (Habitrol) For use as an aid to smoking cessation treatment

Non-Nicotine Replacement Therapies (Non-NRT)

bupropion sustained release tablets (Zyban) X For use as an aid to smoking cessation treatment

varenicline tablets (Chantix) For use as an aid to smoking cessation treatment

81

Smoking Cessation- Dosage and FormulationDrug Dosage in Adults Special Dosing Considerations Availability

nicotine chewing gum; buccal OTC (Nicorette)

Adults smoking < 25 cigarettes daily: 2 mg; adults smoking ≥ 25 cigarettes daily: 4 mg; max of 24 pieces daily; dosage is dependent on time to first cigarette: if first cigarette is 30 minutes or later after awakening = 2 mg; if first cigarette is within 30 minutes of awakening = 4 mg

12-Week Schedule • Weeks 1 to 6:1 piece every 1 to 2 hours • Weeks 7 to 9: 1 piece every 2 to 4 hours • Weeks 10 to 12: 1 piece every 4 to 8 hours

Chew 1 piece of gum at a time; during first 6 weeks of therapy: chew at least 9 pieces per day for improved outcomes

2 mg and 4 mg chewing gum

nicotine lozenge OTC (Nicorette, Commit)

Dosage is dependent on time to first cigarette: if first cigarette is 30 minutes or later after awakening = 2 mg; if first cigarette is within 30 minutes of awakening = 4 mg; max of 20 lozenges daily; max of 5 lozenges in 6 hours

12-Week Schedule: • Weeks 1 to 6: 1 lozenge every 1 to 2 hours • Weeks 7 to 9: 1 lozenge every 2 to 4 hours • Weeks 10 to 12: 1 lozenge every 4 to 8 hours Do not chew or swallow lozenge; use beyond 6 months is not recommended; gradually reduce dose over 12 weeks; during first 6 weeks of therapy: use at least 9 lozenges/day

2 mg and 4 mg lozenges

nicotine inhaler (Nicotrol Inhaler)

Initial: 24 to 64 mg (6 to 16 cartridges) daily for up to 12 weeks

After 3 months, gradually reduce dose over 6 to 12 weeks; use > 6 months is not recommended

10 mg/cartridge

nicotine nasal spray (Nicotrol NS)

Initial: 1 or 2 doses per hour, as needed, whenever patient feels the need to smoke; maintenance: 8 to 40 doses daily for 3 to 6 months; (1 dose = 2 sprays total or 1 spray in each nostril)

Min 8 mg daily or 16 sprays; max 5 doses or 10 sprays per hour; max 40 mg daily or 80 sprays (slightly less than a ½ bottle)

Box of four 10 mL bottles (10 mg/mL) (Each 10 mL bottle contains 200 applications and each actuation delivers approximately 0.5 mg nicotine)

82

Smoking Cessation- Dosage and FormulationDrug Dosage in Adults Special Dosing Considerations Availability

nicotine transdermal OTC (Nicoderm CQ)

Adults smoking ≥ 10 cigarettes daily: start with 21 mg daily for 6 weeks then decrease to 14 mg daily for 2 weeks then 7 mg daily for 2 weeks; adults smoking < 10 cigarettes daily: start with 14 mg daily for 6 weeks then decrease to 7 mg daily for 2 weeks

Patch should be applied to intact skin; after transdermal nicotine has been in place for 24 hours, remove and apply a new patch to an alternate site; do not reuse the same sites for at least 1 week

Transdermal patch: 7 mg/24 hr; 14 mg/24 hr; 21 mg/24 hr; 21 mg –14 mg – 7 mg/24 hr system kit

nicotine transdermal OTC (Habitrol)

Adults smoking ≥ 10 cigarettes daily: start with 21 mg daily for 4 weeks then decrease to 14 mg daily for 2 weeks then 7 mg daily for 2 weeks; adults smoking < 10 cigarettes daily: start with 14 mg daily for 6 weeks then decrease to 7 mg daily for 2 weeks

Applied to intact skin; after transdermal nicotine has been in place for 24 hrs, remove and apply a new patch to an alternate site; do not reuse the same site for at least 1 week

Transdermal patch: 7 mg/24 hr; 14 mg/24 hr; 21 mg/24 hr; 21 mg –14 mg – 7 mg/24 hr system 8 week kit

Non-Nicotine Replacement Therapies (Non-NRTs)

bupropion SR (Zyban) Initiate 1 to 2 weeks prior to quit date; first 3 days: 150 mg daily; maintenance dose: 150 mg twice daily, at least 8 hours apart

For smoking cessation, doses > 300 mg/day should not be used

150 mg SR tablets (avail. as Buproban)

varenicline tablets (Chantix)

Initiate 1 week prior to stop smoking date or, alternatively, begin varenicline dosing and then quit smoking between days 8 and 35 of treatment: 0.5 mg once daily on days 1 to 3; 0.5 mg twice daily on days 4 to 7; 1 mg twice daily for a total of 12 weeks

An additional 12 weeks of treatment is recommended for successful quitters to increase long-term abstinence; for patients unable or unwilling to quit abruptly, a gradual approach may be used: begin dosing and reduce smoking by 50% within the first 4 weeks, by an additional 50% in the next 4 weeks, and continue reducing with the goal of complete abstinence by 12 weeks; then continue treatment for an additional 12 weeks, for a total of 24 weeks of treatment

Reduce the dose in patients with severe renal impairment (estimated creatinine clearance < 30 mL/min). Starting dose should be 0.5 mg daily with titration to a maximum of 0.5 mg twice daily; An additional attempt of therapy is recommended for those who fail to quit smoking or relapse when factors contributing to the failed attempt have been addressed; For patients unable or unwilling to quit abruptly, a gradual approach may be used; however, patients may attempt to quit smoking sooner than the recommended dosing schedule

0.5 mg and 1 mg tablets; Packages include: Starting Month Pack; Pack includes 1 card of 0.5 mg x 11 tablets and 3 cards of 1 mg x 14 tablets; Continuing Month Pack Pack includes 4 cards of 1 mg x 14 tablets

83

Smoking Cessation- Guideline Update


84

Antiparkinson’s Agents

Antiparkinson’s Agents- IndicationsTherapeutic Class Drug Generic Parkinson’s Disease Drug-induced

EPS RLS

Anticholinergics benztropine X X X (except TD)

trihexyphenidyl X X X

Dopa decarboxylase Inhibitor carbidopa (Lodosyn) X X (only as adjunct to

levodopa/carbidopa)

Dopamine precursor/dopa decarboxylase inhibitor levodopa/carbidopa (Sinemet) X X

levodopa/carbidopa SR (Sinemet CR) X X

levodopa/carbidopa extended-release (Rytary) X

levodopa/carbidopa-oral disintegrating (ODT) X X

levodopa/carbidopa enteral suspension (Duopa) X (advanced PD)

MAO-B inhibitors rasagiline (Azilect) X X

safinamide (Xadago) X (only as adjunct to

levodopa/carbidopa)

selegiline (Eldepryl) X X (only as adjunct to

levodopa/carbidopa)

selegiline – oral disintegrating (ODT) (Zelapar) X (only as adjunct to

levodopa/carbidopa) 86

Antiparkinson’s Agents- IndicationsTherapeutic Class Drug Generic Parkinson’s Disease Drug-

induced EPS RLS

Dopamine agonists bromocriptine (Parlodel) X X (only as adjunct to

levodopa/carbidopa)

pramipexole (Mirapex) X X X

pramipexole ER (Mirapex ER) X X

ropinirole (Requip) X X X

ropinirole ER (Requip XL) X X

rotigotine (Neupro) X X

COMT inhibitors entacapone (Comtan) X X (only as adjunct to

levodopa/carbidopa)

tolcapone (Tasmar) X X (only as adjunct to

levodopa/carbidopa)

Dopamine precursor/dopa decarboxylase inhibitor/COMT inhibitor levodopa/carbidopa/ entacapone (Stalevo)

X X

Other: gabapentin prodrug gabapentin enacarbil (Horizant) X

Other: N-Methyl-D-aspartate (NMDA) receptor type amantadine X X X

87

EPS = extrapyramidal symptoms; RLS = restless legs syndrome; TD = tardive dyskinesia; PD= Parkinson’s Disease

Antiparkinson’s Agents- Dosage and FormulationTherapeutic Class Drug Initial Dose Maximum Daily

Dose Recommended Dosing Schedule

Availability

Parkinson’s Disease

Anticholinergics benztropine 0.5 mg 6 mg 1 to 2 times daily 0.5 mg, 1 mg, 2 mg tablets

trihexyphenidyl 1 mg 15 mg 3 to 4 times daily 2, 5 mg tablets; 2 mg/5 mL elixir

Dopamine precursor carbidopa (Lodosyn) 25 mg 200 mg 3 to 4 times daily 25 mg tablets

Dopamine precursor / dopa decarboxylase inhibitor

levodopa/carbidopa (Sinemet) 25/100 mg 200 mg carbidopa 3 to 4 times daily 10/100 mg, 25/100 mg, 25/250 mg tablets

levodopa/carbidopa SR (Sinemet CR) 50/200 mg 200 mg carbidopa twice daily 25/100 mg, 50/200 mg sustained-release tablets

levodopa/carbidopa ER (Rytary) 23.75/95 mg 612.5 mg carbidopa

3 times daily 23.75/95 mg, 36.25/145 mg, 48.75/195 mg, 61.25/245 mg extended-release capsules

levodopa/carbidopa ODT 25/100 mg 200 mg carbidopa 3 to 4 times daily 10/100 mg, 25/100 mg, 25/250 mg orally disintegrating tablets

levodopa/carbidopa enteral suspension (Duopa)

Based on current levodopa dose

(see label package insert for

details)

2000 mg levodopa (500 mg

carbidopa)

Infuse over 16 hours using the CADD®-

Legacy 1400 portable infusion pump

20 mg/ 4.63 mg/mL enteral suspension in a 100 mL cassette

88

Antiparkinson’s Agents- Dosage and Formulation

Therapeutic Class Drug Initial Dose Maximum Daily Dose Recommended Dosing Schedule Availability

MAO-B Inhibitors rasagiline (Azilect) 0.5 to 1 mg 1 mg once daily 0.5 mg, 1 mg tablets

safinamide (Xadago) 50 mg 100 mg once daily 50 mg, 100 mg tablets

selegiline (Eldepryl) 5 mg 10 mg twice daily with breakfast and lunch 5 mg capsules; 5 mg tablets (generic only)

selegiline ODT (Zelapar)

1.25 mg 2.5 mg once daily before breakfast & without liquid

1.25 mg disintegrating tablets

rotigotine (Neupro) Early stage: 2 mg Advanced stage: 4 mg

Early stage: 6 mg Advanced stage: 8 mg

once daily 1 mg, 2 mg, 3 mg, 4 mg, 6 mg, 8 mg patch

Dopamine agonists

bromocriptine (Parlodel)

1.25 mg 100 mg twice daily with meals 2.5 mg tablets (SnapTabs); 5 mg caps

pramipexole (Mirapex) 0.125 mg 4.5 mg 3 times daily 0.125 mg, 0.25 mg, 0.5 mg, 0.75 mg, 1 mg, 1.5

mg tablets

pramipexole ER (Mirapex ER)

0.375 mg 4.5 mg once daily; swallow tablet whole and must not be chewed, crushed, or

divided

0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3 mg, 3.75

mg, 4.5 mg tablets

ropinirole (Requip) 0.25 mg 24 mg 3 times daily 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg, 5 mg

tablets

ropinirole ER (Requip XL)

2 mg 24 mg once daily as a whole tablet and must not be chewed, crushed, or divided

2 mg, 4 mg, 6 mg, 8 mg, 12 mg tablets

89

Antiparkinson’s Agents- Dosage and Formulation

Therapeutic Class Drug Initial Dose Maximum Daily Dose Recommended Dosing Schedule

Availability

COMT inhibitors entacapone (Comtan) 200 mg 1,600 mg 200 mg with each dose of levodopa/carbidopa

200 mg tablets

tolcapone (Tasmar) 100 mg 600 mg 3 times daily 100 mg tablets

Dopamine precursor/dopa decarboxylase inhibitor/COMT inhibitor

levodopa/carbidopa/ entacapone (Stalevo)

1 tablet Based on maximum dose of entacapone: 50,75,100, 125 and 150 mg: 8 tablets/day;

Based maximum dose of carbidopa: 200 mg: 6

tablets/day

every 3 to 5 hours 50/12.5/200 mg, 75/18.75/200 mg, 100/25/200 mg, 125/31.25/200 mg, 150/37.5/200 mg, 200/50/200 mg tablets

NMDA-Type amantadine 100 mg 400 mg 100 mg twice 100 mg capsules; 100 mg tablets; 50 mg/5 mL syrup

Restless Leg Syndrome

Dopamine agonists pramipexole (Mirapex) 0.125 mg 0.75 mg once daily 2 to 3 hours prior to bedtime

0.125 mg, 0.25 mg, 0.5 mg, 0.75 mg, 1 mg, 1.5 mg tablets

ropinirole (Requip) 0.25 mg 4 mg once daily 1 to 3 hours prior to bedtime

0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg, 5 mg tablets

rotigotine (Neupro) 1 mg 3 mg once daily 1 mg, 2 mg, 3 mg, 4 mg, 6 mg, 8 mg patch

Gabapentin prodrug gabapentin enacarbil (Horizant)

600 mg 1,200 mg once daily with food at 5 PM 300 mg, 600 mg tablets

90

Antiparkinson’s Agents- Guideline Update


91

Sedative Hypnotics

Sedative Hypnotics- Indications

Drug Generic Short-term Treatment of Insomnia Treatment of Insomnia Treatment of Non-24-hour Sleep-wake Disorder

doxepin (Silenor) X

estazolam X X

eszopiclone (Lunesta) X X

flurazepam X X

quazepam (Doral) X X

ramelteon (Rozerem) X

suvorexant (Belsomra) X

tasimelteon (Hetlioz) X

temazepam (Restoril) X X

triazolam (Halcion) X X

zaleplon (Sonata) X X

zolpidem (Ambien) X X

zolpidem sublingual (Edluar) X

zolpidem sublingual (Intermezzo) X X (Middle of the night

awakening)

zolpidem (Zolpimist) X

zolpidem ER (Ambien CR) X X

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Sedative Hypnotics- Dosage and FormulationDrug Bedtime Dose Dose Adjustment Availability

doxepin (Silenor) 6 mg: take 30 minutes before bedtime & not within 3 hrs of meal

Elderly: begin with 3 mg and increase to 6 mg, if required; 3 mg if clinically indicated for individual patients

Tablet: 3 mg, 6 mg

estazolam 1 mg to 2 mg Elderly, underweight, or debilitated: 0.5 mg to 1 mg Tablet: 1 mg, 2 mg

eszopiclone (Lunesta) 1 mg Dosing can be raised to 2 mg or 3 mg if clinically indicated; elderly: total dose should not exceed 2 mg; severe hepatic impairment: should not exceed 2 mg; concurrent use with strong CYP 3A4 inhibitor: should not exceed 2 mg

Tablet: 1 mg, 2 mg, 3 mg

flurazepam Women±: 15 mg Men: either 15 mg or 30 mg

Women: May increase to 30 mg Elderly and debilitated patients: 15 mg

Capsule: 15 mg, 30 mg

quazepam (Doral) Initial dose: 7.5 mg May be increased to 15 mg if necessary for efficacy Tablet: 15 mg

ramelteon (Rozerem) 8 mg: 30 minutes prior to bedtime --- Tablet: 8 mg

suvorexant (Belsomra) 10 mg: within 30 minutes of bedtime, with at least 7 hours remaining before awakening

Dose can be increased to 20 mg if the 10 mg dose is well-tolerated but not effective

Tablet: 5 mg, 10 mg, 15 mg, 20 mg

tasimelteon (Hetlioz) 20 mg --- Cap: 20 mg

temazepam (Restoril) 7.5 mg to 30 mg Elderly and debilitated: start at 7.5 mg initially until individual responses are determined

Capsule: 7.5 mg, 15 mg, 22.5 mg, 30 mg

triazolam (Halcion) 0.125 mg to 0.5 mg Elderly or debilitated: 0.125 mg to 0.25 mg Tab: 0.125 mg, 0.25 mg

zaleplon (Sonata) 10 mg to 20 mg; may also use 5 mg for low weight individuals; may be taken immediately before bedtime or after the patient has gone to bed and has experienced difficulty falling asleep

Elderly, low-weight, or hepatic impairment: 5 mg to 10 mg; concurrent use of cimetidine: initial dose: 5 mg; mild to moderate hepatic impairment: 5 mg

Capsule: 5 mg, 10 mg

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Sedative Hypnotics- Dosage and FormulationDrug Bedtime Dose Dose Adjustment Availability

zolpidem (Ambien, Edluar, Zolpimist)

Men: 5 mg or 10 mg Women: 5 mg; use the lowest dose effective for patient; should be taken immediately before bedtime with at least 7–8 hours remaining before the planned time of awakening The 5 mg dose can be increased to 10 mg, if needed, but the higher dose is more likely to impair next morning driving and other activities that require full alertness; the total dose should not exceed 10 mg once daily.

Elderly, debilitated, or hepatic insufficiency: 5 mg once daily in both men and women immediately before bedtime; concurrent CNS depressants: dosage adjustment may be necessary

Tablet: 5 mg, 10 mg; Sublingual Tablet: 5 mg, 10 mg; Oral Spray: 5 mg

zolpidem ER (Ambien CR)

Men: 6.25 mg or 12.5 mg Women: 6.25 mg; use the lowest dose effective for patient; should be taken immediately before bedtime with at least 7 to 8 hours remaining before the planned time of awakening The 6.25 mg dose can be increased to 12.5 mg, if needed, but the higher dose is more likely to impair next morning driving and other activities that require full alertness; the total dose should not exceed 12.5 mg daily.

Elderly, debilitated, or hepatic insufficiency: 6.25 mg once daily in both men and women immediately before bedtime; concurrent CNS depressants: dosage adjustment may be necessary

Tablet: 6.25 mg, 12.5 mg

zolpidem sublingual (Intermezzo)

Men: 3.5 mg Women: 1.75 mg Take if there is more than 4 hours remaining before planned time of waking

Elderly, hepatic insufficiency, concurrent CNS depressants: 1.75 mg

Sublingual Tablets: 1.75 mg, 3.5 mg

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Sedative Hypnotics- Guideline Update

• American Academy of Sleep Medicine (AASM), 2017− Recommends that pharmacotherapy should be used to treat patients who failed to respond to cognitive behavioral therapy

− Recommendation (versus no treatment):− Sleep onset insomnia: zaleplon, triazolam, and ramelteon

− Sleep maintenance insomnia: suvorexant and doxepin

− Sleep onset and sleep maintenance insomnia: eszopiclone, zolpidem, temazepam

• Not recommend: trazodone, tiagabine, OTC medications, supplements (e.g., diphenhydramine, tryptophan, melatonin), or herbal products (e.g., valerian)

• American College of Physicians (ACP), 2016− Management of chronic insomnia disorder in adults

− Cognitive behavioral therapy initial treatment for chronic insomnia disorder pharmacological therapy

− FDA has approved medications for short-term use (4 to 5 weeks), long-term use not recommended, re-evaluate if insomnia does not remit within 7 - 10 days

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Antihyperuricemics

Antihyperuricemics- Indications

Drug Generic Indication

allopurinol (Zyloprim) X • Management of patients with signs and symptoms of primary or secondary gout (acute attacks, tophi, joint destruction, uric acid lithiasis, and/or nephropathy)

• Management of patients with leukemia, lymphoma, and malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels

• Management of patients with recurrent calcium oxalate calculi whose daily uric acid excretion exceeds 800 mg/day in male patients and 750 mg/day in female patients

colchicine tablet (Colcrys)

X • Gout flares – treatment and prevention in adults • Management of familial Mediterranean fever in adults and children ages ≥ 4 years

colchicine capsule (Mitigare)

X Prophylaxis of gout flares in adults

febuxostat (Uloric) Chronic management of hyperuricemia in patients with gout

lesinurad (Zurampic) In combination with a xanthine oxidase inhibitor, for the treatment of hyperuricemia associated with gout in patients who have not achieved target serum uric acid levels with xanthine oxidase inhibitor monotherapy

pegloticase (Krystexxa)

Treatment of chronic gout in adult patients refractory to conventional therapy

probenecid X Treatment of hyperuricemia associated with chronic gout or secondary to other causes

probenecid / colchicine

X Treatment of chronic gouty arthritis when complicated by frequent, recurrent, acute attacks of gout

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Antihyperuricemics- Dosage and FormulationDrug Initial Dose Titration Dose Adjustments/ Comments Availability

allopurinol 100 mg daily To reduce the possibility of flare-up of acute gouty attacks start at 100 mg/day, increased by 100 mg weekly until serum urate ≤ 6 mg/dL; Maximum daily dose is 800 mg; Mild gout: 200–300 mg per day; Moderate to severe tophaceous gout: 400–600 mg per day

Renal Impairment CrCl 10-20 mL/min: 200 mg daily CrCl < 10 mL/min: 100 mg/day CrCl < 3 mL/min: interval between dosing may also need lengthened

100 mg, 300 mg tablets

febuxostat (Uloric)

40 mg daily If serum uric acid > 6 mg/dL after 2 weeks, increase to 80 mg daily

Can be taken without regard to food or antacid use

40 mg, 80 mg tablets

lesinurad (Zurampic)

200 mg orally once daily in the AM at the same time as a xanthine oxidase inhibitor

--- Administer with food and water and at the same time as a xanthine oxidase inhibitor

200 mg tablets

pegloticase (Krystexxa)

8 mg administered as an IV infusion every 2 weeks

--- --- 8 mg/mL in a 2 mL single-use vial

probenecid 250 mg twice daily for 1 week, then 500 mg twice daily

Dose may be increased by 500 mg increments/day every 4 weeks; Maximum dose is 2 gm per day

Administer with food or antacids to minimize GI adverse effects

500 mg tablet

probenecid / colchicine

1 tablet daily for 1 week, then 1 tablet twice daily

If tolerated and if symptoms are not controlled or the 24-hour uric acid excretion is not > 700 mg, increase by 1 tablet/day every 4 weeks; most patients do not need > 4 tablets daily; continue for 6 months once serum uric acid concentrations are within normal limits; thereafter, dose may be decreased by 1 tablet/day every 6 months

Do not initiate combination therapy until an acute gout attack has been resolved; if a patient is controlled on therapy and an acute attack occurs, the maintenance dosage may be continued

0.5 mg/500 mg tablet

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Antihyperuricemics- Dosage and FormulationDrug Initial Dose Titration Dose Adjustments/ Comments Availability

colchicine tablet (Colcrys)

Gout Flare Treatment: 1.2 mg at the first sign of a flare, then 0.6 mg 1 hour later; maximum dose is 1.8 mg over 1 hr

--- Gout Flare Treatment: Renal (CrCl < 30 mL/min) or Severe Hepatic Insufficiency: do not repeat treatment for 2 weeks; consider alternative therapy for patients requiring repeated courses Hemodialysis: 0.6 mg once and do not repeat more than once every 2 weeks

0.6 mg tablet; administer orally without regard to meals

Gout Flare Prevention: 0.6 mg once or twice daily in adults and adolescents (> 16 years); maximum daily dose is 1.2 mg

Gout Flare Prevention: Renal (CrCl < 30mL/min): 0.3 mg daily; monitor dose increases closely Hemodialysis: 0.3 mg twice weekly with close monitoring Severe Hepatic Impairment: consider dose reduction and monitor for adverse effects

FMF: Adults and children > 12 years: 1.2-2.4 mg/ day Ages 6 - 12 years: 0.9-1.8 mg/day Ages 4 to 6 years: 0.3-1.8 mg/day

FMF: Give total daily dose in 1 or 2 divided doses; increase or decrease the dose as indicated and as tolerated in increments of 0.3 mg/day, not to exceed the maximum recommended daily dose

FMF: Renal Insufficiency: For CrCl of 30 to 80 mL/min, dose reduction may be necessary For CrCl < 30 mL/min including dialysis: 0.3 mg daily and monitor for adverse effects when increasing dose Severe Hepatic Impairment: consider dose reduction and monitor for adverse effects

colchicine capsule (Mitigare)

0.6 mg once or twice daily; maximum daily dose is 1.2 mg

--- Renal and hepatic insufficiency: Dose reduction or alternatives should be considered in patients with severe renal or hepatic impairment

0.6 mg capsule; administer orally without regard to meals

100

Antihyperuricemics- Guideline Update

• American College of Physicians (ACP), 2017

−Management of acute and recurrent gout

−Acute gout

− Corticosteroids, NSAIDs, or colchicine recommended

− Corticosteroids first-line therapy; safer, low-cost, and as effective as NSAIDs

−Does not promote 1 NSAID over another

−Does not recommend starting long-term (≥ 12 months) urate lowering therapy in most patients after and initial gout attack or in patients with infrequent attacks (< 2 attacks per year)

− Patients with ≥ 2 attacks per year or those with problematic gout should consider the benefits/risks of medication before starting therapy

−Allopurinol (300 mg daily) and febuxostat (40 mg daily) are equally efficacious at decreasing serum urate levels

− Reduces the risk for acute gout attacks after 1 year; therapy does not reduce the risk within the first 6 months

− Prophylactic low-dose colchicine or NSAID therapy reduces the risk for acute attacks when starting urate lowering therapy

− Continuing therapy for > 8 weeks was more effective than shorter durations

− Pegloticase and lesinurad were not included in recommendation (stating unlikely be prescribed by PCP)

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Bile Salts

Bile Salts- Indications, Dosage, and Formulation

Drug Indication Dosage Availability

chenodiol (Chenodal)

Dissolve gallstones in patients with radiolucent stones in well-opacifying gallbladders, in whom selective surgery would be undertaken except for the presence of increased surgical risk due to systemic disease or age

13 to 16 mg/kg/day in 2 divided doses, AM and PM, starting with 250 mg twice daily for the first 2 weeks and increasing by 250 mg daily each week until recommended or maximum tolerated dose is reached; dosages < 10 mg/kg/day are not recommended-they are usually ineffective and may increase the risk of cholecystectomy

250 mg tablets

cholic acid (Cholbam)

Treatment of bile acid synthesis disorders due to single enzyme defects; adjunctive treatment of peroxisomal disorders including Zellweger spectrum disorders in patients who exhibit manifestations of liver disease, steatorrhea, or complications from decreased fat soluble vitamin absorption; limitation of use: the safety and effectiveness of cholic acid on extrahepatic manifestations of bile acid synthesis disorders due to SEDs or PDs including Zellweger spectrum disorders have not been established

10 to 15 mg/kg once daily or in 2 divided doses with food, in pediatric patients and adults (detailed weight-based dosing in number of capsules/day provided in prescribing information); a 10% increase in the recommended dosage may be needed in patients with newly diagnosed, or a family history of, familial hypertriglyceridemia due to poor absorption; the recommended dosage in patients with concomitant familial hypertriglyceridemia is 11 to 17 mg/kg once daily or in 2 divided doses with food, adjust based on clinical response; should not be crushed or chewed; capsules may be opened with the contents mixed in infant formula, breast milk, or soft food if patient is unable to swallow

50 mg, 250 mg capsules

obeticholic acid (Ocaliva)

Treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA (defined as a trial of at least 1 year), or as a single therapy in adults unable to tolerate UDCA; this indication is approved under accelerated approval based on a reduction in alkaline phosphatase (ALP); an improvement in survival or disease-related symptoms has not been established; continued approval for this indication may be contingent upon results of confirmatory trials

5 mg taken orally once daily with or without food; after 3 months, if an inadequate reduction in ALP and/or total bilirubin has not been achieved, and therapy is tolerated, the dose can be increased to 10 mg once daily (maximum dose), if tolerated; detailed dosing recommendations are provided in the prescribing information for management of select intolerable adverse effects and use in patients with moderate to severe hepatic impairment

5 mg, 10 mg tablets

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Bile Salts- Indications, Dosage, and Formulation

Drug Generic Indication Dosage Availability

ursodiol (URSO 250) X Treatment of patients with primary biliary cirrhosis 13 to 15 mg/kg/day in 2 to 4 divided doses with food

250 mg tablets

ursodiol (URSO Forte) X Treatment of patients with primary biliary cirrhosis 13 to 15 mg/kg/day in 2 to 4 divided doses with food; scored tablets can be broken in half to provide recommended dosage

500 mg tablets

ursodiol USP (Actigall) X Dissolve gallstones in patients with radiolucent, noncalcified gallbladder stones < 20 mm in greatest diameter in whom elective cholecystectomy would be undertaken except for the presence of increased surgical risk; prevent gallstone formation in obese patients experiencing rapid weight loss

Gallstone dissolution: 8 to 10 mg/kg/day in 2 to 3 divided doses; prevent gallstone formation in obese patients experiencing rapid weight loss: 300 mg twice daily

300 mg capsules

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Bile Salts- Guideline Update

• American Association for the Study of Liver Diseases (AASLD) Guidelines, 2009

− Primary Biliary Cholangitis

− Ursodiol plays a key role in the treatment of primary biliary cirrhosis/cholangitis

− Role of obeticholic acid was not addressed as it was not available during guideline development

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washington pharmacy advisory committee meeting · 11/15/2017 · acute myeloid leukemia (aml)...

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