Washington Pharmacy Advisory Committee Meeting · 11/15/2017 · Acute Myeloid Leukemia (AML)...
Transcript of 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
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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)
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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
Bone Marrow Transplant (BMT)
Peripheral Blood
Progenitor Cell Collection &
Therapy
Hematopoietic Syndrome of Acute
Radiation Syndrome
Severe Chronic Neutropenia
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 --- --- --- --- ---
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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
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
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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
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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
Bone Marrow Transplant (BMT)
Peripheral Blood Progenitor Cell Collection and
Therapy
Hematopoietic Syndrome of
Acute Radiation Syndrome
Severe Chronic Neutropenia
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
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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
• Substitute for red blood cell (RBC) transfusion in patients who require immediate correction of anemia
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
• Substitute for red blood cell (RBC) transfusion in patients who require immediate correction of anemia
• 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
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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
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Erythropoiesis Stimulating Proteins- Clinical Considerations
• 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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Erythropoiesis Stimulating Proteins- Clinical Considerations
• 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
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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
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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
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Ophthalmics, Anti-Inflammatory/Immunomodulator- Guideline Updates
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• 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
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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
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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
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Ophthalmic Antibiotics- Dosage and Formulation
Drug Dosage for Blepharitis or Conjunctivitis Dropper Dosage for Corneal Ulcers Availability
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
Ophthalmic Antibiotics- Dosage and Formulation
Drug Dosage for Blepharitis or Conjunctivitis Dropper Dosage for Corneal Ulcers Availability
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
• No new guidelines
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
• No new guidelines
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
• Treatment of corticosteroid-responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe
• 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.)
Treatment of corticosteroid-responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe
fluorometholone acetate (Flarex)
Treatment of corticosteroid-responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe
loteprednol 0.5% gel, ointment (Lotemax)
Treatment of post-operative inflammation and pain following ocular surgery
loteprednol 0.5% suspension (Lotemax)
• Treatment of corticosteroid-responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the globe
• 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
Ophthalmics, Anti-Inflammatories- Dosage and FormulationDrug Dosage Availability
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
Ophthalmics, Anti-Inflammatories- Dosage and FormulationDrug Dosage Availability
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
• No new guidelines
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
• No new guidelines
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
• No new guidelines
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
• No new guidelines
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)
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 2 years and older
fexofenadine ODT (Allegra ODT)
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 6 years and older
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
• No new guidelines
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
• No new guidelines
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
• No new guidelines
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
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Antiparkinson’s Agents- Guideline Update
• No new guidelines
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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
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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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