imipenem/cilastatin (i-me-pen-em/sye-la-stat-in) Primaxin

 Indications

Treatment of: Lower respiratory tract infections, Urinary

tract infections, Abdominal infections, Gynecologic

infections, Skin and skin structure infections, Bone and

joint infections, Bacteremia, Endocarditis, Polymicrobic

infections. 

Action

Imipenem binds to the bacterial cell wall, resulting in

cell death. Combination with cilastatin prevents renal

inactivation of imipenem, resulting in high urinary concentrations.

Imipenem resists the actions of many enzymes

that degrade most other penicillins and penicillin-

like anti-infectives. Therapeutic Effects:

Bactericidal action against susceptible bacteria. Spectrum:

Spectrum is broad. Active against most grampositive

aerobic cocci: Streptococcus pneumoniae,

Group A beta-hemolytic streptococci, Enterococcus,

Staphylococcus aureus. Active against many gram-negative

bacillary organisms: Escherichia coli, Klebsiella,

Acinetobacter, Proteus, Serratia, Pseudomonas aeruginosa.

Also displays activity against: Salmonella,

Shigella, Neisseria gonorrhoeae, Numerous anaerobes.

Pharmacokinetics

Absorption: Well absorbed after IM administration

(imipenem 95%, cilastatin 75%). IV administration results

in complete bioavailability.

Distribution: Widely distributed. Crosses the placenta;

enters breast milk.

Metabolism and Excretion: Imipenem and cilastatin

—70% excreted unchanged by the kidneys.

Half-life: Imipenem and cilastatin—1 hr (qin renal

impairment).

TIME/ACTION PROFILE (blood levels)

ROUTE ONSET PEAK DURATION

IM rapid 1–2 hr 12 hr

IV rapid end of infusion

6–8 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Cross-sensitivity

may occur with penicillins and cephalosporins.

Use Cautiously in: Previous history of multiple hypersensitivity

reactions; Seizure disorders; Renal impairment

(doseprequired if CCr 70 mL/min/1.73

m2); OB, Lactation, Pedi: Safety not established; Geri:

May be atqrisk for toxic reactions due to age-related

qin renal function.

Adverse Reactions/Side Effects

CNS: SEIZURES, dizziness, somnolence. CV: hypotension.

GI: CLOSTRIDIUM DIFFICILE-ASSOCIATED DIARRHEA

(CDAD), diarrhea, nausea, vomiting. Derm: rash,

pruritus, sweating, urticaria. Hemat: eosinophilia.

Local: phlebitis at IV site. Misc: allergic reaction including

ANAPHYLAXIS, fever, superinfection.

Interactions

Drug-Drug: Do not admix with aminoglycosides

(inactivation may occur). Probenecidprenal excretion

andqblood levels.qrisk of seizures with ganciclovir

or cyclosporine (avoid concurrent use of ganciclovir).

Maypserum valproate levels (qrisk of

seizures).

Route/Dosage

IV (Adults): Mild infections—250–500 mg q 6 hr.

Moderate infections—500 mg q 6–8 hr or 1 g q 8

hr. Serious infections—500 mg q 6 hr to 1 g q 6–8

hr.

IV (Children 3 mo [non-CNS infections]): 15–

25 mg/kg q 6 hr; higher doses have been used in older

children with cystic fibrosis.

IV (Children 4 wk–3 mo): 25 mg/kg q 6 hr.

IV (Children 1–4 wk): 25 mg/kg q 8 hr.

IV (Children 1 wk): 25 mg/kg q 12 hr.

IM (Adults): 500–750 mg q 12 hr.

IM (Children): 10–15 mg/kg q 6 hr.

Renal Impairment

IV (Adults): If dose for normal renal function is 1

g/day CCr 41–70 mL/min—125–250 mg q 6–8 hr,

CCr 21–40 mL/min—125–250 mg q 8–12 hr, CCr

6–20 mL/min—125–250 mg q 12 hr; if dose for

normal renal function is 1.5 g/day CCr 41–70 mL/

min—125–250 mg q 6–8 hr, CCr 21–40 mL/

min—125–250 mg q 8–12 hr, CCr 6–20 mL/

min—125–250 mg q 12 hr; if dose for normal renal

function is 2 g/day CCr 41–70 mL/min—125–

500 mg q 6–8 hr, CCr 21–40 mL/min—125–250

mg q 8–12 hr, CCr 6–20 mL/min—125–250 mg q

12 hr; if dose for normal renal function is 3 g/day

CCr 41–70 mL/min—250–500 mg q 6–8 hr, CCr

21–40 mL/min—250–500 mg q 6–8 hr, CCr 6–20

mL/min—250–500 mg q 12 hr; if dose for normal

renal function is 4 g/day CCr 41–70 mL/min—

250–750 mg q 6–8 hr, CCr 21–40 mL/min—250–

500 mg q 6–8 hr, CCr 6–20 mL/min—250–250 mg

q 12 hr.

Availability (generic available)

Powder for IV injection: 250 mg imipenem/250 mg

cilastatin, 500 mg imipenem/500 mg cilastatin. Powder

for IM injection: 500 mg imipenem/500 mg cilastatin,

750 mg imipenem/750 mg cilastatin.

imatinib (i-mat-i-nib) Gleevec

 Indications

Newly diagnosed Philadelphia positive (Ph)

chronic myeloid leukemia (CML). CML in blast crisis,

accelerated phase, or in chronic phase after failure of

interferon-alpha treatment. Kit (CD117) positive

metastatic/unresectable malignant gastrointestinal stomal

tumors (GIST). Adjuvant treatment following resection

of Kit (CD117) positive GIST. Pediatric patients

with Ph CML after failure of bone marrow transplant

or resistance to interferon-alpha. Adult patients with

relapsed or refractory Ph acute lymphoblastic leukemia

(ALL). Newly diagnosed Ph ALL (in combination

with chemotherapy). Myelodysplastic/myeloproliferative

disease (MDS/MPD) associated with

platelet-derived growth factor receptor (PDGFR) gene

re-arrangements. Aggressive systemic mastocytosis

(ASM) without the D816V c-Kit mutation or with c-Kit

mutational status unknown. Hypereosinophilic syndrome

and/or chronic eosinophilic leukemia (HES/

CEL). Unresectable, recurrent, or metastatic dermatofibrosarcoma

protuberans (DFSP).

Action

Inhibits kinases which may be produced by malignant

cell lines. Therapeutic Effects: Inhibits production

of malignant cell lines with decreased proliferation of

leukemic cells in CML, HES/CEL, and ALL and malignant

cells in GIST, MDS/MPD, ASM, and DFSP.

Pharmacokinetics

Absorption: Well absorbed (98%) following oral

administration.

Distribution: Unknown.

Protein Binding: 95%.

Metabolism and Excretion: Mostly metabolized

by the CYP3A4 enzyme system to N-demethyl imatinib,

which is as active as imatinib. Excreted mostly in feces

as metabolites. 5% excreted unchanged in urine.

Half-life: Imatinib—18 hr; N-desmethyl imatinib—

40 hr.

TIME/ACTION PROFILE (blood levels of

imatinib)

ROUTE ONSET PEAK DURATION

PO unknown 2–4 hr 24 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity; OB: Potential

for fetal harm; Lactation: Potential for serious adverse

reactions in nursing infants; breast feeding should be

avoided.

Use Cautiously in: Hepatic impairment (dosep

recommended if bilirubin 3 times normal or liver

transaminases 5 times normal); Cardiac disease (severe

HF and left ventricular dysfunction may occur);

Rep: Women of reproductive potential; Pedi: Children

1 yr (safety not established); Geri:qrisk of edema.

Adverse Reactions/Side Effects

CNS: fatigue, headache, weakness, dizziness, somnolence.

CV: HF. EENT: epistaxis, nasopharyngitis,

blurred vision. Resp: cough, dyspnea, pneumonia.

GI: HEPATOTOXICITY, abdominal pain, anorexia, constipation, diarrhea, dyspepsia, nausea, vomiting. Derm:

DRUG RASH WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS

(DRESS), petechiae, pruritus, skin rash. F and E:

edema (including pleural effusion, pericardial infusion,

pulmonary edema, and superficial edema), hypokalemia.

Endo:pgrowth (in children), hypothyroidism.

Hemat: BLEEDING, NEUTROPENIA, THROMBOCYTOPENIA.

Metab: weight gain. MS: arthralgia, muscle cramps,

musculoskeletal pain, myalgia. Misc: TUMOR LYSIS SYNDROME,

fever, night sweats.

Interactions

Drug-Drug: Blood levels and effects areqby concurrent

use of potent CYP3A4 inhibitors (e.g. ketoconazole,

itraconazole, clarithromycin, atazanavir,

indinavir, nefazodone, nelfinavir, ritonavir, saquinavir,

or voriconazole). Blood levels and effects

may bepby potent CYP3A4 inducers (e.g., dexamethasone,

phenytoin, carbamazepine, rifampin, rifabutin,

and phenobarbital; if used concurrently,q

dose of imatinib by 50%.qblood levels of simvastatin.

Imatinib inhibits the following enzyme systems:

CYP2C9, CYP2D6, CYP3A4/5 and may be expected to alter

the effects of other drugs metabolized by these systems.

Drug-Food: Blood levels and effects areqby grapefruit

juice; concurrent use should be avoided.

Route/Dosage

Chronic Myeloid Leukemia

PO (Adults): Chronic phase—400 mg once daily,

may beqto 600 mg once daily; accelerated phase or

blast crisis—600 mg once daily; may beqto 800 mg/

day given as 400 mg twice daily based on response and

circumstances.

PO (Children): Newly diagnosed Ph CML—340

mg/m2 once daily (not to exceed 600 mg); CML recurrent

after failure of bone marrow transplant or resistance

to interferon-alpha—260 mg/m2 once daily.

Gastrointestinal Stromal Tumors

PO (Adults): Metastatic or unresectable—400 mg

once daily; may beqto 400 mg twice daily if well tolerated

and response insufficient; Adjuvant treatment after

resection—400 mg once daily.

Ph Acute Lymphoblastic Leukemia

PO (Adults): 600 mg once daily.

PO (Children): 340 mg/m2 once daily (not to exceed

600 mg).

Myelodysplastic/Myeloproliferative Diseases

PO (Adults): 400 mg once daily.

Aggressive Systemic Mastocytosis

PO (Adults): 400 mg once daily. For patients with

eosinophilia—100 mg once daily;qto 400 mg once

daily if well tolerated and response insufficient.

Hypereosinophilic Syndrome and/or

Chronic Eosinophilic Leukemia

PO (Adults): 400 mg once daily. For patients with

FIP1L1–PDGFRa fusion kinase 100 mg once daily;q

to 400 mg once daily if well tolerated and response insufficient.

Dermatofibrosarcoma Protuberans

PO (Adults): 400 mg twice daily.

Hepatic Impairment

PO (Adults):pdose by 25% in severe hepatic impairment.

Renal Impairment

PO (Adults): CCr 40–59 mL/min—Do not exceed

dose of 600 mg/day; CCr 20–39 mL/min—pinitial

dose by 50%;qas tolerated.

Availability (generic available)

Tablets: 100 mg, 400 mg.

iloperidone (eye-loe-per-i-done) Fanapt

 Indications

Schizophrenia.

Action

May act by antagonizing dopamine and serotonin in the

CNS. Therapeutic Effects: Decreased symptoms of

schizophrenia.

Pharmacokinetics

Absorption: Well absorbed (96%) following oral

administration.

Distribution: Unknown.

Metabolism and Excretion: Extensively metabolized

by the liver. Metabolism is genetically determined;

primarily by CYP3A4 and CYP2D6 enzyme systems,

with individual variability in metabolism via

CYP2D6 (extensive metabolizers [EM] and poor metabolizers

[PM] and some in-between; 7–10% of Caucasians

and 3–8% of Black/African Americans are considered

PM). Two major metabolites (P88 and P95)

may be partially responsible for pharmacologic activity.

58% excreted in urine as metabolites in EM and 45% in

PM; 20% eliminated in feces in EM and 22.1% in PM.

Half-life: EMs—iloperidone–18 hr, P88–26 hr,

P95–23 hr; PMs—iloperidone–33 hr, P88–37 hr,

P95–31 hr.

TIME/ACTION PROFILE (antipsychotic effect)

ROUTE ONSET PEAK DURATION

PO 2–4 wk 2–4 hr† unknown

† Blood level.

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Concurrent

use of drugs known to prolong QTc interval; Bradycardia,

recent MI or uncompensated heart failure (qrisk

of serious arrhythmias); Congenital long QT syndrome,

QTc interval 500 msec or history of cardiac arrhythmias;

Electrolyte abnormalities, especially hypomagnesemia

or hypokalemia (correct prior to therapy); Severe

hepatic impairment; Lactation: Breast feeding

should be avoided.

Use Cautiously in: Known cardiovascular disease

including heart failure, history of MI/ischemia, conduction

abnormalities, cerebrovascular disease, or other

conditions known to predispose to hypotension including

dehydration, hypovolemia, concurrent antihypertensive

therapy (qrisk of orthostatic hypotension);

Concurrent use of CYP3A4 or CYP2D6 inhibitors;

KnownpWBC or history of drug-induced leukopenia/

neutropenia; Circumstances that may result inqbody

temperature, including strenuous exercise, exposure to

extreme heat, concurrent anticholinergic activity, or dehydration

(may impair thermoregulation); Patients at

risk for aspiration or falls; Moderate hepatic impairment;

OB: Neonates atqrisk for extrapyramidal symptoms

and withdrawal after delivery when exposed during

the 3rd trimester; use only if potential maternal

benefit justifies potential fetal risk; Pedi: Safety and effectiveness

not established; Geri: Elderly patients with

dementia-related psychoses (qrisk of death, CVA or

TIA). 

Adverse Reactions/Side Effects

CNS: NEUROLEPTIC MALIGNANT SYNDROME, SUICIDAL

THOUGHTS, dizziness, drowsiness, fatigue, agitation, delusion,

restlessness, extrapyramidal disorders. EENT:

nasal congestion. CV: orthostatic hypotension, tachycardia,

palpitations, QTc interval prolongation. GI: dry

mouth, nausea, abdominal discomfort, diarrhea. GU:

priapism, urinary incontinence. Endo: dyslipidemia,

hyperglycemia, hyperprolactinemia. Neuro: tardive

dyskinesia. Metab: weight gain, weight loss. MS:p

bone density, musculoskeletal stiffness. Misc: ANAPHYLAXIS,

ANGIOEDEMA.

Interactions

Drug-Drug: Avoid use of drugs known to the prolong

QTc interval including the quinidine, procainamide,

amiodarone, sotalol, chlorpromazine,

thioridazine, moxifloxacin, pentamidine, and

methadone. Concurrent use of strong CYP2D6 inhibitors

including fluoxetine and paroxetineqlevels

and the risk of toxicity; dosepis required. Concurrent

use of strong CYP3A4 inhibitors including

ketoconazole and clarithromycinqlevels and the

risk of toxicity; dosagepis required. Concurrent use of

antihypertensives including diuretics mayqrisk of

orthostatic hypotension. Concurrent anticholinergics

mayqrisk of impaired thermoregulation.

Route/Dosage

PO (Adults): Initiate treatment with 1 mg twice daily

on the first day, then 2 mg twice daily the second day,

thenqby 2 mg/day every day until a target dose of 12–

24 mg/day given in two divided doses is reached; Concurrent

strong CYP2D6 or CYP3A4 inhibitors—p

dose by 50%, if inhibitor is withdrawnqdose to previous

amount. Re-titration is required if iloperidone is

discontinued 300 days; Poor metabolizers of

CYP2D6—pdose by 50%.

Availability

Tablets: 1 mg, 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, 12 mg.

ifosfamide (eye-foss-fam-ide) Ifex

 Indications

Germ cell testicular carcinoma (with other agents).

Used with mesna, which prevents ifosfamide-induced

hemorrhagic cystitis.

Action

Following conversion to active compounds, interferes

with DNA replication and RNA transcription, ultimately

disrupting protein synthesis (cell-cycle phase–nonspecific).

Therapeutic Effects: Death of rapidly replicating

cells, particularly malignant ones.

Pharmacokinetics

Absorption: Administered IV only; inactive prior to

conversion to metabolites.

Distribution: Excreted in breast milk.

Metabolism and Excretion: Metabolized by the

liver to active antineoplastic compounds.

Half-life: 15 hr.

TIME/ACTION PROFILE (effects on blood

counts)

ROUTE ONSET PEAK DURATION

IV unknown 7–14 days 21 days

Contraindications/Precautions

Contraindicated in: Hypersensitivity; OB, Lactation:

Pregnancy or lactation.

Use Cautiously in: Patients with childbearing potential;

Active infections;pbone marrow reserve; Geri:

Geriatric patients; Other chronic debilitating illness; Renal

impairment; Pedi: Children.

Adverse Reactions/Side Effects

CNS: CNS toxicity (somnolence, confusion, hallucinations,

coma), cranial nerve dysfunction, disorientation,

dizziness. CV: cardiotoxicity. GI: nausea, vomiting, anorexia,

constipation, diarrhea, hepatotoxicity. GU:

hemorrhagic cystitis, dysuria, sterility, renal toxicity.

Derm: alopecia. Hemat: ANEMIA, LEUKOPENIA,

THROMBOCYTOPENIA. Local: phlebitis. Misc: allergic

reactions.

Interactions

Drug-Drug: CYP3A4 inhibitors, including ketoconazole,

fluconazole, itraconazole, sorafenib,

and aprepitant maypits effectiveness. CYP3A4 inducers,

including carbamazepine, phenytoin, phenytoin,

phenobarbital, and rifampin mayqthe formation

of a toxic metabolite and mayqrisk of toxicity.

qmyelosuppression with other antineoplastics or radiation

therapy. Toxicity may beqby allopurinol or

phenobarbital. Maypantibody response to andq

risk of adverse reactions from live-virus vaccines.

Drug-Food: Grapefruit juice mayqlevels; avoid

concurrent use.

Route/Dosage

Other Regimens are Used

IV (Adults): 1.2 g/m2/day for 5 days; coadminister

with mesna. May repeat cycle q 3 wk.

Availability (generic available)

Powder for injection (requires reconstitution): 1

g/vial, 3 g/vial. Solution for injection: 50 mg/mL.

idaruCIZUmab (eye-da-roo-siz-ue-mab ) Praxbind

 Indications

To counteract the anticoagulant effect of dabigatran for

emergency surgery/urgent procedures or life-threatening

uncontrolled bleeding.

Action

Human monoclonal antibody fragment (Fab) that selectively

binds to dabigatran and its metabolites, preventing

its binding to thrombin and negating its anticoagulant

effects. Does not reverse any other

anticoagulants. Therapeutic Effects: Reversal of

the anticoagulant effect of dabigatran.

Pharmacokinetics

Absorption: IV administration results in complete

bioavailability.

Distribution: Unknown.

Metabolism and Excretion: Biodegraded to

smaller molecules. 60% excreted in urine, remainder

via protein catabolism primarily in the kidneys.

Half-life: 10.3 hr.

TIME/ACTION PROFILE

ROUTE ONSET PEAK DURATION

IV immediate unknown 24 hr

Contraindications/Precautions

Contraindicated in: None noted.

Use Cautiously in: Geri: Elderly patients may be

more sensitive to drug effects; OB: Safety not established.

Consider maternal benefits and fetal risks; Lactation:

Safety not established, consider beneficial effects

of breast feeding and possible adverse effects in infant;

Pedi: Safety and effectiveness not established.

Exercise Extreme Caution in: Hereditary fructose

intolerance (risk of serious adverse reactions due

to sorbitol excipient); History of serious hypersensivity

(including anaphylactoid reactions) to idarucizumab.

Adverse Reactions/Side Effects

CNS: delerium. CV: THROMBOEMBOLISM. GI: constipation.

F and E: hypokalemia. Misc: hypersensitivity

reactions, fever.

Interactions

Drug-Drug: None noted.

Route/Dosage

IV (Adults): 5 g as single dose.

Availability

Solution for injection (contains sorbitol): 2.5 g/

50 mL single-use vial.

idaruCIZUmab (eye-da-roo-siz-ue-mab ) Praxbind

 Indications

To counteract the anticoagulant effect of dabigatran for

emergency surgery/urgent procedures or life-threatening

uncontrolled bleeding. 

Action

Human monoclonal antibody fragment (Fab) that selectively

binds to dabigatran and its metabolites, preventing

its binding to thrombin and negating its anticoagulant

effects. Does not reverse any other

anticoagulants. Therapeutic Effects: Reversal of

the anticoagulant effect of dabigatran.

Pharmacokinetics

Absorption: IV administration results in complete

bioavailability.

Distribution: Unknown.

Metabolism and Excretion: Biodegraded to

smaller molecules. 60% excreted in urine, remainder

via protein catabolism primarily in the kidneys.

Half-life: 10.3 hr.

TIME/ACTION PROFILE

ROUTE ONSET PEAK DURATION

IV immediate unknown 24 hr

Contraindications/Precautions

Contraindicated in: None noted.

Use Cautiously in: Geri: Elderly patients may be

more sensitive to drug effects; OB: Safety not established.

Consider maternal benefits and fetal risks; Lactation:

Safety not established, consider beneficial effects

of breast feeding and possible adverse effects in infant;

Pedi: Safety and effectiveness not established.

Exercise Extreme Caution in: Hereditary fructose

intolerance (risk of serious adverse reactions due

to sorbitol excipient); History of serious hypersensivity

(including anaphylactoid reactions) to idarucizumab.

Adverse Reactions/Side Effects

CNS: delerium. CV: THROMBOEMBOLISM. GI: constipation.

F and E: hypokalemia. Misc: hypersensitivity

reactions, fever.

Interactions

Drug-Drug: None noted.

Route/Dosage

IV (Adults): 5 g as single dose.

Availability

Solution for injection (contains sorbitol): 2.5 g/

50 mL single-use vial. 

ibuprofen (eye-byoo-proe-fen) Advil, Advil Infants, Advil Junior Strength, Advil Migraine, Children’s Advil, Children’s Europrofen, Children’s Motrin, Motrin, Motrin IB, Motrin Infants Drops, Motrin Junior Strength, PediaCare IB Ibuprofen ibuprofen (injection) Caldolor, NeoProfen (ibuprofen lysine)

 Indications

PO, IV: Treatment of: Mild to moderate pain, Fever.

PO: Treatment of: Inflammatory disorders including

rheumatoid arthritis (including juvenile) and osteoarthritis,

Dysmenorrhea. IV: Moderate to severe pain with

opioid analgesics. Closure of a clinically significant PDA

in neonates weighing 500–1500 g and 32 wk gestational

age (ibuprofen lysine only)

Action

Inhibits prostaglandin synthesis. Therapeutic Effects:

Decreased pain and inflammation. Reduction of fever.

Pharmacokinetics

Absorption: Oral formulation is well absorbed

(80%) from the GI tract; IV administration results in

complete bioavailability.

Distribution: Does not enter breast milk in significant

amounts.

Protein Binding: 99%.

Metabolism and Excretion: Mostly metabolized

by the liver; small amounts (1%) excreted unchanged

by the kidneys.

Half-life: Neonates: 26–43 hr; Children: 1–2 hr;

Adults: 2–4 hr.

TIME/ACTION PROFILE

ROUTE ONSET PEAK DURATION

PO (antipyretic) 0.5–2.5 hr 2–4 hr 6–8 hr

PO (analgesic) 30 min 1–2 hr 4–6 hr

PO (anti-inflammatory)

7 days 1–2 wk unknown

IV (analgesic) unknown unknown 6 hr

IV (antipyretic) within 2 hr 10–12 hr† 4–6 hr

† With repeated dosing. 

Contraindications/Precautions

Contraindicated in: Hypersensitivity (cross-sensitivity

may exist with other NSAIDs, including aspirin);

Active GI bleeding or ulcer disease; Chewable tablets

contain aspartame and should not be used in patients

with phenylketonuria; Coronary artery bypass graft

(CABG) surgery; History of recent MI; Severe HF; OB:

Avoid after 30 wk gestation (may cause premature closure

of fetal ductus arteriosus); Pedi: Ibuprofen lysine:

Preterm neonates with untreated infection, congenital

heart disease where patency of PDA is necessary for

pulmonary or systemic blood flow, bleeding, thrombocytopenia,

coagulation defects, necrotizing enterocolitis,

significant renal dysfunction.

Use Cautiously in: Cardiovascular disease or risk

factors for cardiovascular disease (mayqrisk of serious

cardiovascular thrombotic events, MI, and stroke,

especially with prolonged use or use of higher doses);

avoid use in patients with recent MI or HF; Renal or hepatic

disease, dehydration, or patients on nephrotoxic

drugs (mayqrisk of renal toxicity); Aspirin triad patients

(asthma, nasal polyps, and aspirin intolerance);

can cause fatal anaphylactoid reactions; Chronic alcohol

use/abuse; Geri:qrisk of adverse reactions secondary

to age-relatedpin renal and hepatic function, concurrent

illnesses, and medications; Coagulation

disorders; OB: Use cautiously up to 30 wk gestation;

avoid after that; Lactation: Use cautiously; Pedi: Safety

not established for infants 6 mo (oral and IV Caldolor);

Hyperbilirubinemia in neonates (may displace bilirubin

from albumin-binding sites).

Exercise Extreme Caution in: History of GI

bleeding or GI ulcer disease.

Adverse Reactions/Side Effects

CNS: headache, dizziness, drowsiness, intraventricular

hemorrhage (ibuprofen lysine), psychic disturbances.

EENT: amblyopia, blurred vision, tinnitus. CV: HF,

MYOCARDIAL INFARCTION, STROKE, arrhythmias, edema,

hypertension. F and E: hyperkalemia. GI: GI BLEEDING,

HEPATITIS, constipation, dyspepsia, nausea, necrotizing

enterocolitis (ibuprofen lysine), vomiting, abdominal

discomfort. GU: cystitis, hematuria, renal

failure. Derm: EXFOLIATIVE DERMATITIS, STEVENS-JOHNSON

SYNDROME, TOXIC EPIDERMAL NECROLYSIS, rash, injection

site reaction. Hemat: anemia, blood dyscrasias,

prolonged bleeding time. Misc: allergic reactions

including ANAPHYLAXIS.

Interactions

Drug-Drug: May limit the cardioprotective effects of

low-dose aspirin. Concurrent use with aspirin mayp

effectiveness of ibuprofen. Additive adverse GI side effects

with aspirin, oral potassium, other NSAIDs,

corticosteroids, or alcohol. Chronic use with acetaminophen

mayqrisk of adverse renal reactions. May

peffectiveness of diuretics, ACE inhibitors, or other

antihypertensives. Mayqhypoglycemic effects of insulin

or oral hypoglycemic agents. Mayqserum

lithium levels and risk of toxicity.qrisk of toxicity

from methotrexate. Probenecidqrisk of toxicity

from ibuprofen.qrisk of bleeding with cefotetan,

corticosteroids, valproic acid, thrombolytics,

warfarin, and drugs affecting platelet function including

clopidogrel, abciximab, eptifibatide, or tirofiban.

qrisk of adverse hematologic reactions with

antineoplastics or radiation therapy.qrisk of

nephrotoxicity with cyclosporine.

Drug-Natural Products:qbleeding risk with, arnica,

chamomile, feverfew, garlic, ginger, ginkgo,

Panax ginseng, and others.

Route/Dosage

Analgesia

PO (Adults): Anti-inflammatory—400–800 mg 3–

4 times daily (not to exceed 3200 mg/day). Analgesic/

antidysmenorrheal/antipyretic—200–400 mg every

4–6 hr (not to exceed 1200 mg/day).

PO (Children 6 mo–12 yr): Anti-inflammatory—

30–50 mg/kg/day in 3–4 divided doses (maximum

dose: 2.4 g/day). Antipyretic—5 mg/kg for temperature

102.5F (39.17C) or 10 mg/kg for higher temperatures

(not to exceed 40 mg/kg/day); may be repeated

every 4–6 hr. Cystic fibrosis (unlabeled)—

20–30 mg/kg/day divided twice daily.

PO (Infants and Children): Analgesic—4–10 mg/

kg/dose every 6–8 hr.

IV (Adults): Analgesic—400–800 mg every 6 hr as

needed (not to exceed 3200 mg/day); Antipyretic—

400 mg initially, then 400 mg every 4–6 hr or 100–

200 mg every 4 hr as needed (not to exceed 3200 mg/

day).

IV (Children 12–17 yr): Analgesic and antipyretic—

400 mg every 4–6 hr as needed (not to exceed

2400 mg/day).

IV (Children 6 mo–12 yr): Analgesic and antipyretic—

10 mg/kg (not to exceed 400 mg) every 4–6

hr as needed (not to exceed 40 mg/kg/day or 2400 mg/

day whichever is less).

Pediatric OTC Dosing

PO (Children 11 yr/72–95 lb): 300 mg every 6–8

hr.

PO (Children 9–10 yr/60–71 lb): 250 mg every 6–

8 hr.

PO (Children 6–8 yr/48–59 lb): 200 mg every 6–

8 hr.

PO (Children 4–5 yr/36–47 lb): 150 mg every 6–

8 hr.

PO (Children 2–3 yr/24–35 lb): 100 mg every 6–

8 hr. 

PO (Children 12–23 mo/18–23 lb): 75 mg every

6–8 hr.

PO (Infants 6–11 mo/12–17 lb): 50 mg every 6–8

hr.

PDA Closure

IV (Neonates Gestational age 32 weeks, 500–

1500 g): 10 mg/kg followed by two doses of 5 mg/kg

at 24 and 48 hr after initial dose.

Availability (generic available)

Tablets: 100 mgOTC, 200 mgOTC, 300 mg, 400 mg, 600

mg, 800 mg. Capsules (liquigels): 200 mgOTC. Chewable

tablets (fruit, grape, orange, and citrus flavor

): 50 mgOTC, 100 mgOTC. Oral suspension (fruit,

berry, grape flavor): 100 mg/5 mLOTC. Pediatric

drops (berry flavor): 50 mg/1.25 mLOTC. Solution

for injection: 100 mg/mL (Caldolor), 17.1 mg/mL as

lysine, 10 mg/mL as ibuprofen base (Neoprofen). In

combination with: decongestantsOTC, hydrocodone

(Reprexain), famotidine (Duexis). See Appendix B.

ibandronate (i-ban-dro-nate) Boniva

 Indications

Treatment/prevention of postmenopausal osteoporosis.

Action

Inhibits resorption of bone by inhibiting osteoclast activity.

Therapeutic Effects: Reversal/prevention of

progression of osteoporosis with decreased fractures.

Pharmacokinetics

Absorption: 0.6% absorbed following oral administration

(significantlypby food).

Distribution: Rapidly binds to bone.

Protein Binding: 90.9–99.5%.

Metabolism and Excretion: 50–60% excreted in

urine; unabsorbed drug is eliminated in feces.

Half-life: PO—10–60 hr; IV—4.6–25.5 hr.

TIME/ACTION PROFILE

ROUTE ONSET PEAK DURATION

PO unknown 0.5–2 hr up to 1 mo

IV unknown 3 hr up to 3 mo

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Abnormalities

of the esophagus which delay esophageal emptying

(i.e. strictures, achalasia); Uncorrected hypocalcemia;

Inability to stand/sit upright for at least 60 min; CCr

30 mL/min.

Use Cautiously in: History of upper GI disorders;

Concurrent use of NSAIDs or aspirin; Invasive dental

procedures, cancer, receiving chemotherapy, corticosteroids,

or angiogenesis inhibitors, poor oral hygiene,

periodontal disease, dental disease, anemia, coagulopathy,

infection, or poorly-fitting dentures (mayqrisk of

jaw osteonecrosis); OB: Use only if potential benefit

outweighs risks to mother and fetus; Lactation: Lactation;

Pedi: Children 18 yr (safety not established);

Geri: Consider age relatedpin body mass, renal and

hepatic function, concurrent disease states and drug

therapy.

Adverse Reactions/Side Effects

GI: diarrhea, dyspepsia, dysphagia, esophageal cancer,

esophagitis, esophageal/gastric ulcer. MS: musculoskeletal

pain, pain in arms/legs, femur fractures, osteonecrosis

(primarily of jaw). Derm: ERYTHEMA MULTIFORME,

STEVENS-JOHNSON SYNDROME. Resp: asthma

exacerbation. Misc: ANAPHYLAXIS, injection site reactions.

Interactions

Drug-Drug: Calcium-, aluminum-, magnesium-,

and iron- containing products, including antacidsp

absorption (ibandronate should be taken 60 min before).

Concurrent use of NSAIDs including aspirin,

mayqrisk of gastric irritation.

Drug-Food: Milk and other foodspabsorption.

Route/Dosage

PO (Adults): 150 mg once monthly.

IV (Adults): 3mg every 3 mo.

Availability (generic available)

Tablets: 150 mg. Injection: 3 mg/3 mL in prefilled

single-use syringe. 

hydroxyprogesterone caproate (hye-drox-ee-pro-jess-te-rone kap-roe-ate) Makena

 Indications

Topthe risk of preterm birth in women with a singleton

pregnancy who have a history of previous singleton

preterm birth.

Action

A synthetic analog of progesterone. Produces secretory

changes in the endometrium.qs basal temperature.

Produces changes in the vaginal epithelium. Relaxes

uterine smooth muscle. Stimulates mammary alveolar

growth. Inhibits pituitary function. Action in reducing

risk of recurrent preterm birth is unknown. Therapeutic

Effects:prisk of preterm birth in women at

risk.

Pharmacokinetics

Absorption: Slowly absorbed following IM administration.

Distribution: Unknown.

Protein Binding: Extensively bound to plasma proteins.

Metabolism and Excretion: Extensively metabolized

by the liver.

Half-life: 7.8 days.

TIME/ACTION PROFILE (blood levels)

ROUTE ONSET PEAK DURATION

IM unknown 4.6 days 7 days

Contraindications/Precautions

Contraindicated in: Hypersensitivity to hydroxyprogesterone

or castor oil; History of or known thrombosis/

thromboembolic disorder; History of or known/

suspected breast cancer or other hormone-sensitive

cancer; Unexplained abnormal vaginal bleeding unrelated

to pregnancy; Cholestatic jaundice of pregnancy;

Benign/malignant liver tumors or active liver disease;

Uncontrolled hypertension.

Use Cautiously in: Risk factors for thromboembolic

disorders (mayqrisk); Diabetes mellitus or risk

factors for diabetes mellitus (may impair glucose tolerance);

History of preeclampsia, epilepsy, cardiac or renal

impairment (may be adversely affected by fluid retention);

History of depression (may worsen); Safe and

effective use in children 16 yr has not been established.

Adverse Reactions/Side Effects

CNS: depression. CV: hypertension. GI: diarrhea,

jaundice, nausea. Derm: urticaria, pruritus. F and

E: fluid retention. Hemat: THROMBOEMBOLISM. Local:

injections site reactions. Misc: allergic reactions

including ANGIOEDEMA.

Interactions

Drug-Drug: Mayqmetabolism andpblood levels

and effectiveness of drugs metabolized by the

CYP1A2, CYP2A6, and CYP2B6 enzyme systems. 

Route/Dosage

IM (Adults): 250 mg once weekly starting between 16

wks, 0 days and 20 wks, 6 days continuing until wk 37

of gestation or delivery, whichever occurs first.

Availability

Solution for IM injection (contains castor oil):

1250 mg/5 mL vial (250 mg/mL).

hydroxychloroquine, Plaquenil

 Indications

Treatment of uncomplicated malaria in geographic areas

where chloroquine-resistance is not reported. Prophylaxis

of malaria in geographic areas where chloroquine-

resistance is not reported. Treatment of acute

and chronic rheumatoid arthritis. Treatment of chronic

discoid lupus erythematosus and systemic lupus erythematosus.

Action

Inhibits protein synthesis in susceptible organisms by

inhibiting DNA and RNA polymerase. Therapeutic

Effects: Death of plasmodia responsible for causing

malaria. Also has anti-inflammatory properties. Spectrum:

Active against chloroquine-sensitive strains of:

Plasmodium falciparum, Plasmodium malariae, a-

Plasmodium ovale, and Plasmodium vivax.

Pharmacokinetics

Absorption: Highly variable (31–100%) following

oral administation.

Distribution: Widely distributed; high concentrations

in RBCs; crosses the placenta; excreted into breast

milk.

Metabolism and Excretion: Partially metabolized

by the liver to active metabolites; partially excreted unchanged

by the kidneys.

Half-life: 40 days.

TIME/ACTION PROFILE (blood levels)

ROUTE ONSET PEAK DURATION

PO rapid† 1–2 hr days–weeks

†Onset of antirheumatic action may take 6 wk.

Contraindications/Precautions

Contraindicated in: Hypersensitivity to hydroxychloroquine

or chloroquine; Previous visual damage

from hydroxychloroquine or chloroquine.

Use Cautiously in: Concurrent use of hepatotoxic

drugs; Hepatic impairment or alcoholism; Use of high

doses (5 mg/kg base), duration of use 5 yr, renal

impairment, concurrent use of tamoxifen or macular

disease (qrisk of retinopathy); G6PD deficiency; Psoriasis;

Porphyria; Bone marrow depression; Obesity (determine

dose by ideal body weight); OB, Lactation:

Avoid use unless treating/preventing malaria or treating

amebic abscess; Geri:prenal function mayqrisk of

adverse reactions; Pedi: Safety and effectiveness for

chronic use not established.

Adverse Reactions/Side Effects

CNS: SEIZURES, SUICIDAL THOUGHTS/BEHAVIORS, aggressiveness,

anxiety, dizziness, fatigue, headache, irritability,

nightmares, personality changes, psychoses.

EENT: corneal deposits, nystagmus, retinopathy, tinnitus,

vertigo, visual disturbances. CV: HF, TORSADE DE

POINTES, heart block, QT interval prolongation. Endo:

hypoglycemia. GI: HEPATOTOXICITY, abdominal pain,

anorexia, diarrhea,qliver enzymes, nausea, vomiting. 

Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC

SYMPTOMS (DRESS), ERYTHEMA MULTIFORME, STEVENS-

JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS,

acute generalized exanthematous pustulosis, alopecia,

hair color changes, hyperpigmentation, photosensitivity,

pruritus, rash, urticaria. Hemat: AGRANULOCYTOSIS,

APLASTIC ANEMIA, leukopenia, thrombocytopenia. Metab:

pweight. Neuro: ataxia, dyskinesia, dystonia,

neuromyopathy, peripheral neuritis, tremor. Resp:

PULMONARY HYPERTENSION, bronchospasm. Misc: ANGIOEDEMA.

Interactions

Drug-Drug: Concurrent use of other QT intervalprolonging

drugs mayqrisk of torsade de pointes.

Mayqthe risk of hepatotoxicity when administered with

hepatotoxic drugs. Mayqrisk of hypoglycemia when

used with antidiabetic agents. Use with mefloquine

mayqrisk of seizures. Antacids may bind to andpthe

absorption of hydroxychloroquine; separate administration

by 4 hr. Cimetidine mayqlevels; avoid concurrent

use. Urinary acidifiers mayqrenal excretion.

Mayqlevels of digoxin or cyclosporine.

Route/Dosage

200 mg hydroxychloroquine sulfate155 mg of hydroxychloroquine

base.

Malaria

PO (Adults): Prophylaxis—400 mg sulfate (310 mg

base) once weekly; start 2 wk prior to entering malarious

area; continue for 4 wk after leaving area. Treatment—

800 mg sulfate (620 mg base), then 400 mg

sulfate (310 mg base) at 6 hr, 24 hr, and 48 hr after

initial dose.

PO (Children 31 kg): Prophylaxis—6.5 mg/kg

sulfate (5 mg/kg base) (not to exceed 400 mg sulfate

[310 mg base]) once weekly; start 2 wk prior to entering

malarious area; continue for 4 wk after leaving

area. Treatment—13 mg/kg sulfate (10 mg/kg base)

(not to exceed 800 mg sulfate [620 mg base]) initially,

then 6.5 mg/kg sulfate (5 mg/kg base) (not to exceed

400 mg sulfate [310 mg base]) at 6 hr, 24 hr, and 48

hr after initial dose.

Rheumatoid Arthritis

PO (Adults): 400–600 mg sulfate (310–465 mg

base) per day in 1–2 divided doses; once adequate response

obtained, maypdose to maintenance dose of

200–400 mg sulfate (155–310 mg base) per day in

1–2 divided doses.

Lupus Erythematosus

PO (Adults): 200–400 mg sulfate (155–310 mg

base) per day in 1–2 divided doses.

Availability (generic available)

Tablets: 200 mg sulfate (155 mg base). Cost: Generic—$

14.88/100.

HYDROmorphone (hye-droe-mor-fone) Dilaudid, Dilaudid-HP, Exalgo, Hydromorph Contin, Jurnista

 Indications

Moderate to severe pain (alone and in combination

with nonopioid analgesics). Moderate to severe chronic

pain in opioid-tolerant patients requiring use of daily,

around-the-clock long-term opioid treatment and for

which alternative treatment options are inadequate (extended-

release). Antitussive (lower doses).

Action

Binds to opiate receptors in the CNS. Alters the perception

of and response to painful stimuli while producing

generalized CNS depression. Suppresses the cough reflex

via a direct central action. Therapeutic Effects:

Decrease in moderate to severe pain. Suppression

of cough.

Pharmacokinetics

Absorption: Well absorbed following oral, rectal,

subcut, and IM administration. Extended-release product

results in an initial release of drug, followed by a

second sustained phase of absorption.

Distribution: Widely distributed. Crosses the placenta;

enters breast milk.

Metabolism and Excretion: Mostly metabolized

by the liver.

Half-life: Oral (immediate-release), or injection—

2–4 hr; Oral (extended-release)—8–15 hr.

TIME/ACTION PROFILE (analgesic effect)

ROUTE ONSET PEAK DURATION

PO-IR 30 min 30–90 min 4–5 hr

PO-ER unknown unknown unknown

Subcut 15 min 30–90 min 4–5 hr

IM 15 min 30–60 min 4–5 hr

IV 10–15 min 15–30 min 2–3 hr

Rect 15–30 min 30–90 min 4–5 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Some products

contain bisulfites and should be avoided in patients

with known hypersensitivity; Severe respiratory depression

(in absence of resuscitative equipment) (extended-

release only); Acute or severe bronchial asthma

(extended-release only); Paralytic ileus (extended-release

only); Acute, mild, intermittent, or postoperative

pain (extended-release only); Prior GI surgery or narrowing

of GI tract (extended-release only); Opioid nontolerant

patients (extended-release only); Severe hepatic

impairment (extended-release only).

Use Cautiously in: Head trauma;qintracranial

pressure; Severe pulmonary disease; Moderate or severe

renal disease (extended-release only) (doseprecommended);

Moderate hepatic impairment (extendedrelease

only) (doseprecommended); Hypothyroidism;

Seizure disorder; Adrenal insufficiency; Alcoholism;

Undiagnosed abdominal pain; Prostatic hypertrophy;

Biliary tract disease (including pancreatitis); OB: Labor

and delivery; OB, Lactation: Avoid chronic use; prolonged

use of opioids during pregnancy can result in

neonatal opioid withdrawal syndrome; Geri: Geriatric

or debilitated patients (qrisk of respiratory depression;

dosepsuggested).

Adverse Reactions/Side Effects

CNS: confusion, sedation, dizziness, dysphoria, euphoria,

floating feeling, hallucinations, headache, unusual

dreams. EENT: blurred vision, diplopia, miosis.

Resp: RESPIRATORY DEPRESSION. CV: hypotension,

bradycardia. Endo: adrenal insufficiency. GI: constipation,

dry mouth, nausea, vomiting. GU: urinary retention.

Derm: flushing, sweating. Misc: physical dependence,

psychological dependence, tolerance.

Interactions

Drug-Drug: Exercise extreme caution with MAO inhibitors

(may produce severe, unpredictable reactions—

reduce initial dose of hydromorphone to 25%

of usual dose, discontinue MAO inhibitors 2 wk prior to

hydromorphone). Use with benzodiazepines or

other CNS depressants including other opioids,

non-benzodiazepine sedative/hypnotics, anxiolytics,

general anesthetics, muscle relaxants, antipsychotics,

and alcohol may cause profound sedation,

respiratory depression, coma, and death; reserve

concurrent use for when alternative treatment options

are inadequate. Administration of partial antagonists

(buprenorphine, butorphanol, nalbuphine, or

pentazocine) may precipitate opioid withdrawal in

physically dependent patients. Nalbuphine or pentazocine

maypanalgesia. Drugs that affect serotonergic

neurotransmitter systems, including tricyclic antidepressants,

SSRIs, SNRIs, MAO inhibitors, TCAs,

tramadol, trazodone, mirtazapine, 5–HT3 receptor

antagonists, linezolid, methylene blue, and

triptansqrisk of serotonin syndrome.

Drug-Natural Products: Concomitant use of

kava-kava, valerian, chamomile, or hops canq

CNS depression.

Route/Dosage

Doses depend on level of pain and tolerance. Larger

doses may be required during chronic therapy.

Analgesic

PO (Adults 50 kg): Immediate-release—4–8 mg

every 3–4 hr initially (some patients may respond to doses as small as 2 mg initially); or once 24-hr opioid

requirement is determined, convert to extended-release

by administering total daily oral dose once daily.

PO (Adults and Children 50 kg): 0.06 mg/kg

every 3–4 hr initially, younger children may require

smaller initial doses of 0.03 mg/kg. Maximum dose 5

mg.

IV, IM, Subcut (Adults 50 kg): 1.5 mg every 3–4

hr as needed initially; may beq.

IV, IM, Subcut (Adults and Children 50 kg):

0.015 mg/kg mg every 3–4 hr as needed initially; may

beq.

IV (Adults): Continuous infusion (unlabeled)—

0.2–3 mg/hr depending on previous opioid use. An initial

bolus of twice the hourly rate in mg may be given

with subsequent breakthrough boluses of 50–100% of

the hourly rate in mg.

Rect (Adults): 3 mg every 6–8 hr initially as needed.

Hepatic Impairment

PO (Adults): Moderate hepatic impairment (extended–

release)—pinitial dose by 75%.

Renal Impairment

PO (Adults): Moderate renal impairment (extended–

release)—pinitial dose by 50%; Severe renal

impairment (extended–release)—pinitial dose

by 75%.

Antitussive

PO (Adults and Children 12 yr): 1 mg every 3–4

hr.

PO (Children 6–12 yr): 0.5 mg every 3–4 hr.

Availability (generic available)

Immediate-release tablets: 2 mg, 4 mg, 8 mg. Extended-

release tablets (abuse-deterrent): 4

mg, 8 mg, 12 mg, 16 mg, 32 mg. Controlled-release

capsules: 3 mg, 4.5 mg, 6 mg, 9 mg, 12

mg, 18 mg, 24 mg, 30 mg. Oral solution: 1

mg/mL. Injection: 1 mg/mL, 2 mg/mL, 4 mg/mL, 10

mg/mL. Suppositories: 3 mg.

HYDROcodone (hye-droe-koe-done) Hysingla ER, Zohydro ER HYDROcodone/ acetaminophen Anexsia, Norco HYDROcodone/ibuprofen Reprexain

 Indications

Extended-release product: Management of pain that

is severe enough to warrant daily, around-the-clock,

long-term opioid treatment where alternative treatment

options are inadequate. Combination products:

Management of moderate to severe pain. Antitussive

(usually in combination products with decongestants).

Action

Bind to opiate receptors in the CNS. Alter the perception

of and response to painful stimuli while producing

generalized CNS depression. Suppress the cough reflex

via a direct central action. Therapeutic Effects:

Decrease in severity of moderate pain. Suppression of

the cough reflex.

Pharmacokinetics

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

Metabolism and Excretion: Mostly metabolized

by the liver; eliminated in the urine (50–60% as metabolites,

10% as unchanged drug).

Half-life: 2.2 hr; Extended-release—8 hr.

TIME/ACTION PROFILE (analgesic effect)

ROUTE ONSET PEAK DURATION

PO 10–30 min 30–60 min 4–6 hr

PO-ER unknown unknown unknown

Contraindications/Precautions

Contraindicated in: Hypersensitivity to hydrocodone

(cross-sensitivity may exist to other opioids); Significant

respiratory depression; Paralytic ileus; Acute or

severe bronchial asthma or hypercarbia; Congenital

long QT syndrome (Hysingla only); Hypersensitivity to

acetaminophen/ibuprofen (for combination products);

Ibuprofen-containing products should be avoided in

patients with bleeding disorders or thrombocytopenia;

Acetaminophen-containing products should be avoided

in patients with severe hepatic or renal disease; Ibuprofen-

containing products should be avoided in patients

undergoing coronary artery bypass graft surgery; OB,

Lactation: Avoid chronic use; Products containing alcohol,

aspartame, saccharin, sugar, or tartrazine (FDC

yellow dye #5) should be avoided in patients who have

hypersensitivity or intolerance to these compounds.

Use Cautiously in: Head trauma;qintracranial

pressure; Severe renal, hepatic, or pulmonary disease;

Cardiovascular disease (ibuprofen-containing products

only); History of peptic ulcer disease (ibuprofen-containing

products only); Alcoholism; Difficulty swallowing;

Patients with undiagnosed abdominal pain; Prostatic

hyperplasia; OB: Labor and delivery; OB, Lactation:

Avoid chronic use; prolonged use of opioids during

pregnancy can result in neonatal opioid withdrawal

syndrome; Geri: Geriatric or debilitated patients (initial

doseprequired; more prone to CNS depression, constipation).

Adverse Reactions/Side Effects

Noted for hydrocodone only; see acetaminophen/ibuprofen

monographs for specific information on individual

components.

CNS: confusion, dizziness, sedation, euphoria, hallucinations,

headache, unusual dreams. EENT: blurred vision,

diplopia, miosis. Resp: respiratory depression.

CV: hypotension, bradycardia, QT interval prolongation

(Hysingla only). GI: constipation, dyspepsia, nausea,

choking, dysphagia, esophageal obstruction, vomiting.

GU: urinary retention. Endo: adrenal

insufficiency. Derm: sweating. Misc: physical dependence,

psychological dependence, tolerance.

Interactions

Drug-Drug: Use with extreme caution in patients receiving

MAO inhibitors; may produce severe, unpredictable

reactions—do not use within 14 days of each

other. Concurrent use of CYP3A4 inhibitors including

ritonavir, ketoconazole, itraconazole, fluconazole,

clarithromycin, erythromycin, nefazodone,

diltiazem, verapamil, nelfinavir, and fosamprenavirqlevels

and risk of opioid toxicity; careful monitoring

during initiation, dose changes, or discontinuation

of the inhibitor is recommended. Concurrent use with

CYP3A4 inducers including barbiturates, carbamazepine,

efavirenz, corticosteroids, modafinil,

nevirapine, oxcarbazepine, phenobarbital, phenytoin,

rifabutin, or rifampin maypfentanyl levels

and analgesia; if inducers are discontinued or dosage p,

patients should be monitored for signs of opioid toxicity

and necessary dose adjustments should be made.

Use with benzodiazepines or other CNS depressants

including otheropioids, non-benzodiazepine

sedative/hypnotics, anxiolytics, general anesthetics,

muscle relaxants, antipsychotics, and alcohol

may cause profound sedation, respiratory depression,

coma, and death; reserve concurrent use for when alternative

treatment options are inadequate. Administration

of partial antagonist opioids (buprenorphine,

butorphanol, nalbuphine, or pentazocine) mayp

analgesia or precipitate opioid withdrawal in physically

dependent patients. Anticholinergic drugs mayq

risk of urinary retention and constipation. Drugs that

affect serotonergic neurotransmitter systems, including

tricyclic antidepressants, SSRIs, SNRIs, MAO inhibitors,

TCAs, tramadol, trazodone, mirtazapine,

5–HT3 receptor antagonists, linezolid,

methylene blue, and triptansqrisk of serotonin syndrome.

Drug-Natural Products: Concomitant use of

kava-kava, valerian, skullcap, chamomile, or

hops canqCNS depression.

Route/Dosage

PO (Adults): Analgesic—2.5–10 mg q 3–6 hr as

needed; if using combination products, acetaminophen

dosage should not exceed 4 g/day and should not exceed

5 tablets/day of ibuprofen-containing products;

Antitussive—5 mg q 4–6 hr as needed; Extended-release

(Zohydro ER)—10 mg q 12 hr; mayqas needed

in increments of 10 mg q 12 hr q 3–7 days; Extendedrelease

(Hysingla)—20 mg once daily; mayqas

needed in increments of 10–20 mg/day q 3–5 days.

PO (Children): Analgesic (1–13 yr)—0.1–0.2 mg/

kg q 3–4 hr. Antitussive —0.6 mg/kg/day divided q

6–8 hr; (maximum doses 2 yr: 1.25 mg/dose; 2–12

yr: 5 mg/dose; 12 yr: 10 mg/dose).

Renal Impairment

PO (Adults): CCr 45 mL/min—Extended-release

(Hysingla):pinitial dose by 50%.

Hepatic Impairment

PO (Adults): Extended-release (Hysingla)—pinitial

dose by 50%.

Availability

Hydrocodone (generic available)

Extended-release capsules (Zohydro ER) (abuse

deterrent): 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 50

mg. Extended-release tablets (Hysingla ER)

(abuse deterrent): 20 mg, 30 mg, 40 mg, 60 mg, 80

mg, 100 mg, 120 mg. Syrup: 1 mg/mL. In combination

with: chlorpheniramine (Tussicaps, Tussionex,

Vituz); chlorpheniramine and pseudoephedrine

(Zutripro); guaifenesin (Flowtuss, Obredon); guaifenesin

and pseudoephedrine (Hycofenix); pseudoephedrine

(Rezira). See Appendix B.

Hydrocodone/Acetaminophen (generic

available)

Tablets: 2.5 mg hydrocodone/325 mg acetaminophen,

5 mg hydrocodone/325 mg acetaminophen (Anexsia 5/

325, Norco), 7.5 mg hydrocodone/325 mg acetaminophen

(Anexsia 7.5/325, Norco), 10 mg hydrocodone/

325 mg acetaminophen (Norco). Cost: Generic—5

mg/325 mg $15.08/100, 7.5 mg/325 mg $30.93/100,

10 mg/325 mg $41.59/100. Elixir/oral solution: 7.5

mg hydrocodone plus 325 mg acetaminophen/15 mL,

10 mg hydrocodone plus 325 mg acetaminophen/15

mL. Cost: Generic—$58.12/473 mL.

Hydrocodone/Ibuprofen (generic available)

Tablets: 2.5 mg hydrocodone/200 mg ibuprofen (Reprexain),

5 mg hydrocodone/200 mg ibuprofen, 7.5

mg hydrocodone/200 mg ibuprofen, 10 mg hydrocodone/

200 mg ibuprofen (Reprexain). Cost: Generic—

7.5 mg/200 mg $48.40/100.

hydralazine/isosorbide dinitrate (hye-dral-a-zeen eye-so-sor-bide di-ni-trate) BiDil

 Indications

Management of heart failure in black patients.

Action

BiDil is a fixed-dose combination of isosorbide dinitrate,

a vasodilator with effects on both arteries and

veins, and hydralazine, a predominantly arterial vasodilator.

Therapeutic Effects: Improved survival, increased

time to hospitalization and decreased symptoms

of heart failure in black patients.

Pharmacokinetics

See pharmacokinetic sections in hydralazine and isosorbide

dinitrate monographs of Davis’s Drug Guide for

Nurses for more information.

Absorption: Hydralazine—10–26% absorbed in

HF patients, absorption can be saturated leading to

largeqin absorption with higher doses; isosorbide

dinitrate—variable absorbed (10–90%) reflecting

first-pass hepatic metabolism.

Distribution: Hydralazine—widely distributed,

crosses the placenta, minimal amounts in breast milk;

isosorbide dinitrate—accumulates in muscle and venous

wall.

Metabolism and Excretion: Hydralazine—

mostly metabolized by GI mucosa and liver; isosorbide

dinitrate—undergoes extensive first-pass metabolism

in the liver, mostly metabolized by the liver, some metabolites

are vasodilators.

Half-life: Hydralazine—4 hr; isosorbide dinitrate—

2 hr. 

TIME/ACTION PROFILE (effect on BP)

ROUTE ONSET PEAK DURATION

hydralazine 45 min 2 hr 2–4 hr

isosorbide 15–40 min unknown 4 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity to either component;

Concurrent use of PDE-5 inhibitor (avanafil,

sildenafil, tadalafil, vardenafil) or riociguat.

Use Cautiously in: Severe renal/hepatic disease

(dose modification may be necessary); Head trauma or

cerebral hemorrhage; Geri: Start with lower doses; OB:

May compromise maternal/fetal circulation; Lactation:

Safety not established; Pedi: Safety not established.

Adverse Reactions/Side Effects

Hydralazine

CNS: dizziness, drowsiness, headache. CV: tachycardia,

angina, arrhythmias, edema, orthostatic hypotension.

GI: diarrhea, nausea, vomiting. Derm: rash. F

and E: sodium retention. MS: arthralgias, arthritis.

Neuro: peripheral neuritis. Misc: drug-induced lupus

syndrome.

Isosorbide Dinitrate

CNS: dizziness, headache, apprehension, weakness.

CV: hypotension, tachycardia, paradoxic bradycardia,

syncope. GI: abdominal pain, nausea, vomiting. Misc:

cross-tolerance, flushing, tolerance.

Interactions

Drug-Drug: Concurrent use of avanafil, sildenafil,

tadalafil, or vardenafil may result in severe hypotension;

concurrent use contraindicated. Concurrent use

of riociguat may result in severe hypotension; concurrent

use contraindicated.qrisk of hypotension with

other antihypertensives, acute ingestion of alcohol,

and phenothiazines. MAO inhibitors may exaggerate

hypotension. Maypthe pressor response to epinephrine.

Beta blockersptachycardia from hydralazine

(therapy may be combined for this reason).

Metoprolol and propranolol mayqhydralazine levels.

Hydralazineqlevels of metoprolol and propranolol.

Route/Dosage

PO (Adults): 1 tablet 3 times daily, may beqto 2 tablets

3 times daily.

Availability

Tablets: hydralazine 37.5 mg/isosorbide dinitrate 20 mg.

hydrALAZINE (hye-dral-a-zeen) Apresoline

 Indications

Moderate to severe hypertension (with a diuretic). Unlabeled

Use: HF unresponsive to conventional therapy

with digoxin and diuretics.

Action

Direct-acting peripheral arteriolar vasodilator. Therapeutic

Effects: Lowering of BP in hypertensive patients

and decreased afterload in patients with HF. 

Pharmacokinetics

Absorption: Rapidly absorbed following oral administration;

well absorbed from IM sites.

Distribution: Widely distributed. Crosses the placenta;

enters breast milk in minimal concentrations.

Metabolism and Excretion: Mostly metabolized

by the GI mucosa and liver by N-acetyltransferase

(rate of acetylation is genetically determined [slow acetylators

haveqhydralazine levels andqrisk of toxicity;

fast acetylators havephydralazine levels andpresponse]).

Half-life: 2–8 hr.

TIME/ACTION PROFILE (antihypertensive

effect)

ROUTE ONSET PEAK DURATION

PO 45 min 2 hr 2–4 hr

IM 10–30 min 1 hr 3–8 hr

IV 5–20 min 15–30 min 2–6 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Some products

contain tartrazine and should be avoided in patients

with known intolerance.

Use Cautiously in: Cardiovascular or cerebrovascular

disease; Severe renal and hepatic impairment

(dose modification may be necessary); OB, Lactation:

Has been used safely during pregnancy.

Adverse Reactions/Side Effects

CNS: dizziness, drowsiness, headache. CV: tachycardia,

angina, arrhythmias, edema, orthostatic hypotension.

GI: diarrhea, nausea, vomiting. Derm: rash.

MS: arthralgias, arthritis. Neuro: peripheral neuropathy.

Misc: drug-induced lupus syndrome.

Interactions

Drug-Drug:qhypotension with acute ingestion of

alcohol, other antihypertensives, or nitrates. MAO

inhibitors may exaggerate hypotension. Mayppressor

response to epinephrine. NSAIDs maypantihypertensive

response. Beta blockersptachycardia

from hydralazine (therapy may be combined for this

reason). Metoprolol and propranololqlevels.q

levels of metoprolol and propranolol.

Route/Dosage

PO (Adults): Hypertension—10 mg 4 times daily initially.

After 2–4 days mayqto 25 mg 4 times daily for

the rest of the 1st week; may thenqto 50 mg 4 times

daily (up to 300 mg/day). Once maintenance dose is

established, twice-daily dosing may be used. HF—25–

37.5 mg 4 times daily; may bequp to 300 mg/day in

3–4 divided doses.

PO (Children 1 mo): Initial—0.75–1 mg/kg/day

in 2–4 divided doses, not to exceed 25 mg/dose; may

qgradually to 5 mg/kg/day in infants and 7.5 mg/kg/

day in children (not to exceed 200 mg/day) in 2–4 divided

doses.

IM, IV (Adults): Hypertension—5–40 mg repeated

as needed. Eclampsia—5mg q 15–20min; if no response

after a total of 20 mg, consider an alternative

agent.

IM, IV (Children 1mo): Initial—0.1–0.2 mg/kg/

dose (not to exceed 20 mg) every 4–6 hr as needed,

up to 1.7–3.5 mg/kg/day in 4–6 divided doses.

Availability (generic available)

Tablets: 10 mg, 25 mg, 50 mg, 100 mg. Injection: 20

mg/mL. In combination with: isosorbide dinitrate

(BiDil). See Appendix B.

HUMAN PAPILLOMAVIRUS VACCINE (hyoo-man pa-pil-lo-ma)

 Indications

Gardasil and Gardasil 9: Prevention of cervical, vulvar,

vaginal, and anal cancers and genital warts (in females)

and anal cancer and genital warts (in males).

Cervarix: Prevention of cervical cancer.

Action

Vaccination results in antibodies to HPV viruses that are

causative agents for cervical, vulvar, vaginal, and anal

cancers and genital warts. Therapeutic Effects:

Prevention of cervical, vulvar, vaginal, and anal cancers

and genital warts.

Pharmacokinetics

Absorption: Well absorbed following IM administration.

Distribution: Unknown.

Metabolism and Excretion: Unknown.

Half-life: Unknown.

TIME/ACTION PROFILE (antibody response)

ROUTE ONSET PEAK DURATION

IM unknown 6 mo* unknown

*After third vaccination.

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Thrombocytopenia/

bleeding disorder; OB: Limited data available;

use only if potential benefit justifies potential risk to fetus.

Use Cautiously in: Current/recent febrile illness;

Immunosuppression maypantibody response; Lactation:

Excretion into breast milk unknown; Pedi: Children

9 yr (safety not established). 

Adverse Reactions/Side Effects

Neuro: fainting. Local: injection site reactions.

Misc: ANAPHYLAXIS (RARE).

Interactions

Drug-Drug: Immunosuppressants or antineoplastics

maypantibody response.

Route/Dosage

IM (Adults and Children—males and females 9–

26 yr): Gardasil and Gardasil 9—Three 0.5 mL

doses at 0, 2, and 6 mo.

IM (Adults and Children—females 9–25 yr):

Cervarix—Three 0.5 mL doses at 0, 2, and 6 mo.

Availability

Sterile preparation for intramuscular administration

(Gardasil): 20 mcg of HPV 6 L1 protein, 40

mcg of HPV 11 L1 protein, 40 mcg of HPV 16 L1 protein,

and 20 mcg of HPV 18 L1 protein/0.5-mL dose.

Sterile preparation for intramuscular administration

(Gardasil 9): 30 mcg of HPV 6 L1 protein, 40

mcg of HPV 11 L1 protein, 60 mcg of HPV 16 L1 protein,

40 mcg of HPV 18 L1 protein, 20 mcg of HPV 31

L1 protein, 20 mcg of HPV 33 L1 protein, 20 mcg of

HPV 45 L1 protein, 20 mcg of HPV 52 L1 protein, and

20 mcg of HPV 58 L1 protein/0.5-mL dose. Sterile

preparation for intramuscular administration

(Cervarix): 20 mcg of HPV type 16 L1 protein and 20

mcg of HPV type 18 L1 protein.