classification

PHARMACOTHERAPEUTIC: Immunologic agent. CLINICAL: Immunosuppressant (see p. 123C).

Action

Inhibits T-lymphocyte activation by binding to intracellular proteins, forming a complex, inhibiting phosphatase activity. Therapeutic Effect: Suppresses immunologically mediated inflammatory response; prevents organ transplant rejection.

Pharmacokinetics

Variably absorbed after PO administration (food reduces absorption). Protein binding: 99%. Metabolized in liver. Primarily eliminated in feces. Not removed by hemodialysis. Half-life: 21–61 hrs.

Uses

PO/injection: Prophylaxis of organ rejection in pts receiving allogeneic liver, kidney, heart transplant. Should be used concurrently with adrenal corticosteroids. In heart and kidney transplants pts, should be used in conjunction with azathioprine or mycophenolate. Topical: Moderate to severe atopic dermatitis in immunocompetent pts. OFF-LABEL: Prevention of organ rejection in lung, small bowel recipients; prevention and treatment of graft-vs-host disease in allogeneic hematopoietic stem cell transplantation.

Precautions

Contraindications: None known. Cautions: Hypersensitivity to HCO-60 polyoxyl 60 hydrogenated castor oil (used in solution for injection). Immunosuppressed pts, renal/hepatic impairment, concurrent use with cyclosporine (increases risk of nephrotoxicity). Concurrent use of strong CYP3A4 inhibitors or inducers. Pts at risk for pure red cell aplasia (e.g., concurrent use of mycophenolate). Topical: Exposure to sunlight.

 ​Lifespan considerations

Pregnancy/Lactation: Crosses placenta. Hyperkalemia, renal dysfunction noted in neonates. Distributed in breast milk. Breastfeeding not recommended. Pregnancy Category C. Children: May require higher dosages (decreased bioavailability, increased clearance). May make post-transplant lymphoproliferative disorder more common, esp. in pts younger than 3 yrs. Elderly: Age-related renal impairment may require dosage adjustment.

Interactions

DRUG: Aluminium-containing antacids may increase tacrolimus concentration. CYP3A4 inhibitors (e.g., erythromycin, ketoconazole), protease inhibitors, calcium channel blockers may increase concentration/effects. CYP3A4 inducers (e.g., rifampin) may decrease concentration/effects. May increase levels of cyclosporine. HERBAL: Echinacea, St. John’s wort may decrease concentration/effects. FOOD: Food decreases rate/extent of absorption. Grapefruit products may increase concentration, toxicity (potential for nephrotoxicity). LAB VALUES: May increase serum glucose, BUN, creatinine, potassium, triglycerides, cholesterol, bilirubin, amylase, AST, ALT. May decrease serum magnesium, Hgb, Hct, platelets. May alter leukocytes.

Availability (Rx)

Capsules (Prograf): 0.5 mg, 1 mg, 5 mg. Injection Solution (Prograf): 5 mg/ml. Ointment (Protopic): 0.03%, 0.1%.

Reconstitution • Dilute with appropriate amount (250–1,000 ml, depending on desired dose) 0.9% NaCl or D₅W to provide concentration between 0.004 and 0.02 mg/ml.

Rate of Administration • Give as continuous IV infusion. • Continuously monitor pt for anaphylaxis for at least 30 min after start of infusion. • Stop infusion immediately at first sign of hypersensitivity reaction.

Storage • Store diluted infusion solution in glass or polyethylene containers and discard after 24 hrs. • Do not store in PVC container (decreased stability, potential for extraction).

IV incompatibilities

Acyclovir.

IV compatibilities

Calcium gluconate, dexamethasone (Decadron), diphenhydramine (Benadryl), dobutamine (Dobutrex), dopamine (Intropin), furosemide (Lasix), heparin, hydromorphone (Dilaudid), insulin, leucovorin, lorazepam (Ativan), morphine, nitroglycerin, potassium chloride.

PO: ADULTS, ELDERLY: 0.1–0.15 mg/kg/day in 2 divided doses 12 hrs apart. Begin oral therapy no sooner than 6 hrs post-transplant. CHILDREN: 0.15–0.2 mg/kg/day in 2 divided doses 12 hrs apart. Begin oral therapy no sooner than 6 hrs post-transplant.

IV: ADULTS, ELDERLY, CHILDREN: 0.03–0.05 mg/kg/day as continuous infusion.

Side effects

Frequent (greater than 30%): Headache, tremor, insomnia, paresthesia, diarrhea, nausea, constipation, vomiting, abdominal pain, hypertension. Occasional (29%–10%): Rash, pruritus, anorexia, asthenia (loss of strength, energy), peripheral edema, photosensitivity.

Adverse effects/toxic reactions

Nephrotoxicity (characterized by increased serum creatinine, decreased urinary output), neurotoxicity (tremor, headache, altered mental status), pleural effusion occur commonly. Thrombocytopenia, leukocytosis, anemia, atelectasis, sepsis, infection occur occasionally.

Assess past medical history, esp. renal function; medication history, use of other immunosuppressants. Have aqueous solution of epinephrine 1:1,000, O₂ available at bedside before beginning IV infusion. Assess pt continuously for first 30 min following start of infusion and at frequent intervals thereafter.

classification

PHARMACOTHERAPEUTIC: Phosphodiesterase inhibitor. CLINICAL: Erectile dysfunction adjunct.

Action

Inhibits phosphodiesterase type 5, the enzyme responsible for degrading cyclic guanosine monophosphate in corpus cavernosum of penis, pulmonary vascular smooth muscle; resulting in smooth muscle relaxation, increased blood flow. Therapeutic Effect: Facilitates erection, improves exercise ability.

Pharmacokinetics

Rapidly absorbed after PO administration. Protein binding: 94%. Metabolized in liver. Primarily eliminated in feces. Drug has no effect on penile blood flow without sexual stimulation. Half-life: 17.5 hrs.

Uses

Cialis: Treatment of erectile dysfunction (ED). Treatment of benign prostatic hyperplasia (BPH). Simultaneous treatment of ED and BPH. Adcirca: Treatment of pulmonary arterial hypertension (PAH).

Precautions

Contraindications: Concurrent use of nitrates in any form, severe hepatic impairment. Cautions: Concurrent use of alpha-adrenergic blockers, renal/hepatic impairment (not recommended in pts with severe hepatic impairment or cirrhosis), anatomical deformation of penis, pts who may be predisposed to priapism (sickle cell anemia, multiple myeloma, leukemia), left ventricular outflow obstruction (e.g., aortic stenosis), bleeding disorders, peptic ulcer, elderly, concurrent use of strong CYP3A4 inhibitors.

 ​Lifespan considerations

Pregnancy/Lactation: Pregnancy Category B. Children: Not indicated in this pt population. Elderly: No age-related precautions noted.

Interactions

DRUG: Alcohol increases risk of orthostatic hypotension. Alpha-adrenergic blocks, other antihypertensive agents may increase risk of hypotension. Nitrates contraindicated; may cause life-threatening hypotension. CYP3A4 inhibitors (e.g., erythromycin, itraconazole, ketoconazole, ritonavir, saquinavir) may increase concentration. HERBAL: St. John’s wort may alter concentration/effects. FOOD: Grapefruit products may increase concentration, toxicity. LAB VALUES: May alter hepatic function levels, increase GGTP.

Availability (Rx)

Tablets (Cialis): 2.5 mg, 5 mg, 10 mg, 20 mg. (Adcirca): 20 mg.

• May give without regard to food. • Take at least 30 min before anticipated sexual activity. • Administer Adcirca dose once daily all at same time. Do not divide dosage.

PO: ADULTS, ELDERLY: Once daily dosing: 2.5 mg. Range: 2.5–5 mg based on tolerability. Maximum: 2.5 mg (with CYP3A4 inhibitors). As needed dosing: 10 mg at least 30 min prior to anticipated sexual activity. Range: 5–20 mg. No more than one dose/24 hr. Maximum: 10 mg (with CYP3A4 inhibitors) no more frequently than q72h.

Side effects

Occasional: Headache, dyspepsia (heartburn, indigestion, epigastric pain), back pain, myalgia, nasal congestion, flushing, sudden hearing loss, visual field loss, postural hypotension.

Adverse effects/toxic reactions

Prolonged erections (lasting over 4 hrs), priapism (painful erections lasting over 6 hrs) occur rarely. Angina, chest pain, MI have been reported.

Assess cardiovascular status before initiating treatment for erectile dysfunction. Obtain baseline renal/hepatic function tests. Screen for use of nitrate-based medications.

classification

PHARMACOTHERAPEUTIC: Nonsteroidal antiestrogen. CLINICAL: Anti-neoplastic (see p. 90C).

Action

Competes with estradiol for estrogen-receptor binding sites in breast, uterus, vaginal cells. Therapeutic Effect: Inhibits DNA synthesis, estrogen response.

Pharmacokinetics

Well absorbed from GI tract. Metabo-lized in liver. Primarily eliminated in feces by biliary system. Half-life: 7 days.

Uses

Adjunct treatment in advanced breast cancer after primary treatment with surgery and radiation, reduce risk of breast cancer in women at high risk, reduce risk of invasive breast cancer in women with ductal carcinoma in situ (DCIS), metastatic breast cancer in women and men. OFF-LABEL: Induction of ovulation, treatment of desmoid tumors. Treatment of mastalgia, gynecomastia; ovarian, endometrial cancer; uterine sarcoma; precocious puberty in females; risk reduction in women with Paget’s disease of breast.

Precautions

Contraindications: Concomitant coumarin-type therapy when used in treatment of breast cancer in high-risk women, history of deep vein thrombosis (DVT) or pulmonary embolism (in high-risk women for breast cancer and in women with DCIS). Cautions: Leukopenia, thrombocytopenia, pregnancy, history of thromboembolic events, hyperlipidemia, concomitant drug therapy affecting CYP and Pgp (hepatic) metabolic pathways.

 ​Lifespan considerations

Pregnancy/Lactation: If possible, avoid use during pregnancy, esp. first trimester. May cause fetal harm. Unknown if distributed in breast milk. Breastfeeding not recommended. Pregnancy Category D. Children: Safe and effective in girls 2–10 yrs with McCune Albright syndrome, precocious puberty. Elderly: No age-related precautions noted.

Interactions

DRUG: May increase effects of warfarin. May decrease effects of anastrozole. Cytotoxic agents may increase risk of thromboembolic events. Moderate/strong CYP2D6 inhibitors (e.g., fluoxetine, sertraline) may decrease efficacy and increase risk of breast cancer. HERBAL: Avoid black cohosh, dong quai in estrogen-dependent tumors. St. John’s wort may decrease concentration/effects. FOOD: None known. LAB VALUES: May increase serum cholesterol, calcium, triglycerides, hepatic enzymes.

Availability (Rx)

Solution, Oral (Soltamox): 10 mg/5 ml. Tablets: 10 mg, 20 mg.

• Give without regard to food.

PO: ADULTS, ELDERLY: 20–40 mg/day. Give doses greater than 20 mg/day in divided doses. Duration is 5 yrs for premenopausal women and 2–3 yrs followed by an aromatase inhibitor to complete 5 yrs.

Side effects

Frequent: Women (greater than 10%): Hot flashes, nausea, vomiting. Occasional: Women (9%–1%): Changes in menstruation, genital itching, vaginal discharge, endometrial hyperplasia, polyps. Men: Impotence, decreased libido. Men and women: Headache, nausea, vomiting, rash, bone pain, confusion, weakness, drowsiness.

Adverse effects/toxic reactions

Retinopathy, corneal opacity, decreased visual acuity noted in pts receiving extremely high dosages (240–320 mg/day) for longer than 17 mos.

Obtain estrogen receptor assay prior to therapy. Obtain baseline breast and gynecologic exams, mammogram results. CBC, serum calcium levels should be checked before and periodically during therapy.

Fixed-combination(s)

Jalyn: tamsulosin/dutasteride (an androgen hormone inhibitor): 0.4 mg/0.5 mg.

classification

PHARMACOTHERAPEUTIC: Alpha₁-adrenergic blocker. CLINICAL: Benign prostatic hyperplasia agent.

Action

Targets receptors around bladder neck, prostate capsule. Therapeutic Effect: Relaxes smooth muscle, improves urinary flow, symptoms of prostatic hyperplasia.

Pharmacokinetics

Well absorbed, widely distributed. Protein binding: 94%–99%. Metabolized in liver. Primarily excreted in urine. Unknown if removed by hemodialysis. Half-life: 9–13 hrs.

Uses

Treatment of symptoms of benign prostatic hyperplasia (BPH), alone or in combination with dutasteride (Avodart). OFF-LABEL: Treatment of bladder outlet obstruction or dysfunction. Facilitate expulsion of ureteral stones.

Precautions

Contraindications: None known. Cautions: Concurrent use of phosphodiesterase (PDE5) inhibitors (sildenafil, tadalafil, vardenafil).

 ​Lifespan considerations

Pregnancy/Lactation: Not indicated for use in women. Pregnancy Category B. Children: Not indicated in this pt population. Elderly: No age-related precautions noted.

Interactions

DRUG: Other alpha-adrenergic blocking agents (e.g., doxazosin, prazosin, terazosin) may increase alpha-blockade effects. Sildenafil, tadalafil, vardenafil may cause symptomatic hypotension. CYP3A4 inhibitors (e.g., ketoconazole) may increase concentration. HERBAL: Avoid saw palmetto (limited experience with this combination). Black cohosh, periwinkle may increase hypotensive effect. St. John’s wort may decrease concentration/effects. FOOD: Grapefruit products may increase potential for orthostatic hypotension. LAB VALUES: None known.

Availability (Rx)

Capsules:  0.4 mg.

• Give at same time each day, 30 min after the same meal. • Do not break, crush, dissolve, or open capsule.

PO: ADULTS: 0.4 mg once a day, approximately 30 min after same meal each day. May increase dosage to 0.8 mg if inadequate response in 2–4 wks.

Side effects

Frequent (9%–7%): Dizziness, drowsiness. Occasional (5%–3%): Headache, anxiety, insomnia, orthostatic hypotension. Rare (less than 2%): Nasal congestion, pharyngitis, rhinitis, nausea, vertigo, impotence.

Adverse effects/toxic reactions

First-dose syncope (hypotension with sudden loss of consciousness) may occur within 30–90 min after initial dose. May be preceded by tachycardia (pulse rate of 120–160 beats/min).

Assess history of prostatic hyperplasia (difficulty initiating urine stream, dribbling, sense of urgency, leaking). Question for sensitivity to tamsulosin, or use of other alpha-adrenergic blocking agents, warfarin. Obtain vital signs.

classification

PHARMACOTHERAPEUTIC: Centrally-acting synthetic analgesic. CLINICAL: Analgesic.

Action

Binds to and activates mu-opioid receptors in the central nervous system, increases norepinephrine by inhibiting its reabsorption into nerve cells. Therapeutic Effect: Produces analgesia.

Pharmacokinetics

Metabolized in liver. Primarily excreted in the urine. Widely distributed. Protein binding: 20%. Half-life: 4 hrs.

Uses

Nucynta: Relief of moderate to severe acute pain in adults 18 yrs and older. Nucynta ER: Management of moderate to severe chronic pain when around-the-clock analgesic needed for extended period. Treatment of diabetic neuropathy pain.

Precautions

Contraindications: Severe respiratory depression, acute or severe bronchial asthma; hypercapnia in uncontrolled settings, known or suspected paralytic ileus, concurrent use or ingestion within 14 days of MAOI use. Cautions: Respiratory disease or respiratory compromise (e.g., hypoxia, hypercapnia, or decreased respiratory reserve), asthma, COPD, severe obesity, sleep apnea syndrome, myxedema coma, CNS depression; pts with head injury, intracranial lesions, pancreatic or biliary disease, renal or hepatic impairment, history of seizures, conditions that increase risk of seizures; pts at risk for hypotension, adrenal insufficiency, hypothyroidism, prostatic hyperplasia/urinary stricture; concurrent use with serotonergic agents; elderly; debilitated or cachetic pts.

 ​Lifespan considerations

Pregnancy/Lactation: Unknown if drug crosses placenta or is distributed in breast milk. Pregnancy Category C. Children: Not recommended for use in this pt population. Elderly: Age-related renal impairment may increase risk of side effects.

Interactions

DRUG: Alcohol, CNS depressants may increase CNS depression, respiratory depression. MAOIs, SSRIs (e.g., fluoxetine), tricyclic antidepressants (e.g., amitriptyline), triptans (e.g., sumatriptan) may increase risk of serotonin syndrome. HERBAL: Kava kava, St. John’s wort, valerian may increase CNS depression. St. John’s wort may increase risk for serotonin syndrome. FOOD: None known. LAB VALUES: None significant.

Availability (Rx)

Tablets: 50 mg, 75 mg, 100 mg.

Tablets, Extended-Release: 50 mg, 100 mg, 150 mg, 200 mg, 250 mg.

• Give without regard to food. • Tablets may be crushed. • Give extended-release tablets whole; do not break, crush, dissolve, or divide.

Indications/routes/dosage

Note: Not recommended in severe renal or hepatic impairment.

Side effects

Frequent (greater than 10%): Nausea, dizziness, vomiting, sleepiness, headache.

Adverse effects/toxic reactions

Respiratory depression, serotonin syndrome have been reported.

Assess onset, type, location, and duration of pain. Obtain vital signs before giving medication. If respirations are 12/min or lower, withhold medication, contact physician. Question history of hepatic impairment.

classification

PHARMACOTHERAPEUTIC: Human glucagon-like peptide-2. CLINICAL: Short bowel syndrome (short gut syndrome, short gut) agent.

Action

Analogue of naturally occurring peptide secreted by L cells of distal intestine, known to increase intestinal, portal blood flow, and inhibit gastric secretion. Therapeutic Effect: Improves intestinal absorption.

Pharmacokinetics

Degrades into small peptides, amino acids via catabolic pathway. Primarily excreted in urine. 86–89% bioavailability following subcutaneous injection. Peak plasma concentration: 3–5 hrs. Half-life: 1.3–2 hrs.

Uses

Treatment of adults with short bowel syndrome (SBS) who are dependent on parenteral support.

Precautions

Contraindications: None known. Cautions: Cardiovascular disease, HF, pts at increased risk for malignancy, biliary tract (gallbladder, pancreatic) disease, hypervolemia, stenosis, renal impairment.

 ​Lifespan considerations

Pregnancy/Lactation: Unknown if distributed in breast milk. Pregnancy Category B. Children: Safety and efficacy not established. Elderly: No age-related precautions noted.

Interactions

DRUG: May increase absorption of any concomitant oral medication. HERBAL: None significant. FOOD: None known. LAB VALUES: None significant.

Availability (Rx)

Injection, Powder for Reconstitution: 5 mg (delivers maximum of 0.38 ml containing 3.8 mg teduglutide).

Reconstitution • If diluent syringe (contains 0.5 ml Sterile Water for Injection) has a white snap-off cap, snap or twist off white cap. • If diluent syringe has a gray screw top, unscrew top counter clockwise. • Push prefilled syringe into vial containing teduglutide. • After all diluent has gone into vial, remove syringe, needle and discard. • Allow vial to sit for 30 sec. • Gently roll vial for 15 sec (do not shake) and let stand for 2 min. • Withdraw prescribed dose, discard remaining fluid. • Use within 3 hrs following reconstitution. • Use abdomen, thighs, upper arms for injection. • Avoid injection sites where skin is tender, bruised, red, or hard.

Storage • Store kit in refrigerator. • Reconstituted solution should appear as a clear, colorless to light straw-colored liquid. • Discard if particulate is present. • Drug should be completely dissolved before solution is withdrawn from vial.

Subcutaneous: ADULTS/ELDERLY: 0.05 mg/kg/day.

Side effects

Frequent (30%–22%): Abdominal pain, nausea, injection site reactions. Occasional (18%–14%): Headache, abdominal distention, vomiting. Rare (9%): Flatulence, hypersensitivity, appetite disorders, sleep disturbances.

Adverse effects/toxic reactions

Upper respiratory tract infection occurs in 12% of pts. Fluid overload (hypervolemia) has been noted in 7% of pts. Potential for hypovolemia is increased in pts with cardiovascular disease, HF. Therapy increases risk for acceleration for neoplastic growth. Cholecystitis, cholangitis, cholelithiasis, pancreatitis has been reported.

Obtain baseline serum chemistries, hepatic function test, lipase, amylase. Colonoscopy (or alternate imaging) with removal of polyps should be completed within 5 mos prior to initiating treatment.

classification

PHARMACOTHERAPEUTIC: Protease inhibitor. CLINICAL: Antiviral.

Action

Inhibits hepatitis C virus (HCV) protease needed for cleavage of HCV-encoded polyproteins by binding to active serine protease sites. Therapeutic Effect: Inhibits viral replication of hepatitis C virus.

Pharmacokinetics

Well absorbed following PO administration. Peak concentration: 4–5 hrs. Protein binding: 59%–75%. Metabolized in liver. Excreted primarily in feces. Minimal removal by hemodialysis. Half-life: 9–11 hrs.

Uses

Treatment of chronic hepatitis C genotype 1 in combination with peginterferon alfa and ribavirin in adults with compensated liver disease, including cirrhosis, who are previously untreated or who have failed previous interferon and ribavirin therapy.

Precautions

◀ ALERT ▶ Safety and efficacy not established in decompensated cirrhosis, organ transplant, HIV, hepatitis B, previous failed therapies with protease inhibitors.

Contraindications: Pregnancy, male partners of pregnant women, drugs utilizing CYP3A for clearance (see drug interactions), any contraindications to peginterferon alfa or ribavirin. Cautions: Baseline anemia, moderate to severe hepatic impairment.

 ​Lifespan considerations

Pregnancy/Lactation: Strictly avoid pregnancy. May cause birth defects or fetal demise. Pregnancy Category B (X when used with ribavirin). Women of childbearing age must use 2 different forms of birth control: intrauterine device and barrier methods during treatment plus at least 6 mos after treatment. Hormonal contraceptives may have decreased effectiveness. Do not initiate therapy until negative pregnancy test confirmed. Unknown if drug crosses placenta or is distributed in breast milk. Children: Safety and efficacy not established. Elderly: No age-related precautions noted.

Interactions

DRUG: Contraindicated with alfuzosin, atorvastatin, dihydroergotamine, ergonovine, ergotamine, lovastatin, methylergonovine, midazolam, pimozide, rifampin, sildenafil, simvastatin, tadalafil, triazolam. May increase concentrations of antiarrhythmics (amiodarone, digoxin, quinidine), antifungals (itraconazole, ketoconazole), calcium channel blockers (amlodipine, diltiazem, nicardipine), clarithromycin, colchicine, desipramine, dexamethasone, fluticasone, immunosuppressants, oral contraceptives, rifabutin, salmeterol, tadalafil, trazadone, vardenafil. HERBAL: St. John’s wort may decrease effectiveness. FOOD: Low-fat meals may decrease absorption. LAB VALUES: May decrease RBC, Hgb, Hct, neutrophils, leukocytes, platelets. May increase serum bilirubin, uric acid levels.

Availability (Rx)

Tablets: 375 mg.

Administration/handling

• Give with food containing approximately 20 grams of fat. Take approximately q7–9hr.

PO: ADULTS, ELDERLY: 750 mg 3 times a day with food for 12 wks. Use triple therapy with peginterferon alfa, ribavirin. Duration based on response-guided therapy (RGT) guidelines.

Side effects

Frequent (56%–26%): Rash, fatigue, pruritus, nausea, diarrhea. Occasional (13%–6%): Vomiting, hemorrhoids, anorectal discomfort, dysgeusia, anal pruritus.

Adverse effects/toxic reactions

Increased risk of thromboembolic events associated with peginterferon, erythropoiesis-stimulating agent. Serious skin reactions including drug rash with eosinophilia, systemic symptoms, Stevens-Johnson syndrome reported. Simultaneous use of contraindicated medications may result in hypertension/hypotension, peripheral vasospasm/ischemia (ergot toxicity), arrhythmias, rhabdomyolysis (statins), hyperkalemia (oral contraception), visual abnormalities, syncope, increased sedation or respiratory depression (sedative/hypnotics), loss of virologic response.

Assess vital signs, O₂ saturation. Obtain CBC, HCV-RNA level, serum chemistries, hepatic function test, TSH. Receive full medication history including vitamins, herbal products; screen for contraindications. Confirm negative pregnancy test before initiating treatment. Question history of anemia, HIV, hepatitis B.

classification

PHARMACOTHERAPEUTIC: Lipoglycopeptide antibacterial. CLINICAL: Antibiotic.

Action

Inhibits bacterial cell wall synthesis by blocking polymerization and cross-linking of peptidoglycan. Disrupts membrane potential and changes cell wall permeability. Therapeutic Effect: Bactericidal. Antibiotic.

Pharmacokinetics

Not metabolized in liver; pathway unspecified. Protein binding: 90%. Primarily excreted unchanged in urine. Not removed by hemodialysis. Half-life: 8–9 hrs.

Uses

Treatment of complicated skin, soft tissue infections caused by gram-positive microorganisms, including methicillin-susceptible or methicillin-resistant S. aureus, vancomycin-susceptible Enterococcus. Treatment of hospital-acquired and ventilator-associated bacterial pneumonia caused by susceptible isolates of S. aureus.

Precautions

Contraindications: Prior hypersensitivity reactions to telavancin. Cautions: Renal impairment, concurrent therapy with other nephrotoxic medications (NSAIDs, ACE inhibitors, aminoglycosides). Avoid use in pts with history of congenital QT syndrome, known prolongation of QT interval, uncompensated HF, severe left ventricular hypertrophy, or receiving treatment with other drugs known to prolong QT interval.

 ​Lifespan considerations

Pregnancy/Lactation: May cause fetal harm at regular dosage. Unknown if distributed in breast milk. Pregnancy Category C. Children: Safety and efficacy not established. Elderly: Age-related renal impairment may increase risk of nephrotoxicity; dosage adjustment recommended.

Interactions

DRUG: Telavancin may increase levels/effects of dronedarone, nilotinib, pimozide, quinine, tetrabenazene, thioridazine, ziprasidone. Ciprofloxacin may increase levels/effect. HERBAL: None significant. FOOD: None known. LAB VALUES: May alter serum potassium. May increase serum bilirubin, AST, ALT, BUN, creatinine, PT, aPTT, INR. May decrease Hgb, Hct, WBC count.

Availability (Rx)

Injection, Powder for Reconstitution: 250-mg, 750-mg single-dose vial.

◀ ALERT ▶ Give by intermittent IV infusion (piggyback). Do not give by IV push (may result in hypotension).

Reconstitution • 250-mg vial: Reconstitute with 15 ml Sterile Water for Injection, D₅W, or 0.9% NaCl to provide concentration of 15 mg/ml (total volume approximately 17 ml). • 750-mg vial: Reconstitute with 45 ml Sterile Water for Injection, D₅W, or 0.9% NaCl to provide concentration of 15 mg/ml (total volume approximately 50 ml). • Prior to administration, further dilute with D₅W or 0.9% NaCl to final concentration of 0.6–8 mg/ml. • Do not shake.

Rate of Administration • Infuse over at least 60 min.

Storage • Discard if particulate is present. • Following reconstitution, drug is stable for 4 hrs at room temperature or 72 hrs if refrigerated in vial or infusion bag.

IV incompatibility

Amphotericin, colistimethate, levofloxacin (Levaquin), micafungin (Mycomine).

IV compatibility

Azithromycin, caspofungin, cefepime, ceftazidine, ceftriaxone, ciprofloxacin, doripenem, doxycycline, gentamicin, ertapenem, fluconazole, meropenem, tobramycin, pantoprazole, piperacillin-tazobactam, tigecycline.

IV Infusion: ADULTS, ELDERLY: 10 mg/kg once every 24 hrs for 7–21 days. Duration based on severity, infection site, and clinical progress of pt.

Side effects

Frequent (33%–27%): Taste disturbance (metallic or soapy), nausea. Occasional (14%–6%): Vomiting, foamy urine, diarrhea, dizziness, pruritus. Rare (4%–2%): Rigors, rash, infusion site pain, anorexia, infusion site erythema.

Adverse effects/toxic reactions

Nephrotoxicity (acute kidney injury, acute tubular necrosis, renal failure); diarrhea due to C. difficile may occur. “Red-man syndrome” characterized by erythema on face, neck, upper torso; tachycardia, hypotension, myalgia, angioedema may occur from too-rapid rate of infusion.

Obtain pregnancy test prior to treatment. Obtain baseline serum BUN, creatinine, creatinine clearance prior to initiating therapy, every 48–72 hrs, and after treatment is completed. Obtain culture and sensitivity tests before giving first dose (therapy may begin before results are known).

Fixed-combination(s)

Micardis HCT: telmisartan/hydrochlorothiazide (a diuretic): 40 mg/12.5 mg, 80 mg/12.5 mg. Twynsta: telmisartan/amlodipine (a calcium channel blocker): 40 mg/5 mg, 40 mg/10 mg, 80 mg/5 mg, 80 mg/10 mg.

classification

PHARMACOTHERAPEUTIC: Angiotensin II receptor antagonist. CLINICAL: Antihypertensive (see p. 11C).

Action

Blocks vasoconstrictor and aldosterone-secreting effects of angiotensin II, inhibiting binding of angiotensin II to AT₁ receptors. Therapeutic Effect: Causes vasodilation, decreases peripheral resistance, decreases B/P.

Pharmacokinetics

Rapidly, completely absorbed after PO administration. Protein binding: greater than 99%. Metabolized in liver. Excreted in feces. Unknown if removed by hemodialysis. Half-life: 24 hrs.

Uses

Treatment of hypertension alone or in combination with other antihypertensives. Reduces risk of stroke, MI, death in pts 55 yrs of age or older with cardiovascular abnormalities (e.g., coronary artery disease, high-risk diabetes mellitus).

Precautions

Contraindications: Concurrent use with aliskiren in pts with diabetes. Cautions: Hypovolemia, hepatic/renal impairment, renal artery stenosis (unilateral, bilateral), biliary obstructive disease, significant aortic/mitral stenosis. Concurrent use with ramipril not recommended.

 ​Lifespan considerations

Pregnancy/Lactation: May cause fetal harm. Unknown if drug is distributed in breast milk. Pregnancy Category C (D if used in second or third trimester). Children: Safety and efficacy not established. Elderly: No age-related precautions noted.

Interactions

DRUG: NSAIDs may decrease antihypertensive effect. May increase digoxin concentration, risk of toxicity. HERBAL: Ephedra, ginger, licorice, ginseng, yohimbe may worsen hypertension. Black cohosh, periwinkle may increase antihypertensive effect. FOOD: None known. LAB VALUES: May increase serum BUN, creatinine, uric acid, cholesterol. May decrease Hgb, Hct.

Availability (Rx)

Tablets: 20 mg, 40 mg, 80 mg.

• Give without regard to meals.

PO: ADULTS: 40 mg once daily. ELDERLY: 20 mg once daily. Range: 20–80 mg/day.

Side effects

Occasional (7%–3%): Upper respiratory tract infection, sinusitis, back/leg pain, diarrhea. Rare (1%): Dizziness, headache, fatigue, nausea, heartburn, myalgia, cough, peripheral edema.

Adverse effects/toxic reactions

Overdosage may manifest as hypotension, tachycardia; bradycardia occurs less often.

Obtain B/P, apical pulse immediately before each dose, in addition to regular monitoring (be alert to fluctuations). If excessive reduction in B/P occurs, place pt in supine position, feet slightly elevated. Assess medication history (esp. diuretics). Question for history of hepatic/renal impairment, renal artery stenosis. Obtain BUN, serum creatinine, Hgb, Hct, vital signs (particularly B/P, pulse rate).

classification

PHARMACOTHERAPEUTIC: Benzodiazepine (Schedule IV). CLINICAL: Sedative-hypnotic (see p. 148C).

Action

Enhances action of inhibitory neurotransmitter gamma-aminobutyric acid (GABA), resulting in CNS depression. Therapeutic Effect: Induces sleep.

Pharmacokinetics

Well absorbed from GI tract. Protein binding: 96%. Widely distributed. Crosses blood-brain barrier. Metabolized in liver. Primarily excreted in urine. Not removed by hemodialysis. Half-life: 9.5–12.4 hrs.

Uses

Short-term treatment of insomnia (5 wks or less). Reduces sleep-induction time, number of nocturnal awakenings; increases length of sleep. OFF-LABEL: Treatment of anxiety, depression, panic attacks.

Precautions

Contraindications: Angle-closure glaucoma, CNS depression, pregnancy, breast-feeding, severe, uncontrolled pain, sleep apnea. Cautions: Mental impairment, pts with drug dependence potential.

 ​Lifespan considerations

Pregnancy/Lactation: Crosses placenta. May be distributed in breast milk. Chronic ingestion during pregnancy may produce withdrawal symptoms, CNS depression in neonates. Pregnancy Category X. Children: Not recommended in those younger than 18 yrs. Elderly: Use small initial doses with gradual dosage increases to avoid ataxia, excessive sedation.

Interactions

DRUG: Alcohol, other CNS depressants may increase CNS depression. HERBAL: St. John’s wort may decrease concentration. Gotu kola, kava kava, St. John’s wort, valerian may increase CNS depression. FOOD: None known. LAB VALUES: None significant.