Drug Update

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This quarterly update of new drugs in the long-term care market is provided by an experienced staff of pharmacists and pharmacologists at our sister publication MPR, the nation's leading supplier of concise prescribing information for more than 20 years. As residents continue to get older and sicker, the need for current, reliable information about new medicines has never been greater. MPR now offers its Long-Term Care Edition, a 230-page subscription-based quarterly covering more than 1,400 formulations. Annual subscriptions are $32.

Symbicort 160/4.5
Company:  AstraZeneca
Pharmacologic class:  Antiasthmatic (corticosteroid + long-acting b2-agonist)

Active ingredients:  Budesonide 160mcg, formoterol fumarate dihydrate 4.5mcg; per inh; pressurized metered-dose inhaler.

Also: SYMBICORT 80/4.5          

Active ingredients:  Budesonide 80mcg, formoterol fumarate dihydrate 4.5mcg; per inh; pressurized metered-dose inhaler.

Indication:  Long-term maintenance treatment of asthma in patients ≥12yrs old not adequately controlled on other asthma-controller medications (eg, low-medium dose inhaled corticosteroids) or those whose disease severity clearly warrants starting treatment with two maintenance therapies.

Pharmacology:  Symbicort combines the anti-inflammatory agent, budesonide, with the long-acting selective b2-agonist, formoterol, in a single metered-dose oral inhaler. 

Clinical trials:  Improvements in efficacy endpoints (eg, 12-hour-average post-dose FEV1 at week 2, and pre-dose FEV1 over the course of the study) were greater with Symbicort than with budesonide or formoterol given alone.  Significant improvement in FEV1 occurred within 15 minutes of beginning therapy with Symbicort.  Improvement in asthma control occurred within one day. 

Adults:  Not adequately controlled on low-medium dose inhaled steroids: start with 80/4.5 strength. Not adequately controlled on medium-high dose inhaled steroids: start with 160/4.5 strength. If not currently on inhaled steroids: choose strength depending on asthma severity. If insufficient response after 1–2 weeks using 80/4.5 strength, may switch to 160/4.5 strength. For all:  2 inh twice daily (AM & PM). Rinse mouth after use.

Children:  Not established (see literature).

Geriatric considerations:  Caution in elderly patients who have concomitant cardiovascular disease that could be adversely affected by b2-agonists.

Contraindications:  Not for acute relief of bronchospasm. Do not initiate in significantly or acutely deteriorating asthma. 

Precautions:  Reevaluate periodically. Do not exceed recommended dose. Not for use with other long-acting b2-agonists or for transferring from oral steroids. Cardiovascular disease (esp. coronary insufficiency, arrhythmias, hypertension). Convulsive disorders. Hypokalemia. Severe hepatic impairment. Hyperresponsiveness to sympathomimetics. Diabetes. Hyperthyroidism. Ketoacidosis. Immunosuppressed. Tuberculosis. Untreated infections. Ocular herpes simplex. If exposed to chickenpox or measles, consider anti-infective prophylactic therapies. If adrenal insufficiency exists following systemic corticosteroid therapy, replacement with inhaled corticosteroids may exacerbate symptoms of adrenal insufficiency (eg, lassitude). Prescribe a short-acting b2-agonist for acute symptoms; monitor for increased need. Monitor potassium, intraocular pressure, bone mineral density if other osteoporosis risk factors exist; and for growth suppression in adolescents; hypercorticism and HPA axis suppression. Pregnancy (Cat.C). Labor & delivery. Nursing mothers.

Interactions:  Caution with MAOIs, tricyclic antidepressants, b-blockers, K+-depleting diuretics, long-term ketoconazole, other potent CYP3A4 inhibitors.

Adverse reactions:  Nasopharyngitis, pharyngolaryngeal pain, sinusitis, congestion, oral candidiasis, headache, upper respiratory infection, flu, back pain, GI upset; rarely: paradoxical bronchospasm, hypersensitivity reactions; severe asthma episodes; increased risk of asthma-related death.

How supplied:  Inhaler—10.2g (120 inh).

Exforge 5/160
Company:  Novartis       

Pharmacologic class:  Calcium channel blocker (dihydropyridine) (CCB) + angiotensin II receptor blocker (ARB)

Active ingredients:  Amlodipine (as besylate) 5mg, valsartan 160mg; tabs.

Also:  EXFORGE 5/320              

Active ingredients:  Amlodipine (as besylate) 5mg, valsartan 320mg; tabs.

Also:  EXFORGE 10/160            

Active ingredients:  Amlodipine (as besylate) 10mg, valsartan 160mg; tabs.

Also:  EXFORGE 10/320            

Active ingredients:  Amlodipine (as besylate) 10mg, valsartan 320mg; tabs.
Indication:  Hypertension (not for initial therapy).

Pharmacology:  Exforge combines two anti-hypertensive drugs that have complementary mechanisms of action: amlodipine, a calcium (Ca+) channel blocker, and valsartan, an angiotensin II (Ang II) antagonist. Amlodipine blocks the influx of Ca+ into vascular smooth muscle and cardiac muscle, with a greater effect on vascular smooth muscle.  It is a peripheral artery vasodilator that causes a reduction in peripheral vascular resistance and a reduction in blood pressure.  Valsartan blocks the vasoconstrictive and aldosterone-secreting effects of Ang II by blocking its receptor sites in vascular smooth muscle and the adrenal gland.

Clinical trials:  In a placebo-controlled study, 1,018 patients with mild-to-moderate hypertension were given three combinations of amlodipine + valsartan, or amlodipine alone (5mg), valsartan alone (80, 160, or 320mg), or placebo.  At week 8, the combination treatments (doses of 5/80, 5/160, 5/320mg) were significantly better than their monotherapy components in the reduction of diastolic BP and systolic BP.
In a placebo-controlled study, 1,250 patients with mild-to-moderate hypertension were given treatments of two combinations of amlodipine + valsartan (10/160 or 10/320mg), amlodipine alone (10mg), valsartan alone (160 or 320mg), or placebo. At week 8, the combination treatments were shown to be significantly better than their monotherapy components in reducing diastolic and systolic BP.

Adults:  Usual maintenance: 1 tab daily. May switch from both components taken separately to same dose in Exforge. Dose-limiting effects of either component taken separately: may switch to Exforge with a lower dose of that component; if inadequate response after 3–4 weeks, may titrate to max 10/320mg per day. May switch patients not controlled on any dihydropyridine CCB alone or ARB alone to Exforge.

Children:  Not recommended.

Geriatric considerations:  May replace separate tablets with corresponding strength of Exforge for convenience. 

Precautions:  Correct hypovolemia before starting (may need to reduce diuretic) or monitor closely for hypotension. Severe heart failure (HF) (if renal function depends on renin-angiotensin-aldosterone system). Severe obstructive coronary disease. Recent MI. Severe aortic stenosis. Hepatic or severe renal impairment. Renal artery stenosis. Dialysis. Surgery. Pregnancy (Cat. C in 1st trimester, Cat. D in 2nd and 3rd trimesters). Nursing mothers: not recommended.

Interactions:  Concomitant K+ supplements, K+ sparing diuretics, K+ containing salt substitutes 
may lead to hyperkalemia and, in HF patients, increased serum creatinine.

Adverse reactions:  Peripheral edema, nasopharyngitis, upper respiratory infection, dizziness; rare: orthostatic  hypotension, postural dizziness.

How supplied:  Tabs—30, 90

Company:  Inspire       

Pharmacologic class:  Antibiotic (macrolide)

Active ingredient:  Azithromycin 1%; oph. soln; contains benzalkonium chloride.
Indication:  Susceptible bacterial conjunctivitis.

Pharmacology:  AzaSite is an ophthalmic solution formulation of the macrolide antibiotic, azithromycin, for the topical treatment of bacterial conjunctivitis caused by CDC coryneform group G, Haemophilus influenzae, Staphylococcus aureus, Streptococcus mitis group, and Streptococcus pneumoniae.

AzaSite offers an advantage in that it is dosed less frequently than other products used to treat bacterial conjunctivitis.  Like other macrolides, azithromycin exerts its antibacterial effect by binding to the 50S ribosomal subunits of susceptible bacteria.

AzaSite is indicated for topical ophthalmic use only, and should not be administered systemically, injected subconjunctivally, or introduced directly into the anterior chamber of the eye.

Clinical trials:  The results of a randomized, placebo-controlled, double-blind, multi-center clinical study indicated that AzaSite was more effective than placebo in treating bacterial conjunctivitis.  In this study, 685 patients (aged 1–96 years) were dosed twice daily for the first two days, then once daily on days 3, 4, and 5.  In patients who had a confirmed clinical diagnosis of bacterial conjunctivitis, treatment with AzaSite was superior to treatment with vehicle on days 6–7.  Clinical resolution was attained in 63% of patients treated with AzaSite compared to 50% of patients treated with vehicle. The microbiological success rate for the eradication of baseline pathogens was about 88%, compared to 66% of patients treated with vehicle.
A randomized, double-blind study conducted in the US and Latin America involving 743 patients (aged 1–87 years) with presumed bacterial conjunctivitis compared treatment with AzaSite to treatment with tobramycin 0.3% ophthalmic solution.  Positive bacterial cultures were established for 316 of the enrollees.  AzaSite was dosed twice daily for the first 2 days, then once daily for the next 3 days.  Tobramycin was dosed at four times daily for 5 days.  The results of this study showed that treatment with AzaSite was equivalent to treatment with tobramycin, with clinical resolution rates of 80% and 78%, respectively.

Adults and children:  <1yr: not recommended.  ≥1yr: 1 drop in affected eye(s) twice daily (8–12 hrs apart) for 2 days then once daily for the next 5 days. 

Precautions:  Remove contact lenses during therapy. Pregnancy (Cat.B). Nursing mothers.
Adverse reactions:  Eye irritation, superinfection; rare: contact dermatitis, corneal erosion, dysgeusia, dry eye, punctate keratitis, others.

Additional patient info:  Wash hands before use. Do not touch dropper tip to eye, fingers, or other objects. Shake bottle once before each use. Tilt head back, invert bottle, remove cap and gently squeeze bottle over eye to instill one drop in each affected eye. Report any signs of allergic reaction to prescriber. Complete full course of therapy. 

Storage:  Refrigerate until opened; discard 14 days after opening.
How supplied:  Soln—2.5mL.

Companies:  UCB and Schwarz Pharma  
Pharmacologic class:  Dopamine agonist (non-ergot)

Active ingredient:  Rotigotine 2mg/24 hours, 4mg/24 hours, 6mg/24 hours; transdermal patch; contains sulfites.

Indication:  Treatment of patients with early-stage idiopathic Parkinson's disease who are not receiving concomitant L-dopa.

Pharmacology:  Neupro is a transdermal patch containing rotigotine, a D3/D2/D1 dopamine agonist. The mechanism of action of rotigotine in treating Parkinson's disease may be due to its ability to stimulate D2 receptors in the caudate-putamen. 
About 45% of the drug is released within 24 hrs after applying the patch.  The drug is detectable in plasma about 3 hours after application, and maximum plasma concentrations are usually reached between 15 and 18 hours post-dose.  Steady-state levels are achieved within 2–3 days of daily dosing.

Clinical trials:  Three double-blind placebo-controlled studies were conducted to evaluate the effectiveness of Neupro in treating the signs and symptoms of early-stage idiopathic Parkinson's disease.  Patients were not on other dopamine agonists or L-dopa during the trials.  The primary outcome assessment was the change from baseline for the combined scores for part II (activities of daily living) and part III (motor component) of the Unified Parkinson's Disease Rating Scale (UPDRS).
A dose-response study indicated that statistically significant mean changes reflecting dose-related improvement were seen for the marketed doses of 4mg/24 hrs and 6mg/24 hrs; an 8mg/24 hrs dose had a similar effect as the 6mg/24 hrs dose.
In the North American study, patients treated with Neupro had a mean change in the UPDRS from baseline to end of treatment that was statistically significant compared to those treated with placebo.
In a three-arm foreign multinational study that compared Neupro to an active, oral comparator and to placebo, patients treated with Neupro at doses up to 8mg/24 hrs had a mean change in the combined UPDRS from baseline to the end of treatment that was statistically better than those given placebo. 
Adults:  Apply to clean, dry, intact skin on abdomen, thigh, hip, flank, shoulder, or upper arm. Initial: apply one 2mg/24 hrs patch once daily; may increase weekly by 2mg/24 hrs; max one 6mg/24 hrs patch once daily. Rotate application site (allow 14 days before reapplying to same site). Shave site at least 3 days before application if hairy. Do not cut patch. Avoid abrupt cessation; reduce by 2mg/24 hrs every other day.

Children:  Not recommended.

Geriatric considerations:  Exposure in older patients (>80yrs) may be higher due to skin changes with age.

Precautions:  Avoid external heat sources. Remove patch before cardioversion, MRI. Consider discontinuing if excessive daytime sleepiness or falling asleep during activities occurs. Cardiovascular disease. Conditions aggravated by fluid retention (eg, CHF). Asthma (sulfite sensitivity). Dyskinesia. Severe hepatic impairment. Monitor for melanoma. Pregnancy (Cat.C). Nursing mothers: not recommended.

Interactions:  Additive CNS depression with alcohol, CNS depressants. May be antagonized by metoclopramide, antipsychotics.

Adverse reactions:  Somnolence (may be sudden), dizziness, GI upset, application site reactions, headache, insomnia, weight change, lab abnormalities; orthostatic hypotension, syncope, hallucinations, intense urges/compulsions, others.

How supplied:  Patches—7, 30.