Famciclovir (Famvir®) and Valacyclovir (Valtrex®)
Both are new antiherpesviral prodrugs (in the same class as acyclovir).
Indication: Acute herpes zoster in the immunocompetent host.
(Their role in genital herpes will be discussed in a future Therapeutics Letter).
Mechanism
of Action: Reduce viral
replication by inhibiting viral DNA polymerase.
Pharmacokinetics: Valacyclovir is a prodrug of, and metabolized to
acyclovir; the oral bioavailability of acyclovir from
valacyclovir is 54% as compared to 15-30% for acyclovir.
Famciclovir is a prodrug for the active metabolite penciclovir;
the mean oral bioavailability of penciclovir from famciclovir is
77%. Penciclovir plus acyclovir are primarily eliminated
unchanged by the kidneys and have mean half-lives of 2.5 hours.
Evidence
of efficacy: If given within 72 hours of the
first herpes zoster lesion, famciclovir(1)
and valacyclovir(2) (like acyclovir(3)) provide modest decreases in the time to
full crusting (e.g. median 5.5 days for famciclovir, 7 days for
placebo(1)), healing and cessation of pain .
The benefit is greatest in patients with the most severe
infections (many lesions and severe pain)(1),(3),(4). At present the
evidence is inconclusive as to whether any antiviral or other
therapy has an effect on the overall clinical impact of
post-herpetic neuralgia.(4) The new prodrugs
have not been studied in children or immunocompromised hosts.
Major
adverse effects: These
drugs, like acyclovir, produce a low incidence (similar to
placebo) of minor adverse effects, including diarrhea, nausea and
headache.
Dose
and Cost: Acute herpes
zoster: famciclovir, 500 mg TID for 7 days ($155.61),
valacyclovir, 1 g TID for 7 days ($126.84), acyclovir, 800 mg 5
times daily for 7 days ($138.60). Longer durations of therapy are
not more effective; shorter courses have not been tested.
Conclusions: Anti-viral drugs have a modest
beneficial effect if given early (rash <72 hr) to
immunocompetent patients (>50 yr) with moderate to severe rash
or pain associated with acute herpes zoster (shingles).
Torsemide is a loop diuretic in the same class as furosemide, bumetanide, and ethacrynic acid.
Indications:
Edema due to congestive heart failure and other conditions.
Hypertension.
Mechanism of Action: Inhibits renal sodium reabsorption in the
ascending loop of Henle.
Pharmacokinetics: Oral bioavailability is 80%. Inactivated
primarily by liver metabolism. Half-life is 3.5 hours.
Evidence of effectiveness: The five trials comparing torsemide with
furosemide suggest that torsemide is approximately twice as
potent as furosemide, possibly due to its longer duration of
action. The claim that torsemide causes less hypokalemia than
furosemide is not substantiated by studies where equipotent doses
are used(5). A low non-diuretic dose, (2.5
mg) of torsemide has an antihypertensive effect similar to low
dose hydrochlorothiazide.
Major adverse effects: Adverse effects which have led to
discontinuation of therapy include: dizziness, headache, nausea,
weakness, vomiting, hyperglycemia, excessive urination,
hyperuricemia, and hypokalemia.
Dose and Cost:
Edema: Torsemide 10-20 mg daily ($0.57- $1.14/day), as compared to furosemide 20-40 mg daily ($0.01/day).
Hypertension: Torsemide 2.5 mg daily ($0.20/day), as compared to HCTZ 25 mg daily (<$0.01/day).
Conclusions: Torsemide is a new loop diuretic which
is more potent and longer acting than furosemide; however, at
present there are no demonstrated therapeutic advantages of
torsemide.
Etodolac is a new non-steroidal anti-inflammatory drug.
Indications: Long term treatment of rheumatoid arthritis and
osteoarthritis.
Mechanism of action: A prostaglandin synthetase inhibitor with some
selectivity for cyclooxygenase 2 enzymes.
Pharmacokinetics: Oral bioavailability is 80%. Inactivated
primarily by liver metabolism. Mean half-life is 7 hours.
Evidence of effectiveness: In 14 randomised controlled trials (RCTs) for
the treatment of osteoarthritis, etodolac was found to be similar
in effectiveness and tolerability to naproxen, piroxicam,
diclofenac, nimesulide and nabumetone. In 12 RCTs for the
treatment of rheumatoid arthritis etodolac was found to be
similar in effectiveness and tolerability to naproxen,
diclofenac, piroxicam and sulindac.
Major adverse effects: The main adverse effects are gastrointestinal
and include dyspepsia, abdominal pain, nausea, and flatulence. In
a large trial 7% of patients withdrew prematurely because of GI
complaints. RCTs using surrogate markers such as endoscopy scores
and GI microbleeding show lower measures with etodolac than with
naproxen and indomethacin. A recent systematic review(6) has confirmed our previous Therapeutics Letter 4 demonstrating the
low risk of serious GI complications in clinical practice with
low dose ibuprofen (<2400mg/day). Etodolac and other
new NSAIDs were not included in this review; longer clinical
experience with these agents are required to determine where they
fit in terms of risk.
Dose and Cost: Osteoarthritis and rheumatoid arthritis: 200-400
mg BID ($1.79-$3.58/day), see Therapeutics
Letter 4 for dose and cost of other NSAIDs. The costs have been updated to
2000 prices on our website.
Conclusions: Etodolac is a new NSAID which has
similar effectiveness to other available NSAIDs. It may prove to
have a relatively low incidence of serious GI toxicity, however
more data are required.
Naltrexone is a long-acting pure opioid antagonist which is effective orally.
Indications:
An adjunct to the maintenance of the opioid-free state in detoxified, formerly opioid-dependent individuals.
For the treatment of alcohol dependence, as a component of a comprehensive psychotherapeutic counseling program to support abstinence and reduce the risk of relapse.
Mechanism of action: Competitively inhibits all opioid receptors.
Opioid receptors are thought to be responsible for some of the
reinforcing effects of alcohol.
Pharmacokinetics: Oral bioavailability is 5 to 40% due to high
first pass metabolism. Inactivated primarily by liver metabolism.
One major active metabolite with mean half-life of 13 hours.
Evidence of effectiveness: Two small RCTs (7),(8) compared 12 weeks of naltrexone with placebo
in the treatment of alcohol dependence. In these studies
naltrexone modestly increased measures of alcohol abstinence
(e.g. abstinence rate for naltrexone 42%, for placebo 20%). At
the present time there are no long-term follow-up data or
evidence that naltrexone leads to any clinically significant
outcomes (e.g. abstinence rates at one year).
Major adverse effects: The main adverse effects in these RCTs were
somnolence, nervousness, vomiting, weight loss, dry mouth,
decreased libido, insomnia, nausea, vomiting, and dyspepsia.
Dose and cost: Naltrexone 50 mg daily ($5.70/day).
Conclusions: Naltrexone is a pure long acting orally
active opioid antagonist which may prove effective as an adjunct
in opioid and alcohol dependence treatment programs.
References:
Tyring S, Barbarash RA, Nahlik JE, et al. Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. A randomized, double-blind, placebo-controlled trial. Collaborative Famciclovir Herpes Zoster Study Group. Annals of Internal Medicine. 1995 July 15; 123(2):89-96.
Beutner KR, Friedman DJ,Forszpaniak C, et al. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrob Agents Chemother. 1996;39:1546-53.
Whitley RJ, Weiss H, Gnann JW, et al. Acyclovir with and without prednisone for the treatment of Herpes Zoster. A placebo-controlled trial. Ann Intern Med. 1996; 125:376-383.
Henry D, Lim LLY, Rodriguez LAG, et al. Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis. BMJ. 1996; 312:1563-6.
Volpicelli JR, Alterman AI, Hayashida M, O'Brien CP. Naltrexone in the treatment of alcohol dependence. Archives of General Psychiatry, 1992; 49(11):876-80.
O'Malley SS, Jaffe AJ, Chang G, et al. Naltrexone and coping skills therapy for alcohol dependence. A controlled study. Archives of General Psychiatry. 1992; 49(11):881-7.
Please send feedback!
Back to Therapeutics Letter.
Back to the Therapeutics
Initiative Home Page.
©Therapeutics Initiative. Last updated: January 28, 1997.