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****** DATA-MEDICOS **********
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EL IVERMECTIN 
THE IVERMECTIN 
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***** DERMAGIC-EXPRESS No.28 ******** 
****** 08 ENERO DE 1.999 ******* 
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EDITORIAL ESPANOL
=================
Hola amigos DERMAGICOS, en esta ocasion les traigo un tema de mucha actualidad, que esta siendo discutido activamente en la lista DERMLIST, durante toda esta semana, se trata del IVERMECTIN. 16 referencias bibliograficas que nos ilustran sus aplicaciones en DERMATOLOGIA, especificamente, escabiosis y pediculosis capitis. Al final una MONOGRAFIA DEL PRODUCTO. Otros Usos: estrongiloidiasis, larva migrans, Oncocercosis y filariasis (bancroftiasis)


Saludos a todos,,, 
Dr. Jose Lapenta.

EDITORIAL ENGLISH
=================
Hello DERMAGIC'S friends, in this occasion brings them a topic that this being discussed actively in the list DERMLIST, during this whole week, it is the IVERMECTIN. 16 bibliographical references that illustrate us their applications in DERMATOLOGY, specifically, escabies and pediculosis capitis. At the end, a MONOGRAPH OF THE PRODUCT. 

Other Uses: estrongyloidiasis, cutaneous larva migrans, Onchocerciasis and bancroftian filariasis. 

Greetings to all, 
Dr. José Lapenta, 
================================================================
DERMAGIC/EXPRESS(28)
================================================================
EL IVERMECTIN // THE IVERMECTIN 
================================================================
1.) The treatment of scabies with ivermectin.
2.) Comparison of ivermectin and benzyl benzoate for treatment of scabies.
3.) Successful use of ivermectin in the treatment of endemic scabies in a nursing home. 
4.) Treatment of HIV-related scabies with emphasis on the efficacy of ivermectin. 
5.) Ivermectin-responsive crusted scabies in HTLV1 carrier. 
6.) Crusted ("Norwegian") scabies in a specialist HIV unit: successful use of ivermectin and failure to prevent nosocomial transmission [see comments] 
7.) Crusted scabies of the scalp in dermatomyositis patients: three cases treated with oral ivermectin. 
8.) Ivermectin for Sarcoptes scabiei hyperinfestation. 
9.) Topical application of ivermectin for human ectoparasites. 
10.) An assessment of topical and oral prescription and over-the-counter treatments for head lice.
11.) Efficacy of ivermectin for the treatment of head lice (Pediculosis capitis).
12.) Physiology, pharmacology and parasitology. 
13.) Efficacy of ivermectin in the treatment of strongyloidiasis complicating AIDS.
14.) Efficacy of ivermectin against Strongyloides stercoralis in humans.
15.) Efficacy of ivermectin in the therapy of cutaneous larva migrans [letter]
16.) IVERMECTIN, the product.
================================================================
================================================================
1.) The treatment of scabies with ivermectin.
================================================================
SO - N Engl J Med 1995 Jul 6;333(1):26-30
AU - Meinking TL; Taplin D; Hermida JL; Pardo R; Kerdel FA
AD - Department of Dermatology and Cutaneous Surgery, University of Miami School of Medicine, FL, USA.
PT - CLINICAL TRIAL; JOURNAL ARTICLE
AB - BACKGROUND. Ivermectin is an anthelmintic agent that has been a safe, effective treatment for onchocerciasis (river blindness) when given in a single oral dose of 150 to 200 micrograms per kilogram of body weight. Anecdotal reports of improvement in patients who suffered from infestation with the mite Sarcoptes scabiei suggest that the ectoparasitic disease scabies might be treated with ivermectin. METHODS. We conducted an open-label study in which ivermectin was administered in a single oral dose of 200 micrograms per kilogram to 11 otherwise healthy patients with scabies and to 11 patients with scabies who were also infected with the human immunodeficiency virus (HIV), 7 of whom had the acquired immunodeficiency syndrome. All patients received a full physical and dermatologic examination; scrapings from the skin of all patients tested positive for scabies. Patients were reexamined two and four weeks after treatment, when the scrapings for scabies were repeated. The patients used no other scabicides during the 30 days before ivermectin treatment or during the 4-week study period. RESULTS. None of the 11 otherwise healthy patients had evidence of scabies four weeks after a single dose of ivermectin. Of the 11 HIV-infected patients, 2 had or = 10 scabies lesions before treatment, 3 had 11 to 49 lesions, 4 had or = 50 lesions, and 2 had heavily crusted skin lesions. In eight of the patients the scabies was cured after a single dose of ivermectin. Two patients received a second dose two weeks after the first. Ten of the 11 patients with HIV infection (91 percent) had no evidence of scabies four weeks after their first treatment with ivermectin. CONCLUSIONS. The anthelmintic agent ivermectin, given in a single oral dose, is an effective treatment for scabies in otherwise healthy patients and in many patients with HIV infection.

================================================================
2.) Comparison of ivermectin and benzyl benzoate for treatment of scabies.
================================================================
SO - Trop Med Parasitol 1993 Dec;44(4):331-2
AU - Glaziou P; Cartel JL; Alzieu P; Briot C; Moulia-Pelat JP; Martin PM
AD - Institut Territoreal de Recherches Medicales Louis Malarde, Papeete, Tahiti, French Polynesia.
PT - CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
AB - A randomized investigator-blinded trial of oral ivermectin 100 micrograms/kg single dose vs. benzyl benzoate 10% application in the treatment of scabies, was conducted in 1992 in French Polynesia. In total, 44 patients aged 5-56 years were included in the study: 23 in the group ivermectin (IVER) and 21 in the group benzyl benzoate (BB). At day 30 after treatment, the cumulative recovery rates were 70% (16/23) in the group IVER, and 48% (10/21) in the group BB, 95% confidence intervals 51-87% and 29-70% respectively. The rates of recovery were greater in the group IVER at day 7, 14 and 30, but the difference was not statistically significant. Our results show that oral ivermectin is a valuable alternative to benzyl benzoate local treatment.
================================================================
3.) Successful use of ivermectin in the treatment of endemic scabies in a nursing home. 
================================================================
Author 
Sullivan JR; Watt G; Barker B 
Address 
Department of Dermatology, Royal Newcastle Hospital, New South Wales, Australia. 
Source 
Australas J Dermatol, 38(3):137-40 1997 Aug 
Abstract 
Ivermectin, an antiparasitic agent, was successfully used as a sole agent to combat endemic
scabies in a closed 33-bed ward of a rural nursing home. Previous topical therapies,
including multiple applications of permethrin, gamma-benzene hexachloride, benzyl benzoate
and precipitated sulfur in white soft paraffin, had failed. Several patients exhibited
hyperkeratotic crusted scabies with head and neck involvement and all residents except one
recently arrived resident had evidence of active infestation. All residents were treated with
200 micrograms/kg of ivermectin and this dose was repeated 2 weeks later in all subjects.
Four weeks after the first dose of ivermectin there was no evidence of active scabies and
all rashes were totally resolved by 6 weeks. The action of ivermectin, its safety and its
indications are discussed. 

================================================================
4.) Treatment of HIV-related scabies with emphasis on the efficacy of ivermectin. 
================================================================
Author 
Taplin D; Meinking TL 
Address 
Department of Dermatology, University of Miami School of Medicine, FL 33101, USA. 
Source 
Semin Cutan Med Surg, 16(3):235-40 1997 Sep 
Abstract 
Since the mid-1980s, worldwide reports confirm that scabies in individuals infected with the
human immunodeficiency virus (HIV) result in a wide range of-clinical manifestations which
differ from those seen in immunocompetent patients. There is also general agreement that
HIV-related scabies is more difficult to treat. Oral ivermectin has been shown in several
countries to be a safe and effective therapy. In otherwise healthy persons, one dose of 200
microg/kg is usually curative. In HIV-related scabies, one treatment may be curative but
repeated doses may be required. Crusted scabies in these individual requires a combination
of oral ivermectin, total body treatments with 5% permethrin cream, and keratolytic agents
to hasten removal of crusts. 
================================================================
5.) Ivermectin-responsive crusted scabies in HTLV1 carrier. 
================================================================
Author 
Cordoliani F; Vasseur E; Baccard M; Fournier S; Feuilhade de Chauvin M; Tancrede E;
Morel P 
Address 
Department of Dermatology, H^opital Saint-Louis, Paris, France. 
Source 
Dermatology, 192(4):351-2 1996 
Abstract 
We report a case of HTLV1 infection revealed by crusted scabies and widespread
dermatophytosis in an African woman. HTLV1 infection was not complicated by adult T cell
leukemia or myelopathy. Crusted scabies is a marker of HTLV1 infection. The importance
of oral ivermectin therapy in crusted scabies is emphasized. 
================================================================
6.) Crusted ("Norwegian") scabies in a specialist HIV unit: successful use of ivermectin and failure to prevent nosocomial transmission [see comments] 
================================================================
Author 
Corbett EL; Crossley I; Holton J; Levell N; Miller R; De Cock KM 
Address 
HIV/AIDS Unit Camden & Islington Community Health Services NHS Trust, Middlesex
Hospital, London, UK. 
Source 
Genitourin Med, 72(2):115-7 1996 Apr 
Abstract 
A nosocomial outbreak of scabies in a specialist inpatient HIV unit resulted from a patient
admitted with crusted scabies. Treatment of his infestation with topical scabicides alone failed
and he remained infectious for several weeks. His infestation was then eradicated with
combined topical treatment and oral ivermectin. In total, 14 (88%) out of 19 ward staff
became symptomatic, and 4 (21%) had evidence of scabies on potassium hydroxide
examination of skin scrapings. The ward infection control policy was changed to distinguish
patients with crusted scabies from those with ordinary scabies. A second patient with
crusted scabies was treated with combined oral and topical therapy early in his admission
and nursed with more stringent isolation procedures. No nosocomial transmission occurred
and his infestation responded rapidly to treatment. Patients with crusted scabies require strict
barrier nursing if nosocomial transmission is to be avoided. Ivermectin combined with
topical scabicides may be a more efficacious treatment than topical scabicides alone in such
patients. 
================================================================
7.) Crusted scabies of the scalp in dermatomyositis patients: three cases treated with oral ivermectin. 
================================================================
Author 
Dourmishev AL; Serafimova DK; Dourmishev LA; Mualla MA; Papaharalambous V;
Malchevsky T 
Address 
Department of Dermatology and Venereology, University of Medicine, Sofia, Bulgaria. 
Source 
Int J Dermatol, 37(3):231-4 1998 Mar 
Abstract 
BACKGROUND: Cutaneous features in the scalp area among adult patients are rarely
considered as a manifestation of scabies. METHODS: Three patients with clinical and
laboratory data of dermatomyositis with scalp involvement (fulfill three or four of Bohan and
Peter's criteria), of 4 years, 8 months, and 3 years duration, were seen at our department
between 1995 and 1996. For relapses of ordinary scabies, they were treated repeatedly
with local scabicide with temporary effect. After a symptom-free period during the treatment
of dermatomyositis with corticosteroids and azathioprine, they developed diffuse redness with
scales and crusts on the scalp areas. Light microscopy examination of material taken from
these crusts showed an abundance of live mites. RESULTS: All patients were successfully
cured of scabies with a twice oral dose of 200 microg/kg ivermectin within 8 days.
CONCLUSIONS: Our patients with crusted scabies of the scalp and dermatomyositis
prompted us to change our standard diagnostic and therapeutic regimens. Fascinating
features included mimicry of scabies in patients with dermatomyositis, location of parasites
on the scalp, suppressed cell-mediated immunity and successful cure of mange by
ivermectin. 
===============================================================
8.) Ivermectin for Sarcoptes scabiei hyperinfestation. 
================================================================
Author 
Huffam SE; Currie BJ 
Address 
Royal Darwin Hospital, Menzies School of Health Research, Darwin, Northern Territory,
Australia. 
Source 
Int J Infect Dis, 2(3):152-4 1998 Jan-Mar 
Abstract 
OBJECTIVES: Crusted (Norwegian) scabies is an unusual variant of scabies caused by
hyperinfestation with Sarcoptes scabiei. It has high morbidity, and secondary bacterial skin
sepsis may result in life-threatening bacteremia. An open label study of oral ivermectin was
carried out in patients with crusted scabies refractory to topical therapy. METHODS:
Patients with refractory crusted scabies were prescribed oral ivermectin, one to three doses
of 200 mg/kg at 14-day intervals, combined with topical scabicide and keratolytic therapy.
RESULTS: Of the 20 patients who received ivermectin, 8 had a complete initial clinical
response, a partial response was achieved in 9, and minimal improvement occurred in 3.
Three doses of ivermectin were curative for 8 of 10 cases, but recurrence of scabies from
presumed reinfestation occurred in at least half of these. CONCLUSION: The authors
conclude that ivermectin is effective for crusted scabies; however, multiple doses may be
required to achieve a cure, and recurrence 6 or more weeks after completing treatment is
common. 
================================================================
9.) Topical application of ivermectin for human ectoparasites. 
================================================================
Author 
Youssef MY; Sadaka HA; Eissa MM; el-Ariny AF 
Address 
Department of Parasitology, Faculty of Medicine, Alexandria University, Alexandria, Egypt. 
Source 
Am J Trop Med Hyg, 53(6):652-3 1995 Dec 
Abstract 
Ivermectin is used in veterinary practice against many ectoparasites and endoparasites and
is the drug of choice for treatment of human onchocerciasis. This study was carried out to
investigate the effect of topical application of this drug against human ectoparasites
(Sarcoptes scabiei and Pediculus humanus capitis). Ivernectin was found to have a curative
effect on head lice after a single topical application. In patients with scabies, the drug was
also found to be effective after a single application. However, in 50% of the cases, another
application was needed five days later. 
================================================================
10.) An assessment of topical and oral prescription and over-the-counter treatments for head lice.
================================================================
Author 
Burkhart CG; Burkhart CN; Burkhart KM 
Address 
Department of Medicine, Medical College of Ohio at Toledo, USA. 
Source 
J Am Acad Dermatol, 38(6 Pt 1):979-82 1998 Jun 
Abstract 
A plethora of head lice cases that require optimal therapeutic assessments are developing in
elementary schools. Over-the-counter therapies continue to be the mainstream solution for
most cases of pediculosis capitis, but the onset of resistant cases dictates a review of
available treatment modalities. The increased efficacy of prescription drugs, namely topical
5% permethrin and oral ivermectin, underline the expanding role that physicians will serve in
the eradication of head lice in our communities. 

================================================================
11.) Efficacy of ivermectin for the treatment of head lice (Pediculosis capitis).
================================================================
SO - Trop Med Parasitol 1994 Sep;45(3):253-4
AU - Glaziou P; Nyguyen LN; Moulia-Pelat JP; Cartel JL; Martin PM
AD - Institut Territorial de Recherches Medicales Louis Malarde, Papeete, Tahiti, French Polynesia.
PT - CLINICAL TRIAL; JOURNAL ARTICLE
AB - Twenty six male and female patients aged 5 to 17 years who had head lice infestation confirmed by eggs presence and received treatments with a single 200 mu/kg oral dose of ivermectin in open fashion. At day 14 after treatment, 20 responded to the treatment (77%), and 6 patients (23%) presented with a complete disappearance of eggs and all clinical symptoms. At day 28, 7 patients were healed (27%), but 4 patients of the 6 healed at day 14 presented with signs of reinfestation. This study suggests that ivermectin is a promising treatment of head lice, and a second dose at day 10 should be appropriate for a further comparative trial.

================================================================
12.) Physiology, pharmacology and parasitology. 
================================================================
Author 
Hennessy DR 
Address 
CSIRO Division of Animal Production, McMaster Laboratory, Blacktown, NSW, Australia.
Source 
Int J Parasitol, 27(2):145-52 1997 Feb 
Abstract 
The developing resistance to current chemical classes of broad-spectrum anthelmintics and
insecticides presents an undeniable threat to the long-term viability of the animal health
industry. Alternative treatment strategies including vaccines, biological control and breeding of
parasite-resistant animals are unlikely to be widely available in the near future and even then
they will be integrated with chemotherapy. The significant cost of research and development
of new therapeutics for food-producing animals, together with the small market share of
animal health products, particularly in Australia and New Zealand, is a positive disincentive
for drug development. The chemical actives that are currently available are all that we are
likely to have for the foreseeable future and they must be used more efficiently.
Understanding the pharmacokinetic behaviour of antiparasitics and recognising the potential
for the animal's physiological characteristics to assist drug action is crucial. Careful
administration, coupled with a reduction of feed intake before oral anthelmintic treatment,
maximises drug availability and therefore increases efficacy of the benzimidazole and
ivermectin compounds. This is a cost-effective option that can be employed immediately,
which not only increases efficacy of "older" compounds but will be instrumental in prolonging
the useful life of the newer drugs. Taking care to apply topical insecticide formulations directly
along the backline immediately after shearing will maximise even diffusion of active around the
sheep flanks to contact lice inhabiting sites remote from the point of drug application. The use
of "intelligent" formulation and delivery of existing compounds, based on knowledge of host
physiological and pharmacological responses, holds the key to effective antiparasitic

================================================================
13.) Efficacy of ivermectin in the treatment of strongyloidiasis complicating AIDS.
================================================================
SO - Clin Infect Dis 1993 Nov;17(5):900-2
AU - Torres JR; Isturiz R; Murillo J; Guzman M; Contreras R
AD - Instituto de Medicina Tropical Felix Pifano C., Universidad Central de Venezuela.
PT - JOURNAL ARTICLE
AB - Nine adult male homosexuals who were infected with the human immunodeficiency virus (five with AIDS-defining conditions) and harbored Strongyloides stercoralis received ivermectin on a compassionate basis for persistent intestinal infection. Hyperinfection was present in all cases. Ivermectin was given either as a single oral dose (200 micrograms/kg) or on a multidose schedule (200 micrograms/kg.d) on days 1, 2, 15, and 16. All seven patients who received multiple doses showed sustained clinical and parasitological cure, whereas one of two patients who received single-dose therapy relapsed promptly and fatally. Remissions have been maintained for at least 7 months and up to 3 years of follow-up. Ivermectin appears promising in the treatment of strongyloidiasis in patients with AIDS. Because of the risk of hyperinfection and/or disseminated disease, multidose courses are warranted. We are not aware of other reports describing the efficacy of antiparasitic drugs for strongyloidiasis in patients with AIDS.

================================================================
14.) Efficacy of ivermectin against Strongyloides stercoralis in humans.
================================================================
SO - Intern Med 1992 Mar;31(3):310-2
AU - Shikiya K; Kinjo N; Uehara T; Uechi H; Ohshiro J; Arakaki T; Kinjo F; Saito A; Iju M; Kobari K
AD - First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
PT - JOURNAL ARTICLE
AB - Okinawa Prefecture is an endemic area of Strongyloides stercoralis infection. Since treatment of this infection remains unsatisfactory, we evaluated the efficacy of ivermectin. Twenty-three patients were treated with a single oral dose of ivermectin (mean +/- SD, 105.5 +/- 20.8 mcg/kg of body weight), followed by a second dose two weeks later. The rate of cure was 85.7% at 2 weeks after the first treatment, and 90.5% at 2 weeks after the second treatment. Side effects occurred in 2 patients (8.7%), but they were mild and transient. The results indicate that ivermectin might be useful and relatively safe for the therapy of Strongyloides stercoralis infection as an alternative to thiabendazole or mebendazole.

================================================================
15.) Efficacy of ivermectin in the therapy of cutaneous larva migrans [letter]
SO - Arch Dermatol 1992 Jul;128(7):994-5
AU - Caumes E; Datry A; Paris L; Danis M; Gentilini M; Gaxotte P
PT - LETTER
================================================================
=============================
16.) IVERMECTINa,b (Systemic), the product
=============================

VA CLASSIFICATION (Primary/Secondary)¾AP200

Commonly used brand name(s): 
============================
Mectizan.
=========
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

aNot commercially available in the U.S.

bNot commercially available in Canada.

Category

Anthelmintic (systemic).

Indications
===========
Note: Because ivermectin is not commercially available in the U.S. or Canada, the bracketed information and the use of the superscript 1 in this monograph reflect the lack of labeled (approved) indications for this product in these countries.

Accepted
========
[Onchocerciasis (treatment)]*¾Ivermectin is used in the treatment of onchocerciasis (river blindness) caused by Onchocerca volvulus.1,2,3,4,5,6,7,8,9,11,16,33

[Filariasis, Bancroft's (treatment)]*¾Ivermectin is used in the treatment of bancroftian filariasis caused by Wuchereria bancrofti.20,21,22,26

[Strongyloidiasis (treatment)]*¾Ivermectin is used as a secondary agent in the treatment of strongyloidiasis caused by Strongyloides stercoralis.29

Unaccepted
==========
Ivermectin is not effective against flukes or protozoa.1,5,6,14

Pharmacology/Pharmacokinetics
=============================
Mechanism of action/Effect:
==========================
Microfilaricidal; precise mechanism of action is unknown. Ivermectin is thought to act as an agonist of the neurotransmitter gamma-aminobutyric acid (GABA), thereby disrupting GABA-mediated central nervous system (CNS) neurosynaptic transmission. This results in paralysis of the parasite's nervous system and leads to death of the parasite. Although not macrofilaricidal, ivermectin may also impair normal intrauterine development of O. volvulus microfilariae and may inhibit their release from the uteri of gravid female worms. Action on microfilariae is less abrupt but more prolonged than that of diethylcarbamazine. Ivermectin promptly decreases skin microfilarial counts, while the number of microfilariae in the cornea and anterior chamber of the eye decreases more slowly.1,2,3,4,5,7,8,9,10,12,14

Distribution:
============
Does not cross the blood-brain barrier in humans and most other mammals.5,14 In animal studies (cattle, sheep, swine, rats), highest concentrations found in the liver and fat; very little drug found in muscle or the kidneys.23

Apparent VolD=46.8 liters.25

Plasma protein binding

High (approximately 93%).32

Half-life:

22 to 28 hours;25 however, some reports have shown a half-life of 12 hours for ivermectin and 3 days for its metabolites.28

Time to peak concentration:

Approximately 3.6 hours after a single 12-mg dose.24

Peak plasma concentration

46 nanograms per mL after a single 12-mg dose.24

Duration of action:

Up to 12 months.1,4,7,8,11,12

Elimination:

In animal studies, small amount (<2%) of ivermectin excreted in the urine; remainder found in feces.23

Precautions to Consider

Pregnancy/Reproduction
=====================
Fertility¾Studies in cattle, sheep, horses, swine, dogs, and rats have not shown that ivermectin has any adverse effects on fertility.8

Pregnancy¾Although adequate and well-controlled studies in humans have not been done, use is not recommended in pregnant women. However, one study of 203 children born to mothers who had been treated with ivermectin during pregnancy (85% during the first trimester and 36% within the first month of pregnancy) found that use of ivermectin was not associated with any significant difference in the rate of miscarriage, stillbirth, or major congenital malformations, and was not associated with any difference in developmental status or disease patterns.31

Studies in rats and rabbits given doses of 1.5 mg per kg of body weight (mg/kg) for several days have not shown that ivermectin is teratogenic or fetotoxic. However, studies in mice given repeated daily doses 5 times higher than the single therapeutic human dose have shown that ivermectin is teratogenic. Ivermectin has also been shown to be fetotoxic in other laboratory animals, but only at maternotoxic concentrations.1,5,8

Breast-feeding
==============
Ivermectin is distributed into breast milk. In one study, a maximum level of 23 nanograms per mL was found on the day after treatment and dropped below 0.1 nanogram per mL approximately 1 week later.27

Pediatrics

Appropriate studies on the relationship of age to the effects of ivermectin have not been performed in children up to 5 years of age.13,14,18

Geriatrics

No information is available on the relationship of age to the effects of ivermectin in geriatric patients.

Medical considerations/Contraindications
=========================================
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)¾not necessarily inclusive (>> = major clinical significance).

Risk-benefit should be considered when the following medical problem exists

Hypersensitivity to ivermectin¾

Patient monitoring

The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; >> = major clinical significance):

For onchocerciasis

>> Ophthalmologic examinations¾(ophthalmologic examinations, including examinations for visual acuity and slit-lamp examinations to determine the number of microfilariae in the cornea and anterior chamber, are recommended prior to and following treatment with ivermectin; if intraocular microfilariae are noted prior to treatment, slit-lamp examinations should be repeated 3, 6, and 12 months following treatment2,3,7,8,9,14)

>> Skin snips¾(skin snips from the lateral sides of one or both scapulae, iliac crests, or calves are recommended prior to and following treatment with ivermectin to determine the number of intradermal microfilariae; skin snips are recommended 3, 6, and 12 months following treatment2,3,6,7,8,9,14)

Side/Adverse Effects
====================
Note: No major CNS toxicity has been reported since ivermectin does not cross the blood-brain barrier in humans.6,7,14

The microfilaricidal action of ivermectin is less abrupt than that of diethylcarbamazine, and no serious systemic or ocular toxicity has been reported in humans.1,2,3,4,7,8 However, the frequency and severity of side effects were found to be related to the degree of parasite infection.19 Side effects usually peak around day 2 or 3.25

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)¾not necessarily inclusive:

Those indicating need for medical attention only if they continue or are bothersome

Incidence less frequent1,2,3,6,7,8,9,25
Dizziness; fever; headache; lymphadenopathy (painful and tender nodes in neck, armpits, or groin); Mazzotti-like reaction, specifically arthralgia or myalgia (joint or muscle pain); skin rash or itching¾due to death of microfilariae in skin; unusual tiredness or weakness

Incidence rare
Postural hypotension (lightheadedness while standing up)

Patient Consultation
====================
As an aid to patient consultation, refer to Advice for the Patient, Ivermectin (Systemic).

In providing consultation, consider emphasizing the following selected information (>> = major clinical significance):

Before using this medication

>> Conditions affecting use, especially:Pregnancy¾Use not recommended in pregnancy

Breast-feeding¾Ivermectin is distributed into breast milk

Proper use of this medication

Taking as a single dose on an empty stomach (1 hour before breakfast)

>> Compliance with therapy; dose may be repeated every 6 to 12 months

Systemic corticosteroids taken concurrently may be indicated in patients with advanced disease and high microfilariae counts in the eye in order to reduce inflammatory reactions to death of O. volvulusmicrofilariae

>> Proper dosing>> Proper storage

Precautions while using this medication

Regular visits to physician to check progress, as well as ophthalmologic examinations

Checking with physician if symptoms worsen

>> Caution if lightheadedness occurs

General Dosing Information
==========================
Ivermectin should be administered as a single dose with a full glass (240 mL) of water on an empty stomach (1 hour before breakfast).8,9

Single doses as low as 50 mcg per kg of body weight have shown significant microfilaricidal activity.4,6,7,12 In addition, a single oral dose (approximately 150 mcg per kg of body weight) usually reduces the dermal microfilarial count to very low levels and maintains them for up to 12 months.1,7

Systemic corticosteroids, although rarely required, may be helpful when administered concurrently to suppress the inflammatory response to the death of microfilariae caused by ivermectin in patients with advanced disease and high microfilariae counts in the eye.1,3,8,14

For treatment of adverse effects

Recommended treatment consists of the following:1,3 8,9
· Systemic corticosteroids for severe allergic reactions.

· Antihistamines.

· Analgesics.

Oral Dosage Forms

Note: Because ivermectin is not commercially available in the U.S. or Canada, the bracketed uses and the use of the superscript 1 in this monograph reflect the lack of labeled (approved) indications for this product in these countries.


IVERMECTIN TABLETS
=====================
Usual adult and adolescent dose

[Onchocerciasis]*¾
Oral, 150 mcg per kg of body weight as a single dose; may be repeated every six to twelve months, depending on the recurrence of symptoms and/or microfilariae1,2,3,4,5,6,7,8,9,10,11,12,14.

[Bancroftian filariasis]*¾
Oral, 20 to 200 mcg per kg of body weight as a single dose have been used.29

Usual adult prescribing limits
==============================
Up to 200 mcg per kg of body weight.1,2,3,4,5,6,7,8,9,10,11,12,13,14

Usual pediatric dose
====================
[Onchocerciasis]*¾
Infants and children up to 5 years of age: Dosage has not been established.

Children 5 years of age and over: Oral, 150 mcg per kg of body weight once every twelve months.13,14

Strength(s) usually available

U.S.¾
Not commercially available.17

Note: The manufacturer is making the product available free-of-charge to large-scale control programs in endemic areas through an independent expert committee. The address is: The Mectizan Donation Program, One Copenhill, Atlanta, GA 30307.13,30 For individual patients, inquiry should be made to CDC Drug Service, Centers for Disease Control, Atlanta, GA.14,15

Canada¾
Not commercially available.

Other¾
6 mg (Rx)[Mectizan].

Packaging and storage:
======================
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer.

Auxiliary labeling:
===================
· Take 1 hour before breakfast.

· May cause lightheadedness.

*Not included in Canadian product labeling.

References
=========
1.) Ivermectin in onchocerciasis. WHO Drug Information 1987; 1(2): 43-5.

2.) Greene BM, Taylor HR, Cupp EW, et al. Comparison of ivermectin and diethylcarbamazine in the treatment of onchocerciasis. N Engl J Med 1985 July 18; 313(3): 133-8.

3.) Lariviere M, Aziz M, Weimann D, et al. Double-blind study of ivermectin and diethylcarbamazine in African onchocerciasis patients with ocular involvement. Lancet 1985 July 27; 2: 174-7.

4.) MSD Press Release: Ivermectin, 9/21/87.

5.) Koch H. Ivermectin: novel systemic antiparasitic agent. Pharm Internat 1984 March: 55-6.

6.) Aziz MA, Diop IB, Diallo S, et al. Efficacy and tolerance of ivermectin in human onchocerciasis. Lancet 1982 July 24; 2: 171-3.

7.) White AT, Newland HS, Taylor HR, et al. Controlled trial and dose-finding study of ivermectin for treatment of onchocerciasis. J Infect Dis 1987 Sept; 156(3): 463-70.

8.) Diallo S, Aziz MA, Lariviere M, et al. A double-blind comparison of the efficacy and safety of ivermectin and diethylcarbamazine in a placebo controlled study of Senegalese patients with onchocerciasis. Trans R Soc Trop Med Hyg 1986; 80(6): 927-34.

9.) Awadzi K, Dadzie KY, Schulz-Key H, et al. The chemotherapy of onchocerciasis. A double-blind comparative study of ivermectin, diethylcarbamazine and placebo in human onchocerciasis in northern Ghana. Ann Trop Med Parasitol 1986 Aug; 80(4): 433-42.

10.) Soboslay PT, Newland HS, White AT, et al. Ivermectin effect on microfilariae of Onchocerca volvulus after a single oral dose in humans. Trop Med Parasitol 1987 Mar; 38(1): 8-10.

11.) Aziz MA. Chemotherapeutic approach to control of onchocerciasis. Rev Infect Dis 1986 May-Jun; 8(3): 500-4.

12.) Awadzi K, Dadzie KY, Schulz-Key H, et al. The chemotherapy of onchocerciasis. An assessment of four single dose treatment regimes of MK-933 (ivermectin) in human onchocerciasis. Ann Trop Med Parasitol 1985 Feb; 79(1): 63-78.

13.) Personal communication, Art Kaufman, MSD International, 3/1/88.

14.) Panel comments, Ivermectin (Systemic), 5/18/88.

15.) Personal communication, Art Kaufman, MSD International, 7/8/88.

16.) WHO Model Prescribing Information: Drugs used in parasitic diseases. Geneva: World Health Organization, 1990: 108.

17.) MSD Press Release, Mectizan, 11/88.

18.) Panel comment, 6/27/88.

19.) Rothova A, Van den Lelij A, Stilma JS et al. Side-effects of ivermectin in treatment of onchocerciasis. Lancet 1989 Jun 24; 1: 1439-41.

20.) Kumaraswami V, Ottesen EA, Vijayasekaran V, et al. Ivermectin for the treatment of Wuchereria bancrofti filariasis. JAMA 1988 June 3; 259(21): 3150-3.

21.) Diallo S, Aziz MA, Ndir O, et al. Dose-ranging study of ivermectin in treatment of filariasis due to Wuchereria bancrofti. Lancet 1987 May 2; 1: 1030.

22.) Mandell, Douglas, Bennett editors. Principles and practice of infectious diseases. 3rd ed. NY: Churchill Livingstone, 1990: 419.

23.) Campbell WC, Fisher MH, Staplay EO, et al. Ivermectin: a potent new antiparasitic agent. Science 1983 Aug 26; 221(4613): 823-8.

24.) Edwards G, Dingsdale A, Helsby N, et al. The relative systemic availability of ivermectin after administration as capsule, tablet, and oral solution. Eur J Clin Pharmacol 1988; 35: 681-4.

25.) Ette EI, Thomas WOA, Achumba JI. Ivermectin: a long-acting microfilaricidal agent. DICP Ann Pharmacother 1990 April; 24: 426-33.

26.) Ottesen EA, Vijayasekaran V, Kumaraswami V, et al. A controlled trial of ivermectin and diethylcarbamazine in lymphatic filariasis. N Engl J Med 4/19/90; 322(16): 1113-7.

27.) Campbell WC editor. Ivermectin and abamectin. New York: Springer-Verlag, 1989: 97.

28.) Panel comment, 6/12/90.

29.) Panel consensus, 6/90.

30.) Panel comment, 6/4/90.

31.) Pacque M, Munoz B, Poetschke G, et al. Pregnancy outcome after inadvertent ivermectin treatment during community-based distribution. Lancet 1990 Dec 15; 336: 1486-9.

32.) Klotz U, Ogbuokiri JE, Okonkwo PO. Ivermectin binds avidly to plasma proteins. Eur J Clin Pharmacol 1990; 39: 607-8.

33.) Collins RC, Gonzales-Peralta C, Castro J, et al. Ivermectin: Reduction in prevalence and infection intensity of Onchocerca volvulus following biannual treatments in five Guatemala communities. Am J Trop Med Hyg 1992; 47(2): 156-69.

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DATA-MEDICOS/DERMAGIC-EXPRESS No (28) 08/01/99 DR. JOSE LAPENTA R. 
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