No subject
Thu Jul 7 11:54:55 BRT 2011
<br>
Nephrotoxicity was dose dependent (in early dose escalation studies).<br>
During Ph III-IV: elevated Creatinine (up to CTC-toxicity grade 3) values w=
ere reversible in nearly all cases. There was a case with accidental severe=
overdose, leaing to an irreversible damage.<br>
Nephrotoxicity during treatment was usually related to dehydration after vo=
miting and episodes of diarrhoea. After rehydration values normalized.<br>
<br>
It was common that VL patients started off with elevated creatinine levels =
which did normalize under effective miltefosine therapy.<br>
<br>
There were a number of individual examples of HIV/AIDS patients receiveing =
Miltefosine continuously for years without any kidney problems. (though at =
VL dosage, not CL dosage, data not pblished).<br>
<br>
I do not remmember the mechanism, this is in the preclinical/ toxicology re=
cords of the drug, to which there is hopefully some access via the current =
company(?).<br>
<br>
I think Shyam Sundar has the best overview on the real nephrotoxic potentia=
l over many years in thousands of patients, and he may want to comment.<br>
<br>
DCL: Miltefosine will most certainly give relief for 2-4 months but then it=
s failure is nearly certain as well. (Sad to say, unless combined almost no=
t worth trying).<br>
<br>
I think, but I am not sure, that DNDi has data on combination therapy toxic=
ology (animal models).<br>
<br>
This is really a desparate case, and I am wondering whether Thalidomid is w=
orth trying? (Not a nice drug, but also not sufficiently tested for this in=
dication I think).<br>
<br>
There must be also patients (in East Africa/ India?) receiving Tuberculosta=
tics eg. (Rifampicin) plus antileishmanial drugs, any clinical toxicity kno=
wn from these combinations?<br>
<br>
Best regards,<br>
Gerlind Anders<br>
<br>
<br>
<br>
<br>
<br>
<br>
-------- Original-Nachricht --------<br>
> Datum: Mon, 11 Jul 2011 17:19:47 -0300<br>
> Von: Carlos Costa <<a href=3D"mailto:chncosta at gmail.com">chncosta at g=
mail.com</a>><br>
> An: <a href=3D"mailto:jaime.soto at prodderma.com">jaime.soto at prodderma.c=
om</a><br>
> CC: Leish-L <<a href=3D"mailto:Leish-l at lineu.icb.usp.br">Leish-l at li=
neu.icb.usp.br</a>><br>
> Betreff: Re: [Leish-l] SPAM-LOW: Re: =A0miltefosine for diffuse leishm=
aniasis<br>
<br>
> Thanks, Jaime.<br>
><br>
> From your review the drug is not eliminated by the kidneys, so there i=
s no<br>
> need for dose adjustment. But we should be very careful with kidney<br=
>
> functions.<br>
><br>
> Is there any information on the mechanism of renal lesion? Tubular?<br=
>
><br>
> Best regards,<br>
><br>
> Carlos.<br>
><br>
> 2011/7/11 Jaime Soto <<a href=3D"mailto:jaime.soto at prodderma.com">j=
aime.soto at prodderma.com</a>><br>
><br>
> > Dear all,****<br>
> ><br>
> > ** **<br>
> ><br>
> > I received some days ago a specific question regarding miltefosin=
e use<br>
> in<br>
> > patients with renal impairment. I delay my answer asking to other=
people<br>
> > because this is not an easy answer; this is the conclusion:****<b=
r>
> ><br>
> > ** **<br>
> ><br>
> > =93Miltefosine is mildly nephrotoxic [Soto. CID 2004; 38:1266=967=
2] in<br>
> > leishmaniasis patients with normal renal function, Whether or not=
<br>
> > miltefosine would further diminish renal function in renally-impa=
ired<br>
> > patients is not known. If renal function is already very low, how=
ever, a<br>
> > further effect on renal function might not be seen. ****<br>
> ><br>
> > ** **<br>
> ><br>
> > My personal view would be to not lower dosing because of a possib=
le<br>
> adverse<br>
> > effect on the kidneys, specially because, in the specific case, f=
ull<br>
> dose<br>
> > could mean the difference between improving and failure.****<br>
> ><br>
> > ** **<br>
> ><br>
> > Regards from Bolivia,****<br>
> ><br>
> > ** **<br>
> ><br>
> > Jaime soto ****<br>
> ><br>
> > =A0****<br>
> ><br>
> > ** **<br>
> ><br>
> > *De:* <a href=3D"mailto:leish-l-bounces at lineu.icb.usp.br">leish-l=
-bounces at lineu.icb.usp.br</a> [mailto:<br>
> > <a href=3D"mailto:leish-l-bounces at lineu.icb.usp.br">leish-l-bounc=
es at lineu.icb.usp.br</a>] *En nombre de *Carlos Costa<br>
> > *Enviado el:* domingo, 10 de julio de 2011 05:44 p.m.<br>
> > *Para:* Jennie Blackwell<br>
> > *CC:* Leish-L<br>
> > *Asunto:* SPAM-LOW: Re: [Leish-l] miltefosine for diffuse<br>
> leishmaniasis***<br>
> > *<br>
> ><br>
> > ** **<br>
> ><br>
> > Hi Jennie,****<br>
> ><br>
> > ** **<br>
> ><br>
> > Thanks for the drug information. Now, I have to check the permiss=
ion for<br>
> > its use in Brazil and how to justify its use to the public system=
in<br>
> order<br>
> > to be acquired by the government. Meanwhile, we are looking for<b=
r>
> miltefosine,<br>
> > paramomycin, and alternative therapies.****<br>
> ><br>
> > ** **<br>
> ><br>
> > But if the immunosuppression is species specific do you think tha=
t a<br>
> > general stimulation would reverse it? Does anyone knows which is =
the<br>
> > mechanism behind the DCL induced immunosuppression? Parasite or h=
ost or<br>
> > both? ****<br>
> ><br>
> > ** **<br>
> ><br>
> > Cheers,****<br>
> ><br>
> > ** **<br>
> ><br>
> > Carlos.****<br>
> ><br>
> > 2011/7/7 Jennie Blackwell <<a href=3D"mailto:jmb37 at cam.ac.uk">=
jmb37 at cam.ac.uk</a>>****<br>
> ><br>
> > Hello Carlos****<br>
> ><br>
> > ** **<br>
> ><br>
> > My memory from late 80s was that these patients responded well to=
<br>
> > interferon-gamma treatment. With all the moves to make drugs more=
<br>
> affordable<br>
> > for disease endemic countries, has it not been possible to consid=
er this<br>
> > option?****<br>
> ><br>
> > ** **<br>
> ><br>
> > In psoriasis they use creams with Vitamin D. Has anyone ever trie=
d this<br>
> for<br>
> > DCL?****<br>
> ><br>
> > ** **<br>
> ><br>
> > I'm sure this is going to elicit a round of responses - but y=
ou know I'm<br>
> > not a clinician so I would just be interested to know!****<br>
> ><br>
> > ** **<br>
> ><br>
> > Cheers, Jennie<br>
> ><br>
> > Jenefer M. Blackwell****<br>
> ><br>
> > TICHR, CCHR, UWA****<br>
> ><br>
> > Phone: +61 8 94897910****<br>
> ><br>
> > From my iPhone****<br>
> ><br>
> ><br>
> > On 07/07/2011, at 3:04, Carlos Costa <<a href=3D"mailto:chncos=
ta at gmail.com">chncosta at gmail.com</a>> wrote:****<br>
> ><br>
> > Dear all,****<br>
> ><br>
> > ** **<br>
> ><br>
> > Maria Cleudimar has cutaneous diffuse leishmaniasis due to *Leish=
mania<br>
> > amazonensis*. She used to be a long time patient form Dr. Jackson=
Costa,<br>
> > in the countryside of Maranh=E3o State, Brazil, since she was 10 =
years<br>
> old,<br>
> > after a disease that started when she was just five. Now, she is =
under<br>
> my<br>
> > and Dorcas care, at the age of 30, living in the city of Teresina=
.****<br>
> ><br>
> > ** **<br>
> ><br>
> > Her long time DCL does not respond to the treatment antimonium an=
ymore.<br>
> > Although we still prescribe liposomal amphotericin B at very low =
dose<br>
> > (3mg/kg/once a week), her situation is deteriorating progressivel=
y, her<br>
> > renal function does not allow any additional dosing since creatin=
ine is<br>
> > presently above 3mg/dL, and previous biopsy had shown tubular dam=
age<br>
> > apparently secondary to the drug, without evidence of amyloidosis=
. We<br>
> tried<br>
> > several combinations of different drugs, without success. Her sit=
uation<br>
> > worsened a lot during her recent pregnancy (the baby is eight mon=
ths old<br>
> > now).****<br>
> ><br>
> > ** **<br>
> ><br>
> > Our hope now stands only in miltefosine, for oral chronic use, bu=
t the<br>
> drug<br>
> > is not licensed or available in Brazil yet (to my knowledge).****=
<br>
> ><br>
> > ** **<br>
> ><br>
> > With her permission I attached some of her pictures, hoping to se=
nsitize<br>
> > critical people in order to help me to get miltefosine and the<br=
>
> permission<br>
> > for prescription in Brazil (or any other oral drug with promising=
<br>
> efficacy,<br>
> > and without nephrotoxicity, if known). Moreover, we need to know =
about<br>
> the<br>
> > dose adjustment for the renal impairment, and how long the drug c=
ould<br>
> safely<br>
> > be used.****<br>
> ><br>
> > ** **<br>
> ><br>
> > One picture shows her face before treatment, and another after th=
e<br>
> > pregnancy, with the baby. One shows the situation of her thighs, =
another<br>
> the<br>
> > calf of the leg and the last one the infiltration of the palate.*=
***<br>
> ><br>
> > ** **<br>
> ><br>
> > Hoping a little from friends, my kindest regards,****<br>
> ><br>
> > ** **<br>
> ><br>
> > Carlos.****<br>
> ><br>
> > ** **<br>
> ><br>
> > PS. Please understand that the pictures are allowed not for publi=
cation<br>
> or<br>
> > public presentation. Cleudimar permission is restricted to this<b=
r>
> forum.****<br>
> ><br>
> > ** **<br>
> ><br>
> ><br>
> > --<br>
> > *Carlos H. N. Costa, MD, DSc.*****<br>
> ><br>
> > *President*****<br>
> ><br>
> > *Sociedade Brasileira de Medicina Tropical *****<br>
> ><br>
> > *(Brazilian Society of Tropical Medicine)*****<br>
> ><br>
> > *Instituto de Doen=E7as Tropicais Natan Portella<br>
> > Universidade Federal do Piau=ED*****<br>
> ><br>
> > *Rua Artur de Vasconcelos 151-Sul*****<br>
> ><br>
> > *64049-750 Teresina-PI<br>
> > Brazil<br>
> > Telephones: +55 86 3221-3413 (work); +55 86 8838-3303 (mobile).<b=
r>
> > *<br>
> > Aviso: As informa=E7=F5es contidas nesta mensagem s=E3o CONFIDENC=
IAIS,<br>
> protegidas<br>
> > pelo sigilo legal, por direitos autorais e destinadas exclusivame=
nte =E0<br>
> > pessoa ou organiza=E7=E3o para a qual a mensagem foi destinada.<b=
r>
> > Warning: This message is meant only for the intended recipient of=
the<br>
> > transmission. =A0It is forbidden any unauthorized use, alteration=
,<br>
> > reproduction and distribution. If you are not the correct recipie=
nt,<br>
> please<br>
> > notify us immediately by return e-mail and delete this message fr=
om your<br>
> > system. ****<br>
> ><br>
> > ** **<br>
> ><br>
> > <cleu antes grav 13jan09.jpg>****<br>
> ><br>
> > <cleu e nene.jpg>****<br>
> ><br>
> > <cleu santada recorte.jpg>****<br>
> ><br>
> > <cleu panturrilhas.jpg>****<br>
> ><br>
> > <cleu palato.jpg>****<br>
> ><br>
> > _______________________________________________<br>
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> ><br>
> ><br>
> ><br>
> ><br>
> > --<br>
> > *Carlos H. N. Costa, MD, DSc.*****<br>
> ><br>
> > *President*****<br>
> ><br>
> > *Sociedade Brasileira de Medicina Tropical *****<br>
> ><br>
> > *(Brazilian Society of Tropical Medicine)*****<br>
> ><br>
> > *Instituto de Doen=E7as Tropicais Natan Portella<br>
> > Universidade Federal do Piau=ED*****<br>
> ><br>
> > *Rua Artur de Vasconcelos 151-Sul*****<br>
> ><br>
> > *64049-750 Teresina-PI<br>
> > Brazil<br>
> > Telephones: +55 86 3221-3413 (work); +55 86 8838-3303 (mobile).<b=
r>
> > *<br>
> > Aviso: As informa=E7=F5es contidas nesta mensagem s=E3o CONFIDENC=
IAIS,<br>
> protegidas<br>
> > pelo sigilo legal, por direitos autorais e destinadas exclusivame=
nte =E0<br>
> > pessoa ou organiza=E7=E3o para a qual a mensagem foi destinada.<b=
r>
> > Warning: This message is meant only for the intended recipient of=
the<br>
> > transmission. =A0It is forbidden any unauthorized use, alteration=
,<br>
> > reproduction and distribution. If you are not the correct recipie=
nt,<br>
> please<br>
> > notify us immediately by return e-mail and delete this message fr=
om your<br>
> > system. ****<br>
> ><br>
> > ** **<br>
> ><br>
> > ** **<br>
> ><br>
> > __________ Informaci=F3n de ESET NOD32 Antivirus, versi=F3n de la=
base de<br>
> > firmas de virus 6280 (20110709) __________****<br>
> ><br>
> > ** **<br>
> ><br>
> > ESET NOD32 Antivirus ha comprobado este mensaje.****<br>
> ><br>
> > ** **<br>
> ><br>
> > <a href=3D"http://www.eset.com" target=3D"_blank">http://www.eset=
.com</a>****<br>
> ><br>
> > ** **<br>
> ><br>
> > __________ Informaci=F3n de ESET NOD32 Antivirus, versi=F3n de la=
base de<br>
> > firmas de virus 6284 (20110711) __________****<br>
> ><br>
> > ** **<br>
> ><br>
> > ESET NOD32 Antivirus ha comprobado este mensaje.****<br>
> ><br>
> > ** **<br>
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.com</a>****<br>
> ><br>
><br>
><br>
><br>
> --<br>
> *Carlos H. N. Costa, MD, DSc.*<br>
> *President*<br>
> *Sociedade Brasileira de Medicina Tropical *<br>
> ***(Brazilian Society of Tropical Medicine)*<br>
> *Instituto de Doen=E7as Tropicais Natan Portella<br>
> Universidade Federal do Piau=ED*<br>
> *Rua Artur de Vasconcelos 151-Sul*<br>
> *64049-750 Teresina-PI<br>
> Brazil<br>
> Telephones: +55 86 3221-3413 (work); +55 86 8838-3303 (mobile).<br>
> *<br>
> Aviso: As informa=E7=F5es contidas nesta mensagem s=E3o CONFIDENCIAIS,=
<br>
> protegidas<br>
> pelo sigilo legal, por direitos autorais e destinadas exclusivamente =
=E0<br>
> pessoa ou organiza=E7=E3o para a qual a mensagem foi destinada.<br>
> Warning: This message is meant only for the intended recipient of the<=
br>
> transmission. =A0It is forbidden any unauthorized use, alteration,<br>
> reproduction and distribution. If you are not the correct recipient,<b=
r>
> please<br>
> notify us immediately by return e-mail and delete this message from yo=
ur<br>
> system.<br>
<font color=3D"#888888"><br>
--<br>
NEU: FreePhone - kostenlos mobil telefonieren!<br>
Jetzt informieren: <a href=3D"http://www.gmx.net/de/go/freephone" target=3D=
"_blank">http://www.gmx.net/de/go/freephone</a><br>
</font></blockquote></div><br><br clear=3D"all"><br>-- <br><font face=3D"ve=
rdana, sans-serif"><b>Carlos H. N. Costa, MD, DSc.</b></font><div><font fac=
e=3D"verdana, sans-serif"><b>President</b></font></div><div><span style=3D"=
font-family:verdana, sans-serif"><b>Sociedade Brasileira de Medicina Tropic=
al=A0</b></span></div>
<div><b><span style=3D"font-family:verdana, sans-serif"></span></b><span st=
yle=3D"font-family:verdana, sans-serif"><b>(Brazilian Society of Tropical M=
edicine)</b></span></div><div><font face=3D"verdana, sans-serif"><b>Institu=
to de Doen=E7as Tropicais Natan Portella<br>
Universidade Federal do Piau=ED</b></font><div><font face=3D"verdana, sans-=
serif"><b>Rua Artur de Vasconcelos 151-Sul</b></font></div><div><font face=
=3D"verdana, sans-serif"><b>64049-750 Teresina-PI<br>Brazil<br>Telephones: =
+55 86 3221-3413 (work); +55 86 8838-3303 (mobile).<br>
</b><br><span style=3D"font-size:x-small">Aviso: As informa=E7=F5es contida=
s nesta mensagem s=E3o CONFIDENCIAIS, protegidas pelo sigilo legal, por dir=
eitos autorais e destinadas exclusivamente =E0 pessoa ou organiza=E7=E3o pa=
ra a qual a mensagem foi destinada.<br>
Warning: This message is meant only for the intended recipient of the trans=
mission.=A0 It is forbidden any unauthorized use, alteration, reproduction =
and distribution. If you are not the correct recipient, please notify us im=
mediately by return e-mail and delete this message from your system. </span=
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