[AF] Respuesta a dobesilato
Santiago Ricarte
sricarte001 en cofb.net
Mie Jun 8 17:23:15 CEST 2005
Hola Marciana mi respuesta es:
1) El beneficio de tomar Dobesilato sin patologia es cero, nulo.
2) Partiendo de la idea de que el medicamento no es una peladilla o una
ricola, el riesgo de que sufra un efecto adverso ahora, o cuando tome otro
medicamento asociado, o cuando sus condiciones fisiologicas cambien, son
posibles y elevadas, y si haces una busqueda en el micromedex
(al final de la carta te lo añado) lo ves claro.
Por lo que he leido( lo añadido al final) y considerando que los
medicamentos no
estan en el super por algo, mi parecer es que la relación beneficio riesgo
es
MUY NEGATIVO
informe al medico por riesgo evitable. La atención farmacéutica eficiente se
adelanta
a la aparición de PRM eliminando los latentes, y mas cuando estos son
absurdos.
tiene un PRM de seguridad LATENTE ( de su integridad fisica) causado por el
uso de un medicamento que no necesita, que le puede alterar altres
medicaciones, que hace aconsejable no esperar a ver que pasa sino retirar el
medicamento por usarse temerariamente.
Firmo aqui porque la lista de abajo es larga
Santiago,
gracias por lo del cuestionador , ten cuidado que tu tambien empiezas a
cuestionar eh? ;-)
BOT Plus
CONSIDERACIONES ESPECIALES:
- Se han obsevado casos de agranulocitosis puede manifestarse mediante
sintomatología inespecífica característica de un proceso infeccioso, en cuyo
caso se deberá realizar un control analítico hematológico y leucocitario y
discontinuar el tratamiento.
- En caso de trastornos gastrointestinales debe reducirse la dosis o
interrumpir el tratamiento temporalmente.
Parte de los efectos en Micromedex
CALCIUM DOBESILATE
CAUTIONS
ADVERSE REACTIONS
ADVERSE REACTIONS, BLOOD
A. AGRANULOCYTOSIS
1. A 64-year-old woman experienced agranulocytosis with white cell counts to
600/microliter with 96% lymphocytes after treatment with calcium dobesilate
500 milligrams twice daily for 15 weeks. Eight months later, generalized
pyoderma, fever to 40 degrees C and agranulocytosis (white cell count
700/microliter) recurred after she had taken calcium dobesilate for 3 weeks.
A lymphocyte transformation test confirmed that calcium dobesilate caused
significant stimulation of the lymphocytes 4, 8 and 14 weeks after her
second occurrence of agranulocytosis (Kulessa et al, 1992).
3.3.4 ENDOCRINE/METABOLIC
A. DRUG FEVER
1. A 54-year-old man who received calcium dobesilate 1500 milligrams/day
(500 milligrams three times daily) for diabetic retinopathy experienced
drug-induced fever. After 8 days of calcium dobesilate, he presented with a
fever of 39 degrees C, generalized myalgia, chills and headache. Fever
persisted for 12 days and ceased within 48 hours after withdrawal of the
drug. Upon rechallenge, 500 milligrams of calcium dobesilate produced a
fever 20 hours later and lasted for 8 hours. This patient fulfilled Young's
criteria for drug-induced fever (Puyana et al, 1990).
3.3.5 GASTROINTESTINAL
A. EPIGASTRIC PAIN
1. Mild epigastric pain occurred in 11 of 41 patients (27%) who received
calcium dobesilate 1500 mg/day for treatment of diabetic retinopathy and
open-angle glaucoma (Vojnikovic, 1991).
3.3.10 SKIN
A. EXANTHEMA
1. A 78-year-old man who received calcium dobesilate for peripheral vascular
impairment was given a diagnosis of acute generalized EXANTHEMATOUS
PUSTULOSIS two days after initiation of calcium dobesilate. He presented
with a generalized pruritic eruption and fever of 38 degrees C. The
scarlatiform rash with nonfollicular pustules was widespread; however, his
palms, soles and mucous membranes were spared. Four days after
discontinuation of calcium dobesilate, with the addition of topical
corticosteroids, the patient's fever and pustules resolved. Two days later
the same reaction occurred after he resumed calcium dobesilate. The eruption
rapidly resolved after discontinuation of calcium dobesilate (Perez et al,
1994).
3.4 TERATOGENICITY/EFFECTS IN PREGNANCY
A. TERATOGENICITY
1. Animal data have not demonstrated teratogenic potential; however, there
are insufficient clinical data in humans (Fachinfo Dobica(R), 1996).
B. EFFECTS IN PREGNANCY
1. There are insufficient clinical data in humans on the use of calcium
dobesilate during pregnancy (Fachinfo Dobica(R), 1996).
4.0 CLINICAL APPLICATIONS
4.1 MONITORING PARAMETERS
4.1.1 THERAPEUTIC
A. PHYSICAL EXAMINATION
1. Improvement in symptoms of chronic venous insufficiency (heaviness,
swelling, etc)
2. Improvement in symptoms of diabetic retinopathy (area of retinal
hemorrhage, blood viscosity, visual field)
4.1.2 TOXIC
A. PHYSICAL EXAMINATION
1. If the patient experiences gastrointestinal intolerance, he or she may
benefit from a decrease in dose, or a temporary discontinuation of therapy
(Fachinfo Dobica(R), 1996).
4.2 PATIENT INSTRUCTIONS
A. CALCIUM DOBESILATE (ORAL)
1. DESCRIPTION: vascular protectant
2. BRAND NAMES: Dexium(R), Dobica(R)
3. SIDE EFFECTS:
a. If you have problems with these or other side effects, tell your doctor.
SOME PATIENTS MAY HAVE OTHER SIDE EFFECTS THAT ARE NOT LISTED BELOW.
(1) Stomach pains, nausea
b. The following side effects may be associated with more serious
complications. CALL YOUR DOCTOR IMMEDIATELY IF ANY OF THE FOLLOWING EFFECTS
OCCUR:
(1) Shortness of breath, allergic skin reactions, fevers
4. CONTRAINDICATIONS: Known hypersensitivity to one of the ingredients,
pregnancy, breastfeeding
5. PRECAUTIONS:
a. Recurrent gastritis, peptic or duodenal ulcers
6. DRUGS/FOODS TO AVOID: Ask your doctor or pharmacist before taking any
other medications, including over-the-counter (nonprescription) products.
7. STORAGE/ADMINISTRATION GUIDELINES:
a. ORAL CAPSULES/TABLETS: Take this medicine exactly as your doctor ordered.
Store at room temperature, and protect from heat, moisture, and direct
light. Keep all medicine away from the reach of children.
8. MISSED DOSE: Take the missed dose as soon as possible. Skip the missed
dose if it is almost time for your next regular dose. Do not take two doses
at the same time.
4.3 PLACE IN THERAPY
A. Although certain successes have been obtained in clinical trials,
opinions about the vasoprotective efficacy of calcium dobesilate for the
treatment of chronic venous insufficiency and varicose veins are divided
(Mutschler, 1996). Its vasoprotective effects have also showed some promise
in the treatment of myocardial infarction and diabetic retinopathy. Further
clinical studies are needed to determine its place in the treatment of these
disease states.
4.4 MECHANISM OF ACTION/PHARMACOLOGY
A. MECHANISM OF ACTION
1. Calcium dobesilate acts on the endothelial layer and basement membrane of
the capillaries. It reduces histamine and bradykinin-induced
hyperpermeability. It increases red blood cell membrane flexibility and
reduces capillary fragility. Calcium dobesilate can reduce the platelet
aggregation stimulated by collagen and thrombin, but not by arachidonic acid
(Fachinfo Dobica(R), 1996; Michal & Gotti, 1988; Hachen & Lorenz, 1982).
2. Calcium dobesilate may also inhibit the formation of sorbitol, thus
providing another possible mechanism for its usefulness in diabetic
retinopathy (Schmidt & Michal, 1989).
3. Glucose inhibits the formation of both type I and type II collagen
formation. Calcium dobesilate does not affect type I inhibition by glucose
but accelerates type II collagen fibrillogenesis, a major structural
component of the arterial wall (Schmut, 1989).
4. Calcium dobesilate has angioprotective action by reducing the
permeability and fragility of microvessels, which should restrict fluid
extravasation into the cardiac interstitium. Its antiplatelet effect should
counteract thrombosis and its reduction of plasma viscosity should prevent
stasis (Szlavy et al, 1990).
B. REVIEW ARTICLES
1. An International Task Force evaluated therapeutic options for managing
venous edema (venous insufficiency); the efficacy of CALCIUM DOBESILATE and
other medications are reviewed (Clement, 2000).
4.5 THERAPEUTIC USES
A. ACUTE MYOCARDIAL INFARCTION
1. OVERVIEW:
FDA APPROVAL: Adult, no; pediatric, no
EFFICACY: Adult, effective
DOCUMENTATION: Adult, good
2. SUMMARY:
- Reduces infarct size following
acute myocardial infarction
- Has a protective effect on the myocardium
in early acute myocardial infarction
3. ADULT:
a. Calcium dobesilate has demonstrated efficacy in reducing infarct size and
shows a protective effect on the myocardium in early acute MYOCARDIAL
INFARCTION. A pilot study in one hundred patients was conducted in patients
presenting with acute myocardial infarction. Fifty patients served as a
control group and did not receive calcium dobesilate. The other 50 patients
received the following schedule of calcium dobesilate within 6 hours of
onset of chest pain: intravenous infusion of 100 milligrams/kilogram (mg/kg)
on admission and 1 and 2 hours post admission followed by 50 mg/kg during
the third hour. From the sixth hour until hospital day four, 25 mg/kg
intravenous boluses were given every 6 hours. Beginning day 4, calcium
dobesilate was administered 1000 milligrams every 8 hours. The treatment
group had a quicker return to 50% of baseline values of CK (18 to 24 hours
in treatment group compared to 36 to 48 hours in control group). Similar
results were noted in EKG ST-segment depression changes. Adverse drug
reactions included transient hypotension in 9 patients receiving calcium
dobesilate. Placebo-controlled studies involving effects on mortality and
survival in large numbers of patients would be desirable before widespread
implementation of calcium dobesilate for treatment of acute myocardial
infarction (Szlavy et al, 1991; Szlavy et al, 1990).
B. ANTI-PLATELET AGGREGATION
1. OVERVIEW:
FDA APPROVAL: Adult, no; pediatric, no
EFFICACY: Adult, effective
DOCUMENTATION: Adult, fair
2. SUMMARY:
- Reduces platelet aggregation
- Increases reaction time
- Decreases platelet aggregation/reaction
time quotient
3. ADULT:
a. In a placebo-controlled dose-response study of 52 patients with increased
platelet aggregation, calcium dobesilate 1500 milligrams/day for 4 days
produced a 22% decrease in platelet aggregation, a 96.4% increase in
reaction time and a 75% decrease in the platelet aggregation/reaction time
quotient as compared to placebo. Doses of 500 mg and 1000 mg daily did not
produce significant changes (Heidrich et al, 1983).
C. CHRONIC VENOUS INSUFFICIENCY
1. OVERVIEW:
FDA APPROVAL: Adult, no; pediatric, no
EFFICACY: Adult, effective
DOCUMENTATION: Adult, good
2. SUMMARY:
- Effective in the treatment of
chronic venous insufficiency
- Reduces volume in the foot and lower legs
- Reduces ankle and calf circumferences
3. ADULT:
a. Calcium dobesilate 500 milligrams orally 3 times daily for 28 days was
highly effective and well tolerated in an open, multicenter study of 373
patients with chronic VENOUS INSUFFICIENCY (Angehrn, 1995). A core group of
287 patients met all the inclusion criteria during treatment, and
statistically significant reductions in ankle and calf circumferences (4.4%
and 2.8%, respectively) were obtained in this group. These figures represent
a leg volume reduction of 0.13 liter. Each symptom measured (pain, daytime
cramps, nighttime cramps, swelling, heavy legs, paresthesia and restless
legs) decreased statistically significantly in frequency, with cumulative
scores demonstrating global improvement for 93.8% of the core group patients
and 95.1% of the entire study population. In the core group, 23.1% of the
patients showed complete clearing of symptoms at the end of the study.
Adverse reactions (gastrointestinal disorders, urticaria and exanthema,
paresthesia, fatigue and weight gain) were reported by 22 patients (5.9%)
and resulted in seven discontinuations of treatment.
b. Calcium dobesilate has produced both subjective and objective improvement
in the treatment of chronic venous insufficiency. In two clinical trials, 55
to 60 patients were given 1000 milligrams twice daily for six weeks, or
placebo. Results were similar in both trials; there were statistically
significant reductions in volume of the foot and lower legs in the calcium
dobesilate group as determined by plethysmography. Patients with active drug
also experienced reductions in the feeling of heaviness, swelling,
tenderness and aching pains. Reductions in maximum venous incremental
volumes and maximum venous outflow capillary filtration correlated well with
the subjective improvement experienced by the patients. From both trials,
there was one complaint of gastrointestinal side effects responsible for
withdrawal from treatment. Calcium dobesilate, producing both objective and
subjective benefits with minimal adverse reactions, offers a potential mode
of therapy for the treatment of chronic venous insufficiency (Casley-Smith,
1988; Hachen & Lorenz, 1982).
D. DIABETIC RETINOPATHY
1. OVERVIEW:
FDA APPROVAL: Adult, no; pediatric, no
EFFICACY: Adult, effective
DOCUMENTATION: Adult, good
2. SUMMARY:
- Reduces blood hyperviscosity, retinal hemorrhages,
visual field defects, and intraocular pressure
- Enhances outflow facility
- Inhibits the formation of sorbitol
3. ADULT:
a. Calcium dobesilate has been shown to decrease blood hyperviscosity and
intraocular pressure in patients with diabetic retinopathy and GLAUCOMA. In
a randomized double-blind trial, 79 non-insulin dependent diabetics with
early retinopathy or OPEN-ANGLE GLAUCOMA received 1500 milligrams daily for
6 months, or placebo. The treatment group experienced statistically
significant decreases in intraocular pressure, visual field defects, surface
area of retinal hemorrhage and blood viscosity. There were also significant
decreases in albumin, prothrombin time, and platelet counts after 6 months
of treatment. Eleven of 41 patients on calcium dobesilate experienced mild
gastric pain, compared to 1 of 38 patients in the placebo group, with no
withdrawals from therapy in either group. Calcium dobesilate also has been
shown to inhibit the formation of sorbitol, another factor related to the
occurrence of diabetic retinopathy. The multiple effects of calcium
dobesilate including decreasing intraocular pressure, enhancing outflow
facility, reducing both retinal hemorrhages and blood hyperviscosity
resulted in improvement of the retinal state and visual fields. These
findings in conjunction with good patient tolerability suggest that calcium
dobesilate may be promising for the treatment of diabetic retinopathy
(Vojnikovic, 1991; Schmidt & Michal, 1989).
E. VARICOSE VEINS
1. OVERVIEW:
FDA APPROVAL: Adult, no; pediatric, no
EFFICACY: Adult, effective
DOCUMENTATION: Adult, poor
2. SUMMARY:
- Decreases venous distensibility index
- Decreases maximum venous outflow
and capillary filtration index
- Reduces ankle edema
3. ADULT:
a. In 1 study, 76% of patients with varicose veins treated with calcium
dobesilate experienced beneficial effects. In this study 60 patients with
varicose veins were randomized to receive either calcium dobesilate 750
milligrams daily or placebo for three months. Twenty-five of 30 patients
completed the 3 month course of active treatment. Nineteen patients (76%)
experienced both objective benefit (statistically significant decreases in
venous distensibility index, maximum venous outflow and capillary filtration
index) and subjective benefit (less heaviness in the legs and reduced ankle
edema). However, data were not presented for the patients who did not
respond to therapy or for the group who served as control. Three of the 30
patients in the calcium dobesilate group discontinued therapy due to
gastrointestinal upset or unspecified allergic reactions (Androulakis &
Panoysis, 1989).
F. VENOUS ULCERS
1. OVERVIEW:
FDA APPROVAL: Adult, no; pediatric, no
EFFICACY: Adult, effective
DOCUMENTATION: Adult, fair
2. SUMMARY:
- Calcium dobesilate may promote healing of
venous ulcers of the leg, although ulceration
may recur in some cases when the medication is
discontinued
3. ADULT:
a. An 8-week course of CALCIUM DOBESILATE (500 milligrams twice daily after
meals) promoted healing of VENOUS STASIS ULCERS and reduced pain, heaviness,
and swelling associated with STASIS DERMATITIS, based on a small, open-label
pilot study (n=25). Clinical symptoms were graded by study participants on a
scale of 0 to 4 (0-absent, 1-mild, 2-moderate, 3-severe, and 4-very severe).
At study end-point, subjective scores had improved for most symptoms,
including PAIN (3.78 to 0.39; p=0.000 baseline compared with
post-treatment), PRURITUS (3.55 to 0.45; p=0.000), TIREDNESS (3.82 to 0.32;
p=0.000), HEAVINESS (3.74 to 0.65; p=0.00), PARESTHESIA (3.80 to 1.20;
p=0.066), CRAMPS (3.92 to 0.61; p=0.001), and LEG SWELLING (3.89 to 0.63;
p=0.000). Mean area of leg ulcers measured 9.82 centimeters (cm) prior to
treatment and 1.35 cm after 8 weeks of calcium dobesilate (p=0.0004). Of 10
patients studied with color Doppler duplex ultrasound before and after
treatment, 4 appeared to have improved competence in the sapheno-femoral
valves, suggested by decreased reversal of flow on distal compression.
Overall, 80% of the patients with ulcers graded the treatment as excellent
and 60% of the patients with stasis dermatitis rated it as good. One subject
dropped out at 7 weeks due to development of urticaria. Recurrence of ulcers
was seen in 5 of 12 patients followed for 3 months post-trial (Kaur et al,
2003).
4.6 COMPARATIVE EFFICACY AND EVALUATION WITH OTHER SIMILAR THERAPEUTIC
AGENTS
A. DIOSMIN
1. HEMORRHOIDS
a. Both calcium dobesilate and diosmin were equally effective and safe when
used to treat acute hemorrhoids. Fifty-one patients were randomized, with 25
receiving dobesilate 500 milligrams (mg) three times daily while 26 were
given diosmin 1000 mg (2 tablets) three times daily. Treatment was assessed
by reduction in a 4-point pain score for 7 discreet symptoms, including
pain, discharge, bleeding and itching. Secondary assessments were made based
on patient subjective ratings of response, use of adjunctive analgesics, and
relapse. Assessment was done at base, 2 and 8 days, then 4 weeks after
treatment, and scores did not reflect any measurable difference in response
at any point. Substantial improvement was noted within 48 hours with both
agents. Patient self-satisfaction with outcome was good in 75% of each
groups, with 8% of each group rating outcome as poor. Three patients in each
group had recurrence of symptoms during treatment (Sarabia et al, 2001).
6.0 REFERENCES
1. Androulakis G & Panoysis PA: Plethysmographic confirmation of the
beneficial effect of calcium dobesilate in primary varicose veins. Angiology
1989; 40:1-4.
2. Angehrn F: Efficacy and safety of calcium dobesilate in patients with
chronic venous insufficiency: an open-label, multicenter study. Curr Ther
Res 1995; 56:346-357.
3. Casley-Smith JR: A double-blind trial of calcium dobesilate in chronic
venous insufficiency. Angiology 1988; 39:853-857.
4. Clement DL: Management of venous edema: insights from an international
task force. Angiology 2000; 51(1):13-17.
5. Fachinformation: Dexium(R) 250 and Dexium(R) 500, calcium dobesilate.
Synthelabo Arzneimittel GmbH, Puchheim, 1996.
6. Fachinformation: Dobica(R), calcium dobesilate. Oranienburger Pharmawerk
GmbH, Oranienburg, 1996.
7. Haas A, Trummer G, Eckhardt M et al: Einfluss von Kalziumdobesilat auf
die Progression der diabetischen Retinopathie. Klin Monatsbl Augenheilkd
1995; 207:17-21.
8. Hachen HJ & Lorenz P: Double-blind clinical and plethysmographic study of
calcium dobesilate in patients with peripheral microvascular disorders.
Angiology 1982; 33:480-488.
9. Heidrich H, Gerke E & Nekarda H: Thrombozytenaggregationshemmung unter
Calciumdobesilat. Arzneimittelforschung 1983; 33:580-582.
10. Kaur C, Sarkar R, Kanwar AJ et al: An open trial of calcium dobesilate
in patients with venous ulcers and stasis dermatitis. Int J Dermatol 2003;
42:147-152.
11. Kulessa W, Becker EW & Berg PA: Wiederholte Agranulozytose nach Einnahme
von Calciumdobesilat. Dtsch Med Wochenschr 1992; 117:372-374.
12. Michal M & Gotti C: Effect of calcium dobesilate on platelet function.
Thrombosis Res 1988; 51:593-605.
13. Mutschler E: Arzneimittelwirkungen: Lehrbuch der Pharmakologie und
Toxikologie; mit einfuehrenden Kapiteln in die Anatomie, Physiologie und
Pathophysiologie. 7. Aufl. Wissenschaftliche Verlagsgesellschaft mbH,
Stuttgart, 1996.
14. Perez B, de las Heras E, Hilara Y et al: Acute generalized exanthematous
pustulosis induced by calcium dobesilate (abstract). J Dermatol Treat 1994;
5:211-213.
15. Plessas CT, Souras S, Karayannacos PE et al: Pharmacokinetic interaction
in beagle dogs of antiplatelet drugs: acetylsalicylic acid, dipyridamole and
calcium dobesilate. Eur J Drug Metab Pharmacokinet 1989; 14:79-83.
16. Puyana J, Fraj J, De La Hoz B et al: Drug-induced fever: a clinical
report and challenge test with calcium dobesilate. Int Arch Allergy Appl
Immunol 1990; 92:364-365.
17. Sarabia M, Leon S, Vivas J et al: Calcium dobesilate versus purified
flavonoid fraction of diosim in the treatment of hemorrhoidal crises: a
randomized, controlled study with an initial double-blind, double-dummy
period. Curr Ther Res 2001; 62(7):524-529.
18. Schmidt M & Michal M: Inhibition of sorbitol formation in human
erythrocytes by calcium dobesilate. Arzneimittelforschung 1989; 39:493-495.
19. Schmut O: Effect of calcium dobesilate on the inhibition of collagen
fibrillogenesis by glucose in vitro. Arzneimittelforschung 1989; 39:
1555-1557.
20. Szlavy L, Repa I & Hachen HJ: The influence of CLS 2210 on the course of
myocardial infarction: a pilot study in man. Angiology 1991; 42:639-647.
21. Szlavy L, Repa I, Lengyel I et al: Calcium dobesilate (CLS 2210)
protects the myocardium in early acute myocardial infarction: a preliminary
randomized, double-blind, placebo-controlled study of its effects on
biochemical markers. J Cardiovasc Pharmacol 1990; 15: 89-95.
22. Van Nueten JM, Van Beek J & Janssen PAJ: The vascular effects of
flunarizine as compared with those of other clinically used vasoactive
substances. Arzneimittelforschung 1978; 28:2082-2087.
23. Vojnikovic B: Doxium(R) (calcium dobesilate) reduces blood
hyperviscosity and lowers elevated intraocular pressure in patients with
diabetic retinopathy and glaucoma. Ophthalmic Res 1991; 23:12-20.
7.0 AUTHOR INFORMATION
Original publication: 09/1995
Most recent revision: 06/2003
List of contributors:
1. Prof Dr Dr Ernst Mutschler
2. Dr. Horst W. Schuchmann
3. Debra Offricht, PharmD
4. DRUGDEX(R) Editorial staff
For further information on contributing authors,
see editorial board listings.
(DE1684)
End of Document
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