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SURAMIN

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Suramin is a polysulfonated naphthylurea macrofilaricide and microfilaricide (Anderson & Fuglsang, 1978; Spencer et al, 1975).
    B) Suramin is a cumulative drug, with slow renal excretion (Duke, 1968; JEF Reynolds , 1999).

Specific Substances

    1) Antrypol
    2) Bayer-205
    3) Fourneau-309
    4) Naganinum
    5) Naganol
    6) CAS 145-63-1 (suramin)
    7) CAS 129-46-4 (suramin sodium)

Available Forms Sources

    A) USES
    1) Suramin is used in the treatment of onchocerciasis as an anthelmintic (Anderson & Fuglsang, 1978), and African trypanosomiasis (Spencer et al, 1975).
    2) Suramin is available in the U.S. as an investigational anti-infective agent and may be obtained through the Centers for Disease Control and Prevention.
    3) It has also been used as an antineoplastic (metastatic prostrate cancer, relapsed nodular lymphoma, adrenocortical carcinoma) and as a treatment for AIDS (LaRocca et al, 1990; (Katz et al, 1995; JEF Reynolds , 1999).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) WITH THERAPEUTIC USE
    1) Stomatitis, persistent diarrhea, fatigue, and weakness have been associated with therapeutic use. Exfoliative dermatitis and prolonged fever have developed rarely.
    B) WITH POISONING/EXPOSURE
    1) Overdose cases are not available in the literature. Suramin is poorly absorbed orally; overdose cases would be due to incorrect dosage given intravenously. Since suramin is generally given in several bolus doses, and pharmacologic effects are cumulative, overdose effects would be expected to be extensions of the therapeutic effects.
    2) Suramin has a half-life of over 30 days, so effects seen may extend over a lengthy period of time.
    0.2.3) VITAL SIGNS
    A) WITH THERAPEUTIC USE
    1) Low grade fever may occur as a late effect of therapeutic use.
    0.2.4) HEENT
    A) WITH THERAPEUTIC USE
    1) Keratopathy, optic atrophy, and hyperopic shift have been associated with therapeutic use of suramin.
    0.2.6) RESPIRATORY
    A) WITH THERAPEUTIC USE
    1) Respiratory failure may be a complication of polyneuropathy.
    0.2.7) NEUROLOGIC
    A) WITH THERAPEUTIC USE
    1) Severe lassitude, polyneuropathy, and paresthesias have been reported after therapeutic use.
    0.2.8) GASTROINTESTINAL
    A) ANIMAL STUDIES - Splenomegaly has been reported in animal experiments.
    B) WITH THERAPEUTIC USE
    1) Diarrhea and stomatitis occur with therapeutic use. Splenomegaly has been reported following human therapeutic use.
    0.2.9) HEPATIC
    A) ANIMAL STUDIES - Hepatomegaly occurred during animal experiments.
    B) WITH THERAPEUTIC USE
    1) Elevated liver enzymes have been reported following therapeutic use.
    0.2.10) GENITOURINARY
    A) WITH THERAPEUTIC USE
    1) Acute renal failure was reported following suramin therapy.
    2) Azotemia, proteinuria, and albuminuria occur with therapeutic use.
    0.2.12) FLUID-ELECTROLYTE
    A) WITH THERAPEUTIC USE
    1) Hyponatremia occurs occasionally.
    0.2.13) HEMATOLOGIC
    A) WITH THERAPEUTIC USE
    1) Leukopenia, neutropenia, thrombocytopenia, anemia, and prolongation of prothrombin time occur with high therapeutic doses.
    0.2.14) DERMATOLOGIC
    A) WITH THERAPEUTIC USE
    1) Tenderness of the soles and the palms is common with therapeutic administration and is related to the death of adult worms with destruction of the microfilariae. Minor skin rashes, itching, and desquamation of the skin over the lower legs is common.
    2) Exfoliative dermatitis occurs rarely. Toxic cutaneous eruptions which have included infrequent reports of erythema multiforme exfoliative dermatitis and fatal toxic epidermal necrolysis have been reported.
    0.2.16) ENDOCRINE
    A) WITH THERAPEUTIC USE
    1) Hypoadrenalism and adrenal insufficiency have been reported in patients receiving high dose therapy.
    0.2.20) REPRODUCTIVE
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

Laboratory Monitoring

    A) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count, urinalysis, and liver and kidney function tests is suggested for patients with significant exposure.
    B) During therapy and overdose, monitor liver enzymes, renal function, and hematological parameters.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) There are no specific antidotes; treatment is symptomatic and supportive. The half-life is over 30 days, so renal, hematologic, liver, and adrenal effects are likely to be long lasting. Hydrocortisone may be required as adrenal replacement.

Range Of Toxicity

    A) Effects are cumulative due to slow renal excretion.
    B) THERAPEUTIC DOSES - Adults over 60 kilograms: Minor or "light" Infections: 1 gram (administered intravenously over two to 3 minutes) is given weekly for a total of 6 grams. As an antineoplastic: 50 to 460 milligrams per square meter, per day
    C) The possibility of developing polyneuropathy was 40% when blood suramin levels were over 350 micrograms per milliliter.

Clinical Effects

Summary Of Exposure

    A) WITH THERAPEUTIC USE
    1) Stomatitis, persistent diarrhea, fatigue, and weakness have been associated with therapeutic use. Exfoliative dermatitis and prolonged fever have developed rarely.
    B) WITH POISONING/EXPOSURE
    1) Overdose cases are not available in the literature. Suramin is poorly absorbed orally; overdose cases would be due to incorrect dosage given intravenously. Since suramin is generally given in several bolus doses, and pharmacologic effects are cumulative, overdose effects would be expected to be extensions of the therapeutic effects.
    2) Suramin has a half-life of over 30 days, so effects seen may extend over a lengthy period of time.

Vital Signs

    3.3.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Low grade fever may occur as a late effect of therapeutic use.
    3.3.3) TEMPERATURE
    A) WITH THERAPEUTIC USE
    1) A low grade fever may occur as a late effect of suramin therapy (Stein et al, 1986; Tefferi et al, 1993; JEF Reynolds , 1999).

Heent

    3.4.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Keratopathy, optic atrophy, and hyperopic shift have been associated with therapeutic use of suramin.
    3.4.3) EYES
    A) PHOTOPHOBIA
    1) WITH THERAPEUTIC USE
    a) Late effect of suramin therapy can include photophobia, lacrimation, and edema (JEF Reynolds , 1999).
    B) OPTIC ATROPHY
    1) WITH THERAPEUTIC USE
    a) Optic atrophy has been associated with suramin-treated patients with ocular onchocerciasis (Thylefors & Rolland, 1979). Its suggested that a prolonged inflammatory response to dying microfilariae in the optic nerve may be responsible; however, a direct toxic or allergic effect cannot be ruled out (JEF Reynolds , 1999).
    C) KERATOPATHY
    1) WITH THERAPEUTIC USE
    a) Suramin has been implicated in creation of toxic vortex keratopathy (Teich et al, 1986; Holland et al, 1988; Rosen et al, 1996).
    b) In a prospective study, conducted by Hemady et al (1996), 13 of 114 patients developed keratopathy, bilateral corneal epithelial deposits, following suramin therapy to treat metastatic cancer of the prostate. The keratopathy resolved following the use of topical lubricants.
    D) BLURRED VISION
    1) WITH THERAPEUTIC USE
    a) In a series of 114 patients treated with suramin for prostate cancer, seven (6%) complained of blurred vision and were found to have a hyperopic shift in refractive error of 1.13 diopter following suramin therapy to treat metastatic cancer of the prostate (Hemady et al, 1996).
    3.4.4) EARS
    A) DEAFNESS
    1) WITH THERAPEUTIC USE
    a) Unilateral deafness occurred in one patient following suramin treatment for agnogenic myeloid metaplasia (Tefferi et al, 1993).

Respiratory

    3.6.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Respiratory failure may be a complication of polyneuropathy.
    3.6.2) CLINICAL EFFECTS
    A) APNEA
    1) WITH THERAPEUTIC USE
    a) Polyneuropathy has resulted in respiratory paralysis which necessitated endotracheal intubation (LaRocca et al, 1990a).

Neurologic

    3.7.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Severe lassitude, polyneuropathy, and paresthesias have been reported after therapeutic use.
    3.7.2) CLINICAL EFFECTS
    A) FATIGUE
    1) WITH THERAPEUTIC USE
    a) Severe lassitude may occur with therapeutic doses (Duke, 1968).
    B) NEUROPATHY
    1) WITH THERAPEUTIC USE
    a) SUMMARY - In general, severe polyneuropathy with generalized flaccid paralysis has been associated with serum concentrations greater than 350 micrograms/milliliter (JEF Reynolds , 1999).
    b) Four of 38 patients developed severe polyneuropathy after suramin was used as an antineoplastic for 5 to 12 weeks in cumulative doses of 12.6 to 23.6 grams. The neuropathy was characterized by flaccid paralysis, some with bulbar and respiratory involvement (LaRocca et al, 1990a).
    c) Eight of 81 patients (10%) involved in a phase I clinical trial of suramin developed grade III/IV sensorimotor polyneuropathy at a suramin concentrations of 275 mcg/mL. Seven of the eight patients also had accompanying distal sensory symptoms, including dysesthesias, paresthesias, sensory loss, and/or pain (Bitton et al, 1995).
    C) PARESTHESIA
    1) WITH THERAPEUTIC USE
    a) Self-limiting paresthesias were reported in about 30% of patients taking suramin for AIDS (Broder et al, 1985; Collins et al, 1986).

Gastrointestinal

    3.8.1) SUMMARY
    A) ANIMAL STUDIES - Splenomegaly has been reported in animal experiments.
    B) WITH THERAPEUTIC USE
    1) Diarrhea and stomatitis occur with therapeutic use. Splenomegaly has been reported following human therapeutic use.
    3.8.2) CLINICAL EFFECTS
    A) INFLAMMATORY DISEASE OF MUCOUS MEMBRANE
    1) WITH THERAPEUTIC USE
    a) Stomatitis occurs with therapeutic doses (Duke, 1968).
    B) DIARRHEA
    1) WITH THERAPEUTIC USE
    a) Persistent diarrhea occurs with therapeutic doses (Duke, 1968).
    C) SPLENOMEGALY
    1) WITH THERAPEUTIC USE
    a) Four patients involved in a study of suramin for treatment of agnogenic myeloid metaplasia developed accelerated splenomegaly (Tefferi et al, 1993).
    3.8.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) SPLENOMEGALY
    a) RATS - Splenomegaly has been reported in rats given suramin (Rees et al, 1982).

Hepatic

    3.9.1) SUMMARY
    A) ANIMAL STUDIES - Hepatomegaly occurred during animal experiments.
    B) WITH THERAPEUTIC USE
    1) Elevated liver enzymes have been reported following therapeutic use.
    3.9.2) CLINICAL EFFECTS
    A) LIVER ENZYMES ABNORMAL
    1) WITH THERAPEUTIC USE
    a) Elevated levels of transaminases and alkaline phosphatase have been reported in 22.5% of patients after therapeutic administration (LaRocca et al, 1990).
    3.9.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) HEPATOMEGALY
    a) RATS given suramin developed enlarged livers (Rees et al, 1982).

Genitourinary

    3.10.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Acute renal failure was reported following suramin therapy.
    2) Azotemia, proteinuria, and albuminuria occur with therapeutic use.
    3.10.2) CLINICAL EFFECTS
    A) ACUTE RENAL FAILURE SYNDROME
    1) WITH THERAPEUTIC USE
    a) CASE REPORT - A 52-year-old male received nine doses of suramin to treat prostate cancer and subsequently developed acute renal failure. Suramin therapy was discontinued, but the patient's serum creatinine continued to rise over the next 6 days to a peak level of 10.8 mg/dl. Over the next 3 weeks the patient's renal function gradually returned to baseline (Figg et al, 1994).
    b) Reversible renal failure occurred in one patient following suramin therapy to treat agnogenic myeloid metaplasia (Tefferi et al, 1993).
    B) PRERENAL AZOTEMIA
    1) WITH THERAPEUTIC USE
    a) Increased azotemia and oliguria occurred after therapeutic doses (Spencer et al, 1975).
    C) ALBUMINURIA
    1) WITH THERAPEUTIC USE
    a) Albuminuria and proteinuria occurred after therapeutic use (Duke, 1968; Stein et al, 1986).
    2) WITH POISONING/EXPOSURE
    a) Albuminuria and proteinuria occurred after therapeutic use (Duke, 1968; Stein et al, 1986), and would be expected in overdose.
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) URINARY TRACT DISORDER
    a) RENAL ENLARGEMENT - Rats treated with suramin developed a mucopolysaccharidosis (Constantopoulos et al, 1980) and abnormal enlargement of the kidney (Rees et al, 1982).

Hematologic

    3.13.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Leukopenia, neutropenia, thrombocytopenia, anemia, and prolongation of prothrombin time occur with high therapeutic doses.
    3.13.2) CLINICAL EFFECTS
    A) LEUKOPENIA
    1) WITH THERAPEUTIC USE
    a) Leukopenia and neutropenia were reported in a small number of patients taking suramin therapeutically (LaRocca et al, 1990a; (Tefferi et al, 1993), and in 15% of patients taking the drug for cancer (LaRocca el al, 1990).
    B) THROMBOCYTOPENIC DISORDER
    1) WITH THERAPEUTIC USE
    a) SUMMARY - Thrombocytopenia has occurred following therapeutic use for AIDS or cancer treatment (JEF Reynolds , 1999). Multiple mechanisms may be responsible which may include an immune mediated response.
    b) Thrombocytopenia was reported in a small number of patients (12.5%) taking suramin therapeutically (LaRocca et al, 1990).
    c) Severe thrombocytopenia was reported following suramin therapy to treat metastatic carcinomas. In two case reports, the thrombocytopenia appeared to be immune-mediated (Seidman et al, 1993; Tisdale et al, 1996).
    C) MYELOSUPPRESSION
    1) WITH THERAPEUTIC USE
    a) Fatal myelosuppression has been reported in one case (Rosen et al, 1996).
    D) ANEMIA
    1) WITH THERAPEUTIC USE
    a) Anemia was reported in 10% of cases where the drug was taken therapeutically for cancer (LaRocca et al, 1990).
    b) Hypochromic anemia occurred in two of four patients involved in a study to determine the toxicity and efficacy of suramin in treating agnogenic myeloid metaplasia (Tefferi et al, 1993).
    E) PROTHROMBIN TIME LOW
    1) WITH THERAPEUTIC USE
    a) Prothrombin time is often prolonged when suramin is taken therapeutically (Loke et al, 1987; Horne et al, 1988; Shojania, 1988; Seidman et al, 1993; Tisdale et al, 1996).

Dermatologic

    3.14.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Tenderness of the soles and the palms is common with therapeutic administration and is related to the death of adult worms with destruction of the microfilariae. Minor skin rashes, itching, and desquamation of the skin over the lower legs is common.
    2) Exfoliative dermatitis occurs rarely. Toxic cutaneous eruptions which have included infrequent reports of erythema multiforme exfoliative dermatitis and fatal toxic epidermal necrolysis have been reported.
    3.14.2) CLINICAL EFFECTS
    A) ITCHING OF SKIN
    1) WITH THERAPEUTIC USE
    a) Tenderness of the soles and the palms is common with therapeutic administration (Duke, 1968), and may lead to itching. This effect may be due to the death of adult worms, rather than a direct toxic effect.
    b) Pruritus can also be related to a hypersensitivity reaction (JEF Reynolds , 1999).
    B) ERUPTION
    1) WITH THERAPEUTIC USE
    a) Minor skin rashes occur when this agent is used therapeutically for AIDS (Stein et al, 1986), and as an antineoplastic (22.5%) (LaRocca et al, 1990).
    C) GENERALIZED EXFOLIATIVE DERMATITIS
    1) WITH THERAPEUTIC USE
    a) Exfoliative dermatitis occurs rarely with therapeutic administration (Duke, 1968).
    D) ERYTHEMA MULTIFORME
    1) WITH THERAPEUTIC USE
    a) Toxic cutaneous eruptions, including generalized maculopapular eruptions, keratocanthomas, porokeratosis, and erythema multiformes have been reported following therapeutic use of suramin (O'Donnell et al, 1992; Katz et al, 1995; Lowitt et al, 1995; Kobayashi et al, 1996).
    E) LYELL'S TOXIC EPIDERMAL NECROLYSIS, SUBEPIDERMAL TYPE
    1) WITH THERAPEUTIC USE
    a) Rare reports of fatal toxic epidermal necrolysis have occurred with therapeutic use (May & Allolio, 1991; Falkson & Rapoport, 1992).
    b) CASE REPORT - A report of fatal toxic epidermal necrolysis developed in a 53-year-old female during suramin use (May & Allolio, 1991). Onset of an extensive rash was sudden and occurred within 16 days of the start of therapy.

Endocrine

    3.16.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Hypoadrenalism and adrenal insufficiency have been reported in patients receiving high dose therapy.
    3.16.2) CLINICAL EFFECTS
    A) ADRENAL CORTICAL HYPOFUNCTION
    1) WITH THERAPEUTIC USE
    a) Hypoadrenalism has been reported in patients who are taking high dose suramin (Stein et al, 1986; Stein et al, 1989).
    b) An increased incidence of adrenal cortical damage was noted when suramin was used in the treatment of pemphigus (an autoimmune illness) (Tobias, 1934) Wells et al, 1937).
    3.16.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) ADRENAL INSUFFICIENCY
    a) Hypoadrenalism has been reported in pigs (Humphries & Donaldson, 1941), but not in rats (Frisch & Gardner, 1958).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) ANAPHYLACTOID REACTION
    1) WITH THERAPEUTIC USE
    a) CASE REPORT - A 73-year-old male developed acral paresthesias, severe dyspnea, throat tightness, and wheezing following 1 dose of suramin (1500 mg infused over an hour). The patient also experienced urticarial eruptions over his arms and abdomen, and facial edema. The symptoms resolved following administration of epinephrine and diphenhydramine (Thibault et al, 1993).

Reproductive

    3.20.1) SUMMARY
    A) At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy or lactation.
    3.20.2) TERATOGENICITY
    A) ANIMAL STUDIES
    1) Teratogenicity has been reported in mice receiving suramin, but not in rats (JEF Reynolds , 1999).
    3.20.3) EFFECTS IN PREGNANCY
    A) SUMMARY
    1) The World Health Organization (WHO) has recommended that pregnant women with Tb rhodesiense trypanosomiasis and meningoencephalitic disease should receive suramin when needed (JEF Reynolds , 1999). Treatment should be delayed in pregnant women with onchocerciasis until after delivery.

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, no data were available to assess the carcinogenic potential of this agent.
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the carcinogenic potential of this agent.

Genotoxicity

    A) At the time of this review, no data were available to assess the mutagenic or genotoxic potential of this agent.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count, urinalysis, and liver and kidney function tests is suggested for patients with significant exposure.
    B) During therapy and overdose, monitor liver enzymes, renal function, and hematological parameters.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count, urinalysis, and liver and kidney function tests is suggested for patients with significant exposure.
    2) Elevated transaminases are possible.
    B) HEMATOLOGIC
    1) Monitor hematological parameters for potential anemia and possible leukocytosis.
    C) COAGULATION STUDIES
    1) Monitor for increased prothrombin time.
    4.1.3) URINE
    A) URINALYSIS
    1) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring urinalysis is suggested for patients with significant exposure.
    2) Monitor liver and kidney function tests. Proteinuria and albuminuria are possible.

Methods

    A) CHROMATOGRAPHY
    1) Suramin can be qualitatively and quantitatively determined by reverse phase ion pairing high performance liquid chromatography (Klecker & Collins, 1985; Ruprecht et al, 1986; Tjaden et al, 1990).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) A number of chemicals produce abnormalities of the hematopoietic system, liver, and kidneys. Monitoring complete blood count, urinalysis, and liver and kidney function tests is suggested for patients with significant exposure.
    B) During therapy and overdose, monitor liver enzymes, renal function, and hematological parameters.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY -
    1) Suramin is poorly absorbed orally and is generally administered intravenously; decontamination may not be necessary except after very large ingestions.
    6.5.3) TREATMENT
    A) SUPPORT
    1) No specific antidote is available. The half-life is over 30 days, so renal, hematologic, liver, and adrenal effects are likely to be long lasting.
    B) ADRENAL HYPOFUNCTION
    1) Adrenal suppression occurs with therapeutic doses, and would be expected in overdose. Replacement hydrocortisone may be required. Observe patient for signs of adrenal insufficiency (LaRocca et al, 1990).

Enhanced Elimination

    A) SUMMARY
    1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent.
    B) PLASMAPHERESIS
    1) LaRocca et al (1990a) treated 4 polyneuropathy patients with a 5-day course of plasmaphoresis following the onset of neurologic symptoms. No appreciable effect was noted.

Range Of Toxicity

Summary

    A) Effects are cumulative due to slow renal excretion.
    B) THERAPEUTIC DOSES - Adults over 60 kilograms: Minor or "light" Infections: 1 gram (administered intravenously over two to 3 minutes) is given weekly for a total of 6 grams. As an antineoplastic: 50 to 460 milligrams per square meter, per day
    C) The possibility of developing polyneuropathy was 40% when blood suramin levels were over 350 micrograms per milliliter.

Therapeutic Dose

    7.2.1) ADULT
    A) GENERAL
    1) Effects are cumulative due to slow renal excretion.
    B) DISEASE STATE
    1) ANTIPARASITIC AGENT -
    a) Test Dose - 100 milligrams is given to test for rare idiosyncrasy (Duke, 1968).
    b) Adults over 60 kilograms - (Minor or "light" infections) 1 gram (administered intravenously over 2 to 3 minutes) is given weekly for a total of 6 grams (Duke, 1968).
    2) ANTINEOPLASTIC AGENT -
    a) 50 to 460 milligrams per square meter per day (Stein et al, 1989).

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) The minimum lethal human dose to this agent has not been delineated.

Maximum Tolerated Exposure

    A) GENERAL/SUMMARY
    1) The maximum tolerated human exposure to this agent has not been delineated.

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) GENERAL
    a) POLYNEUROPATHY - The possibility of developing polyneuropathy was 40% when suramin blood levels were over 350 micrograms per milliliter (LaRocca et al, 1990a).
    b) ANTIPARASITIC - Normal doses produce peak levels of 100 to 200 micrograms per milliliter of plasma (Collins et al, 1986).

Pharmacology Toxicology

Pharmacologic Mechanism

    A) AIDS - Suramin is a potent inhibitor of reverse transcriptase and shows some anti-HIV activity in vitro (De Clercq, 1979; Cheson et al, 1987). Suramin is thought to block the infectivity and cytopathic effect of the human T-lymphotropic virus type III/lymphadenopathy associated virus (Broder et al, 1985; Mitsuya et al, 1984; Stein et al, 1986). Actual clinical trials have not been promising (Kaplan et al, 1987; Cheson et al, 1987).
    B) ANTINEOPLASTIC -
    1) Suramin has been tested as an antineoplastic on the assumption that it may inhibit a variety of nuclear and cytoplasmic enzymes (Spigelman et al, 1987; Constantopoulos et al, 1980), and displace various tumor growth factors from their respective surface receptors (Coffey et al, 1987).
    2) Suramin disrupts mammalian cell function by blocking growth factor-receptor interactions and by inhibiting the activity of critial cell growth and multiplication enzymes (LaRocca et al, 1990).
    C) ENZYMES -
    1) Suramin inhibits lysosomal enzymes, which leads to the accumulation of glycosaminoglycans and gangliosides intra- and extra-cellularly (Constantopoulos et al, 1980; Constantopoulos et al, 1981).
    2) Concentrations of suramin as low as 0.07 to 0.7 microgram/mole inhibit the reverse transcriptase activity associated with RNA tumor viruses (De Clercq, 1979).
    D) ANTIPARASITIC - Suramin has been shown to be useful prophylactically and as an early treatment for systemic trypanosomiasis. Due to poor CNS penetration, suramin is not as effective in disseminated trypanosomiasis (LaRocca et al, 1990).
    E) Suramin is known to be an inhibitor of anaerobic glycolysis, of protein kinase C and also reverses (in vitro) growth factor mediated oncogene induced transformation (Armand et al, 1990).

References

General Bibliography

    1) Anderson J & Fuglsang H: Further studies on the treatment of ocular onchocerciasis with diethylcabamazine and suramin. Br J Ophthalmol 1978; 62:450-457.
    2) Armand JP, Cvitkovic E, & Roussy IG: Suramin: a new therapeutic concept. Eur J Cancer 1990; 26:417-418.
    3) Bitton RJ, Figg WD, & Venzon DJ: Pharmacologic variables associated with the development of neurologic toxicity in patients treated with suramin. J Clin Oncol 1995; 13:2223-2229.
    4) Broder S, Collins J, & Markham PD: Effects of suramin on HTLV-III/LAV infection presenting as Kaposi's sarcoma or AIDS-related complex: clinical suppression of virus replication in vivo. Lancet 1985; 2:627-630.
    5) Cheson BD, Levine AM, & Mildvan D: Suramin therapy in AIDS and related disorders: report of the US Suramin Working Group. JAMA 1987; 258:1347-1351.
    6) Coffey RJ, Leof EB, & Shipley GD: Suramin inhibition of growth factor receptor binding and mitogenicity in AKR-2B cells. J Cell Physiol 1987; 132:143-148.
    7) Collins JM, Klecker W, & Yarchoan R: Clinical pharmacokinetics of suramin in patients with HTLV-III/LAV infection. J Clin Pharmacol 1986; 26:22-26.
    8) Constantopoulos G, Rees S, & Cragg B: Experimental animal model for mucopolysaccharidosis: suramin-induced glycosaminoglycan and sphingolipid accumulation in the rat. Proc Natl Acad Sci USA 1980; 77:3700-3704.
    9) Constantopoulos G, Rees S, & Cragg BG: Effect of suramin on the activities of degradativeenzymes of sphingolipids in rats. Res Commun Chem Pathol Pharmacol 1981; 32:87-97.
    10) Cooper M, Jamis-Dow C & Weiss G et al: Suramin: a clinically relevant physiologic pharmacokinetic model. Proc Am Soc Clin Oncol, Annual Meeting 9, 1990.
    11) De Clercq E: Suramin: a potent inhibitor of the reverse transcriptase of RNA tumor virus. Cancer Lett 1979; 8:9-22.
    12) Duke BOL: Onchocerciasis. Br Med J 1968; 4:301-307.
    13) Falkson G & Rapoport BL: Lethal toxic epidermal necrolysis during suramin treatment. Eur J Cancer 1992; 28A:1294.
    14) Figg WD, Cooper MR, & Thibault A: Acute renal toxicity associated with suramin in the treatment of prostate cancer. Cancer 1994; 74:1612-1614.
    15) Frisch E & Gardner LI: Failure of seramin (Bayer 205; Germanin) to cause changes in the adrenal cortex of the rat. Endocrinology 1958; 63:500-501.
    16) Hawking F: Concentration of Bayer 205 (Germanin) in human blood and cerebrospinal fluid after treatment. Trans R Soc Trop Med Hyg 1940; 34:37-52.
    17) Hawking F: Suramin: with special reference to onchocerciasis. Adv Pharm Chemother 1978; 15:289-322.
    18) Hemady RK, Sinbaldi VJ, & Eisenberger MA: Ocular symptoms and signs associated with suramin sodium treatment for metastatic cancer of the prostate. Amer J Opthalmol 1996; 121:291-296.
    19) Holland EJ, Stein CA, & Palestine AG: Suramin keratopathy. Am J Ophthalmol 1988; 106:216-220.
    20) Horne MK III, Stein CA, & LaRocca RV: Circulating glycosaminoglycan anticoagulants associated with suramin treatment. Blood 1988; 71:273-279.
    21) Humphries EM & Donaldson L: Degeneration of the adrenal cortex produced by germanin. Am J Pathol 1941; 17:767-775.
    22) JEF Reynolds : Martindale: The Extra Pharmacopoeia (electronic version). The Pharmaceutical Press. London, UK (Internet Version). Edition expires 1999; provided by Truven Health Analytics Inc., Greenwood Village, CO.
    23) Kaplan LD, Wolfe RP, & Volberding P: Lack of response to suramin in patients with AIDS and AIDS related complex. Am J Med 1987; 82:615-620.
    24) Katz SK, Medenica MM, & Kobayashi K: Erythema multiforme induced by suramin. J Amer Acad Dermatol 1995; 32:292-293.
    25) Klecker RW & Collins JM: Quantification of suramin by reverse-phase ion-pairing high performance liquid chromatography. J Liq Chromatog 1985; 8:1685-1696.
    26) Kobayashi K, Pezen DS, & Vogelzang NJ: Keratocanthomas and skin neoplasms associated with suramin therapy. Arch Dermatol 1996; 132:96-98.
    27) Loke RHT, Anderson MG, & Coleman JC: Suramin treatment for chronic active Hepatitis B - toxic and ineffective. J Med Virol 1987; 21:97-99.
    28) Lowitt MH, Eisenberger M, & Sina B: Cutaneous eruptions from suramin: a clinical and histopathologic study of 60 patients. Arch Dermatol 1995; 131:1147-1153.
    29) May E & Allolio B: Fatal toxic epidermal necrolysis during suramin therapy. Eur J Cancer 1991; 27:1338.
    30) Mitsuya M, Popovic M, & Yarchoan R: Suramin protection of T cells in vitro against infectivity and cytopathic effect of HTLV-III. Science 1984; 226:172-174.
    31) O'Donnell BP, Dawson NA, & Weiss RB: Suramin-induced skin reactions. Arch Dermatol 1992; 128:75-79.
    32) Rees S, Constantopoulos G, & Barranger JA: Organomegaly and histopathology in an animal model of mucopolysaccharidosis induced by suramin. Naunyn-Schmiedeberg's Arch Pharmacol 1982; 319:262-270.
    33) Rosen PJ, Mendoza EF, & Landaw EM: Suramin in hormone-refractory metastatic prostate cancer: A drug with limited efficacy. J Clin Oncol 1996; 14:1626-1636.
    34) Ruprecht RM, Lorsch J, & Trites DH: Analysis of levels by ion-pair HPLC under isocratic conditions. J Chromatogr 1986; 378:498-502.
    35) Seidman AD, Schwartz M, & Reich L: Immune-mediated thrombocytopenia secondary to suramin. Cancer 1993; 71:851-854.
    36) Shojania AM: Circulating glycosaminoglycan anticoagulants associated with suramin treatment (letter). Blood 1988; 72:1103-1104.
    37) Spencer HC, Gibson JJ Jr, & Brodsky RE: Imported African trypanosomiasis in the United States. Ann Intern Med 1975; 82:633-638.
    38) Spigelman Z, Dowers A, & Kennedy S: Antiproliferative effects of suramin on lymphoid cells. Cancer Res 1987; 47:4694-4698.
    39) Stein CA, LaRocca RV, & Thomas R: Suramin: an anticancer drug with a unique mechanism of action. J Clin Oncol 1989; 7:499-508.
    40) Stein CA, Saville W, & Yarchoan R: Suramin and function of the adrenal cortex (letter). Ann Intern Med 1986; 104:286-287.
    41) Tefferi A, Silverstein MN, & Plumhoff EA: Suramin toxicity and efficacy to agnogenic myeloid metaplasia. J Natl Canc Instit 1993; 85:1520-1522.
    42) Teich SA, Handwerger S, & Mathur-Wagh U: Toxic keratopathy associated with suramin therapy (letter). N Engl J Med 1986; 314:1455-1456.
    43) Thibault A, Figg WD, & Cooper MR: Anaphylactoid reaction with suramin. Pharmacother 1993; 13:656-657.
    44) Thylefors B & Rolland A: The risk of optic atrophy following suramin treatment of ocular onchocerciasis. Bull World Health Organ 1979; 57:479-480.
    45) Tisdale JF, Figg WD, & Reed E: Severe thrombocytopenia in patients treated with suramin: evidence for an immune mechanism in one. Amer J Hematol 1996; 51:152-157.
    46) Tjaden UR, Pattyn G, & Reeuwijk HJ: Bioanalysis of suramin in human plasma by ion-pair high-performance liquid chromatography (HPLC). J Chromatogr 1990; 525:141-149.
    47) Tobias N: Juvenile pemphigus: treatment with Germanin (Bayer 205); report of a fatal case. Am J Dis Child 1934; 48:1084-1091.
    48) Vansterkenberg ELM, Wilting J, & Janssen LHM: Influence of pH on binding of suramin to human serum albumin. Biochem Pharmacol 1989; 38:3029-3035.