Suramin Sodium

(rINN)
Synonyms: Antrypol; Bayer-205; CI-1003; Fourneau-309; Naganinum; Naganol; Suramin Hexasodium Sodique; Suraminum Natricum. The symmetrical 3″-urea of the sodium salt of 8-(3-benzamido-4-methylbenzamido)naphthalene-1,3,5-trisulphonic acid; Hexasodium 8,8′-{carbonylbis[imino-3,1-phenylenecarbonylimino(4-methyl-3,1-phenylene)carbonylimino]}bis(1,3,5-naphthalenetrisulfonate).
Cyrillic synonym: Сурамин Натрий.

💊 Chemical information

Chemical formula: C51H34N6Na6O23S6 = 1429.2.
CAS — 145-63-1 (suramin); 129-46-4 (suramin sodium).
ATC — P01CX02.
ATC Vet — QP51AE02.

Pharmacopoeias.

In Fr., Int., and It.

💊 Adverse Effects

An immediate and potentially fatal reaction, with nausea, vomiting, shock, seizures, and loss of consciousness, may follow the injection of suramin sodium in some patients and thus it is usual practice to give a small test dose before starting treatment. Abdominal pain, mouth ulceration, and skin reactions such as urticaria and pruritus may occur. The risk of hypersensitivity reactions is reported to be greater when onchocerciasis is present. Other adverse effects include paraesthesia, hyperaesthesia of the palms and soles, skin eruptions, blood dyscrasias, fever, polyuria, increased thirst, raised liver enzyme values, fatigue, and effects on the eye including photophobia and lachrymation. Proteinuria is common; haematuria and casts in the urine may also occur. There have been occasional reports of adrenal insufficiency.

Effects on the blood.

Thrombocytopenia has been reported in patients receiving suramin, generally during treatment for AIDS or cancer.1-4 An immune-mediated mechanism has been proposed3 although there is evidence that multiple mechanisms may be involved.4 Other adverse effects on the blood include neutropenia,1,5 anaemia,1 deterioration of pre-existing lymphocytopenia,5 and fatal myelosuppression.5 Agranulocytosis and haemolytic anaemia have occurred rarely.
1. Levine AM, et al. Suramin antiviral therapy in the acquired immunodeficiency syndrome. Ann Intern Med 1986; 105: 32–7
2. Arlt W, et al. Suramin in adrenocortical cancer: limited efficacy and serious toxicity. Clin Endocrinol (Oxf) 1994; 41: 299–307
3. Seidman AD, et al. Immune-mediated thrombocytopenia secondary to suramin. Cancer 1993; 71: 851–4
4. Tisdale JF, et al. Severe thrombocytopenia in patients treated with suramin: evidence for an immune mechanism in one. Am J Hematol 1996; 51: 152–7
5. Rosen PJ, et al. Suramin in hormone-refractory metastatic prostate cancer: a drug with limited efficacy. J Clin Oncol 1996; 14: 1626–36.

Effects on the eyes.

Late effects on the eyes associated with suramin include photophobia, lachrymation, and palpebral oedema. Keratopathy characterised by corneal deposits has been reported in patients receiving suramin. In a study of 114 patients receiving suramin for prostatic cancer, 13 developed corneal deposits similar to those reported with chloroquine therapy after 34 to 98 days of therapy.1 Symptoms in 10 of the 13 included lachrymation and foreign body sensation. The remaining 3 patients were asymptomatic. Shifts in refractive error were also found. Keratopathy has also been reported in patients with AIDS receiving suramin.2 In patients treated with suramin for ocular onchocerciasis, the incidence of optic atrophy was higher after 3 years than in untreated patients.3 A prolonged inflammatory response to dying microfilariae in the optic nerve might be responsible, although a direct toxic or allergic effect could not be ruled out.
1. Hemady RK, et al. Ocular symptoms and signs associated with suramin sodium treatment for metastatic cancer of the prostate. Am J Ophthalmol 1996; 121: 291–6
2. Teich SA, et al. Toxic keratopathy associated with suramin therapy. N Engl J Med 1986; 314: 1455–6
3. Thylefors B, Rolland A. The risk of optic atrophy following suramin treatment of ocular onchocerciasis. Bull WHO 1979; 57: 479–80.

Effects on the kidneys.

In addition to the proteinuria commonly seen during suramin therapy, there have been reports of individual cases of renal glycosuria1 and of acute renal dysfunction.2
1. Awadzi K, et al. The chemotherapy of onchocerciasis XVIII: aspects of treatment with suramin. Trop Med Parasitol 1995; 46: 19–26
2. Figg WD, et al. Acute renal toxicity associated with suramin in the treatment of prostate cancer. Cancer 1994; 74: 1612–14.

Effects on the nervous system.

Neurological disorders reported in patients receiving suramin include paraesthesia and polyneuropathy. Severe polyneuropathy with generalised flaccid paralysis has generally been associated with serum-suramin concentrations greater than 350 micrograms/mL,1,2 but motor neuropathy was reported in 8 patients with serum concentrations of 275 micrograms/mL.3
1. La Rocca RV, et al. Suramin-induced polyneuropathy. Neurology 1990; 40: 954–60
2. Arlt W, et al. Suramin in adrenocortical cancer: limited efficacy and serious toxicity. Clin Endocrinol (Oxf) 1994; 41: 299–307
3. Bitton RJ, et al. Pharmacologic variables associated with the development of neurologic toxicity in patients treated with suramin. J Clin Oncol 1995; 13: 2223–9.

Effects on the skin.

Pruritus and urticaria may occur as hypersensitivity reactions to suramin. Late skin reactions include erythematous maculopapular rashes.1 Severe reactions including erythema multiforme,2 exfoliative dermatitis, and fatal toxic epidermal necrolysis3,4 have been reported.
1. O’Donnell BP, et al. Suramin-induced skin reactions. Arch Dermatol 1992; 128: 75–9
2. Katz SK, et al. Erythema multiforme induced by suramin. J Am Acad Dermatol 1995; 32: 292–3
3. May E, Allolio B. Fatal toxic epidermal necrolysis during suramin therapy. Eur J Cancer 1991; 27: 1338
4. Falkson G, Rapoport BL. Lethal toxic epidermal necrolysis during suramin treatment. Eur J Cancer 1992; 28A: 1294.

💊 Precautions

Suramin sodium should be used under close supervision, and the general condition of patients improved as far as possible before treatment starts. Patients who have a severe reaction to the first dose should never receive suramin again. It should not be used in elderly or infirm patients or in the presence of severe hepatic or renal disease. The urine should be tested before treatment starts and weekly during treatment; dosage should be reduced if moderate proteinuria develops and stopped if it becomes severe or if casts appear in the urine.

Pregnancy.

Suramin has been reported to be teratogenic in mice but not in rats.1 WHO2 recommends that when necessary suramin should be used in pregnant women with T. b. rhodesiense trypanosomiasis, even those with meningoencephalitic disease, because melarsoprol is contra-indicated; in onchocerciasis, suramin treatment should be delayed until after delivery.
1. Mercier-Parot L, Tuchmann-Duplessis H. Action abortive et tératogène d’un trypanocide, la suramine. C R Soc Biol 1973; 167: 1518–22
2. WHO. WHO model formulary. Geneva: WHO, 2004.

💊 Pharmacokinetics

After intravenous injection, suramin becomes bound to plasma proteins and plasma concentrations over 100 micrograms/mL are maintained for several weeks. Unbound suramin is excreted in the urine. Penetration of suramin into the CSF appears to be poor.
Suramin accumulated during treatment and plasma concentrations exceeded 100 micrograms/mL for several weeks. After the last dose the terminal half-life of suramin ranged from 44 to 54 days. At least 99.7% was bound to plasma proteins. Renal clearance accounted for most of the elimination of suramin from the body. There appeared to be little or no metabolism of suramin. In another study,2 ten male patients with onchocerciasis received weekly infusions of suramin for 6 weeks, according to the dose regimen recommended by WHO (see below). In these patients the median elimination half-life was about 92 days, and in each case, the maximum plasma concentration remained below 300 micrograms/mL.
1. Collins JM, et al. Clinical pharmacokinetics of suramin in patients with HTLV-III/LAV infection. J Clin Pharmacol 1986; 26: 22–6
2. Chijioke CP, et al. Clinical pharmacokinetics of suramin in patients with onchocerciasis. Eur J Clin Pharmacol 1998; 54: 249–51.

💊 Uses and Administration

Suramin is a trypanocide used in the treatment of African trypanosomiasis and as an anthelmintic in the treatment of onchocerciasis. Suramin is given as suramin sodium by slow intravenous injection, usually as a 10% solution. Because of the danger of severe reactions it is advisable to give a test dose before starting treatment. In African trypanosomiasis suramin is used mainly for the early (haematolymphatic) stages of Trypanosoma brucei rhodesiense infection; pentamidine may be preferred for early-stage treatment of T. b. gambiense infection. Suramin is not used as sole therapy for latestage infections with CNS involvement. Early-stage trypanosomiasis may be treated with a dose of 5 mg/kg of suramin on day 1, 10 mg/kg on day 3, then 20 mg/kg on days 5, 11, 17, 23, and 30. Another schedule consists of 5 doses of 1 g given over 3 weeks after a test dose of 100 to 200 mg. In late-stage trypanosomiasis injections of suramin are often given before starting treatment with melarsoprol; 5 and 10 mg/kg are given on days 1 and 3 respectively, and in some regimens 20 mg/kg is also given on day 5. For doses used in onchocerciasis see below.

Malignant neoplasms.

Suramin is reported to have antineoplastic activity and has been studied in a number of malignant neoplasms, in particular hormone-resistant prostatic cancer. However, its clinical usefulness is hindered by dose-limiting toxicity and problems in developing a simple dose schedule. It has also been investigated as a chemosensitiser.
1. Stein CA, et al. Suramin: an anticancer drug with a unique mechanism of action. J Clin Oncol 1989; 7: 499–508
2. Kilbourn RG. Suramin: new therapeutic concepts for an old drug. Cancer Bull 1991; 43: 265–7
3. Rapoport BL, et al. Suramin in combination with mitomycin C in hormone-resistant prostate cancer: a phase II clinical study. Ann Oncol 1993; 4: 567–73
4. Woll PJ, et al. Suramin for breast and prostate cancer: a pilot study of intermittent short infusions without adaptive controls. Ann Oncol 1994; 5: 597–600
5. Arlt W, et al. Suramin in adrenocortical cancer: limited efficacy and serious toxicity. Clin Endocrinol (Oxf) 1994; 41: 299–307
6. Eisenberger MA, Reyno LM. Suramin. Cancer Treat Rev 1994; 20: 259–73
7. Rosen PJ, et al. Suramin in hormone-refractory metastatic prostate cancer: a drug with limited efficacy. J Clin Oncol 1996; 14: 1626–36
8. Small EJ, et al. Suramin therapy for patients with symptomatic hormone-refractory prostate cancer: results of a randomized phase III trial comparing suramin plus hydrocortisone to placebo plus hydrocortisone. J Clin Oncol 2000; 18: 1440–50
9. Chen D, et al. Nontoxic suramin as a chemosensitizer in patients: dosing nomogram development. Pharm Res 2006; 23: 1265–74.

Onchocerciasis.

Although suramin is the only drug in clinical use for onchocerciasis that is effective against adult worms, its use is restricted because of the frequency of associated compli cations and its intrinsic toxicity. Treatment of onchocerciasis is currently based on continuous suppression of microfilariae by regular use of ivermectin. WHO1 advises that suramin should only be considered for the curative treatment of individuals in areas without transmission of onchocerciasis and of individuals leaving an endemic area, and for severe hyperreactive onchodermatitis where symptoms are not adequately controlled with ivermectin. WHO2 also recommends that it should not be used to treat onchocerciasis in the elderly or infirm, in patients with severe liver or renal disease, in totally blind patients (unless they require relief from intensely itchy lesions), or in pregnant women (who should be treated after delivery). A total dose of 66.7 mg/kg in six incremental weekly doses is recommended.1,2 The first (test) dose of suramin sodium 3.3 mg/kg should be given very cautiously by slow intravenous injection; this is followed at weekly intervals by incremental doses of 6.7 mg/kg, 10.0 mg/kg, 13.3 mg/kg, 16.7 mg/kg and 16.7 mg/kg.2
1. WHO. Onchocerciasis and its control: report of a WHO expert committee. WHO Tech Rep Ser 852 1995
2. WHO. WHO model formulary. Geneva: WHO, 2004.

African trypanosomiasis.

Suramin is used in the treatment of the early haematolymphatic phase of African trypanosomiasis caused by Trypanosoma brucei rhodesiense and for T. b. gambiense infections which are resistant to pentamidine.1 In some regions, suramin is used with pentamidine for T. b. gambiense infections but it has not been shown to be clinically superior to pentamidine alone.2 Although suramin does not reach sufficient concentrations in the CSF to produce a cure in the meningoencephalitic phase, it is used to reduce the number of trypanosomes in the blood and lymph before treatment with melarsoprol.1 Case reports have suggested that suramin with metronidazole3 or eflornithine4 could be useful in T. b. rhodesiense infections, although response to suramin plus eflornithine was disappointing in a study involving 6 patients.5
1. WHO. WHO model formulary. Geneva: WHO, 2004
2. Pépin J, Khonde N. Relapses following treatment of early-stage Trypanosoma brucei gambiense sleeping sickness with a combination of pentamidine and suramin. Trans R Soc Trop Med Hyg 1996; 90: 183–6
3. Foulkes JR. Metronidazole and suramin combination in the treatment of arsenical refractory rhodesian sleeping sickness—a case study. Trans R Soc Trop Med Hyg 1996; 90: 422
4. Taelman H, et al. Combination treatment with suramin and eflornithine in late stage rhodesian trypanosomiasis: case report. Trans R Soc Trop Med Hyg 1996; 90: 572–3
5. Clerinx J, et al. Treatment of late stage rhodesiense trypanosomiasis using suramin and eflornithine: report of six cases. Trans R Soc Trop Med Hyg 1998; 92: 449–50.

💊 Preparations

Proprietary Preparations

Ger.: Germanin.
Published December 21, 2018.