      Document 0186
 DOCN  DRG0186
 UNIQUE IDENTIFIER        DRG-0061
 NAME OF SUBSTANCE        Spiramycin [USAN 1995]
 REGISTRY NUMBER          8025-81-8
 STANDARD CHEMICAL NAME   Leucomycin [USAN 1995]
 SYNONYMS                 Foromacidin [USAN 1990]
 SYNONYMS                 Leucomycin [USAN 1995]
 SYNONYMS                 Provamycin [Merk Index 1989]
 SYNONYMS                 Rovamycin [USAN 1995]
 SYNONYMS                 Rovamicina [Merck Index 1989]
 SYNONYMS                 Selectomycin [Merck Index 1989]
 SYNONYMS                 Sequamycin [Merck Index 1989]
 PROTOCOL ID NUMBERS      NIAID ACTG 113
 PROTOCOL ID NUMBERS      FDA 011A
 SECONDARY SOURCE ID      NSC-55926 [USAN 1995]
 SECONDARY SOURCE ID      NSC-64393 (as hydrochloride) [USAN 1995]
 SECONDARY SOURCE ID      RP 5337 [USAN 1995]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Spiramycin is a macrolide
                          antibiotic with an antibacterial spectrum
                          similar to that of erythromycin and
                          clindamycin. It is bacteriostatic at serum
                          concentrations but may be bactericidal at
                          achievable tissue concentrations. Its
                          mechanism of action is not clear, but it is
                          known to act on the 50s subunit of bacterial
                          ribosomes and to interfere with
                          translocation. Absorption from the GI tract
                          is irregular; approximately 20-50% of an oral
                          dose is absorbed. Peak plasma levels are
                          achieved within 2-4 hours of an oral dose.
                          Peak plasma concentrations after 1 g oral
                          dose or 1.5 million unit IV infusion are ca.
                          1 mcg/ml and 1.5-3.0 mcg/ml. It is widely
                          distributed in the body and has a short
                          distribution half-life (10.2+/-3.72 minutes)
                          when administered orally. The drug is
                          excreted primarily in the bile. [USP DI 1995]
 DISEASES STUDIED/TREATED Treatment of chronic diarrhea due to
                          cryptosporidium in patients with HIV
                          infection [MMWR 1984 March 9;33(9):117-9]
                          [Rhone-Poulenc Rorer Pharmaceuticals]
 DISEASES STUDIED/TREATED Per 4/2/93 communication - spiramycin is not
                          helpful or available for treatment of HIV
                          cryptosporidiosis [MMWR March 9,
                          1984;9;33(9)] [Rhone-Poulenc Rorer
                          Pharmaceuticals]
 CLASSIFICATION CODE      Antibacterial [USAN 1995]
 CLASSIFICATION CODE      Antiprotozoal [Remington's Pharmaceutical
                          Sciences, 1988]
 OTHER MAJOR USES         Treatment of bacterial infections.
                          Alternative drug for treatment of
                          toxoplasmosis. Often given in combination
                          with pyrimethamine-sulfamethoxazole.
                          Spiramycin appears to be useful in treating
                          acute Toxoplasma gondii infections during
                          pregnancy as congenital infections (IND use
                          in US) [Current Medical Diagnosis and
                          Treatment, 1986] [Conn's Current Therapy
                          1995]
 SUBSTANCE INTERACTIONS   May increase serum theophylline concentration
                          and occasionally cause symptoms of toxicity.
                          Cross resistance between microorganism
                          resistant to erythromycin and carbomycin. Can
                          increase the effects of oral anticoagulant
                          and of digoxin. Spiramycin and metronidazole
                          in combination can be efficacious in the
                          treatment of those patients with AIDS and
                          diarrhea in which cryptosporidium is
                          identified. [Meyler's Side Effects of Drugs
                          1989] [Int Conf AIDS 1993 June 6-11;9(1);
                          abstract no. PO-B19-1847]
 ADVERSE EFFECTS          Serious side effects from spiramycin are
                          rare. Nausea, vomiting, diarrhea and
                          indigestion are common side effects from oral
                          administration. Less frequent side effects
                          (oral administration) are fatigue, epistaxis,
                          sweating, heaviness in the chest, and a cool
                          sensation in the mouth or pharynx. Acute
                          colitis is experienced by 1% of patients. IV
                          administration is associated with
                          paresthesias in the extremities, irritation
                          at injection site, dysesthesia, giddiness,
                          pain, stiffness, burning sensation and hot
                          flashes. Long-term use of spiramycin may
                          result in superinfection. [USP DI 1995]
 CONTRAINDICATIONS        Contraindicated with the concomitant use of
                          ergotamine. [Meyler's Side Effects of Drugs
                          1989]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: A macrolide antibiotic of
                          the erythromycin/carbomycin type produced by
                          Streptomyces ambofaciens from soil of
                          Northern France [AmFAR Tx Dir 1993;6(3)]
                          [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DATA: Composed of spiramycin I
                          (C43H74N2O14) 63 %, spiramycin II
                          (C47H80N2O16) 24 %, spiramycin III
                          (C48H82N2O16) 13 %, amorphous base soluble in
                          most organic solvents [Remington's
                          Pharmaceutical Sciences, 1988]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: White or slightly
                          yellow amorphous powder [USP DI 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C43H74N2O14 (Spiramycin I)
                          [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 134-137 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Slightly soluble in water;
                          soluble in most organic solvents [Merck Index
                          1989]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Available as 500 mg capsules
                          (equivalent to 1.5 million International
                          Units [MIU]) or injections containing 1.5 MIU
                          per vial. [USP DI 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intravenous, subcutaneous,
                          oral. [NIAID ACTG 113]
 SUBSTANCE DELIVERY DATA  STORAGE: Vials should be stored at room
                          temperature. [NIAID ACTG 113]
 MANUFACTURERS            Rhone-Poulenc Rorer Pharmaceuticals
 REFERENCES               Wu KZ, Chew SK, Oh HM, Lin RV, Allen DM,
                          Monteiro EH. Acquired immunodeficiency
                          syndrome and Cryptosporidium infection.
                          Singapore Med J. 1994 Aug;35(4):418-9.
 REFERENCES               Mifsud AJ, Bell D, Shafi MS. Respiratory
                          cryptosporidiosis as a presenting feature of
                          AIDS [letter]. J Infect. 1994 Mar;28:227-9.
 REFERENCES               Zhou SL, Tan M, Shen G. Comparison of the
                          pharmacokinetics and bioavailability of
                          spiramycin in human serum and saliva
                          [letter]. J Antimicrob Chemother. 1994
                          Dec;34(6):1080-2.
 REFERENCES               Sanchez-Mejorada, Ponce-de-Leon S, Santiago
                          Y, Carranza D. Efficacy of combined
                          spiramycin and metronidazole in diarrheas due
                          to Cryptosporidium or with unidentified cause
                          in patients with AIDS. Int Conf AIDS. 1993
                          Jun 6-11;9(1):443 (abstract no. PO-B19-1847).
 REFERENCES               Dylewski J, Clecner B, Dubois J, St-Pierre C,
                          Murray G, Bouchard C, Phillips R. Comparison
                          of spiramycin and doxycycline for treatment
                          of Chlamydia trachomatis genital infections.
                          Antimicrob Agents Chemother. 1993
                          Jun;37(6):1373-4.
 REFERENCES               Buhl MR, White JM. Spiramycin-induced
                          thrombocytopenia in a HIV-infected patient
                          [letter]. Scand J Infect Dis. 1992;24(1):115.
 REFERENCES               Weikel C, Lazenby A, Belitsos P, McDewitt M,
                          Fleming HE Jr, Barbacci M. Intestinal injury
                          associated with spiramycin therapy of
                          Cryptosporidium infection in AIDS. J
                          Protozool. 1991 Nov-Dec;38(6):147S.
 REFERENCES               Ruf B, Pohle HD. Role of clindamycin in the
                          treatment of acute toxoplasmosis of the
                          central nervous system. Eur J Clin Microbiol
                          Infect Dis. 1991 Mar;10(3):183-6.
 REFERENCES               Garrido Davila JI, Ramirez Ronda CH. Updates
                          on AIDS cryptosporidiosis: a review. Bol Asoc
                          Ned P R. 1991 Feb;83(2):65-8.
 REFERENCES               Brites CB, Moreira Junior ED, Bina JC,
                          Johnson Junior WD, Badaro R. Multiple drug
                          regimen for severe diarrhea associated with
                          Crptosporidium in AIDS patients. Rev Soc Bras
                          Med Trop. 1991 Apr-Jun;24(2):117.
 ENTRY MONTH              8911
 LAST REVISION DATE       951128
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
