Spiramycin

J01F - Macrolides, lincosamides and streptogramins ATC J01FA02 Small molecule

🧬 Cross-allergy: Macrolides

JFDA label: RAZEX

Mechanism of Action

Inhibitor of Bacterial 70S ribosome — Bacterial 70S ribosome inhibitor

Target	Action	Gene / class
Bacterial 70S ribosome efficacy	INHIBITOR

Indications

Off-label

Acute toxoplasmosis in pregnancy (

Class profile

gramStatus	Gram+
spectrumBreadth	Moderate
atypicalCoverage	No
isBactericidal	0
moaCategory	Protein synthesis inhibitor (50S ribosomal, 23S rRNA)
pdIndex	Time-dependent
postAntibioticEffect	Prolonged
mrsaCoverage	0
resistanceMechanisms	Target site methylation (erm genes),Efflux pumps

Contraindications

Source: Lexicomp

Hypersensitivity to spiramycin, other macrolides (eg, erythromycin) or any component of the formulation Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Hepatobiliary disorders (1)

Not Known Increased serum transaminases

Gastrointestinal disorders (3)

Not Known Diarrhea · nausea · vomiting

Skin and subcutaneous tissue disorders (3)

Not Known Pruritus · skin rash · urticaria

Dosing

Source: Lexicomp

Mild to moderate infections: Oral: 6,000,000 to 9,000,000 units (4 to 6 capsules of Rovamycine “500” per day) in 2 divided doses Severe infections: Oral: 12,000,000 to 15,000,000 units (8 to 10 capsules of Rovamycine “500” per day) in 2 divided doses Gonorrhea: Oral: 12,000,000 to 13,500,000 units (8 to 9 capsules of Rovamycine “500”) as a single dose Acute toxoplasmosis in pregnancy ( Oral: 1 g (3,000,000 units) every 8 hours to prevent transmission to fetus (Daffos 1988; Hohlfield 1980; Montoya 2008). At ≥18 weeks, if there is no evidence of transmission to the fetus, spiramycin can be continued until term. Note: If intrauterine fetal Toxoplasma infection is confirmed, treatment should be switched to pyrimethamine plus sulfadiazine and folinic acid (Montoya 2008).

Susceptible infections: Oral: Dosage by body weight; usual dosage 150,000 units/kg; expressed as the number of 750,000 unit (Rovamycine “250”) capsules per day. Daily dose should be administered in 2 to 3 divided doses. 15 kg = 3 capsules per day 20 kg = 4 capsules per day 30 kg = 6 capsules per day Note: In severe infections, dosage may be increased by 50%.

Refer to adult dosing.

No dosage adjustment required.

Warnings & Precautions

Source: Lexicomp

Altered cardiac conduction

Macrolides have been associated with rare QTc prolongation and ventricular arrhythmias, including torsade de pointes; use with caution in patients at risk of prolonged cardiac repolarization.

Superinfection

Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment. Disease-related concerns:

Hepatic impairment

Use with caution in patients with pre-existing liver disease; hepatic impairment, including hepatocellular and/or cholestatic hepatitis, with or without jaundice, has been observed. Discontinue if symptoms of malaise, nausea, vomiting, abdominal colic, and fever.

Pregnancy & Lactation

Pregnancy

FDA category B

Crosses placenta. Specific safety information is not available. However, spiramycin has been used to treat Toxoplasma gondii to prevent transmission from mother to fetus.

Lactation

Excreted in breast milk in bacteriostatic concentrations.

Monitoring

Efficacy	Culture and susceptibility testing; clinical resolution (temperature, WBC, CRP, procalcitonin)
Toxicity	Renal function (dose adjustment in renal impairment); hepatic function for hepatically cleared agents; signs of C. difficile infection (diarrhoea)
Clinical pearl	Culture results guide de-escalation to narrower-spectrum therapy. Review antibiotic appropriateness at 48–72 h (antimicrobial stewardship).
Counseling	Complete the full course. Report persistent diarrhoea, rash, or lack of improvement after 48–72 h.

Chemistry & Properties

Formula	C43H74N2O14
Molecular weight	843.1 g/mol
IUPAC name	2-[(4R,5S,6S,7R,9R,10R,11E,13E,16R)-6-[(2S,3R,4R,5S,6R)-5-[(2S,4R,5S,6S)-4,5-dihydroxy-4,6-dimethyloxan-2-yl]oxy-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-10-[(2R,5S,6R)-5-(dimethylamino)-6-methyloxan-2-yl]oxy-4-hydroxy-5-methoxy-9,16-dimethyl-2-oxo-1-oxacyclohexadeca-11,13-dien-7-yl]acetaldehyde
CAS	24916-50-5
PubChem CID	5289394
InChIKey	`ACTOXUHEUCPTEW-CEUOBAOPSA-N`
logP	2.1 (XLogP 2.1)
Polar surface area	195.0 Å²
H-bond acceptors / donors	16 / 4

SMILES

CC1CC=CC=CC(C(CC(C(C(C(CC(=O)O1)O)OC)OC2C(C(C(C(O2)C)OC3CC(C(C(O3)C)O)(C)O)N(C)C)O)CC=O)C)OC4CCC(C(O4)C)N(C)C

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	4.633 h
Volume of distribution	1.179 L/kg
Protein binding	53.1%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2C19	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Registered Products (4)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Dentagyl Tablet	Tablet 125 mg, 750.000 IU	20 tab	The Arab Pharmaceutical Manufacturing PSC/Salt	3.320
Oragin Tablets	Tablet 125 mg, 750000 IU	20 tab pack varies	THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN	3.320
RAZEX	Tablet 3 MIU	10 tab	THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN	3.650
Oragin Tablets	Tablet 125 mg, 750000 IU	660 tab pack varies	THE JORDANIAN PHARMACEUTICAL MANUFACTURING COMPANY/JORDAN	93.130