DEMECLOCYCLINE HYDROCHLORIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DEMECLOCYCLINE HYDROCHLORIDE (DEMECLOCYCLINE HYDROCHLORIDE).
Binds to the 30S ribosomal subunit, inhibiting protein synthesis by preventing aminoacyl-tRNA from attaching to the mRNA-ribosome complex.
| Metabolism | Hepatic metabolism, primarily via glucuronidation, with some renal excretion of unchanged drug. |
| Excretion | Renal: 40-50% unchanged; fecal/biliary: 10-15% |
| Half-life | 10-17 hours; prolonged in renal impairment (up to 40–50 hours) |
| Protein binding | 75-91% bound primarily to albumin |
| Volume of Distribution | 1.5-2.0 L/kg; high due to tissue penetration |
| Bioavailability | Oral: 60-80% (decreased by food, milk, calcium, iron, antacids) |
| Onset of Action | Oral: 1-2 hours; IV: immediate (not available in all regions) |
| Duration of Action | 12-24 hours; clinical effect persists ~6 hours after peak |
150 mg orally every 6 hours or 300 mg orally every 12 hours. Maximum daily dose: 1200 mg.
| Dosage form | TABLET |
| Renal impairment | CrCl < 50 mL/min: Avoid use due to anti-anabolic effect and increased risk of azotemia. If unavoidable, reduce dose or extend interval; specific guidelines not established. |
| Liver impairment | No adjustment required for mild to moderate hepatic impairment. In severe impairment (Child-Pugh C), caution advised due to potential for hepatotoxicity; monitor liver function. |
| Pediatric use | Children ≥8 years: 8–12 mg/kg/day orally, divided every 6–12 hours. Maximum: 1200 mg/day. Not recommended in children <8 years due to permanent tooth discoloration and enamel hypoplasia. |
| Geriatric use | No specific dose adjustment; use with caution due to age-related renal decline. Monitor renal function and avoid in CrCl < 50 mL/min. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DEMECLOCYCLINE HYDROCHLORIDE (DEMECLOCYCLINE HYDROCHLORIDE).
| Breastfeeding | Demeclocycline is excreted into human breast milk, but the milk-to-plasma (M/P) ratio is not specifically reported for demeclocycline. For tetracyclines as a class, the M/P ratio is approximately 0.6-0.8. The concentration in milk is low, but theoretical risks include dental discoloration and bone growth inhibition in the nursing infant. The American Academy of Pediatrics considers tetracyclines to be compatible with breastfeeding, but alternatives are preferred due to potential adverse effects. Caution is advised, and the lowest effective dose should be used if necessary. |
| Teratogenic Risk | Demeclocycline, like other tetracyclines, is associated with fetal risk throughout pregnancy. In the first trimester, there is a potential for teratogenic effects, though data are limited; however, tetracyclines are generally avoided due to possible malformations. In the second and third trimesters, exposure can cause permanent discoloration of deciduous teeth (yellow-gray-brown) and reversible inhibition of bone growth due to chelation with calcium in developing bone and teeth. The risk is highest after 25 weeks of gestation. Additionally, maternal hepatotoxicity and pancreatitis have been reported with tetracyclines during pregnancy, particularly with high doses or intravenous administration. |
■ FDA Black Box Warning
Use during tooth development (last half of pregnancy, infancy, childhood to age 8 years) may cause permanent tooth discoloration and enamel hypoplasia.
| Serious Effects |
["Hypersensitivity to demeclocycline or any tetracycline","Pregnancy and breastfeeding","Children under 8 years of age","Severe renal impairment"]
| Precautions | ["Photosensitivity reaction (exaggerated sunburn) can occur; avoid prolonged sun exposure and sunlamps.","Use in pregnancy may cause fetal harm; avoid if pregnant.","Use in children <8 years may cause permanent tooth discoloration.","Clostridium difficile-associated diarrhea (CDAD) possible.","May worsen renal function in patients with renal impairment; avoid in severe renal disease.","Superinfection with non-susceptible organisms, including fungi."] |
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| Fetal Monitoring | Monitor for maternal signs of hepatotoxicity (elevated liver enzymes, bilirubin), pancreatitis (amylase, lipase), and renal function (serum creatinine, BUN) due to rare but serious adverse effects. In the fetus, if exposure occurs during the second or third trimester, monitor for signs of bone growth inhibition and dental discoloration postnatally. No specific fetal monitoring is required during pregnancy beyond standard prenatal care, but ultrasound may be considered for fetal growth assessment if prolonged exposure occurs. |
| Fertility Effects | Tetracyclines may affect fertility in both males and females. In males, they can impair spermatogenesis and reduce sperm motility, as seen in animal studies. In females, tetracyclines have been associated with inhibition of ovulation in animal models. Reversible infertility has been reported in both sexes. These effects are generally reversible upon discontinuation, but data specific to demeclocycline are limited. |