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 |
| Molecular Weight | 465.28 |
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 | Avoid; tetracyclines can cause fetal harm. Use only if no alternative and potential benefit justifies risk. |
| 2nd trimester | Avoid; risk of maternal hepatotoxicity and fetal bone/tooth discoloration. Use only if no alternative. |
| 3rd trimester | Avoid; may cause permanent discoloration of deciduous teeth and reversible inhibition of bone growth. |
Clinical note
Comprehensive clinical and safety monograph for DEMECLOCYCLINE HYDROCHLORIDE (DEMECLOCYCLINE HYDROCHLORIDE).
| Placental transfer | Democlocycline crosses the placenta; reported placental transfer in animal studies and human case reports. |
| Breastfeeding | Avoid breastfeeding during treatment due to potential for serious adverse reactions in nursing infants, including teeth discoloration and bone growth inhibition. Consider alternative therapies. |
■ 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 democlocycline or any tetracyclineRenal failure (use of tetracyclines in renal impairment may increase BUN and cause azotemia)PregnancyLactationChildren under 8 years of age (risk of permanent tooth discoloration and bone growth inhibition)
| 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. |
| Food/Dietary | Dairy products (milk, yogurt, cheese), calcium-fortified foods, antacids containing calcium/magnesium/aluminum, iron supplements, bismuth subsalicylate, zinc, and sucralfate reduce absorption and should be separated by at least 2-3 hours. |
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| Lactation Rating | L5 (Avoid if possible; may cause serious toxicity to nursing infant) |
| 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. |
| 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. |
| Clinical Pearls | Demethylchlortetracycline is a tetracycline antibiotic with antidiuretic hormone (ADH) antagonistic properties, making it uniquely useful for treating hyponatremia in syndrome of inappropriate antidiuretic hormone secretion (SIADH). Avoid in children <8 years and pregnancy (risk of tooth discoloration, bone growth inhibition). Monitor renal and hepatic function; dose adjustment needed in renal impairment. Photosensitivity reactions are more common with demeclocycline than other tetracyclines; warn patients to avoid sun exposure. May cause false-positive urine glucose tests (copper sulfate method). |
| Patient Advice | Take on an empty stomach 1 hour before or 2 hours after meals with a full glass of water; do not take with dairy products, antacids, or iron supplements. · Complete the full course even if you feel better; skipping doses can lead to resistance. · Avoid prolonged sun or UV light exposure; use sunscreen and protective clothing. · If you become pregnant or plan to breastfeed, inform your doctor immediately. · Report symptoms like severe diarrhea, rash, or yellowing of the skin or eyes. · Store at room temperature, away from heat and moisture; keep out of reach of children. |