Comparative Pharmacology
Head-to-head clinical analysis: ACTICLATE versus SUMYCIN.
Peer-Reviewed Evidence
Head-to-head clinical analysis: ACTICLATE versus SUMYCIN.
ACTICLATE vs SUMYCIN
Head-to-head clinical comparison of therapeutic indices and safety profiles.
Inhibits P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), thereby increasing intestinal absorption and decreasing clearance of substrates; also inhibits CYP3A4 isoenzymes, reducing metabolism of CYP3A4 substrates.
Tetracycline antibiotic inhibiting bacterial protein synthesis by binding to the 30S ribosomal subunit, blocking aminoacyl-tRNA binding to the A site.
Adjuvant therapy to antibiotics for treatment of refractory infections caused by multidrug-resistant organismsOff-label: Treatment of hyperuricemia in gout (as a urate-lowering agent when combined with allopurinol)Investigationally: Reversal of P-gp-mediated resistance in certain malignancies
Treatment of infections caused by susceptible strains of bacteria including respiratory tract infections, urinary tract infections, skin and soft tissue infections, and sexually transmitted diseasesAcne vulgarisRosaceaPeriodontitis (adjunctive therapy)
100 mg orally twice daily (12 hours apart) on an empty stomach (1 hour before or 2 hours after meals). Avoid milk, antacids, iron, calcium, magnesium, and zinc within 2 hours of administration.
250-500 mg orally every 6 hours or 500 mg orally every 12 hours (maximum 2 g/day)
None Documented
None Documented
Terminal elimination half-life is approximately 18-22 hours in patients with normal renal function; prolonged to 30-50 hours in moderate renal impairment (CrCl 30-50 mL/min).
6-12 hours; prolonged in renal impairment (up to 24-48 hours in anuria)
Primarily hepatic via CYP3A4 and CYP2D6; also undergoes glucuronidation and renal excretion.
Not extensively metabolized; primarily excreted unchanged in urine via glomerular filtration.
Renal excretion of unchanged drug accounts for approximately 60% of the dose; fecal elimination via biliary secretion contributes about 30%; minor metabolism (<10%) produces inactive metabolites.
Renal (60-80% unchanged via glomerular filtration), biliary/fecal (20-40%)
Approximately 75-80% bound primarily to serum albumin and to a lesser extent to alpha-1-acid glycoprotein.
20-40%, primarily to albumin
Volume of distribution is 1.5-2.5 L/kg, indicating extensive tissue distribution; penetrates well into lung, skin, and soft tissues.
1.5-2.0 L/kg; indicates extensive tissue distribution (e.g., lung, liver, bone)
Oral bioavailability is approximately 95% with minimal first-pass metabolism; food reduces absorption by 20-30%.
Oral: 30-50% (tetracycline base); higher for hydrochloride salt (60-80%)
eGFR 30-60 mL/min/1.73m²: No adjustment needed; eGFR <30 mL/min: Avoid use (contraindicated due to tetracycline accumulation).
CrCl 50-80 mL/min: 250 mg every 6 hours or 500 mg every 12 hours; CrCl 10-50 mL/min: 250 mg every 8-12 hours; CrCl <10 mL/min: 250 mg every 24 hours
Child-Pugh Class A or B: No adjustment; Child-Pugh Class C: Avoid use (insufficient data, potential hepatotoxicity).
No dose adjustment required; however, use with caution in severe hepatic impairment due to potential hepatotoxicity.
Weight ≥45 kg and age ≥12 years: 100 mg every 12 hours for 10 days. Weight <45 kg or age <12 years: Not recommended (risk of permanent tooth discoloration and bone growth inhibition).
25-50 mg/kg/day orally divided every 6 hours (maximum 2 g/day)
Use with caution due to increased risk of intracranial hypertension and photosensitivity. Consider renal function; no specific dose adjustment beyond renal dosing.
No specific dose adjustment; monitor renal function and adjust dose based on creatinine clearance.
None.
Use during tooth development (last half of pregnancy, infancy, and childhood to 8 years) may cause permanent tooth discoloration and enamel hypoplasia; use during pregnancy may cause fetal harm; use in patients with renal impairment may lead to azotemia, hyperphosphatemia, and acidosis.
May cause significant drug interactions due to inhibition of P-gp, BCRP, and CYP3A4; monitor for increased toxicity of coadministered drugs (e.g., digoxin, methotrexate, anticancer agents). Use with caution in patients with hepatic impairment.
Photosensitivity reaction; superinfection with Clostridium difficile; hepatotoxicity; renal toxicity; use in pregnancy and children under 8 years; caution in renal impairment; may cause intracranial hypertension.
Hypersensitivity to active ingredient; concurrent use with narrow therapeutic index drugs that are P-gp or CYP3A4 substrates (e.g., digoxin, colchicine, cyclosporine) unless benefit outweighs risk.
Hypersensitivity to tetracyclines; pregnancy; breastfeeding; children under 8 years; severe hepatic impairment.
Data Pending Review
Data Pending Review
Dairy products (milk, yogurt, cheese), calcium-fortified foods, and high-calcium meals reduce doxycycline absorption. Take doxycycline at least 1-2 hours before or after consuming these foods. Avoid concurrent use with antacids, iron supplements, bismuth subsalicylate, and magnesium-containing laxatives. Alcohol is not known to interact but may increase gastrointestinal irritation.
Avoid dairy products (milk, yogurt, cheese) and calcium-fortified foods within 2-3 hours of dosing. Also avoid iron-fortified foods and beverages (e.g., fortified cereals, spinach) near administration time. High-fat meals may delay absorption. No known restrictions with alcohol but may exacerbate GI upset.
FDA Pregnancy Category D. Tetracyclines, including doxycycline (active ingredient in ACTICLATE), can cause fetal harm when administered to a pregnant woman. Use during tooth development (second and third trimesters) may cause permanent discoloration of teeth (yellow-gray-brown) and enamel hypoplasia. Use during skeletal development may cause reversible inhibition of bone growth. Avoid during pregnancy; alternative therapy should be considered.
Sumycin (tetracycline) is classified as FDA Pregnancy Category D. First trimester: Avoid due to possible teratogenic effects (limb anomalies, neural tube defects) based on animal data, but human data are limited. Second and third trimesters: Contraindicated due to risk of permanent tooth discoloration (yellow-gray-brown) and enamel hypoplasia in the fetus, and reversible inhibition of bone growth. Use after the 4th month of pregnancy is strongly discouraged.
Doxycycline is excreted in human milk at low concentrations. The milk-to-plasma ratio is approximately 0.6-0.9. Theoretical risk of dental discoloration and bone growth inhibition in nursing infants exists due to cumulative effects, although absorption by the infant is limited. Caution is advised; consider temporary discontinuation of breastfeeding during treatment or use alternative agent.
Tetracycline is excreted into breast milk in low concentrations (M/P ratio approximately 0.5-0.8). However, due to the potential for serious adverse reactions (e.g., dental discoloration, bone growth inhibition) in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Doxycycline is contraindicated in pregnancy; no dose adjustment is applicable. If inadvertent exposure occurs in first trimester, no dose adjustment needed, but drug should be discontinued. No pharmacokinetic data suggesting need for dose adjustment if used for life-threatening conditions (e.g., anthrax), but risk-benefit must be carefully assessed.
Due to physiological changes in pregnancy (increased plasma volume, renal blood flow), tetracycline clearance may be increased; however, standard dosing is not recommended in pregnancy because of fetal risks. No dose adjustment guidelines exist for pregnancy; use is contraindicated after first trimester.
Category C
Category C
ACTICLATE (doxycycline hyclate) is a tetracycline antibiotic. Avoid concomitant use with antacids, dairy products, or iron supplements as they chelate doxycycline, reducing absorption. Administer with a full glass of water and avoid lying down for 30 minutes to reduce esophageal irritation. Photosensitivity is common; advise sun avoidance and sunscreen use. Do not use in children <8 years or during pregnancy/lactation due to tooth discoloration and bone growth inhibition. Monitor for pseudomembranous colitis and superinfection.
SUMYCIN (tetracycline) is bacteriostatic; avoid in children <8 years and pregnancy due to tooth discoloration and bone growth inhibition. Administer on empty stomach (1 hour before or 2 hours after meals) with full glass of water to reduce esophageal irritation. Avoid concurrent dairy, antacids, iron, calcium, magnesium, and zinc supplements. Monitor for photosensitivity; advise sun protection. May reduce effectiveness of oral contraceptives; recommend backup contraception.
Take doxycycline exactly as prescribed. Do not skip doses or stop early even if you feel better.Take with a full glass of water. Avoid lying down for at least 30 minutes after taking to prevent esophageal irritation.Avoid taking with milk, yogurt, cheese, or calcium-fortified foods. Also avoid antacids, iron, and bismuth subsalicylate within 2 hours of doxycycline.Use sunscreen and protective clothing; doxycycline increases sensitivity to sunlight and can cause severe sunburn.If you miss a dose, take it as soon as you remember unless it is near the time of the next dose. Do not double the dose.Report persistent diarrhea, severe headache, vision changes, or allergic reactions (rash, swelling) to your healthcare provider immediately.
Take on an empty stomach, 1 hour before or 2 hours after meals, with a full glass of water.Avoid dairy products, antacids, iron supplements, and calcium or magnesium-containing products within 2-3 hours of taking this medication.Do not take this medication right before lying down; stay upright for at least 10 minutes after taking to prevent throat irritation.Use sunscreen and protective clothing during sun exposure; avoid tanning beds as this drug increases sun sensitivity.Finish the entire prescribed course even if you feel better; do not skip doses.Tell your doctor if you are pregnant, planning to become pregnant, or breastfeeding; this medication may harm the baby.If you take oral contraceptives, use an additional non-hormonal birth control method while on this medication.Store at room temperature away from light and moisture; do not use after expiration date.