ACTICLATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ACTICLATE (ACTICLATE).
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.
| Metabolism | Primarily hepatic via CYP3A4 and CYP2D6; also undergoes glucuronidation and renal excretion. |
| Excretion | 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. |
| Half-life | 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). |
| Protein binding | Approximately 75-80% bound primarily to serum albumin and to a lesser extent to alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is 1.5-2.5 L/kg, indicating extensive tissue distribution; penetrates well into lung, skin, and soft tissues. |
| Bioavailability | Oral bioavailability is approximately 95% with minimal first-pass metabolism; food reduces absorption by 20-30%. |
| Onset of Action | Oral: onset of antibacterial effect occurs within 2-4 hours after first dose; IV: immediate therapeutic levels achieved at end of infusion. |
| Duration of Action | Duration of action is approximately 12-24 hours for susceptible organisms; clinical effect persists for 24 hours after single dose due to prolonged post-antibiotic effect. |
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.
| Dosage form | TABLET |
| Renal impairment | eGFR 30-60 mL/min/1.73m²: No adjustment needed; eGFR <30 mL/min: Avoid use (contraindicated due to tetracycline accumulation). |
| Liver impairment | Child-Pugh Class A or B: No adjustment; Child-Pugh Class C: Avoid use (insufficient data, potential hepatotoxicity). |
| Pediatric use | 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). |
| Geriatric use | Use with caution due to increased risk of intracranial hypertension and photosensitivity. Consider renal function; no specific dose adjustment beyond renal dosing. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ACTICLATE (ACTICLATE).
| Breastfeeding | 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. |
| Teratogenic Risk | 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. |
■ FDA Black Box Warning
None.
| Serious Effects |
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.
| Precautions | 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. |
| Food/Dietary | 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. |
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| Fetal Monitoring | No specific fetal monitoring required if exposed inadvertently, but ultrasound may be considered to assess bone growth if prolonged exposure occurred in second/third trimester. Monitor for signs of hepatotoxicity in mother (rare). |
| Fertility Effects | No specific effects on fertility reported in humans. Animal studies at high doses have shown reduced fertility in rats, but relevance to humans is uncertain. |
| Clinical Pearls | 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. |
| Patient Advice | 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. |