Acticlate

Name: Acticlate

Acticlate Side Effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • changes in your vision;
  • severe stomach pain, diarrhea that is watery or bloody;
  • fever, swollen glands, body aches, flu symptoms, weakness;
  • skin rash, pale skin, easy bruising or bleeding, severe tingling, numbness, pain, muscle weakness;
  • upper stomach pain (may spread to your back), loss of appetite, dark urine, jaundice (yellowing of the skin or eyes);
  • chest pain, irregular heart rhythm, feeling short of breath;
  • confusion, nausea and vomiting, swelling, rapid weight gain, little or no urinating;
  • new or worsening cough with fever, trouble breathing;
  • increased pressure inside the skull--severe headaches, ringing in your ears, dizziness, nausea, vision problems, pain behind your eyes; or
  • severe skin reaction--fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Common side effects may include:

  • nausea, vomiting, upset stomach;
  • mild diarrhea;
  • skin rash or itching; or
  • vaginal itching or discharge.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Acticlate (doxycycline)?

Other drugs may interact with doxycycline, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

Dosage Forms and Strengths

Acticlate Tablets:

Acticlate (doxycycline hyclate) Tablets, 75 mg are round, convex, light-teal, film-coated, tablets with “75” debossed on one side of the tablet and “AQ101” debossed on the other (each tablet contains 75 mg doxycycline as 86.6 mg doxycycline hyclate).

Acticlate (doxycycline hyclate) Tablets, 150 mg are oval-shaped, convex, mossy-green, film-coated tablets. Each side of the functionally scored tablet has two parallel score lines for splitting into 3 equal portions with “A” debossed on each portion of one side of the tablet, and no debossing on the other (each tablet contains 150 mg doxycycline as 173.2 mg doxycycline hyclate).

Acticlate CAP Capsules:

Acticlate CAP (doxycycline hyclate) Capsules, 75 mg have a navy blue opaque body and cap with the inscription “AQUA 101C75” in black (each capsule contains 75 mg doxycycline as 86.6 mg doxycycline hyclate).

Warnings and Precautions

Tooth Development

The use of drugs of the tetracycline-class during tooth development (last half of pregnancy, infancy and childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). This adverse reaction is more common during long-term use of the drugs but it has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. Use Acticlate and Acticlate CAP in pediatric patients 8 years of age or less only when the potential benefits are expected to outweigh the risks in severe or life-threatening conditions (e.g., anthrax, Rocky Mountain spotted fever), particularly when there are no alternative therapies.

Clostridium difficile Associated Diarrhea

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Acticlate and Acticlate CAP, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antibacterial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Photosensitivity

Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Patients apt to be exposed to direct sunlight or ultraviolet light should be advised that this reaction can occur with tetracycline drugs, and treatment should be discontinued at the first evidence of skin erythema.

Potentaial for Microbial Overgrowth

Acticlate and Acticlate CAP may result in overgrowth of non-susceptible organisms, including fungi. If such infections occur, discontinue use and institute appropriate therapy.

Intracranial Hypertension

Intracranial hypertension (IH, pseudotumor cerebri) has been associated with the use of tetracyclines including Acticlate and Acticlate CAP. Clinical manifestations of IH include headache, blurred vision, diplopia, and vision loss; papilledema can be found on fundoscopy. Women of childbearing age who are overweight or have a history of IH are at greater risk for developing tetracycline associated IH. Concomitant use of isotretinoin and Acticlate and Acticlate CAP should be avoided because isotretinoin is also known to cause pseudotumor cerebri.

Although IH typically resolves after discontinuation of treatment, the possibility for permanent visual loss exists. If visual disturbance occurs during treatment, prompt ophthalmologic evaluation is warranted. Since intracranial pressure can remain elevated for weeks after drug cessation patients should be monitored until they stabilize.

Delayed Skeletal Development

All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in fibula growth rate has been observed in prematures given oral tetracycline in doses of 25 mg per kg every six hours. This reaction was shown to be reversible when the drug was discontinued.

Results of animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues, and can have toxic effects on the developing fetus (often related to retardation of skeletal development). Evidence of embryotoxicity also has been noted in animals treated early in pregnancy. Tetracycline-class drugs can cause fetal harm when administered to a pregnant woman, but data for doxycycline are limited. If any tetracycline is used during pregnancy or if the patient becomes pregnant while taking these drugs, the patient should be apprised of the potential hazard to the fetus.

Antianabolic Action

The antianabolic action of the tetracyclines may cause an increase in BUN. Studies to date indicate that this does not occur with the use of doxycycline in patients with impaired renal function.

Incomplete Suppression of Malaria

Doxycycline offers substantial but not complete suppression of the asexual blood stages of Plasmodium strains.

Doxycycline does not suppress P. falciparum’s sexual blood stage gametocytes. Subjects completing this prophylactic regimen may still transmit the infection to mosquitoes outside endemic areas.

Development of Drug-Resistant Bacteria

Prescribing Acticlate and Acticlate CAP in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Laboratory Monitoring for Long-Term Therapy

In long-term therapy, periodic laboratory evaluation of organ systems, including hematopoietic, renal and hepatic studies should be performed.

Drug Interactions

Anticoagulant Drugs

Because tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage.

Penicillin

Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving tetracyclines, including Acticlate and Acticlate CAP in conjunction with penicillin.

Antacids and Iron Preparations

Absorption of tetracyclines, including Acticlate and Acticlate CAP is impaired by antacids containing aluminum, calcium, or magnesium, bismuth subsalicylate, and iron-containing preparations.

Oral Contraceptives

Concurrent use of tetracyclines, including Acticlate and Acticlate CAP may render oral contraceptives less effective.

Barbiturates and Anti-Epileptics

Barbiturates, carbamazepine, and phenytoin decrease the half-life of doxycycline.

Penthrane®

The concurrent use of tetracycline and Penthrane® (methoxyflurane) has been reported to result in fatal renal toxicity.

Drug and Laboratory Test Interactions

False elevations of urinary catecholamines may occur due to interference with the fluorescence test.

Use in specific populations

Pregnancy

Teratogenic Effects. Pregnancy Category D: [see Warnings and Precautions (5.6)]
There are no adequate and well-controlled studies on the use of doxycycline in pregnant women. The vast majority of reported experience with doxycycline during human pregnancy is short-term, first trimester exposure. There are no human data available to assess the effects of long-term therapy of doxycycline in pregnant women such as that proposed for the treatment of anthrax exposure. An expert review of published data on experiences with doxycycline use during pregnancy by TERIS - the Teratogen Information System - concluded that therapeutic doses during pregnancy are unlikely to pose a substantial teratogenic risk (the quantity and quality of data were assessed as limited to fair), but the data are insufficient to state that there is no risk.1

A case-control study (18,515 mothers of infants with congenital anomalies and 32,804 mothers of infants with no congenital anomalies) shows a weak but marginally statistically significant association with total malformations and use of doxycycline anytime during pregnancy. Sixty-three (0.19%) of the controls and 56 (0.30%) of the cases were treated with doxycycline. This association was not seen when the analysis was confined to maternal treatment during the period of organogenesis (that is, in the second and third months of gestation), with the exception of a marginal relationship with neural tube defect based on only two-exposed cases.2

A small prospective study of 81 pregnancies describes 43 pregnant women treated for 10 days with doxycycline during early first trimester. All mothers reported their exposed infants were normal at 1 year of age.3

Nonteratogenic effects: [see Warnings and Precautions (5.1, 5.6)].

Nursing Mothers

Tetracyclines are excreted in human milk, however, the extent of absorption of tetracyclines including doxycycline, by the breastfed infant is not known. Short-term use by lactating women is not necessarily contraindicated. The effects of prolonged exposure to doxycycline in breast milk are unknown4. Because of the potential for serious adverse reactions in nursing infants from doxycycline, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother [see Warnings and Precautions (5.1, 5.6)].

Pediatric Use

Because of the effects of drugs of the tetracycline-class on tooth development and growth, use Acticlate and Acticlate CAP in pediatric patients 8 years of age or less only when the potential benefits are expected to outweigh the risks in severe or life-threatening conditions (e.g., anthrax, Rocky Mountain spotted fever), particularly when there are no alternative therapies [see Warnings and Precautions (5.1, 5.6) and Dosage and Administration (2.1, 2.5)].

Geriatric Use

Clinical studies of doxycycline hyclate tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Acticlate Tablets each contains less than 1 mg of sodium.

References

  1. Friedman JM, Polifka JE. Teratogenic Effects of Drugs. A Resource for Clinicians (TERIS). Baltimore, MD: The Johns Hopkins University Press: 2000: 149-195. The TERIS (Teratogen Information System) is available at: http://www.micromedexsolutions.com/ (cited: 2016 Jan).
  2. Cziezel AE and Rockenbauer M. Teratogenic study of doxycycline. Obstet Gynecol 1997; 89: 524-528.
  3. Horne HW Jr. and Kundsin RB. The role of mycoplasma among 81 consecutive pregnancies: a prospective study. Int J Fertil 1980; 25: 315-317.
  4. Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); [Last Revision Date 2015 March 10; cited 2016 Jan]. Doxycycline; LactMed Record Number: 100; [about 3 screens]. Available from: http://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm
  5. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-sixth Edition. CLSI Supplement M100S. Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2016.
  6. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard – Tenth Edition. CLSI document M07-A10, Clinical Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.
  7. Clinical and Laboratory Standards Institute (CLSI). Methods for Antimicrobial Dilution and Disk Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria. Third Edition. CLSI Guideline M45, Clinical Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.
  8. Clinical and Laboratory Standards Institute (CLSI). Methods for Mycobacteria, Nocardiae, and Other Aerobic Actinomycetes; Approved Standard – Second Edition. CLSI document M24-A2, Clinical Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2011.
  9. Clinical and Laboratory Standards Institute (CLSI). Methods for Antimicrobial Susceptibility Testing for Human Mycoplasmas; Approved Guideline. CLSI document M43-A, Clinical Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2011.
  10. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Diffusion Susceptibility Tests; Approved Standard – Twelfth Edition. CLSI document M02-A12, Clinical Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.
  11. Clinical and Laboratory Standards Institute (CLSI). Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard – Eighth Edition. CLSI document M11-A8, Clinical Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2012.

For the Consumer

Applies to doxycycline: oral capsule, oral capsule delayed release, oral capsule extended release, oral powder for suspension, oral syrup, oral tablet, oral tablet delayed release

Along with its needed effects, doxycycline (the active ingredient contained in Acticlate) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking doxycycline:

Incidence not known
  • Bloating
  • chills
  • clay-colored stools
  • constipation
  • cough
  • dark urine
  • decreased appetite
  • diarrhea
  • diarrhea, watery and severe, which may also be bloody
  • difficulty with swallowing
  • dizziness
  • fast heartbeat
  • feeling of discomfort
  • fever
  • headache
  • hives, itching, puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • hives or welts, itching, or rash
  • increased thirst
  • indigestion
  • inflammation of the joints
  • joint or muscle pain
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • loss of appetite
  • nausea and vomiting
  • numbness or tingling of the face, hands, or feet
  • pain in the stomach, side, or abdomen, possibly radiating to the back
  • redness and soreness of the eyes
  • redness of the skin
  • sore throat
  • sores in the mouth
  • stomach cramps
  • stomach pain or tenderness
  • swelling of the feet or lower legs
  • swollen lymph glands
  • tightness in the chest
  • unusual tiredness or weakness
  • unusual weight loss
  • yellow eyes or skin

Some side effects of doxycycline may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Incidence not known
  • Back, leg, or stomach pains
  • black, tarry stools
  • bleeding gums
  • blood in the urine or stools
  • blurred vision
  • bulging soft spot on the head of an infant
  • change in the ability to see colors, especially blue or yellow
  • chest pain, discomfort, or burning
  • cracks in the skin
  • decrease in vision
  • difficulty breathing
  • discoloration of the thyroid glands
  • double vision
  • general body swelling
  • heartburn
  • increased sensitivity of the skin to sunlight
  • loss of heat from the body
  • lower back or side pain
  • nosebleeds
  • pain or burning in the throat
  • pain with swallowing
  • painful or difficult urination
  • pale skin
  • pinpoint red spots on the skin
  • rash with flat lesions or small raised lesions on the skin
  • red, swollen skin
  • redness or other discoloration of the skin
  • redness, swelling, or soreness of the tongue
  • scaly skin
  • severe nausea
  • severe stomach pain
  • severe sunburn
  • sores, ulcers, or white spots on the lips or tongue or inside the mouth
  • unusual bleeding or bruising
  • vomiting blood

Doxycycline Levels and Effects while Breastfeeding

Summary of Use during Lactation

A number of reviews have stated that tetracyclines are contraindicated during breastfeeding because of possible staining of infants' dental enamel or bone deposition of tetracyclines. However, a close examination of available literature indicates that there is not likely to be harm in short-term use of doxycycline during lactation because milk levels are low and absorption by the infant is inhibited by the calcium in breastmilk. Short-term use of doxycycline is acceptable in nursing mothers. As a theoretical precaution, avoid prolonged or repeat courses during nursing. Monitor the infant for rash and for possible effects on the gastrointestinal flora, such as diarrhea or candidiasis (thrush, diaper rash).

Drug Levels

Maternal Levels. Fifteen mothers nursing infants between 15 and 30 days old were given doxycycline 200 mg orally followed in 12 hours by another dose of 100 mg. Milk doxycycline levels were measured using a biologic assay 3 and 24 hours after the second dose. Milk doxycycline levels averaged 0.77 mg/L (range 0.4 to 1.4 mg/L) 3 hours after the dose and 0.38 mg/L (range 0.12 to 0.85 mg/L) 24 hours after the dose.[1]

A dose of 100 mg daily of doxycycline was given orally to 10 mothers. On the second day of treatment, milk doxycycline averaged 0.82 mg/L (range 0.37 to 1.24 mg/L) 3 hours after the dose, and 0.46 mg/L (range 0.3 to 0.91 mg/L) 24 hours after the dose.[2] Using the average of the peak and trough milk levels in this study, the estimated average intake of an exclusively breastfed infant would be about 6% of the maternal weight-adjusted dosage.

After a single oral dose of 100 mg in 3 women and 200 mg in 3 women, peak milk levels occurred between 2 and 4 hours after the dose. Average peak milk concentrations were 0.96 mg/L after 100 mg and 1.8 mg/L after 200 mg. Milk levels accumulated to about 3.6 mg/L with doses of 100 mg twice daily for 5 days.[3]

Another study found peak milk levels to occur 5 to 7 hours after oral doses of 100 or 200 mg in 13 women in the immediate postpartum period. Peak levels were 0.6 mg/L with the 100 mg dose in 3 women, and averaged 1.1 mg/L in 11 women who received 200 mg.[4]

After single 200 mg dose of doxycycline to 2 women, average milk levels were 0.8 mg/L 2 hours after the dose, 0.7 mg/L 4 hours after the dose, and 0.4 mg/L 6 hours after the dose.[5]

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

Alternate Drugs to Consider

Tetracycline

References

1. Morganti G, Ceccarelli G, Ciaffi G. Comparative concentrations of a tetracycline antibiotic in serum and maternal milk. Antibiotica. 1968;6:216-23. PMID: 5739581

2. Lutziger H. [Concentration determinations and clinical effectiveness of doxycycline (Vibramycin) in the uterus, adnexa and maternal milk]. Ther Umsch. 1969;26:476-80. PMID: 5355767

3. Tokuda G, Yuasa M, Mihara S et al. [Clinical study of doxycycline in obstetrical and gynecological fields]. Chemotherapy (Tokyo). 1969;17:339-44.

4. Borderon E, Soutoul JH et al. [Excretion of antibiotics in human milk]. Med Mal Infect. 1975;5:373-6.

5. Matsuda S. Transfer of antibiotics into maternal milk. Biol Res Pregnancy. 1984;5:57-60. PMID: 6743732

6. Posner AC, Prigot A, Konicoff NG. Further observations on the use of tetracycline hydrochloride in prophylaxis and treatment of obstetric infections. Antibiot Annu 1954-1955. 1955;594-8.

Administrative Information

LactMed Record Number

100

Last Revision Date

20170411

Disclaimer

Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.

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