Acticlate

Name: Acticlate

Acticlate Interactions

Do not take iron supplements, multivitamins, calcium supplements, antacids, or laxatives within 2 hours before or after taking doxycycline.

Avoid taking any other antibiotics with doxycycline unless your doctor has told you to.

Avoid exposure to sunlight or tanning beds. Doxycycline can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Antibiotic medicines can cause diarrhea, which may be a sign of a new infection. If you have diarrhea that is watery or bloody, stop taking doxycycline and call your doctor. Do not use anti-diarrhea medicine unless your doctor tells you to.

Other drugs may interact with doxycycline, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Indications and Usage for Acticlate

Rickettsial Infections

Acticlate® and Acticlate® CAP are indicated for treatment of Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsial pox, and tick fevers caused by Rickettsiae.

Sexually Transmitted Infections

Acticlate and Acticlate CAP are indicated for treatment of the following sexually transmitted infections:

  • Uncomplicated urethral, endocervical or rectal infections caused by Chlamydia trachomatis.
  • Nongonococcal urethritis caused by Ureaplasma urealyticum.
  • Lymphogranuloma venereum caused by Chlamydia trachomatis.
  • Granuloma inguinale caused by Klebsiella granulomatis.
  • Uncomplicated gonorrhea caused by Neisseria gonorrhoeae.
  • Chancroid caused by Haemophilus ducreyi.

Respiratory Tract Infections

Acticlate and Acticlate CAP are indicated for treatment of the following respiratory tract infections:

  • Respiratory tract infections caused by Mycoplasma pneumoniae.
  • Psittacosis (ornithosis) caused by Chlamydophila psittaci.
  • Because many strains of the following groups of microorganisms have been shown to be resistant to doxycycline, culture and susceptibility testing are recommended.
  • Doxycycline is indicated for treatment of infections caused by the following microorganisms, when bacteriological testing indicates appropriate susceptibility to the drug:
  • Respiratory tract infections caused by Haemophilus influenzae.
  • Respiratory tract infections caused by Klebsiella species.
  • Upper respiratory infections caused by Streptococcus pneumoniae.

Specific Bacterial Infections

Acticlate and Acticlate CAP are indicated for treatment of the following specific bacterial infections:

  • Relapsing fever due to Borrelia recurrentis.
  • Plague due to Yersinia pestis.
  • Tularemia due to Francisella tularensis.
  • Cholera caused by Vibrio cholerae.
  • Campylobacter fetus infections caused by Campylobacter fetus.
  • Brucellosis due to Brucella species (in conjunction with streptomycin).
  • Bartonellosis due to Bartonella bacilliformis.

Because many strains of the following groups of microorganisms have been shown to be resistant to doxycycline, culture and susceptibility testing are recommended.

Acticlate and Acticlate CAP are indicated for treatment of infections caused by the following gram-negative microorganisms, when bacteriological testing indicates appropriate susceptibility to the drug:

  • Escherichia coli
  • Enterobacter aerogenes
  • Shigella species
  • Acinetobacter species
  • Urinary tract infections caused by Klebsiella species.

Ophthalmic Infections

Acticlate and Acticlate CAP are indicated for treatment of the following ophthalmic infections:

  • Trachoma caused by Chlamydia trachomatis, although the infectious agent is not always eliminated as judged by immunofluorescence.
  • Inclusion conjunctivitis caused by Chlamydia trachomatis.

Anthrax Including Inhalational Anthrax (Post-Exposure)

Acticlate and Acticlate CAP are indicated for the treatment of Anthrax due to Bacillus anthracis, including inhalational anthrax (post-exposure); to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis.

Alternative Treatment for Selected Infections when Penicillin is Contraindicated

Acticlate and Acticlate CAP are indicted as an alternative treatment for the following selected infections when penicillin is contraindicated:

  • Syphilis caused by Treponema pallidum.
  • Yaws caused by Treponema pallidum subspecies pertenue.
  • Listeriosis due to Listeria monocytogenes.
  • Vincent’s infection caused by Fusobacterium fusiforme.
  • Actinomycosis caused by Actinomyces israelii.
  • Infections caused by Clostridium species.

Adjunctive Therapy for Acute Intestinal Amebiasis and Severe Acne

In acute intestinal amebiasis, Acticlate and Acticlate CAP may be a useful adjunct to amebicides.

In severe acne, Acticlate and Acticlate CAP may be useful adjunctive therapy.

Prophylaxis of Malaria

Acticlate and Acticlate CAP are indicated for the prophylaxis of malaria due to Plasmodium falciparum in short-term travelers (less than 4 months) to areas with chloroquine and/or pyrimethamine-sulfadoxine resistant strains [see Dosage and Administration (2.4) and Patient Counseling Information (17)].

Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Acticlate and Acticlate CAP and other antibacterial drugs, Acticlate and Acticlate CAP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals to evaluate carcinogenic potential of Acticlate (doxycycline hyclate) and Acticlate CAP (doxycycline hyclate) have not been conducted.
However, a 2 year carcinogenicity study with doxycycline administered daily by oral gavage to adult rats (20, 75, 200 mg/kg/day) demonstrated an increase in uterine polyps in female rats at 200 mg/kg/day (10 times the maximum recommended daily adult dose of Acticlate and Acticlate CAP based on body surface area comparison) with no change in tumor incidence in male rats at the same dose. A 2-year carcinogenicity study with doxycycline administered daily by oral gavage to adult male (maximum dose 150 mg/kg/day) and female (maximum dose 300 mg/kg/day) mice showed no changes in tumor incidence, at approximately 4 and 7 times the maximum recommended daily adult dose of Acticlate and Acticlate CAP, based on a body surface area comparison, respectively.

Mutagenesis and fertility studies have not been conducted with Acticlate and Acticlate CAP. Mutagenesis studies with doxycycline demonstrated no potential to cause genetic toxicity in an in vitro point mutation study with mammalian cells or in an in vivo micronucleus assay in CD-1 mice. However, data from an in vitro mammalian chromosomal aberration assay conducted in CHO cells suggest that doxycycline is a weak clastogen. Oral administration of doxycycline to Sprague-Dawley rats showed adverse effects on fertility and reproduction including increased time for mating, reduced sperm motility, velocity and concentration as well as increased pre and post implantation loss. Reduced sperm velocity was seen at the lowest dosage tested, 50 mg/kg/day which is 2.5 times the maximum recommended daily adult dose of Acticlate and Acticlate CAP. Although doxycycline impairs the fertility of rats when administered at sufficient dosages, the effect of Acticlate and Acticlate CAP on human fertility is unknown.

Animal Toxicology and/or Pharmacology

Hyperpigmentation of the thyroid has been produced by members of the tetracycline-class in the following species: in rats by oxytetracycline, doxycycline, tetracycline PO4, and methacycline; in minipigs by doxycycline, minocycline, tetracycline PO4, and methacycline; in dogs by doxycycline and minocycline; in monkeys by minocycline.

Minocycline, tetracycline PO4, methacycline, doxycycline, tetracycline base, oxytetracycline HCl, and tetracycline HCl, were goitrogenic in rats fed a low iodine diet. This goitrogenic effect was accompanied by high radioactive iodine uptake. Administration of minocycline also produced a large goiter with high radioiodine uptake in rats fed a relatively high iodine diet.

Treatment of various animal species with this class of drugs has also resulted in the induction of thyroid hyperplasia in the following: in rats and dogs (minocycline); in chickens (chlortetracycline); and in rats and mice (oxytetracycline). Adrenal gland hyperplasia has been observed in goats and rats treated with oxytetracycline.

Results of animal studies indicate that tetracyclines cross the placenta and are found in fetal tissues.

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Instructions for Use).
Advise patients taking Acticlate and Acticlate CAP for malaria prophylaxis:

  • that no present-day antimalarial agent, including doxycycline, guarantees protection against malaria.
  • to avoid being bitten by mosquitoes by using personal protective measures that help avoid contact with mosquitoes, especially from dusk to dawn (for example, staying in well-screened areas, using mosquito nets, covering the body with clothing, and using an effective insect repellent).
  • that doxycycline prophylaxis:
    - should begin 1 day to 2 days before travel to the malarious area,
    - should be continued daily while in the malarious area and after leaving the malarious area,
    - should be continued for 4 further weeks to avoid development of malaria after returning from an endemic area,
    - should not exceed 4 months.
    Advise all patients taking Acticlate and Acticlate CAP:
  • that Acticlate Tablets (150 mg) can be broken into two-thirds or one-third at the scored lines to provide 100 mg or 50 mg strength doses, respectively.
  • that they must swallow Acticlate CAP whole. They must not break, open, crush, dissolve or chew the capsule [see Dosage and Administration (2.2)].
  • to avoid excessive sunlight or artificial ultraviolet light while receiving doxycycline and to discontinue therapy if phototoxicity (for example, skin eruptions, etc.) occurs. Sunscreen or sunblock should be considered [see Warnings and Precautions (5.3)].
  • to drink fluids liberally along with Acticlate and Acticlate CAP to reduce the risk of esophageal irritation and ulceration [see Adverse Reactions (6)].
  • that the absorption of tetracyclines is reduced when taken with foods, especially those that contain calcium [see Drug Interactions (7.3)]. However, the absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk [see Clinical Pharmacology (12.3)].
  • that if gastric irritation occurs, Acticlate and Acticlate CAP may be given with food or milk [see Clinical Pharmacology (12.3)].
  • that the absorption of tetracyclines is reduced when taken with antacids containing aluminum, calcium or magnesium, bismuth subsalicylate, and iron-containing preparations [see Drug Interactions (7.3)].
  • that the use of doxycycline might increase the incidence of vaginal candidiasis.

Advise patients that diarrhea is a common problem caused by antibacterial drugs which usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterial drugs, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of antibacterial. If this occurs, patients should contact their physician as soon as possible.

Counsel patients that antibacterial drugs including Acticlate and Acticlate CAP should only be used to treat bacterial infections. They do not treat viral infections (for example, the common cold). When Acticlate and Acticlate CAP are prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Acticlate and Acticlate CAP or other antibacterial drugs in the future.

Manufactured by Catalent Pharma Solutions, Winchester, KY 40391
For Aqua Pharmaceuticals, an Almirall Company Exton, PA 19341

AQUA
PHARMACEUTICALS
an Almirall company



FDA-Approved Patient Labeling

Instructions for Use
Acticlate® (‘aktəˌklāt)
(doxycycline hyclate)
tablets
for oral use

Read this Instructions for Use before you start using Acticlate and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.

Note:

  • Your healthcare provider may need to change your dose of Acticlate during treatment as needed.
  • Acticlate tablets can be taken whole or broken at scored lines.
  • Acticlate tablets are marked with scored lines and may be broken at these scored lines to provide the following doses:

150 mg treatment (take the entire whole tablet)

100 mg treatment (take two-thirds of the tablet)

50 mg treatment (take one-third of the tablet)

How to break your Acticlate tablet:

  • Hold the tablet between your thumb and index finger close to the scored line for your dose of Acticlate as shown above.
  • Apply enough pressure to break the tablet at the scored line.
  • Do not break the Acticlate tablet in any other way.

AQUA
PHARMACEUTICALS
an Almirall company

Manufactured by Catalent Pharma Solutions, Winchester, KY 40391
For Aqua Pharmaceuticals, an Almirall Company Exton, PA 19341

This Instructions for Use has been approved by the U.S. Food and Drug Administration.
Revised: 04/2016
Rx only


For Healthcare Professionals

Applies to doxycycline: injectable powder for injection, oral capsule, oral delayed release capsule, oral delayed release tablet, oral kit, oral powder for reconstitution, oral syrup, oral tablet, oral and topical kit

Nervous system

Very common (10% or more): Headache (up to 26%)
Common (1% to 10%): Sinus headache
Rare (0.01% to 0.1%): Bulging fontanels (in infants), benign intracranial hypertension (pseudotumor cerebri [symptoms include blurred vision, scotomata, diplopia]), tinnitus
Frequency not reported: Hypoesthesia, increased intracranial pressure, paresthesia, somnolence, stupor, taste loss, drowsiness, amnesia, paresthesias of body areas exposed to sunlight, phrenic nerve paralysis after sclerotherapy
Postmarketing reports: Pseudotumor cerebri, headache, dizziness[Ref]

Benign intracranial hypertension resulting in permanent loss of vision has been reported.

A 70-year-old female patient with no significant medical history suddenly developed a severe headache followed by vomiting about 15 minutes after the initial dose of this drug. The patient also experienced memory dysfunction; she could not remember the events of the afternoon prior to the dose of this drug and could not retain the information after she was reminded. The incident lasted about 30 minutes and she was transported to the hospital for further evaluation. No further cause, such as intoxication or trauma, could be elicited. Once at the hospital, the patient was able to remember the events of the afternoon and could retain new information, but amnesia regarding the events of the 30 minutes following the onset of the headache persisted. The patient's laboratory results, computerized tomography scan, MRI scan, cerebrospinal fluid, and electroencephalogram showed no pathology. When the patient was discharged 2 days later, the amnesia for the 30 minutes continued. After elimination of other symptomatic causes, the amnesia was concluded to be due to this drug because of the close relation of the dose and the onset of symptoms.[Ref]

Other

Very common (10% or more): Common cold (up to 22%), influenza symptoms (up to 11%)
Common (1% to 10%): Injury/accidental injury, pain, infection, fungal infection, influenza
Rare (0.01% to 0.1%): Candida infection/candidiasis, flushing, retrosternal pain
Frequency not reported: Malaise, overgrowth of nonsusceptible organisms (superinfection)
Postmarketing reports: Asthenia[Ref]

Gastrointestinal

Very common (10% or more): Nausea (up to 13.4%)
Common (1% to 10%): Nausea/vomiting, toothache, tooth disorder, dyspepsia, diarrhea, periodontal abscess, acid indigestion, upper abdominal pain, abdominal distention, abdominal pain, stomach discomfort, dry mouth
Uncommon (0.1% to 1%): Gum pain, heartburn/gastritis
Rare (less than 0.1%): Glossitis, dysphagia, enterocolitis, inflammatory lesions (with candidal/monilial overgrowth) in the anogenital region, esophagitis, esophageal ulcerations, pancreatitis, pseudomembranous colitis, Clostridium difficile colitis, stomatitis
Frequency not reported: Clostridium difficile-associated diarrhea, esophageal irritation, ulceration, epigastric burning, black hairy tongue, tooth discoloration/adult tooth staining, vomiting, enamel hypoplasia, staphylococcal enterocolitis
Postmarketing reports: Bloody diarrhea, colitis, constipation, superficial tooth discoloration[Ref]

Numerous cases of esophageal ulceration have been reported. In most cases, the patients had taken their medication at bedtime, usually without enough liquid. Patients often presented with severe retrosternal pain and difficulty swallowing. Ulcerations generally resolved within a week after discontinuing the drug. In 1 case report, severe hiccups of 4-day duration associated with esophagitis followed the first dose of this drug.

Esophagitis and esophageal ulcerations have been reported in patients taking the capsule or tablet formulations of tetracycline-class antibiotics. Most of these patients took the drug immediately before going to bed.[Ref]

Musculoskeletal

Common (1% to 10%): Joint pain/arthralgia, back pain/back ache
Uncommon (0.1% to 1%): Muscle pain/myalgia[Ref]

Respiratory

Common (1% to 10%): Nasopharyngitis, sore throat, sinus congestion, coughing, sinusitis, bronchitis, nasal congestion, pharyngolaryngeal pain
Frequency not reported: Bronchospasm

Dermatologic

Common (1% to 10%): Rash (including maculopapular rash, erythematous rash), photosensitivity reaction/dermatitis
Rare (0.01% to 0.1%): Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, photoonycholysis, drug reaction with eosinophilia and systemic symptoms (DRESS)
Frequency not reported: Nail discoloration, phototoxicity, photoallergic reaction, morbilliform rash, onycholysis, pustular rash
Postmarketing reports: Pruritus, urticaria

Tetracyclines:
-Frequency not reported: Hyperpigmentation[Ref]

In a double-blinded study, this drug was found to be more phototoxic than minocycline and demeclocycline. Paresthesias of the body areas exposed to sunlight may be early signs of sunburn reactions.

A case report of a possible photoallergic reaction described scaly erythema and vesicles on the face and neck associated with administration of this drug. Upon rechallenge, a flare with erythema, itching, and burning occurred in the same area.

Another case report was documented in Australian troops treated with 100 mg daily for malaria prophylaxis while on deployment in East Timor, a group of islands within the Malaysian archipelago located close to the equator. Of the 135 troops, 22 exhibited phototoxic reactions to low doses of this drug that resembled severe sunburn with erythematous plaques on the sun-exposed areas. The troops used a sunscreen containing oxybenzone.

An 11-year-old boy treated with this drug for brucellosis was evaluated for painless brown nail discoloration. This drug was initiated for brucellosis but stopped when the boy developed photosensitivity, but 15 days after the initiation of therapy brown nail discoloration developed. Other than the brown discoloration, the boy's physical condition was normal and the discoloration disappeared within 1 month.[Ref]

Genitourinary

Common (1% to 10%): Menstrual cramps, bacterial vaginitis, vulvovaginal mycotic infection
Uncommon (0.1% to 1%): Vaginal infection
Frequency not reported: Vaginal itch, vaginitis
Postmarketing reports: Vaginal candidiasis/moniliasis, anogenital moniliasis[Ref]

Cardiovascular

Common (1% to 10%): Hypertension, increased blood pressure
Frequency not reported: Phlebitis (with IV administration)

Hepatic

Common (1% to 10%): Increased AST
Rare (0.01% to 0.1%): Abnormal hepatic function, hepatic failure, hepatitis, hepatotoxicity, jaundice
Frequency not reported: Acute hepatocellular injury, cholestatic reactions, cholestatic hepatitis, fatty liver degeneration, transient increases in liver function tests[Ref]

Metabolic

Hypoglycemia in a nondiabetic patient has been reported.[Ref]

Common (1% to 10%): Increased blood LDH, increased blood glucose
Rare (0.01% to 0.1%): Decreased appetite, porphyria
Frequency not reported: Hypoglycemia, anorexia[Ref]

Psychiatric

Common (1% to 10%): Anxiety
Frequency not reported: Confusion, depression, hallucination

Hypersensitivity

Common (1% to 10%): Anaphylactic reaction (including angioedema, exacerbation of systemic lupus erythematosus, pericarditis, hypersensitivity, serum sickness, Henoch-Schonlein purpura, hypotension, dyspnea, tachycardia, peripheral edema, urticaria)
Frequency not reported: Hypersensitivity reactions (including urticaria, angioneurotic edema, anaphylactic shock, anaphylaxis, anaphylactoid reactions, anaphylactoid purpura, serum sickness, hypotension, pericarditis, exacerbation of systemic lupus erythematosus, dyspnea, peripheral edema, tachycardia)
Postmarketing reports: Mild allergic reactions[Ref]

Hematologic

Rare (0.01% to 0.1%): Hemolytic anemia, thrombocytopenia, neutropenia, eosinophilia
Frequency not reported: Increased prothrombin time, leukopenia, thrombocytopenic purpura[Ref]

Renal

Rare (0.01% to 0.1%): Increased BUN/blood urea (dose-related)
Frequency not reported: Acute renal failure[Ref]

Endocrine

The long-term use of tetracyclines has been associated with microscopic brown-black discoloration of the thyroid gland; abnormal thyroid function has not been reported.[Ref]

Rare (0.01% to 0.1%): Microscopic brown-black discoloration of the thyroid gland[Ref]

Ocular

Frequency not reported: Diplopia, papilledema, loss of vision (associated with drug-induced benign intracranial hypertension), conjunctivitis, periorbital edema[Ref]

Immunologic

Tetracyclines:
-Frequency not reported: Autoimmune syndromes

Some side effects of Acticlate may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Doxycycline Breastfeeding Warnings

Tetracyclines have been considered contraindicated during breastfeeding due to possible staining of infants' dental enamel or bone deposition of tetracyclines; however, a close review of available literature suggests harmful effects are unlikely with short-term use of this drug during lactation as milk levels are low and infant absorption is inhibited by the calcium in breast milk. According to some experts, this drug is compatible for short courses (e.g., 10 days) if alternative therapy is not appropriate; diarrhea may occur in the nursing infant. The extent of drug absorption by breastfed infants is unknown. Short-term use in lactating women is not explicitly contraindicated by most manufacturers, but the effects of prolonged drug exposure via breast milk are unknown. Long-term or repeat courses are not recommended during nursing as a theoretical precaution. Theoretical risks of dental staining and inhibition of bone growth in nursing infants are considered unlikely by most experts. After 2 oral doses (200 mg followed by 100 mg 12 hours later) in 15 nursing mothers, milk drug levels 3 and 24 hours after dosing averaged 0.77 mg/L (range: 0.4 to 1.4 mg/L) and 0.38 mg/L (range: 0.12 to 0.85 mg/L), respectively. This drug (100 mg/day) was given orally to 10 mothers. On day 2, milk drug levels 3 and 24 hours after dosing averaged 0.82 mg/L (range: 0.37 to 1.24 mg/L) and 0.46 mg/L (range: 0.3 to 0.91 mg/L), respectively. Using peak and trough milk level averages in this study, the estimated intake of an infant only fed breast milk averaged about 6% of the maternal weight-adjusted dose. Peak milk levels averaged 0.96 mg/L after a single 100 mg dose (n=3) and 1.8 mg/L after a single 200 mg dose (n=3). After 100 mg orally twice a day for 5 days, milk drug levels were about 3.6 mg/L. In another study, in the immediate postpartum period, peak milk levels were 0.6 mg/L after oral doses of 100 mg (n=3) and averaged 1.1 mg/L after 200 mg (n=11). After a single 200 mg dose (n=2), milk levels 2, 4, and 6 hours after dosing averaged 0.8, 0.7, and 0.4 mg/L, respectively.

LactMed: Short-term use is considered acceptable; as a precaution (theoretical), prolonged or repeat courses should be avoided throughout breastfeeding. -IV: The manufacturer makes no recommendation regarding use during lactation. -Oral: According to some authorities and manufacturers, a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother; according to other authorities and manufacturers, use is contraindicated. Use of the 40 mg capsule formulation is not recommended. Excreted into human milk: Yes Comments: -According to at least 1 manufacturer: Developmental and health benefits of breastfeeding should be considered as well as the mother's clinical need for the drug; potential side effects in the breastfed child due to the drug or the mother's underlying condition should be considered. -The effects in the nursing infant are unknown; the infant should be monitored for rash and possible effects on the gastrointestinal flora (e.g., diarrhea or candidiasis [thrush, diaper rash]). -Tetracycline, a related drug, is considered compatible with breastfeeding by the American Academy of Pediatrics.

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