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TETRACYCLINES

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Tetracyclines are a class of broad spectrum bacteriostatic antibiotics. Tetracyclines inhibit protein synthesis in susceptible organisms by preventing RNA translation.

Specific Substances

    A) CONSTITUENTS OF THE GROUP
    1) DEMECLOCYCLINE (synonym)
    2) DOXYCYCLINE (synonym)
    3) METHACYCLINE (synonym)
    4) MINOCYCLINE (synonym)
    5) OXYTETRACYCLINE (synonym)
    6) TETRACYCLINE (synonym)
    7) TETRACYCLINE I
    8) TETRACYCLINE II
    9) TETRADECIN (synonym)
    10) TETRAVERINE (synonym)
    11) DESCHLOROBIOMYCIN (synonym
    12) CYCLOMYCIN (synonym)
    13) TIGECYCLINE (synonym)
    14) T-125
    1.2.1) MOLECULAR FORMULA
    1) DOXYCYCLINE HYCLATE: (C22H24N2O8.HCl)2.C2H6O.H2O
    2) DOXYCYCLINE MONOHYDRATE: C22H24N2O8.H2O
    3) MINOCYCLINE HYDROCHLORIDE: C23H27N3O7.HCl
    4) TETRACYCLINE: C22H24N2O8.HCl
    5) TIGECYCLINE: C29H39N5O8

Available Forms Sources

    A) FORMS
    1) DEMECLOCYCLINE: tabs and caps (150, 300 mg)
    2) DOXYCYCLINE: tabs and caps (50, 100 mg), syrup and oral suspension (25 mg/5mL, 50 mg/5mL) and injectable (100, 200 mg)
    3) METHACYCLINE: capsules (100, 300 mg)
    4) MINOCYCLINE: tabs and caps (50, 100 mg) oral suspension (50 mg/5mL), injectable (100 mg)
    5) OXYTETRACYCLINE: tabs and caps (250 mg), injectable (50 mg/mL, 125 mg/mL)
    6) TETRACYCLINE: tabs and caps (100, 250, 500 mg), oral suspension (125 mg/5mL), injectable (100, 250, and 500 mg)
    7) TIGECYCLINE: each 5 mL glass vial contains 50 mg tigecycline a lyophilized powder for reconstitution

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Tetracyclines are used in the treatment of a wide variety of gram-negative and gram-positive infections.
    B) PHARMACOLOGY: Tetracyclines are bacteriostatic and exert their antimicrobial effects by inhibition of protein synthesis.
    C) EPIDEMIOLOGY: Exposure is relatively common. However, severe toxicity is not observed.
    D) WITH THERAPEUTIC USE
    1) ACUTE EFFECTS: COMMON: Nausea and vomiting with therapeutic use. Epigastric burning and ulceration may also occur. Skin hyperpigmentation may develop. Hypersensitivity reactions can develop with therapy in the form of various skin rashes along with more severe reactions including angioedema and anaphylaxis. Renal dysfunction, including elevated BUN, may occur due to the antianabolic activity of tetracyclines.
    a) DEMECLOCYCLINE: A diabetes insipidus syndrome has been reported following demeclocycline.
    2) CHRONIC EFFECTS: Chronic ingestion of therapeutic doses can cause discoloration and enamel defects in the teeth of the fetus if used after the 12th week of pregnancy or in infants during the first 6 to 8 months of life.
    E) WITH POISONING/EXPOSURE
    1) OVERDOSE: Severe toxicity following acute overdosage is unlikely.
    2) MILD TO MODERATE TOXICITY: Nausea and vomiting are common following overdose.
    3) SEVERE TOXICITY: Hypersensitivity reactions can develop with therapy in the form of various skin rashes along with more severe reactions including angioedema and anaphylaxis.
    0.2.7) NEUROLOGIC
    A) Headache, papilledema and benign intracranial hypertension have been reported.
    0.2.8) GASTROINTESTINAL
    A) WITH THERAPEUTIC USE
    1) Nausea, vomiting, epigastric burning, and abdominal discomfort have been noted.
    2) Tetracycline and doxycycline have been implicated in causing esophageal ulceration, but this is thought to be uncommon.
    0.2.9) HEPATIC
    A) WITH THERAPEUTIC USE
    1) Tetracycline and minocycline have been implicated in causing hepatotoxicity.
    2) Minocycline-induced autoimmune hepatitis has been observed in a young adult.
    0.2.10) GENITOURINARY
    A) WITH THERAPEUTIC USE
    1) Increased renal function tests, specifically BUN, may result following chronic or overdoses of tetracyclines, and in persons with pre-existing renal dysfunction.
    2) A decrease in urinary concentrating ability may follow large doses of tetracyclines.
    0.2.14) DERMATOLOGIC
    A) Skin hyperpigmentation has been reported.
    0.2.19) IMMUNOLOGIC
    A) WITH THERAPEUTIC USE
    1) Hypersensitivity reactions including skin rash, angioedema and anaphylaxis have been reported in sensitive individuals.
    2) A lupus-like syndrome has been reported in adolescents following minocycline therapy to treat acne.
    3) Eosinophilic pneumonia was reported following therapeutic administration of minocycline.
    0.2.20) REPRODUCTIVE
    A) Tetracyclines (demeclocycline, doxycycline, minocycline, tetracycline, and tigecycline) are classified as FDA pregnancy category D. Maternal ingestion of tetracyclines during pregnancy may cause tooth discoloration, enamel defects, and other congenital anomalies. Tetracyclines are excreted in human breast milk; however, the extent of absorption of tetracyclines by the breastfed infant is not known.
    0.2.21) CARCINOGENICITY
    A) MINOCYCLINE
    1) At the time of this review, the manufacturer dose not report any carcinogenic potential.
    0.2.22) OTHER
    A) CHRONIC: Black pigmentation of thyroid and bones and tooth discoloration in adults have been reported.

Laboratory Monitoring

    A) No specific lab work (CBC, electrolyte, urinalysis) is needed unless otherwise clinically indicated.
    B) Obtain a baseline CBC and assess renal function following a large overdose.
    C) Plasma tetracycline concentrations are not clinically useful.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Tetracyclines generally have a low order of toxicity. Treatment is symptomatic and supportive. For significant vomiting and/or diarrhea, treat dehydration with IV fluids as necessary.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. ANAPHYLAXIS: Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta adrenergic agonists, corticosteroids or epinephrine. Diphenhydramine: ADULT: 50 mg orally, IV, or IM initially, then 25 to 50 mg orally every 4 to 6 hours for 24 to 72 hours. CHILD: 1.25 mg/kg orally, IV, or IM initially, then 5 mg/kg/day orally in 4 divided doses for 24 to 72 hours. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.
    C) DECONTAMINATION
    1) PREHOSPITAL: Severe toxicity is unlikely, gastrointestinal decontamination is generally NOT required. DILUTION: Tetracycline and doxycycline have been implicated in causing esophageal ulcerations when taken therapeutically with minimal amounts of fluids. Immediately dilute with 4 to 8 ounces (120 to 240 mL) of water or milk (not to exceed 4 ounces or 120 mL in a child).
    2) HOSPITAL: Tetracyclines are generally of a low order of toxicity. In most cases, gastrointestinal decontamination will not be required. Antacids may be useful in managing gastric irritation.
    D) AIRWAY MANAGEMENT
    1) Airway support is unlikely to be necessary following mild to moderate exposure; airway management may be necessary in patients that develop severe anaphylaxis.
    E) ANTIDOTE
    1) None.
    F) ENHANCED ELIMINATION
    1) Hemodialysis and hemoperfusion are unlikely to be of value with these agents because of their high degree of protein binding. Tetracycline is not dialyzable.
    G) PATIENT DISPOSITION
    1) HOME CRITERIA: An asymptomatic child taking an inadvertent 1 to 2 tablets can likely be monitored at home, or an asymptomatic adult taking an inadvertent extra dose can be safely managed at home. Tetracycline and doxycycline have been implicated in causing esophageal ulcerations when taken therapeutically with minimal amounts of fluids. Immediately dilute with 4 to 8 ounces (120 to 240 mL) of water or milk (not to exceed 4 ounces or 120 mL in a child).
    2) OBSERVATION CRITERIA: Patients with a deliberate self-harm ingestion should be evaluated in a healthcare facility and monitored until symptoms resolve. Obtain a baseline CBC and renal and liver function following a significant exposure. Patients may be discharged to home once symptoms have resolved and laboratory studies are within normal limits.
    3) ADMISSION CRITERIA: Patients experiencing severe or persistent anaphylactic symptoms should be admitted for further monitoring and treatment as indicated.
    4) CONSULT CRITERIA: Contact a medical toxicologist or Poison Center for assistance in managing patients with severe toxicity or in whom the diagnosis is unclear. Patients with a deliberate self-harm ingestion should be evaluated by a mental health specialist.
    H) PITFALLS
    1) Patients with underlying or unknown renal insufficiency can be at risk to develop drug accumulation leading to possible liver toxicity.
    I) PHARMACOKINETICS
    1) TETRACYCLINES: These agents are readily absorbed, bound to plasma proteins in varying degrees. These agents are concentrated by the liver in the bile and are excreted in the urine and feces in high concentrations. Half-life for tetracycline is 6 to 10 hours in adults with normal renal function. OTHER AGENTS: DOXYCYCLINE: protein binding 60 to 90%; renal excretion is approximately 40 to 55% following an oral dose; and half-life is 10 to 20 hours in adults with normal renal function. MINOCYCLINE: protein binding 55 to 75%; 5 to 10% of a dose is recovered unchanged in the urine. Half-life is 10 to 20 hours in adults with normal renal function in patients taking demeclocycline/minocylcine.
    J) DIFFERENTIAL DIAGNOSIS
    1) Other agents that may produce anaphylaxis. Gastrointestinal irritation or esophagitis due to other agents such as NSAIDS or a combination of antibiotics and other drugs or alcohol.
    K) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting.
    L) Tetracyclines are generally of a low order of toxicity. In most cases gastrointestinal decontamination will not be required.

Range Of Toxicity

    A) TOXICITY: The minimal toxic or lethal dose is not well established in the literature. Severe toxicity following acute tetracycline overdose is unlikely.
    B) THERAPEUTIC DOSE: ADULT: ORAL: Tetracycline: 1 to 2 g/day; Doxycycline: 100 to 200 mg/day (up to 400 mg/day for some indications); Minocycline: 200 mg/day; Demeclocycline: 600 mg/day. PEDIATRIC: ORAL: Tetracycline (older than 8 years): 25 to 50 mg/kg/day, up to 3 g/day; Demeclocycline: 6.6 to 13.2 mg/kg/day; max 600 mg/day; Doxycycline (older than 8 years): 4 to 8 mg/kg/day, usually up to 200 mg/day (up to 400 mg/day for some indications); Minocycline (older than 8 years): 4 mg/kg initial dose, then 2 mg/kg every 12 hours.

Clinical Effects

Summary Of Exposure

    A) USES: Tetracyclines are used in the treatment of a wide variety of gram-negative and gram-positive infections.
    B) PHARMACOLOGY: Tetracyclines are bacteriostatic and exert their antimicrobial effects by inhibition of protein synthesis.
    C) EPIDEMIOLOGY: Exposure is relatively common. However, severe toxicity is not observed.
    D) WITH THERAPEUTIC USE
    1) ACUTE EFFECTS: COMMON: Nausea and vomiting with therapeutic use. Epigastric burning and ulceration may also occur. Skin hyperpigmentation may develop. Hypersensitivity reactions can develop with therapy in the form of various skin rashes along with more severe reactions including angioedema and anaphylaxis. Renal dysfunction, including elevated BUN, may occur due to the antianabolic activity of tetracyclines.
    a) DEMECLOCYCLINE: A diabetes insipidus syndrome has been reported following demeclocycline.
    2) CHRONIC EFFECTS: Chronic ingestion of therapeutic doses can cause discoloration and enamel defects in the teeth of the fetus if used after the 12th week of pregnancy or in infants during the first 6 to 8 months of life.
    E) WITH POISONING/EXPOSURE
    1) OVERDOSE: Severe toxicity following acute overdosage is unlikely.
    2) MILD TO MODERATE TOXICITY: Nausea and vomiting are common following overdose.
    3) SEVERE TOXICITY: Hypersensitivity reactions can develop with therapy in the form of various skin rashes along with more severe reactions including angioedema and anaphylaxis.

Heent

    3.4.3) EYES
    A) WITH THERAPEUTIC USE
    1) PAPILLEDEMA
    a) Papilledema has been reported following a short course of tetracycline therapy for bronchitis (Walters & Gubbay, 1981).
    b) CASE REPORT: A 19-year-old woman developed severe bilateral papilledema with visual field loss approximately two weeks after beginning minocycline therapy for treatment of acne. Despite disappearance of the papilledema following cessation of minocycline therapy and administration of acetazolamide, the patient experienced permanent visual damage (Shiri & Amichai, 1997).

Neurologic

    3.7.1) SUMMARY
    A) Headache, papilledema and benign intracranial hypertension have been reported.
    3.7.2) CLINICAL EFFECTS
    A) HEADACHE
    1) WITH THERAPEUTIC USE
    a) Headache and benign intracranial hypertension have been reported following chronic administration of tetracycline for acne (Walters & Gubbay, 1981; Pierson et al, 1981; Shiri & Amichai, 1997).
    B) OPTIC DISC EDEMA
    1) WITH THERAPEUTIC USE
    a) Papilledema has been reported following a short course of tetracycline therapy for bronchitis (Walters & Gubbay, 1981).

Gastrointestinal

    3.8.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Nausea, vomiting, epigastric burning, and abdominal discomfort have been noted.
    2) Tetracycline and doxycycline have been implicated in causing esophageal ulceration, but this is thought to be uncommon.
    3.8.2) CLINICAL EFFECTS
    A) GASTRITIS
    1) WITH THERAPEUTIC USE
    a) Acute ingestion of large doses of tetracyclines can cause toxic effects manifested as gastrointestinal irritation, epigastric burning and distress, abdominal discomfort, nausea and vomiting. Nausea and vomiting are also seen with therapeutic doses (Bryant et al, 1987).
    B) ULCER OF ESOPHAGUS
    1) WITH THERAPEUTIC USE
    a) Tetracycline and doxycycline have been implicated in causing esophageal ulceration and esophagitis (Daunt et al, 1985; Amendola & Spera, 1985; Palmer et al, 1999).
    1) In a report of adverse drug reactions to the Australian Adverse Drug Reactions Advisory Committee, 41 cases of esophageal injury were related to doxycycline, and no cases were reported for minocycline (ADRAC, 1988)
    c) CASE REPORT: Cummin & Hangartner (1990) reported a case of esophago-atrial fistula associated with tetracycline administration. An esophageal ulcer was found.
    d) CASE REPORT: Esophagitis was reported in two children who developed chest pain shortly after ingestion of doxycycline. An endoscopy, performed on one of the children, revealed ulcerations in the esophagus. Both children gradually recovered after discontinuation of doxycycline therapy (Palmer et al, 1999).
    C) PANCREATITIS
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: Pancreatitis, characterized by moderate to severe epigastric pain with elevated serum amylase and lipase levels, was reported in two cystic fibrosis patients within one week of beginning minocycline therapy. Both patients completely recovered following minocycline cessation and with supportive care (Boyle, 2001).

Hepatic

    3.9.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Tetracycline and minocycline have been implicated in causing hepatotoxicity.
    2) Minocycline-induced autoimmune hepatitis has been observed in a young adult.
    3.9.2) CLINICAL EFFECTS
    A) LIVER DAMAGE
    1) WITH THERAPEUTIC USE
    a) Tetracycline and minocycline (rarely) have been implicated in producing hepatotoxicity, consisting of clinical symptoms (nausea, vomiting, abdominal pain, mild jaundice) and elevated liver function tests (Burette et al, 1984).
    b) Autoimmune hepatitis and fulminant hepatic failure, requiring liver transplantation, have been associated with long-term minocycline therapy (Pohle et al, 2000; Teitelbaum et al, 1998).
    c) In one patient, hepatitis resolved following administration of immunosuppressive agents and discontinuation of minocycline treatment (Teitelbaum et al, 1998).
    B) AUTOIMMUNE HEPATITIS
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: A 20-year-old healthy woman with no known high-risk factors developed autoimmune hepatitis. She presented with jaundice, fatigue and malaise after taking minocycline (100 mg daily) for one year. Upon admission, liver function studies were as follows: aspartate aminotransferase 1095 Units/L (normal: 12-40), alkaline phosphatase 178 Units/L (normal: 25-90) and gamma-glutamyltransferase 198 Units/L (normal: 7-42). Antinuclear antibodies were strongly positive (1:2560), along with negative liver autoantibodies and negative viral serology. A liver biopsy was not performed due to an improvement in both signs and symptoms with drug cessation. The patient was discharged 2 weeks after admission with complete resolution of symptoms; rechallenge was not done (Ford & Dillon, 2008).

Genitourinary

    3.10.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Increased renal function tests, specifically BUN, may result following chronic or overdoses of tetracyclines, and in persons with pre-existing renal dysfunction.
    2) A decrease in urinary concentrating ability may follow large doses of tetracyclines.
    3.10.2) CLINICAL EFFECTS
    A) TOXIC NEPHROPATHY
    1) WITH THERAPEUTIC USE
    a) Tetracyclines are associated with increased BUN due to their antianabolic activity. Persons with pre-existing renal dysfunction are more prone to the adverse renal effects. Rarely, tetracyclines may cause allergic acute interstitial nephritis (reviewed in Goldfrank, 1998) (Walker et al, 1979)
    b) FANCONI-LIKE SYNDROME, characterized by polydipsia, polyuria, glycosuria, acidosis, aminoaciduria, proteinuria, and hypokalemia, has occurred following ingestion of degraded tetracycline.
    1) Earlier formulations of tetracycline contained an acid excipient that caused the degradation of the antibiotic during storage. Discontinuation of this tetracycline formulation has caused the syndrome to become a rare occurrence (Frimpter et al, 1963).
    c) Seven patients developed nephrotoxicity with increased BUN and serum creatinine levels several days after beginning tetracycline therapy. Six of the 7 patients had pre-existing renal dysfunction. One patient died and 3 of the 6 remaining patients required peritoneal dialysis (Phillips et al, 1974).
    B) DIABETES INSIPIDUS
    1) WITH THERAPEUTIC USE
    a) A diabetes insipidus syndrome after demeclocycline is thought to be dose-dependent, nephrogenic, and reversible.
    b) Decrease in urinary concentrating ability may also follow large doses of other tetracyclines (Riond & Riviere, 1988).

Dermatologic

    3.14.1) SUMMARY
    A) Skin hyperpigmentation has been reported.
    3.14.2) CLINICAL EFFECTS
    A) DISCOLORATION OF SKIN
    1) WITH THERAPEUTIC USE
    a) Skin hyperpigmentation consisting of either focal blue-gray pigmentation at sites of either prior cutaneous inflammation or normal skin of the legs, or diffuse dark-gray discoloration of sun exposed areas has been reported (Gordon et al, 1985; Basler, 1985).
    b) CASE REPORT: An adult developed generalized bluish tinge of the skin, in particular the cheeks, after taking minocycline (long term therapy of 100 mg orally twice daily for several years) or acne and rosacea (Zuckerman et al, 2012).
    c) CASE REPORT: A woman developed bluish discoloration of the oral mucosa, sclerae, ears and teeth following chronic use (20 years) of minocycline use for acne and/or rosacea (Johnston, 2013).

Immunologic

    3.19.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Hypersensitivity reactions including skin rash, angioedema and anaphylaxis have been reported in sensitive individuals.
    2) A lupus-like syndrome has been reported in adolescents following minocycline therapy to treat acne.
    3) Eosinophilic pneumonia was reported following therapeutic administration of minocycline.
    3.19.2) CLINICAL EFFECTS
    A) ACUTE ALLERGIC REACTION
    1) WITH THERAPEUTIC USE
    a) Hypersensitivity reactions occur in the form of various skin rashes along with more severe reactions including angioedema and anaphylaxis (Riond & Riviere, 1988)
    b) CASE REPORT: A 39-year-old woman presented with a 10-day history of asthenia, dyspnea, and chest pain. Medications prior to presentation included minocycline 50 mg twice daily for acne (begun 1 month earlier) and lorazepam taken for several years. Physical exam showed jugular distension and hepatomegaly. Lab analysis showed eosinophilia, elevated liver enzyme levels, and an elevated C- reactive protein. An ECG showed sinus tachycardia and first-degree AV block and an echocardiography revealed normal left- and right-ventricular function with pericardial effusion. The patient discontinued minocycline therapy and, 12 days later, her symptoms resolved with a normalization of lab values (Christe et al, 2000). It was speculated that the pericardial effusion, eosinophilia, and elevated liver enzyme levels were due to a minocycline-induced hypersensitivity reaction.
    B) DRUG-INDUCED LUPUS ERYTHEMATOSUS
    1) WITH THERAPEUTIC USE
    a) A lupus-like syndrome, consisting of fevers, fatigue, and diffuse arthralgias, was reported in 5 adolescent girls during long-term minocycline therapy for treatment of acne. Four of the 5 patients showed positive antinuclear antibodies and 2 patients showed positive antineutrophil cytoplasmic antibodies. The patients recovered following discontinuation of minocycline therapy, although there was a recurrence of symptoms in one patient upon rechallenge with minocycline (Akin et al, 1998).
    C) DRUG INTERACTION
    1) WITH THERAPEUTIC USE
    a) LOFFLER'S SYNDROME
    1) CASE REPORT: A 46-year-old man developed fever, chills, fatigue, dry cough, and progressive dyspnea approximately 2 weeks after beginning minocycline therapy. Lab results revealed eosinophilia and a chest radiograph showed pulmonary infiltrates. Three months after the onset of the pneumonia, a mast cell degranulation test for minocycline was positive in the patient, indicating that the eosinophilic pneumonia may be due to an immediate-type hypersensitivity reaction (Bentur et al, 1997).

Reproductive

    3.20.1) SUMMARY
    A) Tetracyclines (demeclocycline, doxycycline, minocycline, tetracycline, and tigecycline) are classified as FDA pregnancy category D. Maternal ingestion of tetracyclines during pregnancy may cause tooth discoloration, enamel defects, and other congenital anomalies. Tetracyclines are excreted in human breast milk; however, the extent of absorption of tetracyclines by the breastfed infant is not known.
    3.20.2) TERATOGENICITY
    A) ANIMAL STUDIES
    1) TIGECYCLINE
    a) RATS and RABBITS - In animal studies, radiolabeled drug crossed the placenta and was detected in fetal tissue, including fetal bony structures. At systemic exposures 5 and 1 times the human exposure equivalent to the human daily dose based on AUC in rats and rabbits, respectively, tigecycline caused an increase in the incidence of minor skeletal anomalies (delays in bone ossification) (Prod Info TYGACIL(R) injection, 2008).
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects of exposure to tigecycline during pregnancy in humans (Prod Info TYGACIL(R) injection, 2008)
    B) PREGNANCY CATEGORY
    1) The manufacturers have classified demeclocycline, doxycycline, minocycline, tetracycline, and tigecycline as FDA pregnancy category D (Prod Info TYGACIL(R) injection, 2008; Prod Info doxycycline oral tablets, 2006; Prod Info MINOCIN(R) oral capsules, 2006; Prod Info demeclocycline hcl oral tablets, 2004; Prod Info SUMYCIN(R) oral tablets, 2004).
    C) TOOTH DISCOLORATION
    1) Tetracycline use during tooth development (the last half of pregnancy) may cause permanent yellow-gray-brown discoloration of the teeth (Prod Info TYGACIL(R) injection, 2008; Prod Info SUMYCIN(R) oral tablets, 2004).
    D) MATERNAL HEPATOTOXICITY
    1) Pregnant women who receive tetracycline in high doses (greater than 2 g IV) may be more susceptible to developing tetracycline-associated maternal hepatotoxicity, which is a rare but serious syndrome that may result in stillborn or premature birth due to maternal pathology (Prod Info PYLERA(R) oral capsules, 2012).
    E) ANIMAL STUDIES
    1) TIGECYCLINE
    a) RATS and RABBITS - In animal studies, radiolabeled drug crossed the placenta and was detected in fetal tissue, including fetal bony structures. At systemic exposures 5 and 1 times the human exposure equivalent to the human daily dose based on AUC in rats and rabbits, respectively, tigecycline caused slightly reduced fetal weights. At maternotoxic doses in rabbits (exposures equivalent to the human daily dose), there was an increased incidence of fetal loss. Studies of tigecycline in rats have also shown bone discoloration (Prod Info TYGACIL(R) injection, 2008).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) Tetracyclines are excreted in human milk; however, the extent of absorption of tetracyclines by the breastfed infant is not known (Prod Info doxycycline oral tablets, 2006).
    B) ANIMAL STUDIES
    1) TIGECYCLINE
    a) Radiolabeled tigecycline shows that the drug is excreted into the milk of lactating rats. However, due to its limited oral bioavailability, there was little or no systemic exposure detected in the nursing pups (Prod Info TYGACIL(R) injection, 2008).
    3.20.5) FERTILITY
    A) ANIMAL STUDIES
    1) TIGECYCLINE
    a) RATS - Mating and fertility were not affected when rats were given tigecycline at exposures up to 5 times the human daily dose based on AUC. There were also no effects on ovaries or estrous cycles when female rats were given tigecycline at exposures up to 5 times the human daily dose (Prod Info TYGACIL(R) injection, 2008).

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) MINOCYCLINE
    1) At the time of this review, the manufacturer dose not report any carcinogenic potential.
    3.21.4) ANIMAL STUDIES
    A) THYROID ADENOMAS AND CARCINOMAS
    1) Follicular cell tumors of the thyroid gland, including increased incidences of adenomas, carcinomas, and the combined incidence of adenomas and carcinomas in males, and adenomas and the combined incidence of adenomas and carcinomas in females, was reported in rats administered oral minocycline hydrochloride at doses up to 200 mg/kg/day for up to 104 weeks in a carcinogenicity study (Prod Info SOLODYN(R) oral extended release tablets, 2013).
    B) LACK OF EFFECT
    1) MINOCYCLINE
    a) No significantly increased incidence of neoplasms was reported in male and female mice administered oral minocycline hydrochloride at doses up to 150 mg/kg/day for up to 104 weeks in a carcinogenicity study (Prod Info SOLODYN(R) oral extended release tablets, 2013).

Genotoxicity

    A) MINOCYCLINE
    1) There was no evidence of genotoxicity or mutagenicity in the following tests: the Ames bacterial mutation assay, Chinese hamster ovary/hypoxanthine-guanine phosphoribosyl transferase (HGPRT) mammalian cell assay in the presence or absence of metabolic activation, in vitro assay in human peripheral blood lymphocytes, or an in vivo mouse micronucleus test (Prod Info SOLODYN(R) oral extended release tablets, 2013).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No specific lab work (CBC, electrolyte, urinalysis) is needed unless otherwise clinically indicated.
    B) Obtain a baseline CBC and assess renal function following a large overdose.
    C) Plasma tetracycline concentrations are not clinically useful.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) Hematopoietic, renal and hepatic monitoring steps should be obtained periodically, if prolonged therapy is necessary (Prod Info tetracycline HCl oral capsule, 2006).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients experiencing severe or persistent anaphylactic symptoms should be admitted for further treatment and monitoring as indicated.
    6.3.1.2) HOME CRITERIA/ORAL
    A) An asymptomatic child taking an inadvertent 1 to 2 tablets can likely be monitored at home, or an asymptomatic adult taking an inadvertent extra dose can be safely managed at home. Tetracycline and doxycycline have been implicated in causing esophageal ulcerations when taken therapeutically with minimal amounts of fluids. Immediately dilute with 4 to 8 ounces (120 to 240 mL) of water or milk (not to exceed 4 ounces or 120 mL in a child).
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Contact a medical toxicologist or Poison Center for assistance in managing patients with severe toxicity or in whom the diagnosis is unclear. Patients with a deliberate self-harm ingestion should be evaluated by a mental health specialist.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with a deliberate self-harm ingestion should be evaluated in a healthcare facility and monitored until symptoms resolve. Obtain a baseline CBC and renal and liver function following a significant exposure. Patients may be discharged to home once symptoms have resolved and laboratory studies are within normal limits.

Monitoring

    A) No specific lab work (CBC, electrolyte, urinalysis) is needed unless otherwise clinically indicated.
    B) Obtain a baseline CBC and assess renal function following a large overdose.
    C) Plasma tetracycline concentrations are not clinically useful.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) Severe toxicity is unlikely after ingestion. Gastrointestinal decontamination is generally NOT required.
    B) DILUTION
    1) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Tetracyclines are generally of a low order of toxicity. In most cases gastrointestinal decontamination will not be required.
    B) DILUTION
    1) Tetracycline and doxycycline have been implicated in causing esophageal ulcerations when taken therapeutically with minimal amounts of fluids.
    2) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).
    6.5.3) TREATMENT
    A) SUPPORT
    1) Treatment is symptomatic and supportive.
    2) Antacids may be useful in treating gastric irritation.
    B) MONITORING OF PATIENT
    1) No specific lab work (CBC, electrolyte, urinalysis) is needed unless otherwise clinically indicated following a minor exposure.
    2) Monitor renal function after very large ingestion or in patients with baseline impaired renal function.
    3) Plasma tetracycline concentrations are not clinically useful.
    C) ANAPHYLAXIS
    1) SUMMARY
    a) Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta adrenergic agonists, corticosteroids or epinephrine. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.
    2) BRONCHOSPASM
    a) ALBUTEROL
    1) ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007). CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 mg/kg (up to 10 mg) every 1 to 4 hours as needed, or 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    3) CORTICOSTEROIDS
    a) Consider systemic corticosteroids in patients with significant bronchospasm.
    b) PREDNISONE: ADULT: 40 to 80 milligrams/day. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 to 2 divided doses divided twice daily (National Heart,Lung,and Blood Institute, 2007).
    4) MILD CASES
    a) DIPHENHYDRAMINE
    1) SUMMARY: Oral diphenhydramine, as well as other H1 antihistamines can be used as indicated (Lieberman et al, 2010).
    2) ADULT: 50 milligrams orally, or 10 to 50 mg intravenously at a rate not to exceed 25 mg/min or may be given by deep intramuscular injection. A total of 100 mg may be administered if needed. Maximum daily dosage is 400 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    3) CHILD: 5 mg/kg/24 hours or 150 mg/m(2)/24 hours. Divided into 4 doses, administered intravenously at a rate not exceeding 25 mg/min or by deep intramuscular injection. Maximum daily dosage is 300 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    5) MODERATE CASES
    a) EPINEPHRINE: INJECTABLE SOLUTION: It should be administered early in patients by IM injection. Using a 1:1000 (1 mg/mL) solution of epinephrine. Initial Dose: 0.01 mg/kg intramuscularly with a maximum dose of 0.5 mg in adults and 0.3 mg in children. The dose may be repeated every 5 to 15 minutes, if no clinical improvement. Most patients respond to 1 or 2 doses (Nowak & Macias, 2014).
    6) SEVERE CASES
    a) EPINEPHRINE
    1) INTRAVENOUS BOLUS: ADULT: 1 mg intravenously as a 1:10,000 (0.1 mg/mL) solution; CHILD: 0.01 mL/kg intravenously to a maximum single dose of 1 mg given as a 1:10,000 (0.1 mg/mL) solution. It can be repeated every 3 to 5 minutes as needed. The dose can also be given by the intraosseous route if IV access cannot be established (Lieberman et al, 2015). ALTERNATIVE ROUTE: ENDOTRACHEAL ADMINISTRATION: If IV/IO access is unavailable. DOSE: ADULT: Administer 2 to 2.5 mg of 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube. CHILD: DOSE: 0.1 mg/kg to a maximum of 2.5 mg administered as a 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube (Lieberman et al, 2015).
    2) INTRAVENOUS INFUSION: Intravenous administration may be considered in patients poorly responsive to IM or SubQ epinephrine. An epinephrine infusion may be prepared by adding 1 mg (1 mL of 1:1000 (1 mg/mL) solution) to 250 mL D5W, yielding a concentration of 4 mcg/mL, and infuse this solution IV at a rate of 1 mcg/min to 10 mcg/min (maximum rate). CHILD: A dosage of 0.01 mg/kg (0.1 mL/kg of a 1:10,000 (0.1 mg/mL) solution up to 10 mcg/min (maximum dose 0.3 mg) is recommended for children (Lieberman et al, 2010). Careful titration of a continuous infusion of IV epinephrine, based on the severity of the reaction, along with a crystalloid infusion can be considered in the treatment of anaphylactic shock. It appears to be a reasonable alternative to IV boluses, if the patient is not in cardiac arrest (Vanden Hoek,TLet al,null).
    7) AIRWAY MANAGEMENT
    a) OXYGEN: 5 to 10 liters/minute via high flow mask.
    b) INTUBATION: Perform early if any stridor or signs of airway obstruction.
    c) CRICOTHYROTOMY: Use if unable to intubate with complete airway obstruction (Vanden Hoek,TLet al,null).
    d) BRONCHODILATORS are recommended for mild to severe bronchospasm.
    e) ALBUTEROL: ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007).
    f) ALBUTEROL: CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    8) MONITORING
    a) CARDIAC MONITOR: All complicated cases.
    b) IV ACCESS: Routine in all complicated cases.
    9) HYPOTENSION
    a) If hypotensive give 500 to 2000 milliliters crystalloid initially (20 milliliters/kilogram in children) and titrate to desired effect (stabilization of vital signs, mentation, urine output); adults may require up to 6 to 10 L/24 hours. Central venous or pulmonary artery pressure monitoring is recommended in patients with persistent hypotension.
    1) VASOPRESSORS: Should be used in refractory cases unresponsive to repeated doses of epinephrine and after vigorous intravenous crystalloid rehydration (Lieberman et al, 2010).
    2) DOPAMINE: Initial Dose: 2 to 20 micrograms/kilogram/minute intravenously; titrate to maintain systolic blood pressure greater than 90 mm Hg (Lieberman et al, 2010).
    10) H1 and H2 ANTIHISTAMINES
    a) SUMMARY: Antihistamines are second-line therapy and are used as supportive therapy and should not be used in place of epinephrine (Lieberman et al, 2010).
    1) DIPHENHYDRAMINE: ADULT: 25 to 50 milligrams via a slow intravenous infusion or IM. PEDIATRIC: 1 milligram/kilogram via slow intravenous infusion or IM up to 50 mg in children (Lieberman et al, 2010).
    b) RANITIDINE: ADULT: 1 mg/kg parenterally; CHILD: 12.5 to 50 mg parenterally. If the intravenous route is used, ranitidine should be infused over 10 to 15 minutes or diluted in 5% dextrose to a volume of 20 mL and injected over 5 minutes (Lieberman et al, 2010).
    c) Oral diphenhydramine, as well as other H1 antihistamines, can also be used as indicated (Lieberman et al, 2010).
    11) DYSRHYTHMIAS
    a) Dysrhythmias and cardiac dysfunction may occur primarily or iatrogenically as a result of pharmacologic treatment (epinephrine) (Vanden Hoek,TLet al,null). Monitor and correct serum electrolytes, oxygenation and tissue perfusion. Treat with antiarrhythmic agents as indicated.
    12) OTHER THERAPIES
    a) There have been a few reports of patients with anaphylaxis, with or without cardiac arrest, that have responded to vasopressin therapy that did not respond to standard therapy. Although there are no randomized controlled trials, other alternative vasoactive therapies (ie, vasopressin, norepinephrine, methoxamine, and metaraminol) may be considered in patients in cardiac arrest secondary to anaphylaxis that do not respond to epinephrine (Vanden Hoek,TLet al,null).

Enhanced Elimination

    A) SUMMARY
    1) Hemodialysis and hemoperfusion are unlikely to be of value with these agents because of their high degree of protein binding. Tetracycline is not dialyzable.

Range Of Toxicity

Summary

    A) TOXICITY: The minimal toxic or lethal dose is not well established in the literature. Severe toxicity following acute tetracycline overdose is unlikely.
    B) THERAPEUTIC DOSE: ADULT: ORAL: Tetracycline: 1 to 2 g/day; Doxycycline: 100 to 200 mg/day (up to 400 mg/day for some indications); Minocycline: 200 mg/day; Demeclocycline: 600 mg/day. PEDIATRIC: ORAL: Tetracycline (older than 8 years): 25 to 50 mg/kg/day, up to 3 g/day; Demeclocycline: 6.6 to 13.2 mg/kg/day; max 600 mg/day; Doxycycline (older than 8 years): 4 to 8 mg/kg/day, usually up to 200 mg/day (up to 400 mg/day for some indications); Minocycline (older than 8 years): 4 mg/kg initial dose, then 2 mg/kg every 12 hours.

Therapeutic Dose

    7.2.1) ADULT
    A) SPECIFIC SUBSTANCE
    1) DOXYCYCLINE
    a) ADULT: Usual dose: 100 mg ORALLY every 12 hours (Prod Info doxycycline oral tablets, 2006a).
    2) MINOCYCLINE
    a) ADULT: Usual initial dose is 200 mg ORALLY; followed by 100 mg ORALLY every 12 hours (Prod Info MINOCIN(R) oral capsules, 2006).
    b) EXTENDED-RELEASE CAPSULE
    1) ADULT: Usual dose for extended-release capsules is approximately 1 mg/kg ORALLY once daily for 12 weeks (Prod Info XIMINO oral extended-release capsules, 2012; Prod Info SOLODYN(R) Extended-release oral tablets, 2010).
    c) IV INJECTION
    1) ADULT: Initial dose is 200 mg IV followed by 100 mg IV infused over 60 minutes every 12 hours; MAX 400 mg IV in 24 hours (Prod Info MINOCIN(R) intravenous injection, 2015).
    2) IV administration is only recommended when oral therapy is not adequate or tolerated; switch to oral therapy as soon as possible to avoid thrombophlebitis (Prod Info MINOCIN(R) intravenous injection, 2015).
    3) OXYTETRACYCLINE
    a) ADULT: Usual daily dose is 250 mg administered once every 24 hours or 300 mg given in divided doses at 8 to 12 hour intervals (Prod Info TERRAMYCIN(R) ophthalmic ointment, 2003).
    4) TETRACYCLINE HYDROCHLORIDE
    a) ADULT: Usual daily dose is 1 to 2 g; Mild to moderate infections: 50 mg twice daily or 250 mg four times daily; Severe infections: 500 mg four times daily may be necessary (Prod Info SUMYCIN(R) oral tablets, 2004).
    5) TIGECYCLINE
    a) The recommended initial IV dose is 100 mg administered over 30 to 60 minutes, followed by 50 mg every 12 hours for up to 14 days (Prod Info TYGACIL(R) intravenous injection, 2013).
    7.2.2) PEDIATRIC
    A) SPECIFIC SUBSTANCE
    1) DOXYCYCLINE CALCIUM
    a) CHILDREN GREATER THAN 8 YEARS OF AGE: The recommended dose for children weighing 45 kg or less is 4.4 mg per kg of body weight divided into 2 doses on the first day of treatment, followed by 2.2 mg per kg of body weight given as a single daily dose or divided into 2 doses on subsequent days. For more severe infections, up to 4.4 mg per kg of body weight may be given (Prod Info Vibramycin(R) Calcium oral suspension syrup, 2011).
    b) CHILDREN over 45 kg: Administer the usual adult dose (Prod Info Vibramycin(R) Calcium oral suspension syrup, 2011).
    2) MINOCYCLINE
    a) CHILDREN OLDER THAN 8 YEARS OF AGE: Usual dose is 4 mg/kg/dose administered in 1 dose up to 200 mg/day in 2 divided doses (Prod Info MINOCIN(R) oral capsules, 2006).
    b) EXTENDED-RELEASE CAPSULE
    1) CHILDREN 12 YEARS OF AGE AND OLDER: Usual dose for extended-release capsules: Approximately 1 mg/kg ORALLY once daily for 12 weeks (Prod Info XIMINO oral extended-release capsules, 2012; Prod Info SOLODYN(R) Extended-release oral tablets, 2010).
    c) IV INJECTION
    1) CHILDREN OLDER THAN 8 YEARS OF AGE: Initial dose is 4 mg/kg IV followed by 2 mg/kg IV infused over 60 minutes every 12 hours; not to exceed the usual adult dose (Prod Info MINOCIN(R) intravenous injection, 2015).
    2) IV administration is only recommended when oral therapy is not adequate or tolerated; switch to oral therapy as soon as possible to avoid thrombophlebitis (Prod Info MINOCIN(R) intravenous injection, 2015).
    3) OXYTETRACYCLINE
    a) CHILDREN GREATER THAN 8 YEARS OF AGE: 15 to 25 mg/kg body weight up to a maximum of 250 mg per single daily intramuscular injection. Dosage should be divided and given at 8 to 12 hour intervals administered in once daily or in 3 divided doses (Prod Info TERRAMYCIN(R) ophthalmic ointment, 2003).
    4) TETRACYCLINE HYDROCHLORIDE
    a) CHILDREN GREATER THAN 8 YEARS OF AGE: Bacterial Infections: Oral: 25 to 50 mg/kg/day ORALLY, administered in 4 divided doses (Prod Info SUMYCIN(R) oral tablets, 2004).
    5) TIGECYCLINE
    a) CHILDREN BETWEEN 8 AND 11 YEARS OF AGE: Tigecycline should not be used in pediatric patients unless no alternative treatment is available. The suggested IV dose is 1.2 mg/kg every 12 hours. MAXIMUM DOSE: 50 mg every 12 hours (Prod Info TYGACIL(R) intravenous injection, 2013).
    b) CHILDREN BETWEEN 12 AND 17 YEARS OF AGE: Tigecycline should not be used in pediatric patients unless no alternative treatment is available. The suggested IV dose is 50 mg every 12 hours (Prod Info TYGACIL(R) intravenous injection, 2013).

Maximum Tolerated Exposure

    A) SUMMARY
    1) Tetracyclines are normally not toxic in acute ingestions, although anaphylactic reactions have occurred with as little as 250 mg and benign intracranial hypertension with as little as 1 gram.

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Tetracyclines are a broad spectrum bacteriostatic antibiotic.
    1) They are effective against rickettsia, spirochetes, mycoplasma, Bedsonia agents and susceptible strains of staphylococci, pneumococci, alpha and beta hemolytic streptococci, non-hemolytic streptococci and gram negative rods.
    B) The tetracyclines inhibit protein synthesis in susceptible organisms by preventing RNA translation. As chelating agents they interfere with calcium in bone and teeth.

Physicochemical

Physical Characteristics

    A) DOXYCYCLINE is a light yellow, crystalline powder that has a high degree of lipoid solubility and a low affinity for calcium binding (Prod Info Vibramycin(R) Monohydrate oral suspension, 2014; Prod Info DOXY 100(TM) intravenous injection lyophilized powder for solution, 2013).
    B) DOXYCYCLINE HYCLATE is a yellowish, crystalline powder that is soluble in water and chars at 201 degrees C without melting (Prod Info DOXY 100(TM) intravenous injection lyophilized powder for solution, 2013).
    C) DOXYCYCLINE MONOHYDRATE is very slightly soluble in water (Prod Info Vibramycin(R) Monohydrate oral suspension, 2014).
    D) MINOCYCLINE HYDROCHLORIDE is a yellow to amber lyophilized powder for IV infusion (Prod Info MINOCIN(R) intravenous injection, 2015).
    E) TETRACYCLINE is an odorless, yellow, crystalline powder that is stable in air, but strong sunlight causes it to darken. It is freely soluble in dilute acid and in alkali hydroxide solutions; very slightly soluble in water; sparingly soluble in alcohol; and practically insoluble in chloroform and in ether. Potency is affected in solutions with pH below 2 and rapid destruction occurs in alkali hydroxide solutions (Prod Info tetracycline HCl oral capsules, 2013).
    F) TIGECYCLINE is an orange lyophilized powder or cake for IV infusion (Prod Info TYGACIL(R) intravenous injection, 2014).

Ph

    A) DOXYCYCLINE HYCLATE: 1.8 to 3.3 (reconstituted) (Prod Info DOXY 100(TM) intravenous injection lyophilized powder for solution, 2013)
    B) MINOCYCLINE HYDROCHLORIDE: 4.5 to 5 (reconstituted); 4.5 to 6 (diluted solution) (Prod Info MINOCIN(R) intravenous injection, 2015)

Molecular Weight

    A) DOXYCYCLINE HYCLATE: 1025.89 (Prod Info DOXY 100(TM) intravenous injection lyophilized powder for solution, 2013)
    B) DOXYCYCLINE MONOHYDRATE: 462.46 (Prod Info Vibramycin(R) Monohydrate oral suspension, 2014)
    C) MINOCYCLINE HYDROCHLORIDE: 493.94 (Prod Info MINOCIN(R) intravenous injection, 2015)
    D) TETRACYCLINE: 480.9 (Prod Info tetracycline HCl oral capsules, 2013)
    E) TIGECYCLINE: 585.65 (Prod Info TYGACIL(R) intravenous injection, 2014)

Animal Toxicology

Clinical Effects

    11.1.2) BOVINE/CATTLE
    A) A cow given a long-acting oxytetracycline (16 grams), then 26 grams of oxytetracycline daily for 3 days developed renal dysfunction with tubular damage (Vaala et al, 1987).

References

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