NDC 72336-596 Lymepak

Doxycycline Hyclate

NDC Product Code 72336-596

NDC CODE: 72336-596

Proprietary Name: Lymepak What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Doxycycline Hyclate What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Drug Use Information

Drug Use Information
The drug use information is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate. This information is not individual medical advice and does not substitute for the advice of a health care professional. Always ask a health care professional for complete information about this product and your specific health needs.

  • This medication is used to treat a wide variety of bacterial infections, including those that cause acne. This medication is also used to prevent malaria. This medication is known as a tetracycline antibiotic. It works by stopping the growth of bacteria. This antibiotic treats only bacterial infections. It will not work for viral infections (such as common cold, flu). Using any antibiotic when it is not needed can cause it to not work for future infections.

Product Characteristics

Color(s):
GREEN (C48329)
Shape: ROUND (C48348)
Size(s):
9 MM
Imprint(s):
LP1
Score: 1

NDC Code Structure

NDC 72336-596-87

Package Description: 3 BLISTER PACK in 1 CARTON > 14 TABLET, FILM COATED in 1 BLISTER PACK (72336-596-86)

NDC Product Information

Lymepak with NDC 72336-596 is a a human prescription drug product labeled by Lifsa Drugs Llc. The generic name of Lymepak is doxycycline hyclate. The product's dosage form is tablet, film coated and is administered via oral form. The RxNorm Crosswalk for this NDC code indicates multiple RxCUI concepts are associated to this product: 1650143, 2099768 and 2099769.

Dosage Form: Tablet, Film Coated - A solid dosage form that contains medicinal substances with or without suitable diluents and is coated with a thin layer of a water-insoluble or water-soluble polymer.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Lymepak Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.


Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • ANHYDROUS LACTOSE (UNII: 3SY5LH9PMK)
  • SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
  • D&C YELLOW NO. 10 (UNII: 35SW5USQ3G)
  • FD&C BLUE NO. 1 (UNII: H3R47K3TBD)
  • FD&C YELLOW NO. 6 (UNII: H77VEI93A8)
  • HYPROMELLOSE, UNSPECIFIED (UNII: 3NXW29V3WO)
  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • METHYLCELLULOSE (400 MPA.S) (UNII: O0GN6F9B2Y)
  • MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)
  • POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A)
  • SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2)
  • STEARIC ACID (UNII: 4ELV7Z65AP)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Tetracycline-class Drug - [EPC] (Established Pharmacologic Class)
  • Tetracyclines - [CS]

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Lifsa Drugs Llc
Labeler Code: 72336
FDA Application Number: NDA209844 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: NDA - A product marketed under an approved New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 09-10-2021 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2022 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N - NO What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

* Please review the disclaimer below.

Lymepak Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1.1 Early Lyme Disease

LYMEPAK is indicated for the treatment of early Lyme disease (as evidenced by erythema migrans) due to


Borrelia burgdorferi in adults and pediatric patients 8 years of age and older weighing 45 kg and above.

1.2 Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of LYMEPAK and other antibacterial drugs, LYMEPAK 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.

Other

Adults and Pediatric Patients 8 years of age and older weighing 45 kg and aboveAdminister LYMEPAK (100 mg) tablet every 12 hours for 21 days.

Risk SummaryLYMEPAK, like other tetracycline-class antibacterial drugs, may cause discoloration of deciduous teeth and reversible inhibition of bone growth when administered during the second and third trimester of pregnancy


[see


Warnings and Precautions (5.1,


5.2),


Data,


Use in Specific Populations (8.4)].


Available data from published studies over decades have not shown a difference in major birth defect risk compared to unexposed pregnancies with doxycycline exposure in the first trimester of pregnancy


(see


Data).


There are no available data on the risk of miscarriage following exposure to doxycycline in pregnancy.


The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Human Data A retrospective cohort study of 1,690 pregnant patients who received doxycycline prescriptions in the first trimester of pregnancy compared to an unexposed pregnant cohort showed no difference in the major malformation rate. There is no information on the dose or duration of treatment, or if the patients actually ingested the doxycycline that was prescribed.Other published studies on exposure to doxycycline in the first trimester of pregnancy have small sample sizes; however, these studies have not shown an increased risk of major malformations.The use of tetracyclines during tooth development (second and third trimester of pregnancy) may cause permanent discoloration of the teeth (yellow-gray-brown). This adverse reaction is more common during long-term use of the drug but has been observed following repeated short-term courses.

Animal DataResults 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


[see


Warnings and Precautions (5.1,


5.2)].

Risk SummaryBased on available published data, doxycycline is present in human milk. There are no data that inform the levels of doxycycline in breastmilk, the effects on the breastfed infant, or the effects on milk production. Because there are other antibacterial drug options available to treat Lyme disease in lactating women and because of the potential for serious adverse reactions, including tooth discoloration and inhibition of bone growth, advise patients that breastfeeding is not recommended during treatment with LYMEPAK and for 5 days after the last dose.

AbsorptionDoxycycline is virtually completely absorbed after oral administration. Following a 200 mg dose, normal adult volunteers averaged peak serum levels of 2.6 mcg/mL of doxycycline at 2 hours, decreasing to 1.45 mcg/mL at 24 hours.

EliminationExcretion of doxycycline by the kidney is about 40%/72 hours in individuals with normal function (creatinine clearance about 75 mL/min.). This percentage excretion may fall as low as 1–5%/72 hours in individuals with severe renal insufficiency (creatinine clearance below 10 mL/min.).

Specific PopulationsStudies have shown no significant difference in serum half-life of doxycycline (range 18–22 hours) in individuals with normal and severely impaired renal function. Hemodialysis does not alter serum half-life.

Mechanism of ActionDoxycycline inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit. Doxycycline has bacteriostatic activity against a broad range of gram-positive and gram-negative bacteria.

ResistanceCross resistance with other tetracyclines is common.

Antimicrobial ActivityCulture and susceptibility testing are not routinely performed to establish the diagnosis of early Lyme disease; standard methods for susceptibility testing of


Borrelia burgdorferi have not been established. The in vitro susceptibility of


Borrelia burgdorferi to doxycycline has been reported in the literature; however, the clinical significance of these findings is unknown.

  • Important Administration and Safety Information for Patients and CaregiversAdvise all patients taking LYMEPAK:to avoid excessive sunlight or artificial ultraviolet light while receiving LYMEPAK and to discontinue therapy if phototoxicity (e.g., skin eruption, etc.) occurs. Sunscreen or sunblock should be considered
  • [see
  • Warnings and Precautions (5.4)]
  • .
  • To drink fluids liberally along with LYMEPAK 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 which contain calcium. However, the absorption of LYMEPAK is not markedly influenced by simultaneous ingestion of food or milk
  • [see
  • Dosage and Administration (2.2)]
  • .
  • 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 LYMEPAK might increase the incidence of vaginal candidiasis
  • [see
  • Warnings and Precautions (5.10)]
  • .
  • That LYMEPAK can make birth control pills less effective
  • [see
  • Drug Interactions (7.3)]
  • .

Tooth Discoloration and Inhibition of Bone GrowthAdvise patients that LYMEPAK, like other tetracycline-class drugs, may cause permanent tooth discoloration of deciduous teeth and reversible inhibition of bone growth when administered during the second and third trimesters of pregnancy. Tell your healthcare provider right away if you become pregnant during treatment


[see


Warnings and Precautions (5.1,


5.2) and


Use in Specific Populations (8.1,


8.4)].

LactationAdvise women not to breastfeed during treatment with LYMEPAK and for 5 days after the last dose


[see


Use in Specific Populations (8.2)].

Jarisch-Herxheimer Reaction Inform patients that a systemic reaction known as the Jarisch–Herxheimer reaction (JHR) may occur within 24 hours of starting LYMEPAK. Symptoms include shaking chills, fever, and intensification of skin rash and usually resolve within several hours. Advise patients to contact their health care provider if symptoms occur


[see


Warnings and Precautions 5.6]


.

Development of ResistancePatients should be counseled that antibacterial drugs, including LYMEPAK should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When LYMEPAK is 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 LYMEPAK or other antibacterial drugs in the future


[see


Warnings and Precautions 5.9]


.

DiarrheaDiarrhea is a common problem caused by antibacterial drugs, including LYMEPAK, which usually ends when the antibacterials are 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 the antibacterial drug. If this occurs, advise patients to contact their physician as soon as possible


[see


Warnings and Precautions 5.3]


.

2.2 Important Administration Instructions

  • The usual dosage and frequency of administration of LYMEPAK differs from that of the other tetracyclines. Exceeding the recommended dosage may result in an increased incidence of adverse reactions.Administration of adequate amounts of fluid along with the tablets is recommended to wash down the tablet to reduce the risk of esophageal irritation and ulceration
  • [see
  • Adverse Reactions (6)].
  • If gastric irritation occurs, LYMEPAK may be given with food or milk. The absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk.

3 Dosage Forms And Strengths

LYMEPAK tablets are green, round, film-coated tablets engraved with LP-1 on one side. Each tablet contains 100 mg of doxycycline (equivalent to 115 mg doxycycline hyclate).

4 Contraindications

LYMEPAK is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines.

5.1 Tooth Discoloration And Enamel Hypoplasia

The use of LYMEPAK during tooth development (last half of pregnancy, infancy and childhood up 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 of the tetracycline class, but it has been observed following repeated short-term courses. Enamel hypoplasia has also been reported with drugs of the tetracycline class. Advise the patient of the potential risk to the fetus if LYMEPAK is used during the second or third trimester of pregnancy


[see


Use in Specific Populations (8.1,


8.4)].

5.2 Inhibition Of Bone Growth

The use of LYMEPAK during the second and third trimester of pregnancy, infancy and childhood up to the age of 8 years may cause reversible inhibition of bone growth. All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in fibula growth rate has been observed in premature infants given oral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was shown to be reversible when the drug was discontinued. Advise the patient of the potential risk to the fetus if LYMEPAK is used during the second or third trimester of pregnancy


[see


Use in Specific Populations (8.1,


8.4)]


.

5.3 Clostridium Difficile Associated Diarrhea

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including LYMEPAK, 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 antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following the use of antibacterial drugs. 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 use of antibacterial drugs 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.

5.4 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 LYMEPAK, and treatment should be discontinued at the first evidence of skin erythema.

5.5 Severe Skin Reactions

Severe skin reactions, such as exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported in patients receiving doxycycline


[see


Adverse Reactions (6)]


. If severe skin reactions occur, discontinue LYMEPAK immediately and initiate appropriate therapy.

5.6 Jarisch-Herxheimer Reaction

The Jarisch-Herxheimer reaction is a self-limiting systemic reaction that has been reported after the initiation of doxycycline therapy in up to 30% of patients with early Lyme disease. The reaction begins one to two hours after initiation of therapy and disappears within 12 to 24 hours. It is characterized by fever, chills, myalgias, headache, exacerbation of cutaneous lesions, tachycardia, hyperventilation, vasodilation with flushing, and mild hypotension. The pathogenesis of the Jarisch-Herxheimer reaction is unknown, but thought to be due to the release of spirochetal heat-stable pyrogen. Advise the patient of this reaction before starting LYMEPAK. Administer fluids and antipyretics to alleviate symptoms and duration of the reaction if severe.

5.7 Intracranial Hypertension

Intracranial hypertension (IH, pseudotumor cerebri) has been associated with the use of tetracyclines including doxycycline. 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 LYMEPAK should be avoided because isotretinoin is also known to cause pseudotumor cerebri.Although IH may improve 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.

5.8 Antianabolic Action

The antianabolic action of the tetracyclines, including LYMEPAK may cause an increase in blood urea nitrogen (BUN). Studies to date indicate that this does not occur with the use of doxycycline in patients with renal impairment.

5.9 Development Of Drug Resistant Bacteria

Prescribing LYMEPAK 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

5.10 Potential For Microbial Overgrowth

As with other antibacterial drugs, use of LYMEPAK may result in overgrowth of non-susceptible organisms, including fungi. If such infections occur, discontinue doxycycline and institute appropriate therapy.

6 Adverse Reactions

  • The following clinically significant adverse reactions are described elsewhere in the labeling:Tooth Discoloration and Enamel Hypoplasia
  • [see
  • Warnings and Precautions (5.1)]
  • Inhibition of Bone Growth
  • [see
  • Warnings and Precautions (5.2)]
  • Clostridium Difficile Associated Diarrhea
  • [see
  • Warnings and Precautions (5.3)]
  • Photosensitivity
  • [see
  • Warnings and Precautions (5.4)]
  • Severe Skin Reactions
  • [see
  • Warnings and Precautions (5.5)]
  • Jarisch-Herxheimer reaction
  • [see
  • Warnings and Precautions (5.6)]
  • Intracranial Hypertension
  • [see
  • Warnings and Precautions (5.7)]
  • The following adverse reactions have been observed during clinical trials or post-approval use of tetracycline-class drugs, including LYMEPAK. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.Gastrointestinal: Anorexia, nausea, vomiting, diarrhea, glossitis, dysphagia, enterocolitis, and inflammatory lesions (with monilial overgrowth) in the anogenital region, and pancreatitis. Hepatotoxicity has been reported. These reactions have been caused by both the oral and parenteral administration of tetracyclines. Superficial discoloration of the adult permanent dentition, reversible upon drug discontinuation and professional dental cleaning has been reported. Permanent tooth discoloration and enamel hypoplasia may occur with drugs of the tetracycline class when used during tooth development
  • [see
  • Warnings and Precautions (5.1)]
  • . Esophagitis and esophageal ulcerations have been reported in patients receiving capsule and tablet forms of drugs in the tetracycline-class. Most of these patients took medications immediately before going to bed
  • [see
  • Dosage and Administration (2.2)]
  • .
  • Skin: Toxic epidermal necrolysis, Stevens-Johnson syndrome, erytherma multiforme, maculopapular and erythematous rashes. Exfoliative dermatitis has been reported but is uncommon. Photosensitivity is discussed above
  • [see
  • Warnings and Precautions (5.4)]
  • .
  • Renal: Rise in BUN has been reported and is apparently dose-related
  • [see
  • Warnings and Precautions (5.8)]
  • .
  • Immune: Hypersensitivity reactions including urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, serum sickness, pericarditis, exacerbation of systemic lupus erythematosus and drug reaction with eosinophilia and systemic symptoms (DRESS). Jarisch-Herxheimer reaction has been reported in patients treated with doxycycline for early Lyme disease
  • [see
  • Warnings and Precautions (5.6)]
  • .
  • Blood: Hemolytic anemia, thrombocytopenia, neutropenia, and eosinophilia have been reported.
  • Intracranial Hypertension: Intracranial hypertension (IH, pseudotumor cerebri) in adults and bulging fontanels in infants has been associated with the use of tetracycline
  • [see
  • Warnings and Precautions (5.7)]
  • .
  • Thyroid Gland Changes: When given over prolonged periods, tetracyclines have been reported to produce brown-black microscopic discoloration of thyroid glands. No abnormalities of thyroid function are known to occur.

7.1 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.

7.2 Penicillin

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

7.3 Antacids And Iron Preparations

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

7.4 Oral Contraceptives

Concurrent use of tetracycline, including LYMEPAK, may render oral contraceptives less effective.

7.5 Isotretinoin

There have been reports of intracranial hypertension associated with the concomitant use of isotretinoin and doxycycline. Avoid the concomitant use of isotretinoin and LYMEPAK because isotretinoin is also known to cause pseudotumor cerebri (benign intracranial hypertension


[see


Warnings and Precautions (5.7)].

7.6 Barbiturates And Anti-Epileptics

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

7.7 Drug/Laboratory Test Interactions

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

8.4 Pediatric Use

The safety and efficacy of LYMEPAK has been established in pediatric patients 8 years of age and older, weighing 45 kg and greater.Because of the effects of the tetracycline-class of drugs on tooth development and growth, use of LYMEPAK in pediatric patients younger than 8 years of age, weighing less than 45 kg is not recommended


[see


Warnings and Precautions (5.1,


5.2)].

8.5 Geriatric Use

Clinical studies of LYMEPAK did not report specific treatment outcomes of patients aged 65 and over to determine whether they respond differently from younger subjects.

8.6 Hepatic Impairment

The use of tetracyclines has been associated with hepatotoxicity.

8.7 Renal Impairment

Studies have shown no significant difference in the serum half-life of doxycycline


[see


Clinical Pharmacology (12.3)]


. No dosage adjustment is warranted in patients with renal impairment.

10 Overdosage

In case of overdosage, discontinue medication, treat symptomatically and institute supportive measures. Dialysis does not alter serum half-life and thus would not be of benefit in treating cases of overdosage.

11 Description

LYMEPAK contains doxycycline hyclate, USP which is the hyclate salt form of doxycycline, a tetracycline class antibacterial drug derived from oxytetracycline.The chemical name of doxycycline hyclate is 4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2- naphthacenecarboxamide monohydrochloride, compound with ethyl alcohol (2:1), monohydrate. The molecular formula for doxycycline hyclate is (C


22H


24N


2O


8∙HCl)


2∙C


2H


6O∙H


2O and the molecular weight is 1025.89. Doxycycline is a light-yellow crystalline powder. Doxycycline hyclate is soluble in water.


Doxycycline has a high degree of lipid solubility and a low affinity for calcium binding. It is highly stable in normal human serum. Doxycycline will not degrade into an epianhydro form. The chemical structure of doxycycline hyclate is shown in Figure 1.Figure 1: Structure of Doxycycline HyclateLYMEPAK tablets, for oral administration, contain 100 mg of doxycycline (equivalent to 115 mg doxycycline hyclate). Inert ingredients in the tablet formulation are: anhydrous lactose, colloidal silicon dioxide, D&C yellow #10, FD&C blue #1, FD&C yellow #6, hypromellose, magnesium stearate, methylcellulose, microcrystalline cellulose, polyethylene glycol, sodium starch glycolate, stearic acid, and titanium dioxide.

12.1 Mechanism Of Action

LYMEPAK is an antibacterial drug


[see


Microbiology (12.4)]


.

12.3 Pharmacokinetics

Tetracyclines are readily absorbed and are bound to plasma proteins in varying degrees. They are concentrated by the liver in the bile, and excreted in the urine and feces at high concentrations and in a biologically active form.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

Long-term studies in animals to evaluate carcinogenic potential of doxycycline have not been conducted. However, there has been evidence of oncogenic activity in rats in studies with the related antibacterial drugs, oxytetracycline (adrenal and pituitary tumors), and minocycline (thyroid tumors).Likewise, although mutagenicity studies of doxycycline have not been conducted, positive results using in vitro mammalian cell assays have been reported for related antibacterial drugs (tetracycline, oxytetracycline).Doxycycline administered orally at dosage levels as high as 250 mg/kg/day had no apparent effect on the fertility of female rats. Effect on male fertility has not been studied.

13.2 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 PO


4, and methacycline; in minipigs by doxycycline, minocycline, tetracycline PO


4, and methacycline; in dogs by doxycycline and minocycline; in monkeys by minocycline.


Minocycline, tetracycline PO


4, 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.

14.1 Clinical Trial Experience

Doxycycline has been used in clinical practice for early stages of Lyme disease for several decades. Thorough search of the published literature identified 31 studies in which doxycycline treatment was used for the treatment of Lyme disease. Of these 31, three randomized studies evaluating doxycycline treatment in patients with erythema migrans and associated symptoms were identified


1-3. In addition, two natural history studies of Lyme disease evaluated disease progression in patients presenting with erythema migrans and associated symptoms


4,5. Over 200 patients from Lyme-disease hyperendemic areas were enrolled in these five studies, and more than 100 received doxycycline. Evidence of efficacy was derived by comparing the doxycycline treatment in studies using doxycycline 100 mg twice daily for 20-21 days with no treatment in the natural history studies. Clinical resolution of symptoms was defined as absence of objective late manifestations of Lyme disease, specifically those related to the musculoskeletal, nervous, and cardiac systems at 6 months. In comparison to untreated patients, doxycycline-treated patients had a higher response rate at 6 months. Doxycycline-treated patients had a response rate of 75-95% compared to 56-66% in untreated patients.

15 References

  • Dattwyler RJ, Volkman DJ, Conaty SM, Platkin SP, Luft BJ. Amoxycillin plus probenecid versus doxycycline for treatment of erythema migrans borreliosis. Lancet 1990; 336(8728):1404-1406.Massarotti EM, Luger SW, Rahn DW, Messner RP, Wong JB, Johnson RC et al. Treatment of early Lyme disease. Am J Med 1992; 92(4):396-403.Dattwyler RJ, Luft BJ, Kunkel MJ, Finkel MF, Wormser GP, Rush TJ et al. Ceftriaxone compared with doxycycline for the treatment of acute disseminated Lyme disease. N Engl J Med 1997; 337(5):289-294.Steere AC, Hardin JA, Ruddy S, Mummaw JG, Malawista SE. Lyme arthritis: correlation of serum and cryoglobulin IgM with activity, and serum IgG with remission. Arthritis Rheum 1979b; 22(5):471-483.Steere AC, Malawista SE, Newman JH, Spieler PN, Bartenhagen NH. Antibiotic therapy in Lyme disease. Ann Intern Med 1980; 93(1):1-8.

16 How Supplied/Storage And Handling

LYMEPAK tablets contain 100 mg of doxycycline (equivalent to 115 mg doxycycline hyclate). The tablets are green, round, film-coated tablets engraved with LP-1 on one side.NDC # 72135-596-86: is supplied as a child-resistant blister card containing 14 tablets


NDC # 72135-596-87: Unit of use carton containing 3 blister cards, total 42 tablets

Storage And Handling

Store at 20°C to 25°C (68°F to 77°F) excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Protect from light and moisture.

17 Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Patient Information Lymepak (Lime-Pac) (Doxycycline) Tablets, For Oral Use

  • Read this Patient Information before you start taking LYMEPAK and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or treatment.What is LYMEPAK?LYMEPAK is a prescription medicine used for the treatment of early Lyme disease due to a bacteria known as
  • Borrelia burgdorferi in adults and children 8 years of age and older weighing 99 pounds (lbs) (45 kg) and above.
  • It is not known if LYMEPAK is safe and effective in children less than 8 years of age or weighing under 99 lbs (45 kg).Do not take LYMEPAK if you:are allergic to doxycycline or any of the ingredients in LYMEPAK. See the end of this Patient Information leaflet for a complete list of ingredients in LYMEPAK.Before you take LYMEPAK tell your doctor about all of your medical conditions including if you:have diarrhea or watery stools.have vision problems.have or had a yeast or fungal infection in your vagina.are pregnant or plan to become pregnant. LYMEPAK may harm your unborn baby. Taking LYMEPAK while you are pregnant may cause serious side effects on the growth of bone and teeth of your baby. Stop taking LYMEPAK and call your doctor right away if you become pregnant while taking LYMEPAK.are breastfeeding or plan to breastfeed. LYMEPAK can pass into your breast milk and may harm your baby. Talk to your doctor about the best way to feed your baby if you take LYMEPAK. You and your doctor should decide if you will take LYMEPAK or breastfeed. You should not do both. After the last dose you should not breastfeed for 5 daysTell your doctor about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. LYMEPAK and other medicines can affect each other causing serious side effects.Especially tell your doctor if you take:a blood thinner medicine.a penicillin (antibacterial medicine).antacids that contain aluminum, calcium, or magnesium.products containing iron or bismuth subsalicylate.birth control pills. LYMEPAK may reduce the effectiveness of birth control pills. Talk to your doctor about what types of birth control you can use to prevent pregnancy during treatment with LYMEPAK.a medicine taken by mouth that contains isotretinoin or acitretin.a medicine to treat seizures, such as carbamazepine or phenytoin.How should I take LYMEPAK?Take LYMEPAK exactly as prescribed by your doctor. Taking more than your prescribed dose may increase your risk of side effects, including the risk that bacteria will become resistant to LYMEPAK.Take 1 LYMEPAK tablet every 12 hoursTake LYMEPAK with enough fluid to completely swallow the tablet and avoid taking LYMEPAK less than 30 minutes before going to bed to lower your risk of getting irritation or ulcer in your esophagus. Your esophagus is the tube that connects your mouth to your stomach.If irritation of the stomach happens, LYMEPAK may be taken with food or milk.If you took too much LYMEPAK stop taking LYMEPAK and call your doctor right away or go to the nearest hospital emergency room.Your doctor may do blood tests during treatment with LYMEPAK to check for side effects.What should I avoid while taking LYMEPAK?Avoid sunlight or artificial sunlight, such as a tanning booth or sunlamp. You could get severe sunburn. Use sunscreen and wear clothes that cover your skin while out in sunlight. Stop taking LYMEPAK and tell your doctor right away if you get sunburn.What are the possible side effects of LYMEPAK?LYMEPAK may cause serious side effects, including:Harm to an unborn baby. See "
  • What should I tell my doctor before taking LYMEPAK?"
  • Harm to infants and children under 8 years of age:
  • Permanent teeth discoloration. LYMEPAK may permanently turn a baby or child's teeth yellow-gray-brown during tooth development.
  • Slow bone growth. LYMEPAK may slow bone growth in infants and children. Slow bone growth is reversible after stopping treatment with LYMEPAK.
  • Diarrhea. Diarrhea can happen with most antibiotics, including LYMEPAK. This diarrhea may be caused by an infection (
  • Clostridium difficile) in your intestines. Call your doctor right away if you get watery or bloody stools, this can happen anytime while on LYMEPAK, or even two or more months after taking your last dose.
  • Severe Skin ReactionsStop taking LYMEPAK and tell your doctor right away if you get any of the following symptoms during treatment with LYMEPAK:
  • Rash with red, purple, blue or gray discoloration with fevertirednesscoughtrouble breathingfeeling uneasyitching or burning eyessensitivity to lightjoint painpainful skin with blistersskin peeling (chest, face, palms of the hands or soles of the feet)sores or ulcers (mouth, eyes, vagina or penis)swollen lymph nodesJarisch-Herxheimer Reaction. This reaction can happen in people with early Lyme Disease and begins one to two hours after the first dose of LYMEPAK and disappears within 12 to 24 hours. The reaction may include fever, chills, muscle pain, headache, worsening of skin lesions, fast heart rate, fast breathing, flushing of skin, and increase in blood pressure. Tell your doctor if you have any of these symptoms.
  • Increased pressure around the brain (intracranial hypertension). This condition may lead to vision changes and permanent vision loss. You may be more likely to get intracranial hypertension if you are female of childbearing age and are overweight or have a history of intracranial hypertension. Stop taking LYMEPAK and call your doctor right away if you have blurred or double vision, vision loss, or unusual headaches.
  • If you have any of the above serious side effects during treatment with LYMEPAK, your doctor may stop your treatment.Common side effects of LYMEPAK include:nauseavomitingdiarrhealoss of appetiteskin sensitivity to sunlightrashhivesheadachereversible discoloration of the surface of adult teethlower than normal amount of red blood cellsThese are not all the possible side effects of LYMEPAK.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store LYMEPAK?Store LYMEPAK at room temperature between 68°F to 77°F (20°C to 25°C).Keep LYMEPAK inside blister dose card and out of light.Keep LYMEPAK away from moistureKeep LYMEPAK and all medicine out of the reach of children.General information about the safe and effective use of LYMEPAKMedicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not take LYMEPAK for a condition for which it was not prescribed. Do not give LYMEPAK to other people, even if they have the same symptoms you have. It may harm them. You can also ask your doctor or pharmacist for information that is written for health professionals.What are the ingredients in LYMEPAK?Active ingredient: doxycycline
  • Inactive ingredients: anhydrous lactose, colloidal silicon dioxide, D&C yellow #10, FD&C blue #1, FD&C yellow #6, hypromellose, magnesium stearate, methylcellulose, microcrystalline cellulose, polyethylene glycol, sodium starch glycolate, stearic acid, and titanium dioxide.
  • Manufactured By:
  • Chartwell Pharmaceuticals, LLC.
  • Congers, NY 10920 USA
  • Manufactured For:
  • Lifsa Drugs LLC
  • New Brunswick, NJ 08901 USA
  • Made in USAL70364For more information, go to www.lymepak.com or call 1-845-232-1683.This Patient Information has been approved by the U.S. Food and Drug Administration.Revised: 09/2021

* Please review the disclaimer below.