^ Pharmacodynamics
The pharmacodynamics of MINOLIRA for the treatment of acne are unknown.
^ Autoimmune Syndromes
Tetracyclines have been associated with the development of autoimmune syndromes. The long- term use of minocycline in the treatment of acne has been associated with drug-induced lupus- like syndrome, autoimmune hepatitis and vasculitis. Sporadic cases of serum sickness have presented shortly after minocycline use. Symptoms may be manifested by fever, rash, arthralgia, and malaise. In symptomatic patients, immediately discontinue the use of all tetracycline-class drugs, including MINOLIRA.
^ Low Dose Oral Contraceptives
In a multi-center study to evaluate the effect of minocycline extended release tablets on low dose oral contraceptives, hormone levels over one menstrual cycle with and without minocycline extended release tablets 1 mg/kg once-daily were measured. Based on the results of this trial, minocycline-related changes in estradiol, progestinic hormone, FSH and LH plasma levels, of breakthrough bleeding, or of contraceptive failure, cannot be ruled out. To avoid contraceptive failure during treatment with minocycline, advise patients of reproductive potential to use a second form of contraception in addition to low-dose oral contraceptives.
^ Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling (Patient Information and Instruction for Use).
Advise patients of the following:
^ Pseudomembranous Colitis
Clostridium difficile associated diarrhea (CDAD) has been reported with nearly all antibacterial agents, including minocycline, 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 antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
^ Description
Minocycline hydrochloride, a semi synthetic derivative of tetracycline, is [4S (4α,4aα,5aα,12aα)]-4,7-Bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide mono hydrochloride. The structural formula is representated below:
MINOLIRA (minocycline hydrochloride) extended-release tablets for oral administration contain 105 mg or 135 mg of minocycline, equivalent to 113.4 mg or 145.8 mg of minocycline hydrochloride, respectively. MINOLIRA extended-release tablets, 105 mg and 135 mg, contain 25% of minocycline as immediate release beads and 75% of minocycline as extended release beads.
In addition, 105 mg and 135 mg tablets contain the following inactive ingredients: ethyl cellulose NF, hypromellose USP, isopropyl alcohol USP, microcrystalline cellulose NF, polytheylene glycol 400 NF, purified water USP, silicified microcrystalline cellulose NF, sodium stearyl fumarate NF, talc USP, triethyl citrate NF.
Both 105 mg and 135 mg tablets also contain Opadry clear which contains hydroxyl propyl cellulose NF and hypromellose USP.
^ Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug, and may not reflect the rates observed in practice.
The following table summarizes selected adverse reactions reported in clinical trials at a rate of ≥1% for minocycline hydrochloride extended release tablets.
^Patient Information Minolira (min-oh-li'-rah) (minocycline Hydrochloride) Extended-release Tablets
WHAT IS MINOLIRA?
MINOLIRA is prescription medicine used to treat only pimples and red bumps (non-nodular inflammatory lesions) that happen with moderate to severe acne vulgaris in people 12 years and older.
MINOLIRA should not be used for the treatment of infections.
It is not known if MINOLIRA is safe and effective in children under the age of 12 years.
Who should not take MINOLIRA?
Before you take MINOLIRA, tell your healthcare provider about all of your medical conditions, including if you:
Tell your healthcare provider about all the other medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. MINOLIRA and other medicines may affect each other causing serious side effects.
Especially tell your healthcare provider if you take:
How should I take MINOLIRA?
See the detailed "Instructions for Use" that comes with MINOLIRA for information about breaking your MINOLIRA extended-release tablets.
What should I avoid during treatment with MINOLIRA?
What are possible side effects of MINOLIRA?
MINOLIRA may cause serious side effects, including:
The most common side effects of MINOLIRA include:
MINOLIRA may cause fertility problems in males. This may affect your ability to father a child. Talk to your healthcare provider if you have concerns about fertility.
Your healthcare provider may tell you to decrease your dose or completely stop taking MINOLIRA if you develop certain serious side effects during treatment with MINOLIRA.
Your healthcare provider may do blood tests to check you for side effects during treatment with MINOLIRA.
These are not all the side effects of MINOLIRA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may also report side effects to EPI Health, LLC at 1-800-499-4468.
How should I store MINOLIRA?
Keep MINOLIRA and all medicines out of the reach of children. General information about the safe and effective use of MINOLIRA.
Medicines are sometimes prescribed for purposes other than those listed in the Patient Information leaflet. Do not use MINOLIRA for a condition for which it was not prescribed. Do not give MINOLIRA to other people, even if they have the same symptoms you have. It may harm them. You can ask your healthcare provider or pharmacist for information about MINOLIRA that is written for health professionals.
What are the ingredients in MINOLIRA?
Active ingredient: minocycline hydrochloride.
Inactive ingredients: ethyl cellulose, hypromellose, isopropyl alcohol, microcrystalline cellulose, polyethylene glycol 400, purified water, silicified microcrystalline cellulose, sodium stearyl fumarate, talc, triethyl citrate
Both 105 mg and 135 mg tablets also contain Opadry clear which contains hydroxyl propyl cellulose and hypromellose.
Manufactured for: EPI Health, LLC 134 Columbus St. Charleston, SC 29403, USA
Manufactured by: Dr. Reddy's Laboratories Limited FTO-SEZ, Process Unit-01, Devunipalavalasa Village, Srikakulam (District), Andhra Pradesh, India. Pin-:532409
MINOLIRA is a registered trademark of EPI Health, LLC
Item No. MIN-PI-0618/150073673
Issued: 06/2018
^ Overdosage
In case of over dosage, discontinue medication, treat symptomatically and institute supportive measures. Minocycline is not removed in significant quantities by hemodialysis or peritoneal dialysis.
^ Tooth Discoloration
The use of tetracycline class drugs during tooth development (second and third trimesters 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 tetracycline but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. Use of tetracycline drugs is not recommended during tooth development.
The safety and effectiveness of MINOLIRA have not been established in pediatric patients less than 12 years of age.
^ Anticoagulants
Because tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage.
^ Tissue Hyperpigmentation
Tetracyclines are known to cause hyperpigmentation. Tetracycline therapy may induce hyperpigmentation in many organs, including nails, bone, skin, eyes, thyroid, visceral tissue, oral cavity (teeth, mucosa, alveolar bone), sclerae and heart valves. Skin and oral pigmentation has been reported to occur independently of time or amount of drug administration, whereas other tissue pigmentation has been reported to occur upon prolonged administration. Skin pigmentation includes diffuse pigmentation as well as pigmentation over sites of scars or injury.
^ Hepatotoxicity
Post-marketing cases of serious liver injury, including irreversible drug-induced hepatitis and fulminant hepatic failure (sometimes fatal) have been reported with minocycline use in the treatment of acne.
^Instructions For Use Minolira (min-oh-li'-rah) (minocycline Hydrochloride) Extended-release Tablets
Read this Instructions for Use before you start using MINOLIRA 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:
The 105 mg MINOLIRA tablets:
How to break your MINOLIRA tablets?
The 135 mg MINOLIRA tablets:
How to break your MINOLIRA tablets?
How should I store MINOLIRA?
Keep MINOLIRA and all medicines out of the reach of children.
This Instructions for Use has been approved by the U.S. Food and Drug Administration.
Manufactured for: EPI Health, LLC 134 Columbus St. Charleston, SC 29403, USA
Manufactured by: Dr. Reddy's Laboratories Limited FTO-SEZ, Process Unit-01, Devunipalavalasa Village, Srikakulam (District), Andhra Pradesh, India. Pin-:532409
MINOLIRA is a registered trademark of EPI Health, LLC
Item No. MIN-PI-0618/150073673
Issued: 06/2018
^3 Dosage Forms And Strengths
MINOLIRA extended-release tablets are white to off-white, functionally scored, rectangular tablets with brown or gold color speckles and a single score line on both surfaces. MINOLIRA are available in the following two strengths.
^ 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 human 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. The safety and effectiveness of MINOLIRA have not been established in patients less than 12 years of age [see Use in Specific Populations (8.1, 8.4)].
Results of animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues, and can cause retardation of skeletal development on the developing fetus. Evidence of embryotoxicity has been noted in animals treated early in pregnancy [see Use in Specific Populations (8.1)].
^ Teratogenic Effects
Avoid MINOLIRA use during pregnancy.
MINOLIRA, like other tetracycline-class drugs, can cause fetal harm when administered to a pregnant woman. MINOLIRA, like other tetracycline-class drugs, may cause permanent discoloration of the teeth and inhibit bone growth when administered during pregnancy. Based on animal data, tetracyclines cross the placenta, are found in fetal tissues, and can cause skeletal malformation and retardation of skeletal development on the developing fetus. Evidence of embryotoxicity has been noted in animals treated early in pregnancy. If MINOLIRA is used during pregnancy, advise the patient of the potential risk to the fetus and discontinue treatment [see Use in Specific Populations (8.1)].
^ Central Nervous System Effects
Central nervous system side effects including light-headedness, dizziness or vertigo have been reported with minocycline therapy. Patients who experience these symptoms should be cautioned about driving vehicles or using hazardous machinery while on minocycline therapy. These symptoms may disappear during therapy and usually rapidly disappear when the drug is discontinued.
^ Pediatric Use
The safety and effectiveness of MINOLIRA have been established in pediatric patients 12 years of age and older for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris [see Pharmacokinetics (12.3) and Clinical Studies (14)]. Tooth discoloration and inhibition of bone growth have been observed in pediatric patients [see Warnings and Precautions (5.2, 5.3)]. The safety and effectiveness of MINOLIRA have not been established in pediatric patients less than 12 years of age.
^4 Contraindications
MINOLIRA is contraindicated in patients who have shown hypersensitivity to any of the tetracyclines [see Serious Skin/Hypersensitivity Reactions (5.11)].
^ Postmarketing Experience
Adverse reactions that have been reported with minocycline hydrochloride use in a variety of indications include:
Skin and hypersensitivity reactions: fixed drug eruptions, balanitis, erythema multiforme, Stevens-Johnson syndrome, anaphylactoid purpura, photosensitivity, pigmentation of skin and mucous membranes, hypersensitivity reactions, angioneurotic edema, anaphylaxis, DRESS syndrome [see Warnings and Precautions (5.11)].
Autoimmune conditions: polyarthralgia, pericarditis, exacerbation of systemic lupus, pulmonary infiltrates with eosinophilia, transient lupus-like syndrome.
Central nervous system: pseudotumor cerebri, bulging fontanels in infants, decreased hearing.
Endocrine: brown-black microscopic thyroid discoloration, abnormal thyroid function.
Oncology: thyroid cancer.
Oral: glossitis, dysphagia, tooth discoloration.
Gastrointestinal: enterocolitis, pancreatitis, hepatitis, liver failure.
Genitourinary: Preliminary studies suggest that use of minocycline may have deleterious effects on human spermatogenesis [see Nonclinical Toxicoloty (13.1)].
Renal: reversible acute renal failure.
Hematology: hemolytic anemia, thrombocytopenia, eosinophilia.
^ Drug/laboratory Test Interactions
False elevations of urinary catecholamine levels may occur due to interference with the fluorescence test.
^ Geriatric Use
Clinical studies of MINOLIRA did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy.
^Principal Display Panel - Mg Tablet Bottle Label
NDC 71403-102-30 Rx Only
minolira™ (minocycline hydrochloride) extended-release tablets
135 mg*
*Each tablet contains 135 mg of minocycline (33.75 mg as immediate release beads and 101.25 mg as extended release beads), equivalent to 145.8 mg of minocycline hydrochloride.
30 Tablets
EPIHEALTH Advancing Dermatology
^ Serious Skin/hypersensitivity Reaction
Cases of anaphylaxis, serious skin reactions (e.g. Stevens Johnson syndrome), erythema multiforme, and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome have been reported postmarketing with minocycline use in patients with acne. DRESS syndrome consists of cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, and one or more of the following visceral complications such as: hepatitis, pneumonitis, nephritis, myocarditis, and pericarditis. Fever and lymphadenopathy may be present. In some cases, death has been reported. If this syndrome is recognized, discontinue MINOLIRA immediately.
^ Carcinogenesis, Mutagenesis, Impairment Of Fertility
In a carcinogenicity study in which minocycline hydrochloride was orally administered to male and female rats once daily for up to 104 weeks at dosages up to 200 mg/kg/day, minocycline hydrochloride was associated in both genders with 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. In a carcinogenicity study in which minocycline hydrochloride was orally administered to male and female mice once daily for up to 104 weeks at dosages up to 150 mg/kg/day, exposure to minocycline hydrochloride did not result in a significantly increased incidence of neoplasms in either males or females.
Minocycline was not mutagenic in vitro in a bacterial reverse mutation assay (Ames test) or CHO/HGPRT mammalian cell assay in the presence or absence of metabolic activation. Minocycline was not clastogenic in vitro using human peripheral blood lymphocytes or in vivo in a mouse micronucleus test.
Male and female reproductive performance in rats was unaffected by oral doses of minocycline of up to 300 mg/kg/day (which resulted in up to approximately 40 times the level of systemic exposure to minocycline observed in patients administered MINOLIRA). However, oral administration of 100 or 300 mg/kg/day of minocycline to male rats (resulting in approximately 15 to 40 times the level of systemic exposure to minocycline observed in patients administered MINOLIRA) adversely affected spermatogenesis. Effects observed at 300 mg/kg/day included a reduced number of sperm cells per gram of epididymis, an apparent reduction in the percentage of sperm that were motile, and (at 100 and 300 mg/kg/day) increased numbers of morphologically abnormal sperm cells. Morphological abnormalities observed in sperm samples included absent heads, misshapen heads, and abnormal flagella.
^ Metabolic Effects
The anti-anabolic action of the tetracyclines may cause an increase in BUN. While this is not a problem in those with normal renal function, in patients with significantly impaired function, higher serum levels of tetracycline-class drugs may lead to azotemia, hyperphosphatemia, and acidosis. If renal impairment exists, even usual oral or parenteral doses may lead to excessive systemic accumulations of the drug and possible liver toxicity. Under such conditions, lower than usual total doses are indicated, and if therapy is prolonged, serum level determinations of the drug may be advisable.
^ Penicillin
Because bacteriostatic drugs may interfere with the bactericidal action of penicillin, to avoid giving tetracycline-class drugs in conjunction with penicillin.
^ Photosensitivity
Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines; this reaction has been reported less frequently with minocycline. Patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while using minocycline. If patients need to be outdoors while using MINOLIRA, they should wear loose-fitting clothes that protect skin from sun exposure and discuss other sun protection measures with their physician.
^ Antacids And Iron Preparations
Absorption of tetracyclines is impaired by antacids containing aluminum, calcium or magnesium and iron-containing preparations.
^ Development Of Drug-resistant Bacteria
MINOLIRA has not been evaluated in the treatment of infections.
Bacterial resistance to the tetracyclines may develop in patients using MINOLIRA. Because of the potential for drug-resistant bacteria to develop during the use of MINOLIRA, it should be used only as indicated.
^ Superinfection
Use of MINOLIRA may result in overgrowth of nonsusceptible organisms, including fungi. If super infection occurs, discontinue MINOLIRA and institute appropriate therapy.
^ Clinical Studies
The safety and efficacy of minocycline hydrochloride extended-release tablets in the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris was assessed in two 12-week, multi-center, randomized, double-blind, placebo-controlled, trials in subjects ≥12 years. The mean age of subjects was 20 years and subjects were from the following racial groups: White (73%), Hispanic (13%), Black (11%), Asian/Pacific Islander (2%), and Other (2%).
In two efficacy and safety trials, a total of 924 subjects with non-nodular moderate to severe acne vulgaris received minocycline hydrochloride extended-release tablets (approximately 1 mg/kg) or placebo for a total of 12 weeks.
The two primary efficacy endpoints were:
1) Mean percent change in inflammatory lesion counts from Baseline to 12 weeks.
2) Percentage of subjects with an Evaluator's Global Severity Assessment (EGSA) of clear or almost clear at 12 weeks.
Efficacy results are presented in Table 5.
Minocycline hydrochloride did not demonstrate any effect on non-inflammatory lesions (benefit or worsening).
^ Laboratory Monitoring
Periodic laboratory evaluations of organ systems, including hematopoietic, renal and hepatic studies should be performed. Appropriate tests for autoimmune syndromes should be performed as indicated.
^2 Dosage And Administration
The recommended dosage of MINOLIRA is approximately 1 mg/kg once daily for 12 weeks. Higher doses have not shown to be of additional benefit in the treatment of inflammatory lesions of acne, and may be associated with more acute vestibular side effects. The 105 mg and 135 mg tablets may be split on the score line for dosing of patient weight ranges of 45-59 kg and 60-89 kg, respectively (see Table 1).
MINOLIRA may be taken with or without food [see Clinical Pharmacology (12.3)]. Ingestion of food along with MINOLIRA may help reduce the risk of esophageal irritation and ulceration. MINOLIRA tablets should not be chewed or crushed.
In patients with renal impairment, the total dosage should be decreased by either reducing the recommended individual doses and/or by extending the time intervals between doses [see Warnings and Precautions (5.6)].
^ Pharmacokinetics
The pharmacokinetics of minocycline following oral administration of a single dose of MINOLIRA (135 mg) was investigated in 77 healthy male and female adult subjects under fasting conditions. The pharmacokinetic parameters of minocycline under fasting conditions are presented in Table 3.
In a separate trial, a single dose of MINOLIRA (135 mg) was administered orally with a high-fat, high-calorie meal that included dairy products to 36 healthy male and female adult subjects. The estimated calorie content of the meal was 848 Kcal, consisting of 145 Kcal from protein, 250 Kcal from carbohydrates, and 453 Kcal from fat. The pharmacokinetic parameters of minocycline under fed conditions are presented in Table 4.
Minocycline is lipid soluble and distributes into the skin and sebum.
^1 Indications And Usage
MINOLIRA is indicated to treat the inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 12 years of age and older.
^ Mechanism Of Action
The mechanism of action of MINOLIRA for the treatment of acne is unknown.
^Principal Display Panel - Mg Tablet Bottle Label
NDC 71403-101-30 Rx Only
minolira™ (minocycline hydrochloride) extended-release tablets
105 mg*
*Each tablet contains 105 mg of minocycline (26.25 mg as immediate release beads and 78.75 mg as extended release beads), equivalent to 113.4 mg of minocycline hydrochloride.
30 Tablets
EPIHEALTH Advancing Dermatology
^ Intracranial Hypertension
Intracranial hypertension has been associated with the use of tetracycline-class drugs including MINOLIRA. Clinical manifestations of intracranial hypertension 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 a greater risk for developing intracranial hypertension. Concomitant use of isotretinoin and tetracycline should be avoided because isotretinoin, a systemic retinoid, is also known to cause intracranial hypertension.
Although intracranial hypertension typically resolves after discontinuation of treatment, the possibility for permanent visual loss exists. If visual disturbance occurs during treatment, prompt ophthalmologic evaluation is warranted. Because intracranial pressure can remain elevated for weeks after drug cessation, patients should be monitored until they stabilize.