^ Pharmacodynamics
The pharmacodynamics of SOLODYN for the treatment of acne are unknown.
^ Overdosage
In case of overdosage, discontinue medication, treat symptomatically and institute supportive measures. Minocycline is not removed in significant quantities by hemodialysis or peritoneal dialysis.
^3 Dosage Forms And Strengths
^ Laboratory Monitoring
Periodic laboratory evaluations of organ systems, including hematopoetic renal and hepatic studies should be performed. Appropriate tests for autoimmune syndromes should be performed as indicated.
^ Nursing Mothers
Tetracycline-class antibiotics are excreted in human milk. Because of the potential for serious adverse effects on bone and tooth development in nursing infants from the tetracycline-class antibiotics, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother [see Warnings and Precautions (5.1)].
^ Drug/laboratory Test Interactions
False elevations of urinary catecholamine levels may occur due to interference with the fluorescence test.
^ Handling
Keep out of reach of children.
Protect from light, moisture, and excessive heat.
Dispense in tight, light-resistant container with child-resistant closure.
^ 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.
^ Low Dose Oral Contraceptives
In a multi-center study to evaluate the effect of SOLODYN on low dose oral contraceptives, hormone levels over one menstrual cycle with and without SOLODYN 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, can not be ruled out. To avoid contraceptive failure, female patients are advised to use a second form of contraceptive during treatment with minocycline.
^ Superinfection
As with other antibiotic preparations, use of SOLODYN may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, SOLODYN should be discontinued and appropriate therapy instituted.
^ 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.
^ Indication
SOLODYN is indicated to treat only inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 12 years of age and older.
^ Teratogenic Effects
^ 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.
^2 Dosage And Administration
The recommended dosage of SOLODYN 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 following table shows tablet strength and body weight to achieve approximately 1 mg/kg.
SOLODYN Tablets may be taken with or without food [see Clinical Pharmacology (12)]. Ingestion of food along with SOLODYN may help reduce the risk of esophageal irritation and ulceration.
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 (5.4)].
^ Clinical Trial Experience
Because clinical trials are conducted under prescribed conditions, adverse reaction rates observed in the clinical trial 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 SOLODYN.
^ Photosensitivity
Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. This has been reported rarely 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 minocycline, they should wear loose-fitting clothes that protect skin from sun exposure and discuss other sun protection measures with their physician.
^ Serious Skin/hypersensitivity Reaction
Cases of anaphylaxis, serious skin reactions (e.g. Stevens Johnson syndrome), erythema multiforme, and drug rash 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, the drug should be discontinued immediately.
^ Antacids And Iron Preparations
Absorption of tetracyclines is impaired by antacids containing aluminum, calcium or magnesium and iron-containing preparations.
^ Pediatric Use
SOLODYN is indicated to treat only inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 12 years and older. Safety and effectiveness in pediatric patients below the age of 12 has not been established.
Use of tetracycline-class antibiotics below the age of 8 is not recommended due to the potential for tooth discoloration [see Warnings and Precautions (5.1)].
^ Benign Intracranial Hypertension
Pseudotumor cerebri (benign intracranial hypertension) in adults and adolescents has been associated with the use of tetracyclines. Minocycline has been reported to cause or precipitate pseudotumor cerebri, the hallmark of which is papilledema. Clinical manifestations include headache and blurred vision. Bulging fontanels have been associated with the use of tetracyclines in infants. Although signs and symptoms of pseudotumor cerebri resolve after discontinuation of treatment, the possibility for permanent sequelae such as visual loss that may be permanent or severe exists. Patients should be questioned for visual disturbances prior to initiation of treatment with tetracyclines. If visual disturbance occurs during treatment, patients should be checked for papilledema. Concomitant use of isotretinoin and minocycline should be avoided because isotretinoin, a systemic retinoid, is also known to cause pseudotumor cerebri.
^ Tissue Hyperpigmentation
Tetracycline-class antibiotics 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 over sites of scars or injury.
^ How Supplied
SOLODYN (minocycline HCl, USP) Extended Release Tablets are supplied as aqueous film coated tablets containing minocycline hydrochloride equivalent to 80 mg minocycline, are supplied as follows.
The 80 mg extended release tablets are gray, unscored, coated, and debossed with "DYN-080" on one side. Each tablet contains minocycline hydrochloride equivalent to 80 mg minocycline, supplied as follows:
^ Limitations Of Use
SOLODYN did not demonstrate any effect on non-inflammatory acne lesions. Safety of SOLODYN has not been established beyond 12 weeks of use. This formulation of minocycline has not been evaluated in the treatment of infections [see Clinical Studies (14)].
To reduce the development of drug-resistant bacteria as well as to maintain the effectiveness of other antibacterial drugs, SOLODYN should be used only as indicated [see Warnings and Precautions (5.11)].
^ 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.
^ Methoxyflurane
The concurrent use of tetracycline and methoxyflurane has been reported to result in fatal renal toxicity.
^ Development Of Drug-resistant Bacteria
Bacterial resistance to the tetracyclines may develop in patients using SOLODYN, therefore, the susceptibility of bacteria associated with infection should be considered in selecting antimicrobial therapy. Because of the potential for drug-resistant bacteria to develop during the use of SOLODYN, it should be used only as indicated.
^ Geriatric Use
Clinical studies of SOLODYN did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. 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.
^ Patient Counseling Information
[See FDA-approved patient labeling (Patient Information)]
Patients taking SOLODYN (minocycline HCl, USP) Extended Release Tablets should receive the following information and instructions:
^ Penicillin
Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving tetracycline-class drugs in conjunction with penicillin.
^ Pharmacokinetics
SOLODYN Tablets are not bioequivalent to non-modified release minocycline products. Based on pharmacokinetic studies in healthy adults, SOLODYN Tablets produce a delayed Tmax at 3.5–4.0 hours as compared to a non-modified release reference minocycline product (Tmax at 2.25–3 hours). At steady-state (Day 6), the mean AUC(0–24) and Cmax were 33.32 µg×hr/mL and 2.63 µg/mL for SOLODYN Tablets and 46.35 µg×hr/mL and 2.92 µg/mL for Minocin® capsules, respectively. These parameters are based on dose adjusted to 135 mg per day for both products.
A single-dose, four-way crossover study demonstrated that SOLODYN Tablets used in the study (45 mg, 90 mg, 135 mg) exhibited dose-proportional pharmacokinetics. In another single-dose, five-way crossover pharmacokinetic study, SOLODYN Tablets 55 mg, 80 mg, and 105 mg were shown to be dose-proportional to SOLODYN Tablets 90 mg and 135 mg.
When SOLODYN Tablets were administered concomitantly with a meal that included dairy products, the extent and timing of absorption of minocycline did not differ from that of administration under fasting conditions.
Minocycline is lipid soluble and distributes into the skin and sebum.
^ Postmarketing Experience
Adverse reactions that have been reported with minocycline hydrochloride use in a variety of indications include:
Preliminary studies suggest that use of minocycline may have deleterious effects on human spermatogenesis [see Nonclinical Toxicology (13.1)].
^ Pseudomembranous Colitis
Pseudomembranous colitis has been reported with nearly all antibacterial agents and may range from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.
Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is a primary cause of "antibiotic-associated colitis".
After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to discontinuation of the drug alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against Clostridium difficile colitis.
^ 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, liver function tests, ANA, CBC, and other appropriate tests should be performed to evaluate the patients. Use of all tetracycline-class drugs should be discontinued immediately.
^ 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 represented below:
C23H27N3O7•HCl M. W. 493.95
SOLODYN Tablets for oral administration contain minocycline hydrochloride USP equivalent to 45 mg, 55 mg, 65 mg, 80 mg, 90 mg, 105 mg, 115 mg, or 135 mg of minocycline. In addition, 45 mg, 55 mg, 65 mg, 80 mg, 90 mg, 105 mg, 115 mg, and 135 mg tablets contain the following inactive ingredients: lactose monohydrate NF, hypromellose type 2910 USP, magnesium stearate NF, colloidal silicon dioxide NF, and carnauba wax NF. The 45 mg tablets also contain Opadry II Gray which contains: lactose monohydrate NF, hypromellose type 2910 USP, titanium dioxide USP, triacetin USP, and iron oxide black JPE. The 55 mg tablets also contain Opadry II Pink which contains: hypromellose type 2910 USP, titanium dioxide USP, lactose monohydrate NF, polyethylene glycol 3350 NF, triacetin USP, and FD&C Red #40. The 65 mg tablets also contain Opadry II Blue which contains: hypromellose type 2910 USP, lactose monohydrate NF, FD&C Blue #1, polyethylene glycol 3350 NF, FD&C Blue #2, titanium dioxide USP, triacetin USP, and D&C Yellow #10. The 80 mg tablets also contain Opadry II Gray which contains: hypromellose type 2910 USP, lactose monohydrate NF, polyethylene glycol 3350 NF, FD&C Blue #2, FD&C Red #40, titanium dioxide USP, triacetin USP, and FD&C Yellow #6. The 90 mg tablets also contain Opadry II Yellow which contains: hypromellose type 2910 USP, lactose monohydrate NF, titanium dioxide USP, iron oxide yellow NF, polyethylene glycol 3350 NF, and triacetin USP. The 105 mg tablets also contain Opadry II Purple which contains: hypromellose type 2910 USP, lactose monohydrate NF, titanium dioxide USP, D&C Red #27, polyethylene glycol 3350 NF, triacetin USP, and FD&C Blue #1. The 115 mg tablets also contain Opadry II Green which contains: hypromellose type 2910 USP, lactose monohydrate NF, D&C Yellow #10, triacetin USP, FD&C Blue #1, titanium dioxide USP, and FD&C Blue #2. The 135 mg tablets also contain Opadry II Pink which contains: hypromellose type 2910 USP, lactose monohydrate NF, titanium dioxide USP, polyethylene glycol 3350 NF, iron oxide red NF, and triacetin USP.
^4 Contraindications
This drug is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines.
^ Clinical Studies
The safety and efficacy of SOLODYN 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, studies 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 SOLODYN or placebo for a total of 12 weeks, according to the following dose assignments.
The two primary efficacy endpoints were:
SOLODYN did not demonstrate any effect on non-inflammatory lesions (benefit or worsening).
^ Storage
Store at 25°C (77°F); excursions are permitted to 15°–30°C (59°–86°F) [See USP Controlled Room Temperature].
^ Mechanism Of Action
The mechanism of action of SOLODYN for the treatment of acne is unknown.