Included as part of the PRECAUTIONS section.
- MINOCYCLINE, LIKE OTHER TETRACYCLINE-CLASS DRUGS, CAN CAUSE
FETAL HARM WHEN ADMINISTERED TO A PREGNANT WOMAN. IF ANY TETRACYCLINE IS USED
DURING PREGNANCY OR IF THE PATIENT BECOMES PREGNANT WHILE TAKING THESE DRUGS,
THE PATIENT SHOULD BE APPRISED OF THE POTENTIAL HAZARD TO THE FETUS.
SOLODYN should not be used during pregnancy or by individuals of either gender
who are attempting to conceive a child [see Nonclinical Toxicology and Use
in Specific Populations].
- THE USE OF DRUGS OF THE TETRACYCLINE CLASS 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 drug but has
been observed following repeated short-term courses. Enamel hypoplasia has also
been reported. TETRACYCLINE DRUGS, THEREFORE, SHOULD NOT BE USED DURING TOOTH
- 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.
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].
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, ongoing 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.
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.
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
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.
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.
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.
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.
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.
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.
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
Appropriate tests for autoimmune syndromes should be
performed as indicated.
Patient Counseling Information
See FDA-approved patient labeling (Patient Labeling)
Patients taking SOLODYN (minocycline HCl, USP) Extended
Release Tablets should receive the following information and instructions:
- SOLODYN should not be used by pregnant women or women
attempting to conceive a child [see Use in Specific Populations (8.1), Nonclinical
- It is recommended that SOLODYN not be used by men who are
attempting to father a child [see Nonclinical Toxicology (13.1)].
- Patients should be advised that pseudomembranous colitis
can occur with minocycline therapy. If patients develop watery or bloody
stools, they should seek medical attention.
- Patients should be counseled about the possibility of
hepatotoxicity. Patients should seek medical advice if they experience symptoms
which can include loss of appetite, tiredness, diarrhea, skin turning yellow,
bleeding easily, confusion, and sleepiness.
- Patients who experience central nervous system symptoms [see
WARNINGS AND PRECAUTIONS ] should be cautioned about driving vehicles or
using hazardous machinery while on minocycline therapy. Patients should seek
medical help for persistent headaches or blurred vision.
- Concurrent use of tetracycline may render oral
contraceptives less effective [see DRUG INTERACTIONS].
- Autoimmune syndromes, including drug-induced lupus-like
syndrome, autoimmune hepatitis, vasculitis and serum sickness have been
observed with tetracycline-class drugs, including minocycline. Symptoms may be
manifested by arthralgia, fever, rash and malaise. Patients who experience such
symptoms should be cautioned to stop the drug immediately and seek medical
- Patients should be counseled about discoloration of skin,
scars, teeth or gums that can arise from minocycline therapy.
- Photosensitivity manifested by an exaggerated sunburn
reaction has been observed in some individuals taking tetracyclines, including
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. Treatment should be discontinued at
the first evidence of skin erythema.
- SOLODYN should be taken exactly as directed. Skipping
doses or not completing the full course of therapy may decrease the effectiveness
of the current treatment course and increase the likelihood that bacteria will
develop resistance and will not be treatable by other antibacterial drugs in
- Patients should be advised to swallow SOLODYN Tablets
whole and not to chew, crush, or split the tablets.
Carcinogenesis, Mutagenesis, Impairment of Fertility
In a carcinogenicity study in which minocycline HCl was
orally administered to male and female rats once daily for up to 104 weeks at
dosages up to 200 mg/kg/day, minocycline HCl 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 HCl 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 HCl 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
Impairment of Fertility
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 as a result of use of SOLODYN). 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 as a result of use of SOLODYN) 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.
Limited human studies suggest that minocycline may have a
deleterious effect on spermatogenesis.
SOLODYN should not be used by individuals of either
gender who are attempting to conceive a child.
Use In Specific Populations
Pregnancy Category D [see WARNINGS AND
SOLODYN should not be used during pregnancy. If the
patient becomes pregnant while taking this drug, the patient should be apprised
of the potential hazard to the fetus and stop treatment immediately.
There are no adequate and well-controlled studies on the
use of minocycline in pregnant women. Minocycline, like other
tetracycline-class drugs, crosses the placenta and may cause fetal harm when
administered to a pregnant woman.
Rare spontaneous reports of congenital anomalies
including limb reduction have been reported with minocycline use in pregnancy
in post-marketing experience. Only limited information is available regarding
these reports; therefore, no conclusion on causal association can be established.
Minocycline induced skeletal malformations (bent limb
bones) in fetuses when administered to pregnant rats and rabbits in doses of 30
mg/kg/day and 100 mg/kg/day, respectively, (resulting in approximately 3 times
and 2 times, respectively, the systemic exposure to minocycline observed in
patients as a result of use of SOLODYN). Reduced mean fetal body weight was
observed in studies in which minocycline was administered to pregnant rats at a
dose of 10 mg/kg/day (which resulted in approximately the same level of
systemic exposure to minocycline as that observed in patients who use SOLODYN).
Minocycline was assessed for effects on peri-and
post-natal development of rats in a study that involved oral administration to
pregnant rats from day 6 of gestation through the period of lactation
(postpartum day 20), at dosages of 5, 10, or 50 mg/kg/day. In this study, body
weight gain was significantly reduced in pregnant females that received 50
mg/kg/day (resulting in approximately 2.5 times the systemic exposure to
minocycline observed in patients as a result of use of SOLODYN). No effects of
treatment on the duration of the gestation period or the number of live pups
born per litter were observed. Gross external anomalies observed in F1 pups
(offspring of animals that received minocycline) included reduced body size,
improperly rotated forelimbs, and reduced size of extremities. No effects were
observed on the physical development, behavior, learning ability, or
reproduction of F1 pups, and there was no effect on gross appearance of F2 pups
(offspring of F1 animals).
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
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
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.