Minocycline hydrochloride warnings and precautions

# Warnings and Precautions

## Warnings
MINOCYCLINE, LIKE OTHER TETRACYCLINE-CLASS ANTIBIOTICS, 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. THE USE OF DRUGS OF THE TETRACYCLINE CLASS DURING TOOTH DEVELOPMENT (LAST HALF OF PREGNANCY, INFANCY, AND CHILDHOOD 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 DEVELOPMENT UNLESS OTHER DRUGS ARE NOT LIKELY TO BE EFFECTIVE OR ARE CONTRAINDICATED.
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 six 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 have toxic effects on the developing fetus (often related to retardation of skeletal development). Evidence of embryotoxicity has been noted in animals treated early in pregnancy.
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 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.
Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. This has been reported rarely with minocycline.
Central nervous system side effects including lightheadedness, 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 disappear rapidly when the drug is discontinued.

## Precautions
General
As with other antibiotic preparations, use of this drug may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, the antibiotic should be discontinued and appropriate therapy instituted.
Pseudotumor cerebri (benign intracranial hypertension) in adults has been associated with the use of tetracyclines. The usual clinical manifestations are headache and blurred vision. Bulging fontanels have been associated with the use of tetracyclines in infants. While both of these conditions and related symptoms usually resolve after discontinuation of tetracycline, the possibility for permanent sequelae exists.
Incision and drainage or other surgical procedures should be performed in conjunction with antibiotic therapy when indicated.
Prescribing minocycline hydrochloride capsules 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.
INFORMATION FOR PATIENTS
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 tetracycline drugs, and treatment should be discontinued at the first evidence of skin erythema. This reaction has been reported rarely with use of minocycline.
Patients who experience central nervous system symptoms (see WARNINGS) should be cautioned about driving vehicles or using hazardous machinery while on minocycline therapy.
Concurrent use of tetracycline may render oral contraceptives less effective (see Drug Interactions).
Patients should be counseled that antibacterial drugs including minocycline hydrochloride capsules should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When minocycline hydrochloride capsules are 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 minocycline hydrochloride capsules or other antibacterial drugs in the future.
Laboratory Tests
In long-term therapy, periodic laboratory evaluations of organ systems, including hematopoietic, renal, and hepatic studies should be performed.
All patients with gonorrhea should have a serologic test for syphilis at the time of diagnosis. Patients treated with minocycline should have a follow-up serologic test for syphilis after 3 months.
Drug Interactions
Because tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage.
Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving tetracycline-class drugs in conjunction with penicillin.
Absorption of tetracyclines is impaired by antacids containing aluminum, calcium or magnesium, and iron-containing preparations.
The concurrent use of tetracycline and methoxyflurane has been reported to result in fatal renal toxicity.
Concurrent use of tetracyclines with oral contraceptives may render oral contraceptives less effective.
Drug/Laboratory Test Interactions
False elevations of urinary catecholamine levels may occur due to interference with the fluorescence test.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Dietary administration of minocycline in long-term tumorigenicity studies in rats resulted in evidence of thyroid tumor production. Minocycline has also been found to produce thyroid hyperplasia in rats and dogs. In addition, there has been evidence of oncogenic activity in rats in studies with a related antibiotic, oxytetracycline (i.e., adrenal and pituitary tumors). Likewise, although mutagenicity studies of minocycline have not been conducted, positive results in in vitro mammalian cell assays (i.e., mouse lymphoma and Chinese hamster lung cells) have been reported for related antibiotics (tetracycline hydrochloride and oxytetracycline). Segment I (fertility and general reproduction) studies have provided evidence that minocycline impairs fertility in male rats.
Pregnancy
Teratogenic Effects
Pregnancy Category D
(See WARNINGS)
Nonteratogenic Effects
(See WARNINGS)
Labor and Delivery
The effect of tetracyclines on labor and delivery is unknown.
Nursing Mothers
Tetracyclines are excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from the tetracyclines, 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).
Pediatric Use
(See WARNINGS.)