The Tetracycline Antibiotic Minocycline (MINOCIN) and Benign Intracranial Hypertension

Benign intracranial hypertension is, in fact, not benign at all. It is also known as pseudotumor cerebri and involves a persistent rise in cerebrospinal fluid pressure. This adverse drug reaction is characterized by headache, nausea, vomiting and papilledema (a sign of increased pressure within the central nervous system) with partial paralysis of a nerve that controls eye movement and some facial muscles (sixth cranial nerve palsy). Benign intracranial hypertension is sometimes associated with drug treatment and the tetracycline family of antibiotics is a known cause. This family of drugs includes minocycline (MINOCIN), doxycycline (VIBRAMYCIN) and tetracycline (ACHROMYCIN), drugs commonly used to treat asthma.

The symptoms of benign intracranial hypertension are often similar to those of a brain tumor; thus it is quite important to find out if these symptoms are an adverse drug reaction.

The acne drug isotretinoin (ACCUTANE) has also been associated with a number of cases of benign intracranial hypertension. Because of this, the professional product labeling, or “package insert,” for isotretinoin warns not to use the drug together with tetracycline antibiotics.

The Australian Adverse Drug Reactions Advisory Committee (ADRAC) reviewed cases of benign intracranial hypertension they had received over the past 30 years in their February 2003 newsletter. Of the 76 cases reported to ADRAC during that time, 32 (42 percent) had been associated with the use of minocycline.

All of these 32 patients were young, ranging in age from 12 to 30 with a median age of 16 years, and almost all were being treated for acne with long-term minocycline. The majority of patients, 28 (87 percent), were young women. The time to the development of symptoms of benign intracranial hypertension ranged from two weeks to 18 months, with a median time of about two months.

In one case, the patient developed benign intracranial hypertension one day after she was switched from doxycycline to minocycline. In the majority of cases reported to the Australian authorities, the patients recovered after the minocycline was stopped but recovery was often prolonged, taking from two to 12 weeks in most cases. In those cases where treatment was needed, lumbar puncture — or spinal tap, an invasive procedure to check the cerebrospinal fluid — and drug therapy were used. The ADRAC said that some of the reports described the use of multiple lumbar punctures, one patient required “prolonged hospitalization” and one required a special surgical procedure to relieve cerebrospinal fluid pressure.

The Food and Drug Administration (FDA)-approved package insert for minocycline carries the following general precaution:

Pseudotumor cerebri (benign intracranial hypertension) in adults has been associated with the use of tetracycline. The usual clinical manifestations are headache and blurred vision. Bulging fontanels have been associated with the use of tetracycline in infants. While both of these conditions and related symptoms usually resolve after discontinuation of the tetracycline, the possibility for permanent sequelae exits.

Minocycline is an old but still very popular antibiotic that sold almost 5.5 million prescriptions in 2001 and is now used mainly for the treatment of acne.

What You Can Do

If you are taking minocycline or another tetracycline and develop a persistent unexplained headache, this should be reported to the prescribing physician immediately.