Hypertensive crisis secondary to phenylpropanolamine interacting with triple-drug therapy for HIV prophylaxis.

Major advances in therapy of the human immunodeficiency virus (HIV) have occurred during the last several years, with many new and efficacious medications becoming available. Regulatory policies regarding pre–market testing of anti-HIV drugs are more lenient than for other agents, and many newer drugs have been accelerated through the trial process, as their proposed benefits of early availability outweigh the risks of unusual and unpredictable adverse reactions. Hence, many adverse reactions are reported in postmarketing surveillance, leading to modifications in the recommendations and precautions regarding the use of these agents. We report an unusual drug interaction that may have wide implications for prescribers and the recipients of such medications. Ten days before admission, a 28-year-old resident in internal medicine was started on triple-drug HIV prophylaxis after a needle stick injury from a known HIVpositive patient. She was treated with zidovudine, indinavir, and lamivudine at the recommended dosages. One week later, stavudine was substituted for zidovudine, as she was experiencing nausea and vomiting. Her past medical history was notable for Raynaud’s phenomenon of 5 years’ duration and sinus complaints for 20 years. She was intermittently using Tavist-D (clemastine and phenylpropanolamine), an over-the-counter nasal decongestant preparation. There was no family history of hypertension. Her blood pressure recorded at her pre-employment physical examination was 120/70 mm Hg. On the day of admission, she took her medications as scheduled in the morning; in the afternoon, she took clemastine/phenylpropanolamine for her sinus complaints. Six hours later, she had a feeling of chest tightness, associated with difficulty in breathing. Shortly thereafter, she experienced left-sided upper extremity weakness, followed by a severe right-sided temporal headache, described as pulsatile in nature. At this time, her blood pressure was recorded as 220/120 mm Hg with a pulse of 64 beats per minute. In the hospital, these findings were confirmed, including the neurologic deficit. A computerized tomogram (CT) of the head showed no signs of intracranial hemorrhage. Her blood pressure returned to normal without treatment within 4 hours, and the neurologic deficit resolved over the next 8 hours. However, 12 hours later, the same neurologic deficit recurred, although no increase in blood pressure was noted. A repeat CT scan and a magnetic resonance imaging study showed no evidence of infarction or hemorrhage. Reversible cerebral vasoconstriction, secondary to sympathomimetic intoxication, was thought to be the cause of the neurologic deficit. She was treated with nimodipine (60 mg every 4 hours) and aspirin (325 mg daily). Her neurologic deficit improved, and no recurrence was noted. Her blood pressure has been normal since the episode, with 100/60 mm Hg representing a typical recording. Hypertensive crisis can occur in patients with sympathetic overactivity secondary to sympathomimetic agent overdosage, or when sympathomimetic agents are administered inadvertently while the patient is also receiving a monoamine oxidase inhibitor. The temporal association between the administration of clemastine/phenylpropanolamine and the appearance of the symptoms is highly suggestive that this medication was the causative agent. Clemastine, a histamine-1 antagonist with anticholinergic activity, is unlikely to be the etiologic component, as no hypertensive episode has been reported with this medication (1). Phenylpropanolamine is a mixedacting sympathomimetic agent, thought to displace catecholamines from intraneuronal vesicles, as well as having a direct stimulant effect on alpha and beta adrenergic receptors. Phenylpropanolamine has been known to cause hypertensive crisis (2). In our patient phenylpropanolamine alone is unlikely to be causative, however, as the patient had been taking it for several years without any adverse reaction. Recent addition of the anti-HIV regimen leads us to believe that one or more of these medications potentiated the effect of phenylpropanolamine, leading to the hypertensive crisis. We can only speculate as to which anti-HIV medication was responsible for this effect, as complete drug interaction profiles are not available for most newer anti-HIV agents. Indinavir, a protease inhibitor, has been commonly linked to adverse reactions because of its interaction with the cytochrome P450 system. Lamivudine, a nucleoside analog, has been reported to cause headache, insomnia, and abdominal symptoms. No symptoms related to sympathetic hyperactivity have been reported with these agents. Zidovudine, a nucleoside analog, has From the Department of Medicine, State University of New York, Health Science Center at Brooklyn, Brooklyn, New York. Requests for reprints should be addressed to Thomas P. Bradley, MD, State University of New York, Health Science Center at Brooklyn, 450 Clarkson Avenue, Box 50, Brooklyn, New York 11203. Manuscript submitted March 10, 1998, and accepted in revised form September 9, 1998. Hypertension, Phenylpropanolamine, and HIV Prophylaxis/Khurana et al