Correspondence

Hypertension in Children

N Engl J Med 1997; 336:1675-1676June 5, 1997

Article

To the Editor:

Dr. Sinaiko's review of hypertension in children (Dec. 26 issue)1 includes a recommendation to use oral nifedipine capsules for urgent or emergency treatment of hypertension. Dr. Sinaiko states, “For rapid absorption the drug must first be removed from the capsule or the patient must bite through the capsule.” The sublingual absorption of nifedipine is negligible, whereas absorption from the gastrointestinal tract is complete.2 Removing the drug from the capsule is often associated with unintentional losses, such as spillage or loss from the mouth, which make the dose of the drug administered uncertain. A significant decline in blood pressure is typically observed 5 to 10 minutes after oral administration of the short-acting capsule, with the peak effect occurring between 30 and 60 minutes. The 1996 product label for Procardia states, “There is little difference in relative bioavailability when . . . capsules are given orally and either swallowed whole; bitten and swallowed; or, bitten and held sublingually.”

Furthermore, in adults with severe elevations in blood pressure, nifedipine has been reported to cause cerebral ischemia, myocardial ischemia, and symptomatic hypotension.3 Preexisting myocardial ischemia, hypovolemia, or coronary artery disease seems to predispose patients to these events. However, asymptomatic patients without end-organ damage have also had signs and symptoms of ischemia when treated with oral or sublingual nifedipine.4 In 1985 the Cardiorenal Advisory Committee of the Food and Drug Administration rejected the use of short-acting nifedipine capsules given orally or sublingually for hypertensive emergencies, because of the lack of outcome data and the possibility of adverse effects.5 The use of nifedipine in children was not specifically addressed in the advisory committee's decision, but one wonders whether the very small number of children requiring urgent or emergency treatment to lower blood pressure provides a sufficient basis for making a judgment about the safety of nifedipine. The potential for harm would seem to outweigh the potential benefits, considering the proven safety and efficacy of the alternative therapies described by Sinaiko.

Patricia M. Flint, Pharm.D.
Donald B. Middleton, M.D.
St. Margaret Memorial Hospital, Pittsburgh, PA 15215

5 References

1
Sinaiko AR. Hypertension in children. N Engl J Med 1996;335:1968-1973
Full Text | Web of Science | Medline

2
van Harten J, Burggraaf K, Danhof M, van Brummelen P, Breimer DD. Negligible sublingual absorption of nifedipine. Lancet 1987;2:1363-1365
CrossRef | Web of Science | Medline

3
Grossman E, Messerli FH, Grodzicki T, Kowey P. Should a moratorium be placed on sublingual nifedipine capsules given for hypertensive emergencies and pseudoemergencies? JAMA 1996;276:1328-1331
CrossRef | Web of Science | Medline

4
Wachter RM. Symptomatic hypotension induced by nifedipine in the acute treatment of severe hypertension. Arch Intern Med 1987;147:556-558
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5
Winker MA. The FDA's decisions regarding new indications for approved drugs: where's the evidence? JAMA 1996;276:1342-1343
CrossRef | Web of Science | Medline

To the Editor:

In his excellent review, Sinaiko does not include Takayasu's arteritis among the causes of hypertension in children. In our institute, 85 percent of children with this type of vasculitis have severe arterial hypertension. The abnormal blood pressure causes much morbidity.1,2 In children, Takayasu's arteritis is often difficult to recognize. The presence of hypertension is an important clue to its diagnosis.1

Manuel Martínez-Lavín, M.D.
Alfonso Buendía, M.D.
Carlos Pineda, M.D.
Instituto Nacional de Cardiología Ignacio Chávez, 14080 Mexico DF, Mexico

2 References

1
Morales E, Pineda C, Martinez-Lavin M. Takayasu's arteritis in children. J Rheumatol 1991;18:1081-1084
Web of Science | Medline

2
Hong CY, Yun YS, Choi JY, et al. Takayasu arteritis in Korean children: clinical report of seventy cases. Heart Vessels Suppl 1992;7:91-96
CrossRef | Medline

Author/Editor Response

Dr. Sinaiko replies:

To the Editor: Flint and Middleton question the advisability of removing nifedipine from the capsule before administration. They also note the important adverse cardiovascular events reported in adults receiving short-acting nifedipine and suggest that the potential for similar adverse events in children should preclude its use in this age group.

Nifedipine is removed from the capsule in most cases simply because many children have difficulty swallowing the capsule. This practice does not appear to compromise the effectiveness of the drug, despite the possibility of minimal loss of the drug during its administration. It is true that the bioavailability of nifedipine is similar with the various methods of oral administration, but the product label for Procardia further states, “However, biting through the capsule prior to swallowing does result in slightly earlier plasma concentrations than if capsules are swallowed intact.” This suggests a more rapid clinical response when the capsule is bitten before it is swallowed. Blood pressure in children has been reported to fall within 5 to 10 minutes after oral administration, with a maximal response at approximately 30 minutes and a peak response as early as 15 minutes after administration in some patients.1

Nifedipine is widely used, particularly by pediatric nephrologists, to treat severe hypertension in children. There have not been any severe adverse events reported in the literature, and the consensus among pediatricians is that the drug is safe and effective. Ingestion of 70 mg of nifedipine per kilogram of body weight by a 14-month-old child was reported; third-degree atrioventricular block and cardiac arrest developed, but the patient recovered fully.2 Caution must be used in treating severe hypertension in children, and intravenous therapy with labetalol and nitroprusside is frequently used in medical emergencies.3

Extrapolation of drug-test data from adults to children can fail to identify potential differences in dosing, effectiveness, and adverse reactions, so physicians must be alert to the possibility of specific side effects of cardiovascular drugs in children. It would be foolish to ignore the reports of adverse events in adults, but it is important to consider the difference in the risk of cardiovascular events or disease between adults and children, which may account for the seemingly safer risk profile for nifedipine in children. Nifedipine is an easily administered and effective treatment for severe hypertension in children, and it does not appear to be associated with the side effects recognized in adults.

Alan R. Sinaiko, M.D.
University of Minnesota, Minneapolis, MN 55455

3 References

1
Siegler RL, Brewer ED. Effect of sublingual or oral nifedipine in the treatment of hypertension. J Pediatr 1988;112:811-813
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