Because it lowers blood pressure, clonidine should be used with caution in patients with severe coronary insufficiency, recent myocardial infarction, cerebrovascular disease or chronic renal failure. Clonidine should be used with caution in patients with mild to moderate bradyarrhythmia such as low sinus rhythm, with disorders of cerebral or peripheral perfusion, polyneuropathy, and constipation, patients with heart failure or severe coronary heart disease.

Depending on the dose given, clonidine can lower the heart rate and pulse rate. In patients with diseases affecting the rhythmic and AV conduction system of the heart, arrhythmias have been observed after high doses.

Tolerance may develop in some patients, necessitating a re-evaluation of therapy. This usually consists of an increase in dosage or concomitant administration of a diuretic to enhance the hypotensive response to the drug.

The dosage of clonidine should be increased gradually to minimize the sedative effect of the drug. This is of particular importance in those patients who operate automobiles and potentially dangerous machinery.

Patients with a known history of depression should be carefully supervised while under treatment with clonidine, as there have been occasional reports of further depressive episodes occurring in such patients.

In several studies clonidine produced a dose-dependent increase in the incidence and severity of spontaneously occurring retinal degeneration in albino rats treated for 6 months or longer. In view of this retinal degeneration, eye examinations were performed in 908 patients prior to the start of clonidine therapy, who were then examined periodically thereafter. In 353 of these 908 patients, examinations were performed for periods of 24 months or longer. Except for the dryness of the eyes, no drug-related abnormal ophthalmologic findings were recorded and clonidine did not alter retinal function as shown by specialized tests such as the electroretinogram and macular dazzle. It is recommended that as an integral part of their overall long-term care, patients treated with clonidine should receive periodic eye examinations.

As with any drug excreted primarily in the urine, smaller doses of the drug are often effective in treating patients with a degree of renal failure. In patients exhibiting renal failure or insufficiency, periodic determination of the BUN is indicated. If, in the physician's opinion, a rising BUN is significant, the drug should be stopped.

A few instances of a condition resembling Raynaud's phenomenon have been reported. Caution should therefore be observed if patients with Raynaud's disease or thromboangiitis obliterans are to be treated with clonidine.

Pheochromocytoma: Clonidine is not indicated in pheochromocytoma. However, in contrast to guanethidine and reserpine the drug has no crisis-inducing properties, in this condition.

Clonidine does not affect the urinary VMA and catecholamine excretion significantly in patients with pheochromocytoma, so that no false positive or false negative results will occur during the administration of the drug.