Captopril

Respiratory

Two cases of alveolitis have been reported with captopril, one associated with eosinophilia [ ] and the other with a lymphocytic pulmonary infiltrate [ ].

Pulmonary infiltrates with eosinophilia has been reported in association with captopril in adults and children [ ].

• An 8-month-old girl with complex congenital heart disease was given captopril 1 mg tds 4 days after corrective cardiac surgery. Two days later she had a peripheral blood eosinophilia and on postoperative day 17 she returned to the emergency room complaining of clear rhinorrhea, poor feeding, a low-grade fever, and reduced urine output. She was tachypneic with a low oxygen saturation on room air (85%). There was a peripheral eosinophilia and diffuse infiltrates on the chest X-ray. A presumptive diagnosis of captopril-induced pulmonary infiltrates with eosinophilia was made. Captopril was withdrawn and she was given systemic steroids. Other investigations failed to suggest an alternative diagnosis and she improved clinically over 5 days. Serial chest X-rays showed slow resolution of the infiltrates and the full blood count returned to normal.

Sensory systems

A report from the Australian Drug Evaluation Committee has confirmed that dysgeusia (taste disturbance and taste loss) is more likely to complicate treatment with captopril than with other ACE inhibitors; captopril accounted for more than half the cases of taste loss [ ]. Taste loss was dose-related, in that more than 90% of reports detailed a daily dose of 50 mg or more. Most cases recovered on withdrawal, although the sense of taste had not returned 7 months after withdrawal in one case, and in two of the reports there was associated anosmia. Although there was no significant difference between captopril and lisinopril [ ], it appears that captopril, presumably via its sulfhydryl group, is more likely to provoke dysgeusia.

Hematologic

Anecdotal reports of a bone-marrow suppressant effect of captopril have been published. Cases of neutropenia and agranulocytosis [ ] have also been reported, although in some of these there were complicating issues, making a clear association difficult to establish. Usually the incidence is higher in patients with renal insufficiency or collagen vascular disease. In few cases the white cell count returned to normal when captopril was withdrawn. Although agranulocytosis has been attributed to the presence of the sulfhydryl group in captopril, it has also been reported with enalapril [ ].

Agranulocytosis has also been reported in association with toxic epidermal necrolysis [ ].

• A 59-year-old woman with long-standing hypertension took captopril 200 mg bd plus hydrochlorothiazide 50 mg od and 3 days later developed nausea, vomiting, malaise, and a severe, pruritic, erythematous rash, with severe dehydration and orthostatic hypotension. The diuretic was withdrawn and intravenous fluids and diphenhydramine were given. She recovered within 1 week and remained asymptomatic for 4 weeks. She then developed fever, malaise, a new rash, orthostatic hypotension, and diffuse erythroderma. Her posterior pharynx was erythematous. She had neutropenia (900 × 106/l) and captopril was withdrawn. She was treated empirically with antibiotics and intravenous fluids and subcutaneous granulocyte colony-stimulating factor (G-CSF) for 5 days. The erythroderma progressed to large coalescing blisters, which then ruptured, producing large areas of weeping skin over all her limbs. The bone-marrow and skin recovered fully within 2 weeks.

Autoimmune thrombocytopenia, gradually reversible on withdrawal of captopril, was reported in three patients taking captopril [ ].

Pancytopenia has been reported in a premature newborn treated with captopril for renovascular hypertension [ ]. Trilineage bone marrow suppression leading to pancytopenia is a very rare complication, which may be dose-related in the therapeutic range (a collateral or toxic reaction). In this case the authors surmised that accumulation due to renal tubular dysfunction of prematurity, combined with renal artery stenosis, may have explained the adverse effect in the absence of overt renal dysfunction. They recommended that captopril should be used with caution in premature babies and neonates with underlying renal or renovascular disease, even if they do not have overt renal dysfunction.

Hemolytic anemia has been attributed to captopril [ ].

• A 91-year-old African–American woman with hypertension, hypothyroidism, and osteoarthritis developed cardiac failure and uncontrolled atrial fibrillation. After initial heart rate control, anticoagulation, and diuresis, she was given captopril. Over the next 2 days, and in the absence of clinical and imaging evidence of bleeding, her hemoglobin concentration fell from 12.0 to 8.2 g/dl. Further laboratory tests showed evidence of hemolysis and she required 3 units of blood. Captopril was withdrawn and her hemoglobin concentration stabilized and increased over the next 5 days.

Salivary glands

Sialadenitis has been reported in two patients who had taken captopril for hypertension and developed non-painful bilateral parotid and submandibular gland swelling [ ]. In one case there was associated upper chest and face erythema, and in the other conjunctival erythema. The authors concluded that the symptoms had probably been caused by the drug, and they suggested that inflammatory mediators or vasodilators (for example bradykinin) could have induced salivary gland obstruction by spasm or edema, or that the drug may have interfered with salivary secretion at a cellular level.