Nifedipine adverse effects

In contrast, there are 2 case reports of patients who developed theophylline toxicity (theophylline levels raised to 30 mg/L and 41 mg/L), apparently due to the addition of nifedipine. In one case, the toxicity recurred on rechallenge, and resolved when the theophylline dosage was reduced by 60%. During a Swan Ganz catheter study of patient response to nifedipine for pulmonary hypertension, 2 patients developed serious nifedipine adverse effects, which responded to intravenous aminophylline. ... 

Because calcium channel antagonists may be more effective, have few serious adverse effects, and can be given less frequently than nitrates, some authorities consider them the agents of choice for variant angina. Nifedipine, verapamil, and diltiazem are all equally effective as single agents for... 

The H2RAs are generally well tolerated. The most common adverse effects are headache, somnolence, fatigue, dizziness, and either constipation or diarrhea. Cimetidine may inhibit the metabolism of theophylline, warfarin, phenytoin, nifedipine, and propranolol, among other drugs. 

In true hypertensive emergencies, nifedipine capsules are contraindicated because of the unpredictability of the fall in arterial pressure. Given the seriousness of the adverse effects and the complete lack of outcome data, the routine use of short-acting nifedipine in hypertensive emergencies should be abandoned. Other slower and therefore probably safer CCBs can be used. 

The pharmacokinetic properties of these drugs are set forth in Table 12-5. The choice of a particular calcium channel-blocking agent should be made with knowledge of its specific potential adverse effects as well as its pharmacologic properties. Nifedipine does not decrease atrioventricular conduction and therefore can be used more safely than verapamil or diltiazem in the presence of atrioventricular conduction abnormalities. A combination of verapamil or diltiazem with 3 blockers may produce atrioventricular block and depression of ventricular function. In the presence of overt heart failure, all calcium channel blockers can cause further worsening of heart failure as a result of their negative inotropic effect. Amlodipine, however, does not increase the mortality of patients with heart failure due to nonischemic left ventricular systolic dysfunction and can be used safely in these patients. 

In a randomized, controlled study of cyclic iloprost or nifedipine in 46 patients with systemic sclerosis, the predictable adverse effects of iloprost (headache, nausea and vomiting, and diarrhea) were common but quickly resolved after the end of the infusion (5). They rarely required a temporary dose reduction. Hypotension occurred less often than with nifedipine. 

Indications. An indication for nifedipine is angina pectoris (p.318). In angina pectoris, it is effective when given either prophylacti-cally or during acute attacks. Adverse effects are palpitation (reflex tachycardia due to hypotension), headache, and pretibial edema. 

If labour begins prematurely, before 33 weeks gestation, myometrial relax-ants (tocolytic agents) can delay it for 48 hours. Beta-2-agonists, such as ritodrine hydrochloride, are given for up to 48 hours to elicit relaxation. Longer treatment is not recommended, because of risk of adverse effects on the mother. Nifedipine and the oxytocin receptor antagonist atosiban are also used to reduce premature uterine contractile activity. 

A patient taking diltiazem developed the signs and symptoms of mania (114) and another developed mania with psychotic features (115). There have also been reports that nifedipine can cause agitation, tremor, belligerence, and depression (116), and that verapamil can cause toxic delirium (117). Nightmares and visual hallucinations have been associated with nifedipine (118). Depression has been reported as a possible adverse effect of nifedipine (119). 

CALCIUM CHANNEL BLOCKERS SSRIs Reports oft serum levels of nimodipine and episodes of adverse effects of nifedipine and verapamil (oedema, flushing and i BP) attributed to t levels when co-administered with fluoxetine Fluoxetine inhibits CYP3A4-mediated metabolism of calcium channel blockers. It also inhibits intestinal P-gp, which may t the bioavailability of verapamil Monitor BP at least weekly until stable. Warn patients to report symptoms of hypotension (lightheadedness, dizziness on standing, etc.). Consider reducing the dose of calcium channel blocker or using an alternative antidepressant... 

CALCIUM CHANNEL BLOCKERS GRAPEFRUIT JUICE t bioavailability of felodipine and nisoldipine (with reports of adverse effects), and t bioavailability of isradipine, lacidipine, lercanidipine, nicardipine, nifedipine, nimodipine and verapamil (without reported adverse clinical effects) Postulated that flavonoids in grapefruit juice (and possibly Seville oranges and limes) inhibit intestinal (but not hepatic) CYP3A4. They also inhibit intestinal P-gp, which may t the bioavailability of verapamil Avoid concurrent use of felodipine and nisoldipine and grapefruit juice... 

NIFEDIPINE PROTON PUMP INHIBITORS - OMEPRAZOLE Possible t efficacy and adverse effects Small t in bioavailability possible via t intragastric pH Unlikely to be clinically significant... 

Gingival hyperplasia, similar to that seen with phenytoin and ciclosporin, is a rare but well-recognized adverse effect of nifedipine (88). It has also been reported in patients taking felodipine (89,90), nitrendipine (SEDA-16, 200), and verapamil (91), suggesting that this adverse effect is a class effect. Only one case of gingival hyperplasia related to calcium channel blockers was reported to the Norwegian Adverse Drug Reaction Committee up to 1991, despite their widespread use (92). However,... 

The calcium channel blockers have had very limited use in pregnancy. The absence of reports of fetal deaths, malformations, or other maternal or neonatal adverse effects cannot therefore be construed as indicating safety. However, a comparison of nifedipine and hydralazine in 54 patients with severe pre-eclampsia showed that nifedipine is more effective, allowing delivery of more mature infants (134). 

Shettigar UR, Loungani R. Adverse effects of sublingual nifedipine in acute myocardial infarction. Crit Care Med 1989 17(2) 196-7. 

In another study the acute response to inhaled nitric oxide and high doses of oral nifedipine or verapamil was assessed in 33 consecutive patients with primary pulmonary hypertension (2). Ten patients responded acutely to nitric oxide, nine of whom responded acutely to calcium channel blockers, without any complications. The other 23 patients failed to respond to nitric oxide and calcium channel blockers. In these non-responders there were nine serious adverse effects with calcium channel blockers. There was no clinical or baseline hemodynamic feature that predicted the acute vasodilator response. Long-term oral treatment with calcium channel blockers was restricted to the nine acute responders, and there was a sustained clinical and hemodynamic improvement in only six patients. It was concluded that nitric oxide may be used as a screening agent for safely identifying patients with primary pulmonary hypertension who may benefit from long-term treatment with calcium channel blockers. 

Ischemic chest pain is an infrequent but well-documented adverse effect of initiating therapy with nifedipine (5). Its mechanism is unclear, but it may arise from reduced overall coronary blood flow or coronary steal (6). 

Sublingual nifedipine, given for hypertensive crises in elderly patients, can cause adverse effects associated with a precipitous fall in blood pressure, even at low doses. In 93 consecutive hypertensive patients without coronary heart disease, aged 65 years or over, nifedipine reduced blood pressure significantly, increased heart rate, and relieved sjmptoms associated with raised blood pressure (9). However, there were electrocardiographic changes consistent with myocardial ischemia in six of 55 patients with left ventricular hypertrophy and in one patient without left ventricular hypertrophy. 

Tocolytic therapy with nifedipine has been reported in several studies to be at least effective as ritodrine, terbu-taline, or magnesium sulfate, with fewer maternal adverse effects (SEDA-18, 216) (SEDA-20,187) (SEDA-22, 217) (SEDA-23, 211). These observations have been confirmed in two trials in 102 and 54 pregnant women of under 34 weeks gestation, randomized to nifedipine or ritodrine. There were no differences in the time of delivery, but significantly fewer maternal adverse effects in those given nifedipine (41,42). 

The possibility that calcium channel blockers can cause cardiovascular adverse effects in pregnancy has been widely debated (SED-14, 598) (SEDA-20, 185) (SEDA-21, 208) (SEDA-22, 214). An uncomplicated non-Q wave myocardial infarction has been reported during nifedipine therapy for preterm labor (43). 

In a review of almost 800 patients randomized to beta-adrenoceptor agonists or nifedipine, the latter was associated with more frequent prolongation of pregnancy, a lower incidence of respiratory distress syndrome, and lower incidences of maternal and fetal adverse effects (44). 

Several studies have raised concerns about the long-term safety of short-acting nifedipine. The proposed mechanism for this adverse effect lies in abrupt vasodilation with reflex sympathetic activation. There does not appear to be either significant reflex tachycardia or long-term adverse outcomes from treatment with sustained-release forms of nifedipine or with dihydropyiidine Ca blockers such as amlodipine or felodipine, which have more favorable (slower) pharmacokinetics. 

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