Hematologic Effects: Rabeprazole: There have been post-marketing reports of blood dyscrasias (thrombocytopenia and neutropenia). In the majority of cases where an alternative aetiology cannot be identified, the events were uncomplicated and resolved on discontinuation of rabeprazole.
Aceclofenac: Anemia is sometimes seen in patients receiving NSAIDs. This may be due to fluid retention, occult or gross gastrointestinal blood loss or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia. Nonsteroidal anti-inflammatory drugs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function eg, those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored.
Aceclofenac: General: Aceclofenac cannot be expected to substitute for corticosteroids or to treat corticosteroids insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids.
The pharmacological activity of aceclofenac in reducing inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.
Hepatic Effects: Borderline elevations of ≥1 liver tests may occur in up to 15% of patients taking NSAIDs. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Notable elevations of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) (approximately ≥3 times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported.
A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with aceclofenac, if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (eg, eosinophilia, rash, etc), aceclofenac should be discontinued.
Preexisting Asthma: Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other nonsteroidal antiinflammatory drugs has been reported in such aspirin-sensitive patients, aceclofenac should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with preexisting asthma.
Laboratory Tests: Because serious gastrointestinal tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of gastrointestinal bleeding. Patients on long-term treatment with NSAIDs should have their complete blood count (CBC) and a chemistry profile checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (eg, eosinophilia, rash, etc) or if abnormal liver tests persist or worsen, aceclofenac should be discontinued.
Rabeprazole: General: Symptomatic response to therapy with rabeprazole does not preclude the presence of gastric or esophageal malignancy; therefore, the possibility of malignancy should be excluded prior to commencing treatment with rabeprazole.
Patients on long-term treatment (particularly those treated for more than a year) should be kept under regular surveillance.
A risk of cross-hypersensitivity reactions with other proton-pump inhibitor or substituted benzimidazoles cannot be excluded.
Steady-state interactions of rabeprazole and warfarin have not been adequately evaluated in patients.
There have been reports of increased international normalised ratio (INR) and prothrombin time in patients receiving a PPIs and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with a PPIs and warfarin concomitantly may need to be monitored for increases in INR and prothrombin time.
Hepatic enzyme abnormalities have been reported in clinical trials and as postmarketing adverse events. In the majority of cases where an alternative aetiology cannot be identified, the events were uncomplicated and resolved on discontinuation of rabeprazole. No evidence of significant drug-related safety problems were seen in a study of patients with mild to moderate hepatic impairment versus normal age and sex matched controls. However, because there are no clinical data on the use of rabeprazole in the treatment of patients with severe hepatic dysfunction, the physician is advised to exercise caution when treatment with rabeprazole is first initiated in such patients. Patients with healed gastroesophageal reflux disease (GERD) were treated for up to 40 months with rabeprazole and monitored with serial gastric biopsies. Patients without H. pylori infection (221 of 326 patients) had no clinically important pathologic changes in the gastric mucosa. Patients with H. pylori infection at baseline (105 of 326 patients) had mild or moderate inflammation in the gastric body or mild inflammation in the gastric antrum. Patients with mild grades of infection or inflammation in the gastric body tended to change to moderate, whereas those moderate at baseline tended to remain stable. Patients with mild grades of infection or inflammation in the gastric antrum tended to remain stable. At baseline, 8% of patients had atrophy of glands in the gastric body and 15% had atrophy in the gastric antrum. At endpoint, 15% of patients had atrophy of glands in the gastric body and 11% had atrophy in the gastric antrum. Approximately, 4% of patients had intestinal metaplasia at some point during follow-up, but no consistent changes were seen.
Co-administration of atazanavir with rabeprazole and its fixed-dose combination (FDCs) is not recommended (see Interactions).
Effects on the Ability to Drive or Operate Machinery: Aceclofenac: Patients suffering from dizziness, vertigo, or other central nervous system disorders whilst taking NSAIDs should refrain from driving or handling dangerous machinery.
Based on the pharmacodynamic properties and the adverse events profile, it is unlikely that rabeprazole would cause an impairment due to somnolence, it is recommended that driving and operating complex machinery be avoided.
Impairment of Fertility: NSAIDs may impair fertility and is not recommended in women trying to conceive. The temporary discontinuation of aceclofenac should be considered in women having difficulties to conceive or undergoing investigations for infertility.