Rablet-D Special Precautions

General: Rabeprazole: Symptomatic response to therapy with rabeprazole does not preclude the presence of gastric malignancy.
Patients with healed gastroesophageal reflux disease (GERD) were treated for up to 40 months with rabeprazole and monitored with serial gastric biopsies. Patients with 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 graded 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.
Steady-state interactions of rabeprazole and warfarin have not been adequately evaluated in patients. There have been reports of increased international normalized ratio (INR) and prothrombin time in patients receiving a proton-pump inhibitor and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with a proton-pump inhibitor and warfarin concomitantly may need to be monitored for increase in INR and prothrombin time.
Domperidone: Hepatic Insufficiency: Since domperidone is highly metabolised in the liver, domperidone should not be used in patients with hepatic impairment.
Renal Insufficiency: In patients with severe renal insufficiency (serum creatinine >6 mg/100 mL, ie, >0.6 mmol/L), the elimination half-life (t_½) of domperidone was increased from 7.4-20.8 hrs, but plasma drug levels were lower than in healthy volunteers. Since very little unchanged drug is excreted via the kidneys, it is unlikely that the dose of a single administration needs to be adjusted in patients with renal insufficiency. However, on repeated administration, the dosing frequency should be reduced to once or twice daily depending on the severity of the impairment and the dose may need to be reduced. Such patients on prolonged therapy should be reviewed regularly.
Use with Ketoconazole: A slight increase of QT interval (mean <10 msec) was reported in a drug interaction study with oral ketoconazole. Even if the significance of this study is not fully clear, alternative therapeutic options should be considered if antifungal treatment is required.
Effects on the Ability to Drive or Operate Machinery: Domperidone has no or negligible influence on the ability to drive and use machines.
Use in pregnancy: Rabeprazole: Teratology studies have been performed in rats at IV doses up to 50 mg/kg/day (plasma AUC of 11.8 mcg•hr/mL, about 13 times the human exposure at the recommended dose for GERD) and rabbits at IV doses up to 30 mg/kg/day (plasma AUC of 7.3 mcg•hr/mL, about 8 times the human exposure at the recommended dose for GERD) and have revealed no evidence of impaired fertility or harm to the fetus due to rabeprazole. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Rablet-D should be used during pregnancy only if clearly needed.
Domperidone: There are limited post-marketing data on the use of domperidone in pregnant women. Domperidone should only be used during pregnancy when justified by the anticipated therapeutic benefit. A study in rats has shown reproductive toxicity at a high, maternally toxic dose. The potential risk for humans is unknown.
Use in lactation: Rabeprazole: Following IV administration of 14C-labeled rabeprazole to lactating rats, radioactivity in milk reached levels that were 2- to 7-fold higher than levels in the blood. It is not known if unmetabolized rabeprazole is excreted in human breast milk. Administration of rabeprazole to rats in late gestation and during lactation at doses of 400 mg/kg/day (about 195 times the human dose based on mg/m²) resulted in decreases in body weight gain of the pups. Since many drugs are excreted in milk and because of the potential for adverse reactions to nursing infants from rabeprazole, a decision should be made to discontinue nursing or Rablet-D, taking into account the importance of the drug to the mother.
Domperidone: Domperidone is excreted in breast milk of lactating rats (mostly as metabolites: peak concentration of 40 and 800 ng/mL after oral and IV administration of 2.5 mg/kg, respectively). Domperidone concentrations in breast milk of lactating women are 10-50% of the corresponding plasma concentrations and expected not to exceed 10 ng/mL. The total amount of domperidone excreted in human breast milk is expected to be <7 mcg/day at the highest recommended dosing regimen. It is not known whether this is harmful to the newborn. Therefore, breastfeeding is not recommended for mothers who are taking domperidone.
Use in children: Rabeprazole: The safety and effectiveness of rabeprazole in pediatric patients have not been established.
Domperidone: Neurological side effects are rare (see Adverse Reactions). Since metabolic functions and the blood-brain barrier are not fully developed in the first months of life, the risk of neurological side effects is higher in young children.
Overdosing may cause extrapyramidal symptoms in children but other causes should be taken into consideration.
Use in the elderly: Rabeprazole: Of the total number of subjects in clinical studies of rabeprazole, 19% were ≥65 years, while 4% were ≥75 years. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.