Pronizor 30 mg Delayed release capsules

u2022 PRONIZOR 30 mg is indicated for the short-term treatment of active duodenal ulcers and reflux oesophagitis.

u2022 PRONIZOR 30 mg is indicated for Helicobacter pylori-positive duodenal ulcers in conjunction with appropriate antibiotics as part of an eradication program.

u2022 PRONIZOR 30 mg is indicated for the short - term treatment of gastric ulcer.

Posology

One 30 mg capsule once a day for up to eight weeks.

Duodenal ulcer: The recommended dosage is one 30 mg capsule once a day for 2 to 4 weeks. Patients may respond adequately to 15 mg daily for 2 to 4 weeks, and therefore individual dose adjustments should be considered.

PRONIZOR 30 mg is indicated for Helicobacter pylori -positive duodenal ulcers as part of an eradication program, with appropriate antibiotics.

Oesophagitis due to gastro-oesophageal reflux: The recommended dosage is one 30 mg capsule once a day for 4 weeks. Depending on the endoscopic results, a repeat course of 4 weeks may be necessary. Patients may respond adequately to 15 mg daily for 4 weeks with a second 4 week treatment period, at the same dosage, depending on endoscopic results.

Functional dyspepsia: Adults: 15 to 30 mg once a day for 2 to 4 weeks. Elderly : No dose adjustment is necessary. However, 30 mg per day is the maximum daily dose.

Renal impairment : No dose adjustment is necessary in renal failure - this also applies to patients on dialysis.

Paediatric patients Safety and efficacy in children has not been established (see section 4.4).

Method of administration PRONIZOR 30 mg should preferably be taken before a meal.

PRONIZOR is contraindicated in :

• Patients with hypersensitivity to lansoprazole or to any of the other ingredients contained in PRONIZOR 30 mg (see Section 6.1),
• Pregnancy and lactation (see Section 4.6).
• Liver impairment.
• PRONIZOR 30 mg should not be used concomitantly with atazanavir and nelfinavir (see Section 4.5).

Children Safety and efficacy in children has not been established.

Occurrence of acute interstitial nephritis: Acute interstitial nephritis has been observed in patients taking PPIs including PRONIZOR 30 mg Acute interstitial nephritis may occur at any point during therapy and is generally attributed to an idiopathic hypersensitivity reaction. Discontinue PRONIZOR 30 mg if acute interstitial nephritis develops (see section 4.3).

Malignant disease Treatment with PRONIZOR 30 mg may alleviate the symptoms of malignant ulcers and can delay diagnosis. Therefore, the possibility of malignancy of a gastric ulcer or a malignant disease of the oesophagus should be excluded prior to treatment with PRONIZOR 30 mg.

Malabsorption Proton pump inhibitors such as PRONIZOR 30 mg have been reported to result in a substantial reduction in cyanocobalamin (VitaminB12) absorption, probably related to the increase in gastric pH, and indicating a potential risk of vitamin deficiency with long-term therapy. Proton pump inhibitors such as PRONIZOR 30 mg have also been reported to impair the bioavailability of dietary vitamin C. Fat malabsorption, secondary to increased deconjugation of bile acids caused by bacterial overgrowth in the jejunum, has also been reported with proton pump inhibitors such as PRONIZOR 30 mg treatment. It has been suggested that proton pump inhibitors such as PRONIZOR 30 mg can cause calcium malabsorption.

Subacute cutaneous lupus erythematosus (SCLE) Proton pump inhibitors such as PRONIZOR 30 mg are associated with very infrequent cases of SCLE. If lesions occur, especially in sun-exposed areas of the skin, and if accompanied by arthralgia, the patient should seek medical help promptly and the health care professional should consider stopping PRONIZOR 30 mg SCLE after previous treatment with a proton pump inhibitor such as PRONIZOR 30 mg may increase the risk of SCLE with other proton pump inhibitors.

Alcohol and CNS depressants PRONIZOR 30 mg may lead to drowsiness and impaired concentration that may be aggravated by the simultaneous intake of alcohol or other central nervous system depressants.

Hypomagnesaemia Severe hypomagnesaemia has been reported with the use of PPIs like lansoprazole, as contained in PRONIZOR 30 mg for at least three months and in most cases for a year. Serious manifestations of hypomagnesaemia such as fatigue, tetany, delirium, convulsions, dizziness and ventricular dysrhythmia can occur but they may begin insidiously and be overlooked. Hypomagnesaemia may lead to hypocalcaemia and/or hypokalaemia (see section 4.8). Other serious events include tremors, carpo-pedal spasm, atrial fibrillation, supraventricular tachycardia, and abnormal QT interval. In most affected patients, hypomagnesaemia improved after magnesium replacement and discontinuation of the PPI. For patients expected to be on prolonged treatment or who take PRONIZOR 30 mg with digoxin or medicines that may cause hypomagnesaemia (e.g. diuretics), health care professionals should consider measuring magnesium levels before starting PRONIZOR 30 mg treatment and periodically during treatment.

Bone fracture PPIs like lansoprazole, as contained in PRONIZOR 30 mg , especially if used in high doses and over long periods (over 1 year), may increase the risk of hip, wrist and spine fracture, predominantly in the elderly or in presence of other recognised risk factors. Reports suggest that PPIs may increase the overall risk of fracture by 10 u2013 40 %. Some of this increase may be due to other risk factors. Patients at risk of osteoporosis should receive care according to current clinical guidelines and they should have an adequate intake of vitamin D and calcium.

Clostridium difficile associated diarrhoea(CDAD) PPIs like lansoprazole, as contained in PRONIZOR 30 mg has been linked to an increased risk of enteric infections such as CDAD. A diagnosis of CDAD should be considered for patients taking PRONIZOR 30 mg who develop diarrhoea that does not improve. Symptoms include watery stool, abdominal pain, and fever, and patients may go on to develop more serious intestinal conditions. Factors that may predispose an individual to developing CDAD include advanced age, certain chronic medical conditions, and taking broad spectrum antibiotics. Treatment for CDAD includes the replacement of fluids and electrolytes and the use of special antibiotics.

Reflux Oesophagitis gastric glandular cysts Diagnosis of reflux esophagitis should be confirmed by endoscopy.

Effects related to acid inhibition During long-term treatment, gastric glandular cysts have been reported in increased frequency. These physiological changes result from pronounced inhibition of gastric acid secretion.

Gastrointestinal infections caused by bacteria Decreased gastric acidity increases gastric counts of bacteria normally present in the gastrointestinal tract. Treatment with PRONIZOR 30 mg may lead to an increased risk of gastrointestinal infections such as Salmonella, Campylobacter, Shigella or Clostridium difficile.

Presence of alarm symptoms In the presence of symptoms such as, significant unintentional weight loss, recurrent vomiting, dysphagia, haematemesis or melaena, and when gastric ulcer is suspected or present, malignancy should be excluded, as treatment with PRONIZOR 30 mg may alleviate symptoms and delay diagnosis.

H. pylori In patients suffering from gastro-duodenal ulcers, the possibility of H. pylori infection as an etiological factor should be considered.

Long term use Because of limited safety data for patients on maintenance treatment for longer than 1 year, regular review of the treatment should be regularly performed in these patients.

Colitis Colitis has occurred in patients taking lansoprazole as contained in PRONIZOR 30 mg Therefore, in the case of severe and/or persistent diarrhoea, discontinuation of therapy should be considered.

Excipients Contains sucrose. Patients with rare hereditary conditions such as fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take PRONIZOR 30 mg.

Effects of PRONIZOR 30 mg on other medications

Medicines with pH dependent absorption

PRONIZOR 3 0 mg may interfere with the absorption of medicines where gastric pH is critical to bioavailability (e.g. ampicillin esters, iron salts).

HIV medications

PRONIZOR 30 mg should not be used with atazanavir or nelfinavir, as it substantially reduces exposure to the HIV-protease inhibitor (see Section 4.3).

Ketoconazole and itraconazole

The absorption of ketoconazole and itraconazole from the gastrointestinal tract is enhanced by the presence of gastric acid. Administration of PRONIZOR 30 mg may result in subtherapeutic concentrations of ketoconazole and itraconazole and the combination should be avoided.

Digoxin

Co-administration of PRONIZOR 30 mg and digoxin may lead to increased digoxin plasma levels. The plasma levels of digoxin should therefore be monitored and the dose of digoxin adjusted if necessary when initiating and ending PRONIZOR 30 mg treatment.

Medicines metabolised by P450 enzymes

PRONIZOR 30 mg CAPSULES may increase plasma concentrations of medicines that are metabolised by CYP3A4. Caution is advised when combining PRONIZOR 30 mg with medicines which are metabolised by this enzyme and have a narrow therapeutic window.

Theophylline

An increase in clearance of theophylline may be seen if given concomitantly with PRONIZOR 30 mg Patients may require additional titration of their theophylline dosage when PRONIZOR 30 mg is started or stopped to ensure clinically effective blood levels.

Tacrolimus

Co - administration of PRONIZOR 3 0 mg increases the plasma concentrations of tacrolimus (a CYP3A and P-gp substrate). Monitoring of tacrolimus plasma concentrations is advised when concomitant treatment with PRONIZOR 30 mg is initiated or ended.

Medicines transported by P-glycoprotein

Lansoprazole has been observed to inhibit the transport protein, P-glycoprotein (P-gp) in vitro. The clinical relevance of this is unknown.

Effects of other medicines on PRONIZOR 30 mg

Medicines which inhibit CYP2C19

Fluvoxamine A dose reduction may be considered when combining PRONIZOR 30 mg with the CYP2C19 inhibitor fluvoxamine.

Medicines which induces CYP2C19 and CYP3A4

Enzyme inducers affecting CYP2C19 and CYP3A4 such as rifampicin, and St Johnu00b4s wort ( Hypericum perforatum ) can markedly reduce the plasma concentrations of lansoprazole in PRONIZOR 30 mg.

Others

Warfarin Monitoring of patients receiving concomitant warfarin is recommended. Increased INR and prothrombin time in patients receiving PRONIZOR 30 mg and warfarin concomitantly have been reported. Increases in INR and prothrombin time may lead to abnormal bleeding and even death.

Sucralfate / Antacids

The bioavailability and absorption of PRONIZOR 30 mg may be decreased with concomitant administration of Sucralfate / antacids. PRONIZOR 30 mg should be taken at least 1 hour after taking these medications.

Methotrexate

Lansoprazole as contained in PRONIZOR 30 mg has been reported not to affect the pharmacokinetics of methotrexate.

PRONIZOR 30 mg in contraindicated in pregnancy and lactation (see Section 4.3).

Pregnancy Adequate and well-controlled studies in humans have not been done.

Lactation It is not known whether lansoprazole is distributed into breast milk. However, lansoprazole or its metabolites are distributed into the milk of rats. Because lansoprazole has been shown to cause tumorigenic effects in animals, a decision should be made as to whether breastfeeding should be discontinued or the medication withdrawn, taking into account the importance of PRONIZOR 30 mg to the mother.

PRONIZOR may lead to drowsiness and impaired concentration. Patients should be advised, particularly at the initiation of therapy, against taking charge of vehicles or machinery or performing potentially hazardous tasks where loss of concentration could lead to accidents.

Summary of the safety profile

Table 1: Tabulated summary of adverse events .

System organ class Frequency Undesirable effect Reference Infections and infestations Less frequent Candidiasis, flu syndrome, infection

Neoplasms benign, malignant and unspecified (incl. cysts and polyps) Less frequent Carcinoma, laryngeal neoplasia, skin carcinoma, gastric nodules, fundic polyps

Blood and lymphatic system Disorders Less frequent Thrombocytopenia, anaemia, leucopenia, neutropenia, eosinophilia, haemolysis, lymphadenopathy, agranulocytosis, pancytopenia

Immune system disorders Less frequent Allergic reaction, angioedema, anaphylactic shock

Metabolic and nutrition disorders Less frequent Anorexia, gout, dehydration, hyperglycaemia/hypoglycaemi a, peripheral oedema, weight gain/loss, hypomagnesaemia

Psychiatric disorders Less frequent Agitation, anxiety, apathy, confusion, depersonalisation, depression, emotional lability, hallucinations, hostility aggravated, nervousness, neurosis, sleep disorder, thinking abnormality

Nervous Frequent Headache, dizziness

system disorders Less frequent Somnolence, insomnia, tremor, abnormal dreams, amnesia, convulsion, diplopia, hemiplegia, hyperkinesia, hypertonia, hypoesthesia, paraesthesia, vertigo, restlessness

Eye Disorders Less frequent Blurred vision, abnormal vision, conjunctivitis, dry eyes, eye pain, photophobia, retinal degeneration, visual field defect, visual disturbances

Ear and labyrinth disorders Less frequent Deafness, ear disorder, otitis media, tinnitus

Cardiac disorders Less frequent Chest pain, angina, dysrrhythmia, bradycardia, myocardial infarction, palpitations, tachycardia, cardiospasm

Vascular disorders Less frequent Oedema, cerebro vascular accident / cerebral infarction, hypertension / hypotension, migraine, shock (circulatory failure), syncope, vasodilation

Respiratory, thoracic and mediastinal disorders Less frequent Asthma, bronchitis, increased cough, dyspnoea, epistaxis, haemoptysis, hiccough, pharyngitis, pleural disorder, pneumonia, respiratory disorder, upper respiratory inflammation/ infection, rhinitis, sinusitis, stridor, parosmia

Gastrointestin al disorders Frequent Diarrhoea, nausea, vomiting, constipation, abdominal pain, flatulence, dry mouth or throat

Less frequent Glossitis, taste abnormalities, ulcerative colitis, abdomen enlarged, halitosis, abnormal stools, bezoar, colitis, dyspepsia, dysphagia, enteritis, eructation, oesophageal stenosis, oesophageal ulcer, oesophagitis, faecal discolouration, gastritis, gastroenteritis, gastrointestinal anomaly, gastrointestinal disorder, gastrointestinal haemorrhage, gum haemorrhage, haematemesis, increased appetite, increased salivation, melena, mouth ulceration, oral moniliasis, rectal disorder, rectal haemorrhage, stomatitis, tenesmus, thirst, tongue disorder, ulcerative stomatitis, taste loss, taste perversion, candidiasis of the oesophagus, pancreatitis

Frequency unknown Collagenous colitis; Gastric glandularcysts

Hepato - biliary disorders Frequent Increase in liver enzymes

Less frequent Cholelithiasis, jaundice mostly with liver injury (increase in up to twice the upper limit of normal range of hepatic enzymes), hyper bilirubinaemia, hepatitis

Skin and subcutaneous tissue disorders Frequent Skin rash, pruritus, urticaria

Less frequent Alopecia, acne, contact dermatitis, dry skin, fixed eruption, hair disorder, macula papular rash, nail disorder, skin disorder, sweating, petechiae, purpura, erythema multiforme, photosensitivity, Steven-Johnson syndrome or toxic-epidermal necrolysis

Musculoskele tal and connective tissue disorders Less frequent Arthralgia, myalgia, back pain, chills, neck pain, neck rigidity, arthritis, bone disorder, joint disorder, leg cramps, musculoskeletal pain, myasthenia, synovitis, fracture of the hip, wrist or spine

Renal and urinary disorders Less frequent Dysuria, kidney calculus, kidney pain, polyuria, urethral pain, urinary frequency, urinary tract infection, urinary urgency, urination impaired, interstitial nephritis

Reproductive system and breast disorders Less frequent Pelvic pain, libido decreased / increased, abnormal menses, breast enlargement, breast pain, breast tenderness, dysmenorrhoea, impotence, leukorrhoea, menorrhagia, menstrual disorder, penis disorder, testis disorder, vaginitis, gynaecomastia, galactorrhoea

General disorders and administratio n site conditions Frequent Fatigue

Less frequent Fever, malaise, pain, asthenia

Investigations Less frequent Increase in cholesterol and triglyceride levels, hyponatraemia

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website or to Macleods Pharmaceuticals SA (Pty) Ltd. at [email protected].

Treatment is symptomatic and supportive. In the case of suspected overdose the patient should be monitored. Lansoprazole, as contained in PRONIZOR 30 mg , is not significantly eliminated by haemodialysis.