Vascolok 5 mg/10 mg Tablets

VASCOLOK is indicated for the treatment of mild to moderate hypertension. VASCOLOK may be combined with other antihypertensive medicines. VASCOLOK is indicated for the treatment of angina pectoris.

Posology
For both hypertension and angina, the usual initial dose is 5 mg VASCOLOK once daily which may be increased to a maximum dose of 10 mg depending on the individual patientu2019s response after 10 - 14 days therapy. VASCOLOK 5 tablets should not be broken even though they have a breakline. No dose adjustment of VASCOLOK is required during combined administration of thiazide diuretics, beta blockers, or angiotensin converting enzyme inhibitors.
Paediatric population
Safety and efficacy in children have not been established.
Method of administration
VASCOLOK is for oral use.

VASCOLOK is contraindicated in patients with:
u2022 Hypersensitivity to amlodipine dihydropyridines, or to any of the excipients listed in 6.1.
u2022 severe hypotension
u2022 shock (including cardiogenic shock)
u2022 obstruction of the outflow tract of the left ventricle (e.g. high grade aortic stenosis)
u2022 haemodynamically unstable heart failure after acute myocardial infarction.
Pregnancy or lactation. (see section 4.6).

VASCOLOK should be used with caution in the elderly and patients with severe renal and liver impairment (see 5.2 Pharmacokinetic properties). These patients may need a lower dose. The safety and efficacy of VASCOLOK have not been established in a hypertensive crisis.
Use in heart failure: An increased incidence of pulmonary oedema has been reported. VASCOLOK may have a negative inotropic effect. The AUC of amlodipine may increase in patients with heart failure. Use VASCOLOK with caution in heart failure, severe hypotension, shock (including cardiogenic shock), or high-grade aortic stenosis.
Hepatic impairment: The half-life of amlodipine is prolonged and AUC values are higher in patients with impaired liver function; dosage recommendations have not been established. Amlodipine should therefore be initiated at the lower end of the dosing range and caution should be used, both on initial treatment and when increasing the dose. Slow dose titration and careful monitoring may be required in patients with severe hepatic impairment.
Elderly: In the elderly increase of the dosage should take place with care.
Renal impairment: Amlodipine may be used in such patients at normal doses. Changes in amlodipine plasma concentrations are not correlated with degree of renal impairment. Amlodipine is not dialyzable.
Sodium: VASCOLOK contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 'sodium-free.'
Porphyria: Safety has not been established.
Paediatric population: Safety and efficacy in children have not been established.
Excipient mannitol: VASCOLOK contains mannitol which may have a laxative effect or cause diarrhoea.

VASCOLOK may be administered with thiazide diuretics, beta blockers, angiotensin-converting enzyme inhibitors, long-acting nitrates, sublingual nitroglycerine, non-steroidal anti-inflammatory drugs, antibiotics, and oral hypoglycaemic medicines.
Effects of other medicinal products on amlodipine
CYP3A4 inhibitors: Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors such as protease inhibitors (e.g. ritonavir, indinavir, nefinavir), azole antifungals (e.g. ketoconazole, itraconazole, fluconazole), macrolides (e.g. erythromycin, clarithromycin), and verapamil or diltiazem may increase VASCOLOK exposure. Clinical monitoring and dose adjustment may be required.
CYP3A4 inducers: Upon co-administration of known inducers of the CYP3A4, the plasma concentration of amlodipine may vary. Therefore, blood pressure should be monitored and dose regulation considered both during and after concomitant medication particularly with strong CYP3A4 inducers (e.g. rifampicin, hypericum perforatum). CYP3A4 inducers such as rifampicin, carbamazepine, phenytoin, phenobarbitone may reduce the effects of VASCOLOK. Administration of VASCOLOK with grapefruit or grapefruit juice is not recommended as bioavailability may be increased in some patients resulting in increased blood pressure lowering effects.
Dantrolene (infusion): In animals, lethal ventricular fibrillation and cardiovascular collapse are observed in association with hyperkalemia after administration of verapamil and intravenous dantrolene. Due to risk of hyperkalemia, it is recommended that the coadministration of calcium channel blockers such as amlodipine be avoided in patients susceptible to malignant hyperthermia and in the management of malignant hyperthermia.
Effects of amlodipine on other medicinal products: The blood pressure lowering effects of amlodipine adds to the blood pressure-lowering effects of other medicinal products with antihypertensive properties.
Tacrolimus: There is a risk of increased tacrolimus blood levels when co-administered with amlodipine but the pharmacokinetic mechanism of this interaction is not fully understood. In order to avoid toxicity of tacrolimus, administration of amlodipine in a patient treated with tacrolimus requires monitoring of tacrolimus blood levels and dose adjustment of tacrolimus when appropriate.
Mechanistic Target of Rapamycin (mTOR) Inhibitors: mTOR inhibitors such as sirolimus, temsirolimus, and everolimus are CYP3A substrates. Amlodipine is a weak CYP3A inhibitor. With concomitant use of mTOR inhibitors, amlodipine may increase exposure of mTOR inhibitors.
Simvastatin: Co-administration of multiple doses of 10 mg of VASCOLOK with 80 mg simvastatin resulted in a 77 % increase in exposure to simvastatin compared to simvastatin alone. Limit the dose of simvastatin in patients on VASCOLOK to 20 mg daily.
VASCOLOK may modify insulin and glucose response and therefore diabetic patients may need to adjust their antidiabetic treatment when receiving VASCOLOK. In healthy male volunteers, the co-administration of amlodipine does not significantly alter the effect of warfarin on prothrombin response time.
Cyclosporine: Pharmacokinetic studies with ciclosporin have demonstrated that amlodipine does not significantly alter the pharmacokinetics of ciclosporin. Consideration should be given for monitoring cyclosporine levels in renal transplant patients on amlodipine, and cyclosporine dose reductions should be made as necessary.
Digoxin: Studies have indicated that the co-administration of amlodipine such as in VASCOLOK with digoxin did not change serum digoxin levels but VASCOLOK may reduce the renal clearance of digoxin.
Cimetidine: Co-administration of cimetidine did not alter the pharmacokinetics of VASCOLOK. In vitro data from studies with human plasma indicate that amlodipine has no effect on protein binding of the medicines tested (digoxin, phenytoin, warfarin, or indomethacin).

Pregnancy and Breastfeeding
Safety in pregnancy and lactation has not been established (see section 4.3).
Fertility
Clinical data are insufficient regarding the potential effect of amlodipine on fertility.

VASCOLOK may cause dizziness, headache and fatigue, the ability to react may be impaired which may affect your ability to drive or use machines. Caution is recommended especially at the start of treatment.

a) Summary of the safety profile
The most commonly reported adverse reactions during treatment are somnolence, dizziness, headache, palpitations, flushing, abdominal pain, nausea, ankle swelling, oedema and fatigue.
b) Tabulated list of adverse reactions
The table below shows all adverse drug reactions (ADRs) observed during clinical trials and postmarket spontaneous reports with amlodipine besilate.
System Organ Class Frequency Frequent Less Frequent Not known Blood and lymphatic system disorders Leucopenia, thrombocytopenia Immune system disorders Hypersensitivity reactions, angioedema and erythema multiforme Endocrine disorders Hyperglycaemia Psychiatric disorders Insomnia, mood changes (including anxiety), depression and rarely confusion Nervous system disorders Somnolence, dizziness, headache (especially at the beginning of treatment), flushing Tremor, dysgeusia, syncope, dry mouth, increased sweating, hypoaesthesia, paraesthesia, hypertonia, peripheral neuropathy Extrapyramidal disorder Eye disorders Visual disturbance (including diplopia) Ear and labyrinth disorders Tinnitus Cardiac disorders Oedema, palpitations and chest pain Dysrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction Vascular disorders Flushing Hypotension, vasculitis, syncope. Respiratory, thoracic and mediastinal disorders Dyspnoea Cough, rhinitis Gastrointestinal disorders Abdominal pain, nausea, dyspepsia, altered bowel habits (including diarrhoea and constipation) Vomiting, dry mouth, pancreatitis, gastritis, gingival hyperplasia Hepatobiliary disorders Hepatitis, jaundice, and hepatic enzyme elevations (mostly consistent with cholestasis). Some cases severe enough to require hospitalisation have been reported in association with use of amlodipine as contained in VASCOLOK. Skin and subcutaneous tissue disorders Alopecia, purpura, skin discolouration, hyperhidrosis, allergic reactions with pruritus, rash, exanthema, urticaria. Very rare: Angioedema, erythema multiforme, exfoliative dermatitis, Toxic Epidermal Necrolysis Stevens-Johnson syndrome, Quincke oedema, photosensitivity Musculoskeletal and connective tissue disorders Ankle swelling, muscle cramps, Arthralgia, back pain, myalgia Renal and urinary disorders Micturition disorder, nocturia, increased urinary frequency Reproductive system and breast disorders Impotence, gynaecomastia General disorders and administration site conditions Oedema, fatigue, asthenia, ankle oedema Chest pain, pain, malaise Investigations Increased/decreased weight 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. Healthcare professionals are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reaction Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8 Suspected adverse reactions can also be reported directly to the HCR via [email protected]

Symptoms: Available data for amlodipine suggest that gross overdosage could result in excessive peripheral vasodilation and possibly reflex tachycardia. Marked and probably prolonged systemic hypotension up to and including shock with fatal outcome have been reported. Non-cardiogenic pulmonary oedema has rarely been reported as a consequence of amlodipine overdose that may manifest with a delayed onset (24 u2013 48 hours post-ingestion) and require ventilatory support. Early resuscitative measures (including fluid overload) to maintain perfusion and cardiac output may be precipitating factors.
Treatment: Clinically significant hypotension due to amlodipine overdosage calls for active cardiovascular support. Intravenous calcium gluconate may be beneficial in reversing the effects of calcium channel blockade. Since amlodipine is highly protein-bound, dialysis is not likely to be of benefit. Gastric lavage may be worth-while.