Ramipril/ Felodipine

Registered South African indications:

• Hypertension

Contraindications

• Hypersensitivity to the active ingredients or any of the excipients in this combination product
• Pregnancy
• Lactation
• Severe renal impairment
• Severe hepatic impairment
• History of angioedema
• Unstable haemodynamic conditions
• Haemodynamically significant cardiac valvular obstruction
• Dynamic cardiac outflow obstruction
• Atrioventricular block II or III
• Coadministration with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment

Cautions

• Mild to moderate renal impairment
• Elderly
• Black patients
• Uncontrolled diabetes mellitus
• Patients at risk of hyponatremia
• Renovascular hypertension 
• Pre-existing bilateral renal artery stenosis
• Stenosis of the artery to a solitary kidney
• Surgery
• Collagen vascular disease
• Haemodynamically relevant left-ventricular inflow or outflow impediment
• Patients with decreased blood volume
• Patients with coronary or cerebrovascular insufficiency
• Galactose intolerance 
• Glucose-galactose malabsorption
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: tab

Hypertension - mild to moderate 

Ramipril/ Felodipine
2.5/2.5 (mg) 

• Oral (tab): 1 tab, dly; Max: 2 tab, dly

5/5 (mg)

• Oral (tab): 1 tab, dly; Max: 1 tab, dly

Do not cut/crush/chew/dissolve

Not established for use in children

Recommendations for this combination product as per highest risk category when comparing individual active ingredients

Pregnancy

• FDA Pregnancy Category D (Ramipril)

Breastfeeding

• Contraindicated (Ramipril)

Renal Impairment

• Mild to moderate: Caution; no dose adjustment recommended 
• Severe: Contraindicated

Hepatic Impairment

• Severe: Contraindicated

Elderly

• Caution; no information available

Central Nervous System Disorders

• Headache
• Dizziness
• Paraesthesia
• Syncope
• Impotence
• Sexual dysfunction
• Depressed mood
• Anxiety
• Nervousness
• Restlessness
• Sleep disorder 
• Confusional state
• Disturbance in attention
• Vertigo
• Tremor
• Balance disorder
• Ageusia
• Dysgeusia
• Cerebral ischaemia
• Impaired psychomotor skills 
• Burning sensation
• Parosmia
• Aesthenia

Cardiovascular Disorders

• Tachycardia
• Palpitations
• Flushing
• Hypotension
• Leucocytoclastic vasculitis
• Decreased orthostatic blood pressure 
• Syncope
• Vascular stenosis
• Rayneaud's phenomenon
• Chest pain

Respiratory Disorders

• Non-productive tickling cough
• Bronchitis
• Sinusitis
• Dyspnoea
• Bronchospasm 
• Nasal congestion

Gastrointestinal Disorders

• Nausea and vomiting
• Abdominal pain
• Gingival hyperplasia
• Gingivitis
• Gastrointestinal inflammation
• Digestive disturbances
• Dyspepsia
• Diarrhoea
• Pancreatitis
• Increased pancreatic enzymes
• Small bowel angioedema
• Gastritis
• Constipation
• Dry mouth
• Glossitis
• Aphtous stomatitis

Hepatobiliary Disorders

• Increased liver enzymes
• Increased conjugated bilirubin
• Cholestatic jaundice
• Hepatocellular damage
• Acute hepatic failure
• Hepatitis

Genitourinary Disorders

• Pollakisuria
• Acute renal failure
• Increased urine output 
• Worsening of a pre-existing proteinuria
• Increased blood urea 
• Increased blood creatinine
• Gynaecomastia
• Transient erectile dysfunction
• Decreased libido

Endocrine and Metabolic Disorders

• Hyperglycaemia
• Increased blood potassium
• Anorexia
• Decreased appetite
• Decreased blood sodium
• Syndrome of inappropriate antidiuretic hormone secretion 

Musculoskeletal Disorders

• Arthralgia
• Myalgia
• Muscle spasms

Skin and Subcutaneous Tissue Disorders

• Maculo-papular rash
• Angioedema
• Pruritis
• Hyperhidrosis
• Exfoliative dermatitis
• Urticaria
• Onycholysis
• Photosensitivity reaction
• Toxic epidermal necrolysis
• Stevens-Johnson syndrome
• Erythema multiforme
• Pemphigus
• Psoriasis
• Dermatitis psoriasiform
• Pemphigoid or lichenoid exanthema 
• Enanthema
• Alopecia
• Rash

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions
• Fever
• Eosinophilia
• Decreased white blood cell count 
• Decreased red blood cell count
• Decreased haemoglobin
• Decreased platelet count
• Bone marrow failure
• Pancytopenia
• Haemolytic anaemia
• Anaphylactic or anaphylactoid reactions
• Increased antinuclear antibody

Sensory Disorders

• Visual disturbance 
• Conjunctivitis
• Hearing impaired
• Tinnitus

• Angiotensin-converting enzyme inhibitors
• Angiotensin II receptor blockers 
• Aliskiren
• CYP3A4 inhibitors
• CYP3A4 inducers
• Lithium
• Antihypertensives
• Agents with blood pressure lowering potential
• Allopurinol
• Immunosuppressants
• Corticosteroids
• Procainamide
• Cytostatics
• Non-steroidal anti-inflammatory drugs 
• Vasopressor sympathomimetics
• mTOR inhibitors 
• Vildagliptin
• Racecadotril
• Antidiabetic agents
• Theophylline
• Tacrolimus
• Medicinal products causing hyperkalaemia
• Salt
• Alcohol

• Renal function
• Serum electrolytes

Specific cases may require

• White blood cell count

Ramipril
Ramipril is an angiotensin-converting enzyme (ACE) inhibitor. This enzyme functions to convert angiotensin I to angiotensin II which is involved in vascular control and function through many different mechanisms, including stimulation of aldosterone secretion. By inhibiting the ACE, ramipril thus prevents the downstream vasopressor activity and aldosterone secretion effected by angiotensin II. 

Felodipine
Felodipine is a vascular-selective calcium antagonist, which lowers arterial blood pressure by decreasing systemic vascular resistance. Due to the high degree of selectivity for smooth muscle in the arterioles, felodipine in therapeutic doses has no direct effect on cardiac contractility or conduction. Because there is no effect on venous smooth muscle or adrenergic vasomotor control, felodipine is not associated with orthostatic hypotension. During the first few weeks of therapy, felodipine also has a mild natriuretic, diuretic and kaliuretic effect.

COMBINATION PREPARATIONS 

Ramipril/ Felodipine

Tablet 2.5mg/2.5mg 

• Tri-Plen (Sanofi)

Tablet 5mg/5mg

• Tri-Plen Forte (Sanofi)