Ramipril/ Hydrochlorothiazide [Discontinued in SA Market]

Registered South African indications: 

• Hypertension

Combination products may have additional pharmacological effects not accounted for by the action of the individual ingredients

Ramipril
Contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Pregnancy >30 weeks
• Breastfeeding
• Hypersensitivity to angiotensin-converting enzyme(ACE) inhibitors
• History of angioedema related to ACE inhibitor use
• Patients with hypotensive or haemodynamically unstable states
• Hereditary or idiopathic angioneurotic oedema
• Dialysis or haemofiltration with high-flux membranes
• Low density lipoprotein apheresis
• Significant bilateral renal artery stenosis or renal artery stenosis in a single functioning kidney
• Coadministration with with aliskiren agents in patient with diabetes mellitus or renal impairment

Cautions

• Renal impairment
• Hepatic impairment
• Elderly 
• Patients with strongly activated renin-angiotensin-aldosterone system
• Severe hypertension
• Decompensated congestive cardiac failure
• Significant left ventricular outflow tract obstruction
• Unilateral renal artery stenosis with a second functional kidney
• Fluid or salt depletion
• Liver cirrhosis and ascites
• Major surgery
• Hymenoptera venom desensitising treatment
• Uncontrolled diabetes mellitus
• Black patients
• Metabolic acidosis
• Soy protein allergy

Hydrochlorothiazide
Contraindications 

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Severe renal impairment
• Refractory hypokalaemia, hyponatremia, hypercalcaemia, hyperuricaemia
• Addison’s disease
• Pre-existing hypercalcaemia

Cautions 

• Breastfeeding
• Mild to moderate renal impairment
• Hepatic impairment
• Elderly
• Renal artery stenosis
• Gout
• Hyperglycaemia
• Systemic lupus erythematosus

Additional contraindications for this combination product

• Hepatic impairment
• Hypertrophic obstructive cardiomyopathy
• Bi or unilateral renal artery stenosis in the presence of a single kidney
• Aortic stenosis
• Porphyria
• Coadministration with potassium sparing diuretics
• Lithium therapy
• History of angioedema with angiotension converting enzyme inhibitors or angiotensin receptor blockers
• Anuria
• Sulphonamide sensitivity

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

Hypertension

Ramipril/ Hydrochlorothiazide

2.5/12.5 (mg)
5/12.5 (mg)
10/12.5 (mg) 

• Oral (tab): 1 tab, dly, in morning

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Do not cut/crush/chew/dissolve

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Combination not suitable for initiation

Initial combination strength is determined by the current dose of the individual components

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Max: 10mg ramipril/50mg hydrochlorothiazide

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; dose adjustment recommended (Ramipril)
• Severe: Contraindicated (Hydrochlorothiazide)

Hepatic Impairment

• Caution; dose adjustment recommended (Ramipril)

Elderly

• Caution; dose adjustment recommended (Ramipril) 

Combination products may have additional pharmacological effects not accounted for by the action of the individual ingredients

Ramipril
Central Nervous System Disorders

• Depressed mood
• Anxiety
• Nervousness
• Restlessness
• Sleep disorder including somnolence
• Confusional state
• Disturbance in attention
• Headache
• Dizziness
• Vertigo
• Paraesthesia
• Ageusia
• Dysgeusia
• Tremor
• Cerebral ischaemia 
• Impaired psychomotor skills
• Burning sensation
• Parosmia
• Fatigue

Cardiovascular Disorders

• Myocardial ischaemia
• Tachycardia
• Arrhythmia
• Palpitations
• Oedema
• Hypotension
• Decreased orthostatic blood pressure
• Syncope
• Flushing
• Vascular stenosis
• Hypoperfusion
• Vasculitis
• Raynaud's phenomenon
• Chest pain

Respiratory Disorders

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

Gastrointestinal Disorders

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

Hepatobiliary Disorders

• Increased hepatic enzymes
• Increased conjugated bilirubin
• Cholestatic jaundice
• Hepatocellular damage
• Acute hepatic failure
• Cholestatic or cytolytic hepatitis 

Genitourinary Disorders

• Renal impairment
• Acute renal failure acute
• Increased urine output
• Worsening of a pre-existing proteinuria
• Haematuria
• Transient erectile impotence
• Libido decreased

Endocrine and Metabolic Disorders

• Syndrome of inappropriate anti-diuretic hormone secretion
• Hyperkalaemia
• Anorexia
• Hyponatraemia
• Gynaecomastia

Musculoskeletal Disorders

• Muscle spasms
• Myalgia
• Arthralgia

Skin and Subcutaneous Tissue Disorders

• Rash in particular maculo-papular rash
• Angioedema
• Pruritus
• Hyperhidrosis
• Exfoliative dermatitis
• Urticaria
• Onycholysis
• Photosensitivity reaction
• Toxic epidermal necrolysis
• Stevens-Johnson syndrome
• Erythema multiforme
• Pemphigus
• Aggrevation of psoriasis
• Dermatitis psoriasiform
• Pemphigoid or lichenoid exanthema
• Alopecia

Immune, Blood and Lymphatic System Disorders

• Eosinophilia
• Leukopenia
• Decreased red blood cell count
• Anaemia
• Thrombocytopenia
• Bone marrow failure
• Pancytopenia
• Haemolytic anaemia
• Anaphylactic reactions
• Increased antinuclear antibody
• Pyrexia

Sensory Disorders

• Blurred vision
• Conjunctivitis
• Tinnitus
• Impaired hearing

Hydrochlorothiazide
Central Nervous System Disorders

• Weakness
• Lethargy
• Drowsiness
• Restlessness
• Seizures
• Headache
• Paraesthesia
• Dizziness

Cardiovascular Disorders

• Postural hypotension

Gastrointestinal Disorders

• Nausea and vomiting
• Constipation
• Diarrhoea
• Intestinal ulceration

Hepatobiliary Disorders

• Cholestatic jaundice
• Pancreatitis

Genitourinary Disorders

• Oliguria
• Impotence

Endocrine and Metabolic Disorders

• Hypochloraemic alkalosis
• Hyponatremia
• Hypokalaemia
• Hyperglycaemia
• Hyperuricaemia
• Gout
• Hypomagnesaemia
• Anorexia

Musculoskeletal Disorders

• Muscle pain
• Cramps

Skin and Subcutaneous Tissue Disorders

• Hypersensitivity reactions

Immune, Blood and Lymphatic System Disorders

• Thrombocytopaenia
• Granulocytopaenia
• Leucopenia
• Aplastic anaemia
• Haemolytic anaemia

Sensory Disorders

• Dry mouth
• Thirst
• Yellow vision

Combination products may have additional pharmacological effects not accounted for by the action of the individual ingredients

Ramipril

• Diuretics
• Aliskiren agents
• Agents that act on the renin-angiotensin-aldosterone system
• Agents that increase serum potassium
• Drugs and substances that decreased blood pressure
• Sympathomimetics
• Allopurinol
• Immunosupressants
• Corticosteroids
• Procainamide
• Cytostatics
• Lithium
• Antidiabetic agents
• Acetylsalicylic acid
• Non-steroidal anti-inflammatory drugs
• mTOR inhibitors
• Dipeptidyl-peptidase 4 inhibitors

Hydrochlorothiazide

• Digoxin
• Neuromuscular blocking agents
• Central nervous system depressants
• Corticosteroids
• Corticotrophin
• Beta-2 agonists
• Adrenaline
• Lithium

• Renal function
• Serum electrolytes

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. 

Hydrochlorothiazide
Hydrochlorothiazide acts primarily in the distal convoluted tubule where it inhibits sodium chloride transport. It competes for the chloride site and affects the electrolyte reabsorption by increasing sodium and chloride excretion. This reduces plasma volume indirectly and increases plasma renin activity, aldosterone secretion and urinary potassium loss. 

COMBINATION PREPARATIONS

Ramipril/ Hydrochlorothiazide

Tablet 2.5mg/12.5mg 

• Co Ramiwin (Sanofi) originator

Tablet 5mg/12.5mg 

• Co Ramiwin (Sanofi) originator

Tablet 10mg/12.5mg 

• Co Ramiwin (Sanofi) originator
• Tritace Plus (Sanofi) originator