Lercanidipine/ Enalapril

Registered South African indications:

• Essential hypertension
  - In those whose blood pressure has been stabilised on the individual components when given concurrently

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

Enalapril
Contraindications 

• Hypersensitivity to the active ingredient or any of the excipients in this combination product 
• Pregnancy 
• History of angioedema associated with previous angiotensin converting enzyme inhibitor therapy
• Porphyria
• Hereditary or idiopathic angioedema
• Coadministration with aliskiren-containing products in patients with diabetes mellitus or renal impairment

Cautions

• Breastfeeding 
• Renal impairment 
• Elderly 

Lercarnidipine
Contraindications 

• Hypersensitivity to the active ingredient or any of the excipients in this combination product 
• Pregnancy
• Breastfeeding
• Severe renal impairment
• Severe hepatic impairment
• Left ventricular outflow tract obstruction
• Untreated congestive cardiac failure
• Unstable angina pectoris
• Myocardial infarction <1month
• Women of child-brearing potential unless effective contraception used
• Coadministration with strong CYP3A4 inhibitors
• Coadministration with cyclosporin
• Coadministration with grapefruit juice

Cautions

• Mild to moderate renal impairment
• Mild to moderate hepatic impairment
• Elderly
• Sick sinus syndrome
• Left ventricular dysfunction
• Ischaemic heart disease
• Angina pectoris

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

Essential hypertension
- In those whose blood pressure has been stabilised on the individual components when given concurrently

Enalapril/ Lercanidipine
10/10 (mg)
20/10 (mg) 

• Oral (tab): 1 tab, daily

---

Administer 15 minutes before meals 

Not established for use in children

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

Pregnancy

• Contraindicated (Lercanidipine, Enalapril)  
• Lercanidipine 
• There are no adequate data from the use of lercanidipine in pregnant women. Non-clinical data provide no evidence of a teratogenic effect in the rat and the rabbit and reproductive performance in the rat was unimpaired. Since other dihydropyridine compounds have been found teratogenic in animals, lercanidipine should not be administered during pregnancy or to women with child-bearing potential unless effective contraception is used
• Enalapril 
  The use of ACE inhibitors is not recommended during the first trimester of pregnancy. The use of ACE inhibitors is contraindicated during the second and third trimesters of pregnancy
  Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Unless continued ACE inhibitor therapy is considered essential, patients planning pregnancy should be changed to alternative anti-hypertensive treatments which have an established safety profile for use in pregnancy
  When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately, and, if appropriate, alternative therapy should be started
  Exposure to ACE inhibitor therapy during the second and third trimesters is known to induce human foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia). Maternal oligohydramnios, presumably representing decreased foetal renal function, has occurred and may result in limb contractures, craniofacial deformations and hypoplastic lung development
  Should exposure to ACE inhibitors have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended
  Infants whose mothers have taken ACE inhibitors should be closely observed for hypotension

Breastfeeding

• Contraindicated (Lercanidipine) 
• Lercanidipine 
  Because of high lipophilicity of lercanidipine, distribution in milk may be expected. Therefore, it should not be administered to nursing mothers
• Enalapril 
  Limited pharmacokinetic data demonstrate very low concentrations in breast milk. Although these concentrations seem to be clinically irrelevant, the use of enalapril in breastfeeding is not recommended for preterm infants and for the first few weeks after delivery, because of the hypothetical risk of cardiovascular and renal effects and because there is not enough clinical experience. In case of an older infant, the use of enalapril in breastfeeding mother may be considered if this treatment is necessary for the mother and the child is observed for any adverse effect

Renal Impairment

• Mild to moderate: Caution; dose adjustment recommended (Enalapril) 
• Severe: Contraindicated (Lercanidipine)

Hepatic Impairment

• Mild to moderate: Caution; dose adjustment recommended (Lercanidipine)
• Severe: Contraindicated (Lercanidipine)

Elderly

• Caution; no dose adjustment recommended (Enalapril, Lercanidipine) 

Porphyria Information

• Not yet classified (NC)

Drugs in Sport

• Permitted - No warning

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

Enalapril
Central Nervous System Disorders

• Dizziness
• Headache
• Syncope
• Taste alteration
• Somnolence
• Paresthesia
• Vertigo
• Depression
• Confusion
• Nervousness
• Sleep disorders
• Fatigue
• Malaise
• Aesthenia

Cardiovascular Disorders

• Chest pain
• Rhythm disturbances
• Angina pectoris
• Tachycardia
• Palpitations
• Myocardial infarction
• Cerebrovascular accident
• Hypotension 
• Flushing
• Orthostatic hypotension
• Raynaud's phenomenon

Respiratory Disorders

• Cough
• Dyspnoea
• Rhinorrhoea
• Sore throat
• Hoarseness
• Bronchospasm
• Asthma
• Pulmonary infiltrates
• Rhinitis
• Allergic alveolitis
• Eosinophilia pneumonia

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Abdominal pain
• Ileus
• Pancreatitis
• Dyspepsia
• Constipation
• Anorexia
• Gastric irritation
• Dry mouth
• Peptic ulcer
• Stomatitis
• Aphthous ulcerations
• Glossitis
• Intestinal angioedema

Hepatobiliary Disorders

• Hepatic failure
• Hepatitis
• Increased liver enzymes
• Increased serum bilirubin

Genitourinary Disorders

• Renal impairment
• Renal failure
• Proteinuria
• Oliguria

Endocrine and Metabolic Disorders

• Impotence
• Gynaecomastia
• Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
• Hypoglycaemia
• Hyperkalaemia
• Increased serum creatinine
• Increased blood urea
• Hyponatraemia

Musculoskeletal Disorders

• Muscle cramps
• Arthralgia
• Arthritis

Skin and Subcutaneous Tissue Disorders

• Rash
• Hypersensitivity
• Angioneurotic oedema
• Diaphoresis
• Pruritus
• Urticaria
• Alopecia
• Erythema multiforme
• Stevens-Johnson syndrome
• Exfoliative dermatitis
• Toxic epidermal necrolysis
• Pemphigus
• Erythroderma
• Serositis
• Vasculitis
• Myalgia
• Myositis
• Rash
• Photosensitivity

Immune, Blood and Lymphatic System Disorders

• Anaemia 
• Neutropenia
• Decreased haematocrit
• Thrombocytopenia
• Agranulocytosis
• Bone marrow depression
• Pancytopenia
• Lymphadenopathy
• Autoimmune diseases
• Eosinophilia
• Leucocytosis

Sensory Disorders

• Tinnitus
• Blurred vision

Others 

• Fever

Lercanidipine
Central Nervous System Disorders

• Headache
• Dizziness
• Somnolence

Cardiovascular Disorders

• Tachycardia
• Palpitations
• Peripheral oedema
• Angina pectoris
• Chest pain
• Myocardial infarction
• Hypotension
• Flushing

Gastrointestinal Disorders

• Dyspepsia
• Diarrhoea
• Abdominal pain
• Vomiting
• Gingival hypertrophy

Hepatobiliary Disorders

• Increased hepatic transaminases

Genitourinary Disorders

• Polyuria
• Urinary frequency

Musculoskeletal Disorders

• Myalgia

Skin and Subcutaneous Tissue Disorders

• Rash

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity

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

Enalapril

• Diuretics
• Lithium
• Antihypertensive agents
• Agents that increase serum potassium
• Anti-inflammatory agents
• Oestrogen
• Calcium antagonists
• Sympathomimetics
• Narcotic drugs 
• Antipsychotics
• Alcohol
• Angiotensin II receptor blockers 
• Aliskiren
• Anaesthetic medicinal products
• Tricyclic antidepressants 
• Non-steroidal anti-inflammatory drugs
• Selective cyclooxygenase-2 inhibitors 
• Gold
• mTOR inhibitor therapy
• Hypoglycaemic agents

Lercanidipine

• CYP3A4 inhibitors
• CYP3A4 inducers
• CYP3A4 substrates
• Cyclosporin
• Grapefruit juice
• Alcohol
• Beta blockers

None routine. Specific cases may require

• Renal function
• Serum potassium
• Full blood count

Enalapril
Enalapril is hydrolysed to enalaprilat which is a specific, long-acting, non-sulfhydryl angiotensin-converting enzyme inhibitor. Angiotensin-converting enzyme inhibitor is a peptidyl dipeptidase which catalyses the conversion of angiotensin I to the pressor substance angiotensin II. This results in reduced plasma renin activity and decreased aldosterone secretion. The blood pressure lowering effect of enalapril is primarily through suppression of the renin-angiotensin-aldosterone system.

Lercanidipine
Lercanidipine is a calcium antagonist of the dihydropyridine group that inhibits the transmembrane influx of calcium into cardiac and smooth muscle. This has a direct relaxant effect on vascular smooth muscle thus lowering total peripheral resistance. It is devoid of negative inotropic effects due to its high vascular selectivity.

COMBINATION PREPARATIONS

Enalapril/ Lercanidipine

Tablet 10mg/10mg

• Zaneril (Acino Pharma) fct originator

Tablet 20mg/10mg

• Zaneril (Acino Pharma) fct originator