Labetalol

Registered South African indications:

• Hypertension
• Hypertension in pregnancy >20 weeks

• Maintaining hypotensive status during general anaesthesia

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Severe hepatic impairment
• Hypotension
• Cardiogenic shock
• Bradycardia <45-50 beats per minute
• Second or third-degree heart block
• Uncontrolled, incipient or digitalis-refractory heart failure
• History of wheezing or asthma
• Prinzmetal's angina
• Severe periphery circulatory disturbances
• Sick sinus syndrome (including sino-atrial block) (inj)
• Untreated pheochromocytoma
• Metabolic acidosis
• History of obstructive airway disease (inj)
• Uncompensated heart failure (inj)
• Unstable/uncontrolled heart insufficiency (inj)
• Sinus node dysfunction (inj)

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment (tab)
• Severe renal impairment (inj)
• Mild to moderate hepatic impairment
• Elderly
• Cataract surgery with history of tamsulosin/alpha-1 blocker treatment
• Poor cardiac reserve
• Heart failure
• Ischaemic heart disease patients
• Abrupt withdrawal
• Peripheral circulatory disorders
  - Reynaud's disease or syndrome
  - Intermittent claudication
• Bradycardia <50-55 beats per minute
• First-degree heart block
• History of psoriasis
• Patients at risk of sudden haemorrhage
• History of severe anaphylactic reaction to a variety of allergens
• Diabetes mellitus (inj)
• Thyrotoxicosis (inj)
• Patients requiring treatment with adrenaline (inj)
• Poor left ventricular function (inj)
• Respiratory impairment
• Galactose intolerance (tab)
• Lapp lactase deficiency (tab)
• Glucose-galactose malabsorption (tab)

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

Hypertension - mild to moderate

• Oral (tab): Initial: 100mg, 12hrly; Titrate by 100mg, 12hrly at 14 day intervals; Max: 2400mg/24hrs

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Daily doses of up to 2400mg require that such doses be divided into a three or four times a day regimen

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Additive hypotensive effects are expected if labetalol is administered together with other antihypertensives. When transferring patients from such agents, labetalol should be introduced with a dosage of 100mg, 12hrly and previous therapy should be gradually decreased

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Hypertension - severe

• IV: 50mg over 1min; Repeat at intervals of 5min if necessary; Max: 200mg

OR

• IV: Infuse 1mg/ml sol. 160mg/hr; Dose range: 50 - 200mg

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Infusion should be continued until a satisfactory response is obtained

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Larger doses may be needed in patients with phaeochromocytoma

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Patients should always receive labetalol (inj) in the supine or left lateral position

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Raising the patient into the upright position within 3 hours of the labetalol (inj) administration should be avoided since excessive postural hypotension may occur

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If long-term control of hypertension following the use of labetalol injection is needed, labetalol tabs should start with 100mg, 12hrly

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Hypertension of pregnancy

• IV: Infuse 1mg/ml sol. at 20mg/hr; Titrate by doubling dose at intervals of 30mins; Max: 160mg/hr
• Oral (tab): 100mg, 12hrly; Titrate by 100mg, 12hrly at 7 day intervals; Max: 2400mg/24hrs

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During second and third trimesters, severity of the hypertension may require further dose titration to 8hrly regimen, ranging from 100-400mg, 8hrly

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Maintaining hypotensive status during general anaesthesia

• IV: Initial: 10-20mg; Titrate by 5-10mg at intervals of 5 mins

Hypertension due to other causes

• IV: Infuse 50-200mg at 120-160mg/hr until satisfactory response achieved

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Larger doses may be needed especially in patients with phaeochromocytoma

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Angina co-existing with hypertension

• See hypertension dosage

Not established for use in children

Pregnancy

• Caution
• Although no teratogenic effects have been demonstrated in animals, labetalol should only be used during the first trimester of pregnancy if the potential benefit outweighs the potential risk. Labetalol crosses the placental barrier and the possible consequences of alpha- and beta-adrenoceptor blockade in the foetus and neonate should be borne in mind. Perinatal and neonatal distress (bradycardia, hypotension, respiratory depression, hypoglycaemia, hypothermia) has been rarely reported. Sometimes these symptoms have developed a day or two after birth. Response to supportive measures (e.g. intravenous fluids and glucose) is usually prompt but with severe pre-eclampsia, particularly after prolonged intravenous labetalol, recovery may be slower. This may be related to diminished liver metabolism in premature babies
• Beta-blockers reduce placental perfusion, which may result in intrauterine foetal death, immature and premature deliveries. There is an increased risk of cardiac and pulmonary complications in the neonate in the post-natal period. Intra-uterine and neonatal deaths have been reported with labetalol but other drugs (e.g. vasodilators, respiratory depressants) and the effects of pre-eclampsia, intrauterine growth retardation and prematurity were implicated
• Such clinical experience warns against unduly prolonging high dose labetalol and delaying delivery and against co-administration of hydralazine
• Due to the pharmacological action of alpha-and beta-adrenoceptor blockade, adverse effects on the foetus and neonate when used in the later stages of pregnancy (bradycardia, hypotension, respiratory depression, hypoglycaemia), should be borne in mind, as labetalol crosses the placental barrier
• Close monitoring 24-48 hours after birth is required
• Labetalol should only be used during pregnancy if the benefits for the mother outweigh the risks for the foetus

Breastfeeding

• Caution
• Labetalol is excreted in breast milk. Breastfeeding is not recommended (tab)
• Labetalol (inj) is excreted in breast milk in small amounts (approximately 0.004-0.07% of the maternal dose). No adverse effects have been reported so far. Caution should be exercised when labetalol is administered to breastfeeding women

Fertility

• There are no human data on the potential effects of labetalol on fertility. Non-clinical data is considered insufficient

Renal Impairment

• Caution; no dose adjustment recommended (tab)
• Mild to moderate: eGFR>29ml/min/1.73m²: No dose adjustment recommended (inj)
• Severe: eGFR 15-29 ml/min/1.73m²: Caution; no dose adjustment recommended (inj)

Hepatic Impairment

• Child-Pugh Classes A & B: Caution; dose adjustment recommended
  Consider lower initial doses; Titrate gradually according to response; Dosage should not exceed 200mg daily
  Avoid if alternative
• Child-Pugh Class C: Contraindicated
  Consider alternatives

Elderly

• IV: Caution; no dose adjustment recommended 
• Oral (tab): Caution; dose adjustment recommended 
  Initial: 50mg, 12hrly

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Prohibited - In certain sports
  Prohibited - In and out of competition:
  Archery (WA)
  Shooting (ISSF) (IPC)
  Prohibited - In competition:
  Automobile (FIA)
  Billiards (all disciplines) (WCBS)
  Darts (WDF)
  Golf (IGF)
  Skiing / Snowboarding (FIS) in ski jumping, freestyle aerials/halfpipe and snowboard halfpipe/big air
  Underwater sports (CMAS) in constant-weight apnoea with or without fins, dynamic apnoea with and without fins, free immersion apnoea, Jump Blue apnoea, spearfishing, static apnoea, target shooting and variable weight apnoea

Central Nervous System Disorders

• Depressed mood
• Lethargy
• Hallucinations
• Psychoses
• Confusion
• Sleep disturbances
• Nightmares
• Headache
• Tiredness
• Dizziness
• Tremor

Cardiovascular Disorders

• Bradycardia
• Heart block
• Heart failure
• Hypotension
• Ankle oedema
• Increase of existing intermittent claudication
• Postural hypotension
• Cold or cyanotic extremities
• Raynaud's phenomenon
• Paraesthesia of the extremities

Respiratory Disorders

• Bronchospasm (patients with asthma or history thereof)
• Nasal congestion
• Interstitial lung disease

Gastrointestinal Disorders

• Epigastric pain
• Nausea and vomiting
• Diarrhoea

Hepatobiliary Disorders

• Raised liver function tests
• Jaundice (cholestatic and hepatocellular)
• Hepatitis
• Hepatic necrosis

Genitourinary Disorders

• Acute urinary retention
• Difficulty in micturition
• Ejaculatory failure

Endocrine and Metabolic Disorders

• Hyperkalaemia
• Masking of symptoms of thyrotoxicosis or hypoglycaemia

Musculoskeletal Disorders

• Cramps
• Toxic myopathy

Skin and Subcutaneous Tissue Disorders

• Sweating
• Tingling sensation in the scalp
• Lichenoid rash
• Systemic lupus erythematosus
• Exacerbation of psoriasis
• Alopecia (reversible)

Immune, Blood and Lymphatic System Disorders

• Positive antinuclear antibodies unassociated with disease
• Thrombocytopenia
• Drug fever
• Hypersensitivity
  - Rash
  - Pruritis
  - Angioedema
  - Dyspnoea

Sensory Disorders

• Impaired vision
• Dry eyes

• Calcium antagonists
• Verapamil
• Diltiazem
• Digitalis glycosides
• Clonidine
• Monoamine oxidase inhibitors (except monoamine oxidase-B inhibitors)
• Class I antiarrhythmic agents
• Disopyramide
• Quinidine
• Amiodarone
• Insulin
• Oral antidiabetic agents
• Anaesthetic agents
• Cyclopropane
• Trichloroethylene
• Cimetidine
• Hydralazine
• Angiotensin-converting enzyme inhibitors
• Angiotensin-II antagonists
• Aldesleukin
• Alprostadil
• Anxiolytics
• Hypnotics
• Moxisylyte
• Diuretics
• Alpha-blockers
• Non-steroidal anti-inflammatory drugs
• Corticosteroids
• Oestrogens
• Progesterones  
• Calcium antagonists
• Dihydropyridine derivatives
• Nifedipine
• Prostaglandin synthetase inhibitors
• Sympathomimetics
• Phenylpropanolamine
• Tricyclic antidepressants
• Imipramine
• Barbiturates
• Phenothiazines
• Chlorpromazine
• Other antihypertensive agents
• Antimalarials
• Quinine
• Mefloquine
• Ergot derivatives
• Volatile inhalation anaesthetics (inj)
• Adrenaline (inj)
• Cholinesterase inhibitors (inj)
• Nitrates
• Antipsychotics
• General anaesthesia

Other

• Alcohol
• Laboratory tests (see additional prescribing points)

• Blood pressure (standing and sitting/supine)
• Pulse

None routine. Specific cases may require:

• Cardiac monitor (inj)
• Blood pressure monitor (inj)

Injection 5mg/ml - EML (Hospital)

Tablet 100mg - NON-EML

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Interference with laboratory testing

• Labetalol fluoresces in alkaline solution at an excitation wavelength of 334 nanometres and a fluorescence wavelength of 412 nanometres, and may therefore interfere with the assays of certain fluorescent substances including catecholamines
• The presence of labetalol metabolites in the urine may result in falsely elevated levels or urinary catecholamines, metanephrine, normetanephrine and vanillylmandelic acid, (VMA) when measured by fluorimetric or photometric methods. In screening patients suspected of having a phaeochromocytoma and being treated with labetalol hydrochloride, a specific method such as high performance liquid chromatography with a solid phase extraction should be employed in determining levels of catecholamines
• Labetalol has been shown to reduce the uptake of radioisotopes of metaiodobenzylguanidine (MIBG). Care should therefore be taken in interpreting results from MIBG scintigraphy

Labetalol hydrochloride lowers the blood pressure by blocking peripheral arteriolar alpha-adrenoceptors thus reducing peripheral resistance, and by concurrent beta-blockade, protects the heart from reflex sympathetic drive that would otherwise occur. Cardiac output is not significantly reduced at rest or after moderate exercise. Increases in systolic pressure during exercise are reduced but corresponding changes in diastolic pressure are essentially normal.

Tablet 100mg

• Trandate (GSK) originator (Not marketed: 07/2022)

Injection (per 1ml) 5mg

• Trandate (Pharmacare) originator