Moxovas H

Uses

Hydrochlorothiazide is used for-

• Edema associated with congestive heart failure, hepatic cirrohosis, various forms of renal dysfunction and corticosteroid and estrogen therapy
• Management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe form of hypertension
• Management of diabetes insipidus
• Management of proximal renal tubular acidosis
• Idiopathic hypercalciuria and calcium nephrolithiasis, osteoporosis and exercise induced hyperkalemia

Moxonidine belongs to a group of drugs called anti-hypertensives that lower blood pressure. Moxonidine is used to treat high blood pressure.

Moxovas H is also used to associated treatment for these conditions: Acidosis, Renal Tubular, Calcium Nephrolithiasis, Cirrhosis of the Liver, Congestive Heart Failure (CHF), Diabetes Insipidus, Edema, High Blood Pressure (Hypertension), Hypertension,Essential, Hypokalemia caused by diuretics, Nephrotic Syndrome, Premenstrual tension with edema, Sodium retention, Stroke, Prophylaxis of preeclampsiaHigh Blood Pressure (Hypertension)

How Moxovas H works

Hydrochlorothiazide is transported from the circulation into epithelial cells of the distal convoluted tubule by the organic anion transporters OAT1, OAT3, and OAT4. From these cells, hydrochlorothiazide is transported to the lumen of the tubule by multidrug resistance associated protein 4 (MRP4).

Normally, sodium is reabsorbed into epithelial cells of the distal convoluted tubule and pumped into the basolateral interstitium by a sodium-potassium ATPase, creating a concentration gradient between the epithelial cell and the distal convoluted tubule that promotes the reabsorption of water.

Hydrochlorothiazide acts on the proximal region of the distal convoluted tubule, inhibiting reabsorption by the sodium-chloride symporter, also known as Solute Carrier Family 12 Member 3 (SLC12A3). Inhibition of SLC12A3 reduces the magnitude of the concentration gradient between the epithelial cell and distal convoluted tubule, reducing the reabsorption of water.

Stimulation of central alpha 2-adrenergic receptors is associated with sympathoadrenal suppression and subsequent reduction of blood pressure. As this class was further explored it was discovered that sympathoadrenal activity can also be suppressed by a second pathway with a newly discovered drug target specific to imidazolines . Specifically, moxonidine binds the imidazoline receptor subtype 1 (I1) and to a lesser extent αlpha-2-adrenoreceptors in the RSV causing a reduction of sympathetic activity, reducing systemic vascular resistance and thus arterial blood pressure.

Moreover, since alpha-2-adrenergic receptors are considered the primary molecular target that facilitates the most common side effects of sedation and dry mouth that are elicited by most centrally acting antihypertensives, moxonidine differs from these other centrally acting antihypertensives by demonstrating only low affinity for central alpha-2-adrenoceptors compared to the aforementioned I1-imidazoline receptors .

Dosage

Moxovas H dosage

Adults-

For Edema: The usual adult dosage is 25 to 100 mg daily as a single or divided dose.

For Control of Hypertension: The usual initial dose in adults is 25 mg daily given as a single dose. The dose may be increased to 50 mg daily, given as a single or two divided doses. Doses above 50 mg are often associated with marked reductions in serum potassium. In some patients (especially the elderly) an initial dose of 12.5 mg daily may be sufficient.

Infants and children-

For diuresis and for control of hypertension: The usual pediatric dosage is 1 to 2 mg/kg/day in single or two divided doses, not to exceed 37.5 mg per day in infants up to 2 years of age or 100 mg per day in children 2 to 12 years of age. In infants less than 6 months of age, doses up to 3 mg/kg/day in two divided doses may be required.

Adults (including the elderly): Your treatment will normally start with one 200 microgram tablet, taken in the morning. After three weeks, your doctor may increase this dose to 400 micrograms daily, given in a single dose in the morning, or in divided doses in the morning and evening. After another three weeks, your doctor may need to increase this dose to 600 micrograms daily, given in divided doses (morning and evening). You should not take more than 400 micrograms as a single dose, or more than 600 micrograms in any one day.

If you forget to take a dose, take one as soon as you remember, unless it is nearly time to take the next one. Do not take a double dose to make up for a forgotten dose.

If you forget to take a dose, take one as soon as you remember, unless it is nearly time to take the next one. Do not take a double dose to make up for a forgotten dose.

Side Effects

Generally, Hydrochlorothiazide is well tolerated. However, a few side effects may occur like weakness, restlessness, dizziness, headache, fever, diarrhea, vomiting, sialadenitis, cramping, constipation, gastric irritation, nausea, anorexia, and hypotension. In rare case hyperglycemia, glycosuria, hyperuricemia and muscle spasm may occur.

The following side effects have been reported at the approximate frequencies shown:

• Very common: dry mouth, drowsiness
• Common: headache, dizziness (vertigo), flushing (vasodilation), weakness or loss of strength, confusion, sleep disturbances, nausea (feeling sick), being sick (vomiting), stomach upsets (dyspepsia), diarrhoea, rash or itching (pruritus), back pain

Toxicity

The oral LD₅₀ of hydrochlorothiazide is >10g/kg in mice and rats.

Patients experiencing an overdose may present with hypokalemia, hypochloremia, and hyponatremia. Treat patients with symptomatic and supportive treatment including fluids and electrolytes. Vasopressors may be administered to treat hypotension and oxygen may be given for respiratory impairment.

• Contraindicated due to known hypersensitivity to an ingredient (Physiotens tablets contain lactose), heart failure, severe renal impairment, < 16 years old, >75 years old, bradycardia, severe bradyarrhythmia, sick sinus syndrome, second or third degree atrioventricular block, malignant arrhythmias.
• Used with caution in patients with history of severe coronary artery disease (CAD), unstable angina, angioneurotic edema.
• Pregnancy Category B3:Avoid use during pregnancy (inadequate data in pregnant woman) and lactation (maternal blood stream transfer to breast milk shown) unless benefit clearly justifies risk.
• Lack of specific therapeutic experience in cases of intermittent claudication, Raynaud's disease, Parkinson's disease, epileptic disorders, gluacoma, and depression suggest moxonidine should not be used in such instances .
• Carcinogenicity and genotoxicity does not appear significant.
• Concurrent administration of other hypotensives or sedative and hypnotics can enhance the hypotensive effect and intensify sedation respectively.
• Avoid concurrent Tricyclic Antidepressant (TCA) use to avoid reduction of monoxidine efficacy.
• Generally well tolerated with dry mouth and headache the most common adverse effects
• Symptoms of overdose correlate with pharmacodynamic properties:hypotension, sedation, orthostatic dysregulation, bradycardia, dry mouth with no specific counter-treatment known.

Precaution

Thiazides should be used with caution in patients with severe renal disease, impaired hepatic function or progressive liver disease and gout.

Tell your doctor before you start to take this medicine if you:

• have a heart problem called "1st-degree AV-block"
• have a severe coronary heart disease, or have angina (chest pain at rest)
• have poor circulation
• have kidney disease
• have been told you have cerebrovascular insufficiency (poor blood supply to the brain which means you are at a greater risk of stroke)
• are below 16 years of age
• have a rare hereditary problem of galactose intolerance, Lapp lactase deficiency or glucosegalactose malabsorption as you should not take this medicine

Patients who are intolerant to lactose should note that Moxonidine tablets contain a small amount of lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

Interaction

Alcohol, Barbiturates, or Narcotics: Potentiation of orthostatic hypotension may occur.

Antidiabetic Drugs (oral agents and insulin): Thiazides can impair control of diabetes mellitus by diet and antidiabetic Drugs. Antihypertensive Drugs: Additive effect or potentiation.

Talk to your doctor if you are taking any of the following:

• beta-blockers, such as propranolol or atenolol, used to treat heart problems
• other medicines used to reduce blood pressure such as furosemide a diuretic, or captopril an angiotensin-converting enzyme inhibitor
• antidepressants such as amitriptyline
• sleeping tablets such as zopiclone, tranquilizers such as nitrazepam, lorazepam or phenobarbital
• Moxonidine is removed from body by kidneys through the process called "tubular excretion". Other medicines removed from the kidneys in the same way could affect how moxonidine works.

Do not drink alcohol whilst taking Moxonidine.

Volume of Distribution

The volume of distribution varies widely from one study to another with values of 0.83-4.19L/kg.

1.8±0.4L/kg.

Elimination Route

An oral dose of hydrochlorothiazide is 65-75% bioavailable, with a T_max of 1-5 hours, and a C_max of 70-490ng/mL following doses of 12.5-100mg. When taken with a meal, bioavailability is 10% lower, C_max is 20% lower, and T_max increases from 1.6 to 2.9 hours.

90% of an oral dose is absorbed with negligible interference from food intake or first pass metabolism, resulting in a high bioavailability of 88%.

Half Life

The plasma half life of hydrochlorothiazide is 5.6-14.8h.

Plasma elimination half life is 2.2 - 2.3 hours while renal elimination half life is 2.6-2.8 hours.

Clearance

The renal clearance of hydrochlorothiazide in patients with normal renal function is 285mL/min. Patients with a creatinine clearance of 31-80mL/min have an average hydroxychlorothiazide renal clearance of 75mL/min, and patients with a creatinine clearance of ≤30mL/min have an average hydroxychlorothiazide renal clearance of 17mL/min.

Administered twice daily due to short half life .

However, lower dosage adjustments and close monitoring is necessary in elderly and renal impairment patients due to reduced clearance. In particular, the exposure AUC can increase by about 50% following a single dose and at steady state in elderly patients and moderately impaired renal function with GFR between 30-60 mL/min can cause AUC increases by 85% and decreases in clearence to 52 %.

Elimination Route

Hydrochlorothiazide is eliminated in the urine as unchanged hydrochlorothiazide.

Elimination is nearly entirely via the kidneys with a majority (50 -75%) of overall moxonidine being eliminated unchanged through renal excretion. Ultimately, more than 90% of a dose is eliminated by way of the kidneys within the first 24 hours after administration, with only approximately 1% being eliminiated via faeces.

Pregnancy & Breastfeeding use

Pregnancy: Evidence of fetal risk in hydrochlorothiazide therapy is found, but it is indicated if benefits outweigh risks. Thiazides are indicated in pregnancy when edema is due to pathologic causes.\

Lactation: Neonatal side effects have been seen incase of hydrochlorothiazide therapy and therefore it is not recommended.

Moxonidine is not recommended if you are pregnant, planning on becoming pregnant or are breastfeeding. Ask your doctor or pharmacist for advice before taking any medicine if you are pregnant or breastfeeding.

Contraindication

Hydrochlorothiazide is contraindicated to the patients of anuria and those who are sensitive to hydrochlorothiazide or to other sulfonamide-derived drugs. Therapy is not to be initiated in diabetes mellitus.

Do NOT take Moxonidine if you:

• Are allergic (hypersensitive) to moxonidine or any of the other ingredients of this medicine
• Have a slow heart rate or suffer from an abnormal heart rhythm or a change in the rate of the heart beat (called “sick sinus syndrome” or “2nd or 3rd degree AV-block”
• Have, or have had, heart failure or other heart problems

Special Warning

Elderly: in some patients specially the elderly an initial dose of 12.5 mg daily may be sufficient.

Children: An initial dose for children has been 1 to 2 mg per kg body-weight in 2 divided doses. Infants under 6 months may need doses upto 3 mg per kg daily.

Patients with kidney problems: If you have moderate problems with your kidneys, you should not take more than one 200 microgram tablet as a single dose or more than 400 micrograms in total, a day.

Children under 16 years of age: Moxonidine is not recommended for use in children.

Acute Overdose

The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. Rarely, autoimmune hemolytic anemia and other hypersensitivity reactions may complicate the picture.

In the event of over dosage, symptomatic and supportive measures should be employed. Emesis should be induced or gastric lavage performed. Correct dehydration, electrolyte imbalance, hepatic coma and hypotension by established procedures. Hemodialysis can be used successfully to treat severe intoxication.

If you (or someone else) swallow a lot of the tablets all together, or if you think a child has swallowed any of the tablets, contact your nearest hospital casualty department or your doctor immediately. An overdose is likely to cause headache, sleepiness, dry mouth, loss of balance, dizziness, low blood pressure, slowing of the pulse, vomiting, feeling tired, weakness and pain in your stomach. Please take this leaflet, any remaining tablets and the container with you to the hospital or doctor so that they know which tablets were consumed.

Storage Condition

Store between 15-30°C. Protect from light, moisture and freezing.

Do not store above 30° C. Keep blister in the outer carton in order to protect from light

Innovators Monograph

You find simplified version here Moxovas H