Hydromet is a combination of two drugs, methyldopa, and hydrochlorothiazide. Methyldopa is a centrally acting drug that reduces the sympathetic outflow to the heart, kidneys, and blood vessels. Hydrochlorothiazide is a diuretic that reduces intravascular volume.
Hydromet (Methyldopa and hydrochlorothiazide) Uses:
-
Hypertension:
- Used in management of hypertension
Methyldopa and hydrochlorothiazide Dose in Adults:
Methyldopa and hydrochlorothiazide (Hydromet) Dose in the treatment of Hypertension: Oral:
Note: Dose is individualized.
-
Replacement therapy:
- Initial:
- Methyldopa 250 mg/hydrochlorothiazide 15 mg twice to three times per day, methyldopa 500 mg/hydrochlorothiazide 30 mg once per day, or methyldopa 500 mg/hydrochlorothiazide 50 mg once per day are all acceptable dosages.
- Maximum each day dose, based on the hydrochlorothiazide content:
- Oral: 50 mg per day.
- Initial:
Use in Children:
Not indicated.
Pregnancy Risk Factor: C
- Animal reproduction research has not employed this combination.
- Hydrochlorothiazide with methyldopa
Use of hydrochlorothiazide and methyldopa during breastfeeding
- Breast milk contains hydrochlorothiazide and methyldopa.
- The manufacturer advises that a choice be made regarding whether to cease nursing or stop using the medication because there are major adverse reactions for nursing babies.
- This should be done taking into consideration the importance of mother's treatment.
Methyldopa and hydrochlorothiazide (Hydromet) Dose in Kidney Disease:
- The manufacturer's labelling does not mention dosage modifications (use is contraindicated with anuria).
For hydrochlorothiazide, the following modifications have been suggested:- CrCl ≥10 mL/minute:
- No dosage adjustment is necessary.
- Usually ineffective with CrCl <30 mL/minute unless in combination with a loop diuretic.
- CrCl <10 mL/minute:
- Use not recommended.
- CrCl ≥10 mL/minute:
Dose in Liver disease:
There are no dosage adjustments provided in the manufacturer's labeling; use is contraindicated in patients with active hepatic disease.
Methyldopa and hydrochlorothiazide (Hydromet) Side effects:
See individual agents (Methyldopa and hydrochlorothiazide)
Contraindications to Methyldopa and hydrochlorothiazide (Hydromet):
- Hypersensitivity to methyldopa, medicines derived from sulfonamides, hydrochlorothiazide, or any other ingredient in the formulation
- Active cirrhosis (active cirrhosis), acute hepatitis
- Hepatic disorders were previously linked to the use of methyldopa
- Use of MAO inhibitors concurrently
- Anuria
Notification:
- The FDA-approved product labelling that warns against combining this medication with other sulfonamide-containing drug classes has come under fire.
- There is not much evidence of cross-reactivity between thiazide-related diuretics and allergens.
- Cross-sensitivity is possible due to similarities in chemical structure and/or pharmaceutical actions.
- However, this cannot be excluded with absolute certainty.
Warnings and precautions
-
Electrolyte disturbances:
- Hydrochlorothiazide can cause hypokalemia, hypochloremic acidkalosis, hypomagnesemia and hyponatremia.
-
Gout
- In certain people with a history of gout or who are at risk for chronic renal failure, hydrochlorothiazide can cause gout.
- Doses of 25 mg and more can increase the risk.
-
Hematologic effects
- Rare reports of reversible Granulocytopenia or Thrombcytopenia caused by methyldopa have been documented.
- Hemolytic anaemia is uncommon; 10% to 20% of individuals experience positive Coombs test results between 6 and 12 months of treatment; routinely run CBC.
- If you experience Coombs' positive hemolyticanemia while receiving treatment, discontinue and do not resume.
- After stopping, Coombs can take a few weeks or months to get back to normal.
-
Hepatic effects
- Patients with liver disease or dysfunction may experience liver problems, including fatal hepatic necrosis.
- Monitor your liver function every 6-12 weeks or whenever unexplained symptoms occur.
- Stop the therapy if there is a fever, abnormal liver function tests, or jaundice.
-
Hypersensitivity reactions
- Hydrochlorothiazide may cause hypersensitivity reactions.
- Patients with a history bronchial or allergy disorder are at greater risk.
-
Neuromuscular effects:
- Rarely, when using methyldopa, have patients with severe bilateral cerebrovascular disorders shown choreoathetotic movements.
- It is critical to stop treatment if any of these symptoms appear.
-
Ocular effects
- Acute angle-closure vision loss or transitory myopia caused by hydrochlorothiazide may occur in patients with acute visual acuity and ocular pain.
- If intraocular pressure is not controlled, additional treatments may be required.
- Penicillin allergy and sulfonamide allergy history are examples of risk factors.
-
Photosensitivity
- Hydrochlorothiazide may cause photosensitization.
-
Sedation
- Sedation is usually temporary and may occur during initiation or when the dose of methyldopa increases.
-
Allergy to sulfonamide ("sulfa")
- Possibility of cross-reactivity between members of a specific class (eg two antibiotic sulfonamides).
- Concerns about cross-reactivity have been brought up for all substances with the sulfonamide structure.
- A lot of drugs that belong to the chemical class of sulfonamide have product labelling that has FDA approval.
- For individuals who have previously experienced an allergic reaction to sulfonamides, this includes a broad contraindication.
- Nonantibiotic sulfonamides are not likely to cause anaphylaxis (inter-reactions due to antibody production).
- T-cell-mediated (type IV), reactions (eg maculopapular skin rash) are less understood. It is difficult to exclude this possibility based on current knowledge.
- Some clinicians will limit exposure to classes in cases of severe reactions (Stevens Johnson syndrome/TEN).
- A fuller understanding of allergic pathways shows that it may not be possible for non-antibiotic or antibiotic sulfonamides to cross-react with each other.
-
Bariatric surgery
- Diuretics should not be used for the first 24 hours following bariatric surgery to prevent dehydration. Dehydration or electrolyte problems could happen.
- If oral fluid consumption targets have been reached, diuretics may be restarted if necessary.
-
Diabetes:
- Diabetes mellitus or prediabetes people shouldn't use hydrochlorothiazide.
-
Hepatic impairment
- Patients with significant hepatic impairment should use hydrochlorothiazide with caution.
- In cases of advanced or severe liver illness, avoid acid/base imbalances and electrolyte imbalances. A coma or hepatic emboli may result from this.
-
Hypercalcemia:
- Patients with hypercalcemia may be advised to limit their use
- Thiazide diuretics may lower renal calcium excretion.
-
Hypercholesterolemia:
- Patients with high or moderate cholesterol should not use Hydrochlorothiazide.
-
Hypokalemia
- Hypokalemia patients should be treated with Hydrochlorothiazide.
-
Parathyroid disease
- Thiazide diuretics decrease calcium excretion.
- Long-term use of these drugs can cause pathologic changes in parathyroid glands, including hypophosphatemia and hypercalcemia.
- It is best to stop using them before testing for parathyroid function.
-
Renal impairment
- Patients with impaired renal function may experience cumulative effects, including azotemia.
- Hydrochlorothiazide should be stopped in severe renal disease. It may cause azotemia.
- Uremia is home to the active metabolites methyldopa.
-
Systemic lupus erythematosus (SLE):
- SLE activation or exacerbation can be caused by hydrochlorothiazide.
Methyldopa and hydrochlorothiazide: Drug Interaction
|
Ajmaline |
Sulfonamides might make ajmaline more harmful or poisonous. In particular, there may be an elevated risk for cholestasis. |
|
Alcohol (Ethyl) |
Increases the effectiveness of thiazide and thiazide-like diuretics in lowering orthostatic blood pressure. |
|
Alfuzosin |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Allopurinol |
The possibility of allergic or hypersensitive reactions to allopurinol may be increased by thiazide and thiazide-like diuretics. The serum concentration of Allopurinol may rise in response to thiazides and thiazide-like diuretics. In particular, Thiazide Diuretics may raise Oxypurinol's levels, an active metabolite of Allopurinol. |
|
Aminolevulinic Acid (Topical) |
Aminolevulinic Acid's photosensitizing impact may be enhanced by photosensitizing agents (Topical). |
|
Amphetamines |
May lessen the effectiveness of antihypertensive agents. |
|
Angiotensin-Converting Enzyme Inhibitors |
Angiotensin-Converting Enzyme Inhibitors' hypotensive effects may be enhanced by thiazide and thiazide-like diuretics. Angiotensin-Converting Enzyme Inhibitors' nephrotoxic effects may be increased by thiazide and thiazide-like diuretics. |
|
Anticholinergic Agents |
May raise the levels of thiazide and thiazide-like diuretics in the blood. |
|
Antidiabetic Agents |
The therapeutic value of anti-diabetic agents may be diminished by thiazide and thiazide-like diuretics. |
|
Antidiabetic Agents |
The therapeutic benefit of anti-diabetic agents may be reduced by hyperglycemia-associated agents. |
|
Antipsychotic Agents (Second Generation [Atypical]) |
Antipsychotic drugs' hypotensive effects may be enhanced by blood pressure-lowering medications (Second Generation [Atypical]). |
|
Barbiturates |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Benazepril |
Benazepril's hypotensive impact may be strengthened by hydrochlorothiazide. Benazepril may have a more nephrotoxic effect when combined with hydrochlorothiazide. Benazepril may lower the level of HydroCHLOROthiazide in the blood. |
|
Benperidol |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Beta2-Agonists |
Thiazide and Thiazide-Like Diuretics might have an enhanced hypokalemic impact. |
|
Bradycardia-Causing Agents |
May intensify other bradycardia-causing agents' bradycardic effects. |
|
Brigatinib |
May lessen the effectiveness of antihypertensive agents. Antihypertensive Agents' bradycardic action may be strengthened by brutinib. |
|
Brimonidine (Topical) |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Calcium Salts |
The excretion of calcium salts may be decreased by thiazide and thiazide-like diuretics. Metabolic alkalosis can also be brought on by continued concurrent usage. |
|
CarBAMazepine |
Thiazide and Thiazide-Like Diuretics may intensify CarBAMazepine's negative/toxic effects. Particularly, there could be a higher risk of hyponatremia. |
|
Cardiac Glycosides |
Cardiac Glycosides may have an increased negative or toxic effect when used with thiazide and thiazide-Like Diuretics. Particularly, the hypokalemic and hypomagnesemic impact of thiazide diuretics may worsen cardiac glycoside toxicity. |
|
COMT Inhibitors |
The metabolism of COMT Substrates might be decreased. |
|
Corticosteroids (Orally Inhaled) |
Thiazide and Thiazide-Like Diuretics might have an enhanced hypokalemic impact. |
|
Corticosteroids (Systemic) |
Thiazide and Thiazide-Like Diuretics might have an enhanced hypokalemic impact. |
|
Cyclophosphamide |
Thiazide and Thiazide-Like Diuretics may intensify Cyclophosphamide's harmful or hazardous effects. Particularly, granulocytopenia could be worsened. |
|
Dexketoprofen |
Sulfonamides' harmful or poisonous effects could be amplified. |
|
Dexmethylphenidate |
May lessen the effectiveness of antihypertensive agents. |
|
Diacerein |
Could make diuretics' therapeutic effects stronger. Particularly, there may be a higher chance of hypokalemia or dehydration. |
|
Diazoxide |
Thiazide and Thiazide-Like Diuretics may intensify Diazoxide's harmful or toxic effects. |
|
Diazoxide |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Dichlorphenamide |
The hypokalemic impact of dichlorphenamide may be enhanced by thiazide and thiazide-like diuretics. |
|
DULoxetine |
The hypotensive impact of DULoxetine may be enhanced by blood pressure lowering medications. |
|
Herbs (Hypertensive Properties) |
May lessen the effectiveness of antihypertensive agents. |
|
Herbs (Hypotensive Properties) |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Hypotension-Associated Agents |
The hypotensive action of hypotension-associated agents may be strengthened by blood pressure lowering medications. |
|
Ipragliflozin |
The toxic and harmful effects of thiazide and thiazide-like diuretics may be increased. In particular, there may be an elevated risk for intravascular volume depletion. |
|
Ivabradine |
The arrhythmogenic impact of ivabradine may be enhanced by thiazide and thiazide-like diuretics. |
|
Ivabradine |
Bradycardia-Causing Agents may intensify Ivabradine's bradycardic impact. |
|
Lacosamide |
Bradycardia-Causing Substances may intensify Lacosamide's AV-blocking effects |
|
Levodopa-Containing Products |
Levodopa-Containing Products' hypotensive effects may be strengthened by blood pressure-lowering medications. |
|
Licorice |
Thiazide and Thiazide-Like Diuretics might have an enhanced hypokalemic impact. |
|
Lormetazepam |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Methenamine |
The therapeutic effects of methenamine may be diminished by thiazide and thiazide-like diuretics. |
|
Methylphenidate |
May lessen the effectiveness of antihypertensive agents. |
|
Midodrine |
Bradycardia-Causing Agents' bradycardic effect might be enhanced. |
|
Molsidomine |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Multivitamins/Fluoride (with ADE) |
May intensify the effects of thiazide and thiazide-like diuretics on hypercalcemia. |
|
Multivitamins/Minerals (with AE, No Iron) |
The serum concentration of multiple vitamins and minerals may rise after taking thiazide and thiazide-like diuretics (with AE, No Iron). Particularly, thiazide diuretics may reduce calcium excretion, and long-term concurrent usage may result in metabolic alkalosis. |
|
Naftopidil |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Neuromuscular-Blocking Agents (Nondepolarizing) |
The neuromuscular-blocking action of neuromuscular-blocking agents may be enhanced by thiazide and thiazide-like diuretics (Nondepolarizing). |
|
Nicergoline |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Nicorandil |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Nitroprusside |
Nitroprusside's hypotensive impact may be strengthened by blood pressure-lowering medications. |
|
Nonsteroidal Anti-Inflammatory Agents |
Nonsteroidal Anti-Inflammatory Agents' nephrotoxic effects may be intensified by thiazide and thiazide-like diuretics. Thiazide and Thiazide-Like Diuretics may have less of a therapeutic impact when used with nonsteroidal anti-inflammatory drugs. |
|
Opioid Agonists |
Could make diuretics' harmful or toxic effects worse. Opioid antagonists may reduce diuretics' therapeutic benefit. |
|
Oxcarbazepine |
Thiazide and Thiazide-Like Diuretics may intensify OXcarbazepine's negative/toxic effects. Particularly, there could be a higher risk of hyponatremia. |
|
Pentoxifylline |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Pholcodine |
Pholcodine's hypotensive impact may be strengthened by blood pressure lowering medications. |
|
Phosphodiesterase 5 Inhibitors |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Porfimer |
The photosensitizing effect of Porfimer may be strengthened by photosensitizing agents. |
|
Prostacyclin Analogues |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Quinagolide |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Reboxetine |
Thiazide and Thiazide-Like Diuretics might have an enhanced hypokalemic impact. |
|
Ruxolitinib |
Bradycardia-Causing Agents' bradycardic effect might be enhanced. Management: The Canadian product labelling for roxolitinib advises against using it in conjunction with medications that can cause bradycardia whenever feasible. |
|
Selective Serotonin Reuptake Inhibitors |
The hyponatremic effects of thiazide and thiazide-like diuretics may be enhanced. |
|
Serotonin/Norepinephrine Reuptake Inhibitors |
May reduce the effectiveness of alpha2-agonists as an antihypertensive. |
|
Terlipressin |
Bradycardia-Causing Agents' bradycardic effect might be enhanced. |
|
Tofacitinib |
Bradycardia-Causing Agents' bradycardic effect might be enhanced. |
|
Toremifene |
Toremifene's hypercalcemic impact may be enhanced by thiazide and thiazide-like diuretics. |
|
Valsartan |
HydroCHLOROthiazide may increase Valsartan's ability to lower blood pressure. The serum concentration of HydroCHLOROthiazide may rise in response to Valsartan. |
|
Verteporfin |
Verteporfin's photosensitizing effect may be strengthened by photosensitizing agents. |
|
Vitamin D Analogs |
The hypercalcemic impact of vitamin D analogues may be enhanced by thiazides and thiazide-like diuretics. |
|
Yohimbine |
May lessen the effectiveness of antihypertensive agents. |
|
Risk Factor D (Consider therapy modification) |
|
|
Amifostine |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. |
|
Beta-Blockers |
The AV-blocking effect of beta-blockers may be strengthened by alpha2-agonists. Additionally, sinus node dysfunction might be aggravated. Beta-Blockers may make Alpha2-Agonists' rebound hypertensive impact more potent. When the Alpha2-Agonist is quickly removed, this consequence may happen. Management: Keep a close eye on your heart rate when taking clonidine and a beta blocker. When it's safe to do so, discontinue beta blockers a few days before discontinuing clonidine, and keep a close eye on your blood pressure. There are no recommendations for further alpha2-agonists. Levobunolol and metipranolol are exceptions. |
|
Bile Acid Sequestrants |
The absorption of thiazide and thiazide-like diuretics may be reduced. Also reduced is the diuretic reaction. |
|
Ceritinib |
Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Exceptions are discussed in separate monographs. |
|
Iron Preparations |
May lower the level of methyldopa in the blood. Iron Carboxymaltose, Iron Gluconate, Iron Hydroxide Polymaltose Complex, Iron Pyrophosphate Citrate, Ferumoxytol, Iron Dextran Complex, Iron Isomaltoside, and Iron Sucrose are exceptions. |
|
Lithium |
The excretion of lithium may be reduced by thiazide and thiazide-like diuretics. |
|
Mirtazapine |
May reduce the effectiveness of alpha2-agonists as an antihypertensive. Management: Take into account forgoing concurrent use. If the combination cannot be avoided, keep an eye out for either enhanced effects or decreased effects of alpha2-agonists if mirtazapine is started or dose increased. |
|
Multivitamins/Minerals (with ADEK, Folate, Iron) |
May lower the level of methyldopa in the blood. Management: To reduce this interaction, think about giving these products at least two hours apart; nevertheless, the effectiveness of this strategy seems to be limited. Keep an eye out for diminished therapeutic effects. |
|
Obinutuzumab |
May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. |
|
Riluzole |
Methyldopa might make Riluzole's harmful or hazardous effects worse. In particular, there may be an elevated risk of hepatotoxicity. Management: Due to the possibility of additive hepatotoxicity in patients receiving treatment with riluzole, consider alternatives to methyldopa. |
|
Siponimod |
Siponimod's bradycardic action may be enhanced by bradycardia-causing substances. Management: Steer clear of combining siponimod with medications that can slow your heart rate. |
|
Sodium Phosphates |
The nephrotoxic effects of sodium phosphates may be increased by diuretics. In particular, there may be an increased risk of acute phosphate nephropathy. Treatment: You might want to temporarily stop taking diuretics or look for an alternative to the oral sodium phosphate bowel preparation in order to prevent this combo. If the combination cannot be avoided, drink well and keep an eye on your kidney and fluid levels. |
|
Topiramate |
The hypokalemic impact of topiramate may be enhanced by thiazide and thiazide-like diuretics. The blood concentration of topiramate may rise in response to thiazide and thiazide-like diuretics. When using a thiazide diuretic, monitor for elevated topiramate levels and any negative consequences (such as hypokalemia). Serum potassium levels should be closely watched when receiving concurrent treatment. There may be a need to lower topiramate dosage. |
|
Tricyclic Antidepressants |
May reduce the effectiveness of alpha2-agonists as an antihypertensive. Management: Take into account avoiding this pairing. If utilised, keep an eye out for the alpha2-agonist's diminished effects. When stopping an alpha2-agonist in a patient on a TCA, proceed with extreme caution. |
|
Risk Factor X (Avoid combination) |
|
|
Aminolevulinic Acid (Systemic) |
Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). |
|
Bromperidol |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. |
|
Dofetilide |
The QTc-prolonging action of dofetilide may be strengthened by hydrochlorothiazide. The serum levels of Dofetilide may rise in response to HydroCHLOROthiazide. |
|
Fexinidazole [INT] |
Fexinidazole [INTability ]'s to induce arrhythmias may be enhanced by the use of thiazide and thiazide-like diuretics. |
|
Fexinidazole [INT] |
Bradycardia-Causing Agents may intensify Fexinidazole's [INT] ability to induce arrhythmias. |
|
Iobenguane Radiopharmaceutical Products |
Methyldopa may diminish the therapeutic effect of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer methyldopa until at least 7 days after each iobenguane dose. |
|
Levosulpiride |
Thiazide and Thiazide-Like Diuretics may intensify Levosulpiride's negative/toxic effects. |
|
Mecamylamine |
Sulfonamides may intensify Mecamylamine's harmful or hazardous effects. |
|
Monoamine Oxidase Inhibitors |
Methyldopa's negative/toxic effects might be amplified. |
|
Promazine |
Promazine's ability to prolong QTc may be enhanced by thiazide and thiazide-like diuretics. |
Monitoring parameters:
- Blood pressure;
- CBC;
- liver enzymes
- Serum electrolytes, BUN, creatinine;
- Coombs test
How to administer Methyldopa and hydrochlorothiazide (Hydromet)?
To reduce daytime sedation when the methyldopa component dose is larger, think about administering the medication in the evening.
Mechanism of action of Methyldopa and hydrochlorothiazide (Hydromet):
- A false transmitter used by methyldopa to excite central alpha-adrenergic receptors causes a reduction in sympathetic outflow to the heart, kidneys, and peripheral vasculature.
- The drug hydrochlorothiazide increases sodium, water, and potassium ion excretion by increasing sodium reabsorption from the distal tubules.
International Brand Names of Methyldopa and hydrochlorothiazide:
- Apo-Methazide
- Dopatens-H
- Hydromet
- Tensifort
Methyldopa and hydrochlorothiazide Brand Names in Pakistan:
There is no brand available in Pakistan.
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