DRUGS & SUPPLEMENTS

Reserpine; Hydrochlorothiazide; Hydralazine

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Reserpine; Hydrochlorothiazide; Hydralazine uses

Reserpine; Hydrochlorothiazide; Hydralazine consists of Hydralazine Hydrochloride, Hydrochlorothiazide, Reserpine.

Hydralazine Hydrochloride:


1 INDICATIONS AND USAGE

Reserpine; Hydrochlorothiazide; Hydralazine is a combination of isosorbide dinitrate, a nitrate vasodilator, and Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride, an arteriolar vasodilator, indicated for:

  • the treatment of heart failure as an adjunct therapy to standard therapy in self-identified black patients to improve survival, prolong time to hospitalization for heart failure and to improve patient-reported functional status (1.1)

Limitations of use:

  • There is little experience in patients with NYHA class IV heart failure (1.2)

1.1 Treatment of Heart Failure in Self-identified Black Patients

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) is indicated for the treatment of heart failure as an adjunct to standard therapy in self-identified black patients to improve survival, to prolong time to hospitalization for heart failure, and to improve patient-reported functional status.

1.2 Limitations of Use

There is little experience in patients with NYHA class IV heart failure.

2 DOSAGE AND ADMINISTRATION

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) should be initiated at a dose of one Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) Tablet, three times a day. Titrate to a maximum of two tablets three times daily, if tolerated.

Although titration of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) can be rapid (3-5 days), some patients may experience side effects and may take longer to reach their maximum tolerated dose. The dosage may be decreased to as little as one-half Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) Tablet three times a day if intolerable side effects occur. Efforts should be made to titrate up as soon as side effects subside.

One tablet three times a day titrated to a maximum tolerated dose up to two tablets three times a day (2)

Dosage may be decreased to as little as one-half tablet three times a day if intolerable side effects occur. Efforts should be made to titrate up as soon as side effects subside (2)

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3 DOSAGE FORMS AND STRENGTHS

The Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) (20 mg isosorbide dinitrate and 37.5 mg Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride) tablets are orange, biconvex, approximately 8 mm in diameter, scored, film-coated, and debossed with "20" on one side over the score and "N" on the other side.

Tablets (scored): 20 mg isosorbide dinitrate and 37.5 mg Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride (3)

4 CONTRAINDICATIONS

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) is contraindicated in patients who are allergic to organic nitrates.

Do not use Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) in patients who are taking PDE-5 inhibitors, such as avanafil, sildenafil, tadalafil, or vardenafil. Concomitant use can cause severe hypotension, syncope, or myocardial ischemia .

Do not use Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) in patients who are taking the soluble guanylate cyclase (sGC) stimulator riociguat. Concomitant use can cause hypotension.

  • Patients who are allergic to organic nitrates (4)
  • Use of phosphodiesterase type 5 (PDE5) inhibitors, such as avanafil, sildenafil, tadalafil, or vardenafil, or soluble guanylate cyclase (sGC) stimulator (riociguat). (4)

5 WARNINGS AND PRECAUTIONS

  • May cause symptomatic hypotension
  • Symptomatic Lupus Erythematosus Syndromes: Consider discontinuation if clinically appropriate (5.2)
  • Myocardial ischemia and angina ( 5.3)
  • Peripheral Neuritis: May be treated with Pyridoxine (5.4)

5.1 Hypotension

Symptomatic hypotension, particularly with upright posture, may occur with even small doses of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride). Hypotension is most likely to occur in patients who have been volume or salt depleted; correct prior to initiation of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) .

5.2 Systemic Lupus Erythematosus

Reserpine; Hydrochlorothiazide; Hydralazine hydrochloride has been reported to cause a drug-induced systemic lupus erythematosus (SLE) syndrome. Symptoms and signs usually regress when Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride is discontinued.

5.3 Worsening Ischemic Heart Disease

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride can cause tachycardia and hypotension potentially leading to myocardial ischemia and angina, particularly in patients with hypertrophic cardiomyopathy.

5.4 Peripheral Neuritis

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride has been associated with peripheral neuritis, evidenced by paresthesia, numbness, and tingling, which may be related to an antipyridoxine effect. Pyridoxine should be added to Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) therapy if such symptoms develop.

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6 ADVERSE REACTIONS

Most common adverse reactions than on placebo) were headache and dizziness (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Arbor Pharmaceuticals, LLC at 1-866-516-4950 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) has been evaluated for safety in 517 heart failure patients in A-HeFT. A total of 317 of these patients received Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) for at least 6 months, and 220 received Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) for at least 12 months. In A-HeFT, 21% of the patients discontinued Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) for adverse reactions compared to 12% who discontinued placebo. Overall, adverse reactions were more common in Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) -treated than in placebo-treated patients. Table 1 lists adverse reactions reported with an incidence, after rounding, ≥ 2% higher on Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) than on placebo in A-HeFT, regardless of causality. The most common reasons for discontinuing Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) in the A-HeFT trial was headache (7%).

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride)

(N=517)

%

Placebo

(N=527)

%

Headache 50 21
Dizziness 32 14
Asthenia 14 11
Nausea 10 6
Hypotension 8 4
Sinusitis 4 2
Ventricular tachycardia 4 2
Paresthesia 4 2
Vomiting 4 2
Amblyopia 3 1

In the V-HeFT I and II clinical studies, a total of 587 patients with heart failure were treated with the combination of isosorbide dinitrate and Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride. The type, pattern, frequency and severity of adverse reactions reported in these studies were similar to those reported in A-HeFT, described above and no unusual adverse reactions were reported.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Use of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride): The following adverse reactions have been identified with use of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride).

  • Cardiac Disorders: Palpitations
  • Ear and labyrinth disorders: Tinnitus, vertigo
  • Eye Disorders: Eyelid edema, vision blurred
  • Gastrointestinal Disorders: Abdominal discomfort, constipation
  • General Disorders and Administration Site Conditions: Facial pain, flushing, chest discomfort, chest pain, peripheral edema
  • Musculoskeletal and Connective Tissue Disorders: Pain in extremity, myalgia
  • Nervous Disorders: Dysgeusia, hypoaesthesia, migraine, syncope
  • Renal and Urinary Disorders: Chromaturia, pulmonary renal syndrome
  • Respiratory, Thoracic and Mediastinal Disorders: Dyspnea
  • Reproductive System and Breast Disorders: Erectile dysfunction
  • Skin and Subcutaneous Tissue Disorders: Erythema, hyperhidrosis, pruritus, face swelling

Use of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) Hydrochloride or Isosorbide Dinitrate: The following reactions have been reported with use of either Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride or isosorbide dinitrate.

  • Blood and Lymphatic System Disorders: Blood dyscrasias, agranulocytosis, purpura, eosinophilia, splenomegaly.
  • Eye Disorders: Lacrimation, conjunctivitis.
  • Gastrointestinal Disorders: Paralytic ileus.
  • Hepatobiliary Disorders: Hepatitis.
  • Psychiatric Disorders: Psychotic reactions, disorientation.
  • Renal and Urinary Disorders: Difficulty in urination.
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7 DRUG INTERACTIONS

7.1 Phosphodiesterase Inhibitors

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) is contraindicated in patients who are using a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), PDE5 inhibitors such as avanafil, sildenafil, vardenafil, and tadalafil have been shown to potentiate the hypotensive effects of organic nitrates. Do not use Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) in patients who are taking the soluble guanylate cyclase (sGC) stimulator riociguat. Concomitant use can cause hypotension .

8 USE IN SPECIFIC POPULATIONS

  • Pregnancy: Reserpine; Hydrochlorothiazide; Hydralazine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus (8.1)
  • Geriatric Use: Isosorbide dinitrate and Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) may be eliminated more slowly in elderly patients. Initiate therapy at the low end of the dosing range (8.5)

8.1 Pregnancy

Pregnancy Category C:

There are no studies using Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) in pregnant women.

Isosorbide dinitrate has been shown to cause a dose-related increase in embryo-toxicity (excess mummified pups) in rabbits at 70 mg/kg (12 times the MRHD of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) on a body surface area basis).

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride is teratogenic in mice at 66 mg/kg and possibly in rabbits at 33 mg/kg (2 and 3 times the MRHD of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) on a body surface area basis). There are no animal studies assessing the teratogenicity of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride).

A meta-analysis of randomized controlled trials comparing Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride with other antihypertensive agents for severe hypertension in pregnancy found that Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride was associated with significantly more maternal hypotension, placental abruption, caesarean sections and oliguria, with more adverse effects on fetal heart rate and with lower Apgar scores.

A combination of propranolol and Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride was administered to 13 patients with long-standing hypertension during 15 pregnancies. These pregnancies resulted in 14 live births and one unexplained stillbirth. The only neonatal complications were two cases of mild hypoglycemia. Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride and its metabolites have been detected using a non-selective assay in maternal and umbilical plasma in patients treated with the drug during pregnancy.

Isosorbide dinitrate has been used for effective acute and sub-chronic control of hypertension in pregnant women, but there are no studies using it in a chronic regimen and assessing its effects on pregnant women and/or the fetus.

8.3 Nursing Mothers

No studies have been performed with Reserpine; Hydrochlorothiazide; Hydralazine. It is not known if either Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) or isosorbide dinitrate is excreted in human milk.

8.4 Pediatric Use

The safety and effectiveness of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) in children have not been established.

8.5 Geriatric Use

Clinical studies of Reserpine; Hydrochlorothiazide; Hydralazine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in response between elderly and younger patients. In general, dose selection for an elderly patient should start at the low end of the dosing range, reflecting the greater frequency of decreased hepatic and renal function, and of concomitant disease or other drug therapies.

Isosorbide dinitrate, its active metabolites, and Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) may be eliminated more slowly in elderly patients.

8.6 Renal Impairment

There are no studies of renal impairment using Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride). No dose adjustment is required for Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) or isosorbide dinitrite .

Dialyzability of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) has not been determined. Dialysis is not an effective method for removing isosorbide dinitrate or its metabolite isosorbide-5-mononitrate from the body.

8.7 Hepatic Impairment

The effect of hepatic impairment on the pharmacokinetics of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) alone has not been determined. Isosorbide dinitrate concentrations increase in patients with cirrhosis. There are no studies of hepatic impairment using Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride).

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10 OVERDOSAGE

The signs and symptoms of overdosage with Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) are expected to be those of excessive pharmacologic effect, i.e., vasodilatation, reduced cardiac output and hypotension, and signs and symptoms include headache, confusion, tachycardia, and generalized skin flushing. Complications can include myocardial ischemia and subsequent myocardial infarction, cardiac arrhythmia, and profound shock. Syncope, coma and death may ensue without appropriate treatment.

Human Experience: There are no documented cases of overdosage with Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride). No deaths from acute poisoning have been reported.

Treatment: There is no specific antidote. Support of the cardiovascular system is of primary importance. Shock should be treated with plasma expanders, vasopressors, and positive inotropic agents. The gastric contents should be evacuated, taking adequate precautions to prevent aspiration. These manipulations have to be carried out after cardiovascular status has been stabilized, since they might precipitate cardiac arrhythmias or increase the depth of shock.

In patients with renal disease or congestive heart failure, therapy resulting in central volume expansion is not without hazard. Treatment of isosorbide dinitrate overdose in these patients may be difficult, and invasive monitoring may be required.

No data are available to suggest physiological maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of the components of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride). Dialysis is not effective in removing circulating isosorbide dinitrate. The dialyzability of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) has not been determined.

Methemoglobinemia: Nitrate ions liberated during metabolism of isosorbide dinitrate can oxidize hemoglobin into methemoglobin. There are case reports of significant methemoglobinemia in association with moderate overdoses of organic nitrates. Methemoglobin levels are measurable by most clinical laboratories. Methemoglobinemia could be serious in chronic heart failure patients because of already compromised vascular bed-tissue gas exchange dynamics. Classically, methemoglobinemic blood is described as chocolate brown, without color change on exposure to air. When methemoglobinemia is diagnosed, the treatment of choice is methylene blue, 1 to 2 mg/kg intravenously.

11 DESCRIPTION

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) is a fixed-dose combination of isosorbide dinitrate, a vasodilator with effects on both arteries and veins, and Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride, a predominantly arterial vasodilator.

Isosorbide dinitrate is described chemically as 1,4:3,6-dianhydro-D-glucitol dinitrate and its structural formula is:

Isosorbide dinitrate is a white to off-white, crystalline powder with the empirical formula C6H8N2O8 and a molecular weight of 236.14. It is freely soluble in organic solvents such as alcohol, chloroform and ether, but is only sparingly soluble in water.

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride is described chemically as 1-hydrazinophthalazine monohydrochloride, and its structural formula is:

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride is a white to off-white, crystalline powder with the empirical formula C8H8N4-HCl and a molecular weight of 196.64. It is soluble in water, slightly soluble in alcohol, and very slightly soluble in ether.

Each Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) Tablet for oral administration contains 20 mg of isosorbide dinitrate and 37.5 mg of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride.

The inactive ingredients in Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) tablets include: anhydrous lactose, microcrystalline cellulose, sodium starch glycolate, colloidal silicon dioxide, magnesium stearate, hypromellose, FD&C Yellow No. 6 aluminum lake, polyethylene glycol, titanium dioxide, polysorbate 80.

Chemical Structure Chemical Structure

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

The mechanism of action underlying the beneficial effects of Reserpine; Hydrochlorothiazide; Hydralazine in the treatment of heart failure has not been established.

Isosorbide dinitrate is a vasodilator affecting both arteries and veins. Its dilator properties result from the release of nitric oxide and the subsequent activation of guanylyl cyclase, and ultimate relaxation of vascular smooth muscle.

Several well-controlled clinical trials have used exercise testing to assess the anti-anginal efficacy of chronically-delivered nitrates. In the large majority of these trials, active agents were no more effective than placebo after 24 hours (or less) of continuous therapy. Attempts to overcome nitrate tolerance by dose escalation, even to doses far in excess of those used acutely, have consistently failed. Only after nitrates have been absent from the body for several hours is response to nitrates restored.

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride is a selective dilator of arterial smooth muscle. Animal data suggests that Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) may also mitigate tolerance to nitrates.

12.2 Pharmacodynamics

The basis for the beneficial clinical effects of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) is not known. In a small study of patients with chronic heart failure administered single doses of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) 75 mg, isosorbide dinitrate 20 mg, and the combination, the combination elicited a statistically significant decrease in pulmonary capillary wedge pressure compared to Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) alone. The increase in cardiac output, renal blood flow and limb blood flow with the combination, however, was not greater than with Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) alone. There is no study of hemodynamic effects following multiple dosing.

12.3 Pharmacokinetics

Absorption

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride): Following a single 75-mg oral dose of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) plus 40 mg of isosorbide dinitrate to 19 healthy adults, peak plasma concentrations of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) (88 ng/mL/65 kg) and isosorbide dinitrate (76 ng/mL/65 kg) were reached in 1 hour. The half-lives were about 4 hours for Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) and about 2 hours for isosorbide dinitrate. Peak plasma concentrations of the two active metabolites, isosorbide-2-mononitrate and isosorbide-5-mononitrate, were 98 and 364 ng/mL/65 kg, respectively, at about 2 hours. No information is currently available regarding the effect of food on the bioavailability of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) or isosorbide dinitrate from Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) tablets.

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride: About 2/3 of a 50-mg dose of 14C-hydralazine hydrochloride given in gelatin capsules was absorbed in hypertensive subjects. In patients with heart failure, mean absolute bioavailability of a single oral dose of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) 75 mg varies from 10 to 26%, with the higher percentages in slow acetylators. Administration of doses escalating from 75 mg to 1000 mg three times daily to congestive heart failure patients resulted in an up to 9-fold increase in the dose normalized AUC, indicating non-linear kinetics of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride), probably reflecting saturable first pass metabolism.

Isosorbide dinitrate : Absorption of isosorbide dinitrate from tablets after oral dosing is nearly complete. The average bioavailability of isosorbide dinitrate is about 25%, but is highly variable (10%-90%) because of first-pass metabolism, and increases progressively during chronic therapy. Serum concentrations reach their maximum about one hour after ingestion.

Distribution

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride: After intravenous administration of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) in a dose of 0.3 mg/kg, the steady-state volume of distribution in patients with congestive heart failure was 2.2 L/kg.

Isosorbide dinitrate: The volume of distribution of isosorbide dinitrate is 2 to 4 L/kg. About 28% of circulating isosorbide dinitrate is protein bound.

Under steady-state conditions, isosorbide dinitrate accumulates significantly in muscle (pectoral) and vein (saphenous) wall relative to simultaneous plasma concentrations.

Metabolism

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) is metabolized by acetylation, ring oxidation and conjugation with endogenous compounds including pyruvic acid. Acetylation occurs predominantly during the first-pass after oral administration which explains the dependence of the absolute bioavailability on the acetylator phenotype. About 50% of patients are fast acetylators and have lower exposure.

After oral administration of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride), the major circulating metabolites are Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) pyruvate hydrazone and methyltriazolophthalazine. Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) is the main pharmacologically active entity; Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) pyruvate hydrazone has only minimal hypotensive and tachycardic activity. The pharmacological activity of methyltriazolophthalazine has not been determined. The major identified metabolite of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) excreted in urine is acetylhydrazinophthalazinone.

Isosorbide dinitrate undergoes extensive first-pass metabolism in the liver and is cleared at a rate of 2 to 4 L/minute with a serum half-life of about 1 hour. Isosorbide dinitrate's clearance is primarily by denitration to the 2-mononitrate (15 to 25%) and the 5-mononitrate (75 to 85%). Both metabolites have biological activity, especially the 5-mononitrate which has an overall half-life of about 5 hours. The 5-mononitrate is cleared by denitration to isosorbide, glucuronidation to the 5-mononitrate glucuronides, and by denitration/hydration to sorbitol. The 2-mononitrate appears to participate in the same metabolic pathways with a half-life of about 2 hours.

Elimination

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride): Metabolism is the main route for the elimination of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride). Negligible amounts of unchanged Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) are excreted in urine.

Isosorbide dinitrate: Most isosorbide dinitrate is eliminated renally as conjugated metabolites.

Special Populations

No pharmacokinetic studies in special populations were conducted with Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride). Pharmacokinetics in special populations is based on individual components.

Geriatric Patients -The pharmacokinetics of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) and isosorbide dinitrate, alone or in combination, have not been determined in patients over 65 years of age.

Pediatric Patients - The pharmacokinetics of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) and isosorbide dinitrate, alone or in combination, have not been determined in patients below the age of 18 years.

Gender - There are no studies of gender-dependent effects with Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride). In a single dose study with isosorbide dinitrate, no gender-dependent differences in the pharmacokinetics of isosorbide dinitrate and its mononitrate metabolites were found.

Renal Impairment - The effect of renal impairment on the pharmacokinetics of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) has not been determined. In a study with 49 hypertensive patients on chronic therapy with Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) in daily doses of 25-200 mg, the daily dose of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) in 19 subjects with severely impaired renal function (creatinine clearance 5-28 mL/min) and in 17 subjects with normal renal function (creatinine clearance >100 mL/min) using a population PK approach was not different, suggesting no need for dose adjustment in patients with renal impairment. The dialyzability of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) has not been determined. In three studies, renal insufficiency did not affect the pharmacokinetics of isosorbide dinitrate. Dialysis is not an effective method for removing isosorbide dinitrate or its metabolite isosorbide-5-mononitrate from the body.

Hepatic Impairment - The effect of hepatic impairment on the pharmacokinetics of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) alone has not been determined. Isosorbide dinitrate concentrations increase in patients with cirrhosis.

Drug-Drug Interactions

No pharmacokinetic drug-drug interaction studies were conducted with Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride).

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride): Administration of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) can increase the exposure to a number of drugs including beta-blockers. In healthy males administered a single oral dose of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) 50 mg and propranolol 1 mg/kg, the Cmax and AUC for propranolol approximately doubled. In healthy subjects administered a single oral dose of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) 50 mg and metoprolol 100 mg, the Cmax and AUC for metoprolol increased by 50% and 30%, respectively. In pre-eclamptic women, twice-daily doses of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) 25 mg and metoprolol 50 mg increased the Cmax and AUC for metoprolol by 90% and 40%, respectively.

In healthy males administered single oral doses of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) 25 mg and either lisinopril 20 mg or enalapril 20 mg, Cmax and AUC for lisinopril were each increased 30%, but enalapril concentrations were unaffected.

Intravenous co-administration of 0.2 mg/kg Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) HCl and 40 mg furosemide in Japanese patients with congestive heart failure resulted in a 20% increase in the clearance of furosemide.

Isosorbide dinitrate: The vasodilating effects of coadministered isosorbide dinitrate may be additive to those of other vasodilators, including alcohol.

A single dose of 20 mg of isosorbide dinitrate was administered to healthy subjects after pretreatment with 80 mg propranolol three times daily for 48 hours, resulting in no impact on the pharmacokinetics of isosorbide dinitrate and isosorbide-5-mononitrate.

When single 100-mg oral doses of atenolol were administered 2 hours before isosorbide dinitrate at a 10-mg dose no differences in the pharmacokinetics of isosorbide dinitrate or its mononitrates were observed.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride: An increased incidence of lung tumors (adenomas and adenocarcinomas) was observed in a lifetime study in Swiss albino mice given Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride continuously in their drinking water at a dosage of about 250 mg/kg per day (6 times the MRHD provided by Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) on a body surface area basis). In a 2-year carcinogenicity study of rats given Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride by gavage at dose levels of 15, 30, and 60 mg/kg/day (up to 3 times the MRHD of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) on a body surface area basis), microscopic examination of the liver revealed a small, but statistically significant increase in benign neoplastic nodules in males (high-dosage) and females (both high and intermediate dosage groups). Benign interstitial cell tumors of the testes were also significantly increased in the high-dose group.

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride is mutagenic in bacterial systems, and is positive in rat and rabbit hepatocyte DNA repair studies in vitro. Additional in vivo and in vitro studies using lymphoma cells, germinal cells, fibroblasts from mice, bone marrow cells from Chinese hamsters and fibroblasts from human cell lines did not demonstrate any mutagenic or clastogenic potential for Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride.

Isosorbide dinitrate: No long-term animal studies have been performed to evaluate the mutagenic or carcinogenic potential of isosorbide dinitrate. A modified two-litter reproduction study among rats fed isosorbide dinitrate at 25 or 100 mg/kg/day (up to 9 times the Maximum Recommended Human Dose of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) on a body surface area basis) revealed no evidence of altered fertility or gestation.

14 CLINICAL STUDIES

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) or a combination of isosorbide dinitrate and Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride was studied in two placebo-controlled clinical trials in 1,692 patients with mild to severe heart failure (mostly NYHA class II and III) and one active control trial (vs. enalapril) in 804 patients. The results of the trials follow:

Placebo-controlled Study : In the multicenter trial V-HeFT I, the combination of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) and isosorbide dinitrate 75 mg/40 mg 4 times daily (n=186) was compared to placebo (n=273) in men with impaired cardiac function and reduced exercise tolerance (primarily NYHA class II and III) and on therapy with digitalis glycosides and diuretics. There was no overall significant difference in mortality between the two treatment groups. There was, however, a trend favoring Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) and isosorbide dinitrate, which on retrospective analysis, was attributable to an effect in blacks (n=128). Survival in white patients (n=324) was similar on placebo and the combination treatment.

Active-controlled Study: In a second study of mortality, V-HeFT II, the combination of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) and isosorbide dinitrate 75 mg/40 mg 4 times daily was compared to enalapril in 804 men with impaired cardiac function and reduced exercise tolerance (NYHA class II and III), and on therapy with digitalis glycosides and diuretics. The combination of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) and isosorbide dinitrate was inferior to enalapril overall, but retrospective analysis showed that the difference was observed in the white population (n=574); there was essentially no difference in the black population (n=215).

Based on these retrospective analyses suggesting an effect on survival in black patients, but showing little evidence of an effect in the white population, a third study was conducted among black patients with heart failure.

Placebo-controlled Study: The A-HeFT trial evaluated Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) vs. placebo among 1,050 self-identified black patients (over 95% NYHA class III) at 169 centers in the United States. All patients had stable symptomatic heart failure. Patients were required to have LVEF ≤ 35% or left ventricular internal diastolic dimension > 2.9 cm/m2 plus LVEF < 45%. Patients were maintained on stable background therapy and randomized to Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) (n=518) or placebo (n=532). Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) was initiated at 20 mg isosorbide dinitrate/37.5 mg Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride three times daily and titrated to a target dose of 40/75 mg three times daily or to the maximum tolerated dose. Patients were treated for up to 18 months.

The randomized population was 60% male, 1% NYHA class II, 95% NYHA class III and 4% NYHA class IV, with a mean age of 57 years, and was generally treated with standard treatments for heart failure including diuretics (94%, almost all loop diuretics), beta-blockers (87%), angiotensin converting enzyme inhibitors (ACE-I; 78%), angiotensin II receptor blockers (ARBs; 28%), either ACE-I or ARB (93%), digitalis glycosides (62%) and aldosterone antagonists (39%).

The primary endpoint was a composite score consisting of all-cause mortality, first hospitalization for heart failure, and responses to the Minnesota Living with Heart Failure questionnaire. The trial was terminated early, at a mean follow-up of 12 months, primarily because of a statistically significant 43% reduction in all-cause mortality in the BiDil-treated group (p=0.012; see Table 2 and Figure 1). The primary endpoint was also statistically in favor of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) (p ≤ 0.021). The BiDil-treated group also showed a 39% reduction in the risk of a first hospitalization for heart failure (p<0.001; see Table 2 and Figure 2) and had statistically significant improvement in response to the Minnesota Living with Heart Failure questionnaire, a self-report of the patient's functional status, at most time points. Patients in both treatment groups had mean baseline questionnaire scores of 51 (out of a possible 105).

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride)

(N=518)

Placebo

(N=532)

Hazard Ratio

(95% CI)

P
Composite -0.16±1.93 -0.47±2.04 - 0.021
All-cause mortality 6.2% 10.2% 0.57

(0.37, 0.89)

0.012
Hospitalization

for heart failure

16.4% 24.4% 0.61

(0.46, 0.80)

<0.001

Effects on survival and hospitalization for heart failure were similar in subgroups by age, gender, baseline disease, and use of concomitant medications, as shown in Figure 4.

Patients treated with Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) in the A-HeFT study had randomly measured blood pressures on average 3/3 mmHg lower than did patients on placebo. The contribution of the difference in blood pressure to the overall outcome difference is unknown. Whether both Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) and isosorbide dinitrate contribute to the overall outcome difference has not been studied in outcome trials. Isosorbide dinitrate and Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) have not been systematically studied for the treatment of heart failure as separate agents, and neither drug is indicated for heart failure.

Figure 1 Figure 2 Figure 3 Figure 4

16 HOW SUPPLIED/STORAGE AND HANDLING

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) Tablets contain 20 mg of isosorbide dinitrate and 37.5 mg of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) hydrochloride. They are biconvex, approximately 8 mm in diameter, scored, film-coated, orange tablets debossed "20" on one side over the score and "N" on the other side.

  • NDC 24338-010-18: Bottles of 180

Store at 25°C (77°F), excursions permitted to 15-30°C (59-86°F). Keep bottles tightly closed.

Protect from light. Dispense in a light-resistant, tight container.

17 PATIENT COUNSELING INFORMATION

Patients should be informed of possible side effects and advised to take the medication regularly and continuously as directed.

  • Headache

Inform patients that headaches often accompany treatment with Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride), especially during initiation of treatment. Advise patients to consult a physician to adjust the dose of Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) if headache continues with repeated dosing.

  • Hypotension

Warn patients about lightheadedness on standing.

Advise patients that inadequate fluid intake or excessive fluid loss from perspiration, diarrhea or vomiting may lead to an excessive fall in blood pressure and cause lightheadedness or even syncope. If syncope does occur, advise patients to discontinue Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) and notify their prescribing physician as soon as possible.

  • Phosphodiesterase-5 Inhibitors

Advise patients to inform their physicians if they are taking, or planning to take, sildenafil, vardenafil, or tadalafil. Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) should not be taken concomitantly with phosphodiesterase-5 inhibitors.

  • Worsening Ischemic Heart Disease

Advise patients to inform their physicians of any worsening of symptoms of myocardial ischemia, especially those with hypertrophic cardiomyopathy.

  • Systemic Lupus Erythematosus-like Symptoms

Advise patients if symptoms suggestive of systemic lupus erythematosus-such as arthralgia, fever, chest pain, prolonged malaise-occur to notify their prescribing physician.

  • Peripheral Neuritis

Advise patients if symptoms of peripheral neuritis-paresthesia, numbness, and tingling-occur to notify the prescribing physician.

Manufactured for:

arbor PHARMACEUTICALS, LLC

Atlanta, GA 30328

Manufactured by:

Kremers Urban Pharmaceuticals Inc.,

a subsidiary of Lannett Company, Inc.

Seymour, IN 47274, USA

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride) is a registered trademark of Arbor Pharmaceuticals, LLC

COPYRIGHT © Arbor Pharmaceuticals, LLC, 2016

U.S. Patent number 6,784,177; 6,465,463

All rights reserved

BDPI3.01

PRINCIPAL DISPLAY PANEL - 180 Tablet Bottle Label

NDC 24338-010-18

Rx only

Reserpine; Hydrochlorothiazide; Hydralazine (Hydralazine Hydrochloride)®

isosorbide dinitrate 20 mg/hydralazine HCl 37.5 mg

180 Tablets

Store at room temperature 15°C - 30°C (59°F - 86°F)

BDTL1.03 Rev. 03/16

CIA75473D

U.S. Patent #s 6,784,177; 6,465,463

Hydrochlorothiazide:


Reserpine; Hydrochlorothiazide; Hydralazine information

Reserpine; Hydrochlorothiazide; Hydralazine (Hydrochlorothiazide) is an antihypertensive, diuretic drug that acts on the electrolyte reabsorption in the renal tubular mechanism increasing the excretion of chloride and sodium in equivalent amounts. The exact mechanism of its antihypertensive action is not known at this time.

Reserpine; Hydrochlorothiazide; Hydralazine indications

Reserpine; Hydrochlorothiazide; Hydralazine (Hydrochlorothiazide) is typically employed for the treatment of patients suffering from hypertension, either as monotherapy or in combination with other antihypertensive medication. It is also employed in some cases as a diuretic agent. Reserpine; Hydrochlorothiazide; Hydralazine (Hydrochlorothiazide) therapy may also be prescribed for the treatment of hepatic cirrhosis, edema (in patients suffering from congestive heart failure), nephrotic syndrome, drug induced edema, chronic renal failure or acute glomerulonephritis. Health care professionals may prescribe this drug in order to treat other medical conditions as well; if you would like to know more about the reasons you have been prescribed this drug, it is advised to ask your personal physician.

Reserpine; Hydrochlorothiazide; Hydralazine warnings

Reserpine; Hydrochlorothiazide; Hydralazine (Hydrochlorothiazide) may not be used in the treatment of patients who are allergic to this drug, any of its components or other sulfonamide-derived medication. Also, this drug may not be suitable for use in patients that are suffering from anuria, azotemia or impaired renal functions. Caution should be employed if the patient is suffering from hepatic disease. Other medical conditions may also influence the examining health care provider's decision of prescribing Reserpine; Hydrochlorothiazide; Hydralazine (Hydrochlorothiazide); it is strongly recommended to make sure that the health care professional is fully aware of your health condition and medical history before starting a treatment with this drug.

Use of Reserpine; Hydrochlorothiazide; Hydralazine (Hydrochlorothiazide) during pregnancy or breast-feeding is also not recommended. This medicine may affect an unborn baby and it also passes into breast milk. As such, use of this drug in pregnant women or breast-feeding mothers should not be employed.

Reserpine; Hydrochlorothiazide; Hydralazine intake guidelines

You should always take Reserpine; Hydrochlorothiazide; Hydralazine (Hydrochlorothiazide) as you have been directed by the prescribing health care specialist. While in some cases daily administration of the drug is recommended, other patients may be prescribed an intermittent therapy. Also, the number of daily doses may vary. As such, it is best that you do not follow another patient's intake schedule. If you have difficulties understanding the intake guidelines that your prescribing health care professional has provided, you should ask for further explanations from an authorized health care specialist - such as a pharmacist, a doctor or a nurse.

Reserpine; Hydrochlorothiazide; Hydralazine dosage

The exact Reserpine; Hydrochlorothiazide; Hydralazine (Hydrochlorothiazide) dosage may vary greatly from one case to another, depending on the condition being treated, on the patient's medical history and general health condition, on his or her age as well as on a number of other factors. As such you are advised to use the exact Reserpine; Hydrochlorothiazide; Hydralazine (Hydrochlorothiazide) dosage that has been prescribed to you and never use the dosage prescribed to another patient or a dosage that you have been prescribed in the past. Taking a different Reserpine; Hydrochlorothiazide; Hydralazine (Hydrochlorothiazide) dose may cause the treatment to not have the desired effect, and if you take this drug in larger doses you may have a higher risk of developing side effects, or you may suffer from an overdose.

Reserpine; Hydrochlorothiazide; Hydralazine overdose

You should never exceed the Reserpine; Hydrochlorothiazide; Hydralazine (Hydrochlorothiazide) prescribed dosage, in order to avoid an overdose with this medication. However, if you consider that you are affected by an overdose with this drug it is advised to immediately consult your personal health care provider, the local poisons center or to go to the nearest medical facility to seek emergency medical attention. The common symptoms of an overdose with Reserpine; Hydrochlorothiazide; Hydralazine (Hydrochlorothiazide) are dehydration and cardiac arrhythmia. The patient may also suffer from electrolyte depletion and thus may present the relevant signs and symptoms.

Reserpine; Hydrochlorothiazide; Hydralazine missed dose

In case you have missed a dose of Reserpine; Hydrochlorothiazide; Hydralazine (Hydrochlorothiazide), it is advised that you take the dose as soon as you remember. If the moment when you remember is too close to another intake of the medication, you should completely skip the missed Reserpine; Hydrochlorothiazide; Hydralazine (Hydrochlorothiazide) dose and take the next scheduled dose on time. You should never take a larger dose of the drug in order to make up for a missed dose, unless your prescribing health care provider directs you to do so.

Reserpine; Hydrochlorothiazide; Hydralazine side effects

In some patients Reserpine; Hydrochlorothiazide; Hydralazine (Hydrochlorothiazide) may cause side effects. While they are not very common, it is recommended to let your personal health care provider know if you begin experiencing any side effects. Several types of symptoms are possible: dizziness, headache, paresthesias, gastric irritation, anorexia, nausea and vomiting, diarrhea or constipation, pancreatitis, jaundice, hypotension. Metabolic side effects may include glycosuria, hyperglycemia, hyperuricemia, hypokalemia or hyponatremia. Renal failure or dysfunction may develop, as well as interstitial nephritis. Some patients reported experiencing muscle spasms, restlessness, unusual weakness and blurred vision. In some cases photosensitivity, anaphylactic reactions, respiratory distress, fever, rashes, vasculitis or toxic epidermal necrolysis have occurred.

Reserpine; Hydrochlorothiazide; Hydralazine drug reactions

Reserpine; Hydrochlorothiazide; Hydralazine (Hydrochlorothiazide) may interact with barbiturates and narcotics, as well as with alcohol. If you are also following a treatment course with antidiabetic drugs, their dosage may need to be adjusted before starting to take Reserpine; Hydrochlorothiazide; Hydralazine (Hydrochlorothiazide). This drug may have an additive effect with other antihypertensive medication. ACE inhibitors, ACTH, corticosteroids and skeletal muscle relaxants may also interact with this drug causing unwanted effects. This drug may not be properly absorbed if the patient is also taking Colestipol resins or Cholestyramine. NSAIDs, lithium and Pressor amines may affect or be affected by Reserpine; Hydrochlorothiazide; Hydralazine (Hydrochlorothiazide), and as such it is strongly recommended to let the prescribing health care provider know if you are taking these or any other drugs before starting a therapy course with this medicine. Other drug interactions that are not listed here are also possible.

Reserpine:


An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine; Hydrochlorothiazide; Hydralazine (Reserpine) inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use.

Indication: Foe the treatment of hypertension

Reserpine; Hydrochlorothiazide; Hydralazine (Reserpine) is an adrenergic blocking agent used to treat mild to moderate hypertension via the disruption of norepinephrine vesicular storage. The antihypertensive actions of Reserpine; Hydrochlorothiazide; Hydralazine (Reserpine) are a result of its ability to deplete catecholamines from peripheral sympathetic nerve endings. These substances are normally involved in controlling heart rate, force of cardiac contraction and peripheral resistance.

Reserpine; Hydrochlorothiazide; Hydralazine pharmaceutical active ingredients containing related brand and generic drugs:

infoActive ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Reserpine; Hydrochlorothiazide; Hydralazine available forms, composition, doses:

infoForm of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Reserpine; Hydrochlorothiazide; Hydralazine destination | category:

infoDestination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Reserpine; Hydrochlorothiazide; Hydralazine Anatomical Therapeutic Chemical codes:

infoA medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Reserpine; Hydrochlorothiazide; Hydralazine pharmaceutical companies:

infoPharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."HYDROCHLOROTHIAZIDE TABLET [QUALITEST PHARMACEUTICALS]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."HYDRALAZINE HYDROCHLORIDE TABLET [BRYANT RANCH PREPACK]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. Dailymed."RESERPINE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Reserpine; Hydrochlorothiazide; Hydralazine?

Depending on the reaction of the Reserpine; Hydrochlorothiazide; Hydralazine after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Reserpine; Hydrochlorothiazide; Hydralazine not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Reserpine; Hydrochlorothiazide; Hydralazine addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sDrugs.com conducted a study on Reserpine; Hydrochlorothiazide; Hydralazine, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Reserpine; Hydrochlorothiazide; Hydralazine consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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