Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringe Taj Pharma

DESCRIPTION

Clonidine Hydrochloride (clonidine hydrochloride injection) is a centrally-acting analgesic solution for use in continuous epidural infusion devices.

Clonidine Hydrochloride, USP, is an imidazoline derivative and exists as a mesomeric compound.

The chemical names are Benzenamine,2,6-dichloro-N-2-imidazolidinylidene monohydrochloride and 2- [(2,6-dichlorophenyl)imino]imidazolidine monohydrochloride.

COMPOSITION:

Clonidine Hydrochloride (clonidine hydrochloride injection) is supplied as a clear, colorless, preservative-free, pyrogen-free, aqueous sterile solution (pH 5 to 7) as single-dose Prefilled Syringe.

Each mL of the Clonidine Hydrochloride USP contains:
Clonidine Hydrochloride, USP       150 mcg

9 mg Sodium Chloride, USP in Water for Injection, USP. Hydrochloric Acid and/or Sodium Hydroxide may have been added for pH adjustment. Each 1 mL vial contains 1 mg (100 mcg) of clonidine hydrochloride.

CLINICAL PHARMACOLOGY

Mechanism of Action Epidurally administered clonidine produces dose-dependent analgesia not antagonized by opiate antagonists. The analgesia is limited to the body regions innervated by the spinal segments where analgesic concentrations of clonidine are present. Clonidine is thought to produce analgesia at presynaptic and postjunctional alpha-2-adrenoceptors in the spinal cord by preventing pain signal transmission to the brain.

Pharmacokinetics

Following a 10 minute intravenous infusion of 300 mcg clonidine HCl to five male volunteers, plasma clonidine levels showed an initial rapid distribution phase (mean±SD t ⁄ =11±9 minutes) followed by a slower elimination phase (t ⁄ =9±2 hours) over 24 hours. Clonidine’s total body clearance (CL) was 219±92 mL/min. Following a 700 mcg clonidine HCl epidural dose given over five minutes to four male and five female volunteers, peak clonidine plasma levels (4.4±1.4 ng/mL) were obtained in 19±27 minutes. The plasma elimination half-life was determined to be 22±15 hours following sample collection for 24 hours. CL was 190±70 mL/min. In cerebral spinal fluid (CSF), peak clonidine levels (418±255 ng/mL) were achieved in 26±11 minutes. The clonidine CSF elimination half-life was 1.3±0.5 hours when samples were collected for 6 hours. Compared to men, women had a lower mean plasma clearance, longer mean plasma half-life, and higher mean peak level of clonidine in both plasma and CSF. In cancer patients who received 14 days of clonidine HCl epidural infusion (rate=30 mcg/hr) plus morphine by patient-controlled analgesia (PCA), steady state clonidine plasma concentrations of 2.2±1.1 and 2.4±1.4 ng/mL were obtained on dosing days 7 and 14, respectively. CL was 279±184 and 272±163 mL/min on these days. CSF concentrations were not determined in these patients.

Distribution
Clonidine is highly lipid soluble and readily distributes into extravascular sites including the central nervous system. Clonidine’s volume of distribution is 2.1±0.4 L/kg. The binding of clonidine to plasma protein is primarily to albumin and varies between 20 and 40% in vitro. Epidurally administered clonidine readily partitions into plasma via the epidural veins and attains systemic concentrations (0.5 – 2.0 ng/mL) that are associated with a hypotensive effect mediated by the central nervous system.

Excretion
Following an intravenous dose of C-clonidine, 72% of the administered dose was excreted in urine in 96 hours of which 40-50% was unchanged clonidine. Renal clearance for clonidine was determined to be 133±66 mL/min. In a study where C-clonidine was given to subjects with varying degrees of kidney function, elimination half-lives varied (17.5 to 41 hours) as a function of creatinine clearance. In subjects undergoing hemodialysis only 5% of body clonidine stores were removed.

Metabolism
In humans, clonidine metabolism follows minor pathways with the major metabolite, p-hydroxyclonidine, being present at less than 10% of the concentration of unchanged drug in urine. Special Populations The pharmacokinetics of epidurally administered clonidine has not been studied in the pediatric population or in patients with renal or hepatic disease.

Clinical Trials
In a double-blind, randomized study of cancer patients with severe intractable pain below the C4 dermatome not controlled by morphine, 38 patients were randomized to an epidural infusion of Clonidine Hydrochloride  plus epidural morphine, whereas 47 subjects received epidural placebo plus epidural morphine. Both groups were allowed rescue doses of epidural morphine. Successful analgesia, defined as a decrease in either morphine use or Visual Analog Score (VAS) pain, was significantly more common with epidural clonidine than placebo (45% vs 21%, p=0.016). Only the subgroup of 36 patients with ‘‘neuropathic’’ pain, characterized by the investigator as well-localized, burning, shooting, or electriclike pain in a dermatomal or peripheral nerve distribution had significant analgesic effects relative to placebo in this study. The most frequent adverse events with clonidine were hypotension (45% vs 11% for placebo, p< 0.001), postural hypotension (32% vs 0%, p< 0.001), dizziness (13% vs 4%, p=0.234), anxiety (11% vs 2%, p=0.168) and dry mouth (13% vs 9%, p=0.505). Both mean blood pressure and heart rate were reduced in the clonidine group. At the conclusion of the two week study period in the clinical trial, all patients were abruptly withdrawn from study drug or placebo. Four patients of the clonidine group suffered rebound hypertension upon withdrawal of clonidine; one of these patients suffered a cerebrovascular accident. Asymptomatic bradycardia was noted in one clonidine patient.

INDICATIONS AND USAGE
Clonidine Hydrochloride  is indicated in combination with opiates for the treatment of severe pain in cancer patients that is not adequately relieved by opioid analgesics alone. Epidural clonidine is more likely to be effective in patients with neuropathic pain than somatic or visceral pain (see Clinical Trials). The safety of this drug product has only been established in a highly selected group of cancer patients, and only after an adequate trial of opioid analgesia. Other use is of unproven safety and is not recommended. In a rare patient, the potential benefits may outweigh the known risks (see WARNINGS).

CONTRAINDICATIONS
Clonidine Hydrochloride is contraindicated in patients with a history of sensitization or allergic reactions to clonidine. Epidural administration is contraindicated in the presence of an injection site infection, in patients on anticoagulant therapy, and in those with a bleeding diathesis. Administration of Clonidine Hydrochloride above the C4 dermatome is contraindicated since there are no adequate safety data to support such use (see WARNINGS).

WARNINGS
Use in Postoperative or Obstetrical Analgesia Clonidine Hydrochloride (epidural clonidine) is not recommended for obstetrical, post-partum, or peri-operative pain management. The risk of hemodynamic instability, especially hypotension and bradycardia, from epidural clonidine may be unacceptable in these patients.

Hypotension

Because severe hypotension may follow the administration of clonidine, it should be used with caution in all patients. It is not recommended in most patients with severe cardiovascular disease or in those who are otherwise hemodynamically unstable. The benefit of its administration in these patients should be carefully balanced against the potential risks resulting from hypotension.

Vital signs should be monitored frequently, especially during the first few days of epidural clonidine therapy. When clonidine is infused into the upper thoracic spinal segments, more pronounced decreases in the blood pressure may be seen.

Clonidine decreases sympathetic outflow from the central nervous system resulting in decreases in peripheral resistance, renal vascular resistance, heart rate, and blood pressure. However, in the absence of profound hypotension, renal blood flow and glomerular filtration rate remain essentially unchanged.

In the pivotal double-blind, randomized study of cancer patients, where 38 subjects were administered epidural Clonidine Hydrochloride at 30 mcg/hr in addition to epidural morphine, hypotension occurred in 45% of subjects. Most episodes of hypotension occurred within the first four days after beginning epidural clonidine. However, hypotensive episodes occurred throughout the duration of the trial. There was a tendency for these episodes to occur more commonly in women, and in those with higher serum clonidine levels. Patients experiencing hypotension also tended to weigh less than those who did not experience hypotension. The hypotension is usually responsive to intravenous fluids and, if necessary, appropriate parenterally-administered pressor agents.

Published reports on the use of epidural clonidine for intraoperative or postoperative analgesia also show a consistent and marked hypotensive response to clonidine. Severe hypotension may occur even if intravenous fluid pretreatment is given.

Withdrawal

Sudden cessation of clonidine treatment, regardless of the route of administration, has, in some cases, resulted in symptoms such as nervousness, agitation, headache, and tremor, accompanied or followed by a rapid rise in blood pressure. The likelihood of such reactions appears to be greater after administration of higher doses or with concomitant beta-blocker treatment. Special caution is therefore advised in these situations. Rare instances of hypertensive encephalopathy, cerebrovascular accidents and death have been reported after abrupt clonidine withdrawal. Patients with a history of hypertension and/or other underlying cardiovascular conditions may be at particular risk of the consequences of abrupt discontinuation of clonidine. In the pivotal double-blind, randomized cancer pain study, four of 38 subjects receiving 720 mcg of clonidine per day experienced rebound hypertension following abrupt withdrawal. One of these patients with rebound hypertension subsequently experienced a cerebrovascular accident.

Careful monitoring of infusion pump function and inspection of catheter tubing for obstruction or dislodgement can help reduce the risk of inadvertent abrupt withdrawal of epidural clonidine. Patients should notify their physician immediately if clonidine administration is inadvertently interrupted for any reason. Patients should also be instructed not to discontinue therapy without consulting their physician.

When discontinuing therapy with epidural clonidine, the physician should reduce the dose gradually over 2 to 4 days to avoid withdrawal symptoms.

An excessive rise in blood pressure following discontinuation of epidural clonidine can be treated by administration of clonidine or by intravenous phentolamine. If therapy is to be discontinued in patients receiving a beta-blocker and clonidine concurrently, the beta-blocker should be withdrawn several days before the gradual discontinuation of epidural clonidine.

Infections

Infections related to implantable epidural catheters pose a serious risk. Evaluation of fever in a patient receiving epidural clonidine should include the possibility of a catheter-related infection such as meningitis or epidural abscess.

PRECAUTIONS

General

Cardiac Effects: Epidural clonidine frequently causes decreases in heart rate. Symptomatic bradycardia can be treated with atropine. Rarely, atrioventricular block greater than first degree has been reported. Clonidine does not alter the hemodynamic response to exercise, but may mask the increase in heart rate associated with hypovolemia.

Respiratory Depression and Sedation: Clonidine administration may result in sedation through the activation of alpha-adrenoceptors in the brainstem. High doses of clonidine cause sedation and ventilatory abnormalities that are usually mild. Tolerance to these effects can develop with chronic administration. These effects have been reported with bolus doses that are significantly larger than the infusion rate recommended for treating cancer pain.

Depression: Depression has been seen in a small percentage of patients treated with oral or transdermal clonidine. Depression commonly occurs in cancer patients and may be exacerbated by treatment with clonidine. Patients, especially those with a known history of affective disorders, should be monitored for the signs and symptoms of depression.

Pain of Visceral or Somatic Origin: In the clinical investigations, at doses tested, Clonidine Hydrochloride was most effective in well-localized, ‘‘neuropathic’’ pain that was characterized as electrical, burning, or shooting in nature, and which was localized to a dermatomal or peripheral nerve distribution. Clonidine Hydrochloride may be less effective, or possibly ineffective in the treatment of pain that is diffuse, poorly localized, or visceral in origin.

Information for Patients

Patients should be instructed about the risks of rebound hypertension and warned not to discontinue clonidine except under the supervision of a physician. Patients should notify their physician immediately if clonidine administration is inadvertently interrupted for any reason. Patients who engage in potentially hazardous activities, such as operating machinery or driving, should be advised of the potential sedative and hypotensive effects of epidural clonidine. They should also be informed that sedative effects may be increased by CNS-depressing drugs such as alcohol and barbiturates, and that hypotensive effects may be increased by opiates.

Drug Interactions

Clonidine may potentiate the CNS-depressive effect of alcohol, barbiturates or other sedating drugs. Narcotic analgesics may potentiate the hypotensive effects of clonidine. Tricyclic anti-depressants may antagonize the hypotensive effects of clonidine. The effects of tricyclic anti-depressants on clonidine’s analgesic actions are not known.

Beta-blockers may exacerbate the hypertensive response seen with clonidine withdrawal. Also, due to the potential for additive effects such as bradycardia and AV block, caution is warranted in patients receiving clonidine with agents known to affect sinus node function or AV nodal conduction, e.g., digitalis, calcium channel blockers, and beta-blockers.

There is one reported case of a patient with acute delirium associated with the simultaneous use of fluphenazine and oral clonidine. Symptoms resolved when clonidine was withdrawn and recurred when the patient was rechallenged with clonidine.

Epidural clonidine may prolong the duration of pharmacologic effects of epidural local anesthetics, including both sensory and motor blockade.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a 132-week study in rats, clonidine hydrochloride administered as a dietary admixture at 5-8 times (based on body surface area) the 50 mcg/kg maximum recommended daily human dose (MRDHD) for hypertension did not show any carcinogenic potential. Clonidine was inactive in the Ames test of mutagenicity. Fertility of male or female rats was unaffected by oral clonidine hydrochloride doses as high as 150 mcg/kg, or about 0.5 times the MRDHD. Fertility of female rats did, however, appear to be affected in another experiment at oral dose levels of 500-2000 mcg/kg, or 2-7 times the MRDHD.

Usage in Pregnancy/Teratogenic Effects

Reproduction studies in rabbits at clonidine hydrochloride doses up to approximately the MRDHD revealed no evidence of teratogenic or embryotoxic potential. In rats, however, doses as low as onethird the MRDHD were associated with increased resorptions in a study in which dams were treated continuously from 2 months prior to mating. Increased resorptions were not associated with treatment with the same or higher doses up to 0.5 times the MRDHD when dams were treated on days 6-15 of gestation. Increased resorptions were observed at higher levels (7-times the MRDHD) in rats and mice treated on days 1-14 of gestation. Clonidine readily crosses the placenta and its concentrations are equal in maternal and umbilical cord plasma; amniotic fluid concentrations can be 4-times those found in serum. There are no adequate and well-controlled studies in pregnant women during early gestation when organ formation takes place. Studies using epidural clonidine during labor have demonstrated no apparent adverse effects on the infant at the time of delivery. However, these studies did not monitor the infants for hemodynamic effects in the days following delivery. Clonidine hydrochloride injection should be used during pregnancy only if the potential benefits justify the potential risk to the fetus. Labor and Delivery There are no adequate controlled clinical trials evaluating the safety, efficacy, and dosing of Clonidine Hydrochloride in obstetrical settings. Because maternal perfusion of the placenta is critically dependent on blood pressure, use of Clonidine Hydrochloride as an analgesic during labor and delivery is not indicated (see WARNINGS). Nursing Mothers Concentrations of clonidine in human breast milk are approximately twice those found in maternal plasma. Caution should be exercised when clonidine is administered to a nursing woman. Because of the potential for severe adverse reactions in nursing infants, a decision should be made to either discontinue nursing or to discontinue clonidine. Pediatric Use The safety and effectiveness of Clonidine Hydrochloride  in this limited indication and clinical population have been established in patients old enough to tolerate placement and management of an epidural catheter, based on evidence from adequate and well controlled studies in adults and experience with the use of clonidine in the pediatric age group for other indications. The use of Clonidine Hydrochloride  should be restricted to pediatric patients with severe intractable pain from malignancy that is unresponsive to epidural or spinal opiates or other more conventional analgesic techniques. The starting dose of Clonidine Hydrochloride  should be selected on per kilogram basis (0.5 mcg per kg per hour) and cautiously adjusted based on the clinical response.

ADVERSE REACTIONS

Adverse reactions seen during continuous epidural    clonidine infusion are dose-dependent and typical for a compound of this pharmacologic class. The adverse events most frequently reported in the pivotal controlled clinical trial of continuous epidural clonidine administration consisted of hypotension, postural hypotension, decreased heart rate, rebound hypertension, dry mouth, nausea, confusion, dizziness, somnolence, and fever. Hypotension is the adverse event that most frequently requires treatment. The hypotension is usually responsive to intravenous fluids and, if necessary, appropriate parenterally-administered pressor agents. Hypotension was observed more frequently in women and in lower weight patients, but no dose-related response was established.

Implantable epidural catheters are associated with a risk of catheter-related infections, including meningitis and/or epidural abscess. The risk depends on the clinical situation and the type of catheter used, but catheter related infections occur in 5%-20% of patients, depending on the kind of catheter used, catheter placement technique, quality of catheter care, and length of catheter placement.

The inadvertent intrathecal administration of clonidine has not been associated with a significantly increased risk of adverse events, but there are inadequate safety and efficacy data to support the use of intrathecal clonidine.

Epidural clonidine was compared to placebo in a twoweek double-blind study of 85 terminal cancer patients with intractable pain receiving epidural morphine. The following adverse events were reported in two or more patients and may be related to administration of either Clonidine Hydrochloride or morphine.

Incidence of Adverse Events in the Two-Week Trial

Adverse EventsClonidine N = 38 n (%)Placebo N = 47 n (%)
Total Number of Patients Who Experienced at Least One Adverse Event37 (97.4)38 (80.5)
Hypotension17 (44.8)5 (10.6)
Postural Hypotension12 (31.6)0 (0)
Dry Mouth5 (13.2)4 (8.5)
Nausea5 (13.2)10 (21.3)
Somnolence5 (13.2)10 (21.3)
Dizziness5 (13.2)2 (4.3)
Confusion5 (13.2)5 (10.6)
Vomiting4 (10.5)7 (14.9)
Nausea/Vomiting3 (7.9)1 (2.1)
Sweating2 (5.3)0 (0)
Chest Pain2 (5.3)0 (0)
Hallucination2 (5.3)1 (2.1)
Tinnitus2 (5.3)0 (0)
Constipation1 (2.6)2 (4.3)
Tachycardia1 (2.6)2 (4.3)
Hypoventilation1 (2.6)2 (4.3)

An open label long-term extension of the above trial was performed. Thirty-two subjects received epidural clonidine and morphine for up to 94 weeks with a median dosing period of 10 weeks. The following adverse events (and percent incidence) were reported: hypotension/postural  hypotension (47%); nausea (13%); anxiety/confusion (38%); somnolence (25%); urinary tract infection (22%); constipation, dyspnea, fever, infection (6%  each); asthenia,  hyperaesthesia,  pain,  skin ulcer, and vomiting (5% each). Eighteen percent of subjects discontinued this study as a result of catheter-related problems (infections, accidental dislodging, etc.), and one subject developed meningitis, possibly as a result of a catheter-related infection. In this study, rebound hypertension was not assessed, and ECG and laboratory data were not systematically sought.

The following adverse reactions have also been reported with the use of any dosage form of clonidine. In many cases patients were receiving concomitant medication and a causal relationship has not been established:

Body as a Whole: Weakness, 10%; fatigue, 4%; headache and withdrawal syndrome, each 1%. Also reported were pallor, a weakly positive Coomb’s test, and increased sensitivity to alcohol.

Cardiovascular: Palpitations and tachycardia, and bradycardia, each 0.5%. Syncope, Raynaud’s phenomenon, congestive heart failure, and electrocardiographic abnormalities (i.e., sinus node arrest, functional bradycardia, high degree AV block) have been reported rarely. Rare cases of sinus bradycardia and atrioventricular block have been reported, both with and without the use of concomitant digitalis.

Central Nervous System: Nervousness and agitation, 3%; mental depression, 1%; insomnia, 0.5%. Cerebrovascular accidents, other behavioral changes, vivid dreams or nightmares, restlessness, and delirium have been reported rarely.

Dermatological: Rash, 1%; pruritus, 0.7%; hives, angioneurotic edema and urticaria, 0.5%; alopecia, 0.2%.

Gastrointestinal: Anorexia and malaise, each 1%; mild transient abnormalities in liver function tests, 1%; hepatitis, parotitis, ileus and pseudo obstruction, and abdominal pain, rarely.

Genitourinary: Decreased sexual activity, impotence, and libido, 3%; nocturia, about 1%; difficulty in micturition, about 0.2%; urinary retention, about 0.1%.

Hematologic: Thrombocytopenia, rarely.

Metabolic: Weight gain, 0.1%; gynecomastia, 1%; transient elevation of glucose or serum phosphatase rarely.

Musculoskeletal: Muscle or joint pain, about 0.6%; leg cramps, 0.3%.

Oro-otolaryngeal: Dryness of the nasal mucosa was rarely reported.

Ophthalmological: Dryness of the eyes, burning of the eyes and blurred vision were rarely reported.

OVERDOSAGE

Hypertension may develop early and may be followed by hypotension, bradycardia, respiratory depression, hypothermia, drowsiness, decreased or absent reflexes, irritability, and miosis. With large oral overdoses, reversible cardiac conduction defects or arrhythmias, apnea, coma, and seizures have been reported. As little as 100 mcg of oral clonidine has produced signs of toxicity in pediatric patients.

There is no specific antidote for clonidine overdosage. Supportive care may include atropine sulfate for bradycardia, intravenous fluids and/or vasopressor agents for hypotension. Hypertension associated with overdosage has been treated with intravenous furosemide, diazoxide or alpha-blocking agents such as phentolamine. Naloxone may be a useful adjunct in the treatment of clonidine induced respiratory depression, hypotension, and/or coma; blood pressure should be monitored since the administration of naloxone has occasionally resulted in paradoxical hypertension. Tolazoline administration has yielded inconsistent results and is not recommended as first-line therapy. Dialysis is not likely to significantly enhance the elimination of clonidine.

The largest overdose reported to date involved a 28-year old white male who ingested 100 mg of clonidine hydrochloride powder. This patient developed hypertension followed by hypotension, bradycardia, apnea, hallucinations, semi-coma, and premature ventricular contractions. The patient fully recovered after intensive treatment. Plasma clonidine levels were  60  ng/mL  after  1 hour, 190  ng/mL after 1.5 hours, 370 ng/mL after 2 hours, and 120 ng/mL after 5.5 and 6.5 hours. In mice and rats, the oral LD50 of clonidine is 206 and 465 mg/kg, respectively.

DOSAGE AND ADMINISTRATION

The recommended starting dose of Clonidine Hydrochloride for continuous epidural infusion is 30 mcg/hr. Although dosage may be titrated up or down depending on pain relief and occurrence of adverse events, experience with dosage rates above 40 mcg/hr is limited.

Familiarization with the continuous epidural infusion device is essential. Patients receiving epidural clonidine from a continuous infusion device should be closely monitored for the first few days to assess their response.

Renal Impairment

Dosage should be adjusted according to the degree of renal impairment, and patients should be carefully monitored. Since only a minimal amount of clonidine is removed during routine hemodialysis, there is no need to give supplemental clonidine following dialysis.

Clonidine Hydrochloride must not be used with a preservative.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]

Preservative Free. Discard unused portion.

Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringe Taj Pharma

Read all of this leaflet carefully before you start taking this medicine

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor or pharmacist.

This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

If any of the side effects gets troublesome or serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

  1. What Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes are and what they are used for
  2. Before you receive Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes
  3. How Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes will be given
  4. Possible side effects
  5. How to store Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes
  6. Further information
  1. What Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes are and What they are used for

The name of your medicine is Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes 150 micrograms in 1 ml Solution for Injection (called Clonidine Hydrochloride USP Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes in this leaflet). Your medicine is a solution for injection.

Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes contain a medicine called clonidine. This belongs to a group of medicines called antihypertensives.

Clonidine Hydrochloride USP 150mcg/1ml is used to lower high blood pressure in cases of hypertensive crisis (a rapid rise in blood pressure that needs treating straight away).

  1. Before you receive Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes

You should not be given Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes if:

You are pregnant, likely to get pregnant or are breast-feeding

You are allergic (hypersensitive) to clonidine or any of the other ingredients of Clonidine Hydrochloride USP 150mcg/1ml (see section 6: Further information)

You have a slow heart rate due to heart problems

You are under 18 years old

You should not receive this medicine if any of the above apply to you. If you are not sure, talk to your doctor or pharmacist before having Clonidine Hydrochloride USP Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes.

Take special care with Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes

Check with your doctor or pharmacist before having Clonidine Hydrochloride USP Clonidine Hydrochloride USP 150mcg/1ml if:

  • You have Raynaud’s disease (a problem with circulation to the fingers and toes) or other blood circulation problems, including circulation to the brain
  • You have heart or kidney problems
  • You have or have ever had depression
  • You have constipation
  • You have a nerve disorder that causes your hands and feet to feel different (‘altered sensation’)

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before receiving Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes.

As you may get dry eyes whilst taking this medicine, this may be a problem if you wear contact lenses.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines. This includes medicines obtained without a prescription and herbal medicines. This is because Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes can affect the way some other medicines work. Also some other medicines can affect the way Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes works.

In particular tell your doctor or pharmacist if you are taking any of the following medicines:

  • Other medicines that make you drowsy
  • Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) such as ibuprofen
  • Medicines for depression such as imipramine or mirtazapine
  • Medicines for severe mental illness such as schizophrenia. These are also known as ‘antipsychotics’ and include chlorpromazine and haloperidol

Please also tell your doctor or pharmacist if you are taking any of the following medicines for high blood pressure or other heart problems:

  • Beta blockers such as atenolol
  • Water tablets (‘diuretics’) such as frusemide
  • Alpha blockers such as prazosin or doxazosin. These can also be used for prostate problems in men.
  • Vasodilators such as diazoxide or sodium nitroprusside
  • Calcium antagonists such as verapamil or diltiazem hydrochloride
  • ACE inhibitors such as captopril or lisinopril
  • Digitalis glycosides such as digoxin

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before receiving Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes.

Tests

If you are having any blood tests, tell the person giving the test that you are taking this medicine. This is because Clonidine Hydrochloride USP 150mcg/1ml can affect results relating to your liver.

Operations

If you are going to have an operation, you will need to still receive Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes.

Having Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes with food and drink

You may feel drowsy while receiving Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes. Drinking alcohol while receiving Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes can make this worse.

Pregnancy and breast-feeding

You should not be given Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes if you are pregnant, likely to get pregnant or are breast-feeding.

Driving and using machines

You may feel drowsy, dizzy, or could have some disturbances of vision. If affected, you should not drive, operate machinery or take part in any activities where these may put you or others at risk.

Important information about some of the ingredients of Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes contain sodium chloride,

the sodium content per 1 ml ampoule is less than 1 mmol (23 mg). The total sodium content if you are given 5 ampoules in 24 hours is less than

1 mmol (23 mg). This means that Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes are essentially sodium free.

  1. How Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes will be given

Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes are usually given by a doctor or nurse. You will normally be given 1 to 2 Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes but over 24 hours up to 5 ampoules may be given.

Your doctor will start you on a low dose but may increase the dose if you need more medicine to control your blood pressure.

Receiving the injection

  • Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes are slowly injected into a vein over 10-15 minutes
  • Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes may be diluted with other solutions if needed

Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes are not recommended for children or adolescents under 18 years old.

If you have more Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes than you should

It is unlikely that you will be given too much of this medicine. However, tell the doctor or nurse if you think that you have been given too much.

If you have any further questions on the use of Clonidine Hydrochloride USP 150mcg/1ml, ask your doctor or pharmacist.

  1. Possible Side Effects

Like all medicines, Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes can cause side effects, although not everybody gets them.

The side effects described below have been experienced by people taking Clonidine Hydrochloride USP 150mcg/1ml. They are listed as either very common, common, uncommon, rare or not known.

Very common (affects more than 1 in 10 people)

  • Dizziness, feeling tired and more relaxed than usual (sedation)
  • Feeling dizzy when you stand up (because your blood pressure has fallen sharply)
  • Dry mouth

Common (affects less than 1 in 10 people, more than 1 in 100 people)

  • Depression, sleeping problems
  • Headache
  • Constipation, feeling sick (nausea), pain below the ear (from the salivary gland), being sick (vomiting)
  • Erectile dysfunction
  • Fatigue

Uncommon (affects less than 1 in 100 people, more than 1 in 1,000 people)

  • Problems with understanding what is happening around you, hallucinations, nightmares
  • Your hands and feet feeling different (‘altered sensation’)
  • Regular unusually slow heart beat
  • Raynaud’s phenomenon (a problem with circulation to the fingers and toes)
  • Itching, rash, urticaria (nettle rash)
  • A feeling of discomfort and fatigue (‘malaise’)

Rare (affects less than 1 in 1,000 people, more than 1 in 10,000 people)

  • Breast growth (‘gynaecomastia’) in men
  • Dry eyes
  • Irregular heartbeat
  • Drying out of the lining of the nose
  • Pseudo-obstruction of the large bowel, which causes colicky pain, vomiting and constipation. Contact your doctor straight away if you have all these side effects.
  • Hair loss
  • Increase in your blood sugar

Not known

  • Confusion, loss of libido
  • Blurred vision
  • Abnormally slow heart beat

Two cases of hepatitis (inflammation of the liver) have also been reported. This might show up in some blood tests. Your body may also hold onto more water than usual (fluid retention).

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly (see details below). By reporting side effects you can help provide more information on the safety of this medicine.

  1. How to Store Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes

Keep out of the reach and sight of children.

The ampoules should not be stored above 30°C and should be kept in the outer carton.

Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes should not be used after the expiry date which is stated on the ampoule label and carton. The expiry date refers to the last day of that month.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

  1. Further Information

What Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes contain

  • The active substance is clonidine hydrochloride. Each 1 ml contains 150 micrograms of clonidine hydrochloride
  • The other ingredients in the injection are: sodium chloride, water for injections and hydrochloric acid

What Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes looks like and contents of the pack

Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes is clear glass containing a clear, colourless solution. Clonidine Hydrochloride USP 150mcg/1ml Prefilled Syringes.

  1. Manufactured in India by:
    TAJ PHARMACEUTICALS LTD.
    Mumbai, India
    Unit No. 214.Old Bake House,
    Maharashtra chambers of  Commerce Lane,
    Fort, Mumbai – 400001
    at:Gujarat, INDIA.
    Customer Service and Product Inquiries:
    1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
    Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
    E-mail: tajgroup@tajpharma.com