Drug Interaction:
Interacting drugs -summary
Methyl dopa + Methyldopate +
Lithium- increased neurotoxic effects with or without increased lithium serum
levels
Haloperidol- concomittant admn produces adverse mental symptoms
Levodopa- Methyl dopa potentiate effect of Levodopa
Methyl dopa+ Propanolol- cause paradoxical hypertension
Sympathomimics - Methyl dopa potentiates pressor effect
Tolbutamide- Tolbutamide metabolism impaired by Methyl dopa
Indication:
FIXED DOSE COMBINATIONS APPROVED BY DCG(I) FROM JANUARY 1961 TILL NOVEMBER 2014
Name of Drug Indication Date of Approval
Methyldopa 250mg + Feb 1969
HCTZ 15mg tablet
Hypertension
Antiadrenergic Agents- Centrally acting includes-
Methyl Dopa, Clonidine, Guannfacine Hcl, Guanabenz Acetate,
Adverse Reaction:
Allergic- fever, lupus-like syndrome.
Other- nasal stuuffiness, rise in BUN, mild arthalgia, myalgia, septic shock-like syndrome
CNS- sedation, usualy transcient, headache, asthenia or weakness, dizziness, lightheadedness,
mental acuity,
Cardiovascular- bradycardia, aggravation of anginaectoris, orthostatic hypotension, edema.
Discontinue if edema progresses or signs of hert failure.
GI- nausea, vomiting, distention, constipation, flatus, diarrhea, colitis, mild dry mouth
Hepatic- abnormal liver function tests, jaundice, hepatitis, liver disorders,
Hematologic- postive Coobs test, hemolytic anemia, bone marrow depression, leukopenia,
granulocytopenia, postive tests for antibody, LE cells and rheumatoid factor
Dermatologic- rash as in eczema, or lichenoid eruption, toxic epidermal necrolysis
Endocrine- breast enlargement, gynaecomastia, lactation, hyperprolactinemia, amenorhea,
galactorrhea
GU- impotence, failure to ejaculate, decreased libido
Contra-Indications:
Hepatitis,hypersens,Cirrhosis.Pheochromocytoma,depression,pre-existing postural hypotension.
Special precautions:
Discontinue drug in hemolytic anaemia.Anaesthesia,renal/hepatic impairment,pregnancy,
elderly.
Paradoxical choreathetotic movements- have been observed rarely in patients with severe bilateral cerbrovascular disease. Should these occur, discontinue therapy immediately.
Sedation- usually transcient may occur during initial therapy or whenever the dose is increased. Therefore patients should observe caution while driving or performing other tasks requiring alertness during these periods.
Urine discoloration- rarely when urine is exposed to air after voiding it may darken because of breakdown of methyldopa or its metabolites
Sulfite sensitivity- some o f these products contain sulfites that may cause allergic type reactions including anaphylactic symptoms and live-threatening asthmatic episodes.
Warnings-
A postive Coombs test, hemolytic anemia and liver disorders- may occur with methyldopa therapy
aPostive Coombs test /hemolytic anemia- with prolonged therapy, 10 to 20% of patients develop a postive direct Coombs test.
Liver disorders- perform perodic detreminations of hepatic function particularly during the first 6 to 12 weeks of therapy or when unexplained fever occurs.
Hematologic disorders- rarely, a reversible reduction of white cell WBC count with a rimary effect on granulocytosis has been seen, but promptly returns to normal on discontinuation of the drug.
Renal function impairment- use with caution in patients with renal failure.
Hepatic function impairment- use with caution in patients with previous liver disease or dysfunction.
Pregnancy-safety fort use during pregnancy has not been established. Use only when needed.
Lactation- the possiblity of effects on the nursing infant cannot be ruled out.
Dosages/ Overdosage Etc:
Indications:
Hypertension
Dosage:
Adults- Initial therapy 250mg 2 or 3 times a day in the first 24 hours. Adjust dosage at intervals
of not less than 2 days.
Children- Individualise dose based on 10mg/kg/day in 2 or 4 doses.
Overdosage-
Symptoms
Sedation, coma, acute hypotension, weakness, bradycardia, dizziness, lightheadness,constipation, distention, flatus, diarrhea, nausea, vomiting and other responses attributable to brain, and gastrointestinal malfunction. Atriovenrticular conduction may be impaired. Delayed absorption from the gut may delay onset of maximum hypotension.
Treatment
1. Employ gastric evacuation and general supportive when when ingestion is recent.
2. When ingestion has been earlier, infusions may be helpful to promote urinary excretion
3. Otherwise,management includes special attention to cardiac rate and output, blood volume , electrolye imbalance ,paralytic ileus , urinary function and cerbral activity.
4. Sympathomimetics drugs eg norepinephrine , epinephrine, metraminol bitatrate ) may be indicated
5. In severe cases consider hemodialysis
Missed dose-
1. If you miss a dose of this medicine, take it as soon as possible.
2. However, if it is almost time for the next dose,skip the missed dose and go back to your regular dosing schedule.
3. Do not double doses.
Other Information:
Hemolytic anemia - ( 270 )
Hemolytic anemias are encountered much less requently than the anemias due to decreased red cell production.
Although they are a diverse group the hemolytic anemias have a number of clinical features common
Drugs causing adverse reactions - ( 385 )
1. Methydopa
2. Levodopa
3. Mefenamic acid
4. Melphalan
5. Isoniazid
6. Rifampicin
7. Sulfonamides
8. Penicilins
9. Cephalosporins
10. Insulins
11. Quinidine
12. Chlorpromazine
13. Phenacetin
14. p-aminosalicylic acid
Patient Information:
METHYLDOPA - ANTIHYPERTENSIVES
Hypertensives
1. Consider compliance to weight reduction, sodium, and alcohol restriction
2. Discontinue smoking, continue excercise and behavoiur modificatin
3. Do not discontinue medication unless directed by physician, do not discontinue abruptly
4. Avoid cough , cold or allergy medications containing sympathomimetics
5. If dizziness (orthostatic hypotension ) occurs, avoid sudden changes in posture
6.Taking a hot bath or shower may aggravate the dizziness
7. Many of these medications may cause drowsiness, especially during the first days of therapy or when the dose is increased
8. Observe caution while driving or performing other tasks requiring alertness, coordination, or physical dexterity
9. If dehydration occurs due to nausea, vomiting, diarrhea, etc., the hypotensive effect may be increased. If this occurs, contact physician, a lower dose may be necessary
10.Allergies- tell your doctor if you have ever had any unusual or allergic reaction to methyldopa. Also tell your doctor if you are allergic to any other substances, such as foods, presrvatives or dyes.
11.Pregnancy - studies in pregnant women during the third semester (last three months of pregnancy) have not shown that methyldopa causes birth defects or other problems.
12.Breast feeding- although methyldopa passes into breast milk it has not been reported to cause problems in nursing babies
13. Children - this medicine is not expected to cause different side effects or problems in children than it does in adults.
14. Elderly- dizziness or lightheadedness and drowsiness may be more likely to occur in the elderly who are more sensitive to the effects of methyldopa
15. Other medicines -
Let your doctor know what other medicines you are taking, so that he can advice you accordingly.
MAOI - taking methyldopa while you are taking or within 2 weeks of taking MAOI may cause
nervousness in patients receiving MAOI, headache, severe high blood pressure and hallucinations
have been reported.
16. Other medical problems -
Tell your doctor if you have any other medical problems especially -
Angina or
Parkinsons disease - methyldopa may make these condition worse
Kidney diseasse or
Liver disease - effects of methyldopa may be increased
Mental depression - methyldopa can cause mental depression
Pheochromocytoma- methyldopa may interfere with tests for the condition, in addition there have
been reports of increased blood pressure
If you have taken methyldopa in the past and developed liver problems
17. Missed dose -
If you miss a dose of this medicine, take it as soon as possible. however, if it is almost time for the next dose, skip the missed dose. Do not double doses.
18. Storage -
Keep out of reach of children. Store away from heat or direct sunlight. Do not store
the capsule in bathroom, near the kitchen sink, or in other damp places.
19. Outdated medicines -
Do not keep outdated medicine or medicine no longer needed. Be sure that any
discarded medicine is out of reach of children.
Pharmacology/ Pharmacokinetics:
Antiadrenergic Agents- Centrally acting includes-
Methyl Dopa, Clonidine, Guannfacine Hcl, Guanabenz Acetate,
Pharmacology:
Mechanism of action of methyldopa not been conclusively demonstrated,but is probably due to the drugs metabolism to alpha-methyl norepinephrine,which lowers arterial pressure by stimulation of central inhibitory alpa-adrenergic receptors.
Pharmacokinetics:
approximately 2 days are required to establish maximal antihypertensive effects for hypertension to return after discontinuance of therapy. Effective IV doses cause a decline in blood pressure which may begin in 4 to 6 hours and last 10 to 16 hours.
Matabolism:
The elimination half-life is aprrox 2 hours,however,antihypertensive activity persists for upto 24 hours.
Interaction with Food:
Rate and bioavailability reduced
Pregnancy and lactation:
Pregnancy:
Safety for use during pregnancy has not been established.
Lactation:
Methyl dopa is excreted in breast milk. Use with caution on nursing mothers.
