Contraindiaction drugs for pregnency
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drugs absolutely contraindicated in pregnancy list 2024
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Drugs Contraindicated in Pregnancy
Drugs can harm the fetus through teratogenesis (structural malformations), fetotoxicity (organ damage), or both. The timing of exposure matters - organogenesis (weeks 3-8) is the most sensitive period for structural defects, while later exposure can damage developed organs.
1. Cardiovascular Drugs
| Drug / Class | Risk to Fetus |
|---|---|
| Warfarin | Teratogenic - fetal warfarin syndrome (nasal hypoplasia, stippled epiphyses, CNS defects), bleeding risk; use heparin instead - Lippincott Pharmacology |
| ACE Inhibitors (enalapril, captopril, lisinopril) | Pregnancy category X in 2nd/3rd trimesters - renal agenesis, neonatal anuria, oligohydramnios, intrauterine growth restriction (IUGR), fetal death - Creasy & Resnik's Maternal-Fetal Medicine |
| Angiotensin II Receptor Blockers (ARBs) (losartan, valsartan) | Similar fetotoxicity to ACE inhibitors - renal agenesis, neonatal anuria, IUGR, persistent patent ductus arteriosus, death - Rosen's Emergency Medicine |
| Statins (atorvastatin, simvastatin, lovastatin, rosuvastatin, etc.) | Potential fetal risk; all statins carry warnings to advise patients of fetal risk |
| Endothelin antagonists (bosentan, ambrisentan) | Teratogenic; absolutely contraindicated in pregnancy - Katzung's Pharmacology |
| Dronedarone | Contraindicated in pregnancy |
2. Antiepileptic / Mood-Stabilizing Drugs
| Drug | Risk |
|---|---|
| Valproate (valproic acid) | Neural tube defects (spina bifida) 1-4%, facial clefts, cardiac anomalies, cognitive deficits (IQ reduction), fetal valproate syndrome - Rosen's EM; Kaplan & Sadock's Psychiatry |
| Carbamazepine | Neural tube defects (~1%), craniofacial defects; avoid if possible |
| Phenytoin | Fetal hydantoin syndrome - cleft lip/palate, cardiac defects, digital/nail hypoplasia; neural tube defects |
| Phenobarbital | Teratogenic; cardiac malformations |
| Topiramate | Cleft palate/lip; oral clefts rate ~3.9-4.3% - Creasy & Resnik's |
3. Dermatological Drugs
| Drug | Risk |
|---|---|
| Isotretinoin (Accutane) | Highly teratogenic - retinoic acid embryopathy: CNS malformations, microtia, facial dysmorphism, cardiac defects; iPLEDGE program required |
| Acitretin (Soriatane) | Teratogenic retinoid; long half-life (metabolites persist up to 3 years) |
| Tazarotene | Topical retinoid; contraindicated |
| Finasteride | Risk of feminization of male fetus |
4. Antibiotics & Antiparasitic Drugs
| Drug | Risk |
|---|---|
| Tetracyclines (doxycycline, tetracycline) | Discoloration and dysplasia of fetal teeth and bones |
| Fluoroquinolones (ciprofloxacin, levofloxacin) | Cartilage damage; generally avoided |
| Chloramphenicol (late pregnancy) | "Grey baby" syndrome in neonate |
| Streptomycin / Aminoglycosides | Ototoxicity / deafness in fetus |
| Trimethoprim (1st trimester) | Folate antagonist - neural tube defects |
| Ribavirin | Teratogenic - absolute contraindication |
5. Antihypertensive Drugs (specific situations)
| Drug | Risk |
|---|---|
| Nitroprusside | Cyanide toxicity to fetus with prolonged use |
| Methyldopa | Relatively safe (first-line), but noted caution for liver toxicity |
6. Hormonal / Reproductive Drugs
| Drug | Risk |
|---|---|
| Androgens / Testosterone | Virilization of female fetus |
| Diethylstilbestrol (DES) | Vaginal adenocarcinoma in female offspring; reproductive anomalies |
| Misoprostol (when used as abortifacient) | Moebius sequence (facial nerve palsy), limb defects if pregnancy continues |
7. Anticancer / Immunosuppressive Drugs
| Drug | Risk |
|---|---|
| Methotrexate | Folate antagonist - absolutely contraindicated; aminopterin syndrome, neural tube defects, skeletal anomalies - Goodman & Gilman's |
| Thalidomide | Phocomelia (limb reduction defects) - historically catastrophic |
| Cyclophosphamide | Teratogenic; fetal growth restriction |
| Mycophenolate mofetil | Teratogenic - ear, limb, and facial malformations |
8. NSAIDs & Analgesics
| Drug | Risk |
|---|---|
| Aspirin / NSAIDs (3rd trimester) | Premature closure of ductus arteriosus, neonatal platelet dysfunction, oligohydramnios |
9. Psychotropic Drugs
| Drug | Risk |
|---|---|
| Lithium | Ebstein's anomaly (cardiac); neonatal toxicity |
| Benzodiazepines (diazepam, triazolam, temazepam) | Neonatal withdrawal, cleft palate (controversial) |
| Valproate (also listed above) | High teratogenic risk; use other mood stabilizers if possible |
10. Radioactive / Imaging Agents
| Agent | Risk |
|---|---|
| Radioactive iodine (I-131) | Fetal thyroid ablation; absolutely contraindicated - Scott-Brown's ENT |
Key Principle
The safest approach is to avoid all non-essential drugs in the first trimester, use the lowest effective dose of any necessary drug, and always weigh maternal benefit against fetal risk. Heparin (does not cross placenta) is the anticoagulant of choice in pregnancy.
Sources: Lippincott Illustrated Reviews Pharmacology; Creasy & Resnik's Maternal-Fetal Medicine; Rosen's Emergency Medicine; Katzung's Basic and Clinical Pharmacology; Goodman & Gilman's Pharmacological Basis of Therapeutics; Kaplan & Sadock's Textbook of Psychiatry; eMPR Drugs Contraindicated in Pregnancy
Maleria management
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malaria management WHO guidelines 2024 treatment
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Malaria: Management
Overview
Malaria is caused by Plasmodium species - primarily P. falciparum (most dangerous), P. vivax, P. ovale, P. malariae, and P. knowlesi. Management depends on: species identified, severity of disease, geographic drug resistance patterns, patient age, and pregnancy status.
Step 1: Diagnosis
Blood Film (Gold Standard)
- Thick film - concentrates parasites (40-100x), maximizes sensitivity; examine minimum 100-200 fields
- Thin film - species identification, quantification of parasitemia
- Parasitemia >10⁵/μL = high risk of death; >20% parasites with visible pigment = poor prognosis
Rapid Diagnostic Tests (RDTs)
- Detect PfHRP2 (P. falciparum-specific), lactate dehydrogenase, or aldolase antigens
- Main diagnostic method in endemic areas
- Limitation: do not quantify parasitemia; PfHRP2-deleted mutant parasites (emerging in East Africa/Horn of Africa) can give false negatives
Lab Findings
| Finding | Details |
|---|---|
| Anaemia | Normochromic, normocytic |
| Platelets | Usually reduced (~10⁵/μL); normal count should prompt alternate diagnosis |
| WBC | Usually normal or slightly raised in severe disease |
| Metabolic acidosis | Low glucose, bicarbonate, phosphate; raised lactate, creatinine, bilirubin in severe malaria |
| CSF (cerebral malaria) | Opening pressure ~160 mmH₂O; slight protein elevation |
Step 2: Classify Severity
Uncomplicated Malaria
Fever + parasitemia, able to tolerate oral medications, no signs of organ dysfunction.
Severe / Complicated Malaria (WHO Criteria)
Any one of the following constitutes severe malaria:
- Cerebral malaria (impaired consciousness, coma)
- Severe anaemia (Hb <7 g/dL)
- Respiratory distress / acidosis
- Hypoglycaemia (<2.2 mmol/L)
- Acute kidney injury
- Pulmonary oedema / ARDS
- Abnormal bleeding / DIC
- Hyperparasitaemia (>5% RBCs parasitised)
- Jaundice + organ dysfunction
- Circulatory collapse / shock ("algid malaria")
- Haemoglobinuria ("blackwater fever")
- Repeated convulsions
Step 3: Treatment
A. Uncomplicated P. falciparum Malaria
First-line: Artemisinin-Based Combination Therapy (ACT) - WHO Recommended
| ACT Regimen | Dose (Adults) | Duration |
|---|---|---|
| Artemether-lumefantrine (Coartem) - only ACT approved in the US | 4 tablets (20 mg/120 mg each) twice daily | 3 days |
| Artesunate-amodiaquine | As per weight-based dosing | 3 days |
| Artesunate-mefloquine | As per weight-based dosing | 3 days |
| Dihydroartemisinin-piperaquine | As per weight-based dosing | 3 days |
| Atovaquone-proguanil (Malarone) - alternative | 4 tablets (250/100 mg) daily | 3 days |
ACT combines a rapidly acting artemisinin derivative with a longer-acting partner drug to prevent recrudescence and slow the development of resistance. - Harrison's 22E
Alternative Regimens (if ACT unavailable)
- Quinine sulfate 650 mg 3x daily x 3-7 days + Doxycycline 100 mg twice daily x 7 days (or Clindamycin 600 mg twice daily x 7 days)
- Mefloquine 750 mg then 500 mg after 6-8 hours (or 1250 mg single dose)
B. Uncomplicated P. vivax / P. ovale Malaria
| Drug | Dose | Notes |
|---|---|---|
| Chloroquine phosphate | 1 g oral, then 500 mg at 6, 24, 48 hrs | Blood-stage treatment |
| + Primaquine (radical cure) | 30 mg base daily x 14 days | Eradicates hepatic hypnozoites; check G6PD first |
| OR Tafenoquine (radical cure) | 300 mg single dose | Also requires G6PD screening |
Primaquine and tafenoquine are the ONLY drugs that kill liver hypnozoites, preventing relapse in P. vivax and P. ovale. - Goldman-Cecil Medicine
Note on chloroquine resistance in P. vivax: Resistance is increasing in Indonesia, Papua New Guinea, parts of Asia and South America. Use ACT + primaquine in these regions.
C. P. malariae / P. knowlesi
- P. malariae: Chloroquine (as above; no radical cure needed - no hypnozoites)
- P. knowlesi: ACT recommended (same as P. falciparum)
D. Chloroquine-Sensitive P. falciparum (limited areas: Central America, Caribbean, parts of Middle East)
| Drug | Dose |
|---|---|
| Chloroquine phosphate | 1 g, then 500 mg at 6, 24, 48 hrs |
E. Severe / Complicated Malaria - Parenteral Treatment
Patients with severe malaria and those unable to take oral drugs should receive parenteral antimalarial therapy immediately. - Harrison's 22E
| Drug | Dose | Notes |
|---|---|---|
| IV Artesunate (FIRST-LINE) | 2.4 mg/kg IV at 0, 12, 24 hrs, then daily | Superior to quinine for severe malaria |
| IM Artemether | 3.2 mg/kg IM, then 1.6 mg/kg/day | If IV artesunate unavailable |
| IV Quinine dihydrochloride | 20 mg/kg loading over 4 hrs; then 10 mg/kg every 8 hrs | Cardiac monitoring required; risk of hypoglycaemia |
After IV therapy: Once patient tolerates oral drugs, complete a full oral course (Coartem, Malarone, or quinine + doxycycline).
Step 4: Adjunctive Management in Severe Malaria
| Problem | Management |
|---|---|
| Cerebral malaria | Maintain airway; avoid steroids (harmful); treat seizures with benzodiazepines |
| Hypoglycaemia | IV dextrose (50%); monitor closely - quinine worsens hypoglycaemia |
| Severe anaemia | Transfuse if Hb <7 g/dL or if symptomatic |
| Fluid management | Cautious IV fluids - pulmonary oedema risk; avoid aggressive hydration |
| Acute kidney injury | Renal replacement therapy if needed |
| Seizures | Benzodiazepines (diazepam, lorazepam) |
| Bacterial co-infection | Broad-spectrum antibiotics if suspected (common in African children) |
Step 5: Radical Cure - Preventing Relapse
| Species | Hypnozoites? | Additional Drug Required |
|---|---|---|
| P. falciparum | No | Not needed |
| P. malariae | No | Not needed |
| P. vivax | Yes | Primaquine x 14 days OR tafenoquine single dose |
| P. ovale | Yes | Primaquine x 14 days OR tafenoquine single dose |
Always check G6PD status before giving primaquine or tafenoquine - severe haemolytic anaemia can occur in G6PD-deficient patients.
Step 6: Drug Properties Summary
| Drug | Mechanism | Key Toxicity |
|---|---|---|
| Artemisinin / ACTs | Free radical damage to parasite proteins | Generally well tolerated; rare neurotoxicity |
| Chloroquine | Inhibits haem polymerization | Retinopathy (chronic), QT prolongation, pruritis |
| Primaquine | Oxidative stress on hepatocytes | Haemolytic anaemia in G6PD deficiency |
| Tafenoquine | Similar to primaquine | Haemolysis in G6PD deficiency |
| Quinine | Inhibits haem polymerization | Cinchonism (tinnitus, hearing loss), hypoglycaemia, QT prolongation |
| Mefloquine | Similar to quinine | Neuropsychiatric effects (nightmares, psychosis), QT prolongation |
| Atovaquone-proguanil | Mitochondrial electron transport inhibition | Nausea, vomiting |
| Doxycycline | Protein synthesis inhibition | Photosensitivity, oesophagitis (must be taken with water) |
Step 7: Prophylaxis (Travelers / Endemic Areas)
| Drug | Dose | Indication |
|---|---|---|
| Atovaquone-proguanil (Malarone) | 1 tablet daily (start 1-2 days before travel, continue 7 days after) | Chloroquine-resistant areas; well tolerated |
| Doxycycline | 100 mg daily (start 1-2 days before, continue 4 weeks after) | All areas; cheap but photosensitivity risk |
| Mefloquine | Weekly (start 2-3 weeks before, continue 4 weeks after) | Where sensitive; neuropsychiatric side effects |
| Chloroquine | Weekly | Only in chloroquine-sensitive areas |
| Primaquine | Daily | P. vivax-endemic areas (G6PD check required) |
Resistance Concerns (2024-2026)
- Artemisinin partial resistance has emerged and spread from Southeast Asia (Greater Mekong Subregion) into East Africa (Rwanda, Uganda), driven by kelch13 mutations - a major global threat
- Piperaquine resistance alongside artemisinin resistance in parts of Southeast Asia = high clinical failure rates for DHA-piperaquine
- Chloroquine resistance in P. falciparum is now global except Central America and the Caribbean
- Triple ACTs (combining two partner drugs with artemisinin) are being explored to counter resistance
Special Situations
| Population | Consideration |
|---|---|
| Pregnancy (1st trimester) | Quinine + clindamycin preferred; ACT if no alternative (recent WHO update now permits ACT in 1st trimester) |
| Pregnancy (2nd/3rd trimester) | ACT is safe and recommended |
| Children | Weight-based ACT dosing; artemether-lumefantrine widely used |
| HIV co-infection | Increased malaria severity; cotrimoxazole prophylaxis provides partial protection; drug interactions with ARVs (avoid amodiaquine with efavirenz) |
Sources: Harrison's Principles of Internal Medicine 22E (2025); Goldman-Cecil Medicine, International Edition; Katzung's Basic and Clinical Pharmacology, 16th Ed; WHO Guidelines for Malaria, updated August 2025; CDC Treatment Guidelines 2024
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