Diclofenac (Injection / Tablet) in Pregnancy

General Safety Status by Trimester

Effect on Uterine Contractions

• Diclofenac inhibits prostaglandin synthesis (via COX inhibition). Since prostaglandins (especially PGE2 and PGF2α) stimulate uterine contractions, diclofenac reduces uterine contractility.
• In vitro studies confirm diclofenac decreases uterine contractility - this is mechanistically linked to:
  • Delayed onset of labor (tocolytic-like effect)
  • Increased risk of postpartum haemorrhage (atony due to reduced contractility) - PMC3683088
  • Prolonged gestation and possible stillbirth in animal models

Specific Fetal and Pregnancy Risks

• The ductus arteriosus (DA) connects the pulmonary artery to the aorta in the fetus. NSAIDs cause constriction/closure.
• Risk is greatest after 30 weeks gestation.
• A retrospective study found 4% of fetuses with second-trimester NSAID exposure ≥1 week developed narrowing or closure of the DA - Rheumatology (2022), p. 1293.
• Consequences: fetal pulmonary hypertension, right heart failure, fetal death. Pfizer FDA labeling specifically warns about this.

• NSAIDs reduce fetal urine output by inhibiting prostaglandin-mediated renal perfusion.
• Can occur even in the second trimester (and possibly first half of pregnancy per some studies).
• Consequences:
  • Fetal lung hypoplasia (underdeveloped lungs)
  • Joint contractures (stiff, immobile joints)
  • Increased risk of early delivery
  • Fetal demise in severe cases

• NSAIDs are associated with increased risk of spontaneous abortion when used in repeated doses early in pregnancy - Miller's Anesthesia (10e), p. block24.
• Prostaglandins help maintain corpus luteum function; inhibition may impair early implantation.

• Prostaglandins regulate fetal renal blood flow.
• Neonates born to mothers who took NSAIDs may have transient or persistent renal impairment.

• Diclofenac inhibits ~70% of COX-1 at therapeutic levels, reducing platelet aggregation.
• Risk of vaginal bleeding and postpartum haemorrhage - confirmed in prospective cohort data (PMC3683088).

• Second-trimester exposure to diclofenac was associated with low birth weight (<2500g) (adjusted OR 3.1) in cohort data, though this association had wide confidence intervals.

Summary of Contraindications

• Absolutely avoid from 20 weeks onward (FDA 2020 labeling update).
• Strictly contraindicated in the third trimester.
• If used in first/second trimester, use the lowest effective dose for the shortest duration (a few days maximum).
• Always use under physician supervision with fetal monitoring if continued past 20 weeks.

Safer Alternatives in Pregnancy

Clinical Assessment: 60-Year-Old Male with Polyarthritis + HTN + DM

Step 1: Differential Diagnosis

Most Likely Diagnoses

Important Point on Gout + Comorbidities:

Important Point on CPPD:

Step 2: Key Investigations

Blood Tests

Imaging

Synovial Fluid Analysis (if effusion present)

• Urate crystals (needle-shaped, negatively birefringent under polarized light) = Gout
• Calcium pyrophosphate crystals (rhomboid, weakly positive birefringent) = CPPD
• WBC count: >2000 = inflammatory; >50,000 = septic

Step 3: Diagnosis Confirmation

• Joint involvement pattern (MCP, PIP, wrist, MTP = high score)
• Serology: RF and/or ACPA
• Acute phase reactants: CRP/ESR
• Duration: >6 weeks

Step 4: Management (with Comorbidity Considerations)

⚠️ Special Precautions Given HTN + DM

A. If RA is Confirmed

1. DMARDs (Disease-Modifying Anti-Rheumatic Drugs) - start early:
   • Methotrexate 7.5-25 mg weekly (first-line DMARD) + folic acid 5 mg/week
   • If methotrexate contraindicated: Hydroxychloroquine or Sulfasalazine
   • Combination DMARDs if single-agent inadequate
2. Bridging therapy for inflammation:
   • Low-dose prednisolone (5-10 mg/day) - short course only; monitor blood glucose closely
   • Paracetamol (acetaminophen) for pain - safest analgesic in this patient
3. If inadequate response to DMARDs:
   • Biologic DMARDs: TNF-α inhibitors (etanercept, adalimumab), IL-6 inhibitors (tocilizumab)
   • JAK inhibitors (tofacitinib) - note cardiovascular risk in elderly
4. Physiotherapy + joint protection

B. If Gout (Acute Phase)

• Colchicine 0.5-1 mg twice daily (preferred over NSAIDs given HTN + DM) - adjust dose if eGFR <60
• Short-course oral prednisolone (30-35 mg/day x 3-5 days) if colchicine not tolerated
• Avoid NSAIDs if renal function compromised

• Allopurinol - first-line; start at 50-100 mg/day, titrate to target uric acid <6 mg/dL
• Febuxostat - alternative if allopurinol intolerant (note: cardiovascular caution in HTN)
• Dietary advice: reduce red meat, organ meats, shellfish, alcohol (especially beer), fructose-rich drinks
• Note: Stop thiazide diuretic if being used for HTN and switch to losartan (ARB with mild uricosuric effect - beneficial in gout + HTN)

C. If CPPD (Pseudogout)

• Acute: Colchicine or NSAIDs (short course with renal caution) or intra-articular steroid
• Chronic: No urate-lowering drug; manage underlying DM, hypothyroidism, hyperparathyroidism
• Hydroxychloroquine or methotrexate for refractory cases

Step 5: Monitoring Plan

Summary Table

• Harrison's Principles of Internal Medicine 22E, block40 (RA diagnosis)
• Robbins & Kumar Basic Pathology, block8 (Gout and CPPD)
• Rheumatology 2-Volume Set (2022, Elsevier), p. 1294 (medication use in comorbidities)
• Polyarthritis differential diagnosis - PMC
• AAFP Polyarticular Joint Pain 2023

Clinical Assessment: 32F - Post-coital Spotting + Dyspareunia + Vaginal Protrusion

Quick Clinical Picture

• 32-year-old female
• Post-coital spotting (1 day) + intracoital pain (dyspareunia)
• Pregnancy test: negative
• USG uterus + ovaries: normal
• PV examination: blood on gloves, tenderness, small protrusion in vagina

Step 1: Differential Diagnosis

1. Cervical Polyp (Most Likely) ★★★★★

• Smooth, reddish-purple, lobular, friable structure protruding from the cervical os or endocervical canal
• Bleeds easily on touch - explains blood on gloves
• Causes dyspareunia due to trauma during intercourse
• Cervical/endocervical polyps are the most common benign neoplastic growth on the cervix (incidence ~4% of gynecologic patients)
• The ability to manipulate the lesion in 4 directions with a swab distinguishes a polyp from a polypoid cervical irregularity
• Most are benign; malignancy risk is only ~1:1000 (higher in peri/postmenopausal women - this patient is only 32, so lower risk)
• USG being normal is consistent - small cervical polyps may not be visible on routine pelvic USG

2. Cervical Ectropion (Eversion/Erosion) ★★★★☆

• Eversion of endocervical columnar epithelium to the outside - creates a reddish, velvety, friable area on the ectocervix
• Very common in women of reproductive age, especially those on OCP or with previous pregnancies
• Bleeds on contact (touch/intercourse) - explains post-coital spotting and blood on gloves
• May appear as a protrusion if there is prominent eversion
• Generally not painful but can cause dyspareunia if inflamed

3. Early Cervical Carcinoma ★★★☆☆ (Must Exclude)

• Cannot be dismissed - post-coital bleeding with a visible cervical lesion is a red flag for cervical cancer until proven otherwise
• Early-stage cervical cancer (Stage Ia/Ib) can present as a small exophytic/polypoid growth on the cervix with contact bleeding
• Studies show cervical cancer prevalence of 3-5.5% in women presenting with post-coital bleeding, and CIN (pre-cancerous) prevalence of 6.8-17.5%
• 32 years is an age where cervical cancer does occur, particularly HPV-related
• The protrusion described could represent an early exophytic lesion

4. Cervicitis (Chlamydia / Gonorrhoea / Trichomonas) ★★★☆☆

• In women under 35, the most important cause to exclude is Chlamydial infection
• Inflamed, friable cervix bleeds on contact
• May cause mucopurulent discharge, contact bleeding, dyspareunia
• Ask for: new partner, unprotected sex, abnormal discharge, STI history

5. Prolapsed / Pedunculated Submucous Fibroid ★★☆☆☆

• A submucous leiomyoma can prolapse through the cervical os appearing as a firm protrusion
• Typically presents with heavy periods and chronic bleeding, but can cause post-coital bleeding
• USG may appear normal if fibroid is small or at the os level; saline sonohysterogram would be more sensitive

6. Condyloma Acuminata (HPV Warts) ★★☆☆☆

• HPV-related exophytic growths on cervix/vaginal walls
• Cauliflower-like, friable, can bleed on contact
• Co-association with HPV = also increases cervical dysplasia risk

7. Cervical Intraepithelial Neoplasia (CIN) ★★☆☆☆

• Pre-cancerous change - usually asymptomatic but can cause contact bleeding
• Not typically visible as a protrusion on PV exam unless advanced (CIN3/carcinoma in situ)

8. Vaginal Trauma / Laceration ★★☆☆☆

• PV exam specifically mentions pain + protrusion, making this less likely
• Should still check vaginal walls on speculum exam for tears

Step 2: Investigations (Priority Order)

Immediate (in the clinic - same visit)

Within 1-2 weeks

Blood tests

Step 3: Management Based on Likely Diagnosis

A. Cervical Polyp (if confirmed)

1. Polypectomy - most polyps can be removed in the outpatient/office setting:
   • Twist and avulse (twisting at the base) for small pedunculated polyps
   • Electrocautery/diathermy excision for larger polyps
   • Ring forceps avulsion for endocervical polyps
2. Send all removed tissue for histopathology - even though benign appearance, must exclude malignancy
3. Follow up with Pap smear/colposcopy
4. No further treatment needed if histology benign

B. Cervical Ectropion (if confirmed)

• Reassurance if asymptomatic - ectropion is a normal variant in young women
• If symptomatic (repeated post-coital bleeding, discharge):
  • Cryotherapy (cold coagulation) or silver nitrate cautery - ablates columnar epithelium
  • Diathermy/electrocoagulation
  • Review OCP use (ectropion often improves after stopping OCP)
• Send Pap smear first before any treatment

C. Cervicitis / STI (if confirmed)

• Chlamydia: Azithromycin 1g single dose OR Doxycycline 100mg BD x 7 days
• Gonorrhoea: Ceftriaxone 500mg IM single dose + Azithromycin 1g
• Trichomoniasis: Metronidazole 400mg BD x 5-7 days
• Treat partner(s) simultaneously
• Abstain from intercourse during treatment

D. Suspicious for Malignancy (if colposcopy/biopsy confirms)

• Urgent referral to gynecological oncology
• Staging workup: MRI pelvis, CT chest/abdomen/pelvis
• Management: LEEP/cone biopsy for CIN; surgery ± radiotherapy ± chemotherapy for invasive cancer

Step 4: Key Clinical Red Flags Requiring Urgent Action

Summary Flowchart

32F + Post-coital bleeding + Vaginal protrusion
         ↓
Speculum examination + Pap smear + Swabs
         ↓
   Visible lesion?
   ├── YES → Colposcopy + Directed biopsy
   │         ├── Benign (polyp/ectropion) → Treat accordingly
   │         └── CIN/Malignancy → Oncology referral
   └── NO → Swab results + HPV test
             ├── STI positive → Treat with antibiotics
             └── All negative → Reassure + Repeat Pap in 6 months

• Postcoital Bleeding: Etiology, Diagnosis, Management - PMC4086375
• Clinicopathological evaluation of postcoital bleeding - WJBPHS 2025
• Post-coital bleeding and colposcopy outcomes - Tropical J Obstet Gynaecol 2023
• Abnormal cervical appearance - PMC3031439